tbuckley/cabot-search huggingface dataset:
An open-label pilot study of vemurafenib in previously treated metastatic melanoma patients with brain metastases.
Authors: R. Dummer, J. Rinderknecht, S. M. Goldinger, I. Wagner, L. Mitchell, M. L. Veronese, S. Nick, P. Hilfiker, S. Gobbi
Journal: Journal of Clinical Oncology (2011)

8548 Background: Melanoma is a common cause of cerebral metastases, and indicates a poor prognosis. The BRAF inhibitor vemurafenib (V; RG7204, PLX4032) has shown dramatic activity in Phase I and II studies in metastatic melanoma harboring V600-mutated BRAF. These studies excluded patients with active brain metastasis. The activity of V for brain metastases is unknown. Methods: Open label, single arm trial of V to evaluate the safety and efficacy of V in patients with metastatic melanoma with BRAF V600 mutations (by the cobas 4800 BRAF V600 Mutation Test) and non-resectable-brain mets, pretreated by radiotherapy and/or chemotherapy. Patients may have symptoms related to their brain mets and be on a stable dose of steroids. V is administered continuously at the dose of 960 mg BID. Twenty patients are planned to be include in this study. Staging (MRI brain and CT thorax/abdomen) is scheduled every 4 weeks in the first 2 months and then every 8 weeks. In addition, the serum S100 levels are determined. Results: Four patients with V600 BRAF positive melanoma metastatic to the brain and pretreated with temozolamide and/or total brain radiotherapy V are on treatment between 2 and 10 weeks to date. All patients are young (between 24 and 48 years), have 3 to more than 10 brain mets, ECOG PS 0-2 and are on dexamethasone. Two patients were taking morphine to control pain and neurological symptoms. There was no dose reduction for V. AEs included rash, fatigue in two patients and disseminated Herpes zoster and mild transient paresis of nervus facialis in one patient. Two patients' staging reports are currently available. Patient 1 presented an confirmed partial response in brain and body (RECIST) associated with a reduction of S-100 from 141.6µg/l (pre-treatment) to 4.4µg/l (day 43). Dexamethasone and morphine doses were reduced. Patient 2 showed a minor response in brain and body at week 4 associated with a reduction of S-100 from 35.6µg/l (day 1) to 3.26µg/l (day 15). Conclusions: V has been well tolerated in symptomatic patients with melanoma metastatic to the brain to date. There are early but strong indications for activity in brain mets.
Translating systems biology into medical applications : Report of the 3rd Bertinoro Systems Biology Workshop
Authors: G Clermont, C Auffray, Yves Moreau, D Rocke, D Delavi, D Dubhashi, D Marshall, P Raasch, F Dehne, P Provero, J Tegner, M.A Langston, M Benson
Journal: Genome biology (2009)
P3-056: A novel strategy for the treatment of metastatic pulmonary tumors: Radiofrequency Ablation (RFA) in conjunction with surgery
Authors: Yoshifumi Sano, Susumu Kanazawa, Hidefumi Mimura, Hideo Gobara, Takao Hiraki, Masaomi Yamane, Shinichi Toyooka, Takahiro Oto, Motoi Aoe, Hiroshi Date
Journal: Journal of Thoracic Oncology (2007)
A phase I/II study of erlotinib in combination with chemoradiation in patients with surgically resected locally advanced squamous head and neck cancer (HNSCC).
Authors: F. Arias de la Vega, I. Herruzo, M. de las Heras, A. de la Torre, V. Arrazubi, J. Contreras, J. Garcia Saenz, J. Romero, J. Serrano, F. A. Calvo
Journal: Journal of Clinical Oncology (2010)

TPS266 Background: Standard postoperative treatment for high-risk locally advanced HNSCC is concurrent chemoradiation (CRT). Despite innovative strategies, prognosis of these patients remains poor. Up to 90% of HNSCC overexpresses the EGF receptor. Erlotinib (e) is an oral tyrosine-kinase inhibitor of EGFR, with activity in HNSCC. The Spanish Group of Clinical Research in Radiation Oncology (GICOR) sponsors a multicenter non randomized phase I/II study evaluating the addition of E to CRT therapy of patients (pts) with surgically resected locally advanced HNSCC. Methods: The study comprises an early dose-escalating phase I, consisting on 3 cohorts of 3-6 pts each, with increasing doses of E (100-150 mg po qd) and cisplatin (C) (30-40 mg/m2, iv, d 1) for 7 weeks (w). Radiation therapy (RT) is delivered as a standard regimen of daily 1.8 Gy (5 fractions/w) to a maximum total dose of 63 Gy along 7 w. Pts should have diagnosis of HNSCC, with at least one of these criteria: T3 or T4 primary lesion (except T3N0 with negative resection margins), pathologic N2-N3 disease, and poor prognostic findings. Other criteria: age 18-70 y; life expectancy ≥ 12 w; PS 0-1; no evidence of metastasis; adequate organic function and written informed consent. The aim of the phase I is to define the maximum tolerated dose (MTD), as the dose level at which 2 of 3 or 3 of 6 pts develop a dose-limiting toxicity (DLT). DLT, in turn, is defined as any grade (g) 3-4 hematological or nonhematological clinically severe toxicity, including g 3-4 diarrhea, g 4 mucositis resulting in more than 2 w interruption of RT; g 3-4 mucositis complicated with a decrease ECOG PS; g 3-4 skin rash; or any clinically relevant toxicity resulting in interruption of treatment for more than 2 w. Phase I has been already completed, being a regimen of C 30 mg/m2 + E 150 mg/day the recommended dose for the phase II (Arias et al. J Clin Oncol 26: 2008, abstr. 6068). The primary objective of the phase II is to evaluate the progression-free survival (PFS) of pts treated at the recommended dose; secondary objectives locoregional PFS and overall survival. Planned sample size is 70 pts, and 32 have been enrolled since the beginning of the phase II (mid-2008). No significant financial relationships to disclose.
PBI-4050 Decreases Hepatic Stellate Cell Activation and Ameliorates Fibrosis in Carbon Tetrachloride (CCL4)- Induced Hepatic Fibrosis Model
Authors: F. Sarra-Bournet, B. Grouix, K. Hince, A. Felton, M. Tremblay, S. Abbott, J.-S. Duceppe, B. Zacharie, P. Laurin, L. Gagnon
Journal: Journal of Hepatology (2016)
Preclinical characterization of GNS561 as a novel first in class autophagy inhibitor to kill hepatocellular carcinoma cancer stem cells.
Authors: Firas Bassissi, Sonia Brun, Elena Patricia Gifu, Jerome Courcambeck, Gregory Nicolas, Clarisse Dubray, Antoine Beret, Nolwenn Amrani, Claude Caron de Fromentel, Philippe Merle, Philippe Halfon
Journal: Journal of Clinical Oncology (2016)

e15600 Background: In spite of successful approval and wide application of sorafenib, the prognosis for patients with advanced hepatocellular carcinoma (HCC) remains poor. In recent years, highly tumorigenic sub-populations of cancer cells named Cancer Stem Cells (CSCs) have been implicated in post-treatment tumor recurrence. Indeed, CSCs are resistant to chemotherapy, and they have the ability to regenerate all the cell types within the tumor. For this reason, innovative drugs with original mechanism of action which tackle CSCs would likely improve cancer treatment of patients Methods: Antitumor activity of a new small-molecule GNS561 was tested on a panel of cancer cell lines. Its effect on HCC CSCs subpopulation was assessed by flow cytometry (ALDH activity, CD133 expression) and by sphere formation assay. Tolerance and plasma and liver pharmacokinetic were evaluated after single and repeated dosing in mice and rats. In vivoGNS561 activity was tested in orthotopic mouse models Results: GNS561 demonstrated autophagy inhibition and apoptosis induction activities related to lysosome disruption. It showed potent antitumor activity against a panel of human cancer cell lines. In HCC cell lines, GNS 561 was active on both whole populations (mean EC50 2µM) and subpopulations displaying CSC features (high ALDH and CD133 positivity). Further, GNS561 was effective against a panel of HCC tumors even from patients harboring sorafenib resistance. In mouse, GNS561 was found well tolerated and highly selectively trapped in the liver (exposure ratio liver/plasma about 170), and showed a significant tumor growth inhibition in orthotopic HCC mouse models Conclusions: Our results provide a rationale for testing autophagy flux disruption as a novel therapeutic strategy for HCC. GNS561 is a liver selective drug active against both the whole tumor bulk and CSCs, which offers great promise for HCC treatment
Liver Transplantation for Acute Hepatic Decompensation Achieves Excellent Outcomes without Increased Recidivism Rates: A Single Center Experience
Authors: H. Monsour, D. Victor, M. Boktour, J. Galati, J. Ontiveros, L. Theriot, R. McFadden, C. Mobley, A. Saharia, S. Gordon-Burroughs, M. Ghobrial
Journal: Journal of Hepatology (2016)
Transthoracic anastomotic leak after esophagectomy: Still a catastrophe?
Authors: Martin McCarter, Carrie Ryan, Robert Meguid, Alessandro Paniccia
Journal: Journal of Clinical Oncology (2016)

126 Background: Leaks from intrathoracic esophagogastric anastomosis are thought to be associated with higher rates of morbidity and mortality than leaks from cervical anastomosis. We challenge this assumption, and hypothesize that there is no significant difference in mortality based on the position of the esophagogastric anastomosis. Methods: A systematic literature search was conducted using PubMed and Embase databases on all studies published between January 2000 and June 2015 comparing transthoracic (TTE) and transhiatal (THE) esophagectomies. Studies that used alternate reconstruction approaches were excluded. Outcomes analyzed were leak rate, leak-associated mortality, overall 30-day mortality, and overall morbidity. Meta-analyses were performed using Mantel Haenszel statistical analyses on studies that reported on leak rates of both approaches. Nominal data are presented as frequency and interquartile range (IQR); measures of the association between treatments and outcomes are presented as odds ratio (OR) with 95% confidence interval (CI). Results: Twenty-one studies (including 3 randomized controlled trials) were included comprising of 7167 patients (54% TTE). THE approach yields a higher anastomotic leak rate (12%; IQR: 11.6% - 22.1%) than TTE (9.8%; IQR: 6.0% - 12.2%) (OR: 1.83 [0.34-06.92]), without any difference in leak-associated mortality (7.1% TTE vs. 4.6% THE; OR: 1.83, [0.39-8.52]). There was no difference in overall 30-day mortality (3.9% TTE vs. 4.3% THE; OR: 0.86, [0.66-1.13]) and morbidity (59.0% TTE vs. 66.6% THE; OR: 0.76, [0.37-1.59]). Conclusions: Transthoracic esophagectomy is associated with a lower leak rate and does not result in higher morbidity or mortality than transhiatal esophagectomy. The previously assumed higher rate of transthoracic leak-associated mortality is overstated, thus allowing surgeon discretion and other factors to influence the choice of intrathoracic versus cervical esophagogastric anastomosis.
Progression Free Survival (PFS) in Alemtuzumab Based RIC Allogeneic Transplantation for Myeloma Is Improved with Use of Pre-Emptive DLI (pDLI).
Authors: Karthik Ramasamy, Shameem Mahmood, Laurence Pearce, ZiYi Lim, Dariusz Ladon, Antonio Pagliuca, Stephen Devereux, Ghulam J. Mufti, Stephen Schey
Journal: Blood (2007)
Frequency of Resistance to Commonly used Antibiotics among A German Cohort of Patients with Spontaneous Bacterial Peritonitis Challenges Current Treatment Recommendations
Authors: P. Lutz, H.-D. Nischalke, B. Krämer, F. Goeser, D.J. Kaczmarek, M. Parcina, J. Nattermann, A. Hoerauf, C.P. Strassburg, U. Spengler
Journal: Journal of Hepatology (2016)
Breath Print Analysis by e-nose is Associated with Adverse Outcomes of Cirrhotic Patients Independently from the Other Prognostic Indices
Authors: A. De Vincentis, U. Vespasiani-Gentilucci, G. Galati, P. Gallo, G. Pennazza, M. Santonico, C. Vernile, R. Antonelli-Incalzi, A. Picardi
Journal: Journal of Hepatology (2016)
Simeprevir and Sofosbuvir with or without Ribavirin in Genotype 1 Chronic Hepatitis C Patients: Efficacy and Safety in Real Life
Authors: H. Ramos, J. Gómez, P. Linares, I. Martín, C. Almohalla, F. Jorquera, I. García, M. Vásquez, P. Conde, E. Badia, B. Alvarez, G. Karpman, S. Lorenzo, V. Gozalo, D. Joao, M. de Benito, L. Ruiz, F. Jiménez, F. Sáez-Rouela
Journal: Journal of Hepatology (2016)
Biomarkers immune monitoring technology primer: Immunoscore® Colon
Authors: Fabienne Hermitte
Journal: Journal for ImmunoTherapy of Cancer (2016)

The Immunoscore® assay for Colon Cancer (IS Colon) is the first standardized immune-based assay for the classification of cancer. It assesses the host immune response to Colon Cancer (CC) by measuring intra- and peri-tumoral T cell infiltration in formalin-fixed paraffin-embedded (FFPE) tissue
A Randomized Trial of Short-Course Preemptive Ganciclovir Compared with Conventional Ganciclovir Therapy To Prevent Cytomegalovirus Infection after Allogeneic Stem Cell Transplantation.
Authors: Keun W. Park, Jeeyun Lee, Jinny Park, Young Kim Ho, Mark H. Lee, Se-Hoon Lee, Jung H. Kang, Kihyun Kim, Chul W. Jung, Won S. Kim, Joon O. Park, Young H. Im, Young S. Park, Won K. Kang, Keunchil Park
Journal: Blood (2004)
Development and Validation of a Six-Gene Recurrence Risk Score Assay for Gastric Cancer
Authors: Keun-Wook Lee, Sung Sook Lee, Jun-Eul Hwang, Hee-Jin Jang, Hyun-Sung Lee, Sang Cheul Oh, Sang Ho Lee, Bo Hwa Sohn, Sang Bae Kim, Jae-Jun Shim, Woojin Jeong, Minse Cha, Jae-Ho Cheong, Jae Yong Cho, Jae Yun Lim, Eun Sung Park, Sang Cheol Kim, Yoon-Koo Kang, Sung Hoon Noh, Jaffer A. Ajani, Ju-Seog Lee
Journal: Clinical Cancer Research (2016)

This study was aimed at developing and validating a quantitative multigene assay for predicting tumor recurrence after gastric cancer surgery.Gene expression data were generated from tumor tissues of patients who underwent surgery for gastric cancer (n = 267, training cohort). Genes whose expression was significantly associated with activation of YAP1 (a frequently activated oncogene in gastrointestinal cancer), 5-year recurrence-free survival, and 5-year overall survival were first identified as candidates for prognostic genes (156 genes, P < 0.001). We developed the recurrence risk score (RRS) by using quantitative RT-PCR to identify genes whose expression levels were significantly associated with YAP1 activation and patient survival in the training cohort.We based the RRS assay on 6 genes, IGFBP4, SFRP4, SPOCK1, SULF1, THBS, and GADD45B, whose expression levels were significantly associated with YAP1 activation and prognosis in the training cohort. The RRS assay was further validated in an independent cohort of 317 patients. In multivariate analysis, the RRS was an independent predictor of recurrence [HR, 1.6; 95% confidence interval (CI), 1.02-2.4; P = 0.03]. In patients with stage II disease, the RRS had an HR of 2.9 (95% CI, 1.1-7.9; P = 0.03) and was the only significant independent predictor of recurrence.The RRS assay was a valid predictor of recurrence in the two cohorts of patients with gastric cancer. Independent prospective studies to assess the clinical utility of this assay are warranted. Clin Cancer Res; 22(24); 6228-35. ©2016 AACR.
Perilipin a is a Novel Biomarker of Circulating Adipocyte-Derived Extracellular Vesicles in Both Murine Models of Obesity and Obese Humans
Authors: A. Eguchi, M. Lazic, A.M. Armando, S.A. Phillips, O. Quehenberger, D.D. Sears, A.E. Feldstein
Journal: Journal of Hepatology (2016)
High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells
Authors: Thomas Horn, Stéphane Ferretti, Nicolas Ebel, Angela Tam, Samuel Ho, Fred Harbinski, Ali Farsidjani, Matthew Zubrowski, William R. Sellers, Robert Schlegel, Dale Porter, Erick Morris, Jens Wuerthner, Sébastien Jeay, Joel Greshock, Ensar Halilovic, Levi A. Garraway, Giordano Caponigro, Joseph Lehár
Journal: Cancer Research (2016)

Like classical chemotherapy regimens used to treat cancer, targeted therapies will also rely upon polypharmacology, but tools are still lacking to predict which combinations of molecularly targeted drugs may be most efficacious. In this study, we used image-based proliferation and apoptosis assays in colorectal cancer cell lines to systematically investigate the efficacy of combinations of two to six drugs that target critical oncogenic pathways. Drug pairs targeting key signaling pathways resulted in synergies across a broad spectrum of genetic backgrounds but often yielded only cytostatic responses. Enhanced cytotoxicity was observed when additional processes including apoptosis and cell cycle were targeted as part of the combination. In some cases, where cell lines were resistant to paired and tripled drugs, increased expression of antiapoptotic proteins was observed, requiring a fourth-order combination to induce cytotoxicity. Our results illustrate how high-order drug combinations are needed to kill drug-resistant cancer cells, and they also show how systematic drug combination screening together with a molecular understanding of drug responses may help define optimal cocktails to overcome aggressive cancers. Cancer Res; 76(23); 6950-63. ©2016 AACR.
A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension
Authors: Michael H Olsen, Sonia Y Angell, Samira Asma, Pierre Boutouyrie, Dylan Burger, Julio A Chirinos, Albertino Damasceno, Christian Delles, Anne-Paule Gimenez-Roqueplo, Dagmara Hering, Patricio López-Jaramillo, Fernando Martinez, Vlado Perkovic, Ernst R Rietzschel, Giuseppe Schillaci, Aletta E Schutte, Angelo Scuteri, James E Sharman, Kristian Wachtell, Ji Guang Wang
Journal: The Lancet (2016)
Dpy30 is critical for maintaining the identity and function of adult hematopoietic stem cells
Authors: Zhenhua Yang, Kushani Shah, Alireza Khodadadi-Jamayran, Hao Jiang
Journal: The Journal of Experimental Medicine (2016)

As the major histone H3K4 methyltransferases in mammals, the Set1/Mll complexes play important roles in animal development and are associated with many diseases, including hematological malignancies. However, the role of the H3K4 methylation activity of these complexes in fate determination of hematopoietic stem and progenitor cells (HSCs and HPCs) remains elusive. Here, we address this question by generating a conditional knockout mouse for Dpy30, which is a common core subunit of all Set1/Mll complexes and facilitates genome-wide H3K4 methylation in cells. Dpy30 loss in the adult hematopoietic system results in severe pancytopenia but striking accumulation of HSCs and early HPCs that are defective in multilineage reconstitution, suggesting a differentiation block. In mixed bone marrow chimeras, Dpy30-deficient HSCs cannot differentiate or efficiently up-regulate lineage-regulatory genes, and eventually fail to sustain for long term with significant loss of HSC signature gene expression. Our molecular analyses reveal that Dpy30 directly and preferentially controls H3K4 methylation and expression of many hematopoietic development-associated genes including several key transcriptional and chromatin regulators involved in HSC function. Collectively, our results establish a critical and selective role of Dpy30 and the H3K4 methylation activity of the Set1/Mll complexes for maintaining the identity and function of adult HSCs.
Randomized Controlled Trial of Entecavir Prophylaxis in Patients with Inflammatory Arthritis and Inactive HBV Infection Undergoing Biologics Treatment: The First Interim Report
Authors: C.-J. Lee, Y.-H. Huang, H.-Y. Lin, C.-T. Chou, C.-Y. Tsai, W.-S. Chen, M.-H. Chen, H.-C. Lin
Journal: Journal of Hepatology (2016)
Investigation d'infections humaines à salmonella enterica sérotype Java en Ecosse : association possible avec de la volaille importée
Authors: D J Brown, H Mather, L M Browning, J E Coia
Journal: Eurosurveillance (2003)

La comparaison des profils de PFGE de souches de Salmonella enterica Java issues de cas d'infection humaine (29) et de viande de volaille (30) en Ecosse a mis en evidence deux clusters. Tous les isolats de volaille importee des Pays-Bas appartenaient au cluster A, qui incluait egalement 10 isolats humains. Trente-et-un des 37 isolats de ce cluster avaient une empreinte identique JavX1, similaire au profil X8 d'une souche particuliere de S. Java predominante dans la filiere avicole dans plusieurs pays europeens. Le cluster B incluait 19 isolats humains et deux de volailles d'origine inconnue. Ces resultats combines aux donnees epidemiologiques et sur les origines de la viande de volaille suggerent fortement que la volaille importee constitue une source importante d'infections humaines a S. Java en Ecosse.
Serum LYSYL Oxidase-Like-2 (SLOXL2) Levels Correlate with Disease Severity in Patients with Primary Sclerosing Cholangitis
Authors: A.J. Muir, Z. Goodman, C.L. Bowlus, S. Caldwell, P. Invernizzi, V. Luketic, G. Minuk, G.M. Hirschfield, R.P. Myers, D. Ding, R. Aguilar, G.M. Subramanian, J.G. McHutchison, B. Eksteen, C. Levy
Journal: Journal of Hepatology (2016)
Integrin αvβ3 Transduces Survival and Angiogenic Signals to T Cell Lymphomas and Is a Therapeutic Target
Authors: Maria Florencia Cayrol, Maria Celeste Diaz Flaque, Tharu Fernando, Shao Ning Yang, Marcela Bolontrade, Mariana Amoros, Ricardo Farias, Giorgio Inghirami, Graciela Cremaschi, Leandro Cerchietti
Journal: Blood (2014)
Prospective, karyotype analysis in adult acute lymphoblastic leukemia: A LALA group (French-Belgium-Switzerland) report of 730 cases
Authors: C Charrin, N Dastugue, B Bilhou-Nabera, MJ Mozicconacci, M Jotterand-Bellomo, C Bastard, Anne Hagemeijer-Hausman, O Marek, S Taviaux, JL Lai, Lheritier, D Fiere, X Thomas
Journal: Blood (2002)