tbuckley/cabot-search huggingface dataset:
Cancer genomics-based approach for development of new immunotherapeutics for lung cancers.
Authors: Yataro Daigo, Atsushi Takano, Koji Teramoto, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2014)

3036 Background: Oncoantigens are oncogenic and high immunogenicity proteins specifically expressed in cancer cells, and are promising targets for immunotherapy. Methods: We have established a strategy as follows to identify new oncoantigens; (1) screening of highly expressed genes in the majority of 120 llung cancers using cDNA microarray representing 27,648 genes, (2) verification of no expression of each gene in normal tissues, (3) validation of the clinicopathological significance of its high level of expression with tissue microarray covering 400 lung cancers, (4) characterization of a critical role of each gene in the growth or invasiveness of cancer cells by RNAi and cell growth/invasion assays, (5) screening of the epitope peptides recognized by HLA-A*0201- or A*2402-restricted cytotoxic T lymphocyte (CTL) for clinical trials. Results: We identified 40 oncoantigens and identified dozens of 10-amino-acid peptides, each of which was a candidate to be presented on the surface of HLA-A*0201 or HLA-A*2402 that induced in vitro CTL response. We conducted a phase I study for HLA-A*2402-positive, advanced non-small cell lung cancer patients who failed to standard therapy, using the combination of 1, 2 or 3 mg/body of each peptides from LY6K, CDCA1, and KIF20A mixed with adjuvant once a week. 18 evaluable patients have been enrolled, and this cancer vaccine therapy demonstrated tolerability and had very high immunogenicity of even 1 mg/body dose to induce antigen-specific CTLs in cancer patients. The clinical response of the vaccination was evaluated according to RECIST; one complete response case was observed, 8 patients showed stable disease, and 9 showed progressive disease, indicating that disease control rate was 50%. We are also screening predictive and monitoring biomarkers for peptide vaccine therapy through immunogenomics approach by analyzing pattern of CTL response, genomic/proteomic profiles of CTLs and cancer tissues, and genetic variation of patients. Conclusions: The cancer vaccine therapy using the cocktail of three peptides demonstrated good tolerability as well as the promising disease control rate, and therefore warrants further clinical studies with screening of their companion diagnostics. Clinical trial information: NCT01069575.
Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact
Authors: Panagiotis Baliakas, Sabine Jeromin, Michalis Iskas, Anna Puiggros, Karla Plevova, Florence Nguyen-Khac, Zadie Davis, Gian Matteo Rigolin, Andrea Visentin, Aliki Xochelli, Julio Delgado, Fanny Baran-Marszak, Evangelia Stalika, Pau Abrisqueta, Kristina Durechova, George Papaioannou, Virginie Eclache, Maria Dimou, Theodoros Iliakis, Rosa Collado, Michael Doubek, M. Jose Calasanz, Neus Ruiz-Xiville, Carolina Moreno, Marie Jarosova, Alexander C. Leeksma, Panayiotis Panayiotidis, Helena Podgornik, Florence Cymbalista, Achilles Anagnostopoulos, Livio Trentin, Niki Stavroyianni, Fred Davi, Paolo Ghia, Arnon P. Kater, Antonio Cuneo, Sarka Pospisilova, Blanca Espinet, Anastasia Athanasiadou, David Oscier, Claudia Haferlach, Kostas Stamatopoulos
Journal: Blood (2019)
Metabolic profiling of antiangiogenic agents on glioma cells.
Authors: Antoine F Carpentier, Tanja Mesti, Claire Banissi, Philippe Savarin, Mohamed N Triba, Janja Ocvirk
Journal: Journal of Clinical Oncology (2014)

e13023 Background: The direct impact on glioma cells metabolism of drugs targeting the VEGF, such as Bevacizumab (Bev) or VEGFR Tyrosine Kinase Inhibitor (TKI), are poorly known. Glioma cells not only secrete high levels of vascular endothelial growth factor (VEGF) but also express VEGF receptors (VEGFR), supporting the existence of an autocrine loop. Methods: U87 cells were treated with Bev or SU1498, a selective VEGFR2 TKI. Cell proliferation and morphology was assessed after 24 and 48 hours. VEGFR expression was checked with FACS flow cytometry and VEGF secretion into the medium assessed with an ELISA kit. Metabolomic studies on cells were performed using High Resolution Magic Angle Spinning Spectroscopy (HR-MAS). Results: Metabolomic studies with HR MAS showed that Bev had no significant effect on cell metabolism, while SU1498 induced a marked increase in lipids and a decrease in glycerophosphocholine. U87 cells secreted VEGF and expressed low level of VEGFR2, but no detectable VEGFR1. Exposure to SU1498, but not Bev, significantly impacted cell proliferation and morphology. Conclusions: In patients treated with VEGFR TKI, monitoring lipids with magnetic resonance spectroscopic (MRS) might be a valuable marker to assess drug cytotoxicity. Although both drugs target the VEGF pathway, only SU1498 showed a clear impact on cell proliferation, cell morphology and metabolism. Bevacizumab is thus less likely to modify glioma cells phenotype due to a direct therapeutic pressure on the VEGF autocrine loop.
Abstract 15079: Complete Revascularization for Multivessel Disease ST Elevation Myocardial Infarction: Insights From an Updated Meta-Analysis
Authors: Amartya Kundu, Partha Sardar, Saurav Chatterjee, Jay Giri, Debabrata Mukherjee
Journal: Circulation (2015)

Introduction: Multivessel Disease is commonly seen in ST Elevation Myocardial Infarction (STEMI). Current guidelines recommend primary percutaneous coronary intervention (PCI) on only the culprit vessel , unless the patient is hemodynamically unstable. Recent trials have reported significant benefit on cardiovascular endpoints with complete revascularization of vessels during STEMI. The purpose of this meta analysis was to assess the benefit of complete revascularization (either single setting or staged PCI) compared to culprit only PCI in STEMI patients with multivessel disease. Methods: We searched PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science ,CINAHL databases and presentations at major cardiovascular scientific sessions from inception through June 5th, 2015. Randomized Trials comparing complete revascularization strategies (single-setting PCI or staged PCI) and culprit-only PCI were included. The primary outcome of interest was major adverse cardiovascular events (MACE) defined as a composite of all-cause mortality, new myocardial infarction (MI) and repeat revascularization. Results: Seven trials enrolling a total of 2006 patients were included in the final analysis. Complete revascularization (single-setting PCI + staged PCI) was associated with a significant reduction in MACE, when compared to culprit only PCI [OR 0.52; 95 % CI 0.32 to 0.85; P = 0.009]. However, there was no significant difference in all cause mortality [OR 0.75; 95 % CI 0.51 to 1.12] or recurrent MI [OR 0.74;95 % CI 0.4 to 1.39] with complete revascularization. Conclusion: In patients with STEMI and multivessel disease, complete revascularization is associated with a significant reduction in major adverse cardiovascular outcomes, driven primarily by a reduction in repeat revascularization, with no evidence of significant difference in all cause mortality or recurrent MI when compared to culprit only PCI.
Incidence and risk of diarrhea in cancer patients treated with pertuzumab: Evidence from published studies.
Authors: Xiaoxiang Guan, Zexing Wang, Yucai Wang
Journal: Journal of Clinical Oncology (2014)

e22216 Background: Pertuzumab is a novel HER2 dimerization inhibitor administered in combination with trastuzumab and docetaxel in the treatment of HER2-positive metastatic breast cancer. Diarrhea is one of the most common reported adverse events in most clinical trials of pertuzumab. However, the incidence and risk of diarrhea with pertuzumab have not been systematically investigated. Therefore, we conducted this meta-analysis to get a better understanding of the overall incidence and risk of diarrhea in cancer patients receiving pertuzumab. Methods: The PubMed and Web of Science databases were searched for prospective phase II or III clinical trials in which pertuzumab was administered to cancer patients. Overall incidence, relative risk (RR), and 95% confidence intervals (CI) were computed using fixed or random-effects models depending on the heterogeneity of the included studies. Results: A total of 1,918 patients (pertuzumab, n = 1,275; controls, n = 643) with a variety of solid malignancies from 10 clinical trials were included in our meta-analysis. The overall incidences of all-grade and high-grade diarrhea with pertuzumab were 52.2 % (95 % CI 42.7–61.5 %) and 7.1 % (95 % CI 5.7–8.8 %), respectively. The RRs of all-grade and high-grade diarrhea in comparison to controls were increased for all-grade (RR 1.47, 95 % CI 1.31–1.65; P = 0.000) and high-grade (RR 1.73, 95 % CI 1.08–2.77; P = 0.023) diarrhea. Conclusions: The use of pertuzumab is associated with a significant risk of diarrhea. Clinicians should be aware of this risk and provide appropriate, proactive management, which may improve patient quality of life and adherence to therapy and thus possibly optimize clinical outcomes.
Association of biomarkers with cardiac events during abiraterone acetate treatment in castration-resistant prostate cancer (CRPC).
Authors: Silvia Zanardi, Sara Campora, Matteo Puntoni, Marco Piccininno, Arnoldo Piccardo, Mehrdad Shoushtari Zadeh Naseri, Carlotta Defferrari, Ennio Biscaldi, Giancarlo Antonucci, Damiano Ricci, Marco Mori, Andrea De Censi
Journal: Journal of Clinical Oncology (2014)

e16086 Background: Abiraterone acetate is an effective drug for metastatic CRPC, but serious cardiac adverse events may occur. Objectives: We explored the association between the cardiac biomarkers N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and Troponin-T (TnT) and cardiac SAEs during abiraterone therapy in patients with CRPC. Methods: Seventeen patients, in a single institution, were treated with abiraterone acetate, 1 g daily, until disease progression. Concomitant treatment with prednisone, then switched to dexametasone plus canrenone, was administered. Blood samples for PSA, NT-proBNP and TnT were obtained at baseline, 1, 3 and 6 months of treatment. Adverse events were evaluated using NCI-CTCAE v 4. Tumor response was assessed by PET-CT and/or contrast enhancement CT scan and PSA. Results: Five patients (29.4%) experienced G3-4 cardiac SAEs after a median of 13 weeks (range 9-32) of treatment. Specifically, pulmonary edema G4, heart failure G3, acute coronary syndrome G3, synus bradycardia with syncope G4 and pulmonary edema G4 occurred 8, 12, 12, 20 and 32 weeks after treatment initiation, respectively. At baseline, their median NT-proBNP and TnT levels were about four and two fold higher than in patients without cardiac SAEs, and at 4 weeks five and two fold higher, respectively.An overall response rate of 67% according to RECIST and 70% according to EORTC PERCIST criteria was recorded. Median PFS and OS were 407 (IQR 90-496) and 457 (IQR 140-not yet reached) days, respectively. PSA decreased in 57% of patients. Patients with baseline NT-proBNP greater than the median value of 250 pg/mL exhibited no PSA response (BNP <250 pg/mL vs >=250 pg/mL, PSA difference, -25.4 and +36.3 ng/mL respectively, P=0.07). Conclusions: NT-proBNP and TnT levels before and during abiraterone treatment may identify patients at higher risk of cardiac SAE. Time Cardiac SAE (n=5) No Cardiac SAE (n=12) p* n median (IQR) n median (IQR) NT-proBNP [pg/mL] Baseline 5 1052 (226-1159) 12 245 (161-380) 0.3 Month 1 4 725 (139-2227) 9 116 (98-333) 0.3 TnT [pg/mL] Baseline 5 21.3 (18.3-22.5) 12 12.4 (9.8-17.1) 0.07 Month 1 4 23.7 (11.3-43.3) 10 12.4 (9.5-15.0) 0.4
Application of a validated predictive model for venous thrombo-embolism in cancer to patients with glioblastoma.
Authors: Ajay Prakash Abad, Jennifer Serventi, Nimish Mohile
Journal: Journal of Clinical Oncology (2014)

2073 Background: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with Glioblastoma (GBM). Despite a 7-28% incidence of VTE in GBM, there is no data to initiate thromboprophylaxis. A risk score developed by Khorana et al. for non-CNS malignancies incorporates histology, BMI, and pre-chemotherapy blood counts, reliably predicting those patients at highest risk of VTE. We sought to determine if this risk score could identify those GBM patients at highest risk and therefore, potential candidates for thromboprophylaxis. Methods: We performed an IRB-approved retrospective study of all GBM patients at the Wilmot Cancer Center from January 2005 to May 2011. Baseline blood counts and BMI were obtained and charts were reviewed to determine occurrence of VTE. We assigned 1 point each for PLT≥350,000/μl, Hgb<10 g/dl, WBC >11,000/μl, and BMI≥35 kg/m2; all patients received 2 points for having a high-risk histology. We assessed whether patients with a risk score ≥3 had a higher occurrence of VTE compared to patients with a risk score of 2. Results: 167 GBM patients (median age=64) were identified and 20% developed VTE. VTE was characterized as DVT only in 15 patients, PE only in 13 patients, and concomitant DVT/PE in 6 patients. 46% (n=77) had a risk score of 2 (intermediate risk), and 64% (n=90) had a risk score ≥3 (high risk). 15.6% of patients with a score of 2 developed VTE compared to 18.9% with risk score ≥3 (p=0.575). Conclusions: VTE is common in GBM and our rate of 20% is consistent with previous reports. All GBM patients were intermediate or high risk, and the percentage of patients developing VTE (18.9%, score ≥3, 15.6%, score=2) far exceeds that reported in non-CNS cancers (6.7%, score ≥3, 2.0%, score=2). Although there was no statistical difference in this relatively small cohort of patients, our findings suggest that this risk model can discriminate higher risk patients. Future risk models specific to GBM may benefit from incorporating post-operative ambulation status, extent of resection and biomarkers such as tissue factor.
Do conditionally reprogrammed cell cultures represent the tumors they have been isolated from with high fidelity?
Authors: Michael David Johnson, Bassem R Haddad, Robert Clarke, Paula Raffin Pohlmann, Claudine Isaacs
Journal: Journal of Clinical Oncology (2014)

e22140 Background: Establishing cell lines from solid tumors is difficult and time consuming, particularly for some tumor types, with the result that in vitro studies must rely on a limited array of lines, many of which were generated decades ago, often from plural effusions or malignant ascites. Conventional primary tumor cell cultures grow slowly, have a limited lifespan, and rapidly changing properties. How closely cell lines and cultures model their tumors of origin is not clear. This has limited the use of tumor cell cultures for personalized medicine. Conditional Reprogrammed Cell (CRC) culture, is a recently reported method (Liu et al. 2012) that allow indefinite cell cultures to be rapidly generated from epithelial or carcinoma samples with very high success rates (often >80%). We have examined how well breast CRC cultures mimic the properties of tissue from which they were derived. Methods: CRC cultures were established as reported. Their identity was confirmed by DNA fingerprinting assay, their karyotype was determined, and the expression of key tumor markers (ER, PR, HER2, etc) was compared to that of the tissues used to generate the lines. Results: Using this approach cultures have been rapidly established from normal and tumor samples of breast , prostate, pancreas, colorectal, lung, and other tissues, and their fidelity to the tissues of origin was assessed. Conclusions: CRC culture provides a rapid and reliable method to generate cultures that might be used for personalized tumor sensitivity assays.
Melanoma survival disparity by race and insurance status.
Authors: Katherine Chiang, Sean Dawes, Haley R Gittleman, Jill Barnholtz-Sloan, Jeremy S Bordeaux
Journal: Journal of Clinical Oncology (2014)

e20030 Background: In this study, we explore the effect of race and insurance status on melanoma survival rates while controlling for stage of disease at presentation. Methods: Data for this study was obtained from the Ohio Cancer Incidence Surveillance System (OCISS). We selected for individuals diagnosed with microscopically confirmed cases of cutaneous melanoma between 1996 and 2009 with follow-up to 2010. Data collected from OCISS registry included age, race, ethnicity, primary payer, stage of disease, survival time, and vital status. The 2010 US Census and SEER 13 database were also used for demographic data and melanoma incidence rates. Categorical variables were assessed using SPSS Statistics 20.0. Overall survival differences between cohorts were calculated using the Kaplan-Meier method with SAS 9.4 software. Results: A total of 31, 957 patients were diagnosed with primary cutaneous melanoma (CM) in Ohio from 1996 to 2009. Our patient demographic was 90.7% White and 0.5% Black. The primary payer at diagnosis was known for 67% of the patients—23.7% had private insurance, 19.0% of patients had Medicare and 1.6% had Medicaid. We found that the incidence of CM in Ohio is increasing at an average annual rate of 7.2% compared to 1.7% for the United States, the vast majority of which can be attributed to increases in Stage 0 and Stage 1. Chi-square analysis revealed that patients were more likely to present at a later stage of the disease if they were black, have Medicaid, or have Medicare insurance (p<0.05). For any given stage, median survival was greater for whites than blacks, especially for stage 0 (35 month difference, p=.11) and stage 1 (15 month difference, p=0.01). For stage 0 and stage 1, patients with private insurance or no insurance had greater mean survival than patients with Medicaid or Medicare (p<0.05). This phenomenon was not present among patients >65yo. Conclusions: A disparity in melanoma survival rates continue to exist in Ohio. Black patients and patients with Medicare or Medicaid not only present at later stages of disease, but have worse survival rates at any given stage. Patients with no insurance have similar presentation stages and survival rates as patients with insurance.
Interventions to Support Behavioral Self-Management of Chronic Diseases
Authors: John P. Allegrante, Martin T. Wells, Janey C. Peterson
Journal: Annual Review of Public Health (2019)

A majority of the US adult population has one or more chronic conditions that require medical intervention and long-term self-management. Such conditions are among the 10 leading causes of mortality; an estimated 86% of the nation's $2.7 trillion in annual health care expenditures goes toward their treatment and management. Patient self-management of chronic diseases is increasingly essential to improve health behaviors, health outcomes, and quality of life and, in some cases, has demonstrated effectiveness for reducing health care utilization and the societal cost burden of chronic conditions. This review synthesizes the current state of the science of chronic disease self-management interventions and the evidence for their effectiveness, especially when applied with a systematic application of theories or models that account for a wide range of influences on behavior. Our analysis of selected outcomes from randomized controlled trials of chronic disease self-management interventions contained in 10 Cochrane systematic reviews provides additional evidence to demonstrate that self-management can improve quality of life and reduce utilization across several conditions.
A Surveillance Epidemiology and End Results (SEER) database review of epidemiology and outcome of ampullary cancer compared to cholangiocarcinoma.
Authors: Mohammed Nawaf Kanaan, Andrew I. Kovoor, Hani M. Babiker, Haiyan Cui, Steven Malangone, Emad Elquza, Hitendra Patel
Journal: Journal of Clinical Oncology (2014)

e15147 Background: Ampullary adenocarcinoma (AC) is a rare form of cancer with sparse epidemiological and survival data in literature. We aimed to study the epidemiology and survival outcome of AC compared to Cholangiocarcinoma (CC) by reviewing the SEER database. Methods: The SEER database(version 8.1.2) was reviewed for patients (pts) with histologically confirmed AC and CC between 1973-2007. Variables included were: age, race, gender, surgical resection of primary tumor, SEER adjusted stage and overall survival (OS). Primary outcome was 3 year OS. Data was analyzed using Chi square and Kaplan-Meier method using z-test. Results: A total of 3,179 pts with AC and 5273 with CC were included in SEER database between 1973 and 2007. The mean age in AC was higher 67.5 compared to 64.7 years in CC(P value=<0.0001). AC had higher white to black ratio (13:1) compared to CC (10:1) (P value=0.0016). Male to female ratio was similar in both groups. Stage frequency at presentation in AC were localized (23%), regional (65%) and distant (12%) where in CC they were 22%, 36% and 42%, respectively (P value=<0.0001). Surgery rate was higher in AC compared to CC in localized (64 versus 36%, P value=<0.0001), regional (82 versus 35%, P value=<0.0001) and distant stages (22% versus 13%, P value=<0.0001). When compared stage to stage for all pts, AC had better 3 year OS in localized (43% versus 21%), regional (43% versus 12%) and distant disease (3.9% versus 2.6%) as compared to CC. In pts who had surgical treatment, AC still had better 3 year OS in localized (68 versus 59%, P-value=<0.0001), regional (44 versus 28%, P-value=<0.0001) and distant disease (12 versus 9%, P-value=0.45). Conclusions: AC as compared with CC, has statistical significant difference in age and race distribution. When compared stage to stage, AC has a better 3 year OS even after adjusting for potential confounders including the higher surgical resection rate. This difference appears to be statistically insignificant in distant stages.