tbuckley/cabot-search huggingface dataset:
The Prevention of Suicide
Authors: David Lester
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The recent evidence that we are failing to prevent suicide in the United States (225:992, 1973) necessitates some serious thinking about the reasons for this failure. As has been pointed out (Comp Psychiatry 13:555, 1972), part of the difficulty is in predicting who will kill himself. Because the incidence of suicide is so low and because predictive scales are far from perfect, the number of false positives (ie, individuals who the predictive scales predict to be potential suicides, but who do not kill themselves) is unmanageably high. For example, in a hospital of 12,000 psychiatric patients, with a scale that predicted with 75% accuracy, 3,020 patients would be predicted as potential suicides, of whom only 30 would actually kill themselves. This suggests that we could prevent suicide more easily if it were more common, in which case the proportion of false positives would be much lower. This
Trial of poor performance status patients (ToPPS): A randomized phase II trial of pemetrexed versus pemetrexed/bevacizumab versus pemetrexed/carboplatin/bevacizumab in patients with stage IIIb/IV non-small cell lung cancer and ECOG performance status 2.
Authors: D. R. Spigel, R. Lilenbaum, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2010)

TPS287 Background: The optimal management of patients with advanced non-small cell lung cancer (NSCLC) and poor performance status (PS) is unclear. Patients are often excluded from clinical trials and treated with attenuated regimens. Pemetrexed and bevacizumab are new agents in advanced NSCLC treatment and recently have proven safe and active in combination with carboplatin in patients with good PS. This randomized, phase II trial evaluates three treatment regimens for patients with advanced stage IIIB/IV NSCLC and an ECOG PS of 2. The primary objective is to determine the progression-free survival (PFS) of this poor prognosis population. Methods: Patients are randomized to one of three treatment arms in a 1:1:1 ratio. Arm 1: pemetrexed 500 mg/m2 IV every 21 days; Arm 2: pemetrexed 500 mg/m2 IV and bevacizumab 15 mg/kg IV every 21 days; and Arm 3: pemetrexed 500 mg/m2 IV, bevacizumab 15 mg/kg IV, and carboplatin AUC = 5 IV every 21 days. Patients will only receive carboplatin for the first 4 treatment cycles (12 weeks). Patients on Arms 2 and 3 receive bevacizumab until disease progression. Patients are evaluated for response to treatment every 6 weeks (per RECIST 1.1). Eligibility: Patients ≥18 years with stage IIIB/IV unresectable, nonsquamous NSCLC with ECOG PS of 2 and a life expectancy of at least 12 weeks are eligible. Standard exclusions for bevacizumab also apply. Patients with treated central nervous system metastases (≥ 2 weeks prior to treatment start) as well as those being treated with therapeutic anticoagulants are also eligible. Currently, 16 patients are enrolled nationally with a total of 194 planned in this multicenter trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech
Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats
Authors: María Úbeda, Margaret Lario, Leticia Muñoz, María-José Borrero, Macarena Rodríguez-Serrano, Ana-María Sánchez-Díaz, Rosa del Campo, Lourdes Lledó, Óscar Pastor, Laura García-Bermejo, David Díaz, Melchor Álvarez-Mon, Agustín Albillos
Journal: Journal of Hepatology (2015)
Use of an Aqueous Soluble Tetrazolium/Formazan Assay for Cell Growth Assays in Culture
Authors: A H Cory, T C Owen, J A Barltrop, J G Cory
Journal: Cancer Communications (1991)

A new tetrazolium analog of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) was evaluated as a substitute for MTT in the microculture screening assay for in vitro cell growth. This new tetrazolium compound, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium, inner salt (MTS), in the presence of phenazine methosulfate (PMS), gave a water-soluble formazan product that had an absorbance maximum at 490-500 nm in phosphate-buffered saline. The amount of colored product formed was proportional to the number of cells and the time of incubation of the cells with MTS/PMS. MTS/PMS was reactive in all the cell lines tested which included mouse leukemia L1210 cells, mouse Ehrlich tumor cells, mouse 3T3 fibroblasts, and human colon tumor cells (HT-29). HT-29 and 3T3 fibroblasts reduced MTS/PMS more efficiently than they reduced MTT. Comparable to the amount of product formed from MTT, MTS/PMS gave excellent product formation. The IC50 value for pyrazoloimidazole obtained using MTS/PMS was 200 microM; for 5-fluoro-2'-deoxyuridine, the IC50 value was 0.9 nM. These values compared very favorably with the IC50 values obtained by direct cell counts. Further, the same IC50 values were obtained when the absorbances of the formazan product in the 96-well plates were determined after different times of incubation.
Clinics may miss those in greatest need
Authors: M Q Choyche, A K Maitra
Journal: BMJ (1995)

EDITOR,—We agree with the main thrust of Yvonne Stedman and Max Elstein's editorial advocating more cohesive provision of sexual health services.1 But have the authors taken too narrow a view of where and when patients present? There is no mention of the work of accident and emergency departments in this field.

Males who present to accident and emergency departments with problems of a sexual nature can usually be managed with either reassurance or referral for investigation in the relevant clinic, …
Function of Caveolin-1 in sensitivity to taxanes in MCF-7 breast cancer cells
Authors: Ayesha N. Shajahan, Aifen Wang, Alan Zwart, Minetta Liu, Robert Clarke
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4656 

Taxanes are potent anti-tumor agents that bind to the beta subunits of tubulin and repress the dynamic instability of spindles leading to cell cycle arrest in the G2/M phase. Taxanes are widely used as chemotherapeutic drug for the treatment of metastatic breast lung, ovarian, and digestive cancers. Discovery of predictive biomarkers for drug efficacy is essential for lowering non-specific toxicity and for understanding how cells gain resistance to taxanes. Caveolin-1 (cav-1) is a putative regulator of cell transformation in many cancers. In lung cancer cells, exposure to the taxane Paclitaxel (Taxol) was shown to increase cav-1 expression, suggesting a role of cav-1 in the cytotoxic response to this group of microtubule disrupting agents. However, the mechanism of cav-1 function in taxane-mediated cell death remains unknown. To elucidate the role of this complex signaling protein in response to taxanes in breast cancer, we explored cav-1 function in mediating the cytotoxic effects of Paclitaxel (Pac) and Docetaxel (Doc) in MCF-7 breast cancer adenocarcinoma cells. At low concentrations (10 nM), overexpression of the full-length wild-type cav-1 in MCF-7 (MCF-7/WT-Cav1) cells increased both Pac and Doc mediated growth inhibition compared to cells expressing the empty vector (MCF-7/EV). Treatment of cells with either drug for 24 h, significantly increased cell cycle arrest in the G2/M phase in the MCF-7/WT-Cav1 relative to control cells. Additionally, in comparison to MCF-7/EV cells, treatment of MCF-7/WT-Cav-1 cells with Pac or Doc also increased phosphorylation of Bcl-2 and Jnk1/2, which are known downstream regulators of taxane-mediated cell death. In this study, we investigate how cav-1 sensitizes breast cancer cells to taxanes. Results from our study could be useful in predicting tumor responsiveness to these drugs.
Paclitaxel, ifosfamide, and cisplatin (TIP) salvage therapy for patients (pts) with relapsed testicular germ cell tumors (GCT)
Authors: J. Mardiak, T. Salek, Z. Sycova-Mila, Z. Hlavata, J. Obertova, M. Mego, M. Reckova, I. Koza
Journal: Journal of Clinical Oncology (2004)

4632 Background: Using TIP with higher dose of paclitaxel (250mg/m2 ) Donadio et al (ASCO, 2003) achieved the optimal response in 74% of prognostic favorable GCT and 92% of them are relapse-free more than 2 years. We present our results in similar group of patients achieved by TIP with standard dose of paclitaxel. Methods: 17 pts received the TIP for 1. relaps after favorable response (complete response or a partial response with normal serum tumor markers ) to previous cisplatin containing therapy and in 14 pts the favorable response lasted > 6 months. 4 pts relapsed later than 2 years (late relapse). Four cycles of TIP were given 21 days apart. Paclitaxel 175mg/m2 was administered by 3-hour infusion on day 1, followed by ifosfamide 1.2 g/m2 and cisplatin 20 mg/m2on days 1 through 5. The administration of hemopoetic growth factors was not scheduled. Surgical resection of all radiographic residua was considered. Results: The favorable response was achieved in 10 (59%) pts and 3 of them relapsed. Two years estimated relapse free survival is 70%. Twelve pts (70%) remain alive at median f/u 39 months. 3 of 4 pts with late relapse achieved favorable response and two of them are being maintained from 11+ and 39+ months. Myelosuppression was the major toxicity, Gr3–4 leukopenia was experienced by 11% of courses. Nobody had Gr3–4 non-hematological toxicity. Conclusions: TIP with standard dose of paclitaxel is effective and safe regimen for patients with prognostic favorable relapse of GCT. The number of durable response was lower than was achieved by higher dose of paclitaxel. No significant financial relationships to disclose.
SIRT3–AMP-Activated Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction
Authors: Yen-Chun Lai, Diana M. Tabima, John J. Dube, Kara S. Hughan, Rebecca R. Vanderpool, Dmitry A. Goncharov, Claudette M. St. Croix, Adolfo Garcia-Ocaña, Elena A. Goncharova, Stevan P. Tofovic, Ana L. Mora, Mark T. Gladwin
Journal: Circulation (2016)

Background— Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly recognized clinical complication of metabolic syndrome. No adequate animal model of PH-HFpEF is available, and no effective therapies have been identified to date. A recent study suggested that dietary nitrate improves insulin resistance in endothelial nitric oxide synthase null mice, and multiple studies have reported that both nitrate and its active metabolite, nitrite, have therapeutic activity in preclinical models of pulmonary hypertension. Methods and Results— To evaluate the efficacy and mechanism of nitrite in metabolic syndrome associated with PH-HFpEF, we developed a 2-hit PH-HFpEF model in rats with multiple features of metabolic syndrome attributable to double-leptin receptor defect (obese ZSF1) with the combined treatment of vascular endothelial growth factor receptor blocker SU5416. Chronic oral nitrite treatment improved hyperglycemia in obese ZSF1 rats by a process that requires skeletal muscle SIRT3-AMPK-GLUT4 signaling. The glucose-lowering effect of nitrite was abolished in SIRT3-deficient human skeletal muscle cells, and in SIRT3 knockout mice fed a high-fat diet, as well. Skeletal muscle biopsies from humans with metabolic syndrome after 12 weeks of oral sodium nitrite and nitrate treatment (IND#115926) displayed increased activation of SIRT3 and AMP-activated protein kinase. Finally, early treatments with nitrite and metformin at the time of SU5416 injection reduced pulmonary pressures and vascular remodeling in the PH-HFpEF model with robust activation of skeletal muscle SIRT3 and AMP-activated protein kinase. Conclusions— These studies validate a rodent model of metabolic syndrome and PH-HFpEF, suggesting a potential role of nitrite and metformin as a preventative treatment for this disease.
Pharmacodynamic study of BAY 43-9006 in patients with metastatic renal cell carcinoma
Authors: P. J. O’Dwyer, M. Rosen, M. Gallagher, B. Schwartz, K. T. Flaherty
Journal: Journal of Clinical Oncology (2005)

3005 Background: BAY 43-9006 (BAY) is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-β. In preclinical models BAY administration is associated with decreased microvessel density and area in colon and breast cancer xenografts. We investigated alterations in tumor perfusion and vascular permeability associated with BAY using dynamic contrast-enhanced MRI (DCE-MRI). Methods: BAY was given from day 1 to 28 of a 28 day cycle at 400 mg bid. DCE-MRI was performed at baseline and after a median of 6.1 weeks (range 2.7–10.9 weeks). The rate constant for gadolinium transfer from the vasculature to the interstitium (Ktrans) and volume fraction of the tissue extracellular and extravascular space (Ve) were calculated for an index lesion for each patient and were normalized for the arterial input function. Response was assessed with CT scans after 12 weeks, then every 8 weeks for four months, then every 12 weeks using WHO criteria. Results: 17 renal cell carcinoma patients (pts) (median age 59, PS 0–1) have been enrolled on this pharmacodynamic study and 16 underwent baseline and follow-up MRIs. Data are available from both scans for 12 patients. 65% of patients had clear cell histology and had a median of 1 prior therapy (range 0–6). As in previous studies, BAY was well-tolerated at this dose and schedule. Responses using WHO criteria included 7 partial responses (ORR 41%), 7 minor responses (25–50% reduction), 2 stable disease and 1 progression prior to 12 weeks. Median time to progression has not been reached, but is at least 10.8 months. Among the 12 patients with data from both DCE-MRIs, Ktrans declined by 60.9% on average (95% CI 45.5–76.4%), and Ve declined by 23.4% (95% CI 4.8–41.9%). Both high Ktrans at baseline, and percent decline in Ktrans, correlated with time to progression. Conclusions: BAY 43–9006 is well-tolerated as a single-agent and is associated with significant alterations in measures of vascular permeability and tumor perfusion in patients with renal cell carcinoma. Preliminary evidence is adduced that therapeutic efficacy is a consequence of angiogenesis inhibition. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer Bayer Bayer Bayer Bayer
Factors affecting to quit smoking in an outpatient smoking cessation clinic
Authors: Bedriye Atay Yayla, Ali Ihsan Yildiz, Güven Cosgun, Erhan Ugurlu, Fatma Evyapan
Journal: European Respiratory Journal (2011)

Aim: Majority of the smokers intend to stop smoking. But success rate is low and is affected by many factors. Our aim is to determine the rate of the smoking cessation and the factors affecting the success of our smoking cessation outpatient clinic.

Material and methods: We evaluated 201 people admitted to our smoking cessation clinic between February 2009- February 2011. Patients reevaluated at the end of 2 years by phone call.

Results: Patients mean age was: 44,18±13; 69,1% male,30,9 were female with mean 28,95±20,82 pack-years of smoking status. Majority (92,2%) had complaints related to smoking: dyspnea (58,8), sputum (75,5%), halithosis (63,7) 89,7% of the had already unsuccessful attempt to quit. Fagerstrom test showed that 45,6% > 6. At the end of 2 years we could reach 128 patients.There were no difference between the responders and unreached patients according to age, sex, presence of co-morbid diseases, smoking status and tobacco addiction status. The rate of the patients who stopped smoking was 21,8% after 2 years.

Patients with higher Fagerstrom test values (6 > pts) had higher rate of stop smoking (p=0,037); dyslipidemia was the commonest co-morbiditiy among quitters (42,3% p=0,014), patients with >1 follow-up visits had higher rate of quit smoking (p=0,005). Vareniclin was superior (39,3%) to NRT (7,1%) (p < 0,05).

Conclusions: The rate of smoking cessation is mainly affected by the patients tobacco addiction levels, patients concern of potential cardiovascular co-morbidities, and patients determination especially to the requested follow-up visits. Vareniclin is found to be superior to the NRT. Failure of health care professionals (0%) deserved further concern.
The study of the effect of intensity of blood pressure management on the progression of type 1 diabetic nephropathy
Authors: R A Rodby, R Rohde, J Evans, R P Bain, W S Mulcahy, E J Lewis
Journal: Journal of the American Society of Nephrology (1995)

A randomized, prospective, clinical trial has been initiated to continue follow-up in a subset of the patients previously enrolled in the recently completed Study of Angiotensin-Converting Enzyme Inhibition (ACEi) in Type 1 Diabetic Nephropathy. In that study, the use of captopril was associated with a 48% reduction in the risk of doubling the serum creatinine and a 50% reduction in the risk of experiencing dialysis, transplantation, or death, compared with the use of placebo. These effects were independent of captopril's effect on the blood pressure. This study is designed to determine whether the level of mean arterial blood pressure (MAP), using the ACE inhibitor ramipril as the primary therapy, is associated with an improved prognosis of diabetic nephropathy with respect to (1) the rate of decline in renal function; (2) the rate of progression to end-stage renal failure; (3) the clinical course of proteinuria; (4) morbidity; and (5) mortality. Patients are randomized into one of two distinct blood pressure control groups, an Intensive Group #1, MAP < or = 92 mm Hg; and a Moderate Group #2, MAP 100 to 107 mm Hg. Patients previously enrolled in the "Study of ACEi in Type 1 Diabetic Nephropathy" whose serum creatinine was less than 4.0 mg/dL (354 mumol/L) were eligible for randomization into this study. All patients will receive ramipril (2.5 to 10.0 mg/day) as the primary therapy, with the addition or removal of other antihypertensive agents as needed to achieve the assigned blood pressure goal.(ABSTRACT TRUNCATED AT 250 WORDS)
Potential predictive and prognostic biomarkers identified in baseline plasma samples from the VELOUR trial.
Authors: Tasha Nicholle Sims, Bo Gao, Robert Phillips, Israel Lowy
Journal: Journal of Clinical Oncology (2015)

638 Background: Biomarkers of resistance or susceptibility to vascular endothelial growth factor (VEGF) inhibition have not been validated. Ziv-aflibercept (ZALTRAP), a fusion protein that binds and neutralizes ligands of VEGFR1 and VEGFR2 (e.g., VEGFA, PLGF, and VEGFB), is approved for the treatment of metastatic colorectal cancer (mCRC) in combination with FOLFIRI in patients who have progressed after oxaliplatin therapy. We are currently analyzing plasma samples from VELOUR, the registration trial of FOLFIRI +/- ziv-aflibercept, in an effort to identify prognostic and predictive factors. Methods: VELOUR was a prospective, multicenter, multinational, randomized (1:1), double-blind, parallel-arm phase III study conducted in 1,226 patients. Retrospective analysis of circulating proteins from 553 baseline plasma samples was performed. Samples were analyzed for levels of 98 analytes using multiplex assays and ELISA. Biomarker values were dichotomized around the median value and analyzed with respect to overall survival (OS). Results: The biomarker study sub-population was similar to the overall VELOUR population. For OS, the hazard ratio (HR) was 0.809 in the plasma biomarker population vs. HR =0.817 in the overall VELOUR population. For PFS, the HR = 0.752 in the plasma biomarker population vs. HR = 0.758 in VELOUR. Patient demographics, including ECOG status, were similar between the groups. Several biomarkers were identified as potentially predictive or prognostic (or both) of OS, with a HR&lt;0.7 (false discovery rate of 0.05 and interaction p &lt; 0.10). No biomarker subset corresponded to worse OS with ziv-aflibercept treatment. Conclusions: Multiple potential prognostic and predictive biomarkers were identified in VELOUR and will be presented. These results are exploratory and require prospective studies for validation. Patient subsets with elevated expression of alternative angiogenic factors or increased pro-inflammatory markers may correlate with poor outcome overall, and in some cases are not improved by addition of ziv-aflibercept treatment. Further investigation of this dataset continues, including analysis of on-treatment plasma samples in a subset of patients.
Limited Capacity for Motor Activity as a Cause for Declining Food Intake in Cancer
Authors: S. D. Morrison
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Limited Capacity for Motor Activity as a Cause for Declining Food Intake in Cancer Get access S. D. Morrison S. D. Morrison Laboratory of Physiology, Nat~onal Cancer Institute, National Institutes of Health, Pubhc Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 5, November 1973, Pages 1535–1539, https://doi.org/10.1093/jnci/51.5.1535 Published: 01 November 1973 Article history Received: 27 March 1973 Accepted: 17 July 1973 Published: 01 November 1973
The impact of physical activity on patients with stage III colon cancer: Findings from Intergroup trial CALGB 89803
Authors: J. A. Meyerhardt, D. Heseltine, D. Niedzwiecki, D. Hollis, L. B. Saltz, R. J. Mayer, R. L. Schilsky, C. S. Fuchs
Journal: Journal of Clinical Oncology (2005)

3534 Background: Regular physical activity (PA) is strongly associated with a reduced risk of developing colon cancer. The influence of PA on the outcome of patients with established colon cancer is unknown. Methods: We prospectively studied recreational PA among 816 patients with stage III colon cancer enrolled in a randomized trial of post-operative adjuvant chemotherapy (bolus 5-fluorouracil/leucovorin +/- irinotecan). Patients completed detailed surveys of various non-occupational activities midway through adjuvant therapy (Q1) and then again 6 months after completion of therapy (12–14 months after enrollment, Q2). Levels of PA were measured as total metabolic equivalent tasks (MET)-hours-per-week scores & divided into quintiles. We computed Cox proportional hazards for disease-free survival (DFS) and overall survival (OS) according to quintiles of PA as measured on Q2. DFS and OS were measured from completion of Q2 to recurrence or death (DFS) and death (OS), excluding events within the 1st 90 days to avoid biases of decreased activity due to underlying disease. Median follow-up after the post-chemotherapy questionnaire was 2.4 years. Results: Levels of PA were associated with significantly improved DFS among patients with stage III colon cancer. After adjustment for age, gender, baseline performance status, N stage, T stage, preoperative CEA, bowel obstruction and perforation, level of differentiation, treatment arm, and body mass index, the hazard ratio (HR) for DFS for individuals in the highest quintile (>25 MET-hours/week, eg. jog 3–4 hours/week or brisk walk [3–4 mph] daily) was 0.65 (95% CI, 0.38–1.11; p for trend = 0.02) compared to those in the lowest quintile of PA. This relationship varied by gender with a HR = 0.33 [95% CI, 0.11–0.99] for women (p for trend = 0.046) and a HR= 0.89 [95% CI, 0.44–1.78] for men (p for trend = 0.3). Data on OS is not yet mature, though the p trend among all patients with increasing PA is 0.02. Conclusions: Increased PA appears to be associated with DFS and OS among patients with stage III colon cancer. Follow-up data will be more mature at the time of presentation, as will analyses on the impact of PA on treatment-related toxicities No significant financial relationships to disclose.