tbuckley/cabot-search huggingface dataset:
Abstract 4168: Dissect the clinical utility of TCGA genomic data across tumor types
Authors: Han Liang
Journal: Cancer Research (2014)

Abstract A central question for the cancer research community is how to use genomic and proteomic data to guide cancer care. We investigated two potential clinical applications of The Cancer Genome Atlas (TCGA) data: predicting patient prognosis and identifying clinically actionable alterations. For four TCGA cohorts, we systematically evaluated the power of molecular data with or without clinical variables in predicting patient survival; and to facilitate further community efforts, we established an open-access model evaluation platform. We demonstrate that incorporating molecular data with clinical variables can improve predictive power. Interestingly, one model derived from ovarian cancer can predict outcomes in kidney cancer, suggesting the potential utility of cross-tumor analysis. Across 12 cancer types, we identified 10,281 somatic alterations in clinically relevant genes in 2,928 out of 3,277 patients (89.4%), revealing recurrent and potentially targetable alterations not revealed in single-tumor datasets. Our study represents the first systematic and comprehensive analysis evaluating the prognostic power of different types of molecular data across multiple cancer types. In addition, the clinically actionable alterations we identified may inform novel clinical trial design and treatment choice. Citation Format: Han Liang, TCGA Pan-Cancer Clinical/Predictor Group. Dissect the clinical utility of TCGA genomic data across tumor types. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4168. doi:10.1158/1538-7445.AM2014-4168
Breast feeding reduces morbidity
Authors: Michael C Latham
Journal: BMJ (1999)

<h3>Background</h3> A working projection in coil embolization of a cerebral aneurysm is usually determined using three-dimensional volume rendering digital subtraction angiography (3D VRDSA), in which the boundary between an aneurysm and its parent artery cannot be identified simultaneously on the front and back surfaces of the vessel. A new method was devised to obtain a more optimal working projection. <h3>Methods</h3> 83 patients with aneurysms being treated by embolization were retrospectively evaluated. An aneurysm was accurately distinguished from the parent artery by observation of front, back, proximal and distal sides of the vessel on 3D VRDSA (carving method). An optimal working projection with simultaneous identification of the front and back boundary lines was determined using a translucent vessel complex combined with the carved aneurysm. <h3>Results</h3> In 32 aneurysms (38.6%), the optimal working projection was consistent with the working projection that had been used during the procedure. In terminal type aneurysms, the angle difference between the optimal and actual working projections was significantly smaller than in the other types (p&lt;0.05). Aneurysms with a maximal diameter &lt;5 mm showed a significantly larger angle difference between the optimal and actual working projections than aneurysms with a maximal diameter ≥5 mm (p&lt;0.05). <h3>Conclusion</h3> In more than half of the patients, the actual working projection was inaccurate. The carving method might be useful to determine working projections, especially for aneurysms other than the terminal type and/or those with a maximal diameter &lt;5 mm.
Effect of Diagnosis (Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, or Acute Myeloid Leukemia [AML]) on Outcome of AML-Type Chemotherapy
Authors: Elihu Estey, Peter Thall, Miloslav Beran, Hagop Kantarjian, Sherry Pierce, Michael Keating
Journal: Blood (1997)
Abstract P407: Associations between Red Meat Intake and Biomarkers of Inflammation and Glucose Metabolism in Women
Authors: Sylvia H Ley, Qi Sun, Walter C Willett, Heather Eliassen, Kana Wu, An Pan, Fran Grodstein, Frank B Hu
Journal: Circulation (2014)

Background: Greater red meat intake is associated with increased type 2 diabetes and cardiovascular disease risk (CVD). Recently, inclusion of lean red meat in a heart-healthy diet to reduce CVD risk was suggested based on short-term controlled feeding trial evidence, indicating that varying amounts of lean red meat intakes had similar effects on a lipid profile. However, the fat content of red meat may not be solely responsible for the adverse effects of red meat contributing to progression of metabolic abnormalities. Other components and mediating pathways including obesity-related inflammation and insulin resistance may be involved. We hypothesized that greater red meat intake would be associated with biomarkers of inflammation and glucose metabolism and that these potential associations would be partly explained by body mass index (BMI). Design: We analyzed data from diabetes-free female participants in the Nurses’ Health Study (n=3690). Multiple linear regression was conducted to assess the associations of total, unprocessed and processed red meat intakes (quartile categories) with plasma C-reactive protein (CRP), ferritin, adiponectin, fasting insulin, and hemoglobin A1c (HbA1c). The contribution of BMI on the associations between red meat intake and biomarkers was evaluated using publicly available SAS macro. The effect of substituting a serving of red meat with a serving of another major protein food source was estimated. Results: Greater total, unprocessed and processed red meat consumptions were associated with higher plasma CRP, ferritin, fasting insulin, and HbA1c and lower adiponectin after adjustment for demographic information (all p for trend ≤0.03). Adiponectin was not associated with any types of red meat intake when further adjusted for medical and lifestyle factors. After adjustment for BMI, most of these associations with inflammatory and glucose metabolic biomarkers were substantially attenuated and no longer significant. BMI accounted for a statistically significant proportion of associations with CRP, HbA1c, and fasting insulin (all p for contribution ≤0.02), but not with ferritin. Substituting a serving of total red meat intake with alternative protein food in a combination of poultry, fish, legumes and nuts was associated with significantly lower CRP (β±SE: -0.106±0.043), ferritin (-0.212±0.075), HbA1c (-0.052±0.015), and fasting insulin (-0.0119±0.036)(all p≤0.02 for comparing extreme quartiles). Conclusions: Greater red meat intake is associated with unfavorable plasma concentrations of inflammatory and glucose metabolic biomarkers in diabetes-free women. BMI accounts for a significant proportion of the associations with these biomarkers, except for ferritin. Substituting red meat with another protein food is associated with a healthier biomarker profile of inflammatory and glucose metabolism.
Abstract P205: Behavioral Characteristics Associated with Biomarkers of Metabolic Syndrome Among Overweight/Obese Children in Korea
Authors: Ok-Kyung Ham, Youjeong Kang, Eun-Ok Im
Journal: Circulation (2014)

Introduction: Obesity rates have increased twofold among children in Korea over the past decade, posing a significant public health concern. Researchers have reported that 27% of overweight/obese children in Korea have metabolic syndrome (MS). However, there are no studies that elucidate factors influencing MS among children that could provide directions for future interventions for this specific population of children. Purpose: The purpose was to examine behavioral and socioeconomic factors that were associated with biomarkers of MS among overweight/obese Korean children to provide information for the development of tailored education for prevention of MS. Methods: A cross-sectional study was conducted with a convenience sample of 75 overweight/obese children recruited from four elementary schools in South Korea. The instrument included exercise frequency, eating behavior, sleep hours, stress, and screen time. Anthropometric measurements included weight, height, and waist circumference. Physiological variables included blood pressure (BP), fasting blood sugar (FBS), total cholesterol, triglyceride, and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. The data were analyzed using descriptive and inferential statistics including chi-square tests and analysis of covariance (ANCOVA) with age as a covariate. Results: The mean age of the children was 10.6 years (SD=1.01, range 8-13), and 56.8% were boys. Thirty percent were identified as having MS with three or more risk factors (BP ≥ 130/80 mmHg, HDL cholesterol&lt; 40 mg/dL, triglyceride &gt;120 mg/dL, FBS &gt; 100 mg/dL, and &gt; 90 th percentile value for waist circumference). MS was associated with family income, and children from more affluent families were more likely to have MS ( p &lt; 0.05). Children with higher stress were more likely to have elevated systolic BP; children who frequently consumed fast food were more likely to have lower total cholesterol; and children who usually ate a late dinner were more likely to have higher LDL cholesterol compared to their counterparts ( p &lt; 0.05). Screen time, exercise frequency, and sleep duration were not significant ( p &gt; 0.05). Among socioeconomic factors, mother’s employment status and education level were not significant ( p &gt; 0.05). However, children who had fathers with at least college level education were more likely to have elevated diastolic BP, and those from more affluent families were more likely to have elevated systolic BP compared to their counterparts ( p &lt; 0.05). Conclusion: Eating behavior, stress, and family socioeconomic factors were associated with MS and deviation in biomarkers among overweight/obese children. This needs to be incorporated into future development of education programs for this specific population at risk.
Ethonafide-Induced Cytotoxicity is Mediated by Topoisomerase II Inhibition in Human Prostate Cancer Cells.
Authors: Alan Pourpak, Terry H. Landowski, Robert T. Dorr
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5537 

Ethonafide (6-ethoxyazonafide/AMP-53), an anthracene-based analog of amonafide, is a DNA intercalator that inhibits topoisomerase II. The inhibition of topoisomerase II was determined by a cell-free assay using purified topoisomerase II and has not yet been validated as a mechanism of cytotoxicity in cancer. Ethonafide has demonstrated in vitro cytotoxicity in several cancer cell lines and has also demonstrated in vivo activity in tumor xenograft growth inhibition models. Based on these data, we hypothesize that ethonafide induces DNA double strand breaks, through inhibition of topoisomerase II, leading to apoptotic cell death. Using the MTT cytotoxicity assay, the IC50 at 72 hours was 40 nM, 86 nM, and 98 nM in DU-145, PC-3, and LNCaP prostate cancer cell lines, respectively. In DU-145 nuclear extracts, ethonafide inhibited topoisomerase II activity by preventing the relaxation of catenated kDNA at 10 μM, which corresponds to the IC90 at 24 hours. Following a 1-hour exposure, ethonafide stabilized the DNA-topoisomerase II cleavable complex in DU-145 cells in a concentration-dependent manner. Ethonafide also induced concentration-dependent DNA double strand breaks after a 1-hour treatment of DU-145 cells, as measured by the neutral comet assay. As with other topoisomerase II inhibitors, ethonafide induced potent G2/M cell cycle arrest after a 24-hour exposure with sub-toxic concentrations. Following a 24-hour exposure, ethonafide induced apoptosis as demonstrated by cleavage of procaspase-3 and PARP. These data suggest that ethonafide is active against prostate cancer by inhibiting topoisomerase II and stabilizing the cleavable complex leading to DNA double strand breaks and apoptosis.
Heterohemoantibodies in Inbred Mice With Transplanted Tumors and Leukemias&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Kurt Stern, Israel Davidsohn
Journal: JNCI Journal of the National Cancer Institute (1960)

Inbred mice of strains C57BL, C3H, DBA, BALB/c, and AKR bearing a variety of transplanted lymphomas, carcinomas, and sarcomas were given intraperitoneal injections of sheep or chicken red cells. Significant depression of hemolysin titers was observed in all but one group of experiments on animals with transplanted leukemias and lymphomas; this depression was less regular for agglutinin titers. Similar depressions of immune responses to red cell antigens were demonstrated in mice with transplanted carcinomas and sarcomas given single large doses of the antigen; in mice given multiple injections of smaller amounts of red cells, differences in antibody levels between tumor-free and tumor-bearing mice were either absent or less pronounced. Determinations of natural agglutinins for sheep red cells before and after tumor inoculation showed only exceptionally significant changes in antibody titers. These observations were compared with those reported in other investigations on related subjects and discussed with regard to possible mechanisms by means of which tumors interfere with immune responses and their potential role in the tumor-host relationship.
Neurological dysfunctions in mice expressing different levels of the Q/R site–unedited AMPAR subunit GluR–B
Authors: Dirk Feldmeyer, Kalev Kask, Rossella Brusa, Hans–Christian Kornau, Rohini Kolhekar, Andrei Rozov, Nail Burnashev, Vidar Jensen, Øivind Hvalby, Rolf Sprengel, Peter H. Seeburg
Journal: Nature Neuroscience (1999)
Safety of Ximelagatran—Reply
Authors: Victor Gurewich
Journal: JAMA (2005)

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Ginseng augments doxorubicin-induced inhibition of human breast cancer cell proliferation and tumor growth: mechanisms of action
Authors: Laura L. Murphy, Mandy L. King, Kimberly A. Smith
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4660 

Ginseng root extract inhibits the proliferation of human cancer cells in vitro, including those that represent many common cancers. Doxorubicin (or Adriamycin) is a chemotherapy drug used in the treatment of a number of cancers, including breast cancer. As breast cancer patients may take ginseng supplements, this study was designed to examine potential interactions between water-extracted ginseng (GE) and doxorubicin (DOX) on human breast cancer MCF-7 and MDA-MB-231 cell proliferation in vitro and tumor growth in vivo, and to determine the mechanism(s) of GE action on cancer cells. First, cells were treated with a wide concentration-range of GE (0-2mg/ml) or DOX (0-50ng/ml) and cell number was mea sured after 6 days. The IC50 concentrations for GE were 0.5 and 0.6mg/ml and for DOX were 5.6 and 1.5ng/ml in MCF and MDA cells, respectively. When cells were co-treated with DOX and the IC50 concentration of GE, a synergistic interaction occurred with MCF (IC50= 0.23ng/ml) and MDA cells (0.07ng/ml), respectively. Next, female nude mice were inoculated with MCF cells and provided ad libitum treatment with GE (1% in lieu of drinking water) or DOX (1.75mg/kg, ip, 5X/week), alone or in combination. Treatment with GE or DOX significantly decreased tumor size (p 2.5-fold) expression of pRb and pErk1/2 compared to controls. In DOX+GE cells or tumor tissue, there was a significant increase in p21 and decrease in pRb relative to DOX alone. Together, these data indicate that DOX+GE is more efficacious than either DOX or GE alone in the inhibition of human breast cancer cell proliferation in vitro and tumor growth in vivo. Moreover, the synergistic interactions between DOX and GE appear to be mediated, in part, by changes in pRb. (Funded by NCCAM grant no. AT001544)
Ribavirin as Therapy for Chronic Hepatitis C
Authors: A. M. Di Bisceglie, H. S. Conjeevaram, M. W. Fried, R. Sallie, Yoon Park, Cihan Yurdaydin, M. Swain, D. E. Kleiner, K. Mahaney, J. H. Hoofnagle
Journal: Annals of Internal Medicine (1995)

Objective: To evaluate ribavirin, an oral antiviral agent, as therapy for chronic hepatitis C. Design: Randomized, double-blind, placebo-controlled study. Setting: Clinical Center of the National Institutes of Health, a tertiary referral research hospital. Patients: 29 patients with chronic hepatitis C who received oral ribavirin (600 mg twice daily) for 12 months and 29 controls with chronic hepatitis C who received placebo for 12 months. Measurements: Effects of therapy were evaluated by measuring serum aminotransferase and hepatitis C virus (HCV) RNA levels before, during, and for 6 months after therapy and by histologic examination of liver specimens before and at the end of treatment. Results: Patients treated with ribavirin had a prompt decrease in serum aminotransferase levels (54% overall) compared with levels before treatment and levels in controls (5% decrease). Serum aminotransferase levels became normal or nearly normal in 10 patients treated with ribavirin (35% [95% CI, 18% to 54%]) but in no controls (0% [CI, 0% to 12%]). Aminotransferase levels remained normal in only 2 patients after ribavirin therapy was discontinued (7% [CI, 1% to 23%]). Serum HCV RNA levels did not change during or after therapy. Liver biopsy specimens showed a decrease in hepatic inflammation and necrosis among ribavirin-treated patients whose aminotransferase levels became normal. Conclusions: Ribavirin has beneficial effects on serum aminotransferase levels and histologic findings in the liver in patients with chronic hepatitis C, but these effects are not accompanied by changes in HCV RNA levels and are not sustained when ribavirin therapy is discontinued. Thus, ribavirin alone for periods as long as 12 months is unlikely to be of value as therapy for chronic hepatitis C.
Researchers Discover a Range of Factors Undermine Sperm Quality, Male Fertility
Authors: Tracy Hampton
Journal: JAMA (2005)

MONTREAL, QUEBEC—While women hoping to conceive are often reminded of the relentless ticking of their biological clock and the declining quality of their eggs as they age, research is also pointing to concerns for prospective fathers. Male factors play a role in about half of the 15% of couples who are infertile, and scientists are finding that, in addition to aging, a variety of substances can undermine sperm quality. Such factors as smoking and other behaviors, certain medications, and exposure to environmental pollutants can play a role in compromising sperm quality and were the focus of studies reported at a joint meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society held here in October. Unlike aging, however, many of these potential risks to male fertility can be controlled.
Abstract 4213: Evaluation of LMTK3 expression and tumor phenotype in estrogen-dependent colorectal cancer
Authors: Sybil Magturo, Georgios Giamas, Snay Mallick, Austin Layton, Justin Stebbing, Heinz-Josef Lenz, Melissa J. LaBonte
Journal: Cancer Research (2014)

Abstract Background: Incompatible physiology between genders influences development and progression of colorectal cancer (CRC). It is postulated that improved survival of women with CRC may be due to exogenous estrogen exposure. A recent study used the age of 50 as a surrogate for menopause, evaluating survival in two age groups: women ≥50 and ≤50. It was observed that women ≤50 had a survival advantage that was contributed to protection by estrogen- a mechanism lost in menopause; with no significant difference found in men. Lemur tyrosine kinase 3 (LMTK3) was recently identified, that when in association with an estrogen receptor (ER) α modulator increased growth, progression, and altered resistance to endocrine therapy was observed in breast cancer. The ER family (ERα and ERβ) exerts contrasting actions of estrogen on different target tissues, where ERβ is the dominant receptor expressed in the gastrointestinal tract. The different ER distribution between breast and colon cancer led to the hypothesis that LMTK3 overexpression should stabilize ERβ and decrease tumorigenesis in CRC. Methods: CRC cell lines were characterized for LMTK3 mRNA (qRT-PCR) and protein expression (Western blot) in both transfected and non-transfected cell lines. Overexpression of LMTK3 was achieved utilizing pCMV6-XL4-LMTK3. Overexpressing LMTK3 CRC cells were evaluated for alterations to cell viability by MTT, colony formation (CFAs), invasion assays and chemosensitivity to 5-Fluororuacil, oxaliplatin, and tamoxifen. Results: CRC cell lines demonstrated a range of LMTK3, ERα and ERβ mRNA and protein expression. Caco-2, HCT116 and LoVo cells demonstrated estrogen sensitivity as evidenced by treatment with ER antagonist, tamoxifen. CFA demonstrated that the presence of estrogen plus overexpression of LMTK3 decreased cell viability by 27, 28 and 36% in Caco2, HCT116 and LoVo cells respectively, had limited impact on chemosensitivity, and decreased their ability to invade. Conclusion: This study demonstrates that estrogen mediated cell signaling and LMTK3 play an important role in decreasing CRC tumorigenesis. Further studies are underway to better understand estrogen and LMTK3's role in CRC. Citation Format: Sybil Magturo, Georgios Giamas, Snay Mallick, Austin Layton, Justin Stebbing, Heinz-Josef Lenz, Melissa J. LaBonte. Evaluation of LMTK3 expression and tumor phenotype in estrogen-dependent colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4213. doi:10.1158/1538-7445.AM2014-4213