tbuckley/cabot-search huggingface dataset:
New insights to gene expression signatures from primary FFPE tumors for the prediction of response to cetuximab in KRAS and BRAF wild-type colorectal cancer (CRC).
Authors: E. Budinska, M. Delorenzi, W. De Roock, B. Jacobs, S. Walker, C. Wilson, T. Davison, R. D. Kennedy, S. Tejpar
Journal: Journal of Clinical Oncology (2010)

3588 Background: Cetuximab - an anti-EGFR monoclonal antibody improves overall and progression-free survival (PFS) in a subset of advanced-CRC patients. It has been demonstrated that KRAS and BRAF mutations are negative predictors of response to cetuximab and it has become standard to reserve treatment for KRAS wild-type (wt) tumors. However, there is an important proportion of KRAS and BRAF wt patients that do not respond to cetuximab. Our study aimed at identifying markers for response prediction to cetuximab in KRAS and BRAF wt patients via gene expression profiling. Methods: A CRC specific DNA microarray platform (CRCDSA) designed to work with formalin-fixed paraffin-embedded (FFPE) tissue was used for expression profiling of 65 FFPE CRC primary tumor samples. 44 KRAS and BRAF wt patients were selected for the analysis. We fitted a Cox proportional hazards model on PFS (42 events) in order to identify genes related to increased risk of progression after cetuximab treatment. Results: In the top 100 genes significantly associated with progression, the FGFR2 receptor was identified suggesting the activation of a signaling pathway alternative to EGFR. Other interesting genes connected to increased risk of progression were CTSE, S100B, MUC2, APC. Genes negatively correlated with progression were TOE1, XIAP, NAIP (inhibitors of apoptosis). Some of the genes (VAV3, EREG, PLAGL2, DIDO1,YES1) were in agreement with results of the same analysis we have performed on a publicly available dataset derived from metastatic tissues (Khambata-Ford S et al, JCO 2007). Conclusions: By using a transcriptome-focused approach to analyze FFPE primary tumor samples, we have identified novel targets and pathways of potential relevance to response to cetuximab in BRAF and KRAS wt tumors. This could be of significance in the development of new therapeutics for KRAS and BRAF wt nonresponsive patients and demonstrates the usefulness of FFPE primary material for response prediction of metastatic disease. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Almac Diagnostics Merck Serono
Pulmonary artery pressure‐guided heart failure management: <scp>US</scp> cost‐effectiveness analyses using the results of the <scp>CHAMPION</scp> clinical trial
Authors: Melissa Martinson, Rupinder Bharmi, Nirav Dalal, William T. Abraham, Philip B. Adamson
Journal: European Journal of Heart Failure (2016)

Abstract Aims Haemodynamic‐guided heart failure ( HF ) management effectively reduces decompensation events and need for hospitalizations. The economic benefit of clinical improvement requires further study. Methods and results An estimate of the cost‐effectiveness of haemodynamic‐guided HF management was made based on observations published in the randomized, prospective single‐blinded CHAMPION trial. A comprehensive analysis was performed including healthcare utilization event rates, survival, and quality of life demonstrated in the randomized portion of the trial (18 months). Markov modelling with Monte Carlo simulation was used to approximate comprehensive costs and quality‐adjusted life years ( QALYs ) from a payer perspective. Unit costs were estimated using the Truven Health MarketScan database from April 2008 to March 2013. Over a 5‐year horizon, patients in the Treatment group had average QALYs of 2.56 with a total cost of US $56 974; patients in the Control group had QALYs of 2.16 with a total cost of US $52 149. The incremental cost‐effectiveness ratio ( ICER ) was US $12 262 per QALY . Using comprehensive cost modelling, including all anticipated costs of HF and non‐ HF hospitalizations, physician visits, prescription drugs, long‐term care, and outpatient hospital visits over 5 years, the Treatment group had a total cost of US $212 004 and the Control group had a total cost of US $200 360. The ICER was US $29 593 per QALY . Conclusions Standard economic modelling suggests that pulmonary artery pressure‐guided management of HF using the CardioMEMS ™ HF System is cost‐effective from the US ‐payer perspective. This analysis provides the background for further modelling in specific country healthcare systems and cost structures.
An Objective Model to Optimize Treatment Decisions in Advanced Hepatocellular Carcinoma after Sorafenib Failure: The Sorfa Score
Authors: D.J. Pinato, C. Yen, T. Arizumi, P. Giarda, J. Howell, P. Toniutto, R. Ramaswami, M.E. Burlone, M. Kudo, M. Pirisi, R. Sharma
Journal: Journal of Hepatology (2016)
High Levels of Growth Differentiation Factor 15 in Patients with Congenital Dyserythtopoietic Anemia Type I
Authors: Hannah Tamary, Hanna Shalev, Galit Avraham, Meira Zoldan, Itai Levi, Dorine W. Swinkels, Toshihiko Tanno, Jeffery L Miller
Journal: Blood (2008)
HIV Testing Experience Before HIV Diagnosis Among Men Who Have Sex with Men — 21 Jurisdictions, United States, 2007–2013
Authors: Laurie Linley, Qian An, Ruiguang Song, Eduardo Valverde, Alexandra M. Oster, Xiaona Qian, Angela L. Hernandez
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Gay, bisexual, and other men who have sex with men (MSM) continue to be the population most affected by human immunodeficiency virus (HIV) in the United States. In 2014, 81% of diagnoses of HIV infection were among adult and adolescent males, and among these, 83% of infections were attributable to male-to-male sexual contact (1). Since 2006, CDC has recommended HIV testing at least annually for sexually active MSM to foster early detection of HIV infection and prevent HIV transmission (2,3). Several initiatives and strategies during the past decade have aimed to expand HIV testing among MSM to increase early diagnosis and treatment and reduce transmission. To better understand HIV testing patterns among MSM with diagnosed HIV infection, CDC analyzed data for 2007-2013 from jurisdictions conducting HIV incidence surveillance as part of CDC's National HIV Surveillance System (NHSS). Findings from this analysis suggest that increasing percentages of MSM have had a negative HIV test during the 12 months before diagnosis (48% in 2007, 56% in 2013, among those with a known date of previous negative HIV test), indicating a trend toward increased HIV testing and earlier HIV diagnosis among persons most at risk for HIV.
100% SVR4 and Favorable Safety of ABT-493 + ABT-530 Administered for 12 Weeks in Non-Cirrhotic Patients with Genotypes 4, 5, or 6 Infection (Surveyor-I)
Authors: E. Gane, J. Lalezari, A. Asatryan, S. Greenbloom, T. Hassanein, T. Ng, R. Liu, C.-W. Lin, J. Kort, F. Mensa
Journal: Journal of Hepatology (2016)
Single-Cell Immune Signatures in Patients with Chronic Phase Chronic Myeloid Leukemia (CML) Treated with Nilotinib: An ENEST1st Sub Study
Authors: Stein-Erik Gullaksen, Jørn Skavland, Krzysztof Warzocha, Sonia Gavasso, Vinko Tosevski, Noortje Thielen, Jaroslava Voglova, Augustin Ferrant, Werner Linkesch, Josef Thaler, Alois Lang, Jesper Stentoft, Tobias Gedde-Dahl, Henrik Hjorth-Hansen, Waleed Majeed, Gregor Verhoef, Andrzej Hellmann, Georgi G. Mihaylov, Claudia Dumrese, Frank Giles, Andreas Hochhaus, Sieghart Sopper, Leif Stenke, Boris Labar, Jeroen Janssen, Kimmo Porkka, Gert J. Ossenkoppele, Satu Mustjoki, Dominik Wolf, Bjorn T. Gjertsen
Journal: Blood (2015)
Effect of plasma SPARC on outcome in cancer models.
Authors: N. Desai, M. Piacente, X. Liu, O. D'Cruz, L. Hwang, X. Lin, S. Ran, S. Markovic, K. Motamed, V. N. Trieu
Journal: Journal of Clinical Oncology (2010)

10600 Background: SPARC is overexpressed in many cancers, including melanoma, breast, lung, and pancreas. SPARC overexpression in tumors enhances progression, angiogenesis, and metastasis and is generally associated with poor prognosis. However, plasma SPARC levels have not been previously investigated in relation to outcomes in cancer. Methods: Plasma SPARC level in melanoma patients (pts, n = 321 from 76 pts, baseline and post-treatment) was compared to normal controls (n = 50 from 50 pts) using a validated SPARC ELISA. Human SPARC protein was overexpressed in HEK293 cells and purified. Angiogenic activity of SPARC was tested in a 3D HUVEC tube formation assay. HT29 (colon), PC3 (prostate), MDA-MB-231 (breast) xenografts with a range of SPARC expression were grown in nude mice and treated with 5FU, docetaxel, nab-paclitaxel [nab-P], or nab-P + sunitinib with or without exogenously administered SPARC (IP, 200 mg/mouse, 2x wkly). The effect of exogenous (exo) SPARC and an anti-SPARC antibody (IP, 200 mg/mouse, 2x wkly) on lung metastases was examined in MDA-MB-435 (melanoma) or the syngeneic LL/2 (Lewis lung carcinoma) model. Results: Plasma SPARC levels were higher in melanoma pts than normal controls (259 ng/ml [95% CI = 273-327] vs 153 ng/ml [95% CI = 99-207], p < 0.0001). Exo SPARC counteracted antitumor activity of chemotherapy (chemo) in all xenografts. Exo SPARC also abolished synergy of nab-P with antiangiogenic agent sunitinib in vivo. In vitro, SPARC showed angiogenic activity which may partly explain the in vivo observations. Exo SPARC added to nab-P treatment resulted in a 3 fold increase in lung metastasic burden vs nab-P alone in MDA-MB- 435 xenografts. Conversely, SPARC antibody inhibited lung metastasis and increased survival of mice relative to a non-specific mouse IgG control (p = 0.02, log rank) in the LL/2 model. Conclusions: Plasma SPARC levels were higher in melanoma pts than normal controls. Exogenously administered SPARC in melanoma and other xenograft tumors counteracted the activity of chemo. In contrast, a SPARC antibody increased survival relative to controls. These data suggest that plasma SPARC may contribute to poor outcomes and a SPARC antibody may have potential applications in the treatment of cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience Abraxis BioScience Abraxis BioScience Abraxis BioScience Abraxis BioScience
Vasectomy and Prostate Cancer Incidence and Mortality in a Large US Cohort
Authors: Eric J. Jacobs, Rebecca L. Anderson, Victoria L. Stevens, Christina C. Newton, Ted Gansler, Susan M. Gapstur
Journal: Journal of Clinical Oncology (2016)

Purpose In a recent large prospective study, vasectomy was associated with modestly higher risk of prostate cancer, especially high-grade and lethal prostate cancer. However, evidence from prospective studies remains limited. Therefore, we assessed the associations of vasectomy with prostate cancer incidence and mortality in a large cohort in the United States. Patients and Methods We examined the association between vasectomy and prostate cancer mortality among 363,726 men in the Cancer Prevention Study II (CPS-II) cohort, of whom 7,451 died as a result of prostate cancer during follow-up from 1982 to 2012. We also examined the association between vasectomy and prostate cancer incidence among 66,542 men in the CPS-II Nutrition Cohort, a subgroup of the CPS-II cohort, of whom 9,133 were diagnosed with prostate cancer during follow-up from 1992 to 2011. Cox proportional hazards regression modeling was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% CIs. Results In the CPS-II cohort, vasectomy was not associated with prostate cancer mortality (HR, 1.01; 95% CI, 0.93 to 1.10). In the CPS-II Nutrition Cohort, vasectomy was not associated with either overall prostate cancer incidence (HR, 1.02; 95% CI, 0.96 to 1.08) or high-grade prostate cancer incidence (HR, 0.91; 95% CI, 0.78 to 1.07 for cancers with Gleason score ≥ 8). Conclusion Results from these large prospective cohorts do not support associations of vasectomy with either prostate cancer incidence or prostate cancer mortality.
Generic Intravenous Busulfan in Hematopoietic Stem Cell Transplantation: Relevance of Therapeutic Drug Monitoring
Authors: Ezhil Pavai Mohanan, Shareen Stella Backia Royan, John C Panetta, Fouzia Nambiathayil Abubacker, Anu Korula, Aby Abraham, Auro Viswabandya, Biju George, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian
Journal: Blood (2015)
PTEN Is Essential for Normal Cytokine Signaling and Oncogenic Transformation of Pre-B Cells
Authors: Seyedmehdi Shojaee, Valeria Cazzaniga, Hilde Schjerven, Maike Buchner, Christian Hurtz, Huimin Geng, Andreas Hochhaus, Giovanni Cazzaniga, Ari M Melnick, Steven M. Kornblau, Thomas G Graeber, Markus Muschen
Journal: Blood (2014)
Laser Transmyocardial Revascularization (TMLR) Combined with Autologous Bone Marrow Cells (ABMC) for Diffuse Coronary Disease (DCD). Results In 19 Cases
Authors: Adrian Alegre, Beatriz Aguado, M. Perez Alfonso, C. Muñoz, M. Ortiz de Landázuri, F. Madrid Sanchez, C. Cámara, N. García-Fernández, L. Bascones, S. Martinez, N. García-León, M. Roig, J. Duarte, G. Reyes
Journal: Blood (2010)
Adolescent and young adult use of Internet-based cancer survivorship care plans.
Authors: C. E. Hill-Kayser, C. Vachani, M. K. Hampshire, L. A. Jacobs, J. M. Metz
Journal: Journal of Clinical Oncology (2010)

9117 Background: Adolescent and young adult (AYA) cancer survivors are a unique subset of the survivor population. Data suggest that most use the Internet for cancer information, seeking information on late effects, nutrition, exercise, and infertility, but 25-50% report an unmet need for information (Zebrack, 2007). Methods: In 5/07, we launched an Internet-based tool for creation of survivorship care plans (SCP). The care plan tool is available at www.livestrongcareplan.org, and via OncoLink, a cancer information website based at the University of Pennsylvania, serving over 3.9 million pages/ month to 385,000 unique IP addresses. The tool allows users to enter information regarding demographics, diagnosis, and treatment, and produces customized SCP that include guidelines for future care, as well as information on late effects, fertility, and age-appropriate screening. All information is provided by oncology nurses and physicians, and data collection is IRB approved. Results: Between 5/07 and 12/09, 9271 SCP were completed. Of these, 16% (1477) were for AYA survivors, of ages 18-39 (median 30). This group was 69% female and 81% Caucasian, with diagnoses most commonly of breast cancer (32%), lymphoma/leukemia (28%), and testicular cancer (8%); 84% reported treatment with chemotherapy, 75% surgery, and 54% radiation. 52% reported receiving current care from only an oncologist, 14% only a primary care provider, and 30% both. 14% reported receiving survivorship information previously. Of female users, 32% reported being unsure of whether menses would resume, and 17% had undergone treatment-induced menopause. The tool provided a “good” to “excellent” experience to 91% of AYA users, and 89% reported “good” to “excellent” satisfaction with information provided. Conclusions: AYA survivors represent a prominent group of users of this Internet SCP tool. Most have undergone multi-modality treatment, and may be at significant risk for late effects, including fertility issues as evidenced by many reporting treatment-related menopause. Most AYA are followed only by an oncologist, and have not received survivorship information previously. This population reports high-satisfaction with, and willingness to use, this type of tool. No significant financial relationships to disclose.
Trastuzumab mimotope vaccination of HER-2/neu transgenic mice results in prolonged tumor-free survival and reduced tumor load
Authors: A. B. Riemer, K. H. Brämswig, H. Pehamberger, O. Scheiner, C. C. Zielinski, E. Jensen-Jarolim
Journal: Journal of Clinical Oncology (2006)

12510 Background: Passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin) to date is the most effective treatment for patients with HER-2/neu overexpressing breast cancer. In previous studies we could show that active immunization with peptide mimotopes, i.e. structural mimics of the epitope recognized by trastuzumab, leads to formation of antibodies again recognizing HER-2/neu in mice. Functional in vitro analyses of the induced antibodies demonstrated “trastuzumab-like” properties, such as receptor internalization, inhibition of signaling, and antibody-mediated cytotoxicity against HER-2/neu overexpressing breast cancer cells. The aim of the present study was to test the effects of trastuzumab mimotope vaccination in vivo, namely in a HER-2/neu transgenic mouse model. Methods: We used BALB-neuT mice, which carry the activated neu oncogene on the BALB/c background. These mice constitute the most aggressive animal model for HER-2/neu driven carcinogenesis, as all females uniformly develop mammary carcinomas at the age of 12 weeks. One group of mice was immunized with the previously described trastuzumab mimotope - KLH conjugate, a control group with the carrier protein KLH alone, and a further control group was left naïve. Mice were palpated weekly to monitor tumor development and size, and blood samples were taken at regular intervals to follow up the induced immune responses. Results: Trastuzumab mimotope immunizations lead to delayed tumor development and thus to an increase in tumor-free survival. When tumors occurred, they were smaller and grew more slowly than in the control mice. In contrast, control KLH immunizations did not affect tumor growth kinetics as compared to the naïve mice. Serum analysis demonstrated that all immunized animals had mounted an anti-KLH immune response, so we accredit the observed tumor-inhibitory effects in the mimotope group to the biologic properties of induced anti-HER-2/neu antibodies. Conclusion: These results indicate that epitope-specific vaccination with mimotopes elicits trastuzumab-like antibodies that are effective in vivo against HER-2/neu overexpressing tumor cells also in HER-2/neu expressing organisms. [Table: see text]
Non-Factor VIII Coagulation Proteins Fail to Predict Joint Outcome in Severe Hemophilia a
Authors: Beth Boulden Warren, Linda Jacobsen, Elizabeth Villalobos-Menuey, Thomas C. Abshire, Amy D Shapiro, Michael Recht, Deborah Brown, Cindy A. Leissinger, Christine L. Kempton, Heidi Lane, Diane J. Nugent, Marilyn J. Manco-Johnson
Journal: Blood (2015)
FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials
Authors: Katherine M Livingstone, Carlos Celis-Morales, George D Papandonatos, Bahar Erar, Jose C Florez, Kathleen A Jablonski, Cristina Razquin, Amelia Marti, Yoriko Heianza, Tao Huang, Frank M Sacks, Mathilde Svendstrup, Xuemei Sui, Timothy S Church, Tiina Jääskeläinen, Jaana Lindström, Jaakko Tuomilehto, Matti Uusitupa, Tuomo Rankinen, Wim H M Saris, Torben Hansen, Oluf Pedersen, Arne Astrup, Thorkild I A Sørensen, Lu Qi, George A Bray, Miguel A Martinez-Gonzalez, J Alfredo Martinez, Paul W Franks, Jeanne M McCaffery, Jose Lara, John C Mathers
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. <b>Design</b>&nbsp;Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. <b>Data sources</b>&nbsp;Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. <b>Eligibility criteria for study selection</b>&nbsp;Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity. <b>Results</b>&nbsp;We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category. <b>Conclusions</b>&nbsp;We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions. <b>Systematic review registration</b>&nbsp;PROSPERO CRD42015015969.
Outcomes of Patients Undergoing Endoscopic Endonasal Skull Base Surgery at a VA Hospital
Authors: Michael Jones, Stephen Johans, Andrea Ziegler, Kevin C. Welch, Monica O. Patadia, Chirag R. Patel, Anand V. Germanwala
Journal: JAMA Surgery (2016)

obtain good results that compare equally with those of published studies on non-VA patient populations.These initial results suggest veterans can benefit from this procedure and have it done safely at a VA hospital with experienced skull base surgery teams.
Clinical features of patients with lung adenocarcinomas harboring BRAF V600E mutations.
Authors: Tongtong An, Jie Wang, Hua Bai, Zhijie Wang, Jun Zhao, Jianchun Duan, Minglei Zhuo, Meina Wu, Yuyan Wang, Shuhang Wang
Journal: Journal of Clinical Oncology (2013)

8101 Background: To investigate the prevalence, distribution, and prognostic role of activating BRAF mutations in Chinese patients with lung adenocarcinomas (ADCs). Methods: This retrospective study included 192 lung ADCs (97 males 50.5%, 95 females 49.5%). BRAF gene mutations were screened using AmoyDx BRAF V600E mutations detection kit. Mutations of EGFR and KRAS gene were also analyzed. Results: BRAF mutations were present in 8(4.17%) lung ADCs patients. V600E mutations were significantly more prevalent in females (6 of 96; 6.25%) than in males (2 of 97; 2.06%), as indicated by multivariate logistic regression analysis. Other clinocopathologic parameters, including age, smoking history, and tumor stage, were not significantly associated with V600E BRAF mutations. V600E-mutated tumors were not associated with different progression-free and overall survival rates comparing with non V600E-mutated tumors in this study. The frequency of EGFR and KRAS mutations in all patients were 42.7%(82/192) and 8.3%(16/192), respectivelyBRAF and EGFR were concomitantly mutated in three tumors. All tumors with BRAF mutations were found to be negative for KRAS mutations. Conclusions: We report for the first time to our knowledge that V600E BRAF mutation has high concomitant occurrence rate with EGFR mutations in Chinese lung ADCs patients. BRAF mutations were found to be independently associated only with female gender.
European Mitochondrial DNA Haplogroups Impact on Liver Fibrosis Progression among HCV and HIV/HCV Coinfected Patients from Northwest Spain
Authors: A. Tabernilla, I. Rego-Pérez, M. Grandal, B. Pernas, S. Pértega, A. Mena, I. Rodríguez-Osorio, M. Delgado, A. Mariño, H. Álvarez, J.D. Pedreira, F.J. Blanco, E. Poveda
Journal: Journal of Hepatology (2016)
Different Prevalence of HCV Resistance and HCV RNA Quantification Within Tumoral and Non Tumoral Liver Tissues in HCC/Transplanted Patients
Authors: M.C. Sorbo, F.P. Antonucci, M. Manuelli, I. Lenci, D. Sforza, L. Carioti, M.C. Bellocchi, V. Cento, D. Di Paolo, F. De Leonardis, M. Milana, T. Manzia, G. Tisone, M. Angelico, C.F. Perno, F. Ceccherini-Silberstein
Journal: Journal of Hepatology (2016)