tbuckley/cabot-search huggingface dataset:
Patterns of in vitro chemotherapy (CT)-induced apoptosis (APOP) in recurrent/metastatic breast carcinoma (CA): Comparisons of generic multisource drugs (generics) with proprietary single-source drugs (proprietaries).
Authors: Linda D. Bosserman, Karl Rogers, Dirk C. Davidson, Carl Rogaston Willis, James Rutledge, Allan Hallquist, Tracy Young, Swapnil Padmakar Rajurkar, Misagh Karimi, Cary A. Presant
Journal: Journal of Clinical Oncology (2012)

e11562 Background: Therapy of metastatic breast CA involves choices between Generics and Proprietaries, and between combination CTs (Combos) and single-agent CTs. This study determined the relative in vitro CT induced APOP of Generics versus Proprietaries, and Combos versus single agents. Methods: Purified breast CA cells from 67 patient (Pt) biopsies were placed in short-term culture with CT using the microculture kinetic (MiCK) assay. APOP was analyzed every five min over 48 hrs. APOP was defined in kinetic units (KU) of apoptosis. Significant APOP was &gt; 1.0 KU. Significant difference between individual assays was &gt; 0.57 KU based on replicate analyses. Results: 43 Pts were evaluable for comparison of Generics versus Proprietaries. Generics produced APOP &gt; Proprietaries in 36/43 Pts (84%) and = to Proprietaries in 6 Pts (14%). Proprietaries produced APOP &gt; Generics in 1 Pt (2%). In-class comparisons indicated epirubicin had mean APOP &gt; doxorubicin (P=0.01), cisplatin had APOP &gt; carboplatin (P&lt;0.01); vinorelbine had APOP &gt; vincristine (P=0.02); docetaxel had APOP &gt; nab-paclitaxel (P=0.01); whereas docetaxel and paclitaxel APOP were not different (P=0.85). However, in individual Pts, docetaxel had APOP &gt; paclitaxel in 37% of Pts, whereas paclitaxel was better than docetaxel in 31%. For Combos, cyclophosphamide + doxorubicin produced APOP &gt; single agents in 25%, while single agents had APOP = or &gt; cyclophosphamide plus doxorubicin in 67%. Cyclophosphamide plus docetaxel had APOP &gt; single agents in 33%, but single agents had APOP = or &gt; cyclophosphamide plus docetaxel in 66%. Other comparisons will be presented. Conclusions: Generics APOP is often equal to or better than Proprietaries APOP. In individual Pts single agents frequently produced higher APOP than Combos. The MiCK APOP assay can identify individual Pts with metastatic breast CA for whom Generics or single agents produce higher APOP than Proprietaries or Combos. Prospective clinical trials confirming these predictive differences are warranted. These differences could result in significant savings in health care costs.
Tumor-Localized Secretion of Soluble PD1 Enhances Oncolytic Virotherapy
Authors: Mee Y. Bartee, Katherine M. Dunlap, Eric Bartee
Journal: Cancer Research (2017)

Abstract Oncolytic virotherapy represents an attractive option for the treatment of a variety of aggressive or refractory tumors. While this therapy is effective at rapidly debulking directly injected tumor masses, achieving complete eradication of established disease has proven difficult. One method to overcome this challenge is to use oncolytic viruses to induce secondary antitumor immune responses. Unfortunately, while the initial induction of these immune responses is typically robust, their subsequent efficacy is often inhibited through a variety of immunoregulatory mechanisms, including the PD1/PDL1 T-cell checkpoint pathway. To overcome this inhibition, we generated a novel recombinant myxoma virus (vPD1), which inhibits the PD1/PDL1 pathway specifically within the tumor microenvironment by secreting a soluble form of PD1 from infected cells. This virus both induced and maintained antitumor CD8+ T-cell responses within directly treated tumors and proved safer and more effective than combination therapy using unmodified myxoma and systemic αPD1 antibodies. Localized vPD1 treatment combined with systemic elimination of regulatory T cells had potent synergistic effects against metastatic disease that was already established in secondary solid organs. These results demonstrate that tumor-localized inhibition of the PD1/PDL1 pathway can significantly improve outcomes during oncolytic virotherapy. Furthermore, they establish a feasible path to translate these findings against clinically relevant disease. Cancer Res; 77(11); 2952–63. ©2017 AACR.
Subgroup analyses of randomized phase II study on gemcitabine with an EPA-enriched oral supplement in advanced pancreatic cancer.
Authors: Makoto Ueno, Shinichi Ohkawa, Satoshi Kobayashi, Kazuya Sugimori, Taku Kaneko, Ryo Kameda, Tomoko Andou, Haruo Miwa, Ryonho Ko, Katsuaki Tanaka, Manabu Morimoto, Masataka Taguri, Satoshi Morita
Journal: Journal of Clinical Oncology (2014)

e20618 Background: Pancreatic cancer is often associated with cachexia with loss of body weight. Eicosapentaenoic acid (EPA) has been reported to reduce proinflammatory cytokines, leading to alleviation of cachexia. We previously reported results from the randomized phase II study on gemcitabine with an EPA-enriched oral supplement at the 2013 ASCO meeting wherein delayed effect was observed (1-year survival probability: 35%, 19%). In this study, we performed subgroup analyses of the delayed effect considering albumin and CRP. Methods: This phase II study consisted of 67 patients who were randomly categorized into Arm A [administration of 1000 mg/m2 gemcitabine on days 1, 8, and 15, every 4 weeks, as well as daily EPA-enriched oral supplement (prosure, EPA 1.056 mg per pack) at the maximum of 2 packs] or Arm B (gemcitabine monotherapy) at a 2:1 ratio. During the course of disease progression, we examined the changes of CRP and albumin, and the results of 2nd-line treatment in the patients as subgroup analyses. Results: From May 2010 to Oct. 2011, randomized 67 patients were examined (Arm A: 44, B: 23). The 1-year survival probability of Arm A was 35% while Arm B was 19%. The median (IQR) CRP elevation was 1.33mg/dl (0.28, 2.52) in Arm A and 1.30mg/dl (0.15, 5.25) in Arm B (p=0.54). The median (IQR) albumin decrease was -0.30mg/dl (-0.60, 0) in Arm A and -0.40mg/dl (-0.60, -0.20) in Arm B. The median value of albumin at the time of disease progression was 3.7 mg/dl in Arm A and 3.5 mg/dl in Arm B. The median value of CRP at the time of disease progression was 0.73 mg/dl in Arm A and 1.00 mg/dl in Arm B. The patients with high albumin (>4.0 mg/dl) and low CRP (<1.0 mg/dl) at the time of disease progression were 12 in Arm A and 2 in Arm B (p=0.07). Although median PFS of 2nd-line treatment (mainly S-1) was not statistically significant (56 days in Arm A and 42 days in Arm B), some patients demonstrated delayed effect in Arm A. Conclusions: An EPA-enriched oral supplement may inhibit cachexia and induce delayed effect on survival. Clinical trial information: UMIN000003658.
COMPARISON OF CLINICAL CHARACTERISTICS AND LONG-TERM OUTCOMES IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY WITH DIFFERENT OBSTRUCTION LOCATIONS
Authors: Xiying Guo, Chaomei Fan, Yinjian Yang, Shuoyan An, Shanshan Zhai, Fujian Duan, Fei Hang, Yishi Li
Journal: Journal of the American College of Cardiology (2017)
PSYCHOSOCIAL FACTORS AND STATIN INTOLERANCE: DATA FROM THE REASONS FOR GEOGRAPHIC AND RACIAL DIFFERENCES IN STROKE (REGARDS) STUDY
Authors: Matthew Mefford, Robert Rosenson, Vera Bittner, Monika Safford, Rikki Tanner, April Carson, Ben Taylor, Keri Monda, Paul Muntner
Journal: Journal of the American College of Cardiology (2017)
AMERICAN HEART ASSOCIATION PREPARTICIPATION CARDIOVASCULAR SCREENING OF COMPETITIVE ATHLETES HISTORY ELEMENTS APPLIED TO A DIVERSE INTERNATIONAL SCREENING PROGRAM
Authors: Michael Scott Emery, Kyle Hornsby, Rachel Lahr, Zachary A. Boltwood, Dawn Kirchner, Changyu Shen, Jae Yeong Cho, Kye Hun Kim, Hyukjin Park, Lawrence Rink
Journal: Journal of the American College of Cardiology (2017)
Expression of CK-19, galectin-3, and HBME-1 in the differentiation of thyroid lesions: Systematic review and DIAGNOSTIC meta-analysis.
Authors: Leandro Luongo Matos, Adriana Braz Del Giglio, Carolina MATSUBAYASHI Ogawa, Michelle de lima Farah, Maria Aparecida Silva Pinhal, Auro Del Giglio
Journal: Journal of Clinical Oncology (2012)

e21151 Background: The distinction between malignant and benign lesions of the thyroid gland often requires histological demonstration, once the fine-needle aspiration biopsy method applied pre-operatively has some limitations. In an attempt to improve diagnostic accuracy, markers have been studied by immunocyto- and immunohistochemistry techniques, mainly cytokeratin-19 (CK-19), galectin-3 (Gal-3) and Hector Battifora mesothelial-1 (HBME-1). However, current results remain controversial. The aim of the present article was to establish the diagnostic accuracy of CK-19, Gal-3 and HBME-1 markers, as well as their associations, in the differentiation of malignant and benign thyroid lesions. Methods: A systematic review of MEDLINE’s published articles was performed. After establishing the inclusion and exclusion criteria, 65 articles were selected. The technique of meta-analysis of diagnostic accuracy was employed, and global values of sensitivity, specificity, area under the ROC curve (AUC), and diagnostic odds ratio (dOR) were calculated. Results: The positivity ofCK-19 for the diagnosis of malignant thyroid lesions demonstrated sensitivity of 81% (IC95%: 79-83%), specificity of 73% (IC95%: 70-75%), AUC of 87,5% and dOR of 14,7 (IC95%: 8,2-26,4); for Gal-3, sensitivity of 82% (IC95%: 81-84%), specificity of 81% (IC95%: 79-82%), AUC of 90% and dOR of 23,4 (IC95%: 14,0-39,1); and for HBME-1, sensitivity of 77% (IC95%: 76-79%), specificity of 83% (IC95%: 82-85%), AUC of 92,8% and dOR of 41,0 (IC95%: 21,4-78,4). The association of the three markers determined sensitivity of 85% (IC95%: 78-90%), specificity of 97% (IC95%: 90-99%), AUC of 93,3% and dOR of 95,1 (IC95%: 25,2-359,1). Conclusions: The search for new molecular markers must continue in order to enhance the diagnostic accuracy of the differentiation between malignant and benign lesions of the thyroid gland, since the results found still show persistency of false-negative and false-positive tests.
Establishment of a Novel DLBCL Cell Line: AMU-ML2, Derived from a Primary Refractory Patient Shows Homogeneous Staining Region of 8q24 Inducing High Expression of Long Non-Coding RNAs Encoded By PVT1 and Resistance to Vincristine
Authors: Shohei Mizuno, Ichiro Hanamura, Akinobu Ota, Sivasundaram Karnan, Kaori Uchino, Tomohiro Horio, Motonori Mizutani, Mineaki Goto, Miyuki Takahashi, Mayuko Gotou, Yamamoto Hidesuke, Masaya Watarai, Masato Shikami, Yoshitaka Hosokawa, Hiroshi Miwa, Ryuzo Ueda, Masakazu Nitta, Akiyoshi Takami
Journal: Blood (2016)
Hepatic IFIT3 predicts interferon‐α therapeutic response in patients of hepatocellular carcinoma
Authors: Yingyun Yang, Ye Zhou, Jin Hou, Chunmei Bai, Zhenyang Li, Jia Fan, Irene O.L. Ng, Weiping Zhou, Huichuan Sun, Qiongzhu Dong, Joyce M.F. Lee, Chung‐Mau Lo, Kwan Man, Yun Yang, Nan Li, Guoshan Ding, Yizhi Yu, Xuetao Cao
Journal: Hepatology (2017)

Adjuvant interferon-α (IFN-α) therapy is used to control certain types of cancer in clinics. For hepatocellular carcinoma (HCC), IFN-α therapy is effective in only a subgroup of patients; therefore, identifying biomarkers to predict the response to IFN-α therapy is of high significance and clinical utility. As the induced IFN-stimulated gene expression following IFN-α treatment plays pivotal roles in IFN-α effects, we screened IFN-stimulated gene expression in HCC tissues and found that several IFN-stimulated genes were significantly decreased in HCC. Interestingly, expression of IFN-induced protein with tetratricopeptide repeats (IFIT) family members, including IFIT1, IFIT2, IFIT3, and IFIT5, was decreased in HCC tissues. We further analyzed the expression of IFIT family members in HCC and their roles in patients' responses to IFN-α therapy in two independent randomized controlled IFN-α therapy clinical trials of HCC patients. We found that higher expression of IFIT3, but not other IFITs, in HCC tissues predicts better response to IFN-α therapy, suggesting that IFIT3 may be a useful predictor of the response to IFN-α therapy in HCC patients. Mechanistically, IFIT3 enhanced the antitumor effects of IFN-α by promoting IFN-α effector responses both in vitro and in vivo. IFIT3 could bind signal transducer and activator of transcription 1 (STAT1) and STAT2 to enhance STAT1-STAT2 heterodimerization and nuclear translocation upon IFN-α treatment, thus promoting IFN-α effector signaling.Higher IFIT3 expression in HCC tissues predicts better response to IFN-α therapy in HCC patients; IFIT3 promotes IFN-α effector responses and therapeutic effects by strengthening IFN-α effector signaling in HCC. (Hepatology 2017;66:152-166).
CONTEMPORARY USE OF LASER DURING PERCUTANEOUS CORONARY INTERVENTION: RESULTS FROM THE LASER VETERANS AFFAIRS (LAVA) MULTICENTER REGISTRY
Authors: Judit Karacsonyi, Ehrin Armstrong, Huu Tam Truong, Jose Martinez Parachini, Aya Alame, Barbara Danek, Aris Karatasakis, Phuong-Khanh Nguyen-Trong, Rahel Iwnetu, Erica Resendes, Pratik Kalsaria, Michele Roesle, Houman Khalili, Ryan Tsuda, Damianos Kokkinidis, Imre Ungi, Subhash Banerjee, Emmanouil Brilakis, Bavana Rangan
Journal: Journal of the American College of Cardiology (2017)
A multi-centre phase II trial of pegylated liposomal doxorubicin and trastuzumab in HER-2 over-expressing metastatic breast cancer (MBC)
Authors: S. K. Chia, M. Clemons, L. A. Martin, A. Rodgers, K. Gelmon, L. Panasci
Journal: Journal of Clinical Oncology (2004)

630 Background: Although combination therapy with conventional doxorubicin and trastuzumab (H) improves clinical outcome in HER-2 + MBC, a 27% cardiac dysfunction rate prevents clinical use of this combination. In a large phase III trial in MBC, pegylated liposomal doxorubicin (PLD:Caelyx®) was equally efficacious as conventional doxorubicin, but with significantly less cardiotoxicity. As well, the combination of PLD and H are synergistic in multiple breast cancer cell lines. With this rationale we performed a phase II trial of the combination of PLD and H as 1st line therapy in HER-2 + MBC, with cardiac safety as the primary end-point. Methods: Patients with measurable HER-2 + (IHC3+ or FISH positive) MBC were treated with PLD at 50 mg/m2 every 4 weeks and H at a 4 mg/kg loading then 2 mg/kg weekly. Left ventricular ejection fraction (LVEF) was assessed by MUGA at baseline and after every 2nd cycle. Prior adjuvant anthracycline exposure was allowed. Cardiac toxicity was defined as either a LVEF decline ≥ 15% regardless of absolute value; decline ≤ 10% with absolute LVEF < 45%; or symptomatic congestive heart failure (CHF). Results: 30 patients were enrolled from Aug 01 –Sept 03 from 4 Canadian centres. The median age was 59 years (31–75 years). 83% of the patients had visceral metastases, 64% had ER+ tumours and 41% had received prior adjuvant anthracyclines. A median of 5 cycles of PLD has been delivered so far (range 1–9). The mean LVEF at baseline, following cycles 2 and 4 were 63%, 59% and 60% respectively. A total of 3 patients experienced protocol-defined cardiotoxicity. No patient experienced symptomatic CHF. 27% of patients experienced grade 3 palmar-plantar erythrodysesthesia. The response rate (RR) for the evaluable cohort (n=29) was 55%. Within the 17 patients with no prior anthracycline exposure the RR was 65%. Median TTP and OS have not yet been reached. Conclusions: The combination of PLD and H is an active combination as 1st line therapy in HER-2 over-expressing MBC, with limited cardiotoxicity. This promising combination warrants further evaluation in the treatment of HER-2 over-expressing breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering Canada Schering Canada Schering Canada Hoffmann LaRoche; Schering-Plough
BETA-CRYPTOXANTHIN EXERTS BETTER CARDIOPROTECTION AGAINST CARDIAC ISCHEMIA-REPERFUSION INJURY THAN ASTAXANTHIN VIA PROTECTING MITOCHONDRIAL DYSFUNCTION IN MICE
Authors: Wanpitak Pongkan, Liang Xu, Osamu Takatori, Naoto Nagata, Yinhua Ni, Mai Nakayama, Siriporn Chattipakorn, Soichiro Usui, Tsuguhito Ota, Nipon Chattipakorn
Journal: Journal of the American College of Cardiology (2017)
CHARACTERISTICS, RISK FACTORS &amp; OUTCOMES OF EXTRACORPOREAL MEMBRANE OXYGENATION USE IN THE PEDIATRIC CARDIAC INTENSIVE CARE UNIT
Authors: Marissa Brunetti, Lauren B. Retzloff, Jessica L. Lehrich, J. William Gaynor, Sara Pasquali, David Bailly, Susan Davis, Darren Klugman, Joshua Koch, Javier Lasa, Michael Gaies
Journal: Journal of the American College of Cardiology (2017)
A WEANING MARKER FROM VENO-ARTERIAL EXTRA CORPOREAL MEMBRANE OXYGENATION USING A NOVEL MICROCIRCULATORY IMAGING
Authors: Sakir Akin, Dinis dos Reis Miranda, Kadir Caliskan, Osama Soliman, Atila Kara, Ard Struijs, Robert J. van Thiel, L.S.D. Jewbali, Alex Lima, Diederik Gommers, Felix Zijlstra, Can Ince
Journal: Journal of the American College of Cardiology (2017)
Targeting Autophagy in Myelodysplastic Syndromes
Authors: Valeria Visconte, Steffan T. Nawrocki, Bartlomiej P Przychodzen, Kevin R. Kelly, Mei Yin, Yvonne Parker, Michael J. Clemente, John Barnard, Anjali S. Advani, Hetty E. Carraway, Mikkael A. Sekeres, Daniel Lindner, Heesun J Rogers, Jaroslaw P Maciejewski, Jennifer S. Carew
Journal: Blood (2016)
The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma
Authors: Jacob D. Soumerai, Andrew D. Zelenetz, Craig H. Moskowitz, M. Lia Palomba, Paul A. Hamlin, Ariela Noy, David J. Straus, Alison J. Moskowitz, Anas Younes, Matthew J. Matasar, Steven M. Horwitz, Carol S. Portlock, Jason A. Konner, Mrinal M. Gounder, David M. Hyman, Martin H. Voss, Matthew G. Fury, Devika Gajria, Richard D. Carvajal, Alan L. Ho, Jan H. Beumer, Brian Kiesel, Zhigang Zhang, Alice Chen, Richard F. Little, Christine Jarjies, Thu O. Dang, Fallon France, Nishant Mishra, John F. Gerecitano
Journal: Clinical Cancer Research (2017)

Abstract Purpose: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase I study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas. Experimental Design: This dose-escalation study evaluated safety, pharmacokinetics, and preliminary efficacy of veliparib (20–400 mg twice a day, days 1–7 of 28-day cycle) and bendamustine (70 and 90 mg/m2 intravenously, days 1 and 2). A cohort expansion was conducted, which combined veliparib and bendamustine at the maximum tolerated dose (MTD) with rituximab (375 mg/m2, day 1) in patients with B-cell lymphomas. Thirty-four patients were treated in seven dose-escalation cohorts and seven patients in the dose-expansion cohort. Results: The MTD was veliparib 300 mg twice daily plus bendamustine 90 mg/m2. Dose-limiting toxicities (DLT) were anemia, nausea, hypertension, and hyperhidrosis. Grade ≥3 toxicities included lymphopenia (87.8%), anemia (19.5%), neutropenia (12.2%), thrombocytopenia (9.8%), leukopenia (9.8%), nausea (7.3%), and hypophosphatemia (7.3%). Apparent veliparib clearance was slightly lower than previously reported. Of 14 patients with lymphoma evaluable for response, five of seven (71%) on VB and six of seven (86%) on VBR achieved objective response. One patient with multiple myeloma achieved partial response. Conclusions: VB and VBR were generally well-tolerated. VBR had preliminary clinical activity in patients with B-cell lymphoma, which warrants further investigation in a phase II trial. This trial was registered at www.clinicaltrials.gov as NCT01326702. Clin Cancer Res; 23(15); 4119–26. ©2017 AACR.
Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study
Authors: Ming Ding, Tao Huang, Helle KM Bergholdt, Børge G Nordestgaard, Christina Ellervik, Lu Qi
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. <b>Design</b>&nbsp;Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. <b>Setting</b>&nbsp;CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. <b>Participants</b>&nbsp;Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. <b>Main outcome measures</b>&nbsp;The instrumental variable estimation was conducted using the ratio of coefficients approach. Using meta-analysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. <b>Results</b>&nbsp;Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of <i>LCT-13910</i> (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P&lt;0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval −0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using <i>LCT-13910</i> rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (β=1.35, 95% confidence interval −0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: β=−0.21, 95% confidence interval −0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with −0.11 (95% confidence interval −0.20 to −0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). <b>Conclusion</b>&nbsp;The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.