tbuckley/cabot-search huggingface dataset:
Is standard dose appropriate in elderly non-small cell lung carcinoma (NSCLC) patients treated with erlotinib?
Authors: Frederic Bigot, Jennifer Arrondeau, Pascaline Boudou-Rouquette, Jeanne Chapron, Audrey Thomas-Shoemann, Anatole Cessot, Olivier Huillard, Camille Tlemsani, Audrey Le Bel, Michel Vidal, Jerome Alexandre, Anne Chahwakilian, Daniel Dusser, Benoit Blanchet, Francois Goldwasser
Journal: Journal of Clinical Oncology (2015)

9537 Background: Given the median age of 70 years in patients (pts) presenting NSCLC, the impact of age on outcomes including efficacy and toxicity of erlotinib remains unclear. In the BR21 study, analysis of subgroup based on age have reported similar survival benefits of erlotinib compared with placebo; however, elderly pts (³ 70 years) had significantly more toxicity, and were more likely to discontinue treatment (Paul Wheatley-Price et al., J Clin Oncol 2008). Thus we hypothesized that elderly were more exposed than younger pts. Methods: All consecutive pts with advanced or metastatic NSCLC treated with erlotinib between 2010 and 2014 were eligible in this prospective cohort. Erlotinib concentrations in plasma were determined using high-performance liquid chromatography at Day 15 after treatment initiation. We compared dose-normalized concentrations between pts < or ³ 75 years old using the Mann-Whitney U test and the occurrence of acute grade ³ 2 adverse events (AE) or treatment modifications by Fisher’s test. AE reports were graded using the National Cancer Institute Common Terminology Criteria V4. Lean body mass was estimated using Janmahasatian’s equation. Results: Out of 55 pts, erlotinib plasma concentration was analyzed in 45 pts. Median age was 65.6 (range 25-83), and 14 pts were over 75 years old. Among these 45 pts, 58% were female, 93% had an adenocarcinoma subtype; 44% were never smoker. Eighty-six percent of the pts had a performans status at baseline ≤ 2. Elderly pts had significantly lower estimated lean body mass (36.6 kg vs 47.7 kg; p = 0.00038). Within 2 weeks, grade ³ 2 AE occurred in 20% of pts, and 28 % in elderly. In the subgroup of pts over 75 years old, there was a trend for higher dose-normalized concentration at day 15 (1923.3 mg/L vs 1380.9 mg/L; p = 0.07), and the difference was significant in pts older than 80 (7 pts; 2484.6 mg/L vs 1377.4 mg/L; p = 0.0074). Four pts > 75 years old had dose reduction or discontinuation versus 0 in younger pts (p = 0.014, CI95% [1.2532; infinite]). Conclusions: Elderly patients are susceptible to be overexposed to erlotinib at 150mg/day, resulting in increased acute toxicity and treatment discontinuation.
Inhibition of Ataxia-Telangiectasia Mutated and RAD3-Related (<i>ATR</i>) Overcomes Oxaliplatin Resistance and Promotes Antitumor Immunity in Colorectal Cancer
Authors: Eve Combès, Augusto F. Andrade, Diego Tosi, Henri-Alexandre Michaud, Flavie Coquel, Veronique Garambois, Delphine Desigaud, Marta Jarlier, Arnaud Coquelle, Philippe Pasero, Nathalie Bonnefoy, Jerome Moreaux, Pierre Martineau, Maguy Del Rio, Roderick L. Beijersbergen, Nadia Vezzio-Vie, Celine Gongora
Journal: Cancer Research (2019)

Although many patients with colorectal cancer initially respond to the chemotherapeutic agent oxaliplatin, acquired resistance to this treatment remains a major challenge to the long-term management of this disease. To identify molecular targets of oxaliplatin resistance in colorectal cancer, we performed an shRNA-based loss-of-function genetic screen using a kinome library. We found that silencing of ataxia-telangiectasia mutated and RAD3-related (ATR), a serine/threonine protein kinase involved in the response to DNA stress, restored oxaliplatin sensitivity in a cellular model of oxaliplatin resistance. Combined application of the ATR inhibitor VE-822 and oxaliplatin resulted in strong synergistic effects in six different colorectal cancer cell lines and their oxaliplatin-resistant subclones, promoted DNA single- and double-strand break formation, growth arrest, and apoptosis. This treatment also increased replicative stress, cytoplasmic DNA, and signals related to immunogenic cell death such as calreticulin exposure and HMGB1 and ATP release. In a syngeneic colorectal cancer mouse model, combined administration of VE-822 and oxaliplatin significantly increased survival by promoting antitumor T-cell responses. Finally, a DNA repair gene signature discriminated sensitive from drug-resistant patients with colorectal cancer. Overall, our results highlight the potential of ATR inhibition combined with oxaliplatin to sensitize cells to chemotherapy as a therapeutic option for patients with colorectal cancer. SIGNIFICANCE: These findings demonstrate that resistance to oxaliplatin in colorectal cancer cells can be overcome with inhibitors of ATR and that combined treatment with both agents exerts synergistic antitumor effects.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/11/2933/F1.large.jpg.
Engineering stem cell cardiac patch with microvascular features representative of native myocardium
Authors: Zichen Qian, Dhavan Sharma, Wenkai Jia, Daniel Radke, Timothy Kamp, Feng Zhao
Journal: Theranostics (2019)

The natural myocardium is a highly aligned tissue with an oriented vasculature. Its characteristic cellular as well as nanoscale extracellular matrix (ECM) organization along with an oriented vascular network ensures appropriate blood supply and functional performance. Although significant efforts have been made to develop anisotropic cardiac structure, currently neither an ideal biomaterial nor an effective vascularization strategy to engineer oriented and high-density capillary-like microvessels has been achieved for clinical cardiovascular therapies. A naturally derived oriented ECM nanofibrous scaffold mimics the physiological structure and components of tissue ECM and guides neovascular network formation. The objective of this study was to create an oriented and dense microvessel network with physiological myocardial microvascular features.
TCTAP C-214 Where Anatomy Meets Physiology - Quantitative Flow Ratio (QFR) and Three-Dimensional Quantitative Coronary Analysis (3D QCA) Guided Percutaneous Coronary Intervention
Authors: Jin Hyun Lee, Paul J.L. Ong, Jia Min Chua, Ting Hsuan Chuang
Journal: Journal of the American College of Cardiology (2019)
严重皮肤不良反应(SCAR)的可预防性
Authors: G. Chaby, L. Valeyrie‐Allanore, T.A. Duong, B. Lebrun‐Vignes, B. Milpied, B. Sassolas, F. Tetart, P. Wolkenstein, O. Chosidow, L. Fardet
Journal: British Journal of Dermatology (2018)
CTCs as early biomarkers of primary liver cancer in the patients with liver diseases.
Authors: Alexandre Tavartkiladze
Journal: Journal of Clinical Oncology (2015)

e22018 Background: The circulating tumor cells are the metastatic seeds that can break away from the primary site of cancer, and spread to other parts of the body. Understanding circulating tumor cells is critically important, since it is the spread of cancer to other parts of the body—and not the primary cancer - that is often responsible for the death of a person with cancer. The aim of our study was to to establish the existence of a tumor disease (Primary Liver Cancer) In the Patients with liver Diseases. Methods: A total of 28 patients (aged from 37 to 64 years) with Hepatitis C and B and with Liver Fibrosis - F4 by metavir score. All the patients had in normal range AFP and fibrous formation in the liver tissue by ultrasound and CT research but not histological identification. Control group was represented by 18 patients (aged from 34 to 69 years) with Hepatitis C and B and Liver Fibrosis - F1 by metavir score without fibrous formation in the liver. Plasma levels of CTCs were estimated by OncoQuick Test system and Plasma Levels of AFP were estimated by ECLIA method. Results: Our results showed that the patients which had CTCs in Plasma them next 3-6 month revealed Primary Liver Cancer with Gradually increasing of AFP in the plasma than in control group (p < 0,001). In the control Group next 3-6 month the patients which had CTCs in the blood them not had increased AFP in the blood but next 2 years each revealed Primary Liver Cancer with Increased AFP but after 1 to 1.2 year were identified CTCs in the blood (p < 0.01), and the Patient without identified CTCs in the blood not will be developed liver cancer during 3 years (the monitoring of this patients is on going). Conclusions: CTCs in the blood in patients with viral hepatitis is very early biomarkers (cytomarker) to the early detection Primary Liver Cancer and this method is promising method as Diagnostic and also prognostic test in the Early Detection the liver cancer and for the Differentiation a Fibrous Formation in the Liver tissue and Tumor Damage.
Abstract 19908: What Makes Left Atrial Enlargement in Patients With Sinus Rhythm and Atrial Fibrillation
Authors: Aika Daimon, Akiko Goda, Miho Fukui, Kumiko Masai, Yuko Soyama, Masanori Asakura, Tohru Masuyama
Journal: Circulation (2017)

Background: The left atrium plays an important role to maintain cardiac function. The left atrial (LA) enlargement is one of the predictors of adverse outcome in patients with heart failure. LA siz...
Does NICE support NHS England’s plan to restrict interventions?
Authors: John W L Puntis
Journal: BMJ (2019)

The National Institute for Health and Care Excellence’s commitment to shared decision making is welcome, but not reflected in its endorsement of advice from NHS England to commissioners on “17 evidence based interventions.”12 NHS England argued that variation in numbers of interventions between clinical commissioning groups was because doctors were not following established clinical guidelines (p 5).1 Despite this, having set out …
Author Correction: Transposable elements drive widespread expression of oncogenes in human cancers
Authors: Hyo Sik Jang, Nakul M. Shah, Alan Y. Du, Zea Z. Dailey, Erica C. Pehrsson, Paula M. Godoy, David Zhang, Daofeng Li, Xiaoyun Xing, Sungsu Kim, David O’Donnell, Jeffrey I. Gordon, Ting Wang
Journal: Nature Genetics (2019)
Erratum: Beneficial hemodynamic, endocrine, and renal effects of urocortin in experimental heart failure: Comparison with normal sheep (Journal of the American College of Cardiology (2002) 40 (1495-1505))
Authors: M. T. Rademaker, C. J. Charles, E. A. Espiner, S. Fisher, C. M. Frampton, C. M.J. Kirkpatrick, J. G. Lainchbury, M. G. Nicholls, A. M. Richards, W. W. Vale
Journal: Journal of the American College of Cardiology (2003)
GS-01-Efficacy, safety, and tolerability of lubiprostone for the treatment of non-alcoholic fatty liver disease: The LUBIPRONE, doubleblind, randomized, placebo-controlled, phase II study
Authors: Takaomi Kessoku, Kento Imajo, Yuji Ogawa, Takashi Kobayashi, Yasushi Honda, Takayuki Kato, Wataru Tomeno, shingo Kato, Takuma Higurashi, Masato Yoneda, Hiroyuki Kirikoshi, Kazumi Kubota, Masataka Taguri, Takeharu Yamanaka, Haruki Usuda, Koichiro Wada, Satoru Saito, Atsushi Nakajima
Journal: Journal of Hepatology (2019)
Abstract 12667: Heart Rate is associated with Increased Risk of Major Cardiovascular Events, Cardiovascular and All-Cause Death in Patients with Stable Chronic Cardiovascular Disease - An Analysis of ONTARGET/ TRANSCEND
Authors: Sherryn Rambihar, Peggy Gao, Koon Teo, Michael Bohm, Salim Yusuf, Eva Lonn, Transcend Investigators
Journal: Circulation (2010)

Heart rate was proposed as an emergent cardiovascular (CV) risk factor. In a post-hoc analysis of the ONTARGET/TRANSCEND trials, we evaluated associations between baseline and average heart rate (d...
THU-241-Influence of HBV genotype on the risk of hepatocellular carcinoma: mediating roles of different phase of viral infection and epigenetic modifications
Authors: Wan-Jung Wu, Yi-Chun Kuo, Wei-Yi Kao, Shu-Han Yang, Chih-Feng Wu, Chih-Lin Lin, Chun-Jen Liu, Yi-Wen Huang, Ming-Whei Yu
Journal: Journal of Hepatology (2019)
LBO-04-Efficacy and safety of sofosbuvir monotherapy in patients with chronic hepatitis E-The HepNet SofE pilot study
Authors: Markus Cornberg, Sven Pischke, Tobias Müller, Patrick BEHRENDT, Felix Piecha, Julia Benckert, Andrea Smith, Armin Koch, Ansgar Lohse, Svenja Hardtke, Michael P. Manns, Heiner Wedemeyer
Journal: Journal of Hepatology (2019)
FRI-460-What are the predictive factors for long-term survivors with advanced hepatocellular carcinoma treated with sorafenib?
Authors: Daniela Reis, Filipe de Sousa Damião, Carolina Simões, Sofia Carvalhana, Afonso Gonçalves, Rui Tato Marinho, Helena Cortez-Pinto
Journal: Journal of Hepatology (2019)
Validation of ERCC1 (E1) for response prediction to platinum-gemcitabine.
Authors: Gerold Bepler, Wei Chen, Stephan Patrick, Stephanie H. Astrow, Craig Stephens, David R. Gandara, Rafael Rosell, Jose Luis Ramirez, Giorgio V. Scagliotti, Simone Busso, Marco Volante, Silvia Novello
Journal: Journal of Clinical Oncology (2015)

8036 Background: E1 had been suggested as a predictive marker for platinum drugs. However, it has 4 different isoforms with differential DNA repair functions, antibodies used for quantitation lack specificity, and a phase 3 trial designed to validate E1’s predictive power failed to demonstrate the anticipated benefit (trial A). We investigated the interaction of E1 mRNA levels with therapeutic benefit from various therapeutic doublets in pts with advanced NSCLC. Methods: FFPE specimens from trial A were microdissected; RNA was extracted, and analyzed for E1 levels using commercially validated primers and probes. Median and optimized cut-offs were investigated for interaction of E1 levels with survival and validated using a second randomized phase 3 trial (trial B, Ann Oncol 25: 2147–55, 2014). Results: E1 expression analysis on 84 pts in trial A, 38 treated with PG and 46 with other doublets, showed a significant (p = 0.044), inverse association between E1 mRNA levels and disease response in pts treated with PG; i.e., the higher the E1 levels the worse the tumor response. An analysis for treatment interaction (PG vs others) using the optimized E1 cut-off level of 1.44 showed E1 was highly predictive of OS and PFS in pts on PG, with high levels predicting short survival (Cox model interaction p = 0.002 for OS and 0.003 for PFS). Using the median E1 level of 1.73, the interaction p-value was 0.028. E1 levels were not associated with histology, sex, age, and smoking status. Specimens from 86 pts in trial B yielded sufficient RNA for a successful E1 analysis. 19 pts had been treated with PG, 55 with P-docetaxel, and 12 with docetaxel. E1 values were similar to those in trial A. Using the optimized E1 cut-off level of 1.44 from trial A, we found a log-rank p-value of 0.029 for PFS, with high levels predicting short survival for pts treated with PG. A 2ndvalidation on pts treated with PG in Torino, Italy is in progress. We also attempted to develop an RTPCR assay specific for the E1-202 isoform. Despite optimized primer/probe designs and validation using in vitro samples, the majority of FFPE samples failed analysis. Conclusions: E1 mRNA levels, as determined by a commercially available and CLIA/CAP certified assay, are predictive of treatment benefit from PG in advanced NSCLC.
One-Year Mortality After Dialysis Initiation Among Older Adults
Authors: Melissa W. Wachterman, Ann M. O’Hare, Omari-Khalid Rahman, Karl A. Lorenz, Edward R. Marcantonio, Gabrielle K. Alicante, Amy S. Kelley
Journal: JAMA Internal Medicine (2019)

This cohort study examines the incidence of mortality 1 year after the start of hemodialysis in patients 65 years and older.
Superparamagnetic iron oxide nanoparticles of curcumin enhance gemcitabine therapeutic response in pancreatic cancer
Authors: Sheema Khan, Saini Setua, Sonam Kumari, Nirnoy Dan, Andrew Massey, Bilal Bin Hafeez, Murali M. Yallapu, Zachary Edwar Stiles, Anas Alabkaa, Junming Yue, Aditya Ganju, Stephen Behrman, Meena Jaggi, Subhash C. Chauhan
Journal: Biomaterials (2019)
THU-142-Sofosbuvir + velpatasvir + voxilaprevir in DAA failure patients with cirrhosis: Final results of the French compassionate use program
Authors: Christophe Hezode, Dominique Guyader, Eric Nguyen-Khac, Dominique Larrey, Régine Truchi, Vincent Di Martino, Yvon Calmus, Anne Minello Franza, Nathalie Giuily, Saadi Mokhtari, Kerstin Hartig, Laurent Cotte, Didier Ribard, Marc-Antoine Valantin, Luminita Bonyhay, Michel Antoni, Jean-Pierre Bronowicki, Jean-Marc Combis, Christophe Pilette, Christophe Zamora, Erard Domitille, Jean-Pierre Arpurt, Christophe Renou, Marc Bourliere, Véronique Grando, Valérie Canva
Journal: Journal of Hepatology (2019)
Immunologic profile of melanoma brain metastases (MBM) in patients (pts) with prolonged survival.
Authors: Kevin P. Lui, Inês E. D. Pires Silva, Sarah Ann Weiss, Sung Won Han, Farbod Darvishian, Anna C. Pavlick, John Golfinos, Duane Moogk, Michelle Krogsgaard, Iman Osman
Journal: Journal of Clinical Oncology (2015)

9070 Background: Median survival of MBM pts is significantly shorter than pts with extra-cranial metastases. However, a subset of MBM pts exhibit extended survival. Radiation therapy (RT - radiosurgery and whole-brain radiation) is used to treat MBM pts and recent data by several groups including ours demonstrate that RT may potentiate response to immunotherapies by inducing an immunological tumor cell death. In this study, we investigate the immunomodulator effect of RT on MBM tissue and attempt to identify an immunological profile associated with improved post-MBM survival. Methods: Expression of 560 immunoregulatory genes was assessed in 32 MBM tissues (10 post radiation and 22 no radiation) using a customized NCounter GX Human Immunology Kit (Nanostring) comprising of 24 immunology-related gene networks compiled from the Gene Ontology Consortium List of immunologically important genes. We also compared expression of the immunoregulatory genes in long term survivors ( > 1 year) compared to short term survivors ( < 1 year). We then verified the data using RT-PCR and IHC in an expanded cohort of 47 MBM tissues. Results: Irradiated MBM had higher expression of genes involved in: (1) autophagy/apoptosis (ATG12, BCL2L11 and CASP8); (2) adhesion (CD209, ICAM2; ITGA4 , ITGB1 and PECAM-1); (3) immune cell development and activation (IFNAR2, IKZF2, MAP4K2, NFATC3, POU2F2 and TCF4) (p < 0.05). In addition, RT induced upregulation of PD-L1 (transmembrane protein involved in immunoinhibitory signals) and TGF-b (immunosuppressive cytokine and cell cycle regulator) at the gene expression level, as determined by Nanostring and confirmed by RT-PCR, and protein level of PD-L1 by IHC. Genes involved in lymphocyte activation such as CD44, CD81 and IL16 were significantly overexpressed in long term survivors (p < 0.05). Conclusions: Our data demonstrate that RT induces both lymphocyte activation and upregulation of immunosuppressive signals. Our data also suggest that MBM pts with prolonged survival host an immunologically distinct subset of tumors with upregulated lymphocyte activating genes. Identification of MBM pts with enhanced immunogenicity may aid in prognostication and prediction of response to immunotherapy.
Impact of personality traits on predictors of adherence to endocrine therapy.
Authors: Xinni Song, Susan Faye Dent, Shailendra Verma, Mark J. Clemons, Nadine A. Graham, Marc Bedard, Lise Paquet
Journal: Journal of Clinical Oncology (2015)

e20614 Background: Personality traits such as the tendency to react anxiously when confronted with threatening situation (trait anxiety-TA), are known to impact symptom reporting and health outcomes. Non-adherence to endocrine therapy (ET) is a major challenge in the care of breast cancer (BC) patients. Patients who have a poor relationship with their physician, have doubts about the effectiveness of ET and their ability to manage potential ET toxicity (i.e., self-efficacy) are at risk for non-adherence. The aim of the study was to investigate the influence of demographics, clinical and personality traits on these important predictors of adherence to ET. Methods: Women (mean age 59 y) diagnosed with early stage BC completed a survey prior to initiating ET, and at 3, 6 and 12 months (N = 244/184/153/127). Standardized self-report instruments were used to assess TA, self-efficacy, trust in their oncologist, and beliefs that hormonal treatment will control their BC. Results: For each assessment, multiple regressions were conducted to identify factors associated with each outcome variable. Self-efficacy to manage potential ET toxicity was predicted by education (β = 0.14, p < 0.05) and by TA (β = -0.39, p < 0.001). Belief that hormonal treatment will control BC was predicted by education at 6 months only (β = 0.20, p < 0.01) and by TA for each assessment (baseline: β = - 0.34, 3 months: β = - 0.26, 6 months: β = - 0.36, 12 months: β = -0.28; p < 0.001). Trust in their oncologist was predicted by education at 3 months only (β = -0.22, p < 0.01), by receipt of chemotherapy at 3 (β = 0.17, p < 0.05) and 6 months (β = 0.24, p < 0.01) and by TA for each assessment except baseline (β = -0.12, p < 0.1; 3 months: β = -0.29, 6 months: β = -0.32, and 12 months: β = -0.29; p < 0.001). Conclusions: Baseline anxiety traits (TA) predicted outcomes to a larger extent than demographics and clinical factors. Before ET initiation, patients high in TA had more negative views about coping with ET side effects and, over a 12 months period, had lower trust in their oncologist, and thought more negatively about the effectiveness of ET than lower TA patients. The results emphasize the need to identify and offer interventions to high anxiety patients in order to improve their coping abilities and adherence to ET.
Liver-derived cell-free nucleic acids in plasma: Biology and applications in liquid biopsies
Authors: Peiyong Jiang, K.C. Allen Chan, Y.M. Dennis Lo
Journal: Journal of Hepatology (2019)

There is much global research interest surrounding the use of cell-free DNA (cfDNA) for liquid biopsies. cfDNA-based non-invasive prenatal testing for foetal chromosomal aneuploidies was the first successful application of cfDNA technology that transformed clinical practice – it has since been rapidly adopted in dozens of countries and is used by millions of pregnant women every year. Prompted by such developments, efforts to use cfDNA in other fields, especially for cancer detection and monitoring have been actively pursued in recent years. Cancer-associated aberrations including single nucleotide mutations, copy number aberrations, aberrations in methylation and alterations in DNA fragmentation patterns have been detected in the cfDNA of patients suffering from a wide variety of cancers. In addition, the analysis of methylation and fragmentomic patterns has enabled the tissue origin of cfDNA to be determined. In this review, different approaches for detecting circulating liver-derived nucleic acids and cancer-associated aberrations, as well as their potential clinical applications for the detection, monitoring and management of hepatocellular carcinoma, will be discussed.
SAT-298-MR elastography based fibrosis correlates with clinical liver events in patients with non-alcoholic fatty liver disease: A multi-center study
Authors: Ma Ai Thanda Han, Jonathan Grotts, Rola Saouaf, Nabil Noureddin, Walid Ayoub, Andrea Scott, Mary Barbara, Matthew Tjahja, Toluwalase Okubote, Dr. Zeid Kayali, Edward Mena, Naim Alkhouri, Mazen Noureddin
Journal: Journal of Hepatology (2019)