tbuckley/cabot-search huggingface dataset:
Phase I trial of paclitaxel and gemcitabine administered every two weeks in patients with refractory solid tumors
Authors: M.L. Rothenberg, A. Sharma, G.R. Weiss, M.A. Villalona-Calero, J.R. Eckardt, C. Aylesworth, M.A. Kraynak, D.A. Rinaldi, G.I. Rodriguez, H.A. Burris, S.G. Eckhardt, C.D. Stephens, K. Forral, S.J. Nicol, D.D. Von Hoff
Journal: Annals of Oncology (1998)
Altitude training and haemoglobin mass from the optimised carbon monoxide rebreathing method determined by a meta-analysis
Authors: Christopher J Gore, Ken Sharpe, Laura A Garvican-Lewis, Philo U Saunders, Clare E Humberstone, Eileen Y Robertson, Nadine B Wachsmuth, Sally A Clark, Blake D McLean, Birgit Friedmann-Bette, Mitsuo Neya, Torben Pottgiesser, Yorck O Schumacher, Walter F Schmidt
Journal: British Journal of Sports Medicine (2013)

Objective To characterise the time course of changes in haemoglobin mass (Hbmass) in response to altitude exposure. Methods This meta-analysis uses raw data from 17 studies that used carbon monoxide rebreathing to determine Hbmass prealtitude, during altitude and postaltitude. Seven studies were classic altitude training, eight were live high train low (LHTL) and two mixed classic and LHTL. Separate linear-mixed models were fitted to the data from the 17 studies and the resultant estimates of the effects of altitude used in a random effects meta-analysis to obtain an overall estimate of the effect of altitude, with separate analyses during altitude and postaltitude. In addition, within-subject differences from the prealtitude phase for altitude participant and all the data on control participants were used to estimate the analytical SD. The ‘true’ between-subject response to altitude was estimated from the within-subject differences on altitude participants, between the prealtitude and during-altitude phases, together with the estimated analytical SD. Results During-altitude Hbmass was estimated to increase by ∼1.1%/100 h for LHTL and classic altitude. Postaltitude Hbmass was estimated to be 3.3% higher than prealtitude values for up to 20 days. The within-subject SD was constant at ∼2% for up to 7 days between observations, indicative of analytical error. A 95% prediction interval for the ‘true’ response of an athlete exposed to 300 h of altitude was estimated to be 1.1–6%. Conclusions Camps as short as 2 weeks of classic and LHTL altitude will quite likely increase Hbmass and most athletes can expect benefit.
The Impact of Reducing Cardiovascular Medication Copayments on Health Spending and Resource Utilization
Authors: Niteesh K. Choudhry, Michael A. Fischer, Jerry L. Avorn, Joy L. Lee, Sebastian Schneeweiss, Daniel H. Solomon, Christine Berman, Saira Jan, Joyce Lii, John J. Mahoney, William H. Shrank
Journal: Journal of the American College of Cardiology (2012)
Lymphotoxin-Mediated Crosstalk between B Cells and Splenic Stroma Promotes the Initial Type I Interferon Response to Cytomegalovirus
Authors: Kirsten Schneider, Andrea Loewendorf, Carl De Trez, James Fulton, Antje Rhode, Heather Shumway, Sukwon Ha, Ginelle Patterson, Klaus Pfeffer, Sergei A. Nedospasov, Carl F. Ware, Chris A. Benedict
Journal: Cell Host & Microbe (2008)
Inhibition of GSK3B Bypass Drug Resistance of p53-Null Colon Carcinomas by Enabling Necroptosis in Response to Chemotherapy
Authors: Emanuela Grassilli, Robert Narloch, Elena Federzoni, Leonarda Ianzano, Fabio Pisano, Roberto Giovannoni, Gabriele Romano, Laura Masiero, Biagio Eugenio Leone, Serena Bonin, Marisa Donada, Giorgio Stanta, Kristian Helin, Marialuisa Lavitrano
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Evasion from chemotherapy-induced apoptosis due to p53 loss strongly contributes to drug resistance. Identification of specific targets for the treatment of drug-resistant p53-null tumors would therefore increase the effectiveness of cancer therapy. Experimental Design: By using a kinase-directed short hairpin RNA library and HCT116p53KO drug-resistant colon carcinoma cells, glycogen synthase kinase 3 beta (GSK3B) was identified as a target whose silencing bypasses drug resistance due to loss of p53. p53-null colon cancer cell lines with different sets of mutations were used to validate the role of GSK3B in sustaining resistance and to characterize cell death mechanisms triggered by chemotherapy when GSK3B is silenced. In vivo xenograft studies were conducted to confirm resensitization of drug-resistant cells to chemotherapy upon GSK3 inhibition. Colon cancer samples from a cohort of 50 chemotherapy-treated stage II patients were analyzed for active GSK3B expression. Results: Downregulation of GSK3B in various drug-resistant p53-null colon cancer cell lines abolished cell viability and colony growth after drug addition without affecting cell proliferation or cell cycle in untreated cells. Cell death of 5-fluorouracil (5FU)–treated p53-null GSK3B-silenced colon carcinoma cells occurred via PARP1-dependent and AIF-mediated but RIP1-independent necroptosis. In vivo studies showed that drug-resistant xenograft tumor mass was significantly reduced only when 5FU was given after GSK3B inhibition. Tissue microarray analysis of colon carcinoma samples from 5FU-treated patients revealed that GSK3B is significantly more activated in drug-resistant versus responsive patients. Conclusions: Targeting GSK3B, in combination with chemotherapy, may represent a novel strategy for the treatment of chemotherapy-resistant tumors. Clin Cancer Res; 19(14); 3820–31. ©2013 AACR.
Tolerogenicity of resting and activated B cells.
Authors: K M Gilbert, W O Weigle
Journal: The Journal of Experimental Medicine (1994)

Antigen presentation by resting splenic B cells has been shown previously to induce T helper 1 cell (Th1) anergy. In contrast to expectations, it was found here that B cells treated with F(ab')2 goat anti-mouse immunoglobulin (IgM) for 24 or 48 h also presented antigen (Ag) to Th1 cells in a manner that induced dramatic Ag-specific proliferative inactivation. The tolerogenicity of the anti-Ig-treated B cells was consistent with the observation that these B cells were only slightly more efficient than resting B cells in stimulating human gamma globulin (HGG)-induced proliferation of HGG-specific Th1 cells in primary cultures. The activated B cells were, however, more efficient than resting B cells in stimulating a primary mixed leukocyte reaction, and exhibited increased expression of major histocompatibility complex class II molecules, RL388 Ag and transferrin receptor. In addition, unlike resting B cells, which expressed little detectable B7, anti-Ig-treated B cells expressed high levels of B7. The functional capacity of the B7 expressed on the activated B cells was demonstrated by the fact that the Ag-presenting capacity of these B cells was inhibited by the addition to culture of CTLA4Ig, a soluble receptor for B7. It is unlikely that the tolerogenicity of the activated B cells was due to an inability of the Th1 cells to respond to B7 signals; the Th1 clones used in the experiments, unlike the Th2 clones tested, expressed CD28, the ligand for B7. In addition, anti-CD28 monoclonal antibody inhibited the induction of Th1 cell anergy when added to cultures of Th1 cells and Ag-pulsed fixed antigen-presenting cells. Taken together, the results indicate that B cells, even when activated, do not satisfy the costimulatory requirements of the Th1 cells used here, and therefore can present Ag in a tolerogenic fashion to Th1 cells. The costimulator deficiency of activated B cells may reflect an inadequacy in the level of B7 expressed or a lack of some other molecule.
Retention of adenovirus E19 glycoprotein in the endoplasmic reticulum is essential to its ability to block antigen presentation.
Authors: J H Cox, J R Bennink, J W Yewdell
Journal: The Journal of Experimental Medicine (1991)

The E3/19K glycoprotein of adenovirus functions to diminish recognition of adenovirus-infected cells by major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTLs) by binding intracellular class I molecules and preventing them from reaching the plasma membrane. In the present study we have characterized the nature of the interaction between E3/19K and the H-2Kd (Kd) molecule. An E3/19K molecule genetically engineered to terminate six residues from its normal COOH terminus (delta E19), was found to associate with Kd in a manner indistinguishable from wild-type E3/19K. Unlike E3/19K, however, delta E19 was transported through the Golgi complex to the plasma membrane, where it could be detected biochemically and immunocytochemically using a monoclonal antibody specific for the lumenal domain of E3/19K. Importantly, delta E19 also differed from E3/19K in being unable to prevent the presentation of Kd-restricted viral proteins to CTLs. This is unlikely to be due to delta E19 having a lower avidity for Kd than E3/19K, since delta E19 was able to compete with E3/19K for Kd binding, both physically, and functionally in nullifying the E3/19K blockade of antigen presentation. These findings indicate that the ability of E3/19K to block antigen presentation is due solely to its ability to retain newly synthesized class I molecules in the endoplasmic reticulum.
Effect of Calcium Supplementation on the Risk of Large Bowel Polyps
Authors: K. Wallace, J. A. Baron, B. F. Cole, R. S. Sandler, M. R. Karagas, M. A. Beach, R. W. Haile, C. A. Burke, L. H. Pearson, J. S. Mandel, R. Rothstein, D. C. Snover
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Clinical trials have shown that calcium supplementation modestly decreases the risk of colorectal adenomas. However, few studies have examined the effect of calcium on the risk of different types of colorectal lesions or dietary determinants of this effect. Methods: Our analysis used patients from the Calcium Polyp Prevention Study, a randomized, double-blind, placebo-controlled chemoprevention trial among patients with a recent colorectal adenoma. Nine hundred thirty patients were randomly assigned to calcium carbonate (1200 mg/day) or placebo. Follow-up colonoscopies were conducted approximately 1 and 4 years after the qualifying examination. We used general estimating equation (GEE) and generalized linear regression analyses to compute risk ratios and 95% confidence intervals (CIs) to assess the effect of calcium treatment versus placebo on the risk of hyperplastic polyps, tubular adenomas, and more advanced lesions. Additionally, we used GEE analyses to compare the calcium treatment effects for various types of polyps with that for tubular adenomas. We also examined the interaction between calcium treatment and baseline intake of dietary calcium, fat, and fiber. All P values were obtained using Wald tests based on the corresponding models. All tests of statistical significance were two-sided. Results: The calcium risk ratio for hyperplastic polyps was 0.82 (95% CI = 0.67 to 1.00), that for tubular adenomas was 0.89 (95% CI = 0.77 to 1.03), and that for histologically advanced neoplasms was 0.65 (95% CI = 0.46 to 0.93) compared with patients assigned to placebo. There were no statistically significant differences between the risk ratio for tubular adenomas and that for other types of polyps. The effect of calcium supplementation on adenoma risk was most pronounced among individuals with high dietary intakes of calcium and fiber and with low intake of fat, but the interactions were not statistically significant. Conclusion: Our results suggest that calcium supplementation may have a more pronounced antineoplastic effect on advanced colorectal lesions than on other types of polyps.
Viricidal effect of Lactobacillus acidophilus on human immunodeficiency virus type 1: possible role in heterosexual transmission.
Authors: S J Klebanoff, R W Coombs
Journal: The Journal of Experimental Medicine (1991)

Peroxidase, H2O2, and a halide form a powerful antimicrobial system in phagocytes and tissue fluids, and certain microorganisms can serve as the source of H2O2 for this system. H2O2-generating Lactobacillus acidophilus (LB+) is present in the vagina of most normal women and peroxidase has been detected in vaginal fluid. LB+ at high concentration is viricidal to HIV-1, and, at levels where LB+ is ineffective alone, the addition of peroxidase (myeloperoxidase, eosinophil peroxidase) and a halide (chloride, iodide, bromide, thiocyanate) restore viricidal activity. LB+ can be replaced by H2O2, but not by non-H2O2-producing LB, and viricidal activity is inhibited by azide and catalase. The survival of HIV in the female genital tract and thus the likelihood of transmission may be influenced by the activity of the LB(+)-peroxidase-halide system in the vagina.
MicroRNA and vascular smooth muscle cell phenotype: new therapy for atherosclerosis?
Authors: Chunxiang Zhang
Journal: Genome Medicine (2009)

MicroRNAs (miRNAs) represent a class of small, non-coding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Recent studies have identified that miR-145 is the most abundant miRNA in normal arteries and vascular smooth muscle cells (VSMCs), and its expression is significantly downregulated in dediffer-entiated VSMCs and atherosclerotic arteries. miR-145 plays a critical role in modulating VSMC phenotype. Because phenotypic modulation of VSMCs is an initial cellular event in the development of atherosclerosis, miRNAs, and miR-145 in particular, may represent new therapeutic targets for atherosclerosis.
Longitudinal lung function decline and wood dust exposure in the furniture industry
Authors: G. Jacobsen, V. Schlünssen, I. Schaumburg, E. Taudorf, T. Sigsgaard
Journal: European Respiratory Journal (2007)

The aim of the present study was to investigate the relationship between change in lung function and cumulative exposure to wood dust. In total, 1,112 woodworkers (927 males, 185 females) and 235 reference workers (104 males, 185 females) participated in a 6-yr longitudinal study. Forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC), height and weight were measured, and questionnaire data on respiratory symptoms, wood dust exposure and smoking habits were collected. Cumulative inhalable wood dust exposure was assessed using a study-specific job exposure matrix and exposure time. The median (range) for cumulative wood dust exposure was 3.75 (0–7.55) mg·year·m −3 . A dose–response relationship between cumulative wood dust exposure and percent annual decrease in FEV 1 was suggested for female workers. This was confirmed in a linear regression model adjusted for confounders, including smoking, height and age. An additional difference of -14.50 mL·yr −1 and −27.97 mL·yr −1 was revealed for females exposed to 3.75–4.71 mg·yr·m −3 or to &gt;4.71 mg·yr·m −3 , respectively, compared with non-/low-exposed females. For females, a positive trend between wood dust exposure and the cumulative incidence proportion of FEV 1 /FVC &lt;70% was suggested. In conclusion, in the present low-exposed cohort, female woodworkers had an accelerated decline in lung function, which may be clinically relevant.
PD-0001 Can We Predict Time to Tumor Progression in Early Colorectal Cancer Patients Using CTCS Count?
Authors: Michela Roberto, Adriana Romiti, Roberta Di Rocco, Salvatore Raffa, Danilo Ranieri, Annalisa Milano, Valeria Durante, Chiara D'Antonio, Viola Barucca, Mara Torrisi, Paolo Marchetti
Journal: Annals of Oncology (2013)
Platelet Transfusion: A Clinical Practice Guideline From the AABB
Authors: Richard M. Kaufman, Benjamin Djulbegovic, Terry Gernsheimer, Steven Kleinman, Alan T. Tinmouth, Kelley E. Capocelli, Mark D. Cipolle, Claudia S. Cohn, Mark K. Fung, Brenda J. Grossman, Paul D. Mintz, Barbara A. O'Malley, Deborah A. Sesok-Pizzini, Aryeh Shander, Gary E. Stack, Kathryn E. Webert, Robert Weinstein, Babu G. Welch, Glenn J. Whitman, Edward C. Wong, Aaron A.R. Tobian
Journal: Annals of Internal Medicine (2014)

Background: The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients. Methods: These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Recommendation 1: The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence) Recommendation 2: The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence) Recommendation 3: The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence) Recommendation 4: The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence) Recommendation 5: The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence) Recommendation 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence)
Differential effects of antihypertensive drug therapy on vascular smooth muscle cell hypertrophy, hyperploidy, and hyperplasia in the spontaneously hypertensive rat.
Authors: G K Owens
Journal: Circulation Research (1985)

The present report extends our previous studies of smooth muscle cell hypertrophy, hyperploidy, and hyperplasia in the 5-month-old spontaneously hypertensive and Wistar-Kyoto rats to include analyses of 3- and 7-month-old rats and explores the effects of antihypertensive drug treatment on the accelerated growth of vascular smooth muscle in aortas of spontaneously hypertensive vs. Wistar-Kyoto rats. Drug-treated rats were administered a combination of reserpine, hydralazine, and chlorathiazide in their drinking water, either between 3 and 5 months or between 5 and 7 months of age. Drug treatment decreased the blood pressure of spontaneously hypertensive rats to values at or below those of Wistar-Kyoto rats for both age-treatment groups. Smooth muscle growth was evaluated by morphometric analyses of aortic smooth muscle content, flow cytometric and microdensitometric measurements of the frequency of polyploid smooth muscle cells, biochemical estimates of aortic medial smooth muscle cell number, and microdensitometric measurements of individual smooth muscle cell protein content. The following results were obtained. Aortic medial smooth muscle content was not significantly increased in 3-month spontaneously hypertensive compared to Wistar-Kyoto rats, indicating that aortic smooth muscle hypertrophy occurred post-3 months, as well as after blood pressure was elevated. In 5-month-old spontaneously hypertensive and Wistar-Kyoto rats, medial smooth muscle hypertrophy could be accounted for by cellular hypertrophy without hyperplasia; in contrast, medial hypertrophy in 7-month-old spontaneously hypertensive rats involved both cellular hypertrophy and hyperplasia. Antihypertensive treatment prevented the accelerated growth of vascular smooth muscle that occurred in spontaneously hypertensive rats via cellular hypertrophy and hyperploidy, but it did not prevent an increase in smooth muscle cell number in spontaneously hypertensive rats between 5 and 7 months of age. Furthermore, it had no effect on the parallel increases in aortic medial smooth muscle cell number that occurred in both spontaneously hypertensive and Wistar-Kyoto rats between 3 and 5 months of age. Whereas drug treatment prevented accelerated development of smooth muscle cell polyploidism in spontaneously hypertensive rats, in no case (spontaneously hypertensive or Wistar-Kyoto rats) did it reverse changes in ploidy that existed at the time of initiation of drug treatment, although it did cause cellular atrophy in smooth muscle cells of each ploidy class.(ABSTRACT TRUNCATED AT 400 WORDS)
Cisplatin Plus Gemcitabine or Vinorelbine for Elderly Patients With Advanced Non–Small-Cell Lung Cancer: The MILES-2P Studies
Authors: Cesare Gridelli, Paolo Maione, Alfonso Illiano, Franco Vito Piantedosi, Adolfo Favaretto, Alessandra Bearz, Sergio Federico Robbiati, Virginio Filipazzi, Vito Lorusso, Francesco Carrozza, Rosario Vincenzo Iaffaioli, Luigi Manzione, Ciro Gallo, Alessandro Morabito, Francesco Perrone
Journal: Journal of Clinical Oncology (2007)

Two phase I/II trials were done to evaluate the feasibility of cisplatin combined with gemcitabine or vinorelbine in elderly patients with advanced non-small-cell lung cancer (NSCLC).Patients with advanced NSCLC who were older than 70 years of age and who had a performance status of 0 to 1 were eligible. Cisplatin was given on day 1 (a starting dose of 50 mg/m2 with increasing increments of 10 mg/m2 at each level) and gemcitabine (1,000 mg/m2) or vinorelbine (25 mg/m2) on days 1 and 8. Cycles were repeated every 21 days. A two-stage flexible optimal design was applied in the phase II study, and unacceptable toxicity was the primary end point.Overall, 159 patients were enrolled: 38 in phase I and 121 in phase II studies. Cisplatin was feasible at 60 mg/m2 with gemcitabine and at 40 mg/m2 with vinorelbine. With the former combination, 50 of 60 (83.3%) patients were treated without unacceptable toxicity; objective responses were reported in 26 of 60 patients (43.5%; 95% CI, 30.6 to 56.8); median progression-free and overall survivals were 25.3 and 43.6 weeks, respectively. With the latter combination, 50 (82.0%) of 61 patients were treated without unacceptable toxicity; objective responses were reported in 22 of 61 patients (36.1%; 95% CI, 24.2 to 49.4); median progression-free and overall survivals were 21.1 and 33.1 weeks, respectively.Both cisplatin (60 mg/m2) plus gemcitabine and cisplatin (40 mg/m2) plus vinorelbine are feasible and active in the treatment of elderly patients with advanced NSCLC. The former combination, which provides a higher dose of cisplatin, deserves comparison versus single-agent chemotherapy in this setting of patients.