tbuckley/cabot-search huggingface dataset:
Sunitinib in patients with metastatic non-clear renal cell carcinoma: A multicentric retpospective Turkish Oncology Group (TOG) trial.
Authors: Ibrahim Yildiz, Meltem Ekenel, Tulay Akman, Muharrem Kocar, Mukremin Uysal, Metin Kanitez, Vedat Bayoglu, Umut Varol, Deniz Tural, Nilufer Avci, Muhammet Ali Kaplan, Zeki Surmeli, Isa Dede, Arife Ulas, Ozan Yazici, Mert Basaran
Journal: Journal of Clinical Oncology (2014)

e15602 Background: Most of the randomizedstudies that have evaluated the clinical outcome of anti-VEGF treatment in metastatic renal cell carcinoma (RCC) were focused mostly on the clear cell histology. Non-clear cell RCC were excluded or represented by a small number of patients in pivotal studies. In this study, our aim is to determine the clinical benefit and toxicity of sunitinib treatment in non-clear cell RCC patients. Methods: A total of 63 patients who have complete clinical data from 13 oncology centers were retrospectively evaluated. Treatment response, toxicity, progression free survival (PFS) and overall survival (OS) were evaluated. Results: The median age was 63 years (range, 25-82 years), and the study sample consisted of 38 men (60.3%) and 25 women (39.7%). Forty-six patients (88%) had histological subtype of papillary RCC while the other subtypes were chromophobe (n=10) and unclassified (n=7). Before sunitinib treatment, 55 (89%) patients were undergone nephrectomy, 39 (61.9%) patients were treated with cytokine-based therapy and 2 patients were treated by cytotoxic chemotherapy. Twenty-four patients were treated with sunitinib in first-line treatment. The median treatment duration was 7 months (range, 2-86 months). At the time of this analysis, 52 patients had discontinued treatment, 33 of whom were deceased. Seven patients (11.1%) had partial response and 33 patients (52.4%) had stable disease with a disease control rate of (CR-PR-SD) %63.5 while disease progression was found in 23 (36.5%) patients. Median PFS was 7.6 months (95% CI, 5.5-9.7 months) and median OS was 22.0 months (95% CI, 13.4-30.6 months). 1-year OS rate was 64.7%, and 1-year PFS rate was 33.7%. Conclusions: Clinical outcome of the metastatic non-clear cell RCC patients with sunitinib treatment was seem to be worse than the historical data of clear cell RCC patients, in terms of PFS, OS and objective response. Different molecular pathways in different histological subtypes, different chromosomal and genetic changes may affect treatment response. New and more effective targeted therapies and understanding the underlying molecular processes are necessary to improve their survival outcome.
Abstract LB-298: Gut microbiota changes in response to treatment with ursodeoxycholic acid
Authors: J Gregory Caporaso, Talima Pearson, Monia Yellowhair, Jessica Martinez, Peter Lance
Journal: Cancer Research (2016)

Abstract Compelling evidence suggests that the gut flora influences colorectal cancer risk through direct effects on colonic bile acid composition. Bile acids are widely implicated in the etiology of colorectal cancer and the strongest evidence is for the secondary bile acid deoxycholic acid. In a study of patients with prior colorectal adenomas who were randomized to ursodeoxycholic acid (n = 188 males, 64 females), a bile acid based intervention aimed at modulating bile acid composition, or placebo (n = 162 males, 89 females), we determined effects of the intervention on the gut microbiome through 16S rRNA sequencing and bile acid composition using mass spectrometry. We observe a consistent shift in microbial community phylogenetic composition for males (t = 5.83, p = 3.6e-8) and females (t = 3.14, p = 0.003) treated with UDCA. No effect was observed in the placebo group for either males (t = -0.08, p = 0.93) or females (t = -0.09, p = 0.92). This suggests that UDCA treatment, but not placebo treatment, is having an effect on the gut microbial communities of study participants. Interestingly, the microbiomes of the UDCA group do not change more than those of the placebo group: rather the magnitude of change is similar in the two groups, but UDCA treatment seems to drive specific microbiome changes. We also observe significant correlations between the gut microbiome composition and bile acid composition (r = 0.31, p&amp;lt;0.001). Specifically we find that (prior to treatment) bile acids including CA, CDCA, and UDCA are negatively correlated with diversity (richness) and to a lesser extent the abundance of Bacteroidetes (phylum) in the gut. These results are consistent with our previously reported observation that UDCA appears to have a greater effect in men for the prevention of colorectal adenomatous polyps, with risk-increasing effects for women. To our knowledge, this is the first study to correlate fecal bile acid levels with fecal microbial composition in humans or to assess the effect of the therapeutic bile acid UDCA on gut microbial composition. This study supports our observation that the efficacy of UDCA for the prevention of colorectal adenoma may be sex-dependent and suggests that the sex-specific effect may reflect differential effects of UDCA on the gut microbial community and the relationship between sex, the gut microbiome, and risk of colorectal adenomatous polyps. Citation Format: J Gregory Caporaso, Talima Pearson, Monia Yellowhair, Jessica Martinez, Peter Lance. Gut microbiota changes in response to treatment with ursodeoxycholic acid. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-298.
Brain Tumors
Authors: P M Black
Journal: New England Journal of Medicine (1991)

The treatment of brain tumors usually begins with surgery for diagnosis or excision. Subsequent comprehensive care may involve cooperation between neurosurgeons, neurologists, neuroradiologists, neuropathologists, radiation therapists, and oncologists. Histologic features alone are not definitive in planning care; a benign tumor may not be resectable because of its adherence to the hypothalamus or other structures and may therefore be fatal, as is the case in some opticnerve and hypothalamic gliomas. Alternatively, there are some histologically malignant tumors such as medulloblastomas that have substantial cure rates after optimal treatment.Benign Brain TumorsMeningiomasMeningiomas are the most common benign brain tumor and . . .
Bone marrow stem cells and their niche components are adversely affected in advanced cirrhosis of the liver
Authors: Chhagan Bihari, Lovkesh Anand, Sheetalnath Rooge, Dhananjay Kumar, Priyanka Saxena, Smriti Shubham, None Sukriti, Nirupma Trehanpati, Guresh Kumar, Viniyendra Pamecha, Shvetank Sharma, Archana Rastogi, Anupam Kumar, Shiv K. Sarin
Journal: Hepatology (2016)

Bone marrow (BM) is a reservoir for immune and hematopoietic cells and critical for tissue repair and regeneration. All of these functions are severely altered in cirrhosis. We investigated the cellular and functional state of BM in cirrhosis patients. We studied the histological, cellular, and molecular changes in BM of cirrhosis patients (n = 168) and controls (n = 44). Hematopoietic stem cells (HSCs) and associated niche cells, mesenchymal stem cells, Schwann cells, neural fibers, and endothelial cells were evaluated by immunohistochemistry. Cytokines and growth factors were analyzed in peripheral blood and BM plasma. Cirrhotic BM showed an inverse correlation between cluster of differentiation 34+HSCs and Model of End‐Stage Liver Disease ( ρ = ‐0.582, P &lt; 0.001) and Child's scores ( P &lt; 0.038). BMs of cirrhosis patients with higher Model of End‐Stage Liver Disease (&gt;15) showed significantly decreased HSCs, mesenchymal stem cells, Schwann cells, and neural fibers; increased interleukin‐1β ( P = 0.004), tumor necrosis factor‐α ( P = 0.040), and interferon‐γ ( P = 0.03); and decreased oncostatin M ( P = 0.04), stem cell factor ( P = 0.05), and stromal cell‐derived factor 1 ( P = 0.03) compared to those with lower Model of End‐Stage Liver Disease scores (≤15). The cluster of differentiation 34+ cell population was a predictor for the development of sepsis ( P &lt; 0.001), and per unit loss increased the probability of sepsis by 16%. Cirrhosis patients with fewer HSCs had lower hemoglobin ( P = 0.05) and platelet counts ( P = 0.05) and showed early graft dysfunction. Conclusions: Increasing severity of cirrhosis causes derangement of the hematopoietic niche and loss of HSCs, contributing to the hematological and immunological dysfunctions and reduced potential for regeneration; restoring BM functions could provide new therapeutic options in cirrhosis. (H epatology 2016;64:1273‐1288)
Elevated Angiopoietin-2 Level in Patients With Continuous-Flow Left Ventricular Assist Devices Leads to Altered Angiogenesis and Is Associated With Higher Nonsurgical Bleeding
Authors: Corey E. Tabit, Phetcharat Chen, Gene H. Kim, Savitri E. Fedson, Gabriel Sayer, Mitchell J. Coplan, Valluvan Jeevanandam, Nir Uriel, James K. Liao
Journal: Circulation (2016)

Background: Nonsurgical bleeding is the most common adverse event in patients with continuous-flow left ventricular assist devices (LVADs) and is caused by arteriovenous malformations. We hypothesized that deregulation of an angiogenic factor, angiopoietin-2 (Ang-2), in patients with LVADs leads to increased angiogenesis and higher nonsurgical bleeding. Methods: Ang-2 and thrombin levels were measured by ELISA and Western blotting, respectively, in blood samples from 101 patients with heart failure, LVAD, or orthotopic heart transplantation. Ang-2 expression in endothelial biopsy was quantified by immunofluorescence. Angiogenesis was determined by in vitro tube formation from serum from each patient with or without Ang-2–blocking antibody. Ang-2 gene expression was measured by reverse transcription–polymerase chain reaction in endothelial cells incubated with plasma from each patient with or without the thrombin receptor blocker vorapaxar. Results: Compared with patients with heart failure or those with orthotopic heart transplantation, serum levels and endothelial expression of Ang-2 were higher in LVAD patients ( P =0.001 and P &lt;0.001, respectively). This corresponded to an increased angiogenic potential of serum from patients with LVADs ( P &lt;0.001), which was normalized with Ang-2 blockade. Furthermore, plasma from LVAD patients contained higher amounts of thrombin ( P =0.003), which was associated with activation of the contact coagulation system. Plasma from LVAD patients induced more Ang-2 gene expression in endothelial cells ( P &lt;0.001), which was reduced with thrombin receptor blockade ( P =0.013). LVAD patients with Ang-2 levels above the mean (12.32 ng/mL) had more nonsurgical bleeding events compared with patients with Ang-2 levels below the mean ( P =0.003). Conclusions: Our findings indicate that thrombin-induced Ang-2 expression in LVAD patients leads to increased angiogenesis in vitro and may be associated with higher nonsurgical bleeding events. Ang-2 therefore may contribute to arteriovenous malformation formation and subsequent bleeding in LVAD patients.
Predictors of choice of initial antifungal treatment in intraabdominal candidiasis
Authors: L. Lagunes, B. Borgatta, M.T. Martín-Gomez, A. Rey-Pérez, M. Antonelli, E. Righi, M. Merelli, P. Brugnaro, G. Dimopoulos, J. Garnacho-Montero, A.L. Colombo, R. Luzzati, F. Menichetti, P. Muñoz, M. Nucci, G. Scotton, C. Viscoli, M. Tumbarello, M. Bassetti, J. Rello, F. Ansaldi, C. Scarparo, A. Diaz-Martin, I. Palacios-Garcia, C. Rosin, B. Almirante, G. Baldin, A. Vena, E. Bouza, V. de Egea, C. Tascini, F. Menichetti, E. Tagliaferri, M. Sanguinetti, A. Mesini, G. Sganga, M. Busetti, T. Pumarola, M.T. Martin, S.A. Nouér, T. Pelaez, E. Raise, S. Grandesso, V. Del Bono, P. Esteves, C. Trucchi, A. Sartor, G. De Pascale, B. Posteraro, C. Scarparo, P. Esteves
Journal: Clinical Microbiology and Infection (2016)
A multicenter randomized phase II trial comparing nab-paclitaxel to paclitaxel in patients with advanced urothelial cancer progressing on or after a platinum containing regimen: NCIC Clinical Trials Group BL 12 (NCT02033993).
Authors: Srikala S. Sridhar, Normand Blais, Scott A. North, Ben Tran, Kim N. Chi, John W. Robinson, M. Neil Reaume, Geoffrey Liu, Gail T McDonald, Keyue Ding, Wendy R. Parulekar
Journal: Journal of Clinical Oncology (2015)

TPS4573 Background: Metastatic urothelial cancer remains an incurable disease, for which there is no standard second line treatment. A previous phase II study of nab-paclitaxel in this setting demonstrated activity and good tolerability. The current study is designed to characterize the activity of nab-paclitaxel compared to paclitaxel in the second line treatment setting for advanced urothelial cancer. Methods: This is an NCIC Clinical Trials Group (NCIC CTG) led intergroup trial with the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). The primary objective is to compare the progression free survival (PFS) between the two arms. Secondary objectives include: objective response rate, clinical benefit rate, time to response, response duration, toxicity, quality of life, and cost effectiveness. Correlative biological studies relating to tissue predictive and prognostic biomarkers and pharmacogenomics will be conducted. Clinicodemographic factors will be prospectively collected using a health and demographic questionnaire to further understand the relationships between biomarkers and clinical outcome measures. Statistical Design: Planned accrual is 199 patients over 3 years with followup of 4 months. Assuming median PFS of 4 months with paclitaxel, the target hazard ratio is 0.67 (PFS of 4 mo vs. 6 months, 1-sided, 5% significance with 80% power). Estimated sample size accounts for loss to followup or withdrawal of consent. Conduct to Date: Study activation: Mar 2014 (NCIC), Feb 2015 (ANZUP). As of February 2 2015, current accrual is 38. In November 2014 an independent DSMC recommended trial continuation. Supported by Celgene Corporation Clinical trial information: NCT02033993.
THU0465 Fracture Liaison Service Reduces Re-Fracture Rate, Cost-Effective and Cost Saving in Western Australia
Authors: C.A. Inderjeeth, W. Raymond, E. Geelhoed, A. Briggs, K. Briffa, D. Oldham, J. McQuade, D. Mountain
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Osteoporotic fractures impose significant morbidity, mortality and economic burden (1). Earlier research showed low rates of secondary prevention for patients discharged from Emergency Department (ED) with a fracture (2). The Fracture Liaison Service (FLS) aimed to identify, review and then manage these patients following their discharge from the ED. <h3>Objectives</h3> Determine the economic benefits of a FLS in a Western Australian hospital. <h3>Methods</h3> Patients aged &gt;50yrs whom presented to the Emergency Department at Sir Charles Gairdner Hospital (SCGH) after a fracture were invited to the FLS. A retrospective control group from SCGH and a prospective control group from Fremantle Hospital were the comparators. A health economic analysis from the Payer9s Perspective (WA Health) examined recurrent fracture rates and quality of life (EQ-5D). Bottom-up costing included medications, investigations, GP visits and the cost of fracture determined by the literature or the AR-DRG 2013/14 prices for hospital presentation and admission. The mean incremental cost effectiveness ratios were bootstrapped (5000 iterations). Cost-effectiveness acceptability curves were generated and the willingness-to-pay was $50,000AUD. <h3>Results</h3> This FLS reduced the rate of re-fracture compared to the retrospective cohort and other tertiary centre by 9.2 - 10.2%, equating to cost savings of approximately $750,168 - $810,400/1,000 patient-years in the first year compared to control cohorts. There was no difference in the QALYs gained across groups over 12 months. The FLS compared to SCGH retrospective cohort had a mean incremental cost of $6,168 (95CI $133, $18,626) per 1% reduction in the 12 month recurrent fracture risk. The FLS compared to other sites had a mean incremental cost of $6,782 (95CI -$2,562, $25,686) per 1% reduction in the 12 month recurrent fracture risk. The FLS compared to SCGH retrospective cohort had a mean incremental cost of $859 (95CI -$4,074, $4,864) per QALY gained at 12 months. The FLS compared to other sites had a mean incremental cost of -$119 (95CI -$1,665, $700) per QALY gained at 12 months. Figure 1 demonstrates that the FLS is cost-effective in delivering a reduction in the fracture rate at 12 months. However, the QALY gained (EQ-5D) was no different at 12 months between the study groups. <h3>Conclusions</h3> This FLS demonstrated to be effective in reducing rates or recurrent fracture(s) and resulted in significant cost effectiveness and cost-saving. <h3>References</h3> Briggs AM et al.(2015) Hospitalisations, admission costs and re-fracture risk related to osteoporosis in Western Australia are substantial: a 10-year review. ANZ J Public Health. Inderjeeth CA et al. (2010) A multimodal intervention to improve fragility fracture management in patients presenting to Emergency Departments. MJA <h3>Disclosure of Interest</h3> None declared
Abstract LB-271: Targeting fatty acid metabolism regulates the immunosuppressive activity of myeloid-derived suppressor cells
Authors: Amir A. Al-Khami, Fokhrul Hossain, Dorota Wyczechowska, Liqin Zheng, Paulo Rodriguez, Augusto C. Ochoa
Journal: Cancer Research (2016)

Abstract Myeloid-derived suppressor cells (MDSC) play a major role in the immune defects associated with cancer. Although several mechanisms have been suggested as critical for MDSC-induced T cell suppression, there are no current therapies to block the accumulation and/or function of MDSC. Recent studies have highlighted the role of specific energy metabolic pathways in the activation and function of immune cells. However, the metabolic programs of tumor-associated MDSC (T-MDSC) remain unknown. Herein, we found that T-MDSC, but not splenic MDSC or normal myeloid cells, activated fatty acid oxidation (FAO). T-MDSC increased mitochondrial mass and function, key FAO enzymes, and oxygen consumption rate. Of interest, Inhibition of FAO blocked the immunosuppressive mechanisms and functions in T-MDSC and decreased their production of immunosuppressive cytokines. FAO inhibition also resulted in a T cell-dependent decrease in tumor growth and synergized with low-dose chemotherapy and cellular immunotherapy. Furthermore, targeting fatty acid uptake decreased the regulatory activity of T-MDSC. Human MDSC exhibited similar metabolic characteristics. These data support the possibility of targeting fatty acid metabolism as a novel approach to block MDSC and enhance cancer therapy. Citation Format: Amir A. Al-Khami, Fokhrul Hossain, Dorota Wyczechowska, Liqin Zheng, Paulo Rodriguez, Augusto C. Ochoa. Targeting fatty acid metabolism regulates the immunosuppressive activity of myeloid-derived suppressor cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-271.
50P Prognostic value of disseminated tumor cells (DTC) identification in bone marrow from patients with advanced gastric or esophagogastric junction (EGJ) adenocarcinoma (interim results)
Authors: E.S. Obarevich, N.S. Besova, N.N. Tupitsyn, M.M. Davydov, V.A. Gorbunova, T.A. Titova
Journal: Annals of Oncology (2015)
Evaluation of the ERα agonist, GTx-758 (250 mg daily), in men with metastatic (mCRPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC).
Authors: Evan Y. Yu, Michael L. Hancock, Tamas Babicz, William J. Aronson, Zsuzsanna Papai, Lajos Geczi, Robert H. Getzenberg
Journal: Journal of Clinical Oncology (2015)

201 Background: LHRH agents used for androgen deprivation therapy (ADT) were intended to lower total testosterone (T) levels to those achieved by orchiectomy. Studies have now demonstrated that a significant percentage of men do not reach orchiectomy equivalent levels and that lower serum T levels correlate with improved outcomes. GTx-758 (Capesaris®) is an oral estrogen receptor α agonist that has the potential to increase sex hormone binding globulin (SHBG), lower T levels, and ameliorate estrogen deficiency side effects associated with ADT. Methods: In an ongoing Phase 2 open label study (G200712, NCT01615120), men with high risk nmCRPC and mCRPC were continued on their current form of ADT along with either 125 mg or 250 mg of GTx-758 daily, for at least 90 days. Men at increased risk for venous thromboembolic events (VTE) are being excluded. The primary endpoint of this trial is the proportion of men with a PSA decline ≥50%, while secondary endpoints include serum total and free T, SHBG, bone turnover and hot flashes. Results: As of October 2014, the 250 mg cohort of GTx-758 has completed enrollment of 28 patients, 20 of which (1 nmCRPC and 19 mCRPC) are evaluable, having been on study ≥90 days. The principal mechanism of drug action, induction of SHBG is confirmed in these patients with median SHBG levels increasing to 297% of baseline. 250 mg GTx-758 impacts T levels in an additive fashion to LHRH agents, as while on study, 4/4 subjects with total T levels &gt;20 ng/dL have fallen below that level and 9/10 subjects with serum free T levels &gt;0.7 pg/ml have fallen below that level. Six of the 20 (30%) subjects have exhibited a ≥50 decrease in PSA level while 17/20 (85%) had PSA declines of varying magnitude. The bone turnover biomarker C-telopeptide decreased in 81% of the subjects. 250 mg of GTx-758 has been generally well tolerated with one reported possibly drug related SAE (VTE). Conclusions: While the Phase 2 clinical trial is ongoing, these preliminary findings indicate that 250 mg of GTx-758 is generally well tolerated and has additive activity to LHRH agents to further decrease testosterone, increase SHBG, lower PSA and decrease bone turnover. Clinical trial information: NCT01615120.
LP37 : A placebo-controlled, multicenter, double-blind, randomised trial of emricasan in subjects with non-alcoholic fatty liver disease (NAFLD) and raised transaminases
Authors: M. Shiffman, B. Freilich, R. Vuppalanchi, K. Watt, G. Burgess, M. Morris, B. Sheedy, E. Schiff
Journal: Journal of Hepatology (2015)