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2018-04-03T04:06:09.115Z | 1996-06-01T00:00:00.000Z | 24962770 | s2ag/train | Two-phase helical CT for pancreatic tumors: pancreatic versus hepatic phase enhancement of tumor, pancreas, and vascular structures.
PURPOSE
To quantitatively evaluate and validate a two-phase helical computed tomographic (CT) protocol for evaluation of pancreatic tumors.
MATERIALS AND METHODS
Twenty-seven patients with pathologically proved pancreatic adenocarcinomas prospectively underwent two-phase CT examination with helical acquisition during the pancreatic phase (40-70 seconds after infusion of intravenous contrast material at 3 mL/sec) and the hepatic phase (70-100 seconds after infusion). Mean CT attenuation values of tumor, bordering pancreas, and all major peripancreatic vessels were obtained for both time intervals.
RESULTS
Mean tumor-pancreas contrast was significantly greater during the pancreatic phase (67 HU +/- 19) than the hepatic phase (39 HU +/- 16) (P < .001) This was the result of both greater enhancement of normal pancreas and lower tumor enhancement during the pancreatic phase. Opacification of all vascular structures, including the portal vein, was also greater during the pancreatic phase (P < .001).
CONCLUSION
Two-phase helical CT with pancreatic phase acquisition provides statistically significantly better pancreatic, arterial, and portal venous enhancement than that of hepatic phase imaging, with improved tumor-pancreas contrast. | v2 |
2017-04-09T03:33:00.369Z | 1997-10-01T00:00:00.000Z | 4381220 | s2ag/train | Relations between functional, inflammatory, and degenerative parameters during adjuvant arthritis in rats.
We assessed the time-course of adjuvant arthritis (AA) in Lewis rats, using biotelemetry to monitor the rat's spontaneous locomotor activity and body temperature, and studied the evolution of the arthritic index, circulating concentrations of inflammation-promoting cytokines, cartilage proteoglycan synthesis, and the effect of indomethacin as a cyclooxygenase inhibitor to evaluate prostaglandin (PG) contribution in AA. The injection of complete Freund's adjuvant on day 0( D0) induced a marked, transient loss of locomotor activity ( D1- D4; initial phase) and then a second phase of hypomobility peaking on D15 and thereafter irreversible ( D16- D20; arthritic phase). Fever peaked first on D1 and again between D13 and D17. The primary hyperthermia was associated with increases in plasma interleukin-6 and tumor necrosis factor-α concentrations and seemed to be partly PG dependent. Proteoglycan synthesis inhibition in the patellar cartilage increased gradually, spreading from the injected paw to the contralateral paw. It was corrected on D20 by preventive and curative indomethacin treatments. Indomethacin also greatly relieved hypomobility during the systemic phase of AA ( D10- D15). The combination of information about cartilage metabolism, body temperature, locomotor activity, and cytokine in this study permits analysis of analgesic, antipyretic, anti-inflammatory, and chondroprotective properties of drugs in the various phases of AA. Thus, using a new methodology, we have discriminated the different phases of the disease and confirmed the symptomatic and systemic inhibitory effect of indomethacin on fever, activity, and cartilage metabolism. | v2 |
2018-04-03T04:38:57.652Z | 2008-01-01T00:00:00.000Z | 20555820 | s2ag/train | Klotho Expression in Epithelial Ovarian Cancer and its Association with Insulin-Like Growth Factors and Disease Progression
Klotho is an anti-aging hormone and is able to suppress the action of IGFs. High IGF activities are associated with cancer risk and tumor progression. Klotho's role in cancer is unknown. To evaluate Klotho expression in ovarian cancer and its association with IGFs and ovarian cancer progression, a clinical follow-up study of 189 ovarian cancer patients was conducted. Patients were recruited from a teaching hospital at University of Turin in Italy. All patients were diagnosed with epithelial ovarian cancer and underwent surgery for the disease. Fresh tumor tissue was collected from each patient during surgery. Patient clinical and pathological information was collected, including patient age at surgery, disease stage, tumor grade, tumor histology, residual tumor size, debulking result, post-operative chemotherapeutic agent, treatment response, follow-up time and survival outcome. Expressions of total and secreted Klotho as well as IGFs in tumor tissue were analyzed using quantitative real-time PCR. Survival analysis was performed to evaluate the association of Klotho expression with the risk of disease progression and death using Cox proportional hazards regression model. High expression of secreted Klotho was associated with increased risk of disease progression and death. These associations were independent of patient clinical and pathological characteristics. Expression of secreted Klotho was positively correlated with the expression of IGF-I and IGFBP-3 but not with IGF-II. In conclusion, Klotho expression is associated with epithelial ovarian cancer progression, and the protein may serve as an independent marker for ovarian cancer prognosis. Klotho's role in cancer warrants further elucidation. | v2 |
2018-04-03T02:56:42.007Z | 2008-10-01T00:00:00.000Z | 23645770 | s2ag/train | Enhanced plasma levels of LIGHT in patients with acute atherothrombotic stroke
Objectives – As a member of the tumor necrosis factor superfamily (TNFSF), LIGHT (TNFSF14) was recently found to be associated with platelets and released upon activation. Increased plasma levels of LIGHT have been reported in patients with myocardial infarction and unstable angina. The aim of the study was to analyze plasma levels of LIGHT in acute ischemic atherosclerotic stroke. | v2 |
2018-04-03T02:18:52.966Z | 1989-02-01T00:00:00.000Z | 3299070 | s2ag/train | Effects of gonadotropin-releasing hormone and its agonists on prolactin secretion from normal and tumorous pituitary cells.
Previous studies on the effect of gonadotropin-releasing hormone (LHRH) agonist on prolactin (PRL) secretion from normal and tumorous pituitary cells have not been conclusive as to the mechanism of action of these agonists. In this study the short-term administration of a LHRH agonist did not affect circulating PRL levels, but depleted the PRL content of the pituitary gland by 24, 49 and 73% after 2, 3 and 4 days, respectively, in normal female rats and by 75% after 4 days in normal male rats. This effect of the agonist could not be attributed to changes in the sex steroid environment: although plasma 17 beta-estradiol concentrations were significantly suppressed in female rats, circulating testosterone levels had not changed yet in the male rats. Interestingly, the pituitary luteinizing hormone (LH) content was depleted already from day 2 of LHRH agonist administration onwards, while the follicle-stimulating hormone (FSH) content of the pituitary glands had not changed even after 4 days. Culture studies with pituitary cells from normal adult male and female rats for 4-7 days did not reveal a direct effect of synthetic LHRH or an agonist on PRL release. Chronic systemic administration of a LHRH agonist greatly inhibited the growth of the transplantable PRL-secreting rat pituitary tumor 7315a in female rats, while circulating PRL levels were also suppressed. However, no direct effect of the LHRH agonist was observed on PRL release from a tumor cell clone, derived from the 7315a tumor, and no LHRH-binding sites were detectable on the tumor.(ABSTRACT TRUNCATED AT 250 WORDS) | v2 |
2021-11-12T06:17:17.257Z | 2021-01-01T00:00:00.000Z | 243987220 | s2ag/train | Dilatation and curettage in endometrial cancer. What is the correlation with hysterectomy histology? A 14 years retrospective cohort study.
PURPOSE
The aim of the present study is to evaluate the concordance between preoperative endometrial sampling histopathology performed by conventional dilatation and curettage (D&C) and final histopathological diagnosis after total hysterectomy concerning tumor grade and subtype in patients with endometrial cancer (EC).
METHODS
In this comparative retrospective study, 203 women with endometrial cancer were included who underwent at first dilatation and curettage and then total hysterectomy. The preoperative histopathological report obtained by dilatation and curettage was compared with the final histopathology after total hysterectomy to assess the accuracy of endometrial sampling.
RESULTS
Comparison of preoperative with postoperative histopathological results showed an overall 5.9% and 10.9% discordance regarding endometrial cancer histological subtype and grade, respectively. Six (4.9%) of the patients with preoperative grade 1 were grade 2 and 1 (0.8%) was found to be grade 3. Three (8.3%) of the patients with preoperative grade 2 were found to be grade 3 after hysterectomy. Discordance is higher for endometrioid endometrial cancer grade 2 (25%) compared with grade 1 (5.7%) and 3 (18.8%).
CONCLUSION
Patients should be informed and consent for the potential discrepancy between the pre and postoperative histopathological features of malignancy. This discrepancy may result in either under or overtreatment. Thus, it should be accounted for when counseling for a major operation. | v2 |
2018-04-03T01:00:10.489Z | 2017-04-01T00:00:00.000Z | 21405870 | s2ag/train | [A rarely isolated bacterium in microbiology laboratories: Streptococcus uberis].
Streptococcus uberis is a gram-positive bacterium that is mostly responsible for mastitis in cattle. The bacterium rarely has been associated with human infections. Conventional phenotyphic methods can be inadequate for the identification of S.uberis; and in microbiology laboratories S.uberis is confused with the other streptococci and enterococci isolates. Recently, molecular methods are recommended for the accurate identification of S.uberis isolates. The aim of this report is to present a lower respiratory tract infection case caused by S.uberis and the microbiological methods for identification of this bacterium. A 66-year-old male patient with squamous cell lung cancer who received radiotherapy was admitted in our hospital for the control. According to the chest X-Ray, patient was hospitalized with the prediagnosis of ''cavitary tumor, pulmonary abscess''. In the first day of the hospitalization, blood and sputum cultures were drawn. Blood culture was negative, however, Candida albicans was isolated in the sputum culture and it was estimated to be due to oral lesions. After two weeks from the hospitalization, sputum sample was taken from the patient since he had abnormal respiratory sounds and cough complaint. In the Gram stained smear of the sputum there were abundant leucocytes and gram-positive cocci, and S.uberis was isolated in both 5% sheep blood and chocolate agar media. Bacterial identification and antibiotic susceptibility tests were performed by VITEK 2 (Biomerieux, France) and also, the bacterium was identified by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) based VITEK MS system as S.uberis. The isolate was determined susceptible to ampicillin, erythromycin, clindamycin, levofloxacin, linezolid, penicillin, cefotaxime, ceftriaxone, tetracycline and vancomycin. 16S, 23S ribosomal RNA and 16S-23S intergenic spacer gene regions were amplified with specific primers and partial DNA sequence analysis of 16S rRNA polymerase chain reaction (PCR) products were performed by 3500xL Genetic Analyzer (Applied Biosystems, USA). According to the partial 16S rRNA gene sequencing results, bacterium was confirmed as S.uberis. This report makes a significant contribution to the number of case reports of human infections caused by S.uberis as the identification was performed by current microbiological methods in our case. In conclusion, S.uberis should be evaluated as an opportunistic pathogen among the immunosuppressed patients and in addition to phenotypic bacteriological methods, the other recent microbiological methods should also be utilized for the identification. | v2 |
2018-04-03T05:46:34.608Z | 2014-06-01T00:00:00.000Z | 44376470 | s2ag/train | Type VII collagen and squamous cell carcinoma
Recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering disease, is caused by mutations in COL7A1, the gene encoding type VII collagen (Col7), which is the main component of anchoring fibrils. Affected individuals have decreased or undetectable Col7 with skin and mucosal fragility, blistering and scarring. Over 78 7% of patients with severe generalized RDEB will die from metastatic squamous cell carcinoma (SCC) by the age of 45 years, suggesting a link between loss of Col7 and aggressive SCC. Treatment of RDEB by attempting to restore Col7 by protein, cell or gene therapy is currently the subject of intensive research, and existing and likely future clinical trials. In this issue of BJD, Pourreyron et al. engineer SCC keratinocytes derived from RDEB tumours and various controls to overexpress Col7 (up to 35 5-fold vs. normal endogenous levels), using recombinant COL7A1 cDNA in a retroviral vector. They show that high levels of Col7 expression generally induce increased migration and invasion in RDEB SCC keratinocytes, associated with an increase in activation of the phosphoinositide 3-kinase pathway, a pathway involved in regulation of migration/invasion. The authors conclude that caution should be exercised when considering therapeutic strategies where delivery of Col7 is likely to exceed greatly the levels seen under normal physiological conditions. Different models of loss/overexpression of Col7 produce varied results; however, in my opinion, the consensus view is veering towards loss of Col7 being proinvasion. Data from a Ras/IjBa-driven tumorigenesis model suggest that the noncollagenous (NC1) domain of Col7 is necessary for tumour formation by RDEB keratinocytes. However, many RDEB tumours do not express Col7. In ultraviolet-induced SCC cell lines expressing Col7, knock-down of Col7 using small inhibitory RNA promoted cell invasion and disorganized epithelial differentiation in vitro with an increase in transforming growth factor (TGF)-b signalling, a known contributor to cancer progression. In the hypomorphic mouse model of RDEB (10% Col7 expression), chemical carcinogenesis protocols produced more highly invasive tumours compared with benign papillomas in wild-type mice. The extracellular matrix composition in RDEB is permissive for tumour development, and invasion and tumour formation of RDEB SCC keratinocytes can be decreased by overexpressing Col7 in dermal fibroblasts. Finally, detailed proteome analysis of fibroblasts of patients with RDEB compared with control fibroblasts showed a decrease in basement membrane matrix components and an increase in dermal matrix proteins, TGF-b and metalloproteinase expression, but not activity, in RDEB. Patients with dominant dystrophic epidermolysis bullosa who have one normal COL7A1 allele, hence approximately 50% normal Col7, rarely develop SCC. One would hope that restoring Col7 expression in RDEB to close to 50% of normal levels would decrease TGF-b signalling, improve wound healing, decrease scarring and chronic inflammation, and restore basement membrane function towards normal levels, thus reducing the risk of SCC. However, Col7 is a powerful matrix signalling molecule and, as cautioned by Pourreyron et al., if overexpression is planned, preclinical dose–response studies will be needed in animal models. | v2 |
2018-04-03T05:18:30.803Z | 2001-09-01T00:00:00.000Z | 42394110 | s2ag/train | 8-Prenylnaringenin, the phytoestrogen in hops and beer, upregulates the function of the E-cadherin/catenin complex in human mammary carcinoma cells.
The E-cadherin/catenin complex is a powerful invasion suppressor in epithelial cells. It is expressed in the human MCF-7 breast cancer cell line family, but functionally defective in the invasive MCF-7/6 variant. Previous experiments have shown that IGF-I, tamoxifen, retinoic acid and tangeretin are able to upregulate the function of this complex in MCF-7/6 cells. We investigated the effect of 8-prenylnaringenin (8-PN), the phytoestrogen present in hops and beer, on aggregation, growth and invasion in MCF-7/6 cells. 8-PN was found to stimulate E-cadherin-dependent aggregation and growth of MCF-7/6 cells in suspension. These effects could be inhibited by the pure anti-estrogen ICI 182,780. 8-PN did not affect invasion of MCF-7/6 cells in the chick heart assay in vitro. In all these aspects 8-PN mimics the effects of 17beta-estradiol on MCF-7/6 cells. | v2 |
2022-05-09T13:16:02.130Z | 2022-01-01T00:00:00.000Z | 248562460 | s2ag/train | Biosynthesis and characterization of silver nanoparticles prepared using seeds of Sisymbrium irio and evaluation of their antifungal and cytotoxic activities
Abstract Recent studies have shown that green synthesis of silver nanoparticles (AgNPs) and their application in the control of phytopathogenic fungi is a burgeoning field. Sisymbrium irio (Si) (London rocket) is a well-known weed that grows abundantly in Saudi Arabia from February to May. The present study is concerned with the rapid synthesis of silver nanoparticles from the aqueous seed extract of Si) in the presence of sunlight. The biosynthesized Si-AgNPs were characterized using UV-Visible spectroscopy (UV-Vis), energy dispersive X-ray (EDX) microanalysis, dynamic light scattering analysis (DLS), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy analysis (FTIR). The UV-Vis spectrum revealed a prominent surface plasmon resonance (SPR) absorption band (∼439 nm) characteristic of AgNPs. As revealed by TEM analysis, the Si-AgNPs were predominantly spheroidal in shape and measured between 4 and 51 nm, while the Z average of nanoparticles was 94.81 nm as revealed by the DLS spectrum. The FTIR spectrum displayed peaks related to important functional groups (amines, phenols, carboxylic acids, flavonoids, aromatic compounds, and esters) that aid in the reduction, encapsulation, and stability of AgNPs. The Si-AgNPs were further investigated against a panel of potent fungal phytopathogens that included Alternaria alternata, A. brassicae, Fusarium solani, F. oxysporum, and Trichoderma harzianum. The cytotoxic activity of the biosynthesized nanoparticles against human cervical cancer cell lines (HeLa) was also tested. Si-AgNPs at 80 µg·mL−1 demonstrated a marked reduction in mycelial growth and spore germination. Similarly, Si-AgNPs exhibited dose-dependent cytotoxic activity against the HeLa cell line, with an IC50 value of 21.83 ± 0.76 µg·mL−1. The results of the present study demonstrate the robust cytotoxic and antifungal activities of Si-AgNPs. Based on the findings, Si-AgNPs can be exploited to design formulations that can effectively act as anticancer agents, controlling the proliferation of cancer cells while also combating fungal phytopathogens. However, future research to understand their toxicity mechanisms is needed. | v2 |
2018-04-03T01:38:31.906Z | 1998-11-25T00:00:00.000Z | 46782210 | s2ag/train | Comparison of Rigid and Flexible Transbronchial Needle Aspiration in the Staging of Bronchogenic Carcinoma
In staging bronchogenic carcinoma by transbronchial needle aspiration (TBNA), rigid histology needles are generally preferred to flexible cytology needles owing to the widespread opinion that rigid needles have higher diagnostic yield and less false-positive results. The objective of this study was to compare the efficacy and safety of the rigid and flexible TBNAs in staging bronchogenic carcinoma to establish whether a flexible cytology needle method can replace the rigid needle. A prospective study was conducted in 138 consecutive patients with extra- or endobronchial masses suggestive of bronchogenic carcinoma and amenable to surgical procedures. All 8 mm and larger paratracheal, carinal, hilar and/or main bronchial lymph nodes determined before bronchoscopy by computed tomography (CT) were sampled by successive 18-gauge rigid and 21-gauge flexible TBNAs in the same session. The anatomic landmarks were followed precisely during TBNAs, and a proper technique applied in sampling and specimen processing. Malignant lymph node involvement was specified in 97 (72%) cases of bronchogenic carcinoma by rigid, and in 89 (66%) by flexible TBNA. There were 4 (100%) benign cases (3 with tuberculosis and 1 with sarcoidosis) of 101 (73%) with positive rigid TBNAs (82 with histological and 19 with cytological specimens). TBNAs determined malignant lymph node involvement in a total of 104 (78%) patients. Of 30 TBNA-negative patients, 14 were proven to have false-negative TBNAs by mediastinoscopy/mediastinotomy/minithoracotomy, and 16 to have true-negative TBNAs by thoracotomy. Thoracotomy confirmed true positivity in 52 rigid and 49 flexible TBNAs, and false negativity in 4 rigid and 7 flexible TBNAs. Further staging was confirmed in these 7 cases. Four had proven false-negative results by both methods. The presence of small cell carcinoma (21) or N3 disease (27) presented a contraindication to thoracotomy in 48 TBNA-positive patients. Adequate-quality and malignant lymph node specimens were more frequently obtained by both techniques at advanced tumor and node stages. However, malignant lymph node invasion was significantly more frequent in rigid and flexible TBNA specimens only in the presence of advanced tumor status and abnormal endoscopic appearance. The sensitivities of rigid and flexible TBNAs were 74 and 70%, respectively (p > 0.05), but both had a specificity of 100%. Neither false-positive results nor serious complications other than hemorrhage of 30–100 ml (rigid: 5%, flexible: 2%) were encountered with either technique. These results indicate that in bronchogenic carcinoma, hilar and mediastinal lymph nodes can be staged by 21-gauge flexible TBNA (76%) as accurately as by 18-gauge rigid TBNA (79%) if a proper technique is applied and anatomic landmarks are followed precisely (p > 0.05). | v2 |
2022-02-27T06:22:48.443Z | 2022-01-01T00:00:00.000Z | 247130110 | s2ag/train | Impact of Medicaid Expansion on the Diagnosis, Treatment, and Outcomes of Stage II and III Rectal Cancer Patients.
BACKGROUND
Insurance status has been associated with disparities in stage at cancer diagnosis. We examined how Medicaid expansion (ME) impacted diagnoses, surgical treatment, use of neoadjuvant therapies (NCRT), and outcomes for Stage II and III rectal cancer.
STUDY DESIGN
We used 2010-2017 American College of Surgeons National Cancer Database (NCDB) to identify patients ages 18-65, with Medicaid as primary form of payment, and were diagnosed with Stage II or III rectal cancer. Patients were stratified based on Census bureau division's ME adoption rates of High, Medium, Low. Overall trends were examined, and patient characteristics and outcomes were compared before and after ME date of 1/1/2014.
RESULTS
Over 8 years of NCDB data examined, there was an increasing trend of Stage II and III rectal cancer diagnoses, surgical resection, and use of NCRT for Medicaid patients. We observed an increase in age, proportion of White Medicaid patients in Low ME divisions, and proportion of fourth income quartile patients in High ME divisions. Univariate analysis showed decreased use of open surgery for all 3 categories after ME, but adjusted odds ratios (aOR) were not significant based on multivariate analysis. NCRT utilization increased after ME for all 3 ME adoption categories and aOR significantly increased for Low and High ME divisions. ME significantly decreased 90-day mortality.
CONCLUSIONS
Medicaid expansion had important impacts on increasing Stage II and III rectal cancer diagnoses, use of NCRT, and decreased 90-day mortality for patients with Medicaid. Our study supports increasing health insurance coverage to improve Medicaid patient outcomes in rectal cancer care. | v2 |
2020-12-10T09:07:56.074Z | 2020-12-03T00:00:00.000Z | 229438610 | s2ag/train | Panitumumab-Induced Paronychia: A Case Report and a Brief Review of the Literature
Panitumumab is a recombinant, fully humanized IgG2 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). Panitumumab is indicated for patients with metastatic colorectal cancer with progressive refractory disease. Targeted therapies are well known to be well tolerated; however, they may induce toxicities that are distinct from those of classical chemotherapeutic agents. For instance, EGFR inhibitors (EGFRIs) are associated with some specific dermatological adverse effects, one of which is nail toxicity. Since panitumumab is fully humanized, unlike most of the other EGFRIs, it has been reported to have reduced incidence of adverse reactions. Nail-related adverse effects are frequently observed with EGFRIs. A literature search has yielded a list of reviews describing panitumumab-induced nail toxicity. However, as far as we know, there is no case report detailing this adverse effect of panitumumab. Here, we present a case of panitumumab-induced paronychia in a 60-year-old woman with metastatic colon cancer. With this case report, we would like to review the literature and discuss the possible underlying mechanisms of this condition. | v2 |
2022-05-16T19:08:18.272Z | 2022-05-16T00:00:00.000Z | 248809210 | s2ag/train | Outcome of complex surgical resection and reconstruction for rare thoracic cancers: the clinical value of a predictive score
Background. Complex surgical resection and reconstruction for rare thoracic cancers (RTCs) represent a major challenge, given their very low frequency, extreme variability of presentation, multi-modality treatment options and inadequate outcome prediction. We reported the experience of a tertiary referral centre on a consecutive series of RTC patients, to predict outcome by disease and complexity of surgical procedures. Methods. From Jan 2003 to Dec 2018, 1122 surgical procedures were performed with curative intent on 952 RTC patients. Study endpoints were: post-operative hospital stay (Pod), 30-day and 90-day mortality, 5-year and 10-year survival (OS). The follow-up was closed at June 2020. Results. Median Pod was 8 days, with a 2% 30-day and 3.9% 90-day mortality. Overall survival (OS) was 85.7% at 1 year, 61.7% at 5 years and 50.7% at 10 years. Ten-year OS was 64.8% in low, 58.8% in intermediate, and 42.4% in high complexity score (Log-rank tests p<0.0001); 64.4% in patients with 1 or 2 reconstructions and 32.8% in patients with 3 or more reconstructions; 44.5% with vascular and 48% with chest wall reconstruction; 71.8% in germ cell tumors and 0% in mesothelioma. Conclusion. Complex surgical resection and reconstruction was associated with acceptable 90-day mortality and good 10-year survival in all RTCs but mesothelioma. A predictive score based on surgical complexity and cancer type can help the clinical decision making. | v2 |
2018-04-03T06:17:59.042Z | 1998-10-01T00:00:00.000Z | 46316510 | s2ag/train | Cell surface density of p185(c-erbB-2) determines susceptibility to anti-p185(c-erbB-2)-ricin A chain (RTA) immunotoxin therapy alone and in combination with anti-p170(EGFR)-RTA in ovarian cancer cells.
Approximately 30% of ovarian and breast cancers overexpress p185(c-erbB-2) with as many as 10(6) receptors/cell. Normal cells have as few as 10(4) receptors/cell. We have examined the susceptibility of SKOv3 human ovarian cancer cells to anti-c-erbB2 antibodies and immunotoxins as a function of c-erbB-2 density on the cell surface. A panel of SKOv3 clones that expressed different densities of p185(c-erbB-2) receptor were generated through transfection with the c-erbB-2 gene. A significant correlation was found between p185(c-erbB-2) density and susceptibility to killing by anti-p185(c-erbB-2)-ricin A chain (anti-p185(c-erbB-2)-RTA) immunotoxins. With 10(5) copies/cell of p185(c-erbB-2), <10% of clonogenic ovarian cancer cells could be eliminated, whereas in clones that expressed 10(6) copies/cell of p185(c-erbB-2), 99.9% of clonogenic tumor cells were killed. In cell lines that overexpressed p185(c-erbB-2) and also expressed p170(EGFR), anti-p185(cerbB-2)-RTA and anti-p170(EGFR)-RTA immunotoxins exerted synergistic cytotoxicity. Treatment with the two immunotoxins could eliminate 99.99% of clonogenic cells. Importantly, tumor cells that had survived first treatment with anti-p185(c-erbB2)-RTA alone still retained sensitivity to repeat treatment with the same immunotoxin and also proved susceptible to the synergistic cytotoxicity of anti-p185(cerbB-2)-RTA in combination with anti-p170(EGFR)-RTA. Growth characteristics of the clones expressing various levels of p185(c-erbB-2) were also studied. No correlation was found between p185(c-erbB-2) expression levels and the rate of anchorage-dependent growth, anchorage-independent growth, or in vivo growth in nude mice. | v2 |
2021-07-27T00:06:05.087Z | 2021-05-20T00:00:00.000Z | 236398910 | s2ag/train | Heterogeneity between core needle biopsy and synchronous axillary lymph node metastases in early breast cancer patients: Comparison of HER2, estrogen and progesterone receptor expression profiles during primary treatment regime.
e12565 Background: Therapeutic decisions for the primary treatment of breast cancer is commonly based on the expression profiles of estrogen (ER), progesterone (PR) and the human epidermal growth factor 2 (HER2) receptors. However, breast cancer is a very heterogeneous disease, and receptor changes were manifold reported during progression. Little is known about receptor discordance in the primary setting. Here, we compared receptor expression profiles between core needle biopsy (CNB) of the breast tumor tissue and synchronous axillary lymph node metastases (LNM) not at recurrence, but at the primary treatment. Methods: In a German single center study, we retrospectively analyzed 175 breast cancer patients with axillary synchronous LNM. 69,7% of our patients were without any upfront therapy. Profiles of ER, PR and HER2 were immunohistochemically analyzed using the common cut-off at 10% positive tumor cells vs. the controversially discussed low-positive cut-off at 1%. Receptor status was compared between CNB specimens of the primary tumor tissue and axillary LNM. Further, clinicopathological characteristics were correlated to receptor changes. Results: The discordance rates between CNB and axillary LNM were 12.7% for HER2, 6.9% for ER and 22.6% for PR using the ≥1% cut-off, respective 7.5% for ER and 25.6% for PR when using the ≥10% cut-off-level. The most frequently occurring change was a PR loss. Analysis of clinical parameters revealed a significant association of ER change between CNB and LNM in younger patients (p < 0.01) with increased proliferation marker Ki-67 (p = 0.04). Conclusions: Receptor discordance between CNB and synchronous axillary LNM appears to exist at the primary setting already. Hence, receptor profiles of the tumor tissue and the synchronous axillary LNM should be considered for treatment decision. | v2 |
2018-04-03T04:20:19.014Z | 1997-10-25T00:00:00.000Z | 38637470 | s2ag/train | A pharmacophore model of tautomycin, an inhibitor of protein phosphatases 1 and 2A.
Over the last decade there has been a growing realization that phosphatases are extremely important in cellular and organismal functions1}. Tautomycin, an inhibitor of protein phosphatases (PP) 1 and 2A, was isolated from a culture broth of Streptomyces spiroverticillatus in 19872). The structure that we established in 19903) showed some similarities with that of okadaic acid, and the target protein of okadaic acid had already been found to be protein phosphatase in 19884). Indeed, it was later found that the target proteins of tautomycin were also protein phosphatases5'6). However, this molecule is not a tumor promoter on mouseskin and in rat glandular stomach7). These differences in biological activities between tautomycin and the okadaic acid class tumor promoters are interesting topics in structural biology. The threedimensional structures of the related compoundacanthifolicin8) and the obromobenzyl ester derivative of | v2 |
2018-04-03T02:05:32.630Z | 1996-08-01T00:00:00.000Z | 20957320 | s2ag/train | Rectal cancer: the influence of type of operation on local recurrence and survival.
OBJECTIVE
To assess the results of standardised total mesorectal excision of rectal cancer with particular reference to local recurrence and survival.
DESIGN
Prospective open study.
SETTING
Central hospital, Norway.
MAIN OUTCOME MEASURES
Local recurrence, survival.
RESULTS
The resectability rate was 90% (107/118), of whom 81 (76%) underwent curative resection. The overall local recurrence rate in patients who underwent primary resection was 9% with an overall five-year survival rate of 53%. In patients who had had curative operations the local recurrence rate was 4% (3/81), with an overall five year survival of 65% and a cancer specific survival of 85%. None of the patients who had palliative treatment survived five years. In 12 patients whose tumours were thought to be unresectable but who were operated on, of whom nine were given additional radiotherapy (46 Gy), 5 (42%) developed local recurrences and the five year cancer free survival was 25%.
CONCLUSION
Total mesorectal excision and strict adherence to the surgical principles of anatomical dissection in the pelvis and washing out of the rectal stump before anastomosis reduce local recurrences to a minimum. In patients with locally advanced, fixed cancers, preoperative irradiation with more than 46 Gy must precede operation to achieve local control. | v2 |
2018-04-03T02:42:16.770Z | 2004-05-07T00:00:00.000Z | 34794920 | s2ag/train | [Study on relationship of fucosyltransferase gene types in breast cancer with metastasis and prognosis].
OBJECTIVE
To assess the association of five types of fucosyltransferase gene (Fuc-T), the important biosynthesis gene of sialylated carbohydrate antigens (Sialyl Lewis A, Sialyl Lewis X), with metastasis and prognosis of breast cancer.
METHODS
The real-time quantitative PCR of five-type Fuc-T III, IV, V, VI, VII genes was performed in 80 patients with breast cancer.
RESULTS
The result showed that Fuc-TVII gene had higher gene copy compared to other type of Fuc-T in breast cancer. The grading of Fuc-TVII gene was related to lymph node metastasis and poor disease-free survival. Statistically difference was significant (P < 0.01). Fuc-T III, IV, V, VI gene were not significant relation to the metastasis and prognosis in 80 cases.
CONCLUSIONS
These findings suggest that Fuc-TVII gene is a prognostic indicator of breast cancer, and it may be play an important role in the biosynthesis of sialylated carbohydrate antigens in breast cancer. | v2 |
2018-04-03T02:25:16.514Z | 2016-12-01T00:00:00.000Z | 23323860 | s2ag/train | Implementing the Risk of Ovarian Malignancy Algorithm Adding Obesity as a Predictive Factor.
AIM
To evaluate whether obesity represents a risk factor for the onset of ovarian cancer.
PATIENTS AND METHODS
One hundred and sixty-three patients with a body mass index (BMI) >30 kg/m2 (group 1) and 130 women with a BMI of <25 kg/m2 (group 2) were included in the study.
RESULTS
A Risk of Ovarian Malignancy Algorithm (ROMA) index above the cut-off (>13%) was found in 24.5% of group 1 patients, whereas a high ROMA score was identified in 5.3% of group 2 women. During the study, 13 out of 40 group 1 patients with ROMA >13% were deemed eligible for bariatric surgery. After bariatric surgery and decrease of BMI, eight out of these 13 obese women had a ROMA index <13%.
CONCLUSION
The ROMA index may function as a simple test able to screen obese women at risk of developing ovarian cancer. | v2 |
2018-10-07T08:21:21.258Z | 2018-08-29T00:00:00.000Z | 53065960 | s2ag/train | Assessing Waste Taxation: an Empirical Study in a Cge Multi-Pollutant Framework
Economic theory states that incineration and landfill taxes can be a good policy to reduce environmental impacts of these activities by reducing their importance and associated pollutants, while stimulating reuse and recycling of materials. In this research we assess the economic and environmental effects of these taxes in Spain with the use of a detailed dynamic CGE model, under different scenarios. We focus the economic impact on GDP and sectorial production, and the environmental impact on different impact categories: global warming potential, marine eutrophication potential, photochemical ozone formation potential, particulate matter, human toxicity (cancer and non-cancer), ecotoxicity, and depletion of fossil resources). We find in all scenarios that these taxes have a limited economic impact, while reduce all of the environmental impact categories analyzed. | v2 |
2018-04-03T01:02:39.781Z | 2011-05-01T00:00:00.000Z | 27759810 | s2ag/train | [Sublobar resection for non-small cell lung cancer in Iceland].
INTRODUCTION
A sublobar resection is performed on patients with non-small cell lung cancer (NSCLC) who are not candidates for a lobectomy due to reduced pulmonary function or comorbid disease. The aim of this study was to investigate the outcomes of these operations in Iceland.
MATERIAL AND METHODS
A retrospective study of all patients with NSCLC who underwent wedge resection or segmentectomy with curative intent during 1994-2008. Data on indication, pathological TNM-stage, complications and overall survival was analyzed. All histological samples were re-evaluated.
RESULTS
Forty four patients underwent 42 wedge and 5 segmental resections (age 69.1 yrs, 55.3% female), with 38.3% of cases detected incidentally. The majority of patients (55.3%) had a history of coronary artery disease and 40.4% had chronic obstructive pulmonary disease. Mean operative time was 83 minutes (range 30-131), mean intraoperative bleeding was 260 ml (range 100-650) and median hospital stay was 9 days (range 4-24). Pneumonia (14.9%) and prolonged air leakage (12.8%) were the most common complications. Two patients had major complications and 36.2% stayed in the intensive care unit overnight. No deaths occurred within 30 days of surgery. Adenocarcinoma was the most common histological type (66.7%). Most cases were stage IA/IB (78.7%), 17.0% were stage IIA/IIB and 4.3% were stage IIIA. One and 5 year survival was 85.1% and 40.9% respectively.
CONCLUSION
In Iceland, both survival and complication rate after sublobar resection for NSCLC are comparable to results published for lobectomies, even though a higher percentage of patients have underlying cardiopulmonary disease. | v2 |
2018-04-03T05:39:26.451Z | 1988-01-01T00:00:00.000Z | 43708810 | s2ag/train | Von Recklinghausen neurofibromatosis with carcinoid tumor and submucous leiomyomas of the duodenum.
We report on a 63-year-old man with von Recklinghausen neurofibromatosis who developed a carcinoid tumor in the periampullary region and multiple small-sized leiomyomas in the duodenal wall. A high prevalence of gastrointestinal carcinoids has previously been recognized in patients with von Recklinghausen neurofibromatosis, the commonest site of origin being the duodenum or the periampullary region. The association of both conditions seems to be more than casual. Abnormalities in the development of the complex of von Campenhout or high circulating levels of nerve growth factor have been the mechanisms postulated to account for this association. | v2 |
2017-04-08T08:45:43.730Z | 1985-01-01T00:00:00.000Z | 5518810 | s2ag/train | Appearance of systemic amyloidosis in a chronic hemodialysis patient.
Dr. D. Hillion, Department of Nephrology, Centre Hospitalier Intercommunal de Poissy, 10, rue du Champ Gaillard, F-78303 Poissy (France) Dear Sir, Since 1977, amyloid deposits in the transverse carpal ligament of patients on regular dialysis treatment (RTD) were reported. Two unanswered questions persist: (1) Are they localized deposits of a systemic amyloidosis? (2) What is the type of the amyloid? We report a case of systemic non-immunoglobulin-induced (AA) amyloidosis in a patient on RTD. In 1951, Mme C. was 30 years old when a proteinuria was found during her third pregnancy. In 1967, renal failure was diagnosed during a preoperative workup: high blood presssure, urea nitrogen 12mmol/l, proteinuria 1 g/24 h, Addis count: 300 H/min, 2,000 L/min. IVP showed two regular atrophied kidneys. In 1968, subtotal hysterectomy was performed for endometriosis. Regular hemodialysis was started in 1972. From 1972 to 1981 the principal events had been hepatitis and hyperparathyroidism. In 1981, removal of a sacrococcygeal cyst led to the discovery of subcutaneous deposits with the histochemical behavior of amyloid: positive Congo red staining and green berefringence. There were no clinical signs of carpal tunnel syndrome (CTS), nor systemic amyloidosis. Gamma-pathy exploration was negative. In 1982, bone biopsy and parathyr-oidectomy were performed: no amyloid deposits were found in the tissues. In 1983, during a routine examination a stage I cancer of the cervix uteri was found and treated by irradiation. In 1983, spontaneous hemarthrosis of the knees, ankles, wrists and shoulders occurred. In the synovial biopsy specimen, amyloid deposits disrupting the synovial membrane but respecting the underlying vessels were found. In 1984, a massive digestive hemorrhage necessitated a laparotomy: there were no metastases, the bleeding originated in the terminal ileum which was resected, a liver biopsy was performed. Large amyloid deposits were found in the level of ileal submucosa and submucosa vessels, smaller deposits in the hepatic arterioles and sinusoid capillaries. Using the Wright’s technique, potassium permanganate treatment eliminated Congo red stainability. The patient died postoperatively. No autopsy was performed. The successive discovery of the amyloid deposits over a period of 4 years led us to relate them to the duration on RTD. | v2 |
2018-04-03T04:12:44.189Z | 2013-06-11T00:00:00.000Z | 38077610 | s2ag/train | Survival in patients with oral and maxillofacial diffuse large B-cell lymphoma.
The purpose of this study was to determine the survival and prognostic factors of patients with diffuse large B-cell lymphoma (DLBCL) of the oral cavity and maxillofacial region. Retrospectively, the clinical records of patients with a primary diagnosis of DLBCL of the oral cavity and maxillofacial region treated at the A.C. Camargo Hospital for Cancer, São Paulo, Brazil, between January 1980 and December 2005 were evaluated to determine (A) overall survival (OS) at 2 and 5 years and the individual survival percentage for each possible prognostic factor by means of the actuarial technique (also known as mortality tables), and the Kaplan Meier product limit method (which provided the survival value curves for each possible prognostic factor); (B) prognostic factors subject to univariate evaluation with the log-rank test (also known as Mantel-Cox), and multivariate analysis with Cox's regression model (all the variables together). The data were considered significant at p≤0.05. From 1980 to 2005, 3513 new cases of lymphomas were treated, of which 151 (4.3%) occurred in the oral cavity and maxillofacial region. Of these 151 lesions, 48 were diffuse large B-cell lymphoma, with 64% for OS at 2 years and 45% for OS at 5 years. Of the variables studied as possible prognostic factors, multivariate analysis found the following variables have statistically significant values: age (p=0.042), clinical stage (p=0.007) and performance status (p=0.031). These data suggest that patients have a higher risk of mortality if they are older, at a later clinical stage, and have a higher performance status. | v2 |
2020-04-23T06:30:17.914Z | 2006-01-01T00:00:00.000Z | 216064920 | s2ag/train | Paper MEAN DOSE TO LYMPHOCYTES DURING RADIOTHERAPY TREATMENTS
-Using a probabilistic model with parameters from four radiotherapy protocols used in Mexican hospitals for the treatment of cervical cancer, we have calculated the distribution of dose to cells in peripheral blood of patients. Values of the mean dose to the lymphocytes during and after a 6oCo treatment are compared to estimates from an in vivo chromosome aberration study performed on five patients. Calculations indicate that the mean dose to the circulating blood is about 2% of the tumor dose, while the mean dose to recirculating lymphocytes may reach up to 7?6 of the tumor dose. Differences up to a factor of two in the dose to the blood are predicted for different protocols delivering equal tumor doses. The data suggest mean doses h i e r than the predictions of the model. Health Phys. 67(4):326-329; 1994 | v2 |
2018-01-24T17:25:33.048Z | 2009-05-20T00:00:00.000Z | 27019820 | s2ag/train | Neoadjuvant platinum-based chemotherapy (CT) for triple-negative locally advanced breast cancer (LABC): Retrospective analysis of 125 patients.
625 Background: Triple-negative breast cancer (TNBC), defined by lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, accounts for 15-20% of all breast cancers and is associated with poor prognosis. There is no consensus regarding optimal CT for treatment of such patients. Preclinical data suggests TNBC may be sensitive to platinums because of deficiencies in BRCA-associated DNA repair. The aim of this study was to evaluate pathologic complete response (pCR) and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based CT.
METHODS
We identified 674 patients with LABC who received neoadjuvant CT between January 1999 and June 2008 at University of Miami. Of these, 125 (18.5%) had histopathologic confirmation of TNBC. All patients received neoadjuvant platinum salts + docetaxel. 76 (61%) also received neoadjuvant AC, while 42 (34%) received adjuvant AC. pCR was defined as no residual invasive disease in breast and axilla. OS was calculated according to Kaplan-Meier.
RESULTS
Demographics: median age 50 (28-86 years). 60% premenopausal. TNM stage distribution: T1 0.9%, T2 5.2%, T3 53.4%, T4 40.5%, N0 25.0%, N1 36.2%, N2 35.4%, N3 3.4%, M0 100%, inflammatory 11%, median tumor size = 9.5 cm. Follow up duration ranged from 0.3 to 8.9 years. pCR was observed in 42 of 125 patients (34%; 95% CI 26-43%). Among patients receiving neoadjuvant AC, 30 of 76 (40%; 95% CI 28-51%) had pCR, while amongst those receiving adjuvant AC, 12 of 42 (29%, 95% CI 16-45%) had pCR at the time of definitive surgery. Patients achieving pCR had significantly higher OS (5-yr rate = 73% in pCR, vs. 49% in non-pCR; p < 0.001). OS in TNBC patients receiving cisplatin/docetaxel was significantly superior to those receiving carboplatin/docetaxel (11 mortality events out of 78 patients receiving cisplatin based CT vs 24 out of 47 receiving carboplatin based CT logrank p = 0.001).
CONCLUSIONS
To date, this is the largest single institution cohort of locally advanced TNBC uniformly treated with platinum+docetaxel-based CT regimens. Platinum/docetaxel-based neoadjuvant CT provided high rates of pCR and excellent OS for women with locally advanced TNBC. No significant financial relationships to disclose. | v2 |
2019-05-04T13:05:49.373Z | 2015-01-01T00:00:00.000Z | 143538470 | s2ag/train | A Rough Road Map to Reflexivity in Qualitative Research into Emotions
In qualitative research into emotions, researchers and participants share emotion-laden interactions. Few demonstrate how the analytic value of emotions may be harnessed. In this article we provide an account of our emotional experiences conducting research with two groups: adults living with cystic fibrosis and spouse caregivers of cancer patients. We describe our emotion work during research interviews, and discuss its methodological and theoretical implications. Reflections depict competing emotion norms in qualitative research. Experiences of vulnerability and involuntary “emotional callusing” illustrate the insight into participants’ experiences afforded to us through emotion work. This prompted us to extend Hochschild’s theory to incorporate unconscious activity mediated through habitus, allowing us to demonstrate how the “emotional” nature of emotions research can galvanize analytic insight. | v2 |
2021-08-03T00:04:16.886Z | 2021-01-01T00:00:00.000Z | 236763870 | s2ag/train | Regional nodal irradiation in the setting of sentinel node biopsy
: The need for axillary lymph node dissection (ALND) in patients with invasive breast cancer (IBC) has been a topic of great debate in the last decade. The role of axillary management in patients with sentinel lymph node biopsy (SLNB) negative or micrometastatic disease is well established after multiple trials demonstrated no survival benefit with the addition of ALND (NSABP B32, IBCSG 23-01, AATRM048); yet, there remains controversy in the management of SLNB positive disease. ALND has traditionally been the standard of care following positive SLNB, however, results from recent studies have identified that further surgical exploration of the axilla may be overtreatment in these patients. In order to de-escalate treatment, non-surgical options such as regional nodal irradiation (RNI) and neoadjuvant chemotherapy (NAC) have been increasingly explored. Trials evaluating the role of RNI following positive SLNB have suggested that RNI is non-inferior to ALND and provides superior outcomes with an improved toxicity profile (AMAROS, MA.20, EORTC 22922). NAC has been explored in the treatment paradigm in patients with locally advanced disease, however, the role of SLNB and RNI in this setting remains unequivocal. This review aims to provide an update on the role of RNI following SLNB in IBC using an evidence-based approach. Ongoing clinical trials will clarify the role of axillary management after NAC in cN1 patients. In the Alliance A011202 trial, the role of ALND versus axillary nodal irradiation is addressed. Patients with clinical T1–3, N1 breast cancer treated with NAC and subsequent positive SLNB are randomized to receive ALND or axillary nodal irradiation along with radiotherapy to the whole breast or chest wall. Both groups will receive radiotherapy to the supraclavicular fossa. Patients in the ALND arm will receive radiotherapy to the undissected axilla. The target accrual is 1,660 patients and the primary study endpoint is invasive breast cancer recurrence-free interval (IBC-RFI) (NCT01901094). The NSABP B-51/RTOG 1304 trial is investigating the role of RNI in the same patient population who achieve pCR at ALND following NAC. Patients who present with clinical T1–3 tumors and N1 disease who achieve pCR post NAC are randomized to receive axillary RNI versus no further axillary treatment. Patients who receive RNI will also receive radiation to the whole breast or chest wall. The target accrual is 1,636 patients with the primary study endpoint of IBC-RFI (NCT01872975). | v2 |
2019-04-03T13:10:56.223Z | 2018-09-01T00:00:00.000Z | 92438310 | s2ag/train | Abstract B28: Targeted inhibition of EGFR and glutaminase induces metabolic crisis in EGFR-mutant lung cancer
Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors. Tumor cells undergo metabolic crisis and cell death, resulting in rapid tumor regression in vivo in mouse NSCLC xenografts. Consistently, positron emission tomography (PET) imaging with 18F-fluoro-2-deoxyglucose (18F-FDG) and 11C-glutamine (11C-Gln) of xenografts indicated reduced glucose and glutamine uptake in tumors following treatment with CB-839 + erlotinib. Therefore, PET imaging with 18F-FDG and 11C-Gln tracers can be used to noninvasively measure metabolic response to CB-839 and erlotinib combination therapy. Citation Format: Milica Momcilovic, Sean T. Bailey, Jason T. Lee, Clara Magyar, Daniel Braas, Thomas Graeber, Francesco Parlati, Susan Demo, Konstyantyn Krysan, Tonya C. Walser, Steven M. Dubinett, Saman Sadeghi, Heather R. Christofk, David B. Shackelford. Targeted inhibition of EGFR and glutaminase induces metabolic crisis in EGFR-mutant lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B28. | v2 |
2018-04-03T00:10:48.817Z | 2009-10-01T00:00:00.000Z | 205966310 | s2ag/train | Discussion. Free flap breast reconstruction in advanced age: is it safe?
T average life expectancy of the U.S. population continues to increase and with it there is a corresponding increase in the incidence of disease directly correlated with increasing age, such as prostate cancer in males and breast cancer in females. Statistics reveal that by age 80 a woman has a 1 chance in 9 of developing breast cancer.1 The treatment for a substantial number of these women includes mastectomy, and many of them will request breast reconstruction, including procedures performed with the transfer of autologous tissue. For patients requesting breast reconstruction with their own tissue, the microsurgical transfer of abdominal wall tissue constitutes the most popular option for such transfers. The safety corresponding to and the associated medical morbidity of these procedures as a function of age are reported by Drs. Selber and Serletti and their colleagues in the foregoing article. The study is a retrospective analysis derived from a prospectively maintained database spanning more than 15 years of the senior author’s (J.M.S.) practice. The patients were analyzed for important medical comorbidities, including body mass index and smoking status, and recognized risk factors, such as the presence of cardiac disease and other systemic problems known to be associated with the development of medical complications. Several important points are made by the authors from the analysis of their experience. The authors correctly state that a refinement in such elective free flap transfers that involve only the body surface has in fact occurred, and they appropriately differentiate these elective procedures from nonelective operations performed in patients with a higher level of preexisting medical comorbidity, such as patients with head and neck cancer and especially patients with peripheral vascular surgery whose treatments may entail microsurgical reconstructive procedures and who have a higher incidence of coexisting medical problems. Next the authors emphasize the importance of preoperative patient optimization, most significantly including a careful medical evaluation of the cardiopulmonary system. They make the point that patients with any significant history of cardiac disease must be carefully evaluated before surgery by a cardiologist, who is the best medical specialist to evaluate and define preoperative cardiac risk2 and to optimally manage or “fine tune” the patient for surgery. They also state that they exclude patients from microvascular breast reconstruction who are deemed to be at too high a risk, instead offering these patients implant breast reconstruction. The authors comment on the expanded role of the anesthesia service in the preoperative assessment of patients, outlining their use of formal preoperative anesthesia consults in selected patients. This is an increasingly common and important practice in most large medical centers, including my own at the University of Pittsburgh. In addition, the authors emphasize the importance of precisely controlling blood pressure during surgery and outline their protocol for doing so specifically with reference to their use of vasopressors. I continue to believe that the American Society of Anesthesiologists classification assigned to the patient by the anesthesiology service is a very valuable predictor of postoperative morbidity following all types of surgery. The presence of a systemic disease (i.e., breast cancer) automatically raises the patient to an American Society of Anesthesiologists 2 status. Therefore, I am somewhat puzzled that the authors list the mean American Society of Anesthesiologists classification scores as 1.9 and 2.1. In my analysis of the effect of age on predicting medical morbidity following free microvascular flap reconstructive procedures, I found a positive correlation between both advanced age and preoperative American Society of Anesthesiologists status on the incidence of medical complications,3 but the anesthesiology classification was a more accurate predictor of postoperative medical complications than age. This was the same conclusion | v2 |
2018-04-03T02:31:29.442Z | 1985-05-01T00:00:00.000Z | 34052010 | s2ag/train | Role of Computed Tomography and Mediastinoscopy in Preoperative Staging of Lung Carcinoma
One hundred fifty-three patients with bronchogenic carcinoma were evaluated prospectively by CT and mediastinoscopy. Nodes larger than 5 mm were considered potentially metastatic. All results were correlated with surgical findings. Computed tomography is more sensitive (89%) in the detection of mediastinal metastases than mediastinoscopy (67%). Computed tomography has a poor predictive value (47%): however, a negative examination is highly accurate (89%). Within a group of 100 node sites, 72% of the nodes involved by tumor were larger than 1 cm in diameter. Squamous cell carcinoma and adenocarcinoma have the highest percentages of sensitivity by CT. The very low incidence of metastatic involvement in nodes under 5 mm allows one to forego mediastinoscopy in the presence of a negative CT. | v2 |
2018-04-03T02:47:23.051Z | 2006-11-01T00:00:00.000Z | 24598170 | s2ag/train | Clinical value of planar and tomographic dual-isotope scintigraphy using 99mTc-methylene diphosphonate and 131I in patients with thyroid cancer
Purpose131I whole-body scintigraphy is a highly sensitive method for the detection of differentiated thyroid tumours and metastases. However, a lack of anatomical landmarks and the physiological excretion of the tracer complicates the evaluation of the images. Therefore, we determined whether additional bone scintigraphy in combination with 131I scintigraphy, simultaneously acquired via planar and tomographic techniques, positively contributes to the treatment plan in patients with non-conclusive 131I images. MethodsTwenty-one patients with differentiated thyroid cancer and known metastases or unclear findings in the 131I whole-body scan underwent dual-isotope scintigraphy (DIS) within 2–7 days after application of 5000–8000 MBq 131I. Dual-energy planar and tomographic data were acquired simultaneously and the results compared with other imaging modalities. ResultsIn 48% of the cases (10 of 21), DIS supplied important additional information that either altered the treatment plan or staging of the patients. In 28% (six of 21), DIS provided new information that was not known before, but did not change the staging of the patients. In five cases (24%), DIS did not add any new data regarding the extent of the disease. ConclusionsThe simultaneous acquisition of 131I and 99mTc-methylene diphosphonate provides clear landmarks and facilitates the localization of functioning metastases from differentiated thyroid cancer as well as improves the fusion with morphological images. It can be performed easily and also transferred to other isotope combinations. | v2 |
2019-01-22T22:20:13.082Z | 2018-12-01T00:00:00.000Z | 58584170 | s2ag/train | A fluid future for liquid biopsies
O ncologists have dreamed of them for years: noninvasive alternatives to tissue biopsies that can quickly identify tumors by the cells, DNA, or other cell components that they shed into patients’ blood. Now, several promising studies and a wave of prototypes suggest that such tests may be within reach. These new approaches to liquid biopsies, led by methods for detecting circulating tumor DNA, have been generating considerable excitement because of their potential to provide easier, less painful options for early detection; more tailored therapies; and better monitoring and prediction of cancer recurrence in lieu of more expensive imaging scans. That excitement, though, comes with a big caveat. For all the encouraging data from the flood of new panels, several experts agree that most of the tests must significantly improve their performance before they are ready for prime time. “This is the future, but we are not there yet,” says Gonzalo Torga, MD, a postdoctoral research fellow at the Brady Urological Institute at Johns Hopkins School of Medicine in Baltimore, Maryland. One liquid biopsy in development, called CancerSEEK, uses circulating proteins and DNA mutations to detect 8 distinct types of cancer. In a recent study in Science, the blood test correctly identified the disease in approximately 70% of 1005 patients who had already been diagnosed with a stage I, II, or III cancer.1 If it pans out, the test could offer advanced warning for multiple tumors— liver, pancreatic, esophageal, ovarian, and stomach—that currently lack screening tests. Still, although it demonstrated a specificity of more than 99%, CancerSEEK’s sensitivity varied widely, from a high of 98% for ovarian cancer to a low of 33% for breast cancer. Based in Menlo Park, California, GRAIL, a spinoff of sequencing titan Illumina, is trying to develop its own version of a liquid biopsy for early cancer detection. In June 2018, the company reported that combined results from several of its sequencing-based methods rivaled those of CancerSEEK: it correctly diagnosed ovarian, liver, pancreatic, and gallbladder cancer more than 80% of the time, but it was less than 25% accurate in detecting breast cancer. In March 2018, the American Society of Clinical Oncology and the College of American Pathologists released a joint review of 77 articles describing liquid biopsy tests for solid tumors based on circulating tumor DNA analysis.2 Despite the tests’ potential, the expert panel concluded that the majority yielded “insufficient evidence of clinical validity and utility” for advanced cancers and even less evidence for early-stage cancers, treatment monitoring, or detection of residual disease. | v2 |
2018-04-03T00:43:22.365Z | 1983-07-01T00:00:00.000Z | 26339710 | s2ag/train | Neonatal jaundice and developmental defects
trauma, and are rarely associated with biliary malignancy. The most common type is the cholecystoduodenal fistula, and this accounted for 76% of cases in the Mayo Clinic study of 424 patients with fistulae.I Cholangitis is frequently found with the cholecystocolic type.':' Cholecystocolicfistulae are best treated by one-stage closure of the fistula combined with cholecystectomy. The common bile duct will frequently need exploration and drainage due to associated biliary sludge or calculi. G. J. Bates, A. R. Askew, Department of Surgery, University of Queensland, Royal Brisbane Hospital, Herston, Qld. 4029. | v2 |
2018-04-03T01:44:51.575Z | 2012-06-20T00:00:00.000Z | 30806710 | s2ag/train | Pathology and prognosis in pseudomyxoma peritonei: a review of 274 cases
Aims The classification of abdominal mucinous neoplasia is a controversial area. In 2010, WHO published a classification which divides pseudomyxoma peritonei (PMP) into low and high grades. The aim of the authors was to correlate this classification with the prognosis and site of primary neoplasm. Methods The authors reviewed 274 patients with PMP who had undergone surgery at a single institution and classified them according to WHO criteria. The findings were correlated with clinical information and survival data. Results PMP was low grade in 78% of patients and high grade in 22%. The appendix accounted for 94% of lesions, and the most common primary tumour was a low grade appendiceal mucinous neoplasm. Colorectal primaries were more likely to be associated with high grade PMP. There was an excellent correlation between the grade of the PMP and the primary neoplasm; only two cases showed discordant morphology: both were high grade appendiceal adenocarcinomas that were associated with low grade PMP. Nodal metastases were more likely in high grade lesions, but there was no significant difference in the rate of parenchymal organ invasion between low grade and high grade. Low grade morphology was associated with significantly longer survival than high grade (overall 5-year survival of 63% for low grade and 23% for high grade). Conclusions Categorisation as either low grade or high grade by WHO criteria correlates with prognosis. The grade of the PMP is generally consistent with the grade of the primary neoplasm. Colorectal primaries are more likely to be associated with high grade PMP. | v2 |
2022-08-11T06:16:08.814Z | 2022-08-09T00:00:00.000Z | 251469920 | s2ag/train | Physical Activity in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).
PURPOSE
To determine the specific types, durations, and intensities of recreational physical activity associated with the greatest improvements in disease-free survival (DFS) of patients with colon cancer.
METHODS
We conducted a prospective cohort study nested within a randomized multicenter trial of stage III colon cancer that compared 3 versus 6 months of fluorouracil, leucovorin, and oxaliplatin with or without celecoxib. We measured recreational physical activity in the first 3 months of chemotherapy and again 6 months after completion of chemotherapy. The primary end point was DFS.
RESULTS
During a median follow-up of 5.9 years, 457 of 1,696 patients experienced disease recurrence or death. For total recreational physical activity volume, the 3-year DFS was 76.5% with < 3.0 metabolic equivalent task hours per week (MET-h/wk) and 87.1% with ≥ 18.0 MET-h/wk (risk difference [RD], 10.6%; 95% CI, 4.7 to 19.4; P < .001). For light-intensity to moderate-intensity activities, the 3-year DFS was 65.7% with 0.0 h/wk and 87.1% with ≥ 1.5 h/wk (RD, 21.4%; 95% CI, 9.2 to 37.1; P < .001). For vigorous-intensity activity, the 3-year DFS was 76.0% with 0.0 h/wk and 86.0% with ≥ 1.0 h/wk (RD, 10.0%; 95% CI, 4.5 to 18.9; P < .001). For brisk walking, the 3-year DFS was 81.7% with < 1.0 h/wk and 88.4% with ≥ 3.0 h/wk (RD, 6.7%; 95% CI, 3.0 to 13.8; P < .001). For muscle strengthening activity, the 3-year DFS was 81.8% with 0.0 h/wk and 88.8% for ≥ 0.5 h/wk (RD, 7.0%; 95% CI, 3.1 to 14.2; P = .003).
CONCLUSION
Among patients with stage III colon cancer enrolled in a trial of postoperative treatment, larger volumes of recreational physical activity, longer durations of light- to moderate-intensity aerobic physical activity, or any vigorous-intensity aerobic physical activity were associated with the greatest improvements in DFS. | v2 |
2019-11-15T14:09:26.988Z | 2019-11-13T00:00:00.000Z | 208017820 | s2ag/train | Expression and Clinical Significance of POLR1D in Colorectal Cancer
Purpose: RNA polymerase I subunit D (POLR1D) is involved in the synthesis of ribosomal RNA precursors and small RNAs, but its mechanism in the development and progression of colorectal cancer (CRC) remains ambiguous. Thus, this research aimed to investigate POLR1D’s expression and significance in human CRC patients and evaluate its association with clinicopathological characteristics. Methods: Matched fresh-frozen cancerous and non-cancerous tissues were collected from 100 patients diagnosed with CRC. Immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction analyses were adopted to validate the correlation between POLR1D expression and clinicopathological parameters in CRC tissues and adjacent normal tissues (ANTs). Results: POLR1D expression in CRC tissues was significantly higher than in the ANTs. χ2 test and Spearman’s correlative analysis showed that a high POLR1D expression is significantly associated with clinical stage, Dukes stage, tumor differentiation, depth of invasion, and metastasis (p < 0.05). It is not correlated with gender, age, and tumor location and size (p > 0.05). Kaplan-Meier survival curves show that the overall survival (OS) time for the low expression group is remarkably longer than for the high expression group (p < 0.0015). Univariate and multivariate analyses indicate that a high POLR1D expression is an independent prognostic factor for poor OS (p = 0.000). Conclusion: The findings of this study strongly indicate that POLR1D plays a pivotal role in the occurrence and progression of CRC. It might be an independent adverse prognostic factor for CRC patients and could serve as a potential therapeutic target for clinical diagnosis in CRC and anticancer drug development. | v2 |
2018-04-03T00:31:46.739Z | 2009-02-12T00:00:00.000Z | 12709710 | s2ag/train | Addressing bone loss in the cancer survivor.
Osteoporosis, the most common late effect of cancer treatment in the US, occurs with greater frequency among cancer survivors than the general population. Survivors of breast cancer, prostate cancer, and childhood leukemia are at particularly high risk for changes in bone mineral density (BMD) / osteoporosis that can lead to fractures.[1] In breast and prostate cancer patients, bone effects are often the result of endocrine therapy–induced alterations in bone microarchitecture. They also can be caused by other types of cancer therapy, vitamin D deficiency, and other physiological changes that may or may not be related to cancer or its treatment. In childhood leukemia patients, bone effects can be caused by a variety of factors, including corticosteroid therapy, radiation therapy to the brain, and the disease itself. | v2 |
2018-04-03T02:35:12.270Z | 2002-02-01T00:00:00.000Z | 25563400 | s2ag/train | [Possibilities of magnetic resonance tomography in pancreatic cancer diagnosis].
There was conducted examination of 27 patients with pancreatic cancer using clinico-laboratory and instrumental methods: ultrasonic investigation, computeric tomography (CT), magnetic-resonance tomography (MRT). MRT was uninformative when pancreatic tumor was up to 3 cm in diameter. In diagnosis of cystadenocarcinoma, affection of common biliary duct and vessels and in small focal metastatic hepatic affection the results of MRT showed enhanced precision in comparison with CT. Informativity of MRT and CT in diagnosis of metastases in lymph nodes was equal. | v2 |
2018-04-03T01:56:36.829Z | 2002-06-01T00:00:00.000Z | 26088960 | s2ag/train | In vivo induction of proinflammatory cytokines in mouse tissue by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans.
Periodontitis is a chronic inflammatory disease initiated by a multitude of bacteria. Persistent infection leads to generation of various inflammatory mediators, resulting in tissue destruction and osteoclastic resorption of the alveolar bone. This study describes a novel in vivo murine calvarial model to assess the effects of oral pathogens on the expression of three proinflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha] which are involved in bone resorption. We chose Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans as prototype oral pathogens. We also tested the effects of Streptococcus gordonii, an oral commensal supragingival microorganism, considered a non-pathogen. Live bacteria were injected into subcutaneous tissue overlying the parietal bone of mice calvaria for 6 days. At the end of the experimental period, tissues overlying the calvaria were removed and analyzed for proinflammatory cytokine expression by Northern blotting. Cytokine mRNA was not detected in the tissue over the calvaria of control animals. In contrast, P. gingivalis and A. actinomycetemcomitans elicited mRNA expression of all three cytokines, TNFalpha being the highest (TNFalpha > > IL-1beta > IL-6). P. gingivalis was more potent than A. actinomycetemcomitans in inducing cytokine expression. In contrast, S. gordonii induced only low levels of mRNA for IL-1beta and TNFalpha but no IL-6 mRNA induction. These results suggest that oral microorganisms with access to host tissues elicit a battery of proinflammatory cytokines. There were clear differences in profiles and, interestingly, a commensal bacterium also stimulated bone resorptive cytokine expression in host tissues. | v2 |
2018-04-03T01:34:43.486Z | 2003-01-01T00:00:00.000Z | 29895260 | s2ag/train | Cure of Barrett's carcinoma by ifosfamide chemotherapy.
The prognosis of patients with oesophageal cancer is poor, with an overall 5-year survival rate below 15%. The best chance for cure of patients with oesophageal cancer is surgical resection. However, more than 50% of patients have inoperable disease and can only be palliated for dysphagia. Some of these patients participate in studies investigating the activity of single-agent or combination chemotherapy. We report a patient who was cured of metastatic adenocarcinoma in Barrett’s oesophagus by six courses of ifosfamide, a chemotherapeutic agent with little or no activity in other patients with adenocarcinoma of the oesophagus or gastro-oesophageal junction. After a follow-up of 13 years and 7 months, no evidence of tumour recurrence was found, while biopsies from the Barrett’s oesophagus revealed only low-grade dysplasia. This case obviously raises the question as to how patients with inoperable oesophageal carcinoma can sometimes be cured by chemotherapy alone. Eur J Gastroenterol Hepatol 14:1261–1264 & 2002 Lippincott Williams & Wilkins | v2 |
2018-04-03T04:47:13.923Z | 1988-08-01T00:00:00.000Z | 40319210 | s2ag/train | Recurrent rectal cancer: diagnosis with MR imaging versus CT.
During an 18-month period, a prospective study comparing the findings at computed tomography (CT) and magnetic resonance (MR) imaging was conducted on 35 patients who satisfied the following criteria: prior surgery for rectal cancer (11 curative resections, 24 rectal amputations), perineal pain and/or elevated carcinoembryonic antigen (CEA) level, and a soft-tissue mass in the presacral fossa demonstrated at CT. Twenty-two patients had tumor recurrence; 13 patients had only inflammatory changes or radiation fibrosis. At a single examination of each patient (with no reference to prior baseline studies), MR imaging was more accurate than CT, largely because MR imaging was more successful in the distinction of recurrence from fibrosis based on the differences in signal intensity on T2-weighted images. | v2 |
2017-04-14T09:59:22.712Z | 1987-08-15T00:00:00.000Z | 9206310 | s2ag/train | Characterization of cell lines derived from xenografts of childhood rhabdomyosarcoma.
Three human rhabdomyosarcoma cell lines (Rh10, Rh18, and Rh28) have been established from three independently derived xenografts. These lines have been characterized as mesenchymal in origin (reactivity to desmin and vimentin antibodies) and as expressing a human fetal muscle surface antigen recognized by monoclonal antibody 5.1 H11. Measurable levels of creatine phosphokinase have been detected in the cell lines. Rh10 and Rh28 exhibit the same chromosomal translocation and express an atypical lactate dehydrogenase isoenzyme which may be homologous to those previously reported in other tumor types. The karyotype analysis has confirmed that each cell line was derived from its respective tumor and thus provides a unique model for future investigations. | v2 |
2016-10-26T03:31:20.546Z | 2011-10-03T00:00:00.000Z | 27085150 | s2ag/train | Insight into the heterogeneity of breast cancer through next-generation sequencing.
Rapid and sophisticated improvements in molecular analysis have allowed us to sequence whole human genomes as well as cancer genomes, and the findings suggest that we may be approaching the ability to individualize the diagnosis and treatment of cancer. This paradigmatic shift in approach will require clinicians and researchers to overcome several challenges including the huge spectrum of tumor types within a given cancer, as well as the cell-to-cell variations observed within tumors. This review discusses how next-generation sequencing of breast cancer genomes already reveals insight into tumor heterogeneity and how it can contribute to future breast cancer classification and management. | v2 |
2018-04-03T05:02:42.769Z | 1990-06-01T00:00:00.000Z | 41326950 | s2ag/train | [Immunoglobulin and T-cell receptor gene rearrangements in patients with autoimmune diseases].
Immunoglobulin-(Ig-) and T-cell-receptor-(TcR-)gene rearrangements were investigated in peripheral blood lymphocytes (PBL) of patients with various autoimmune disorders. In patients with SLE there was no predominant Ig- or TcR-gene rearrangement. This was also true in patients with a long disease duration and with excessive hypergammaglobulinemia. These results lead us to suggest that B cells are activated polyclonally in these patients. In those cases, where predominantly rearranged Ig- or TcR-genes were found, the autoimmune disorder was associated with a low-grade non-Hodgkin lymphoma (NHL). This coherence of B-cell malignancy and autoimmunity was only found in patients with cryoglobulinemia (KG), cold agglutinin disease (KA), and hemolytic anemia (AIHA). | v2 |
2018-04-03T03:54:01.301Z | 1997-04-01T00:00:00.000Z | 36908850 | s2ag/train | Endoscopic ultrasound-guided real-time fine-needle aspiration biopsy of the pancreas in cancer patients with pancreatic lesions.
BACKGROUND
Endoscopic ultrasound (EUS) is an important new tool in the staging of pancreatic malignancies. Using new curved linear-array instruments, real-time fine-needle aspiration biopsy (RTFNA) of pancreatic lesions can be performed.
METHODS
Forty-five patients with pancreatic lesions (22 males and 23 females) underwent staging with the Olympus EUM-20 (Olympus America Corp, Melville, NY) followed by EUS-RTFNA with the Pentax FG-32PUA (Pentax-Precision Instrument Corp, Orangeburg, NY) and the 22-gauge GIP needle (GIP Medizin Technik, Grassau, Germany).
RESULTS
EUS tumor stages were as follows: TO, n = 1; T1, n = 8; T2, n = 9; and T3 n = 27. Aspiration attempts were unsuccessful in four patients (two technical failures and two inadequate specimens). The remaining 41 lesions (mean size, 3.3 cm) were aspirated under EUS guidance (median passes, three) and the cytologic diagnoses were 25 definite adenocarcinoma, five suspicious for adenocarcinoma (three subsequently confirmed and two clinical course consistent with adenocarcinoma), and 11 negative for malignancy. Of 11 negatives, two were found to have adenocarcinoma, seven were confirmed benign at surgery (four cystadenomas and three inflammatory), one had a benign pseudocyst, and one had abundant inflammatory cells on RTFNA and follow-up time greater than 12 months with computed tomographic (CT) scans consistent with resolving inflammation. There were no false-positive RTFNAs. There were no procedure-related complications. Among those with diagnostic EUS-RTFNA (91%), the sensitivity for malignancy (confirmed plus suspicious) was 94% and negative predictive value 82%.
CONCLUSION
EUS-guided RTFNA is a safe and accurate method for performing pancreatic biopsy. It should be considered in patients with suspected pancreatic malignancies in whom a tissue diagnosis is required or when other modalities have failed. EUS-RTFNA allows for local staging and tissue diagnosis in one procedure. | v2 |
2017-11-08T00:50:00.635Z | 1999-10-01T00:00:00.000Z | 27411000 | s2ag/train | A Lot of Heartburn, a Little Cancer
ABSTRACTThis is a well-designed, population-based, case-control, epidemiological study to determine if individuals with symptoms of gastroesophageal reflux disease are at increased risk for the development of adenocarcinoma of the esophagus and gastric cardia. Over a 3-yr period, from 1994 to 1997, all newly diagnosed cases of adenocarcinoma of the esophagus and gastric cardia in Sweden were identified via a comprehensive countrywide network of contact individuals soon after diagnosis and before surgery. Cases were matched for age and sex with case controls. Of 618 eligible patients with adenocarcinoma of the esophagus or gastric cardia, 451 (85%) participated. At index esophagogas-troduodenoscopy, biopsies were obtained at 2-cm intervals beginning at the cardia and extending proximally until normal squamous epithelium was reached. In addition, biopsies were taken of the tumor and surrounding tissue. A total of 424 of the patients underwent surgery, and 97% of biopsy and surgical specimens were reviewed by a single pathologist. All subjects and controls underwent an extensive interview where questions (range 161–553) were asked concerning the frequency, severity, and duration of heartburn symptoms as well as other potential confounding factors.The results of this study indicate that persons who experience symptoms of heartburn and regurgitation at least once a week are nearly 8 times (odds ratio = 7.7) more likely to develop esophageal adenocarcinoma than those without these symptoms. Furthermore, the risk was found to be “dose dependent” where those who had the most severe reflux symptoms were associated with the highest risk. Persons with particularly long-standing and frequent heartburn symptoms were found to be 43 times more likely to develop esophageal adenocarcinoma than asymptomatic individuals. The authors emphasized that the heartburn-cancer association was independent of the presence of Barrett's esophagus. They based this statement on the fact that only 62% of those with esophageal adenocarcinoma had Barrett's tissue detected. Also of note, the risk of esophageal adenocarcinoma was 3 times higher among those who had used medications for symptomatic reflux compared to those who had not taken medications even after adjusting both groups for severity of symptoms. Reflux symptoms were also associated with a higher risk of adenocarcinoma of the gastric cardia though not nearly as strongly (odds ratio 2.0). As expected, squamous cell cancer was not associated with reflux symptoms (odds ratio 0.9). (Am J Gastroenterol 1999; 94:3061–3062. © 1999 by Am. Coll. of Gastroenterology) | v2 |
2018-04-03T04:37:15.716Z | 1993-03-09T00:00:00.000Z | 39726050 | s2ag/train | [Compliance problems and behavioral medicine implications in the drug therapy of pain].
Many patients, even cancer patients do not take their medication at all or at the prescribed dose showing thus a form of noncompliance. Reasons for this are manyfold and differ from patient to patient. They may undergo dynamic changes in the course of disease. Experience shows, that compliance is mainly improved when patients have the impression to be responsible for their comportment. This is an important goal in therapy of patients with chronic pain. Of particular importance is therefore the doctor-patient relation, i.e. non-compliance thus always indicates a disturbed doctor-patient relation. | v2 |
2018-04-03T02:46:30.442Z | 2011-09-01T00:00:00.000Z | 21769310 | s2ag/train | Inhibition of cyclin-dependent kinase phosphorylation of FOXO1 and prostate cancer cell growth by a peptide derived from FOXO1.
Increasing evidence suggests that FOXO1 possesses a tumor suppressor function. Inactivation of FOXO1 has been documented in many types of human cancer, and restoring the activity of FOXO1 holds promise for cancer treatment. In this study, we identified a FOXO1-derived peptide termed FO1-6nls that inhibits cyclin-dependent kinases 1 and 2 (CDK1/2)-mediated phosphorylation of FOXO1 at the serine 249 residue in vitro and in vivo. Overexpression of FO1-6nls in prostate cancer (PCa) cells not only blocked CDK1-induced cytoplasmic localization of FOXO1 but also augmented FOXO1's transcriptional activity. This effect of FO1-6nls requires its binding to CDK1 and CDK2. Moreover, the ectopic expression of FO1-6nls inhibited the growth of PTEN-positive DU145 PCa cells. Importantly, the growth-inhibitory function of FO1-6nls is dependent on FOXO1. Finally, the ectopic expression of FO1-6nls overcame CDK1-mediated inhibition of FOXO1-induced apoptosis of PCa cells. These results indicate that the FOXO1-derived peptide FO1-6nls can restore FOXO1's tumor suppressor function by specifically opposing CDK1/2-mediated phosphorylation and inhibition of FOXO1 and hence may have a therapeutic potential for the treatment of PCa. | v2 |
2018-04-03T05:51:09.237Z | 2006-08-15T00:00:00.000Z | 44681260 | s2ag/train | Production of VEGF165 by Ewing's sarcoma cells induces vasculogenesis and the incorporation of CD34+ stem cells into the expanding tumor vasculature
The Ewing's sarcoma cell line TC71 overexpresses vascular endothelial growth factor isoform 165 (VEGF165), a potent proangiogenic molecule that induces endothelial cell proliferation, migration, and chemotaxis. CD34+ bone marrow stem cells can differentiate into endothelial and hematopoietic cells. We used a transplant model to determine whether CD34+ cells migrate from the bone marrow to Ewing's sarcoma tumors and participate in the neovascularization process that supports tumor growth. We also examined the role of VEGF165 in CD34+ cell migration. Human umbilical cord CD34+ cells were transplanted into sublethally irradiated severe combined immunodeficient mice. Seven days later, the mice were injected subcutaneously with TC71 tumor cells. Tumors were excised 2 weeks later and analyzed by immunohistochemistry. The tumor sections expressed both human VE‐cadherin and mouse CD31, indicating involvement of donor‐derived human cells in the tumor vessels. To determine the role of VEGF165 in the chemoattraction of CD34+ cells, we generated two VEGF165‐deficient TC71 clones, a stable anti‐sense VEGF165 cell line (Clone 17) and a VEGF165 siRNA‐inhibited clone (TC/siVEGF7‐1). The resulting VEGF165‐deficient tumor cells had normal growth rates in vitro, but had delayed growth when implanted into mice. Immunohistochemical analysis revealed decreased infiltration of CD34+ cells into both VEGF165‐deficient tumors. These data show that bone marrow stem cells contribute to the growing tumor vasculature in Ewing's sarcoma and that VEGF165 is critical for the migration of CD34+ cells from the bone marrow into the tumor. © 2006 Wiley‐Liss, Inc. | v2 |
2018-04-03T05:32:57.038Z | 2013-01-01T00:00:00.000Z | 43317560 | s2ag/train | Stratospheric ozone, global warming, and the principle of unintended consequences--an ongoing science and policy success story.
One of the important technical achievements to protect human health and wellbeing in the 20th century was the widespread development and application of refrigeration for food preservation and building and vehicle cooling using chlorofluorocarbon refrigerants. These compounds are nontoxic at low atmospheric concentrations and nonreactive in the lower atmosphere. In the mid-1970s, as an outgrowth of international concerns for the photochemistry of aircraft engine effluents emitted at high altitude, workers discovered that the coupling of the nitrogen oxide cycle and the halogen (chlorine) cycle could deplete the stratospheric ozone layer (Farman et al., 1985; Molina and Rowland, 1974; Rowland and Molina, 1975). The stratospheric ozone layer is important to human and ecosystem health because it protects the lower atmosphere from ultraviolet radiation that can cause skin cancer and vegetation damage (Slaper et al., 1998; Solomon, 2008). By the 1980s, stratospheric ozone depletion was observed directly (Norman, 1981) and the deterioration was increasing year by year (Anton et al., 2011; Stolarski et al., 1992). Later in the 1980s, halocarbons were identified as strong radiation absorbers in the solar spectrum—climate-forcing greenhouse gases analogous to carbon dioxide (MacCracken, 1987, 2008). This recognition added a second environmental risk of halocarbon accumulation in the atmosphere. Active scientific communication of the environmental issues associated with halocarbon emissions took place in the 1980s and resulted in a series of international regulatory agreements among stakeholders intended to reduce key halocarbon emissions across the world (Jain and Bach, 1994; Kuijpers, 1990, 1993). The nexus of science, technology, and government policy development to address the stratospheric ozone issue illustrates the chain from risk recognition to risk management through regulation of a series of pollutants. The development of international policy to manage halocarbon emissions culminated in the Montreal Protocol of 1987 (Benedick, 1991). The 2013 critical review (Anderson et al., 2013) tells the story of the science underlying the interaction of halogen chemistry with ozone under stratospheric conditions, then discusses the evolution of refrigerant manufacturing and use from their early 19th century beginnings to today’s use of halocarbons in many applications. The review documents the ongoing technological changes brought about by evolving regulation meant to protect the stratospheric ozone layer and mitigate undesired climate change. The review authors include Steven Anderson, a leader of U.S. regulatory policy for halocarbons, Marcel Halberstadt, prior director of the Motor Vehicle Manufacturers Association, and Nathan Borgford-Parnell, an expert on international environmental policy and its application to the refrigeration industry. Their comprehensive and thorough summary of the science, technology, and policy, as well as the industrial response to the issue, provides a unique perspective to this international environmental issue for Air & Waste Management Association (A&WMA) members and other readers of Journal of the Air & Waste Management Association. The lessons learned from the work underlying this public policy and collaborative technological response provide an important roadmap for international environmental risk management. A&WMAmembers and guests are invited to read, attend, and comment on the 43rd Annual Critical Review at A&WMA’s 106th Annual Conference & Exhibition to be held in Chicago, A. Gwen Eklund | v2 |
2017-06-10T20:58:05.576Z | 2005-01-01T00:00:00.000Z | 10730560 | s2ag/train | Expression of bone morphogenetic proteins in human metastatic prostate and breast cancer.
AIM
To analyze the expression of bone morphogenetic proteins (BMPs) in prostate and breast cancers with established metastasis in bone, where prostate cancer causes osteoblastic metastases, and breast cancer osteolytic metastases.
METHODS
Primary tumor specimens from 20 patients with prostate cancer and 15 with breast cancer were studied for BMP-2/4, -3, -5, -6 and -7 immunohistochemistry. All patients had multiple bone metastases proven by bone scan. We also examined BMPs expression in normal prostate and breast tissues. BMPs expression was compared with clinicopathological and biochemical parameters.
RESULTS
Cytoplasmic BMPs immunostaining was observed in both prostate cancer and normal prostate tissue. Expression of BMP-2/4, -5, -6, and -7 proteins was detected in all normal prostate samples, with the predominance of BMP-2/4 (87.8-/+11.4% positive cells) and BMP-7 (94.6-/+0.9% positive cells). In prostate cancer tissues, we found variable expression of all BMPs. BMP-2/4 (83-/+11.6% positive cells) was predominantly expressed in prostate carcinoma, whereas the expression of BMP-7 (24.3-/+19.2% positive cells) was significantly lower than in the normal prostate. In all breast cancers tissues, we found nuclear staining only for BMP-7. In normal breast tissue, the BMP expression was not detectable. The percent of BMP-7 positive cells in breast cancer (86.4-/+7.3%) was higher than in prostatic cancer. Comparing BMP expression levels and clinicopathological parameters, we did not find statistical difference, except for serum alkaline phosphatase, which was significantly higher in patients with prostate cancer.
CONCLUSION
The expression of BMPs differs between prostate and breast cancer cells. Identifying the BMP proteins in cancers may be useful for monitoring the tumor status with reference to metastases. | v2 |
2017-04-27T08:35:35.871Z | 2010-01-01T00:00:00.000Z | 133210 | s2ag/train | Cervical cancer screening programme in Primorsko-Goranska County, Croatia--the results of the pilot study.
The opportunistic cervical cancer screening has been conducted in Croatia since its introduction in the 1960s, in the context of a high quality gynaecological cytology with a long tradition and a wide network of primary care gynaecologists. In 2006, a pilot screening programme under the title "Early detection of cervical cancer was conducted in Primorsko-Goranska County (PGC)", as the first organised cervical cancer screening ever conducted in the Republic of Croatia. The pilot screening programme targeted women aged 20-64 years. The pilot group consisted of 6,000 randomly sampled primary care patients of six gynaecologists. The women were invited via a personal letter and were given a questionnaire. The results of the first and the second year of screening, as well as of both years together were analysed. The response rate to the anamnestic questionnaire was 49.1%. The participation rates to the screening were 35.2% in 2007, and 46.5% in 2008, total of 42.7%. The increase in participation between years 2007 and 2008 was statistically significant (p = 0.01). According to the age, the lowest participation rate of 33.3% was observed in the youngest group of women (20-29) and the highest of 60.7% in the oldest group (60-64). The detection rate of cytological abnormalities was 4.6% with 2.6% of borderline (ASCUS) cytology and referral rate of 1.2%. The highest abnormal Pap test frequencies of 6.8% and 7.1% were observed in the youngest age groups (20-29 and 30-39), and the lowest (2%) in the age group of 60-64. Specimen adequacy was generally of high quality with unsatisfactory rate of 0.8%, with statistically significant improvement in 2008, compared to the previous year (p = 0.001). Although to a limited extension, during two-year pilot cervical cancer screening programme in PGC the participation rates and Pap smear adequacy have improved. We expect that the continuation of the programme will result in further increase of participation and higher overall quality of the programme. | v2 |
2019-08-18T20:01:11.334Z | 2011-10-01T00:00:00.000Z | 202650910 | s2ag/train | Title Page / Table of Contents
s HORMONE RESEARCH IN PÆDIATRICS Basel • Freiburg • Paris • London • New York • New Delhi • Bangkok • Beijing • Tokyo • Kuala Lumpur • Singapore • Sydney HRP_2011_076_S02_tivo.indd I 01.07.2011 11:02:11 This publication was sponsored by Eli Lilly and Company Ferring Pharmaceuticals Ipsen Merck Serono S.A. Novo Nordisk A/S Pfizer Endocrine Care Sandoz International GmbH S. Karger Medical and Scientifi c Publishers Basel • Freiburg • Paris • London New York • Bangalore • Bangkok Shanghai • Singapore • Tokyo • Sydney Disclaimer Th e statements, options and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). Th e appearance of advertisements in the journal is not a warranty, endorsement, or approval of the products or services advertised or of their eff ectiveness, quality or safety. Th e publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Drug Dosage Th e authors and the publisher have exerted every eff ort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant fl ow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. Th is is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specifi ed fee to the Copyright Clearance Center (see ‘General Information’). © Copyright 2011 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland) ISBN 978–3–8055–9835–4 e–ISBN 978–3–8055–9836–1 Electronic production of the abstract book by pharma service – a business unit of documediaS GmbH Günther-Wagner-Allee 13, D–30177 Hannover (Germany) www.pharmaservice.de Printed by Lindendruck Verlagsgesellschaft mbH Fössestrasse 97A, D–30453 Hannover (Germany) www.lindendruck.de Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com HRP_2011_076_S02_tivo.indd II 01.07.2011 11:02:29 Page Abstract No. Date Plenary Lectures 1 PL1 Strengths and Limitations of Evidence-based Medicine 1-2 Sunday, September 25 1 PL2 Frontiers in Diabetes 3-4 Monday, September 26 PL3 ESPE Award Session & Activities 1 no abstracts Monday, September 26 2 PL4 ESPE Award Session & Activities 2 5-6 Tuesday, September 27 2 PL5 New Paradigms in Molecular Medicine 7 Tuesday, September 27 2 PL6 Food for Thought before Going Home 8-9 Wednesday, September 28 Symposia 4 S1 Evidence-based Medicine in Growth Assessment In memory of Professor James Tanner 10-12 Sunday, September 25 4 S2 Early Life Origins of Health and Disease 13-15 Sunday, September 25 5 S3 New Insights in Phosphate Metabolism 16-18 Sunday, September 25 5 S4 Principles of Evidence-based Medicine 19-21 Monday, September 26 6 S5 Long Term Safety of Drugs 22-24 Monday, September 26 7 S6 Unexpected Ef fects of Hormones on the Brain 25-27 Monday, September 26 7 S7 Evidence-based Medicine in Childhood and Adolescent Diabetes ISPAD/ESPE 28-30 Tuesday, September 27 8 S8 The Cortisol-Cortisone Shuttle in Health and Disease 31-33 Tuesday, September 27 8 S9 Impact of Chronic Conditions on Growth 34-36 Tuesday, September 27 9 S10 Evidence-based Medicine in Thyroid Diseases 37-39 Wednesday, September 28 9 S11 New Insights in the Pathogenesis of PCOS APPES/ESPE 40-42 Wednesday, September 28 10 S12 Update on Growth Hormone Long Term Safety 43-46 Wednesday, September 28 New Perspectives 12 NP1 New Perspectives in Brain Imaging 47-48 Monday, September 26 12 NP2 New Perspectives in Molecular Analysis 49-50 Tuesday, September 27 ESPE Working Groups 13 WG1 ESPE Bone and Growth Plate Working Group 51-58 Sunday, September 25 15 WG2 ESPE Disorder of Sex Development Working Group 59-66 Sunday, September 25 17 WG3 ESPE Obesity Working Group: Long and Short-term Consequences of Childhood Obesity 67-69 Sunday, September 25 17 WG4 ESPE Paediatric and Adolescent Gynaecology Working Group: Amenorrhea in Adolescence 70-75 Sunday, September 25 19 WG5 ESPE Turner Syndrome Working Group: Ovarian Failure in Turner Syndrome 76-80 Sunday, September 25 Free Communications 20 FC1 Adipose Tissue and Obesity 81-86 Monday, September 26 22 FC2 Adrenal 87-92 Monday, September 26 23 FC3 Pituitary 93-98 Monday, September 26 26 FC4 Bone and Mineral Metabolism 99-104 Tuesday, September 27 28 FC5 Growth Hormone 105-110 Tuesday, September 27 30 FC6 Sexual Development 111-116 Tuesday, September 27 32 FC7 Cell Growth and Endocrine Oncology 117-122 Tuesday, September 27 34 FC8 Diabetes and the Beta Cell 123-128 Tuesday, September 27 36 FC9 Reproductive System 129-134 Tuesday, September 27 38 FC10 The X Chromosome 135-140 Tuesday, September 27 40 FC11 Diabetes Complications 141-146 Wednesday, September 28 42 FC12 Growth/Acid Labile Subunit 147-152 Wednesday, September 28 44 FC13 Puberty 153-158 Wednesday, September 28 46 FC14 Thyroid 159-164 Wednesday, September 28 Poster Presentations 49 P1-d1 Adrenal and HPA Axis 1 165-176 Sunday, September 25 53 P1-d2 Adrenal and HPA Axis 2 177-186 Monday, September 26 56 P1-d3 Autoimmune Endocrine Disease/Endocrine Oncology 1 187-192 Tuesday, September 27 58 P1-d1 Bone, Growth Plate and Mineral Metabolism 1 193-201 Sunday, September 25 61 P1-d3 Bone, Growth Plate and Mineral Metabolism 2 202-210 Tuesday, September 27 | v2 |
2021-10-26T06:16:47.008Z | 2021-10-23T00:00:00.000Z | 239766710 | s2ag/train | Identification of lipid metabolism-related genes as prognostic indicators in papillary thyroid cancer.
Lipid metabolism plays important roles not only in the structural basis and energy supply of healthy cells but also in the oncogenesis and progression of cancers. In this study, we investigated the prognostic value of lipid metabolism-related genes in papillary thyroid cancer (PTC). The recurrence predictive gene signature was developed and internally and externally validated based on PTC datasets including The Cancer Genome Atlas (TCGA) and GSE33630 datasets. Univariate, LASSO, and multivariate Cox regression analysis were applied to assess prognostic genes and build the prognostic gene signature. The expression profiles of prognostic genes were further determined by immunohistochemistry of tissue microarray using in-house cohorts, which enrolled 97 patients. Kaplan-Meier curve, time-dependent receiver operating characteristic curve, nomogram, and decision curve analyses were used to assess the performance of the gene signature. We identified four recurrence-related genes, PDZK1IP1, TMC3, LRP2 and KCNJ13, and established a four-gene signature recurrence risk model. The expression profiles of the four genes in the TCGA and in-house cohort indicated that stage T1/T2 PTC and locally advanced PTC exhibit notable associations not only with clinicopathological parameters but also with recurrence. Calibration analysis plots indicate the excellent predictive performance of the prognostic nomogram constructed based on the gene signature. Single-sample gene set enrichment analysis showed that high-risk cases exhibit changes in several important tumorigenesis-related pathways, such as the intestinal immune network and the p53 and Hedgehog signaling pathways. Our results indicate that lipid metabolism-related gene profiling represents a potential marker for prognosis and treatment decisions for PTC patients. | v2 |
2018-04-03T00:10:57.317Z | 2011-11-23T00:00:00.000Z | 206678660 | s2ag/train | Rapid Cancer Detection by Topically Spraying a γ-Glutamyltranspeptidase–Activated Fluorescent Probe
A spirocyclic-caged, small-molecule imaging probe fluoresces upon cleavage by a cancer-specific enzyme and can be used during surgical or endoscopic tumor removal procedures. No Tumor Left Behind Although quick action with spray paint usually conjures images of a schoolboy prank, researchers now show that spray painting of tiny tumors might save lives by illuminating these troublemakers that are often overlooked by the naked eye. Ovarian cancer is a deadly gynecological disease, considering its propensity for invading the peritoneal cavity and depositing tumors throughout. Surgeons can miss these disseminated tumors during surgical removal of cancerous lesions, owing to their small size (~1 mm) and unclear borders. To help surgeons visualize and eliminate these clandestine killers, Urano et al. have developed a small-molecule aminopeptidase probe that fluoresces upon contact with cancer cells. The probe—γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG)—is intramolecularly caged, so that it is quenched (nonfluorescent) in its “off” state. When the probe encounters cancer cells, which overexpress the enzyme γ-glutamyltranspeptidase (GGT), the gGlu is cleaved, simultaneously turning “on” the fluorescent HMRG. Urano and colleagues first tested the probe in 11 human ovarian cancer cell lines in vitro and observed rapid fluorescence within 10 min after addition of the imaging agent to the cell cultures. They next moved into several mouse models of disseminated human peritoneal ovarian cancer, using a spray formulation of the probe that allowed the researchers to topically apply the probe during surgery or endoscopy. Within 1 min of spraying the tumors, gGlu-HMRG was enzymatically cleaved, revealing a bright fluorescent region of the peritoneal cavity in which the cancerous lesions were located. These small nodules were quickly and completely removed from living animals with forceps, demonstrating the power of rapid fluorescence-guided tumor resection. This gGlu-based fluorescent probe as well as several other aminopeptidase–based reagents identified by the authors could help surgeons to track down tiny tumors dispersed throughout body cavities, ensuring that no residual tumor is left behind. Complete obliteration of disseminated tumors should improve cancer outcomes after surgery. The ability of the unaided human eye to detect small cancer foci or accurate borders between cancer and normal tissue during surgery or endoscopy is limited. Fluorescent probes are useful for enhancing visualization of small tumors but are typically limited by either high background signal or the requirement for administration hours to days before use. We synthesized a rapidly activatable, cancer-selective fluorescence imaging probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), with intramolecular spirocyclic caging for complete quenching. Activation occurs by rapid one-step cleavage of glutamate with γ-glutamyltranspeptidase (GGT), which is not expressed in normal tissue, but is overexpressed on the cell membrane of various cancer cells, thus leading to complete uncaging and dequenching of the fluorescence probe. In vitro activation of gGlu-HMRG was evident in 11 human ovarian cancer cell lines tested. In vivo in mouse models of disseminated human peritoneal ovarian cancer, activation of gGlu-HMRG occurred within 1 min of topically spraying the tumor, creating high signal contrast between the tumor and the background. The gGlu-HMRG probe is practical for clinical application during surgical or endoscopic procedures because of its rapid and strong activation upon contact with GGT on the surface of cancer cells. | v2 |
2017-10-18T11:55:08.051Z | 2016-10-25T00:00:00.000Z | 9551960 | s2ag/train | Curcumin as Natural Bioactive compound of Medicinal Plant Curcuma longa to combat against different Diseases
Plants are gifts by nature as they gives alot of benefits to human race. Medicinal herb Curcuma longa has a long history of use in medicine due to its anti-inflammatory, antioxidant, analgesic, antimicrobial and against cancer progression. Turmeric contain two classes of secondary metabolites, Curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and turmeric essential oils (TEO). Curcumin is an active constituent of it and is highly pleriopiotic molecule. It works as antimicrobial agent against different strains of fungus, bacteria and viruses by targeting their membrane efficiency and can active against various types of cancers by targeting molecular markers. This compound also shows drastic effects against various diseases like rheumatoid arthritis, neurodegenerative diseases and can also prevent selenium and ionizing radiations induced cataractogenesis. Bioavailability, stability and solubility power of curcumin is increasing as research expands by modifying it by functional groups or in combinational therapeutics. These effects are mediated through its regulation of various transcription factors, modulates mitochondrial functions, growth factors, inflammatory cytokines, protein kinases and other enzymes. Spoilage of food is also minimized by design of a papain that is immobilized in food packaging with curcumin is crosslinked and act as antimicrobial. Curcumin as natural medicinal compound is a novel targeted agent of modern era as it shows beneficial effects in different health perspectives without giving comparatively any side effects. Research reveals that it also has capability to target stem cells, restores immune system and activate self-renewal pathways. This component is easily available, safe and target different diseases at molecular level to eradicate it. | v2 |
2018-04-03T02:42:55.142Z | 2013-05-01T00:00:00.000Z | 25567860 | s2ag/train | [Comparison of antiemesis effects of granisetron, aprepitant and dexamethasone to palonosetron, aprepitant and dexamethasone in treatment of high-emetic risk chemotherapy-induced nausea and vomiting - a retrospective study for efficacy and safety in a single institute].
Nausea and vomiting are among the most problematic symptoms experienced by patients with cancer who are receiving chemotherapy. 5-hydroxytryptamine 3(5-HT3)-receptor antagonists, NK1 receptor antagonists(aprepitant)and dexamethasone are now the standard therapies for preventing chemotherapy-induced nausea and vomiting(CINV)that follow highly emetogenic chemotherapy, such as cisplatin and anthracycline. However, since it is not cleared which 5-HT3-recepter antagonist is a proper treatment for combined use with aprepitant and dexamethasone, we conducted a questionnaire survey, which used the numerical rating scale(NRS), for comparing palonosetron with granisetron in the same patient. Palonosetron showed a significant improvement of nausea for both acute(within 24 hours)and delayed phase(24-120 hours later), regardless of the type of chemotherapy(cisplatin or anthracycline-based regimen). Furthermore, palonosetron had a tolerable safety profile. Our study suggests that palonosetron-based antiemetic treatment will be a preferred choice for preventing CINV following highly emetogenic chemotherapy. | v2 |
2017-04-07T16:57:07.468Z | 2014-02-01T00:00:00.000Z | 16169410 | s2ag/train | Novel EXT1 mutation identified in a pedigree with hereditary multiple exostoses.
Hereditary multiple exostoses (HME) is an autosomal dominant bone disorder characterized by the presence of multiple benign cartilage-capped tumors. EXT1 located on chromosome 8q23-q24 and EXT2 located on 11p11-p12 are the main disease-causing genes which are responsible for ~90% of HME cases. Mutations of EXT1 or EXT2 result in insufficient heparan sulfate biosynthesis, which facilitates chondrocyte proliferation, boosts abnormal bone growth of neighboring regions, causes multiple exostoses, and ultimately leads to possible malignant transformation. A family who displayed typical features of HME was enrolled in the present study. Mutation screening by Sanger sequencing identified a novel heterozygous nonsense mutation c.1902C>A (p.Tyr634X) in the EXT1 gene exclusively in all 3 patients, which is located in the glycosyltransferase domain and results in the truncation of 112 amino acids at the C-terminus of the EXT1 protein. Thus, the present study identified a novel disease-causing EXT1 mutation in a pedigree with HME, which provides additional evidence for developing quick and accurate genetic tools for HME diagnosis. | v2 |
2018-04-03T06:17:59.042Z | 2012-09-01T00:00:00.000Z | 23482660 | s2ag/train | The development of IL‐17/IFN‐γ‐double producing CTLs from Tc17 cells is driven by epigenetic suppression of Socs3 gene promoter
The plasticity of T lymphocytes induced by epigenetic modifications of gene promoters may play a pivotal role in controlling their effector functions, which are sometimes causally associated with immune disorders. IL ‐17‐producing T cells, which induce type 17 immune responses, are newly identified pathogenic effector cells. The type 1 signature cytokine IFN‐γ strongly inhibits their differentiation, indicating a mutually exclusive relationship between type 17‐ and type 1‐immune responses. However, many reports indicate the presence of a unique IL‐17/IFN‐γ‐double producing T‐cell subset in various inflammatory settings, although the mechanisms responsible for their development and their precise functions remain unclear. Here, we demonstrate that IL‐12 permits the conversion of mouse IL‐17‐producing CD8+ T (Tc17) cells to IL‐17/IFN‐γ‐double producing CD8+ T (Tc17/IFN‐γ) cells, and that this conversion is due to repressive epigenetic modifications of Socs3 gene promoters. Moreover, we show that SOCS3 strongly regulates the capability of Tc17 cells to produce IL‐17, in addition to regulating the expression of the type 17‐master regulator RORγt. These findings elucidate the mechanisms underlying the conversion of Tc17 cells into Tc17/IFN‐γ cells. As these cells are known to have potent antitumor activities, manipulation of these conversion mechanisms for therapeutic tumor immunity may be possible. | v2 |
2021-04-18T05:25:02.920Z | 2020-12-01T00:00:00.000Z | 233285450 | s2ag/train | The Evidence Supporting a Systematic Approach to the Care of the Injured Patient:From Prevention to Rehabilitation
INTRODUCTION Trauma is the leading cause of death for individuals under 45 years of age in the Western world and remains the fourth leading cause of death for all ages combined (1,2,3,4). Approximately 0.9 million people worldwide die secondarily to injury (8% of all deaths) (5). It is also a major cause of morbidity in both the short and long-term (6). Furthermore, injury is a leading cause of disability, potential years of life lost and a major contributor to overall health care costs (7,8,9). It is estimated that injury causes 36 life-years lost per death compared to 16 life-years for cancer and 12 years for heart disease and stroke combined (10). In 1994, 8,687 people died following accidents in Canada (1). Approximately four times as many patients suffer severe disability related to accidents each year. The cost of acute medical care for injured patients is in excess of $16 billion per annum (11). This represents the second largest source of medical expenditures in the United States. In addition to the health dollars spent on the acute care of injured patients, an additional $150 billion US are required to cover the annual cost due to death, disability, and lost wages and taxes (9). From a health-economic perspective, the cost of trauma and its consequences makes the elucidation of evidence-based practices paramount. Trauma care systems have been shown to significantly decrease medical care costs. It is estimated that by extending trauma care systems throughout the entire United States, annual medical care payments could be lowered by $3.2 billion (12). If productivity costs due to premature death are taken into account, the total savings could total $10.3 billion. | v2 |
2019-10-19T13:34:38.808Z | 2019-10-18T00:00:00.000Z | 204772200 | s2ag/train | Multidimensional imaging provides evidence for down-regulation of T cell effector function by MDSC in human cancer tissue
Intratumoral physical engagement of T cells with immunosuppressive neutrophils is associated with reduced effector function. Interior tumor views Previous studies indicate that a high frequency of intratumoral neutrophils is associated with a poor clinical prognosis. Si et al. used a variety of microscopy and imaging techniques to examine how intratumoral interactions between tumor-associated neutrophils (TANs) and tumor-infiltrating lymphocytes (TILs) can affect TIL function. They developed 2D and 3D multiparameter immunofluorescence imaging techniques to localize and define functional cell subsets, which were used to identify hotspots of TAN/TIL interactions within tumors. Some of these TANs had a polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) phenotype, and their physical association with TILs reduced antitumor functions of those TILs. This study identifies areas of MDSC activity in human tumors and provides a more detailed perspective of how intratumoral cell interactions influence cell function. A high intratumoral frequency of neutrophils is associated with poor clinical outcome in most cancer entities. It is hypothesized that immunosuppressive MDSC (myeloid-derived suppressor cell) activity of neutrophils against tumor-reactive T cells contributes to this effect. However, direct evidence for such activity in situ is lacking. Here, we used whole-mount labeling and clearing, three-dimensional (3D) light sheet microscopy and digital image reconstruction supplemented by 2D multiparameter immunofluorescence, for in situ analyses of potential MDSC–T cell interactions in primary human head and neck cancer tissue. We could identify intratumoral hotspots of high polymorphonuclear (PMN)–MDSC and T cell colocalization. In these areas, the expression of effector molecules Granzyme B and Ki67 in T cells was strongly reduced, in particular for T cells that were in close proximity or physically engaged with PMN-MDSC, which expressed LOX-1 and arginase I. Patients with cancer with evidence for strong down-regulation of T cell function by PMN-MDSC had significantly impaired survival. In summary, our approach identifies areas of clinically relevant functional interaction between MDSC and T cells in human cancer tissue and may help to inform patient selection in future combination immunotherapies. | v2 |
2017-04-19T07:38:41.397Z | 2015-01-01T00:00:00.000Z | 16031000 | s2ag/train | Comparison of outcomes of locoregionally advanced oropharyngeal and non-oropharyngeal squamous cell carcinoma over two decades.
BACKGROUND
Human papillomavirus (HPV) has emerged as a causative agent and positive prognostic factor for oropharyngeal (OP) head and neck squamous cell cancer (HNSCC). This prompts inquiry into whether therapy improvements or increasing incidence of HPV drives the apparent improvements in HNSCC outcomes observed in non-randomized clinical trials.
PATIENTS AND METHODS
We reviewed all locoregionally advanced HNSCC patients treated with chemotherapy and radiation in prospective institutional trials at a single institution. Patients were divided into three groups (1, 2, 3) according to treatment time period (1993-1998, 1999-2003, 2004-2010, respectively). We reasoned that if a favorable trend was observed over time in OP but not non-OP patients, HPV status may be confounding treatment effects, whereas this would be unlikely if both subgroups improved over time.
RESULTS
Four hundred and twenty-two patients were identified with OP (55.7%) and non-OP (44.3%) HNSCC. Five-year OP overall survival (OS) improved from 42.3% (group 1) to 72.5% (group 2), and 78.4% (group 3), adjusted P = 0.0084. Non-OP 5-year OS was 51.0% (group 1), 58.8% (group 2), and 66.3% (group 3), adjusted P = 0.51. Five-year recurrence-free survival (RFS) improved for OP groups from 42.3% to 68.4% to 75.8% (adjusted P = 0.017). Non-OP 5-year RFS was 42.9%, 53.6%, and 61.7% for sequential groups (adjusted P = 0.30). Five-year OP distant failure-free survival (DFFS) improved from 42.3% to 71.1% to 77.8% (adjusted P = 0.011). Five-year non-OP DFFS was 46.9%, 57.1%, and 66.0% for sequential groups (adjusted P = 0.38).
CONCLUSIONS
Over the past two decades, OP HNSCC outcomes improved significantly, while non-OP outcomes only trended toward improvement. Although our patients are not stratified by HPV status, improving OP outcomes are likely at least partly due to the increasing HPV incidence. These data further justify trial stratification by HPV status, investigations of novel approaches for carcinogen-related HNSCC, and current de-intensification for HPV-related HNSCC. | v2 |
2018-04-03T05:16:29.650Z | 2005-01-01T00:00:00.000Z | 42067700 | s2ag/train | Tumor necrosis factor-alpha-induced protein 1 and immunity to hepatitis B virus.
AIM
To compare the gene expression profile in a pair of HBV-infected twins.
METHODS
The gene expression profile was compared in a pair of HBV-infected twins.
RESULTS
The twins displayed different disease outcomes. One acquired natural immunity against HBV, whereas the other became a chronic HBV carrier. Eighty-eight and forty-six genes were found to be up- or down-regulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-alphaIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RT-PCR. However, upon HBV core antigen stimulation, TNF-alphaIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+ channel tetramerization domain in TNF-alphaIP1 that shares a significant homology with some human, mouse, and C elegan proteins.
CONCLUSION
TNF-alphaIP1 may play a role in the innate immunity against HBV. | v2 |
2017-09-26T14:58:42.200Z | 1998-01-01T00:00:00.000Z | 11252500 | s2ag/train | Considerations in making a diagnosis
Dipl. ABVP a continuing challenge for clinicians. Comparative Medical and Vetennary Services Los Angeles County Department of Health Services Clinical epidemiology, biostatistics, Downey, California 90242 and clinical decision-making are “new” tools that help practitioners make diagnoses.’ Biostatistics and epidemiology allow large amounts of raw data to be analyzed into useful information. As an example, for years we have known that dogs have more mammary tumors than cats. horses. or cattle, and that mammary tumors were common in females, although males also have mammary tissue. We have learned that the rate of mammary tumors in dogs is more than twice that in people. and this tumor type accounts for about 40% of canine tumors. Analysis of a large number of cases has also revealed certain risk factors for mammary tumors. As a result of analyzing large numbers of canine mammary tumors, we now know female dogs spayed before one year of age are less likely to develop mammary tumors. Epidemiology is often considered a new science, but many of the concepts are not new. More than 100 years ago, a physician named William Farr became the first Registrar-General in the General Register Office of England. where he worked for more than 40 years.” In his A n n u a l Reports. Far-r described death rates and noted healthy and unhealthy districts of England. His publication of Vital Statistics in 1885 described the concepts of incidence, prevalence, and the value of retrospective and prospective approaches to studying disease. which are fundamental to epidemiology today. Two-hundred years before Farr, English parish registers published annual breakdowns of death by cause, particularly during plague epidemics: these were the basis for the earliest vital statistics. When making a diagnosis, it is not possible to obtain all clinical information on every patient, nor is it desirable. Practitioners must be selective when confronting a mass of data, which varies in value from the highly significant to the trivial. Understanding epidemiologic concepts helps in selecting probable causes for the presenting complaint and determining whether laboratory tests are indicated. In making clinical decisions. clinicians go through two processes at the same time. While examining the individual patient, they simultaneously generalize their previous training and experience. The generalizing of experience is part of epidemiology. The most important part of making a diagnosis is thinking. In determining the cause of disease, diag- | v2 |
2017-08-15T05:12:53.345Z | 1996-06-01T00:00:00.000Z | 24629900 | s2ag/train | Human osteoclast-like cells selectively recognize laminin isoforms, an event that induces migration and activates Ca2+ mediated signals.
Osteoclast precursors are chemotactically attracted to sites of bone resorption via migration pathways that include transendothelial crossing in blood capillaries. Transendothelial migration involves poorly understood interactions with basal lamina molecules, including laminins. To investigate osteoclast-laminin interactions, we used human osteoclast-like cell lines obtained from giant cell tumors of bone (GCT 23 and GCT 24). These cell lines are a well-characterized model for osteoclast functions, such as bone resorption and the behaviour of osteoclast precursors. Both GCT cell lines adhered to laminin-2 (merosin) coated wells in standard adhesion assays, but failed to adhere to laminin-1 (EHS-laminin). By light microscopy, GCT cells on laminin-2 were partially spread, with a motile morphology. None of the anti-integrin antibodies tested inhibited GCT cells adhesion to laminin-2. Peptides containing the integrin adhesion site RGD or the laminin adhesion sequence IKVAV did not inhibit GCT cell adhesion to laminin-2. By immunofluorescence, beta 1 integrins were organized in focal adhesions. However, in the presence of monensin this reorganization of beta 1 integrins was abolished, indicating that it was probably due to secretion of fibronectin by GCT cells subsequent to adhesion to laminin-2. GCT cells transmigrated through membranes coated with laminin-2, much more efficiently than through membranes coated with collagen. Migration was induced by osteocalcin, as a chemoattractant, in a dose-dependent manner. At low osteocalcin concentrations, transmigration was detectable on laminin-2 but not collagen. In cells loaded with fura-2, a sharp increase in intracellular Ca2+ was detected upon addition of soluble laminin-2, but not laminin-1, due to release from thapsigargin-dependent intracellular stores. In summary, osteoclasts may recognize laminin isoforms differentially. Initial adhesion to laminin-2 appears to be due to integrin-independent mechanisms. Such adhesion, though, may trigger secretion of fibronectin that could then support spreading and efficient chemotactic migration. These mechanisms may play an important role in facilitating chemotactic migration of osteoclast precursors toward the bone surface. | v2 |
2018-04-03T00:11:50.776Z | 2016-03-01T00:00:00.000Z | 10501900 | s2ag/train | Yeast-Derived Particulate β-Glucan Treatment Subverts the Suppression of Myeloid-Derived Suppressor Cells (MDSC) by Inducing Polymorphonuclear MDSC Apoptosis and Monocytic MDSC Differentiation to APC in Cancer
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we demonstrated that activation of a C-type lectin receptor, dectin-1, in MDSC differentially modulates the function of different MDSC subsets. Yeast-derived whole β-glucan particles (WGP; a ligand to engage and activate dectin-1, oral treatment in vivo) significantly decreased tumor weight and splenomegaly in tumor-bearing mice with reduced accumulation of polymorphonuclear MDSC but not monocytic MDSC (M-MDSC), and decreased polymorphonuclear MDSC suppression in vitro through the induction of respiratory burst and apoptosis. On a different axis, WGP-treated M-MDSC differentiated into F4/80+CD11c+ cells in vitro that served as potent APC to induce Ag-specific CD4+ and CD8+ T cell responses in a dectin-1–dependent manner. Additionally, Erk1/2 phosphorylation was required for the acquisition of APC properties in M-MDSC. Moreover, WGP-treated M-MDSC differentiated into CD11c+ cells in vivo with high MHC class II expression and induced decreased tumor burden when inoculated s.c. with Lewis lung carcinoma cells. This effect was dependent on the dectin-1 receptor. Strikingly, patients with non–small cell lung carcinoma that had received WGP treatment for 10–14 d prior to any other treatment had a decreased frequency of CD14−HLA-DR−CD11b+CD33+ MDSC in the peripheral blood. Overall, these data indicate that WGP may be a potent immune modulator of MDSC suppressive function and differentiation in cancer. | v2 |
2021-05-05T00:09:38.864Z | 2021-03-11T00:00:00.000Z | 233712500 | s2ag/train | Salvage Lymphadenectomy as a Treatment of Prostate Cancer Recurrence
Biochemical recurrence (BCR) occurs up to 40% of men who had radical prostatectomy for localized prostate cancer. Regional nodes are usually involved in these cases. Salvage lymphadenectomy (sLND) has been advocated in patients with 'node-only' metastasis with biochemical recurrence, following a definitive treatment of primary prostate cancer. In general, limited case number was reported for each previous study. Four relatively larger reports so far with the highest case number of 189. One randomized controlled study has been completed so far at Phase II level. Salvage LND seems to be safe with relatively low incidence of complications without perioperative mortality. It may postpone adjuvant therapy in selected cases, avoiding systemic side effects and possibly reducing the cost. However, long-term outcome is not very encouraging. © 2021 Guohua Zeng. Hosting by Science Repository. All rights reserved | v2 |
2018-04-03T01:33:43.113Z | 1998-05-01T00:00:00.000Z | 21761460 | s2ag/train | Renal tubular reabsorption of phosphate is positively related to the extent of bone metastatic load in patients with prostate cancer.
Osteolytic metastases are often associated with decreased renal tubular reabsorption of phosphate. There is, however, no specific data on phosphate metabolism in metastases from prostatic cancer, which are generally osteoblastic. The aim of the present study was to investigate renal handling of inorganic phosphate (Pi) in prostatic cancer, in patients without or with skeletal metastases of various extents. Forty-eight patients were the subjects of this study. There were 39 with malignant disease, of whom 27 had bony metastases. Nine other patients had benign prostate hyperplasia. Biochemical indexes of prostatic tumor, renal tubular reabsorption of calcium and Pi, biochemical markers of bone remodeling, and relevant calciotropic hormones were measured and analyzed in relation to the extent of skeletal metastases, as assessed by bone scintigraphy. A higher bone metastatic load was associated with significantly greater prostate-specific antigen and prostatic acid phosphatase levels (P < 0.05), increased levels of biochemical markers of bone formation (P < 0.05) and resorption (P < 0.001), higher maximal renal tubular reabsorption of Pi (TmPi/GFR; P < 0.05), and higher urinary cAMP excretion (P < 0.05). Nine patients among those with bone metastases (n = 27) had higher TmPi/GFR than metastasis-free patients. These had a greater value of osteocalcin (P < 0.001). Also, 8 of these had relatively more extensive skeletal metastatic load. In patients with prostatic cancer, high skeletal metastatic load was accompanied by increased TmPi/GFR despite higher urinary cAMP excretion, which is supposed to reduce the TmPi/GFR. These results support the hypothesis that renal tubular reabsorption of Pi is capable of adaptation to meet demands for minerals in the face of enhanced bone formation. | v2 |
2018-04-03T02:13:11.077Z | 1989-01-01T00:00:00.000Z | 20716810 | s2ag/train | [Increased expression of IGF-2 in tumor tissue of nephroblastoma].
The incidence of nephroblastoma is increased in a number of syndromes with abnormal growth pattern. Elevated IGF 2-expression has been documented in various Wilms' tumors and a defect in the IGF 2 gene has been noted in 1 case. Southern blot analysis of genomic DNA of nephroblastomas in 5 additional patients after restriction enzyme digest with EcoRI, Pvu II, Pst I and Taq I did not reveal any defect in the IGF 2 gene. Slot blot analysis however showed marked overexpression of IGF 2-mRNA reaching up to more than 25 times the level expressed in unaffected kidney tissue adjacent to the tumor and in normal kidney tissue used as controls. | v2 |
2018-04-03T00:59:39.082Z | 2013-12-04T00:00:00.000Z | 27487860 | s2ag/train | Effects of exercise dose and type during breast cancer chemotherapy: multicenter randomized trial.
BACKGROUND
Exercise improves physical functioning and symptom management during breast cancer chemotherapy, but the effects of different doses and types of exercise are unknown.
METHODS
A multicenter trial in Canada randomized 301 breast cancer patients to thrice-weekly supervised exercise during chemotherapy consisting of either a standard dose of 25 to 30 minutes of aerobic exercise (STAN; n = 96), a higher dose of 50 to 60 minutes of aerobic exercise (HIGH; n = 101), or a combined dose of 50 to 60 minutes of aerobic and resistance exercise (COMB; n = 104). The primary endpoint was physical functioning assessed by the Medical Outcomes Survey-Short Form (SF)-36. Secondary endpoints were other physical functioning scales, symptoms, fitness, and chemotherapy completion. All statistical tests were linear mixed model analyses, and the P values were two-sided.
RESULTS
Follow-up assessment of patient-reported outcomes was 99.0%. Adjusted linear mixed-model analyses showed that neither HIGH (+0.8; 95% confidence interval [CI] = -0.8 to 2.4; P = .30) nor COMB (+0.5; 95% CI = -1.1 to 2.1; P = .52] were superior to STAN for the primary outcome. In secondary analyses not adjusted for multiple comparisons, HIGH was superior to STAN for the SF-36 physical component summary (P = .04), SF-36 bodily pain (P = .02), and endocrine symptoms (P = .02). COMB was superior to STAN for endocrine symptoms (P = .009) and superior to STAN (P < .001) and HIGH (P < .001) for muscular strength. HIGH was superior to COMB for the SF-36 bodily pain (P = .04) and aerobic fitness (P = .03). No differences emerged for body composition or chemotherapy completion.
CONCLUSIONS
A higher volume of aerobic or combined exercise is achievable and safe during breast cancer chemotherapy and may manage declines in physical functioning and worsening symptoms better than standard volumes. | v2 |
2018-04-03T06:13:46.494Z | 2009-11-01T00:00:00.000Z | 46125910 | s2ag/train | [Prognostic value of FDG-PET in Hodgkin lymphoma for posttreatment evaluation. Long-term follow-up results].
UNLABELLED
In the past few decades Hodgkin lymphoma (HL) has become a highly curable malignant disease, as a result of using modern polychemotherapy and irradiation. Differentiation of active tumor from fibrosis or necrosis within residual radiographic masses represents a problem of interpretation.
AIMS
The aim of this retrospective study is to assess the value of FDG-PET for prediction of remission or relapse in HL.
PATIENTS AND METHODS
Data of 128 patients, who had residual masses on CT after completion of their planned treatment, have been analyzed. FDG-PET was performed between January 1995 and February 2005.
RESULTS
The median duration of the follow-up from PET was 75.5 months (range: 20-180 months). 89 (70%) patients had negative and 39 (30%) patients had positive FDG-PET results. The numbers of true-positive, true-negative, false-positive and false-negative subjects were 29, 83, 10 and 6, respectively. Sensitivity of post-treatment FDG-PET was 83%, specificity 93%, positive predictive value 74%, negative predictive value 93%, and accuracy 88%. The difference between the event free survival of PET positive and negative cases is highly significant (p = 0.0000), according to the Mantel-Cox test.
CONCLUSION
Our results, in accordance with literature, clearly indicate that patients with negative FDG-PET results are unlikely to progress or relapse during a long follow-up. However, false positive uptake is a problem. We have investigated the effect of age, histological subtype, clinical stage and the type of treatment on the accuracy, but on the basis of these facts we could not find any significant difference. However, the date of the investigation influenced the results: before 2000 the number of false results was significantly higher than after that time, which shows the importance of investigators' experience. | v2 |
2017-08-03T00:18:05.031Z | 2007-01-01T00:00:00.000Z | 8207360 | s2ag/train | Colorectal cancer screening disparities related to obesity and gender
BACKGROUND: Obesity is associated with a higher incidence of colorectal cancer and increased colorectal cancer mortality. Obese women are less likely to undergo breast and cervical cancer screening than nonobese women. It is not known whether obesity is associated with a lower likelihood of colorectal cancer screening. OBJECTIVE: To evaluate whether there is an association between body mass index (BMI) and rates of colorectal cancer screening. To examine whether BMI-related disparities in colorectal cancer screening differ between men and women. DESIGN AND SETTING: The Behavioral Risk Factor Surveillance System, a cross-sectional random-digit telephone survey of noninstitutionalized adults conducted by the Centers for Disease Control and Prevention and state health departments in the 50 states and Washington, DC in 1999. PATIENTS: Survey respondents (N=52,886) between 51 and 80 years of age representing 64,563,332 U.S. adults eligible for colorectal cancer screening. INTERVENTIONS AND MEASURMENTS: Adjusted rates of self-reported colorectal cancer screening with fecal occult blood testing within the past year or endoscopic screening (sigmoidoscopy or colonoscopy) within the past 5 years. RESULTS: The colorectal cancer screening rate was 43.8% overall. The rate of screening by FOBT within the last year or endoscopic screening within the past 5 years was 39.5% for the morbidly obese group, 45.0% for the obese group, 44.3% for the overweight group, and 43.5% for the normal weight group. The difference in screening rates was entirely attributable to differences in BMI among women. After statistical adjustment for potential confounders, morbidly obese women were less likely than normal weight women to be screened (adjusted rate difference, −5.6%; 95% confidence interval, −8.5 to −2.6). Screening rates among normal weight, overweight, and obese women, and among men in different weight groups did not differ significantly. CONCLUSIONS: Colorectal cancer screening rates among age-eligible persons in the U.S. are disturbingly low. Morbidly obese women, who are at higher risk than others to develop and to die from colorectal cancer, are less likely to be screened. Efforts to increase colorectal cancer screening are needed for all age-eligible groups, but should also include targeted screening of morbidly obese women since they could reap substantial clinical benefits from screening. | v2 |
2018-01-24T17:25:33.048Z | 2013-11-01T00:00:00.000Z | 7551760 | s2ag/train | Patient-oncologist cost communication, financial distress, and medication adherence.
2 Background: Little is known about the association between patient-oncologist discussion of cancer treatment out-of-pocket (OOP) cost and medication adherence, a critical component of quality cancer care.
METHODS
We conducted a cross-sectional survey of insured adults receiving anti-cancer therapy. Patients were asked if they had discussed OOP cost with their oncologist. Medication non-adherence was defined as skipping doses to make prescriptions last longer, taking less medication than prescribed to make prescriptions last longer, or not filling prescriptions due to cost. Multivariable analysis assessed the association between cost discussions with an oncologist and non-adherence.
RESULTS
Among 300 respondents (84% response), 77% (n=230) were white and 53% (n=158) were men. 17% (n=52) reported "high" or "overwhelming" financial distress. 19% (n=56) had talked to their oncologist about cost. 27% (n=81) reported medication non-adherence. 14% (n=43) skipped medication doses to make the prescription last longer; 7% (n=3) of these had skipped chemotherapy. 11% (n=34) took less medication than prescribed to make the prescription last longer; 15% (n=5) of these took less chemotherapy. 22% (n=67) did not fill a prescription because of cost; 15% (n=10) of these did not fill a chemotherapy prescription. In adjusted analyses, cost discussion (OR 2.56, 95% CI 1.15-5.68; p=0.02), financial distress (OR 1.57, 95% CI 1.33-1.85, P<0.001) and female gender (OR 2.02, 95% CI 1.005-4.07, p=0.048) were associated with increased odds of non-adherence. Private insurance was associated with lower odds of non-adherence (OR 0.30, 95% CI 0.14-0.60, p<0.001).
CONCLUSIONS
Patients reported non-adherence to medications and chemotherapy in order to make prescriptions last longer or due to cost. While these data cannot determine temporality or the affect of cost discussion on medication non-adherence, patient-oncologist cost communication and financial distress were associated with non-adherence. Future research should examine the timing, content, and quality of cost-related discussions. | v2 |
2018-04-03T00:32:11.896Z | 2016-08-01T00:00:00.000Z | 207141110 | s2ag/train | Role of protein S in castration-resistant prostate cancer-like cells.
Understanding how castration-resistant prostate cancer (CRPC) cells survive the androgen-deprivation condition is crucial for treatment of this advanced prostate cancer (PCa). Here, we reported for the first time the up-regulation of protein S (PROS), an anticoagulant plasma glycoprotein with multiple biological functions, in androgen-insensitive PCa cells and in experimentally induced castration-resistant PCa cells. Overexpression of exogenous PROS in LNCaP cells reduced androgen deprivation-induced apoptosis and enhanced anchorage-dependent clonogenic ability under androgen deprivation condition. Reciprocally, PROS1 knockdown inhibited cell invasiveness and migration, caused the growth inhibition of castration-resistant tumor xenograft under androgen-depleted conditions, and potentiated Taxol (a widely prescribed anti-neoplastic agent)-mediated cell death in PC3 cells. Furthermore, PROS overexpression significantly stimulated AKT activation but failed to evoke oxidative stress in LNCaP cells under normal condition, suggesting that the malignance-promoting effects of the above-mentioned pathway may occur in the order of oxidative stress/PROS/AKT. The potential mechanism may be due to control of oxidative stress-elicited activation of PI3K-AKT-mTOR pathway. Taken together, our gain-of-function, loss-of-function analyses suggest that PROS may facilitate cell proliferation and promote castration resistance in human castration-resistant PCa-like cells via its apoptosis-regulating property. Future study emphasizing on delineating how PROS regulate cellular processes controlling transformation during the development of castration resistance should open new doors for the development of novel therapeutic targets for CRPC. | v2 |
2021-05-10T00:04:02.707Z | 2021-02-01T00:00:00.000Z | 234058610 | s2ag/train | Improving the growth and productivity of faba bean (Vicia faba L.) under deficit irrigation conditions by spraying of potassium selenate and potassium silicate
Water stress is one of the vitally essential environmental stresses that directly affect agricultural production, particularly in arid and semi-arid regions that are considered to be a consequence of worldwide of climate change and decreased water availability for crop production (Carrizo et al., 2020 and Rafie & El-Boraie, 2017). Many of the physiological processes within a plant are negatively affected by drought stress i.e., photosynthesis, cell division, nutrient uptake, damage of plant cell membrane and cell wall, however, a homogenous root system may enhance the plant's ability to grow during droughts (Taiz and Zeiger, 2006). Mitigating the negative effects of drought stress has become very necessary to maintains water balance within the plant, which can be achieved through plant nutrition, especially with the nutrient that is related to osmotic regulation, thus enhancing drought tolerance (Yaseen et al., 2020). Clinical research has shown that about forty forms of human health dangerous illnesses, including, cancer, liver disease, cardiovascular disease and so on, are associated with a deficiency of selenium in the human body (Vinceti et al., 2018). Selenium has antioxidant properties that humans and animals require (FairweatherTait et al., 2011). Therefore, there is an urgent need to overcome the status of human selenium deficiency by increasing the selenium content in A FIELD experiment was elaborated for two seasons (2018/2019 and 2019/2020) under a drip irrigation system in the experimental farm of Department of Soils and Water, Faculty of Agriculture, Al-Azhar University, Cairo, Egypt to investigate the impact of three levels of applied irrigation water: I 1 =100, I 2 =80 and I 3 =60% of irrigation water requirements (IR) and foliar application of potassium selenate (K 2 SeO 4 : 0.3 and 0.6 mM) and potassium silicate (K 2 SiO 3 : 5 and 10 mM) on the growth, yield and quality of faba bean (Vicia faba L., cv Sakha 3) and also the water use efficiency. The results indicated that increasing the applied irrigation water amount from 2219.75 (I 3 ) to 3698.77 m ha (I1) gave the highest mean values of plant height, number of branches (NB), dry seeds weight, the weight of 100 dry seeds and dry seed yield as well as P and K content in seeds. On the contrary, the highest mean values of water use efficiency (WUE), protein and nitrogen (N) content in seeds occurred with 60% of IR for both seasons. Moreover, foliar spraying with potassium silicate at 10 mM led to a highly significant increase of all the studied parameters followed by foliar spraying with potassium selenate at 0.6 mM compared to the untreated plant's treatment. Consequently, it is recommended to grow faba bean plants (Sakha 3) by applying 80% of IR (2958.02 m ha) and foliar spraying with 10 mM potassium silicate and saving 20% of the amount of irrigation water for other uses in agriculture. | v2 |
2019-03-30T13:06:33.733Z | 2003-09-01T00:00:00.000Z | 85989800 | s2ag/train | Book Review: Ocular Tumors of Humans and Animals
As anyone familiar with the fields of veterinary ophthalmology and veterinary ophthalmic pathology can attest, there is a need for textbooks integrating these two disciplines that are fairly comprehensive, yet concise enough to be read and mastered in a relatively short time. In particular, there is a desperate need for reference books with high-quality illustrations for those of us involved in the diagnosis and treatment of ocular neoplasia. In this book, Ocular Tumors of Animals and Humans, Drs. Peiffer and Simons attempt to meet that need, and I believe they have succeeded. In my opinion, this book serves as a guide both to the pathologist interested in ocular histopathology and to the ophthalmologist submitting ocular specimens. This book not only provides excellent illustrations for the pathologist but also offers clinical, diagnostic, and prognostic information. Also invaluable is the information pertaining to the differences between human and animal counterparts. The book has 14 chapters written by acknowledged experts in the appropriate fields. Of these, eight are devoted to neoplasia of specific ocular structures, three to unique ocular neoplastic conditions, two to the basic science of metastasis and ocular immune responses to neoplasia, and one to experimental ocular oncology. All chapters are fairly well organized, concise, clear, and well referenced. Overall, the quality of the images is excellent. Surprisingly, a small number of photomicrographs appear to be of a less distinct quality. In the final analysis, Ocular Tumors in Humans and Animals is a comprehensive reference of ocular neoplasia in humans and animals, yet will appeal to those involved in vision science and carcinogenesis research. I recommend it for ophthalmology residents as a study guide for board examination preparation. I also endorse it as a succinct review and teaching resource for ophthalmic and general pathologists and ophthalmologists with a particular interest in ophthalmic pathology. | v2 |
2018-04-03T00:44:17.254Z | 2008-09-01T00:00:00.000Z | 22917800 | s2ag/train | [Mohs paste for unresectable local lesion of breast cancer].
A 45-year-old woman with a local recurrence on her left chest wall discharged massive exudates. At every gauze exchange, blood was still oozing out. After using Mohs paste twice, the surface had been fixed chemically and dried up, so she did not have to exchange gauze, and there was no more bleeding. A 55-year-old woman was suffering massive exudates and offensive smell from her right primary breast cancer that formed a massive bulge with a deep ulcer in the center. Because her serum hemoglobin declined to 4.4 g/mL due to continuous bleeding, she needed to undergo blood transfusion. After using Mohs paste twice, the bleeding stopped almost completely. Now she uses Mohs paste by herself at home at her convenience. A 69 year-old woman suffered from an offensive odor and continuous bleeding from a local recurrence in the skin of her abdomen. A single use of Mohs paste relieved her from bleeding and the smell. Three patients had experienced no adverse events except mild pain and their QOL improved considerably. Mohs paste is in the hope of improving the QOL for the breast cancer patients with local advanced, unresectable skin lesions. | v2 |
2018-04-03T00:25:55.453Z | 2017-01-01T00:00:00.000Z | 4150200 | s2ag/train | Successful resection of asymptomatic paraganglioma mimicking lymph node metastasis from gastric cancer 5 years after distal gastrectomy:a case report.
A 61-year-old man visited our hospital for treatment of a retroperitoneal tumor. The patient had undergone distal gastrectomy for gastric cancer in the past. At 5 years after distal gastrectomy, a retroperitoneal tumor with a large diameter of 30mm was detected by computed tomography and the patient underwent chemotherapy for suspected lymph node metastasis from gastric cancer at a local hospital. However, the retroperitoneal tumor gradually increased, and it was diagnosed finally as asymptomatic paraganglioma. The patient underwent tumor resection and made a satisfactory recovery. He was discharged 11 days after the surgery in a good general condition. Here, we report a case of successful resection of asymptomatic paraganglioma in a patient 5 years after distal gastrectomy for gastric cancer. | v2 |
2017-08-15T22:26:19.741Z | 2006-08-01T00:00:00.000Z | 11647150 | s2ag/train | Cimetidine Induces Interleukin-18 Production through H2-Agonist Activity in Monocytes
The present study demonstrates a possible mechanism for the improvement of gastrointestinal cancer patients' prognosis by the histamine receptor type 2 (H2R) antagonist cimetidine. This agent, but not the H2R antagonists ranitidine and famotidine, induced the production of an antitumor cytokine, interleukin (IL)-18, by human monocytes and dendritic cells (DC). In fact, ranitidine and famotidine antagonized cimetidine-induced IL-18 production. Cimetidine induced the activation of caspase-1, which is reported to modify immature IL-18 to mature/active IL-18, and the elevation of intracellular cAMP, leading to the activation of protein kinase A (PKA). The PKA inhibitor H89 abolished the IL-18 production induced by cimetidine. Moreover, the effects of cimetidine on IL-18 production were reproduced in peripheral blood mononuclear cells from wild-type mice, but not in those from H2R knockout mice. In conclusion, cimetidine, a partial agonist for H2R, has a pharmacological profile different from ranitidine and famotidine, possibly contributing to its antitumor activity on gastrointestinal cancers. | v2 |
2017-11-02T18:38:02.687Z | 2010-01-01T00:00:00.000Z | 2560300 | s2ag/train | Splenectomy during secondary cytoreductive surgery for epithelial ovarian cancer.
Splenic metastasis from ovarian cancer is unusual. Most splenic metastases are encountered in the setting of widespread visceral metastases. We present 6 cases of splenic metastasis of epithelial ovarian cancer. Three cases underwent a splenectomy as a part of interval debulking surgery, and the rest received a splenectomy as a surgery for recurrent disease. The splenectomies were well-tolerated in all patients and no serious morbidity or mortality resulted. Only one patient experienced a transient elevation in platelet count. | v2 |
2019-03-07T14:18:27.832Z | 2014-12-01T00:00:00.000Z | 70484910 | s2ag/train | P215 Referral Patterns For Mediastinal Staging With Ebus Across A Lung Cancer Network A Report From The Manchester Cancer Ebus Sub-group
Introduction Manchester Cancer is a large Cancer Network in the North West of England, consisting of ten NHS Trusts. There is known variability in lung cancer outcomes across the ten trusts, including resection rates. We have examined the referral patterns of each individual trust for EBUS mediastinal staging and compared this with the trust’s lung cancer resection rates. Methods The Manchester Cancer EBUS sub-group has data for all EBUS referrals from each of the ten NHS trusts in our Network in 2012. The National Lung Cancer Audit Report 2013 provides the number of lung cancer patients diagnosed at each trust for the same time period. From this data we could estimate the proportion of lung cancer patients from each trust that were referred for mediastinal staging with EBUS. Results In 2012, 2302 patients were diagnosed with lung cancer in this Network. In the same period, 193 patients were referred for EBUS mediastinal staging (8.4%). The proportion of lung cancer patients referred for mediastinal staging with EBUS varied significantly across the ten trusts ranging from 3.4% to 30.2% (p < 0.0001). The spearman co-efficient was 0.60 (p = 0.07) suggesting a possible relationship between the proportion of patients referred for EBUS and surgical resection (Figure 1). However, this may be due to a very high rate of staging EBUS at one trust, which if excluded yields a spearman co-efficient of 0.45 (p = 0.22). Discussion It is highly concerning that only 8% of lung cancer patients underwent EBUS nodal staging in our network given 52% of UK patients with histologically confirmed NSCLC are stage I-III at the time of diagnosis. It is of note that the Trust with the highest proportion of patients undergoing EBUS nodal staging have the highest surgical resection rate and three of the four Trusts with the lowest resection rates refer <5% of patients for EBUS nodal staging. Standardisation of referral practice across the Network is a key future goal for the EBUS Sub-group. Abstract P215 Figure 1 | v2 |
2021-07-27T00:06:05.561Z | 2021-05-20T00:00:00.000Z | 236368500 | s2ag/train | Long-term follow up of patients with mesothelioma treated with dendritic cell therapy in three phase I trials.
2618 Background: Immunotherapy targeting PD-(L)1 has become indispensable in the treatment of many malignant tumors. Recently, checkpoint inhibition using anti-PD-1 in combination with anti-CTLA-4 was proved to be effective in patients with malignant pleural mesothelioma (MPM). However, the minority of patients benefit from this treatment. The lack of immunotherapy efficacy in the majority of patients with mesothelioma can be explained by the fact that mesothelioma is a tumor with an “immune-desert” phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. By administration of dendritic cells (DCs), which were cultured, activated, and exposed to antigens ex-vivo, this “immune-desert” phenotype might be turned into an “inflamed” phenotype. Previously, we performed and published three phase I trials using activated DCs, which support this concept. Here, we report the long-term survival of the patients treated with DCs in these three phase 1 studies. Methods: We collected the survival data of the phase 1 trials using DC therapy in patients with MPM. In the first two trials, DCs loaded with autologous tumor lysate were used, while in the third allogeneic tumor lysate was used to load the DCs (Mesopher). Results: Between 2006 and 2015, in the three studies combined, 29 patients with MPM were treated with DC vaccination. At data cut-off, the median OS was 27 months (95% confidence interval (CI): 21 – 47 months). OS at 2 years was 55.2% (95% CI: 39.7%-76.6%), OS at 5 years was 20.7% (95% CI: 10.1%-42.2%). Conclusions: The long-term follow up of MPM patients treated with DC vaccination in the three separate phase 1 trials show a promising signal, with a 2-year OS of over 50% and a 5-year OS of over 20%. In addition, 2 patients are alive after 10 years of treatment. In our opinion, these findings show the potency of DC vaccination therapy in long-term activation of the immune system. DC vaccination therapy in patients with MPM is currently being investigated in a large, randomized phase II-III trial (NCT03610360) and in pancreatic cancer. Additional biomarker studies, as well as treatment combinations with for example ICI, could further improve the outcomes of DC-vaccination therapy. Clinical trial information: NCT02395679. [Table: see text] | v2 |
2018-04-03T02:19:24.684Z | 2006-02-01T00:00:00.000Z | 33175310 | s2ag/train | Cell proliferation depends on mitochondrial Ca2+ uptake: inhibition by salicylate
Store‐operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ influx pathway involved in control of multiple cellular and physiological processes including cell proliferation. Recent evidence has shown that SOCE depends critically on mitochondrial sinking of entering Ca2+ to avoid Ca2+‐dependent inactivation. Thus, a role of mitochondria in control of cell proliferation could be anticipated. We show here that activation of SOCE induces cytosolic high [Ca2+] domains that are large enough to be sensed and avidly taken up by a pool of nearby mitochondria. Prevention of mitochondrial clearance of the entering Ca2+ inhibited both SOCE and cell proliferation in several cell types including Jurkat and human colon cancer cells. In addition, we find that therapeutic concentrations of salicylate, the major metabolite of aspirin, depolarize partially mitochondria and inhibit mitochondrial Ca2+ uptake, as revealed by mitochondrial Ca2+ measurements with targeted aequorins. This salicylate‐induced inhibition of mitochondrial Ca2+ sinking prevented SOCE and impaired cell growth of Jurkat and human colon cancer cells. Finally, direct blockade of SOCE by the pyrazole derivative BTP‐2 was sufficient to arrest cell growth. Taken together, our results reveal that cell proliferation depends critically on mitochondrial Ca2+ uptake and suggest that inhibition of tumour cell proliferation by salicylate may be due to interference with mitochondrial Ca2+ uptake, which is essential for sustaining SOCE. This novel mechanism may contribute to explaining the reported anti‐proliferative and anti‐tumoral actions of aspirin and dietary salicylates. | v2 |
2018-04-03T02:20:58.541Z | 2015-09-15T00:00:00.000Z | 33345260 | s2ag/train | Prognostic factors and immunobiologic insights into Merkel cell carcinoma
Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine cancer that has a propensity for local recurrence and nodal and distant metastasis. For patients with MCC, reported 5-year overall survival (OS) rates vary widely and range from 40% to 62%, whereas the 5-year disease-specific survival (DSS) rate is approximately 65%. Because of its rarity, much of the published literature on MCC reports relatively low numbers of patients and various prognostic features. The small patient numbers and inconsistent reporting endpoints have challenged the identification of clinicopathologic prognostic factors, and predictive factors for therapeutic intervention have not emerged. The lack of consensus on prognostic markers is exemplified by the fact that before 2010, 5 different staging systems for MCC were described in the literature. In 2010, for the first time, the American Joint Committee on Cancer (AJCC) published a separate staging system for MCC. Several studies report that the 7th edition of the AJCC staging system for MCC predicts survival and outcome; however, the validity of this staging system has been questioned because it is primarily based on an analysis of the National Cancer Data Base (NCDB) using OS as the primary outcome measure. Some authors have argued that analyses using large registries such as the NCDB have significant limitations and do not provide comprehensive data that allow an accurate prognostic analysis. These limitations also include the fact that these large registries do not capture data on causes of death or patterns of recurrence and often lack consistent and complete pathology data, particularly for lymph nodes. Other authors have suggested that OS is a poor outcome marker for MCC patients because of the older age of this population and because a considerable proportion of deaths are not due to MCC, as exemplified by Smith et al, who report that 55% of deaths were due to non-MCC causes. Within this setting, questions have arisen about whether other clinicopathologic factors should be considered as prognostic markers for MCC. For instance, the tumor growth pattern has been reported to predict outcomes for MCC patients. Mott et al showed that a diffuse growth pattern was correlated with metastatic disease or death from MCC (P 5 .04). Andea et al reported that a nodular growth pattern was significantly correlated with improved survival in a multivariate analysis. Another promising factor reported to predict survival for MCC patients is lymphovascular invasion (LVI). Fields et al published the largest single-institution study on MCC and evaluated 500 patients from 1969 to 2010. They reported that 49% of cases had LVI and that LVI significantly predicted OS and disease-specific mortality. Lim et al reported a similar LVI rate (40%) but, in contrast, did not show a significant correlation with DSS or disease-free survival (DFS) in a multivariate analysis after adjusting for tumor thickness. Notably, the NCDB study did not present data on LVI for MCC. Similarly, Smith et al were unable to assess LVI as a predictive marker because of incomplete data. Instead, Smith et al evaluated the prognostic significance of tumor thickness in MCC. Although MCC size has been correlated with survival, the prognostic value of tumor thickness remains undefined. There are data suggesting that MCC thickness can be correlated with outcome. In 2004, Mott et al reported that patients with tumors invading subcutaneous fat had significantly worse outcomes (metastatic disease or death from MCC). This study did not specifically analyze tumor thickness, but tumor depth was the best predictor of outcomes among the histologic characteristics analyzed. Several subsequent studies specifically reported on the prognostic value of tumor thickness in MCC. Lim et al showed that a tumor thickness> 10 mm was significantly correlated with worse DSS and DFS, whereas Andea et al reported that tumor thickness was significantly prognostic for survival. Smith et al also report that tumor thickness significantly | v2 |
2018-04-03T04:38:10.854Z | 2008-09-01T00:00:00.000Z | 25322960 | s2ag/train | Can we still afford bladder cancer?
Purpose of review Bladder cancer is the most expensive tumor with regard to both costs per patient per year and lifetime costs per patient. Nonmuscle invasive tumors account for the highest share of the overall costs for bladder cancer. Costs for follow-up (excluding costs for reinterventions) compared with transurethral resection and cystectomy account for a considerably lower portion of the overall costs. Recent findings From an economic standpoint, the biggest potential for savings could, therefore, be in the treatment and re-treatment of nonmuscle invasive tumors. Cost reductions have already been demonstrated with a reduction of hospital admission for such treatments, use of photodynamic diagnosis supported transurethral resection to avoid residual tumors, and adjuvant chemoinstillation and immunoinstillation to prolong or prevent tumor recurrences. Summary Further cost reductions can be achieved with a centralization of patients undergoing cystectomy by shifting these patients to high-volume surgeons in high-volume hospitals, thereby reducing complications and length of hospital stay. In advanced stages predictive markers may identify suitable subgroups for molecular therapies and, therefore, avoid costs of inappropriate treatments. | v2 |
2017-06-17T01:26:58.158Z | 2012-01-01T00:00:00.000Z | 7625260 | s2ag/train | Objective assessment of postoperative gastrointestinal motility in elective colonic resection using a radiopaque marker provides an evidence for the abandonment of preoperative mechanical bowel preparation.
BACKGROUND
It has been suggested that mechanical bowel preparation (MBP) has no benefit in terms of anastomotic healing, infection rate, or improvement in the postoperative course in patients undergoing elective colorectal surgery, and that it should be abandoned. However, the effect of MBP on postoperative gastrointestinal motility has been assessed subjectively. In this randomized trial, we objectively assessed the effect of MBP on postoperative gastrointestinal motility and mobility in elective colonic resection.
METHOD
In total, 79 patients scheduled to undergo elective colonic resection for cancer were randomized to MBP or no-MBP groups prior to surgery. All patients ingested radiopaque markers before surgery to evaluate postoperative gastrointestinal motility, objectively evaluated by the transition of the markers at postoperative days (PODs) 1, 3, 5 and 7. The groups were then further subdivided into open and laparoscopic-assisted colectomy (LAC) groups and evaluated in terms of gastrointestinal motility and postoperative mobility.
RESULTS
There was no significant difference between the no-MBP and MBP groups in terms of perioperative and postoperative course. In the LAC subgroup, there was no significant difference between the no-MBP and MBP groups in terms of marker transition. However, in the open subgroup, there was a significant difference between the groups in terms of the residual ratio of markers in the small intestine at POD 3 (no-MBP 35.3% vs. MBP 69.2%; p=0.041), excretion rate of markers at POD 5 (no-MBP 49.7% vs. MBP 8.8%; p=0.005), and residual ratio in the small intestine at POD 7 (no-MBP 3.1% vs. MBP 28.8%; p=0.028). Additionally, the excretion rate in the no-MBP group was significantly higher than in the MBP group at POD 7 (74.1% vs. 33.8%; p=0.007).
CONCLUSIONS
Our data provide additional evidence to support the abandonment of MBP in elective open colonic surgery. | v2 |
2018-04-03T04:21:37.229Z | 2018-07-01T00:00:00.000Z | 3640710 | s2ag/train | Loss of pRB in Conjunctival Squamous Cell Carcinoma: A Predictor of Poor Prognosis
Conjunctival squamous cell carcinoma (SCC) is the most common tumor of conjunctival epithelium. It is associated with risk of permanent visual impairment and has the capability to recur, metastasize, and cause death. Deregulation of cell cycle control has been reported in a number of malignancies. The aim of the present study was to assess expression of G1/S cell cycle regulatory proteins [retinoblastoma protein (pRb)/P16INK4a/cyclin D1] in conjunctival SCC. Forty-four prospective cases of conjunctival SCC from a tertiary eye care referral center in northern India were included in this study. American Joint Committee on Cancer (AJCC) staging was performed and patients were followed up for 46±3.2 months. pRb loss was seen in 87% and overexpression of p16INK4a and cyclin D1 in 36% and 66%, respectively. Kaplan-Meier analysis revealed reduced disease-free survival in patients with pRb loss (P=0.006). On univariate analysis, pRb loss (P=0.02), orbital invasion (P=0.03), and AJCC stage ≥T3 (P=0.03) emerged as significant high-risk features. On multivariate analysis pRb loss emerged as the most significant poor prognostic indicator in conjunctival SCC cases. Our findings suggest pRb loss to be a useful indicator of aggressive behavior and is recommended for identifying high-risk conjunctival SCC patients. | v2 |
2018-04-03T03:06:25.655Z | 1989-04-01T00:00:00.000Z | 235860 | s2ag/train | [Effects of sulbactam/cefoperazone in patients with respiratory infections in aged and/or with underlying respiratory diseases].
Sulbactam/cefoperazone (SBT/CPZ), a new antibacterial drug, was administered to 14 cases with respiratory infections for a duration of 5 approximately 13 days at a daily dose of 4 g. Diagnoses of these patients were 7 respiratory tract infections, and 7 bronchopneumonias. The underlying diseases were chronic pulmonary emphysema in 6 cases, bronchial asthma in 2 cases, and one each of bronchiectasis, diffuse panbronchiolitis and lung cancer with bronchoesophageal fistula. All patients had underlying respiratory diseases and/or were more than 70 years old. The rate of clinical efficacy was 78.6%. The incidence of penicillinase production by isolated bacteria was 18.2% and that of cephalosporinase was 63.6%. SBT/CPZ was expected to be more effective than CPZ alone in 3 cases judging from the susceptibility of the bacterial strains concerned, to antibiotics. No side effects were observed. We conclude that SBT/CPZ is useful in the treatment of respiratory infections of patients of advanced age and/or with underlying respiratory diseases. | v2 |
2018-04-03T01:54:55.019Z | 2007-09-01T00:00:00.000Z | 31446560 | s2ag/train | Hypoxia inducible factor‐1 influences sensitivity to paclitaxel of human lung cancer cell lines under normoxic conditions
Paclitaxel (PTX) is an anticancer drug that is effective against a wide range of solid tumors. The effect of PTX on two human lung cancer cell lines, PC14PE6 and NCI‐H441 cells, was examined in an orthotopically transplanted animal model with an in vivo imaging devise. Although PTX effectively suppressed tumor growth and improved survival rate in NCI‐H441, it did not influence these in PC14PE6. In vitro experiments confirmed that PC14PE6 cells are resistant to PTX under normoxic conditions and that both cell lines were resistant to PTX under hypoxic conditions. It was found that the expression level of endogenous hypoxia inducible factor (HIF)‐1α in PC14PE6 is much higher than that in NCI‐H441 cells under normoxic conditions. Furthermore, sensitivity to PTX in these cell lines was reversed when HIF‐1α expression was decreased by siRNA specific to HIF‐1α in PC14PE6 and increased by overexpression of the exogenous HIF‐1α gene in NCI‐H441. These results suggest that HIF‐1 influences the PTX sensitivity of these cells. The authors further examined β‐tubulin, a target molecule of PTX, with western blotting and immunohistochemical analysis in these cells. The expression level of β‐tubulin was comparable in these cells under both normoxic and hypoxic conditions while the distribution of β‐tubulin and cell morphology were changed according to HIF‐1α expression levels, suggesting that HIF‐1 influences the conformation and dynamics of microtubules. These data support the potential development of HIF‐1 targeted approaches in combination with PTX, where drug resistance tends to contribute to treatment failure. (Cancer Sci 2007; 98: 1394–1401) | v2 |
2018-04-03T04:01:06.032Z | 2011-11-01T00:00:00.000Z | 37329360 | s2ag/train | Human papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion
Human papillomavirus (HPV) infections account for more than 50% of infection‐linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV‐infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK‐cell infiltration in HPV‐associated preneoplastic cervical lesions. Since HPVs cannot grow in vitro, virus‐like particles (VLPs) were used as a model for studying the NK‐cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF‐α and IFN‐γ) in the presence of HPV‐VLPs. Using flow cytometry and microscopy, we observed that NK‐cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16+ and CD16− NK‐cell lines and a CD16‐blocking antibody, we demonstrated that CD16 is necessary for HPV–VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV‐induced lesions. | v2 |
2018-04-03T00:53:27.506Z | 2010-10-10T00:00:00.000Z | 2778750 | s2ag/train | A decade of surgically removed small renal masses in the Netherlands: characteristics and trends in type of surgery and pathologic reporting.
PURPOSE
To assess nationwide the pathologic characteristics and trends in type of surgery and pathologic reporting in surgically managed renal tumors ≤ 4 cm.
MATERIALS AND METHODS
A review of all pathologic reports of primary small renal masses operated on in the Netherlands during the period 1995 to 2005 was performed. The data source was a nationwide central archive of histocytopathology (Patologisch Anatomisch Landelijk Geautomatiseerde Archief). Tumors were stratified into three groups: ≤ 2, 2.1 to 3.0, and 3.1 to 4.0 cm. Age, sex, type of operation, and tumor pathology were analyzed. For renal-cell carcinomas, grade (3-tiers Fuhrman) and stage (2002 Tumor, Node, Metastasis) were assessed. Trends in type of surgery (radical or partial nephrectomy [PN]) and pathologic reporting during the study period were analyzed.
RESULTS
Of all operated primary kidney tumors, 25.3% were ≤ 4.0 cm. The mean age of the patients was 63.1 years (standard deviation 11.7), and the male/female ratio was 3:2. Only 7.5% were benign tumors, and 9.8% were locally advanced (≥ T₃). Tumors ≤ 3.0 cm were more likely to be benign (P = 0.006) and of lower stage (P ≤ 0.001) than tumors of 3.1 to 4 cm. PN was performed in 16.5% of the cases. Grade and subtype were reported in 55% of the cases. The rate of PNs performed increased during the decade. There was a trend in increased reporting of grade and subtype.
CONCLUSIONS
A quarter of all the operated primary kidney tumors were ≤ 4 cm. Smaller tumors were more likely to be benign and of lower stage. A cutoff size regarding biologic aggressiveness can be settled at the 3 cm size. The PN rate increased along the decade. Grade and subtype reporting rates remained suboptimal, although a positive trend was noted. | v2 |
2021-11-04T15:27:26.769Z | 2021-11-02T00:00:00.000Z | 242076050 | s2ag/train | Search of Predictors of Radiosensitivity in Rectal Adenocarcinoma
Purpose: To analyze a number of immunohistochemical markers as predictors of the radiosensitivity of rectal adenocarcinoma.
Material and methods: The study included 122 patients with histologically verified rectal adenocarcinoma, varying degrees of differentiation, and the stage of the tumor process I-IIIC, T2-T4b /N0-N2b/ M0, with the localization of the tumor in the lower-middle-ampullary parts of the rectum. Predictors included in the research: Ki67, p53, EGFR, Bcl2, COX2, P21, E-cadherin. Preoperative chemoradiotherapy was performed up to 48–50 Gy with the use of medications (5-FU, Cisplatin) as a radio modifiers. The analysis was carried out according to the degree of severity of therapeutic pathomorphosis (according to Mandard), a decrease in the stage before surgery.
Results: A full course of preoperative chemoradiotherapy followed by surgery was performed at 121 patients, one patient died of concomitant cardiac pathology during the break. The first degree of Mandard pathomorphosis (complete resorption) registered at 12 patients. The second degree (preservation of a few tumor cells against the background of fibrotic changes) – at 27 patients. The third degree (a large number of preserved tumor cells against the background of the predominance of fibrosis) – at 38 patients. The fourth degree (tumor cells predominate over fibrotic changes) – at 27 patients. The fifth degree (complete absence of signs of tumor regression, absence of fibrosis) – at 2 patients. A decrease in the stage of the tumor process according to the preoperative comprehensive examination registered in 114 (94.2%) patients, in 9 (7.4%) patients – there was no dynamics. During the observation period from 2006 until nowadays, 10 people are known to have died. Years in remission range from 3 months to 22 years. According to the results of multivariate and multiple regression analyses, it is possible to successfully predict the effectiveness of chemoradiotherapy, both with the use of biomarkers (Ki67, p53, EGFR, Bcl2, COX2, P21, E-cadherin), and traditional indicators (histological type, stage of the disease, gender, degree of differentiation). It turned out, that both traditional indicators and immunohistochemical indicators work equally well, regardless of each other.
Conclusion: Studied immunohistochemical predictors of radiosensitivity of rectal adenocarcinoma, allow to assess the degree of radiosensitivity or radioresistance of the tumor in each patient before the start of preoperative chemoradiotherapy by doing so, it warns us about the effectiveness or ineffectiveness of chemoradiotherapy in a specific clinical situation, which allows us to individualize the approach to treatment, choosing a more suitable treatment method for the patient: neoadjuvant chemotherapy or surgery. | v2 |
2018-04-03T01:31:12.738Z | 1972-09-01T00:00:00.000Z | 29889750 | s2ag/train | Interaction between placental alkaline phosphatase and ABO system polymorphisms during intrauterine life.
The alkaline phosphatase of human placenta differs from that produced by other organs in a number of physicochemical characteristics including heat resistance, substrate specificity, antigenic properties, electrophoretic pattern, and others [1-7]. The enzyme is produced by the fetal side of the placenta [6, 7]; it appears in the maternal circulation during the first trimester of gestation and persists in the serum up to 12 weeks after delivery [8]. This enzyme is the only alkaline phosphatase showing electrophoretic polymorphism related to its structural gene [6, 7]. There are three common alleles, Plo', plfl, and Plil, as well as numerous other alleles with lower frequency (less than 2%o of the total). No linkage between the locus determining the placental alkaline phosphatase and the loci of the ABO and Rh systems has been observed [9]. The gene frequencies vary widely among human populations [6, 7, 10-18]. Normally, this gene is active only during fetal life and, other than in the pregnant woman, the enzyme has been found only in association with certain tumors [19]. Robson and Harris [7] observed that the plil allele is associated with a lower enzyme activity. Recently, Beckman [20] examined the activity of the six common phenotypes in a large series of pregnancies, both in placental extracts and in maternal serum: in the placenta, the activity ratio among Plfi, Pjl8, and Plil is equal to 0.90:0.81:0.33. The facts that placental alkaline phosphatase is normally produced only during fetal life and that it is found early in gestation in the maternal bloodstream suggest that it may play a role in the biological relationship between mother and fetus. Moreover, the existence of a polymorphism showing different enzyme activity among phenotypes and highly variable gene frequencies among ethnic groups suggests that this system may undergo selective forces of different intensity in the various populations. Searching for possible forces acting upon P1 poly- | v2 |
2019-03-12T13:05:11.448Z | 2014-01-01T00:00:00.000Z | 74585150 | s2ag/train | Management Of Oral Squamous Cell Carcinoma With Clinically Negative Neck - A Case Report And Review Of Literature
The management of N0 neck is still controversial. Although the decision to observe or treat the N0 neck is left to the choice of the patient and the head and neck oncologist, in oral cavity carcinoma the only clinically N0 necks for which observation is appropriate are those associated with T1/T2 lip carcinomas, T1/T2 oral tongue carcinomas that are less than 4mm thick, T1/T2 floor of mouth cancers less than or equal to 1.5 mm thick. Lymph nodes in levels I-III are considered sentinel for oral cavity cancers. This well accepted concept forms the basis for prophylactic neck dissections where the likelihood of occult neck disease exceeds 20%. Selective Neck Dissection has been most utilized for elective treatment of regional lymphatics when the risk of metastasis is high. abuse for several years. There was no family history of malignancy. Medical history of the patient had no important episodes. The intraoral examination revealed an irregular, diffuse, reddish exophytic lesion over his left posterior buccal mucosa opposite molars and extending up to retromolar trigone, about 3 × 2 cm in size, oval in shape, non-tender on palpation and firm in consistency (Fig 1). Extra oral examination revealed no lymphadenopathy in submandibular or other neck triangles. Radiographic examination showed no bony invasion. Under the impression of malignancy, an incisional biopsy was performed under local anesthesia on the same day and the s p e c i m e n w a s s u b m i t t e d f o r histopathological examination, which demonstrated well differentiated squamous cell carcinoma. After obtaining the results of blood investigations with no abnormality and a fitness for surgery a written consent was | v2 |
2017-06-19T20:32:35.475Z | 2003-09-01T00:00:00.000Z | 34153260 | s2ag/train | Distinct mechanisms mediate the initial and sustained phases of cell migration in epidermal growth factor receptor-overexpressing cells.
Elevated levels of epidermal growth factor receptor (EGFR) are predictive of increased invasion and metastasis in many human cancers. In the present study, we have shown that two distinct pathways regulate cell migration in EGFR-overexpressing invasive cells such as MDA 468 breast cancer cells: mitogen-activated protein kinase (MAPK or ERK 1 and 2) pathways play a major role in early stages to cell migration; and protein kinase C delta isoforms (PKC-delta) play a significant role in later stages of sustained cell migration. Inhibition of MAPK activity with MAP kinase kinase (MEK) inhibitor PD98059 blocks early stages of cell migration (up to 4 h); however, cells revert back to enhanced cell migration after 4 h. While inhibition of PKC-delta activity with rottlerin or dominant-negative PKC-delta expression blocks sustained cell migration after 4 h and up to 12 h, the combination of MAPK and PKC inhibitors completely blocked transforming growth factor alpha (TGF-alpha)-induced cell migration in EGFR-overexpressing breast cancer cells. However, inhibition of MAPK activity completely blocked cell migration in low EGFR-expressing non-invasive breast cancer cells such as MCF-7 cells. Forced overexpression of EGFR in MCF-7 cells (EGFR/MCF-7 cells) resulted in cell migration patterns seen in MDA 468 cells, that is, MAPK pathways play a major role in early stages to cell migration, and PKC-delta plays a major role in later stages of sustained cell migration. The above data demonstrate that EGFR-overexpressing invasive cells have the ability to compensate the loss of MAPK-mediated signaling through activation of PKC-delta signaling for cell migration, which plays a major role in invasion and metastasis. In addition, data suggest that inhibition of MAPK and PKC-delta signaling pathways should abrogate cell migration and invasion in EGFR-overexpressing human breast cancer cells. | v2 |
2018-01-24T17:25:33.048Z | 2011-05-20T00:00:00.000Z | 7173210 | s2ag/train | Meta-analyses of 22 randomized trials assessing the influence of chemotherapy in advanced/recurrent gastric cancer.
4109 Background: Advanced or recurrent stomach cancer remains an incurable disease and little progress has been obtained in prolonging survival. Multiple drugs and combinations of chemotherapy (CT) have been investigated with limited benefit on overall survival. The GASTRIC project initiated an individual-patient-data (IPD) based meta-analysis to quantify the benefit of various CTs.
METHODS
Randomized clinical trials (RCT) closed to patient accrual before 2004 were searched based on predefined criteria. The primary endpoint was overall survival (OS), the secondary progression-free-survival (PFS). The log-rank test, stratified by trial, was used to compare treatment arms; Peto heterogeneity tests were used. "Experimental" arms were defined as containing more drugs and/or a newer agent. We subsequently restricted analyses to trials that compared a CT with the same plus an additional compound. Eventually, we investigated comparisons of regimens including FUs, anthracyclines, platinums, taxanes, or irinotecan.
RESULTS
Fifty RCTs (N = 7,746) were identified, IPD (N = 4,245) was available from 22 studies. In the comparison of experimental with the control arms, highly significant differences were observed. Addition of a compound also showed a significant improvement in OS and PFS. There was no specific regimen which showed statistically significant differences on OS while platinums- and irinotecan-based regimens showed the statistically significant PFS improvements vs comparative arms.
CONCLUSIONS
This IPD meta-analysis showed that OS and PFS have been modestly but significantly improved by the addition of experimental CT agents to preexisting control or standard regimens, but no specific regimen was identified as clearly superior. [Table: see text]. | v2 |
2018-04-03T04:20:19.014Z | 2012-05-15T00:00:00.000Z | 38618960 | s2ag/train | A pilot study of urinary microRNA as a biomarker for urothelial cancer.
OBJECTIVE
MicroRNAs (miRNAs) are part of a class of small ribonucleic acid (RNAs). They are important regulatory molecules, involved in several cell processes, such as developmental timing, stem cell division and apoptosis. Dysregulated miRNAs have been identified in several human malignancies, including bladder cancer tissue samples, and may confer a "tumour signature" that can be exploited for diagnostic purposes. We report on a prospective pilot study investigating the diagnostic capability of miRNAs in the urine of patients with urothelial cancer.
METHODS
Voided urine samples were collected from patients with urothelial carcinoma just prior to bladder tumour resection, as well as age-matched healthy control patients. Pathology demonstrated both low- and high-grade cancer. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed on the RNA extracts using primers for 4 miRNAs shown previously to be dysregulated in solid urothelial carcinomas with RNU6B as the endogenous control. Standard urine cytology was performed on all samples in a blinded fashion.
RESULTS
Two miRNAs of interest were dysregulated in the urine from cancer patients with miR-125b showing an average 10.42-fold decrease (p < 0.01) and miR-126 showing an average 2.70-fold increase (p = 0.30) in the cancer samples compared to the normal controls. The sensitivity and specificity of the cytology on the same urine samples were 50% and 80%, respectively. Using these 2 miRNAs only, a decision-tree prediction model was generated for a validation cohort of patients yielding a specificity of 100% and a sensitivity of 80%.
DISCUSSION
This preliminary study of candidate urinary miRNA in patients with low- and high-grade urothelial cancer demonstrated a significantly improved diagnostic accuracy over cytology. These results provide rationale for further studies on discovery and validation of candidate miRNAs in voided urine and may potentially lead to the development of a non-invasive and sensitive test for bladder cancer diagnosis and prognosis. | v2 |
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Pes2o Cancer-filtered Dataset
This is a 3-way merged dataset of the allenai/peS2o academic paper dataset filtered with (cancer | oncology | tumor | tumour | oncogene | malignancy) + ((patient | human | rat | mouse) | (safety + dog)) query with about 1.7M specimens in train and 6k in validation. This query returns data in the dataset up until 2023-01.
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