tbuckley/cabot-search huggingface dataset:
Concurrent Radiation and ESHAP Regimen in Localized Extranodal NK/T-Cell Lymphoma Nasal Type, Phase II French Study
Authors: Jean-Marie Michot, Theodore Girinsky, Alina Danu, Anna Antosikova, Christophe Ferme, Julien Lazarovici, Christophe Willekens, Ali N Chamseddine, David Ghez, Camille Bigenwald, Jacques Bosq, Stephane de Botton, Renaud Mazeron, Vincent Ribrag
Journal: Blood (2014)
Flt-1 (VEGFR-1) coordinates discrete stages of blood vessel formation
Authors: John C. Chappell, Julia G. Cluceru, Jessica E. Nesmith, Kevin P. Mouillesseaux, Vanessa B. Bradley, Caitlin M. Hartland, Yasmin L. Hashambhoy-Ramsay, Joseph Walpole, Shayn M. Peirce, Feilim Mac Gabhann, Victoria L. Bautch
Journal: Cardiovascular Research (2016)

In developing blood vessel networks, the overall level of vessel branching often correlates with angiogenic sprout initiations, but in some pathological situations, increased sprout initiations paradoxically lead to reduced vessel branching and impaired vascular function. We examine the hypothesis that defects in the discrete stages of angiogenesis can uniquely contribute to vessel branching outcomes. Time-lapse movies of mammalian blood vessel development were used to define and quantify the dynamics of angiogenic sprouting. We characterized the formation of new functional conduits by classifying discrete sequential stages—sprout initiation, extension, connection, and stability—that are differentially affected by manipulation of vascular endothelial growth factor-A (VEGF-A) signalling via genetic loss of the receptor flt-1 (vegfr1). In mouse embryonic stem cell-derived vessels genetically lacking flt-1, overall branching is significantly decreased while sprout initiations are significantly increased. Flt-1−/− mutant sprouts are less likely to retract, and they form increased numbers of connections with other vessels. However, loss of flt-1 also leads to vessel collapse, which reduces the number of new stable conduits. Computational simulations predict that loss of flt-1 results in ectopic Flk-1 signalling in connecting sprouts post-fusion, causing protrusion of cell processes into avascular gaps and collapse of branches. Thus, defects in stabilization of new vessel connections offset increased sprout initiations and connectivity in flt-1−/− vascular networks, with an overall outcome of reduced numbers of new conduits. These results show that VEGF-A signalling has stage-specific effects on vascular morphogenesis, and that understanding these effects on dynamic stages of angiogenesis and how they integrate to expand a vessel network may suggest new therapeutic strategies.
A phase 3, open-label, randomized, parallel, 2-arm international study of the oral PARP inhibitor talazoparib (BMN 673) in BRCA mutation subjects with locally advanced and/or metastatic breast cancer (EMBRACA).
Authors: Jennifer Keating Litton, Joanne Lorraine Blum, Young-Hyuck Im, Miguel Martin, Lida A. Mina, Henri Hubert Roche, Hope S. Rugo, Fran Visco, Charlie Zhang, Nathalie Andrienne Lokker, Debra L. Lounsbury, Wolfgang Eiermann
Journal: Journal of Clinical Oncology (2015)

TPS1107 Background: Poly-ADP-ribose polymerase (PARP) represents a family of enzymes of which at least two (PARP1 and PARP2) play important roles in DNA repair. PARP inhibition induces synthetic lethality in tumor cells bearing deleterious mutations in the genes BRCA1/2. Talazoparib (BMN 673) is a novel, dual-mechanism PARP inhibitor that potently inhibits the PARP enzyme and effectively traps PARP on DNA [1]. In preclinical models, trapping PARP on DNA was more likely to induce cancer cell death than inhibition of PARP alone [1,2]. Talazoparib is the most potent preclinical PARP inhibitor described to date with the highest efficiency at trapping PARP-DNA complexes [1]. Talazoparib has shown promising single-agent anti-tumor efficacy in several solid tumor types and was generally well tolerated in a Phase 1/2 clinical study [3]. Methods: This international Phase 3 trial (EMBRACA) compares the safety and efficacy of talazoparib versus physician’s choice (capecitabine, eribulin, gemcitabine or vinorelbine) in patients with advanced breast cancer. The primary objective is progression free survival (PFS). Secondary objectives include objective response rate (ORR), overall survival (OS), and safety. Exploratory objectives include duration of response (DOR) and health-related quality of life assessments. Subject eligibility includes ≥ 18 years, histologically/cytologically confirmed breast carcinoma, locally advanced and/or metastatic disease, germline BRCA1/2 mutations, ≤ 2 prior chemotherapy-inclusive regimens, prior treatment with a taxane and/or anthracycline, and ECOG performance status ≤ 1. Subjects (n = 429) will be randomized 2:1 to receive either talazoparib oral capsules (1.0 mg/day, 21-day cycles) or physician’s choice treatment. This trial is currently enrolling patients from the United States, Asia/Pacific, Europe, Israel, and South America (NCT01945775). [1] Murai J et al. Mol Cancer Ther. 2014;13:433-443. [2] Murai J et al. Cancer Res. 2012;72(21):5588-5599. [3] Wainberg ZA et al. J Clin Oncol. 2014;32(suppl):5; abstr 7522 Clinical trial information: NCT01945775.
Over 40s’ health check offers only modest health benefits, study finds
Authors: Ingrid Torjesen
Journal: BMJ (2016)

The NHS Health Check, the risk assessment offered every five years to patients aged 40-74 in England who have no known vascular disease, provides only marginal health benefits, a study funded by the Department of Health has found.1

The department commissioned researchers at Imperial College London to examine the electronic medical records of a random sample of 138 788 patients aged 40-74 registered with 462 English general practices from 2009 to 2013. Changes in outcomes of patients who attended a health check were compared with those who did not, over a median follow-up of two years.

The …
Treatment of Patients With Stable Ischemic Heart Disease—Reply
Authors: Tamar S. Polonsky, Ron Blankstein
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Mixed Diagnoses and Mixed Messages—Reply
Authors: Pablo Alonso-Coello, Carl Llor, Mariam de la Poza Abad
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Therapeutic drug monitoring of patients with psoriasis during tumour necrosis factor (TNF)-α antagonist treatment using a novel interleukin-8 reporter cell line
Authors: Y. Kimura, R. Shimada-Omori, T. Takahashi, K. Tsuchiyama, Y. Kusakari, K. Yamasaki, R. Nishikawa, C. Nishigori, S. Aiba
Journal: British Journal of Dermatology (2016)

Tumour necrosis factor (TNF)-α antagonist therapy is currently used for moderate and severe psoriasis. However, this treatment has several drawbacks, including interindividual variability in clinical response and secondary loss of effectiveness.To evaluate quantitatively the TNF-α-neutralizing activity of the plasma of patients with psoriasis during TNF-α antagonist therapy and to determine poor responders objectively.We used a human interleukin-8 reporter monocyte cell line, THP-G8, that harbours a stable luciferase orange (SLO) gene under the control of the interleukin-8 promoter. After confirming its dose-dependent response to exogenous TNF-α, we examined the suppressive activity of TNF-α antagonists and of the patients' plasma during TNF-α antagonist therapy on TNF-α-induced SLO luciferase activity (TNF-SLO-LA).Pretreatment of TNF-α with TNF-α antagonists or with the plasma of patients with psoriasis who achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) dose dependently suppressed TNF-SLO-LA. There was a significant correlation between change in PASI and percentage suppression (inhibitory rate of a 1 : 2 dilution of patient plasma on TNF-SLO-LA). A percentage suppression of 50·3% has a positive predictive value of 87% of achieving PASI 75, with a sensitivity of 93% and a specificity of 80%.Therapeutic monitoring of patients with psoriasis during TNF-α antagonist therapy using THP-G8 can provide a useful tool to determine objectively the efficacy of the administered TNF-α antagonists.
Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)
Authors: Maura N. Dickler, William T. Barry, Constance T. Cirrincione, Matthew J. Ellis, Mary Ellen Moynahan, Federico Innocenti, Arti Hurria, Hope S. Rugo, Diana E. Lake, Olwen Hahn, Bryan P. Schneider, Debasish Tripathy, Lisa A. Carey, Eric P. Winer, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2016)

To investigate whether anti-vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor-positive metastatic breast cancer (MBC).Women with hormone receptor-positive MBC were randomly assigned 1:1 in a multicenter, open-label, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided α = .025, a target sample size of 352 patients was planned.From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v 2%) and proteinuria (11% v 0%).The addition of bevacizumab to letrozole improved PFS in hormone receptor-positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting.
PTH-233 Combined open and laparoscopic technique (COLT) for recurrent complex incisional hernia repairs
Authors: L Toquero, J Ellul
Journal: Gut (2015)

<h3>Introduction</h3> The aim of this study was to determine the suitability of a novel technique of a combined open and laparoscopic technique (COLT Technique), in the repair of complex recurrent incisional hernias, where laparoscopic or open techniques alone do not achieve optimal results. Immediate and late complication rates, and recurrence rates are compared with that achieved with either laparoscopic or open (component separation) repair alone. <h3>Method</h3> 19 consecutive patients with recurrent complex incisional hernia with significant morbidity were enrolled, and all underwent the COLT Technique. Follow-up was at six, twelve and twenty four weeks, along with subsequent telephone follow-up. The method involved an initial open repair of the incisional hernia, oppposing muscle together to give the repair strength. The approach would convert to a laparoscopic repair for ease of mesh insertion and placement using a simple prolene mesh, negating the need for expensive biological meshes. <h3>Results</h3> Completion to follow-up was recorded in 100% of patients, with an overall healing rate of one hundred per-cent achieved, pain scores were found to be lower than those of the component separation technique. Infection and seroma rates were relatively low (three per-cent), whilst only one recurrence was recorded (three per-cent). Completion times achieved were within one and a half hours. <h3>Conclusion</h3> The COLT technique is an effective and safe treatment option in patients with complex recurrent incisional hernias. Benefits of this procedure include ease of mesh placement, compared with open techniques requiring using the introduction of sutures. Approximation of muscle layers repairing the defect without opening the defect, its cost effectiveness negating the use of expensive biological meshes, early mobilisation and quick recovery. <h3>Disclosure of interest</h3> None Declared.
Beyond the brain: Optogenetic control in the spinal cord and peripheral nervous system
Authors: Kate L. Montgomery, Shrivats M. Iyer, Amelia J. Christensen, Karl Deisseroth, Scott L. Delp
Journal: Science Translational Medicine (2016)

This Review discusses the use of optogenetics in the spinal cord and peripheral nervous system, distills the key results achieved thus far, and discusses the translational potential.
141O Efficacy outcomes by age from 5 observational or phase-4 studies of bevacizumab (Bev) in metastatic colorectal cancer (mCRC)
Authors: J. Hubbard, A. Grothey, E. Van Cutsem, H. Hurwitz, M.F. Kozloff, T. Bekaii-Saab, J. Bennouna, Y. Zafar, C. Revil, N. Sommer, S. Srock, D. Arnold
Journal: Annals of Oncology (2015)
Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes: The DCCT/EDIC Study 30-Year Follow-up
Journal: Diabetes Care (2016)

Early initiation of intensive diabetes therapy aimed at achieving near-normal glycemia reduces the early development of vascular complications in type 1 diabetes. We now assess whether intensive therapy compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the incidence of cardiovascular disease over 30 years of follow-up.The DCCT randomly assigned 1,441 patients with type 1 diabetes to intensive versus conventional therapy for a mean of 6.5 years, after which 93% were subsequently monitored during the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Cardiovascular disease (nonfatal myocardial infarction and stroke, cardiovascular death, confirmed angina, congestive heart failure, and coronary artery revascularization) was adjudicated using standardized measures.During 30 years of follow-up in DCCT and EDIC, 149 cardiovascular disease events occurred in 82 former intensive treatment group subjects versus 217 events in 102 former conventional treatment group subjects. Intensive therapy reduced the incidence of any cardiovascular disease by 30% (95% CI 7, 48; P = 0.016), and the incidence of major cardiovascular events (nonfatal myocardial infarction, stroke, or cardiovascular death) by 32% (95% CI -3, 56; P = 0.07). The lower HbA1c levels during the DCCT/EDIC statistically account for all of the observed treatment effect on cardiovascular disease risk. Increased albuminuria was also independently associated with cardiovascular disease risk.Intensive diabetes therapy during the DCCT (6.5 years) has long-term beneficial effects on the incidence of cardiovascular disease in type 1 diabetes that persist for up to 30 years.
Naturally Processed Tissue- and Differentiation Stage-Specific Autologous Peptides Bound by HLA Class I and II Molecules of Chronic Myeloid Leukemia Blasts
Authors: Kyriakos P. Papadopoulos, Nicole Suciu-Foca, Charles S. Hesdorffer, Sorina Tugulea, Antonella Maffei, Paul E. Harris
Journal: Blood (1997)
ABVD (8 cycles) versus BEACOPP (4 escalated cycles =&gt; 4 baseline) in stage III-IV high-risk Hodgkin lymphoma (HL): First results of EORTC 20012 Intergroup randomized phase III clinical trial.
Authors: Patrice P. Carde, Matthias Karrasch, Catherine Fortpied, Pauline Brice, Hussein Mustafa Khaled, Denis Caillot, Isabelle Gaillard, Serge Bologna, Christophe Ferme, Pieternella Lugtenburg, Franck Morschhauser, Igor Aurer, Bertrand Coiffier, Guy Cantin, Matthew D. Seftel, Max Wolf, Bengt Glimelius, Anna Sureda, Nicolas Mounier
Journal: Journal of Clinical Oncology (2012)

8002 Background: Escalated BEACOPP and derivatives achieved superior time to treatment failure (FFTF) over COPP/ABVD, resulting in higher overall survival (OS) for advanced HL. However, later clinical trials have failed to confirm OS superiority over ABVD. Methods: Eligibility criteria: clinical stage III/IV HL, International prognostic score (IPS) ≥ 3, age&lt;60. We compared ABVD (8 cycles) vs. BEACOPP (escalated 4 cycles ≥ baseline 4), without irradiation. Randomization was stratified for institution and IPS. Primary endpoint was EFS, defined as treatment discontinuation, no complete response (CR) after 8 cycles, progression, relapse or death. Additional endpoints were CR, progression free survival (PFS), OS, quality of life and secondary malignancies. Outcomes were reviewed by study coordinators to ensure consistency across pts. Results: From 2002-2010, 549 pts were randomized (ABVD 275, BEACOPP 274): stage IV 74%, PS 0, 1, 2: 34, 48 and 17%, B-symptoms 81%, median age 35.2y, males 75%. IPS was 4 or higher for 59% of pts. Histology reviewed no HL in 4 cases. CR was 83% in both arms. With a median follow-up of 3.8 yrs, EFS at 4 yrs was 63.7% vs. 69.3% (HR = 0.86, 95%CI=0.64 to 1.15, p=0.312). PFS at 4 yrs was 72.8% vs. 83.4% (HR = 0.58, 95%CI=0.39 to 0.85, p=0.005). OS at 4 yrs was 86.7 vs. 90.3 (HR = 0.71, 95%CI=0.42 to 1.21, p=0.208). Toxic deaths occurred in 6 and 5 pts, with early discontinuation (prior to cycle 5) in 12 &amp; 26 pts, respectively. There were 5 crossovers to BEACOPP and 10 to ABVD. Second malignancies occurred in 8 ABVD and 10 BEACOPP pts (myelodysplasia/leukemia 2 and 4, lung 2 and 1, NHL 3 and 2, other 1 and 3); cumulative incidence curves did not differ significantly. Conclusions: The primary endpoint (EFS) was similar between treatment arms. However, more progressions/relapses were observed with ABVD, while early discontinuations were more frequent with BEACOPP. Nevertheless, even in this high-risk group, OS was not improved with BEACOPP. Additional considerations (treatment burden and cost, fertility issues, long term relapses and immediate and late morbidity) may guide physician/patient decisions toward ABVD or BEACOPP.
MICROEMBOLIC RISK OF CAROTID ARTERY PLAQUE COMPOSITION BY MRI AT THE TIME OF ELECTIVE REVASCULARIZATION
Authors: Jennifer Ran Li, Jose Wiley, Peter Faries, Venkatesh Mani, Chiara Giannarelli, Zahi Fayad, Errol Gordon, Juan Badimon
Journal: Journal of the American College of Cardiology (2015)
ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α
Authors: Fu-Quan Wu, Tian Fang, Le-Xing Yu, Gui-Shuai Lv, Hong-Wei Lv, Dong Liang, Ting Li, Chang-Zheng Wang, Ye-Xiong Tan, Jin Ding, Yao Chen, Liang Tang, Lin-Na Guo, Shan-Hua Tang, Wen Yang, Hong-Yang Wang
Journal: Journal of Hepatology (2016)
Variations of Adenosine 3′,5′-Cyclic Monophosphate Levels in Four Chemically Transformed Rat Transitional Epithelial Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: G L Hahn, L Haynes, F J Chlapowski
Journal: JNCI Journal of the National Cancer Institute (1980)
Intraoral GS-Nitroxide (JP4-039) Reduces Local Mucositis and Distant Marrow Suppression Toxicities In Head and Neck Irradiated Fancd2-/- (FVB/N) Mice
Authors: Hebist Berhane, Karen Xu, Julie P. Goff, Ronny Kalash, Michael W. Epperly, Tracy M. Dixon, Donna Shields, Darcy Franicola, Song Li, Xiang Gao, Peter Wipf, Joel S. Greenberger
Journal: Blood (2013)