tbuckley/cabot-search huggingface dataset:
Two-Year Randomized Controlled Prospective Trial Converting Treatment of Stable Renal Transplant Recipients With Cutaneous Invasive Squamous Cell Carcinomas to Sirolimus
Authors: Judith M. Hoogendijk-van den Akker, Paul N. Harden, Andries J. Hoitsma, Charlotte M. Proby, Ron Wolterbeek, Jan Nico Bouwes Bavinck, Johan W. de Fijter
Journal: Journal of Clinical Oncology (2013)

In light of the significant morbidity and mortality of cutaneous invasive squamous cell carcinomas (SCCs) in renal transplant recipients, we investigated whether conversion to sirolimus-based immunosuppression from standard immunosuppression could diminish the recurrence rate of these skin cancers.In a 2-year randomized controlled trial, 155 renal transplant recipients with at least one biopsy-confirmed SCC were stratified according to age (< 55 v ≥ 55 years) and number of previous SCCs (one to nine v ≥ 10) and randomly assigned to conversion to sirolimus (n = 74) or continuation of their original immunosuppression (n = 81). Development of a new SCC within 2 years after random assignment was the primary end point.After 2 years of follow-up, the risk reduction of new SCCs in the multivariable analysis was not significant, with a hazard ratio (HR) of 0.76 (95% CI, 0.48 to 1.2; P = .255), compared with a non-sirolimus-based regimen. After the first year, there was a significant 50% risk reduction, with an HR of 0.50 (95% CI, 0.28 to 0.90; P = .021) for all patients together and an HR of 0.11 (95% CI, 0.01 to 0.94; P = .044) for patients with only one previous SCC. The tumor burden of SCC was reduced during the 2-year follow-up period in those receiving sirolimus (0.82 v 1.38 per year; HR, 0.51; 95% CI, 0.32 to 0.82; P = .006) if adjusted for the number of previous SCCs and age. Twenty-nine patients stopped taking sirolimus because of various adverse events.Conversion to sirolimus-based immunosuppression failed to show a benefit in terms of SCC-free survival at 2 years.
Dexamethasone protected human glioblastoma U87MG cells from temozolomide induced apoptosis by maintaining Bax:Bcl-2 ratio and preventing proteolytic activities.
Authors: Arabinda Das, Naren L Banik, Sunil J Patel, Swapan K Ray
Journal: Molecular Cancer (2004)

Glioblastoma is the deadliest and most prevalent brain tumor. Dexamethasone (DXM) is a commonly used steroid for treating glioblastoma patients for alleviation of vasogenic edema and pain prior to treatment with chemotherapeutic drugs. Temozolomide (TMZ), an alkylating agent, has recently been introduced in clinical trials for treating glioblastoma. Here, we evaluated the modulatory effect of DXM on TMZ induced apoptosis in human glioblastoma U87MG cells. Freshly grown cells were treated with different doses of DXM or TMZ for 6 h followed by incubation in a drug-free medium for 48 h. Wright staining and ApopTag assay showed no apoptosis in cells treated with 40 μM DXM but considerable amounts of apoptosis in cells treated with 100 μM TMZ. Apoptosis in TMZ treated cells was associated with an increase in intracellular free [Ca2+], as determined by fura-2 assay. Western blot analyses showed alternations in the levels of Bax (pro-apoptotic) and Bcl-2 (anti-apoptotic) proteins resulting in increased Bax:Bcl-2 ratio in TMZ treated cells. Western blot analyses also detected overexpression of calpain and caspase-3, which cleaved 270 kD α-spectrin at specific sites for generation of 145 and 120 kD spectrin break down products (SBDPs), respectively. However, 1-h pretreatment of cells with 40 μM DXM dramatically decreased TMZ induced apoptosis, decreasing Bax:Bcl-2 ratio and SBDPs. Our results revealed an antagonistic effect of DXM on TMZ induced apoptosis in human glioblastoma U87MG cells, implying that treatment of glioblastoma patients with DXM prior to chemotherapy with TMZ might result in an undesirable clinical outcome.
Differential association of protein tyrosine kinases with the T cell receptor is linked to the induction of anergy and its prevention by B7 family-mediated costimulation.
Authors: V A Boussiotis, D L Barber, B J Lee, J G Gribben, G J Freeman, L M Nadler
Journal: The Journal of Experimental Medicine (1996)

When stimulated through their antigen receptor, without costimulation, T cells enter a state of antigen-specific unresponsiveness, termed anergy. B7-mediated costimulation, signaling via CD28, is sufficient to prevent the induction of anergy. Here we show that ligation of T cell receptor (TCR) by alloantigen alone, which results in anergy, activates tyrosine phosphorylation of TCR zeta and its association with fyn. In contrast, TCR ligation in the presence of B7 costimulation, which results in productive immunity, activates tyrosine phosphorylation of TCR zeta and CD3 chains, which associate with activated lck and zeta-associated protein (ZAP) 70. Under these conditions, CD28 associates with activated lck and TCR zeta. These data suggest that the induction of anergy is an active signaling process characterized by the association of TCR zeta and fyn. In addition, CD28-mediated costimulation may prevent the induction of anergy by facilitating the effective association of TCR zeta and CD3 epsilon with the critical protein tyrosine kinase lck, and the subsequent recruitment of ZAP-70. Strategies to inhibit or activate TCR-associated, specific protein tyrosine kinase-mediated pathways may provide a basis for drug development with potential applications in the fields of transplantation, autoimmunity, and tumor immunity.
A Cell Proliferation Signature Is a Marker of Extremely Poor Outcome in a Subpopulation of Breast Cancer Patients
Authors: Hongyue Dai, Laura van't Veer, John Lamb, Yudong D. He, Mao Mao, Bernard M. Fine, Rene Bernards, Marc van de Vijver, Paul Deutsch, Alan Sachs, Roland Stoughton, Stephen Friend
Journal: Cancer Research (2005)

Abstract Breast cancer comprises a group of distinct subtypes that despite having similar histologic appearances, have very different metastatic potentials. Being able to identify the biological driving force, even for a subset of patients, is crucially important given the large population of women diagnosed with breast cancer. Here, we show that within a subset of patients characterized by relatively high estrogen receptor expression for their age, the occurrence of metastases is strongly predicted by a homogeneous gene expression pattern almost entirely consisting of cell cycle genes (5-year odds ratio of metastasis, 24.0; 95% confidence interval, 6.0-95.5). Overexpression of this set of genes is clearly associated with an extremely poor outcome, with the 10-year metastasis-free probability being only 24% for the poor group, compared with 85% for the good group. In contrast, this gene expression pattern is much less correlated with the outcome in other patient subpopulations. The methods described here also illustrate the value of combining clinical variables, biological insight, and machine-learning to dissect biological complexity. Our work presented here may contribute a crucial step towards rational design of personalized treatment.
Thymocyte Contact or Monoclonal Antibody-Mediated Clustering of 3β1 or 6β4 Integrins Activate Interleukin-6 (IL-6) Transcription Factors (NF-κB and NF-IL6) and IL-6 Production in Human Thymic Epithelial Cells
Authors: Dunia Ramarli, Maria Teresa Scupoli, Emma Fiorini, Ornella Poffe, Monica Brentegani, Antonello Villa, Germana Cecchini, Giuseppe Tridente, Pier Carlo Marchisio
Journal: Blood (1998)
The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review
Authors: C. Stey, J. Steurer, S. Bachmann, T.C. Medici, M.R Tramèr
Journal: European Respiratory Journal (2000)

The role of N-acetylcysteine (NAC) in the treatment of chronic bronchitis is unclear. Since a number of studies have been published on this topic, a systematic review of published studies seems justified. A systematic search (Medline, Embase, Cochrane Library, bibliographies, no language restriction) for published randomized trials comparing oral NAC with placebo in patients with chronic bronchitis was performed. Dichotomous data on prevention of exacerbation, improvement of symptoms and adverse effects were extracted from original reports. The relative benefit and number-needed-to-treat were calculated for both individual trials and combined data. Thirty-nine trials were retrieved; eleven (2,011 analysed patients), published 1976-1994, were regarded as relevant and valid according to preset criteria. In nine studies, 351 of 723 (48.5%) patients receiving NAC had no exacerbation compared with 229 of 733 (31.2%) patients receiving placebo (relative benefit 1.56 (95% confidence interval (CI) 1.37-1.77), number-needed-to-treat 5.8 (95% CI 4.5-8.1). There was no evidence of any effect of study period (12-24 weeks) or cumulative dose of NAC on efficacy. In five trials, 286 of 466 (61.4%) patients receiving NAC reported improvement of their symptoms compared with 160 of 462 (34.6%) patients receiving placebo (relative benefit 1.78 (95% CI 1.54-2.05), number-needed-to-treat 3.7 (95% CI 3.0-4.9)). With NAC, 68 of 666 (10.2%) patients reported gastrointestinal adverse effects compared with 73 of 671 (10.9%) taking placebo. With NAC, 79 of 1,207 (6.5%) patients withdrew from the study due to adverse effects, compared with 87 of 1,234 (7.1%) receiving placebo. In conclusion, with treatment periods of approximately 12-24 weeks, oral N-acetylcysteine reduces the risk of exacerbations and improves symptoms in patients with chronic bronchitis compared with placebo, without increasing the risk of adverse effects. Whether this benefit is sufficient to justify the routine and long-term use of N-acetylcysteine in all patients with chronic bronchitis should be addressed in further studies and cost-effectiveness analyses.
Oncologists Want FDA To Rethink REMS
Authors: M. Goozner
Journal: JNCI Journal of the National Cancer Institute (2010)

Acoalition of cancer care stakeholders organized by the National Comprehensive Cancer Network (NCCN) is pressing the U.S. Food and Drug Administration to make major changes in how it deploys risk evaluation and mitigation strategies (REMS) for widely used cancer drugs. The two REMS drawing the biggest concern are for anemia-treating, erythropoietinstimulating agents (ESAs), whose requirements become fully operational next February, and pain-treating opioids, now under review at the agency. A fi rst draft of the opioid REMS is expected early next year. The idea behind the REMS program is to make sure that patients are fully informed about the risks of certain drugs. ESAs, once taken by about half of cancer patients to treat chemotherapy-associated anemia, have been associated with increased risk of cardiovascular disease and death in trials with several types of cancer. When prescribing them, physicians must follow certain procedures under REMS, steps that some oncologists say are reducing the quality of patient care. Although the FDA has not modifi ed the rules in response to comments from oncologists, it says it is working to streamline and standardize the process.
Estrogen and the endometrium: lessons learned from gene expression profiling in rodents and human
Authors: P.G. Groothuis, H.H.N.M. Dassen, A. Romano, C. Punyadeera
Journal: Human Reproduction Update (2007)

To date, research into the biological processes and molecular mechanisms associated with endometrial receptivity and embryo implantation has been a focus of attention, whereas the complex events that occur in the human endometrium during the menstrual and proliferative phase under the influence of estrogen have received little attention. The objective of this review is to provide an update of our current understanding of the actions of estrogen on both human and rodent endometrium, with special emphasis on the regulation of uterine growth and cell proliferation, and the value of global gene expression analysis, in increasing understanding of these processes.
Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk
Authors: Stephan Weidinger, Hansjörg Baurecht, Stefan Wagenpfeil, John Henderson, Natalija Novak, Aileen Sandilands, Huijia Chen, Elke Rodriguez, Grainne M. O'Regan, Rosemarie Watson, Haihui Liao, Yiwei Zhao, Jonathan N.W.N. Barker, Michael Allen, Nick Reynolds, Simon Meggitt, Kate Northstone, George D. Smith, Carolin Strobl, Caroline Stahl, Thomas Kneib, Norman Klopp, Thomas Bieber, Heidrun Behrendt, Colin N.A. Palmer, H.-Erich Wichmann, Johannes Ring, Thomas Illig, W.H. Irwin McLean, Alan D. Irvine
Journal: Journal of Allergy and Clinical Immunology (2008)
Effect of Rosiglitazone on Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
Authors: Hertzel C. Gerstein, Robert E. Ratner, Christopher P. Cannon, Patrick W. Serruys, Héctor M. García-García, Gerrit-Anne van Es, Nikheel S. Kolatkar, Barbara G. Kravitz, Diane M. Miller, Chun Huang, Peter J. Fitzgerald, Richard W. Nesto
Journal: Circulation (2010)

Rosiglitazone has several properties that may affect progression of atherosclerosis. The Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Diabetes Patients With Cardiovascular History (APPROACH) study was undertaken to determine the effect of the thiazolidinedione rosiglitazone on coronary atherosclerosis as assessed by intravascular ultrasound compared with the sulfonylurea glipizide.This was a randomized, double-blind, controlled 18-month study in 672 patients aged 30 to 80 years with established type 2 diabetes mellitus treated by lifestyle, 1 oral agent, or submaximal doses of 2 oral agents who had at least 1 atherosclerotic plaque with 10% to 50% luminal narrowing in a coronary artery that had not undergone intervention during a clinically indicated coronary angiography or percutaneous coronary intervention. The primary outcome was change in percent atheroma volume in the longest and least angulated epicardial coronary artery that had not undergone intervention. Secondary outcomes included change in normalized total atheroma volume and change in total atheroma volume in the most diseased baseline 10-mm segment. Rosiglitazone did not significantly reduce the primary outcome of percent atheroma volume compared with glipizide (-0.64%; 95% confidence interval, -1.46 to 0.17; P=0.12). The secondary outcome of normalized total atheroma volume was significantly reduced by rosiglitazone compared with glipizide (-5.1 mm(3); 95% confidence interval, -10.0 to -0.3; P=0.04); however, no significant difference between groups was observed for the change in total atheroma volume within the most diseased baseline 10-mm segment (-1.7 mm(3); 95% confidence interval, -3.9 to 0.5; P=0.13).Rosiglitazone did not significantly decrease the primary end point of progression of coronary atherosclerosis more than glipizide in patients with type 2 diabetes mellitus and coronary atherosclerosis. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique Identifier: NCT00116831.
Role of NLRP3 (cryopyrin) in acute myocardial infarction
Authors: Eleonora Mezzaroma, Stefano Toldo, Antonio Abbate
Journal: Cardiovascular Research (2013)

We read with interest the article by Sandanger et al .1 on the role of NLRP3 (also known as cryopyrin or NALP3) in acute myocardial infarction (AMI). We want to congratulate the authors for confirming the central role of NLRP3 in the myocardial response to ischaemic injury (as earlier reported by our group in 2011)2 while expanding the findings to explore the differences between the NLRP3 KO and the mouse with deletion of the gene for the Apoptosis-associated Speck-like protein containing a C-terminal Caspase-recruitment domain (ASC KO), which had been characterized by …
Effect of high tibial osteotomy on upper tibial venous drainage: study by intraosseous phlebography in primary osteoarthritis of knee joint.
Authors: A Dey, U C Sarma, P K Dave
Journal: Annals of the Rheumatic Diseases (1989)

The effect of high tibial osteotomy on the upper tibial venous pattern in primary painful osteoarthritis of the knee joint was studied by preoperative and three to six months postoperative intraosseous phlebograms. The normal phlebographic pattern was established by phlebograms in five patients with normal knees. The preoperative engorgement, tortuosity of the medullary sinusoids, and slow dye clearance showed a remarkable conversion to a near normal appearance after the operation. Rest pain disappeared in all patients after the osteotomy, suggesting that venous congestion is the cause of 'rest pain'.
Diabetes in American Indians: Reflections and future directions
Authors: Lewis H Kuller
Journal: Diabetes Care (1993)

The two goals of the next generation of diabetes research should be to reduce the incidence of diabetes mellitus and to decrease the risk of complications from the disease. The prevention of diabetes will require a better understanding of the interaction of genetic and host-environmental factors, especially energy balance, diet and exercise, and specific nutrients. The prevention of weight gain should probably be of highest priority. The prevention of complications needs to focus on hyperinsulinemia, hyperglycemia, blood pressure, smoking, and lipoproteins. Clinical trials are needed to evaluate objectively the benefits of specific interventions. Such trials should be closely linked to community health programs to maximize the health status of the population.
Underlying Causes of the Black-White Racial Disparity in Breast Cancer Mortality: A Population-Based Analysis
Authors: I. Menashe, W. F. Anderson, I. Jatoi, P. S. Rosenberg
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundIn the United States, a black-to-white disparity in age-standardized breast cancer mortality rates emerged in the 1980s and has widened since then.
Evidence for Direct Control of Coronary Vascular Tone by Oxygen
Authors: MIKLOS GELLAI, JAMES M. NORTON, REED DETAR
Journal: Circulation Research (1973)

The interaction between the effects of oxygen and adenosine on acetylcholine-induced contractile tension was observed in helical coronary arterial strips suspended in physiological salt solution. It was found that (1) steady-state contractile tension was unaffected or depressed 5-20% when oxygen pressure (Po 2 ) was diminished to levels as low as 5-10 mm Hg, (2) contractile tension was markedly depressed at a Po 2 of 0 mm Hg, (3) adenosine-induced relaxation of contractile tension was inversely proportional to Po 2 in the tissue bath, and (4) in the presence of adenosine at a concentration just adequate to inhibit contractile tension at a Po 2 of 10 mm Hg, contractile tension was directly proportional to bath Po 2 . The latter two observations were usually most apparent at a Po 2 between 10 and 40 mm Hg. It is proposed that the vasodilating effect of adenosine on the intact coronary vasculature may be most effective during myocardial hypoxia and that physiological control of coronary vascular tone may be more closely related to variations in local Po 2 than to variations in local concentrations of adenosine.
Interactions Among Related Genes of Renin-Angiotensin System Associated With Type 2 Diabetes
Authors: Jin-Kui Yang, Jian-Bo Zhou, Zhong Xin, Lei Zhao, Mei Yu, Jian-Ping Feng, Hui Yang, Ya-Hong Ma
Journal: Diabetes Care (2010)

OBJECTIVE To explore the association between epistasis among related genes of the renin-angiotensin system (RAS) and type 2 diabetes. RESEARCH DESIGN AND METHODS Gene polymorphisms were genotyped in 394 type 2 diabetic patients and 418 healthy control subjects in this case-control study. We used the multifactor dimensionality reduction method to identify gene-gene interactions. RESULTS No single locus was associated with type 2 diabetes, except for the insert/deletion (I/D) polymorphism of the ACE gene in female subjects. In multi-locus analyses, in male subjects the model of rs2106809 (ACE2), rs220721 (Mas), rs699 (AGT), and I/D (ACE) was significant (P = 0.043). This combination was associated with a 4.00 times (95% CI 2.51–6.38; P &amp;lt; 0.0001) greater prevalence of type 2 diabetes. In female subjects, the model of rs2106809 (ACE2), I/D (ACE), and rs1403543 (AGTR2) was significant (P = 0.012). This three-locus combination was associated with a 2.76 times (1.91–3.97; P &amp;lt; 0.0001) greater prevalence of type 2 diabetes. CONCLUSIONS Interactions among RAS-related genes were associated with type 2 diabetes in a Chinese population.
Breast Cancer: Bisphosphonate Therapy for Metastatic Bone Disease
Authors: Jean-Jacques Body
Journal: Clinical Cancer Research (2006)

Abstract The indications of bisphosphonate therapy in breast cancer patients go from the correction of hypercalcemia to the prevention of cancer treatment-induced bone loss. Bisphosphonates are part of our therapeutic armamentarium against metastatic bone pain, and at least 50% of the patients benefit from a clinically relevant analgesic effect. Placebo-controlled trials with oral or i.v. bisphosphonates have shown that prolonged administration can reduce the frequency of skeletal-related events by 30% to 40%. The superiority of zoledronic acid compared with pamidronate has been shown by a multiple-event analysis in a large randomized trial. The short infusion time of zoledronic acid also constitutes a convenient therapy. Where available, oral ibandronate offers an interesting alternative, especially for patients receiving hormone therapy. There are some toxicity concerns with the prolonged use of bisphosphonates. The occasional renal toxicity of zoledronic acid has led to the recommendation to monitor renal function before each infusion and to adjust the dose according to creatinine clearance. Osteonecrosis of the jaw could occur in up to 2.5% of breast cancer patients during long-term bisphosphonate therapy. It is often a significant complication that seems to be linked with the duration of therapy.
THE SECOND OPINION
Authors: C. R. Hanlon
Journal: CA A Cancer Journal for Clinicians (1978)

Medicine as an art demands constant evaluation, weighing new treatments against old practices, benefits against risks, successesagainst failures.On occasion, the evidence leads to different conclusions.Nowhere is this more evident than in the management of the cancer patient.OPINIONS will present the views of specialists on a wide spectrum of contro versial subjects.It is hoped that the frank expression of ideas will provide aframework within which our readers may form their own opinions.