tbuckley/cabot-search huggingface dataset:
Effect of angiotenstin system inhibitors (ASIs) on the outcome of sunitinib treatment (tx) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: D. Keizman, P. Huang, M. A. Eisenberger, R. Pili, J. J. Kim, H. J. Hammers, M. A. Carducci
Journal: Journal of Clinical Oncology (2011)

317 Background: The VEGFR inhibitor sunitinib is a standard tx for mRCC. ASIs include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). ASIs are used in the tx of hypertension (HTN), kidney disease, and heart failure. Preclinical and clinical studies in several cancer types have shown that they may inhibit tumor growth. Their effect on the outcome of sunitinib in mRCC is poorly defined. Aims: to study the effect of ASIs on the outcome sunitinib tx for mRCC. Methods: We performed a retrospective study of an unselected cohort of pts with mRCC, who were treated with 50 mg of oral sunitinib in cycles of 4 weeks followed by 2 weeks of rest. Pts were divided into 2 groups: (1) ASIs users and (2) ASIs naive. The effect of ASIs use on objective response, time to progression (TTP), and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chisquare test and partial likelihood test from cox model. Results: Between 2004–2010, 124 pts with mRCC were treated with sunitinib. There were 44 ASIs users (group 1) and 80 nonusers (group 2). With regard to sunitinib tx initiation time, 39 users started ASIs before, 3 within 1 month, and 2 after 5 months. The groups were balanced regarding the following known clinical prognostic factors: past nephrectomy, RCC histology, time from diagnosis to tx, ≥ 2 metastatic sites, lung/liver/bone metastasis, ECOG performance status, Hb level, corrected ca &gt; 10 mg/dL, platelets count, prior cytokines/ targeted tx, sunitinib induced HTN, % pts that had dose reduction/tx interruption, and mean dose/cycle. Objective response in group 1 vs. 2 was partial response (PR) 48% vs 38% (p=0.24), stable disease (SD) 38% both, and progressive disease (PD) 14% vs. 24% (p=0.19). Median TTP was 12 vs. 6 ms (HR 0.635 in ASIs users, p=0.034). Median OS was 25 vs. 22 ms (p=0.3). Conclusions: ASIs may improve the outcome of pts with mRCC that are treated with sunitinib. This should be investigated prospectively, and if validated, applied in clinical practice and clinical trials. No significant financial relationships to disclose.
Individual variation of hippuric acid and P-cresyl sulfate plasma levels correlate with variation of intestinal microbial phylotypes in hemodialysis patients
Authors: Griet Glorieux, Sara Vieira-Silva, Sunny Eloot, Eva Schepers, Annemieke Dhondt, Raymond Vanholder, Jeroen Raes, Geert Huys, Marie Joossens
Journal: Journal of the American Society of Nephrology (2015)
The assessment of hepatocellular carcinoma risk in patients with chronic hepatitis B under antiviral therapy
Authors: Ioannis Varbobitis, George V. Papatheodoridis
Journal: Clinical and Molecular Hepatology (2016)

Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered. Given that the high-genetic barrier agents, entecavir and tenofovir, are mainly used in CHB because of their favorable effects on the overall long-term outcome of such patients, the most clinically important challenge is the identification of patients who require close HCC surveillance despite on-therapy virological remission. Several risk scores have been developed for HCC prediction in CHB patients. Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated and treated CHB patients, but they do not seem to offer good predictability in Caucasian CHB patients for whom a newer score, PAGE-B, has been recently developed. Keywords: Hepatitis B; Hepatocellular carcinoma; Interferon-alfa; Antivirals
Th2 Cells in Health and Disease
Authors: Toshinori Nakayama, Kiyoshi Hirahara, Atsushi Onodera, Yusuke Endo, Hiroyuki Hosokawa, Kenta Shinoda, Damon J. Tumes, Yoshitaka Okamoto
Journal: Annual Review of Immunology (2016)

Helper T (Th) cell subsets direct immune responses by producing signature cytokines. Th2 cells produce IL-4, IL-5, and IL-13, which are important in humoral immunity and protection from helminth infection and are central to the pathogenesis of many allergic inflammatory diseases. Molecular analysis of Th2 cell differentiation and maintenance of function has led to recent discoveries that have refined our understanding of Th2 cell biology. Epigenetic regulation of Gata3 expression by chromatin remodeling complexes such as Polycomb and Trithorax is crucial for maintaining Th2 cell identity. In the context of allergic diseases, memory-type pathogenic Th2 cells have been identified in both mice and humans. To better understand these disease-driving cell populations, we have developed a model called the pathogenic Th population disease induction model. The concept of defined subsets of pathogenic Th cells may spur new, effective strategies for treating intractable chronic inflammatory disorders.
NCI Cancer Trials Support Unit at year 10.
Authors: S. E. Riordan, M. F. Hering, J. R. Hopkins, R. Lambersky, D. M. Marinucci, K. E. Martier, M. M. Mooney, A. Nelson, R. Rajaram, J. S. Abrams
Journal: Journal of Clinical Oncology (2010)

6077 Background: In a September 1998 report to the National Cancer Institute's (NCI) Board of Scientific Advisors, the NCI envisioned a cancer clinical trials coordinating unit that would enhance trial conduct, increase the number of investigators and patients participating in trials, and reduce the administrative burden on the NCI-sponsored cancer Cooperative Groups (Groups). The NCI Cancer Therapy Evaluation Program (CTEP) launched the Cancer Trials Support Unit (CTSU) in September 1999. Now at year 10, we review the CTSU's progress in meeting NCI's initial objectives. Methods: As the established mechanism for cross-Group enrollment to phase III adult cancer trials, the CTSU has expanded trial options for both physicians and patients, enrolling nearly 50,000 patients to date and facilitating trial accruals and completion. A robust IT infrastructure interfaces with CTEP and Cooperative Group applications and provides support for all stages of trial conduct, including regulatory management, patient enrollments, comprehensive web site services, data management and remote data capture systems, and accrual reimbursement. Additionally, protocol educational materials, consent translations, IRB and audit templates, and help desk services are highly valued site support services provided by the CTSU. Results: As a service organization and trials facilitator, the CTSU provides a comprehensive framework for the management of the Groups' pivotal phase III treatment trials portfolio. Compared to pre-CTSU where Intergroup accrual to adult phase III trials averaged approximately 27%, accrual to phase III trials from Groups other than the lead now averages 41%, resulting in many trials being completed more quickly. Conclusions: Future plans include widespread adoption of the CTSU's automated Oncology Patient Enrollment Network (OPEN); broadening the CTSU portfolio to include more cancer control trials, pilot and phase II trials, select Children's Oncology Group trials, and collaborations with non-Group networks and consortia. Cumulative data for trials as of 10 Jan 2010 No. patients enrolled No. trials opened No. organizations sponsoring trials No. IRB initial approvals processed No. data management trials At end year 5 (2004) 7,286 75 11 69,391 4 At end year 10 (2009) 44,934 187 17 175,900 12 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Westat, Inc. Westat, Inc.
Systems biologists hope for a full integration of their field into cancer research.
Authors: O Wolkenhauer, C. Auffray, S Baltrusch, N Blüthgen, H Byrne, M Cascante, A Ciliberto, T Dale, D Drasdo, D. Fell, J E Ferrell, D Gallahan, R Gatenby, U Guenther, B. Harms, B Herzel, C Junghanss, M Kunz, I van Leeuwen, P Lenormand, F Levi, M Linnebacher, J Lowengrub, P. K. Maini, A. Malik, K Rateitschak, K Sansom, R Schäfer, K Schürrle, C Sers, S. Schnell, D. Shibata, J. Tyson, J. Vera, Michael White, B. Zhivotovsky, R. Jaster
Journal: Cancer Research (2010)
Avoided cost in chemotherapy drugs by patient inclusion in clinical trials.
Authors: Jose Ignacio Chacon, Maria Sanchez Garcia, Ana Rosa Rubio Salvador, Amalia Gonzalez, Iciar Garcia Carbonero, Carmen Esteban, Medina Javier, Ruth Alvarez, Luis Lopez-Gomez, Jesus Andrade, Antonio Irigoyen, Paloma Moya Gomez, Miguel Ángel Cruz
Journal: Journal of Clinical Oncology (2014)

e17544 Background: To determine the direct economic impact attributable to drugs assigned to patients (pts) enrolled in clinical trials (CT) by the medical oncology department of a third level hospital in terms of avoided cost. Methods: Avoided cost: value of drugs that pts included in CT should have received by protocol and that the hospital must not pay because are provided by the CT promoter or because they are replaced by investigational drugs. Retrospective observational study (January 2004 - December 2013). Collecting data from records of CT conducted by the Medical Oncology Department during the study period. Included all CT initiated during the study period with marketed drugs on off-label therapeutic indications for Clinical Research and CT made with no marketed drugs for indications with available alternatives. Avoided cost is calculated on average body surface of pts included in each study. The cost of treatment per pt: per mg of active principle/m2 or per dosage unit as applied. The cost calculation was based on the price registered by the pharmacy department at the time of pts inclusion in CT. Data analyzed: phase CT, scope of application, sponsor’s identity, type of masking and randomization, and type of cancer. Results: A total of 23 evaluable CT were included with a total of 106 pts. See Table. Conclusions: Direct economic impact attributable to drugs included on clinical research protocols is high in terms of avoided cost, and it is configured as an economic indicator in the Medical Oncology Research Unit. n % Phase II 8 34,8 III 13 56,5 IV 2 8,7 Masking Open 21 91,3 Double blind 2 8,7 Randomization Randomized 15 65,2 Nonrandomized 8 34,8 Scope of application National 9 39,1 International 14 60,9 Sponsor Pharmaceutical industry 16 60,5 Cooperative group 7 30,5 Tumor Avoided Cost CT nº Pts nº Avoided cost/pathology (€) Breast 15 82 1.186.469,15 Digestive 3 5 10.966,27 Lymphomas 2 5 28.661,16 Germinal 2 11 114274,27 Gynecologic 1 3 134.695,92 Total 23 106 1475066,77
Cannabis is associated with relapse of psychosis, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Continuing to use cannabis after the onset of psychosis is associated with an increased risk of relapse resulting in psychiatric admission, researchers report in JAMA Psychiatry .1

The prospective cohort study included 220 people who presented to psychiatric services in south London from 2002 to 2013 with a first episode of psychosis. The …
Irinotecan, carboplatin and etoposide regimen in extensive disease small cell lung cancer: Phase II trial
Authors: K. Syrigos, N. Katirtzoglou, A. Charpidou, T. Botsis, E. Karapanagiotou, K. Dilana, I. Gkiozos, K. Pantazopoulos
Journal: Journal of Clinical Oncology (2007)

18153 Background: The prognosis for the patients with small cell lung cancer (SCLC) is very poor with metastases often present at the time of diagnosis. Despite the initial chemo-sensitivity the majority of the patients will relapse and die of their disease. Irinotecan, a topoisomerase I inhibitor, has been reported as an active new agent in SCLC. In combination with cisplatin, it has showed superiority in response rates and progression free survival over the standard regimen of cisplatin and etoposide. We conducted a phase II study in order to evaluate the efficacy and safety of Carboplatin, Irinotecan and Etoposide (CIE) combination in extensive-disease SCLC (ED-SCLC) Methods: Forty six chemo-naïve patients with ED-SCLC and PS 0–2 were enrolled. Forty of theme were men and 6 women. All of them were smokers and the median age was 59.6 years. We administered carboplatin AUC 5 on day 1, irinotecan 120 m 2 on day 2 and etoposide 75 mg/m 2 on days 1, 2, 3 in a 21 days repeated cycles. The treatment was continued for up to 6 cycles. Response assessments were performed after cycles 3 and 6 and every 2 months subsequently. The patients were evaluated for response, survival and toxicity. Clinical (as site of metastasis) and laboratory (such as LDH) parameters were tested as prognostic factors for survival. Results: Two hundred and two cycles were administered with an average of 4.5 cycle per patient. Overall response rate was 52.2% (partial and complete), mean overall survival was 16.3 months (CI: 95%: 13.0–19.7) and there was a 1 year survival rate of 43.47%. Patients with brain metastasis had worse prognosis (P:0.004). The three drug regimen was well tolerated. Only 1 patient had diarrhea grade II, 6 had grade III/IV and 1 patient was referred with abdominal pain. One was presented with fatal thrombocytopenia while two toxic deaths were reported. Nine patients (19.5%) had neutropenia grade III/IV, without being fatal, and 3 were presented with grade III anemia which need blood transfusions. Conclusions: CIE regimen is effective and well tolerated for the treatment of the poor prognosis group of ED-SCLC patients with responses and overall survival comperable to standard regimen (CE). No significant financial relationships to disclose.
L-Leucine Improves the Anemia of the 5q- Syndrome Via Activation of the mTOR (mammalian target of rapamycin) Pathway
Authors: Maria Virgilio, Elspeth Payne, Anupama Narla, Hong Sun, Barry H. Paw, Thomas Look, Benjamin L. Ebert, Nancy Berliner, Arati Khanna-Gupta
Journal: Blood (2011)
National Football League concussion lawsuit: what it means for other sports and observations from Singapore Rugby
Authors: Dinesh Sirisena, Joy Walter, Joanne Probert
Journal: British Journal of Sports Medicine (2016)

With the upcoming fifth International Conference on Concussion in Sport taking place in October 2016, the management of concussion in athletes will again be under increased scrutiny. However, it has rarely left the spotlight with 58 articles published in BJSM alone between 2012 and 2016!

An off-field event fuelling this continued interest has been the American NFL players’ lawsuit; a group of retired NFL athletes won a US$900 million out-of-court settlement from the organisation, stating they were not warned about brain injury risk and that cases were hidden from them. Upheld by the court of appeals, there are calls to include players with chronic traumatic encephalopathy in this decision. This may set a new legal precedent, and already another lawsuit has been filed by American footballers against the National Collegiate Athletic Association on similar grounds.

Media attention on the concussion lawsuit in America highlights the potential medico-legal sequelae if concussion is (or is perceived to be) inadequately detected or managed. Commentary by …
Low Level BCR-ABL Mutations and Response to Treatment: A Substudy of the ENEST1st Trial
Authors: Georg-Nikolaus Franke, Jacqueline Maier, Karoline Schubert, Michael Cross, Sabine Leiblein, Kathrin Wildenberger, Frank Giles, Andreas Hochhaus, Oliver Frank, Dietger Niederwieser, Thoralf Lange
Journal: Blood (2014)
Variation among pathologists' treatment suggestions for melanocytic lesions: A survey of pathologists
Authors: Kachiu C. Lee, Sue Peacock, Martin A. Weinstock, Ge Alice Zhao, Stevan R. Knezevich, David E. Elder, Raymond L. Barnhill, Michael W. Piepkorn, Lisa M. Reisch, Patricia A. Carney, Tracy Onega, Jason P. Lott, Joann G. Elmore
Journal: Journal of the American Academy of Dermatology (2016)
Evaluation of the role of body-surface-area dose adjustment of ZD6126, a novel vascular-targeting agent
Authors: R. Oliver, C. Wheeler, P. Langmuir, I. Melezinek, A. Stone
Journal: Journal of Clinical Oncology (2004)

3065 Background: Dosing of anticancer agents using body-surface-area (BSA) normalization has been standard clinical practice for most i.v. drugs and continues to be practiced without clear biological or physiological support. A review of data from Phase I trials of 33 cancer agents has shown that dosing on a mg/m2 basis reduced variability in exposure in only 5 of the drug candidates examined (Baker et al. J Natl Cancer Inst, 2002 94:1883–8). The authors of this review recommend that BSA dosing should not be adopted unless sufficient clinical information had been generated to support such a dosing strategy. The novel vascular-targeting agent, ZD6126, causes disruption of the microtubular network responsible for maintaining the shape of immature, proliferating endothelial cells in tumor vasculature. This leads to selective vessel occlusion and extensive tumor necrosis. Toxicokinetic data in animals showed male/female differences following exposure to ZD6126 phenol (the active metabolite) and a potential for cytotoxicity at doses 10x greater than anticipated maximum clinical doses. Therefore, dosing normalized to BSA was chosen for initial clinical studies. Methods: During the Phase I program, the safety and pharmacokinetics of ZD6126 were explored at doses of 1–112 mg/m2 administered according to one of 3 schedules. Prior to Phase II evaluation, pharmacokinetic data were available from 71 patients. A high degree of variability was observed in exposure [Cmax and AUC] across the entire dose range, although Cmax and AUC generally increased with dose in a linear fashion. The relationship between BSA and clearance (CL = [Dose/AUC]) of ZD6126 phenol was explored. Results: No clear correlation between CL and BSA was seen. Statistical evaluation of the variability, as assessed by the coefficient of variation, showed that the exposure achieved with unit (mg) dosing would be comparable with that achieved when dosed on a mg/m2basis. Conclusions: These findings indicated that dosing ZD6126 on a unit dose basis would not increase variability in patient exposure to ZD6126 phenol. A unit dosing strategy has therefore been adopted for the Phase II clinical program. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Outcomes of neoadjuvant chemotherapy versus chemoradiation among patients with resected pancreatic head adenocarcinoma.
Authors: Jan Franko, Harold W Hsu, Pragatheeshwar Thirunavukarasu, Daniela Frankova, Charles David Goldman
Journal: Journal of Clinical Oncology (2016)

398 Background: Increasing use of neoadjuvant therapy in pancreatic cancer has been reported. We compared patterns of practice and outcomes of neoadjuvant chemotherapy (nCHT) versus chemoradiation (nCRT) among pancreatic cancer pts receiving pancreaticoduodenectomy. Methods: National Cancer Data Base pancreatic head adenocarcinoma patients (pts) diagnosed between 2003 and 2011 treated by nCHT or nCRT followed by pancreaticoduodenectomy. Backward elimination logistic and Cox regression models were used. Primary outcome measures were 30-day and 90-day postsurgical mortality and overall survival; adjusted odds (aOR) &amp; hazard ratios (aHR) and 95% confidence intervals (CI) are reported. Results: In all 1,432 pts received neoadjuvant treatment with nCHT (n = 523) or nCRT (n = 909). Odds of 30-day mortality were influenced by age (aOR 1.03, CI 0.99-1.06,p = 0.077), average annual resection volume of facility (aOR 0.98, CI 0.97-1.00, p = 0.135), and household income quartile (aOR 1.94, CI 0.97-3.90, p = 0.060), but not by delivery of RT, comorbidities, gender, insurance status or facility type. Odds of 90-day mortality were influenced by age (aOR 1.03, 1.01-1.05,p = 0.004), household income quartile (aOR 1.37, CI 0.87-2.16, p = 0.171), and delivery of nCRT (aOR 1.69, CI 1.04-2.74, p = 0.032), but not by average annual resection volume of facility, comorbidity, gender, insurance status or facility type. Survival odds were influenced by age (aHR 1.01, CI 1.00-1.02, p = 0.001), margin status (aOR 1.50, CI 1.27-1.77, p &lt; 0.001), ypN status (aHR 1.45, CI 1.26-1.68), p &lt; 0.001), adjuvant CHT (aHR 0.81, CI 0.69-0.94, p = 0.006), and nCRT (aHR 1.21, CI 1.04-1.40, p = 0.012). On average pts with nCHT as compared to nCRT lived longer (median OS 26.4 vs. 24.2 months, p = 0.001; actuarial 3 yr 58% vs 49%, and 5 year survival 30% vs 14%). Conclusions: There is no detectable difference in early outcome (30-day postsurgical mortality) among pancreaticoduodenectomy pts treated with nCHT or nCRT. Trend toward a more favorable long-term outcome (30-day postsurgical mortality and overall survival) among those with nCHT without radiation is noted. Further studies with more detailed data sources are needed.
AMECM/DCB scaffold prompts successful total meniscus reconstruction in a rabbit total meniscectomy model
Authors: Zhiguo Yuan, Shuyun Liu, Chunxiang Hao, Weimin Guo, Shuang Gao, Mingjie Wang, Mingxue Chen, Zhen Sun, Yichi Xu, Yu Wang, Jiang Peng, Mei Yuan, Quan-Yi Guo
Journal: Biomaterials (2016)

Tissue-engineered meniscus regeneration is a very promising treatment strategy for meniscus lesions. However, generating the scaffold presents a huge challenge for meniscus engineering as this has to meet particular biomechanical and biocompatibility requirements. In this study, we utilized acellular meniscus extracellular matrix (AMECM) and demineralized cancellous bone (DCB) to construct three different types of three-dimensional porous meniscus scaffold: AMECM, DCB, and AMECM/DCB, respectively. We tested the scaffolds' physicochemical characteristics and observed their interactions with meniscus fibrochondrocytes to evaluate their cytocompatibility. We implanted the three different types of scaffold into the medial knee menisci of New Zealand rabbits that had undergone total meniscectomy; negative control rabbits received no implants. The reconstructed menisci and corresponding femoral condyle and tibial plateau cartilage were all evaluated at 3 and 6 months (n = 8). The in vitro study demonstrated that the AMECM/DCB scaffold had the most suitable biomechanical properties, as this produced the greatest compressive and tensile strength scores. The AMECM/DCB and AMECM scaffolds facilitated fibrochondrocyte proliferation and the secretion of collagen and glycosaminoglycans (GAGs) more effectively than did the DCB scaffold. The in vivo experiments demonstrated that both the AMECM/DCB and DCB groups had generated neomeniscus at both 3 and 6 months post-implantation, but there was no obvious meniscus regeneration in the AMECM or control groups, so the neomeniscus analysis could not perform on AMECM and control group. At both 3 and 6 months, histological scores were better for regenerated menisci in the AMECM/DCB than in the DCB group, and significantly better for articular cartilage in the AMECM/DCB group compared with the other three groups. Knee MRI scores (Whole-Organ Magnetic Resonance Imaging Scores (WORMS)) were better in the AMECM/DCB group than in the other three groups at both 3 and 6 months. At both 3 and 6 months, RT-PCR demonstrated that aggrecan, Sox9, and collagen II content was significantly higher, and mechanical testing demonstrated greater tensile strength, in the AMECM/DCB group neomenisci compared with the DCB group.