tbuckley/cabot-search huggingface dataset:
Esophagogastric junction cancer and classification as esophagus cancer according to molecular fingerprint.
Authors: Williams Fernandes Barra, Andre Salim Khayat, Fabiano C Moreira, Samia Demachki, Andrea KCR Santos, Sidney EB Santos, Paulo P Assumpção
Journal: Journal of Clinical Oncology (2016)

4059 Background: The 7th edition of UICC staging system moved GEJ cancers from gastric staging group to esophagus cancers. Since clinical management is strongly influenced by this staging system, we looked at molecular fingerprints of GEJ tumors and compared to gastric and esophagus profiles, to elucidate whether GEJ cluster in the gastric or esophagus cancer groups, according to mRNA expression pattern, since this might represent tumor identity. Methods: The clinical and expression data were downloaded from TCGA. The total number of samples was 1167 ( 450 stomach, 196 esophagus and 521 colon samples). Both Principal Component Analysis (PCA) and Heat Map (HM) plots were performed in R platform, using Log2 transformation of RPKM normalized data. Differential Expression Analysis was also performed in R, using RAW data and the DESeq2 package. Benjamini and Hochberg False Discovery Rate corrections were used. The mRNAs were tagged as differentially expressed if they met the following criteria: i) FDR adjusted p-value < 0.05; and ii) |Log2(fold-change)| > 2 (expressions greater or lower than 4 fold change). Results: Esophagus squamous cell carcinoma (ESCC) clustered apart of the others tumors, while adenocarcinomas (AC) clustered all together. The HM also demonstrates that ESCC belongs to a different group, while AC of esophagus looks like AC of the cardia and non cardia regions. Even distal gastric cancers are quite similar to AC of the lower esophagus, demonstrating that esophagus AC relies much closer to gastric cancers than to esophagus cancers. We also analyzed 521 samples of colon AC. Both the PCA and HM images clearly demonstrated that AC of the colon are much different than AC of stomach and esophagus, strengthening the results. Conclusions: By using robust molecular fingerprints, in a large series of tumors from an import cancer data bank, it was strongly demonstrated that GEJ tumors look much more like as gastric cancers than esophagus cancers, despite of tumor heterogeneity.
Tumor Cell–Independent Estrogen Signaling Drives Disease Progression through Mobilization of Myeloid-Derived Suppressor Cells
Authors: Nikolaos Svoronos, Alfredo Perales-Puchalt, Michael J. Allegrezza, Melanie R. Rutkowski, Kyle K. Payne, Amelia J. Tesone, Jenny M. Nguyen, Tyler J. Curiel, Mark G. Cadungog, Sunil Singhal, Evgeniy B. Eruslanov, Paul Zhang, Julia Tchou, Rugang Zhang, Jose R. Conejo-Garcia
Journal: Cancer Discovery (2016)

Abstract The role of estrogens in antitumor immunity remains poorly understood. Here, we show that estrogen signaling accelerates the progression of different estrogen-insensitive tumor models by contributing to deregulated myelopoiesis by both driving the mobilization of myeloid-derived suppressor cells (MDSC) and enhancing their intrinsic immunosuppressive activity in vivo. Differences in tumor growth are dependent on blunted antitumor immunity and, correspondingly, disappear in immunodeficient hosts and upon MDSC depletion. Mechanistically, estrogen receptor alpha activates the STAT3 pathway in human and mouse bone marrow myeloid precursors by enhancing JAK2 and SRC activity. Therefore, estrogen signaling is a crucial mechanism underlying pathologic myelopoiesis in cancer. Our work suggests that new antiestrogen drugs that have no agonistic effects may have benefits in a wide range of cancers, independently of the expression of estrogen receptors in tumor cells, and may synergize with immunotherapies to significantly extend survival. Significance: Ablating estrogenic activity delays malignant progression independently of the tumor cell responsiveness, owing to a decrease in the mobilization and immunosuppressive activity of MDSCs, which boosts T-cell–dependent antitumor immunity. Our results provide a mechanistic rationale to block estrogen signaling with newer antagonists to boost the effectiveness of anticancer immunotherapies. Cancer Discov; 7(1); 72–85. ©2016 AACR. See related commentary by Welte et al., p. 17. This article is highlighted in the In This Issue feature, p. 1
Efficacy and Safety of Rituximab Therapy in Neuromyelitis Optica Spectrum Disorders
Authors: Valentina Damato, Amelia Evoli, Raffaele Iorio
Journal: JAMA Neurology (2016)

Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune astrocytopathies characterized by predominant involvement of the optic nerves and spinal cord. In most patients, an IgG autoantibody binding to astrocytic aquaporin 4, the principal water channel of the central nervous system, is detected. Rituximab, a chimeric monoclonal antibody specific for the CD20 B-lymphocyte surface antigen, has been increasingly adopted as a first-line off-label treatment for patients with NMOSDs.To perform a systematic review and a meta-analysis of the efficacy and safety of rituximab use in NMOSDs, considering the potential predictive factors related to patient response to rituximab in this disease.English-language studies published between January 1, 2000, and July 31, 2015, were searched in the MEDLINE, Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov databases. Patient characteristics, outcome measures, treatment regimens, and recorded adverse effects were extracted.Forty-six studies were included in the systematic review. Twenty-five studies that included 2 or more patients with NMOSDs treated with rituximab were included in the meta-analysis. Differences in the annualized relapse rate ratio and Expanded Disability Status Scale score before and after rituximab therapy were the main efficacy measures. Safety outcomes included the proportion of deaths, withdrawals because of toxic effects, and adverse effects.Among 46 studies involving 438 patients (381 female and 56 male [sex was not specified in 1 patient]; mean age at the outset of treatment, 32 years [age range, 2-77 years]), rituximab therapy resulted in a mean (SE) 0.79 (0.15) (95% CI, -1.08 to -0.49) reduction in the mean annualized relapse rate ratio and a mean (SE) 0.64 (0.27) (95% CI, -1.18 to -0.10) reduction in the mean Expanded Disability Status Scale score. A significant correlation was observed between disease duration and the Expanded Disability Status Scale score. Adverse effects were recorded in 114 of 438 (26%) patients treated with rituximab. Specifically, 45 patients (10.3%) experienced infusion-related adverse effects, 40 patients (9.1%) had an infection, 20 patients (4.6%) developed persistent leukopenia, 2 patients (0.5%) were diagnosed as having posterior reversible encephalopathy, and 7 patients (1.6%) died.This systematic review and meta-analysis provides evidence that rituximab therapy reduces the frequency of NMOSD relapses and neurological disability in patients with NMOSDs. However, the safety profile suggests caution in prescribing rituximab as a first-line therapy.
VALOR, an adaptive design, pivotal phase III trial of vosaroxin or placebo in combination with cytarabine in first relapsed or refractory acute myeloid leukemia.
Authors: Farhad Ravandi, Ellen K. Ritchie, Hamid Sayar, Stephen Anthony Strickland, Michael Craig, Dominik L. D. Selleslag, Johan Maertens, Violaine Havelange, Jeffrey E. Lancet, Steven B Ketchum, Gary Acton, Cyrus R. Mehta, Eric Silva, Adam Craig, Judith Ann Fox, Robert K. Stuart, Harry Paul Erba, Norbert Vey, Gary J. Schiller, Eric Jay Feldman
Journal: Journal of Clinical Oncology (2012)

TPS6637 Background: The promising phase 2 activity/tolerability profile of vosaroxin with cytarabine in first relapsed or refractory AML (N=69) with median overall survival (OS) 7.1 mo, combined CR 28% (CR 25%), median LFS 25 mo and 30-day all‑cause mortality 3%, supported phase 3 trial. VALOR (NCT01191801), a phase 3, randomized, controlled, double-blind trial, evaluates vosaroxin and cytarabine versus placebo and cytarabine in patients with first relapsed or refractory AML and incorporates an adaptive design. Primary objective is OS; secondary/tertiary objectives include CR rates, safety, EFS, LFS, and transplantation rate. Key eligibility criteria: persistent AML or first relapsed AML after 1 or 2 induction cycles that include at least 1 regimen of cytarabine with an anthracycline/anthracenedione; adequate cardiac, hepatic, renal function; and adults with no upper age restriction. Methods: VALOR is recruiting patients at over 100 sites in 14 countries in North America, Europe, and Australia/NZ. Enrollment opened Dec 2010; 183 patients enrolled through Dec 2011. Adaptive design: Base case assumed 40% improvement in median OS (hazard ratio, HR=0.71), 90% power, 2-sided alpha of 0.05. At the interim analysis (50% events), DSMB may recommend a 50% sample size increase from 450 to 675 evaluable patients if results indicate a larger sample size is required to reduce the risk of failing to confirm a clinically meaningful OS benefit (Mehta, Pocock, Stat Med 2010). In consideration of FDA and EMA guidance on Data Monitoring Committees and adaptive design with respect to trial integrity, operational bias, firewalls, and data confidentiality and archival, VALOR uses the Access Control Execution System (ACES ) to store, share, and archive confidential DSMB reports in a secure environment with an audit trail, and to facilitate communication between the DSMB and trial sponsor. The DSMB periodically reviews a combination of blinded and unblinded analyses while the study team remains blinded as specified in the DSMB charter. The DSMB recommended VALOR continue as planned after reviewing safety data in Dec 2011.
Financial Burden In Recipients Of Allogeneic Hematopoietic Cell Transplantation
Authors: Nandita Khera, Yu-hui Chang, Shahrukh K Hashmi, James L Slack, Veena Fauble, Timothy Beebe, Vivek Roy, Lisa Sproat, Jose F. Leis, Pierre Noel, Jon Tilburt, Joseph R. Mikhael
Journal: Blood (2013)
Use of loss of function RNA interference screen to evaluate TNK-2 as a factor involved in rhabdomyosarcoma cell growth.
Authors: F. I. Arnaldez, C. L. Yeung, P. J. Grohar, L. J. Helman
Journal: Journal of Clinical Oncology (2010)

9525 Background: Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue tumor. Embryonal (ERMS) and alveolar rhabdomyosarcoma (ARMS) represent different genetic alterations: 11p15 LOH in ERMS and PAX3 (or PAX7)-FOXO1 translocation in ARMS. Patients with metastatic or recurrent disease are essentially non-curable. To find novel therapeutic approaches for these patients, we sought to identify genes necessary for survival of both subtypes of RMS cells using a loss of function shRNA screen. We identified TNK-2 (ACK-1), a non-receptor protein tyrosine kinase known to interact with Cdc-42, a rho family GTPase critical for growth and differentiation, and possibly p130Cas, a scaffold protein involved in regulating growth and development. TNK-2 has not previously been linked to RMS. Methods: RD and RH30 cell lines (ERMS and ARMS respectively) engineered to tightly regulate gene expression via the bacterial tetracycline repressor were infected by a doxycycline regulated retroviral shRNA library. Each shRNA in the library contains a 60 nucleotide barcode, allowing abundance of shRNAs to be measured before and after doxycycline-induced expression. Missing barcodes were interpreted as genes required for cell survival. This approach showed that the TNK-2 gene was required for the survival of RH30 cells to a greater extent than RD cells. To confirm this finding, specific shRNA sequences targeting this gene were delivered to engineered RD and RH30 cell lines, We evaluated cell growth in vitro during 11 days using MTS assay. Results: As expected, the shRNA targeting TNK-2 inhibited cell growth by 21-40% in RH30 cells and by 19-37% in RD cells (compared to non-doxycycline induced control) with a maximum effect on day 6. Expression of a non-targeting shRNA showed less than 6% decrease in cell number. Conclusions: The use of functional genetics to identify novel critical pathways for RMS growth and survival has identified TNK-2 as a critical factor. This non-receptor protein tyrosine kinase has not previously been identified with these tumors and work is ongoing to determine whether this pathway may identify novel therapeutic opportunities. No significant financial relationships to disclose.
Involved field irradiation (IFRT) does not improve outcome in patients with stage III/IV Hodgkin's lymphoma (HL) in complete remission after MOPP/ABV (M/A): Results of the randomised EORTC trial 20884
Authors: Jmm Raemaekers, B Aleman, M Henry-Amar, U Tirelli, A Hagenbeek, P Carde, W Peters, R Tomsic, A van Hoof, M van 't Veer, José Thomas, W Schroyens, J Kluin-Nelemans, C Sebban, D Bron, H Eghbali, A Pinna, A Mandard
Journal: Blood (2001)
A prospective, randomized trial of bivaliruclin in acute coronary syndromes: One year results from the ACUITY Trial
Authors: Gregg W Stone, Michel E Bertrand, A. Michael Lincoff, Jeffrey W Moses, E. Magnus Ohman, Harvey D White, Stuart J Pocock, James H Ware, Brent T McLaurin, David A Cox, Fred Feit, Antonio Colombo, Philip Aylward, Angel R Cequir, Harald Darius, Walter Desmet, Ramin Ebrahimi, Martial Hamon, Lars H Rasmussen, Hans-Jurgen Rupprecht, James Hoekstra, Charles Pollack, Alexandra J Lansky, Roxana Mehran
Journal: Journal of the American College of Cardiology (2007)
Implementation of a novel statistical design to evaluate successive treatment courses for metastatic transitional cell carcinoma. A Phase II trial at the M. D. Anderson Cancer Center
Authors: A. O. Siefker-Radtke, P. F. Thall, N. M. Tannir, S.-M. Tu, L. C. Pagliaro, D. L. Williams, R. E. Millikan
Journal: Journal of Clinical Oncology (2004)

4543 Background: Patients undergoing chemotherapy often receive several successive courses of treatment whereby physicians use an adaptive strategy to decide whether to repeat the same regimen or switch to an alternate regimen. Although this medical practice is quite common, current clinical trial design does not account for such within-patient treatment decision strategies. Methods: We adopted a novel trial design best described as a ‘play-the-winner-and-drop-the-loser’ algorithm (Statist Med 19:1011, 2000) using 4 different chemotherapy regimens for a total of 12 two-stage strategies. This methodology can be used to select one best treatment, or a best pair of treatments as a two-stage strategy. Patients with metastatic urothelial carcinoma were treated with a 6-week course of therapy and then re-randomized to alternate therapy if they did not have at least a 40% reduction in their tumor. After the second 6-week course, a successful regimen or combination was defined as one which provided a >= 90% sustained reduction in tumor volume with no evidence of progression after initial response. Results: Since 2000, 65 patients (of a planned 120) received either ifosfamide-based chemotherapy (ifosfamide, taxol, platinum (ITP) or ifosfamide, adriamycin, gemcitabine (IAG)), and/or a gemcitabine-cisplatin regimen (gemcitabine, cisplatin (GC) or cisplatin, gemcitabine, ifosfamide (CGI)). The median survival for all patients was 16.3 months. After initial therapy, there were 12 CRs (IAG-4, ITP-3, GC-2, CGI-3). Of the 32 patients receiving second-line therapy, there were 7 CRs (IAG-2, ITP-1, GC-3, CGI-1). A total of 147.5 6-week courses were given (IAG-30, ITP-36, GC-42.5, CGI-39). A combination incorporating IAG had the best chance of success as defined by response (6 CRs of 30 courses given). Conclusions: Although results are still early, assigning successive chemotherapy courses using this strategy may have an improved survival as compared with historical data. This trial design provides a novel method for assessing and comparing treatment regimens in a multi-course setting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen; AstraZeneca; Novaritis; Novartis Oncology Amgen Lilly; Roche; Pfizer; Novartis
Relationships between dietary and urinary amino acids: the INTERMAP study
Authors: Lucila Blanco-Cedres, Martha L Daviglus, Jeremiah Stamler, Paul Elliott, Hugo Kesteloot, Peter Declercq, Queenie Chan, Ka He, Daniel B Garside, Xuan Cai, Hirotsugu Ueshima, Beifan Zhou, Alan R Dyer
Journal: Circulation (2007)
P0150 : Liver cirrhosis is independently associated with mortality in patients with bacterial endocarditis: Results of a case control multicenter study of 202 cases
Authors: J.-F. Cadranel, I. Ollivier-Hourmand, C. Bureau, S. Zerkly, T. Thévenot, P. Cacoub, G. Macaigne, L. Alric, A. Garioud, V. Jouannaud, H. Lison, C. Chagneau-Derrode, A. Pariente, A. Pélaquier, M. Bourlière, X. Causse, M. Allaire, J.-B. Nousbaum, J. Dumortier, A. Louvet, I. Rosa-Hézode, N. Ganne-Carrié, R. Chentouh, M. Hattab, J. Gournay, H. Blasco-Perrin, T. Antonini, L. Spahr, J.-P. Bronowicki, C. Silvain, X. Amiot, V. Di Martino, B. Lesgourgues, J.-D. Grangé, M. Bakar, J.-M. Péron, D. Samuel, X. Adhoute, H. Hagège, J.-C. Trinchet, P. Mathurin, J. Denis, K. Dupont, P. Iaria, T. Dao
Journal: Journal of Hepatology (2015)
P0463 : Influence of killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands on vertical transmission and chronicity of hepatitis C virus in children
Authors: E.-J. Pavon-Castillero, A. Ruiz-Extremera, M. Florido, P. Muñoz de Rueda, J.-A. Muñoz-Gamez, J. Casado, A. Carazo, R. Quiles, A. Gila, S. Jimenez-Ruiz, A.B. Martin, J. León, J. Salmeron
Journal: Journal of Hepatology (2015)
Identification of DNA methylation changes in esophageal cancer before/after chemoradiation therapy using a MCA-microarray and bisulfate pyrosequencing.
Authors: T. Tsuda, Y. Watanabe, M. Hirakawa, K. Hosoya, N. Izawa, H. Inaba, N. Matsumoto, M. Toyota, F. Itoh
Journal: Journal of Clinical Oncology (2010)

10550 Background: Systemic chemo- and chemoradiation therapies for esophageal squamous cell carcinoma (ESCC) patients are widely accepted. However we sometimes experience the resistance of ESCC to these therapies, and multicentric occurrence of ESCC after the successful treatment. Although there are studies, which have shown the involvements of promoter methylation of tumor suppressor genes in esophageal carcinogenesis, it remains unclear that the epigenetic changes related to treatments against ESCC. Our aim is to identify how DNA methylation status changes in tumor tissue (T) and also adjacent normal tissue (ADJ) before/after chemoradiation therapy (CRT). Methods: Tumor and adjacent normal biopsy specimens were obtained before/after treatment from 34 patients (124 samples) treated with a uniform CRT protocol. We analyzed genomewide DNA methylation of 12 non-treated test samples (T and matched ADJ: 6 each) by methylated CpG island amplification and microarray (MCAM) method (4×44K, Agilent custom array), and selected candidate genes that were highly methylated in T compared to ADJ. We next analyzed DNA mathylation of CYP26C1 (cytochrome P450, family 26, subfamily C, polypeptide 1), one of the candidate genes, in 112 validation samples by quantitative bisulfate pyrosequencing. Results: CYP26C1 was selected by unsupervised hierarchical clustering after MCAM in test samples. CYP26C1 DNA methylation was significantly higher in T than ADJ in both test and validation samples (p<0.04, T: 60.7±7.6, ADJ: 44.5±11.5). Interestingly, some ADJ also showed high methylation in validation samples. Additionally, CYP26C1 methylation in both T and ADJ were significantly depressed after CRT (T: p<0.01 (45.1±18.3 to 31.6±14.9), ADJ: p<0.0001 (43.8±10.3 to 30.5±13.8)). Conclusions: CYP26C1 has a CpG island in promoter area, which is highly methylated in T of ESCC patients. And, some ADJ showed high CYP26C1 methylation, suggesting possibility of multicentric occurrence of ESCC. Moreover, CYP26C1 methylation depress after CRT both T and ADJ, suggesting a new anti-cancer mechanism of CRT through epigenetic alteration. No significant financial relationships to disclose.
Use of Projection Analyses and Obesity Trends
Authors: Ernest Lo
Journal: JAMA (2016)

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P0143 : Impulsional, point and bidimensional shear wave elastometry for portal hypertension: same stiffness thresholds?
Authors: H. Stefanescu, G. Allegretti, C. Serra, G. Marasco, N. Gamal, F. Conti, A. Colecchia, D. Festi, P. Andreone, L. Bolondi, F. Piscaglia
Journal: Journal of Hepatology (2015)
O-0020 Bevacizumab + Chemotherapy Beyond First Progression in Metastatic Colorectal Cancer Patients Previously Treated with Bevacizumab-Based Therapy: TML Study Subgroup Findings
Authors: Thierry André, Vieitez Jose Maria, Olivier Bouché, Jaafar Bennouna, Javier Sastre, Vicente Alonso-Orduna, Dirk Arnold, Pia Österlund, Richard Greil, Eric Van Cutsem, Roger von Moos, Irmarie Reyes-Rivera, Martina Makrutzki, Stefan Kubicka
Journal: Annals of Oncology (2012)