tbuckley/cabot-search huggingface dataset:
Abstract 1932: The importance of RNA editing enzymes in glioblastoma
Authors: Angela Gallo
Journal: Cancer Research (2016)

Abstract This study was supported by AIRC. Glioblastoma (or grade IV astrocytomas) is a highly heterogeneous and deadly malignant brain tumor and one of the most incurable form of cancer in human that urgently needs new therapeutic targets. There is great interest in elucidating all the molecular basis and functional importance of genetics and epigenetic mechanisms occurring in glioblastoma. In our laboratory, we investigate whether essential post-transcriptional event (such as the A-to-I RNA editing) is a possible molecular mechanism involved in the appearance/progression of glioblastoma. A-to-I RNA editing modifies the nucleotide sequence of RNA target molecules. The ADARs (Adenosine Deaminases that Act on RNA) are the enzymes responsible for this conversion acting on pre-mRNAs or non-coding RNAs (such as microRNA). Inosine, is recognized by the translation and splicing machineries, as Guanosine. Therefore, ADARs can play a direct and critical role in generating alternative protein isoforms (by codon changes and splicing pattern alterations) and modulating gene expression levels (by editing microRNAs and/or 3’-UTRs). In mammals, there are three different ADAR enzymes (ADAR1-3). The deregulation of ADAR2 activity has been connected with several neurological human diseases and Adar2 knockout animals show a lethal neurological phenotype. We demonstrated a direct correlation between a progressive decrease of ADAR2 editing activity and the increased grade of malignancy in paediatric astrocytomas (from grade I to grade IV). We show that the rescue of ADAR2 in glioblastoma cells is able to significantly inhibit in vivo glioblastoma tumor growth. Differently, when we decrease the expression of ADAR2 in malignant but not tumorigenic astrocytoma cell line (A172) we observed a boost of several cancers cell features such as cell proliferation, migration and colony formation. By integrating deep-sequencing and array approaches with bioinformatics analyses and molecular studies, we observed that ADAR2 is essential to edit a small number of mature miRNAs and to significantly modulate the expression of about 90 miRNAs in glioblastoma cells that may contribute to cancer progression. Our findings disclose an additional layer of complexity in miRNome regulation and provide information to better dissect the impact of ADAR2 editing enzyme in glioblastoma. Citation Format: Angela Gallo. The importance of RNA editing enzymes in glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1932.
Results From a Phase IV Open-Label Study Evaluating Changes In Bone Marrow Morphology In Adult Immune Thrombocytopenia (ITP) Patients Receiving Romiplostim: Analysis Of The 1- and 2-Year Romiplostim Cohorts
Authors: Ann Janssens, Francesco Rodeghiero, David Anderson, Beng Chong, Zoltan Boda, Ingrid Pabinger, Libor Cervinek, Xuena Wang, Angela Lopez
Journal: Blood (2013)
2. Biology of Hodgkin's Disease
Authors: Reed-Sternberg Cells, K Karube, K Ohshima, J Suzumiya, M Kikuchi, M Harada, A Tzankov, C Bourgau, A Zimpfer, A Rufle, R Maurer, S Pileri, P Went, S Dirnhofer
Journal: Annals of Oncology (2005)
Liposomal Vincristine (Marqibo) Combined with Hyper-Cmad As Frontline Therapy for Patients with Acute Lymphoblastic Leukemia: A Result of a Phase II Clinical Trial
Authors: Koji Sasaki, Elias Jabbour, Deborah A Thomas, Maria R. Khouri, Musa Yilmaz, Guillermo Garcia-Manero, Farhad Ravandi, Gautam Borthakur, Rebecca Garris, Evguenia Gachimova, Jad Chahoud, Courtney DiNardo, Naveen Pemmaraju, Jorge E. Cortes, Hagop M. Kantarjian, Susan O'Brien
Journal: Blood (2015)
Adjuvant chemotherapy for bladder cancer: A detailed characterization of factors precluding utilization.
Authors: Brian Robin Hu, Ian Roy, Hooman Djaladat, Anne K. Schuckman, Gus Miranda, Tanya B. Dorff, David I. Quinn, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2016)

e16001 Background: Adjuvant chemotherapy (AChT) can improve survival in select patients after radical cystectomy (RC), though it remains underutilized. We detail the factors that preclude candidate patients from receiving AChT. Methods: We analyzed the records of patients who underwent RC for urothelial carcinoma of the bladder (2003-2013) using our IRB approved database. Patients with ≥ pT3, pN+, and/or positive surgical margins were considered candidates for AChT. Patients who received neoadjuvant chemotherapy were excluded. A systematic review of medical records detailed the cited reasons for patients not undergoing AChT. Cases with low concern based upon pathologic staging were classified as ″surgeon discretion.″ Results: A total of 1379 patients underwent RC during this period and 249 (18%) received neoadjuvant chemotherapy. There were 528 (38%) patients who were eligible for AChT. Of these patients, 296 (56%) did not receive AChT, 177 (34%) received AChT, and 55 (10%) had insufficient records for determination of adjuvant treatments. Of the 296 eligible patients who did not receive AChT, there was no documented reason precluding AChT in 83 (28%). In 56 patients (19%) there was more than one reason for not undergoing AChT. The breakdown of cited factors precluding AChT is shown in the Table. The most commonly documented reasons were surgeon discretion based upon pathology, medical co-morbidities, advanced age, poor performance status, and patient preference. The most common medical co-morbidities precluding AChT were renal insufficiency and cardiovascular disease. Conclusions: Over half of eligible patients did not undergo AChT after RC with a wide range of cited reasons as justification. These variables should be considered when planning the optimal treatment regimen (e.g. neoadjuvant chemotherapy) for patients with advanced bladder cancer. Factors precluding eligible patients from adjuvant chemotherapy. Eligible patients n = 203 n Medical co-morbidities 57 Surgeon discretion based upon pathology 54 Poor performance status 47 Advanced age 41 Patient preference 35 Recurrent/metastatic disease 20 Death 17 Outside 90-day window 8 *can include multiple factors per patient
CSF3R Gene Mutations In Myeloid Malignancy Of Childhood
Authors: Hitoshi Sano, Kentaro Ohki, Myoung-ja Park, Yusuke Hara, Norio Shiba, Daisuke Tomizawa, Takashi Taga, Akiko Moriya Saito, Junichiro Fujimoto, Akio Tawa, Keizo Horibe, Souichi Adachi, Yasuhide Hayashi
Journal: Blood (2013)
Abstract 1516: Biomedical informatics applied to the analysis of colon cancer genome: looking for a mutational pattern associated to infectious-origin cancer
Authors: Claudia Machicado, Enrique Machicado
Journal: Cancer Research (2016)

Abstract Colon carcinoma, one of the most common malignancies globally, is the fourth cause of death due to cancer in Peru. Number of diagnosed cases have increased notably in the latest 5 years, which can be partially explained due to eating habits and environmental factors. In the present work we investigated the presence, in colon cancer genome, of genetic mutations reported in infectious-related cancer. Since most of gastric cancer is associated with chronic infection by Helicobacter pylori and Epstein-Barr virus (EBV), we investigated if the mutational pattern of gastric cancer caused by such infectious agents was similar to the colon carcinoma. Biomedical informatics tools were used to analyze the genomes of both gastric and colon carcinoma. Taken the 20 most frequently mutated genes both in gastric and colon cancer, a total of 8 genes in common resulted broadly mutated in both malignancies including p53, ATM, PIK3CA, ARID1A, CREBBP, KMT2D, KMT2C, and TRRAP. From such list, PIK3CA gene has been associated with gastric cancer caused by H. pylori and the mutational profile matched with that found in colon carcinoma. The point mutations of the oncoprotein PIK3CA identified equally in gastric and colon carcinoma were K111E, M1043I and E545G, all of them associated with gastric cancer caused by infection. Further screening of the gastric cancer genome allowed us to identify a point mutation of the oncoprotein β-catenin reported in infective-origin gastric cancer (D32N). Gene amplifications reported in infection-caused gastric cancer were also identified in the colon carcinoma genome in JAK2, CD274 and PDCD1LG2 genes. Finally downregulation of the tumor supresor gene FOXD3 associated to gastric cancer caused by pathogens was also found in colon carcinoma. Given that the origin of such genetic mutations have not been determined in colon cancer, our study brings evidence that colon carcinoma contain genetic mutations associated to infectious-related cancer. Further experimental studies will be required to verify the existence of mutations induced by parasites in colon carcinoma. Citation Format: Claudia Machicado, Enrique Machicado. Biomedical informatics applied to the analysis of colon cancer genome: looking for a mutational pattern associated to infectious-origin cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1516.
Programmed death ligand 1 expression in hepatocellular carcinoma: Relationship With clinical and pathological features
Authors: Julien Calderaro, Benoît Rousseau, Giuliana Amaddeo, Marion Mercey, Cécile Charpy, Charlotte Costentin, Alain Luciani, Elie‐Serge Zafrani, Alexis Laurent, Daniel Azoulay, Fouad Lafdil, Jean‐Michel Pawlotsky
Journal: Hepatology (2016)

The prognosis of hepatocellular carcinoma (HCC) remains poor, with only one third of patients eligible for curative treatments and very limited survival benefits with the use of sorafenib, the current standard of care for advanced disease. Recently, agents targeting the programmed death ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) immune checkpoint were shown to display impressive antitumor activity in various solid or hematological malignancies, including HCC. PD-L1 immunohistochemical expression is thought to represent a biomarker predictive of drug sensitivity. Here, we investigated PD-L1 expression in a series of 217 HCCs and correlated our results with clinical and histological features and immunohistochemical markers (PD-1, cytokeratin 19, glutamine synthetase, and β-catenin expression). PD-L1 expression by neoplastic cells was significantly associated with common markers of tumor aggressiveness (high serum alpha-fetoprotein levels, P = 0.038; satellite nodules, P < 0.001; macrovascular invasion, P < 0.001; microvascular invasion, P < 0.001; poor differentiation, P < 0.001) and with the progenitor subtype of HCC (cytokeratin 19 expression, P = 0.031). High PD-L1 expression by inflammatory cells from the tumor microenvironment also correlated with high serum alpha-fetoprotein levels (P < 0.001), macrovascular invasion (P = 0.001), poor differentiation (P = 0.001), high PD-1 expression (P < 0.001), and the so-called lymphoepithelioma-like histological subtype of HCC (P = 0.003).PD-L1 expression by either neoplastic or intratumoral inflammatory cells is related to tumor aggressiveness and suggests that the response to treatments targeting the PD-L1/PD-1 immune checkpoint could be restricted to particular HCC variants; thus, enrichment of these tumor subtypes in future clinical trials should be considered. (Hepatology 2016;64:2038-2046).
Abstract 1224: Insights into the mechanism of action of NVP-HDM201, a differentiated and versatile Next-Generation small-molecule inhibitor of Mdm2, under evaluation in phase I clinical trials
Authors: Stéphane Ferretti, Ramona Rebmann, Marjorie Berger, Francesca Santacroce, Geneviève Albrecht, Kerstin Pollehn, Dario Sterker, Markus Wartmann, Andreas Hueber, Marion Wiesmann, Michael R. Jensen, Francesco Hofmann, William R. Sellers, Philipp Holzer, Sébastien Jeay
Journal: Cancer Research (2016)

Abstract Activation of p53 by blocking p53-Mdm2 interaction using small-molecule inhibitors is being pursued as a promising cancer therapeutic strategy in p53 wild-type tumors. Here, we report the identification of NVP-HDM201, a novel, highly potent and selective inhibitor of the p53-Mdm2 interaction, with optimized drug-like properties allowing a versatile use with regard to route of administration, dose and scheduling. We determined the pharmacokinetics, pharmacodynamics and efficacy relationship of NVP-HDM201 with various dosing schedules in xenograft bearing mouse and rat models. NVP-HDM201 administered either daily at a low dose or once at a high dose revealed a differentiated engagement of the p53 molecular response. In contrast to the daily low dose treatment regimen, the single high dose NVP-HDM201 regimen resulted in a rapid and dramatic induction of p53-dependent PUMA expression and apoptosis. This was consistent with the finding that a single high dose NVP-HDM201 treatment, administered orally or intravenously, resulted in a robust and sustained tumor regression. Overall, both daily and once every 3 weeks dosing regimen showed comparable long term efficacy in preclinical studies. The ongoing clinical trial is currently designed to compare both dosing regimens with regard to efficacy and tolerability. Citation Format: Stéphane Ferretti, Ramona Rebmann, Marjorie Berger, Francesca Santacroce, Geneviève Albrecht, Kerstin Pollehn, Dario Sterker, Markus Wartmann, Andreas Hueber, Marion Wiesmann, Michael R. Jensen, Francesco Hofmann, William R. Sellers, Philipp Holzer, Sébastien Jeay. Insights into the mechanism of action of NVP-HDM201, a differentiated and versatile Next-Generation small-molecule inhibitor of Mdm2, under evaluation in phase I clinical trials. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1224.
Rapid Simultaneous Detection of Multiple Micro-Ribonucleic Acids By Surface Plasmon Resonance Array in Cell Lysates of Myelodysplastic Syndromes Patients
Authors: Jan E. Dyr, Jaroslav Cermak, Hana Vaisocherova, Zdenek Krejcik, Hana Sipova, Marketa Bockova, Ivana Visova, Tomas Springer, Marie Laura Ermini, Leona Chrastinova, Ondrej Pastva, Kristyna Pimkova, Roman Kotlin, Jaromir Novak, Jiri Homola
Journal: Blood (2014)
Multi-institutional validation of the predictive value of Ki-67 in patients with high-grade urothelial carcinoma of the upper urinary tract.
Authors: Laura-Maria Krabbe, Aditya Bagrodia, Ahmed Q Haddad, Payal Kapur, Dina Khalil, Linda S. Hynan, Christopher G. Wood, Jose A. Karam, Alon Z. Weizer, Jay D. Raman, Mesut Remzi, Nathalie Rioux-Leclerq, Andrea Haitel, Marco Roscigno, Christian Bolenz, Karim Bensalah, Arthur I. Sagalowsky, Shahrokh F. Shariat, Yair Lotan, Vitaly Margulis
Journal: Journal of Clinical Oncology (2015)

371 Background: To validate the independent predictive value of Ki-67 in patients with high-grade upper tract urothelial carcinoma (UTUC). Methods: 475 patients from the international UTUC collaboration who underwent extirpative surgery for high-grade UTUC were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray (TMA) formed from this patient cohort. Ki-67 expression was assessed in a semi-quantitative fashion and considered overexpressed at a cut-off of 20%. Multivariate analyses (MVA) were performed to assess independent predictors of oncological outcomes and Harrell’s C indices (HCI) were calculated for predictive models. Results: Median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was overexpressed in 25.9% of patients. Ki-67 overexpression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ (CIS), and regional lymph node metastases. In Kaplan-Meier analyses, overexpressed Ki-67 was associated with worse recurrence-free (RFS) (HR 12.6, p&lt;0.001) and cancer-specific survival (CSS) (HR 15.8, p&lt;0.001). In MVA, Ki-67 was an independent predictor of RFS (HR 1.6, 95% CI 1.07-2.30, p=0.021) and CSS (HR 1.9, 95% CI 1.29-2.90, p=0.001). Ki-67 improved HCI from 0.66 to 0.70 (p&lt;0.0001) for both RFS and CSS in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for RFS and 0.81 to 0.83 (p=0.005) for CSS in our post-operative model. Conclusions: Ki-67 was validated as an independent prognostic predictor of RFS and CSS in patients treated with extirpative surgery for high-grade UTUC in a large, multi-institutional cohort.
Management of relapsed and refractory multiple myeloma in modern times: Incorporating new agents into decision‐making
Authors: Charles A. Clark, Robert F. Cornell, Emma C. Scott, Jae Chung, Luciano J. Costa
Journal: American Journal of Hematology (2016)

Although upfront treatment of multiple myeloma has become more effective, relapses are the norm, often driven by the emergence of a genetically divergent clone selected by the initial therapy. Recent trials have demonstrated the safety and efficacy of combination therapy also in the relapsed and refractory setting and supported the regulatory approval of several new agents including new proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies. We provide a detailed summary of recent practice-changing trials in relapsed and refractory MM and share a practical approach to assimilate disease and patient-features into treatment decision. Am. J. Hematol. 91:1044-1051, 2016. © 2016 Wiley Periodicals, Inc.
Salvage resection for recurrent or metastatic hepatocellular carcinoma after percutaneous ablation therapy
Authors: Wenjie Hu, Zhenwei Peng, Dongming Li, Shunli Shen, Jiali Li, Shengnan Ruan, Mingfang Zhang, Baoxian Liu, Manxia Lin, Shaoqiang Li, Qiang He, Baogang Peng, Xiaoyan Xie, Mingde Lu, Ming Kuang
Journal: International Journal of Surgery (2016)
Abstract 3841: Curcumin enhances the efficacy of docetaxel- induced apoptosis of prostate cancer cell
Authors: Saswati Banerjee, Santosh K. Singh, James W. Lillard, Rajesh Singh
Journal: Cancer Research (2016)

Abstract Despite the different prostate cancer (PCa) treatment therapies it continues to be one of the leading causes of death in men. Docetaxel is a well-established chemotherapeutic agent used to target metastatic PCa, however long-term treatment with docetaxel results in drug resistant and toxicity in PCa cells. Combining agents is common to improve outcomes, but the combination should not significantly increase toxicity. Curcumin is a non-toxic natural compound with multifaceted chemo preventive potential. In current study we evaluated whether curcumin can reinforce the effect of docetaxel on PCa cell lines (RWPE-1, C4-2b, DU145 and PC3). PCa cell lines were treated with curcumin or docetaxel alone or in combination followed by cell viability (MTT assay) and apoptosis assay (TUNEL assay and flow-cytometric analysis of annexin V/propidium iodide-stained cells). The expressions of pro- and anti-apoptotic markers were quantitated with real-time PCR and western blot assay. Our results indicate that curcumin combined with docetaxel led to lower cell viability than treatment with docetaxel or curcumin alone. Annexin V staining followed by flow cytometric analysis demonstrated that curcumin treatment enhanced the docetaxel-induced apoptosis of PCa cells, which was further confirmed by TUNEL assay. The down-regulation of the anti-apoptotic proteins (Bcl2, Mcl-1) and upregulation of pro-apoptotic proteins (Bax, Bid etc.) further confirm that we can considerably reduce docetaxel dose using synergistic combination therapy with curcumin. Thus, our results strongly suggest that we can reduce dose levels of docetaxel and compensate it with non-toxic curcumin and it could be a potential therapeutic contender in enhancing the efficacy of docetaxel in PCa treatment. Citation Format: Saswati Banerjee, Santosh K. Singh, James W. Lillard, Rajesh Singh. Curcumin enhances the efficacy of docetaxel- induced apoptosis of prostate cancer cell. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3841.
Targeted genomic analysis reveals widespread autoimmune disease association with regulatory variants in the TNF superfamily cytokine signalling network
Authors: Arianne C. Richard, James E. Peters, James C. Lee, Golnaz Vahedi, Alejandro A. Schäffer, Richard M. Siegel, Paul A. Lyons, Kenneth G. C. Smith
Journal: Genome Medicine (2016)

Tumour necrosis factor (TNF) superfamily cytokines and their receptors regulate diverse immune system functions through a common set of signalling pathways. Genetic variants in and expression of individual TNF superfamily cytokines, receptors and signalling proteins have been associated with autoimmune and inflammatory diseases, but their interconnected biology has been largely unexplored. We took a hypothesis-driven approach using available genome-wide datasets to identify genetic variants regulating gene expression in the TNF superfamily cytokine signalling network and the association of these variants with autoimmune and autoinflammatory disease. Using paired gene expression and genetic data, we identified genetic variants associated with gene expression, expression quantitative trait loci (eQTLs), in four peripheral blood cell subsets. We then examined whether eQTLs were dependent on gene expression level or the presence of active enhancer chromatin marks. Using these eQTLs as genetic markers of the TNF superfamily signalling network, we performed targeted gene set association analysis in eight autoimmune and autoinflammatory disease genome-wide association studies. Comparison of TNF superfamily network gene expression and regulatory variants across four leucocyte subsets revealed patterns that differed between cell types. eQTLs for genes in this network were not dependent on absolute gene expression levels and were not enriched for chromatin marks of active enhancers. By examining autoimmune disease risk variants among our eQTLs, we found that risk alleles can be associated with either increased or decreased expression of co-stimulatory TNF superfamily cytokines, receptors or downstream signalling molecules. Gene set disease association analysis revealed that eQTLs for genes in the TNF superfamily pathway were associated with six of the eight autoimmune and autoinflammatory diseases examined, demonstrating associations beyond single genome-wide significant hits. This systematic analysis of the influence of regulatory genetic variants in the TNF superfamily network reveals widespread and diverse roles for these cytokines in susceptibility to a number of immune-mediated diseases.