tbuckley/cabot-search huggingface dataset:
P17.02 * THE CORRELATION BETWEEN RESULTS OF COMPLEX TREATMENT AND 1P/19Q DELETION FOR PATIENTS WITH ANAPLASTIC OLIGODENDROGLIAL TUMORS
Authors: D. Apskalne, A. Ozola, K. Bicans, R. Ozols, K. Auslands
Journal: Neuro-Oncology (2014)

INTRODUCTION: Anaplastic oligodendrogliomas and anaplastic oligoastrocytomas histologically are considered as grade III tumors. Both these forms are highly sensitive to chemotherapy and tend to have similar responses to complex postoperative therapy. Individual sensitivity to chemotherapy of anaplastic oligodendroglial tumors is of high importance, especially if 1p/19q co- deleted. AIM: A retrospective correlative research designed to evaluate the efficiency of complex radiotherapy and chemotherapy in patients with anaplastic oligodendroglial tumors depending on presence of combined 1p/19q loss. METHODS: Patients were eligible with diagnosed anaplastic oligodendrogliomas and anaplastic oligoastrocytomas between 2005 and 2010. 30 patients were included. Identification of combined 1p/19q loss was performed on paraffin-embedded histological material. All 30 patients underwent complex therapy: extent of surgery was total or subtotal resection, next received fractionated radiotherapy 60 Gy and followed by 6 cycles standart Temozolomide (TMZ). Primary endpoints - progression free survival (PFS) and overall survival (OS) were determined in each group respectively. RESULTS: 21 patient with anaplastic oligodendroglioma or anaplastic oligoastrocytoma were diagnosed with 1p/19q loss. Median PFS in this group reached 54.6 months, median OS - 67.7 months. The second group includes 9 patients without 1p/19q loss, with median PFS 43.3 months, median OS - 54.3 months. CONCLUSIONS: Median PFS and OS tend to be higher in patients with combined 1p/19q loss, but there is seen very high PFS and OS results in individual patients without 1p/19q loss.
Abstract LB-282: Myxovirus (influenza virus) resistance 1 (MX1) polymorphism in prostate cancer
Authors: Shanora Glymph, Sanjay Mandal, Ashley Evans, Jaideep Chaudhary
Journal: Cancer Research (2012)

Abstract PURPOSE: Myxovirus (influenza virus) resistance 1 (MX1) is an interferon regulated gene responsible for a specific antiviral state against viral infection. We have previously shown that MX1 is up-regulated by androgens in the normal prostate epithelial cells; however, there is no known role for MX1 in cancer. Meta-analysis of different expression databases e.g. NCBI GEO and Oncomine suggested a strong inverse association between MX1 expression and prostate cancer. To confirm these studies, we performed Immunohistochemistry on normal prostate and prostate cancer tissues. Our data revealed that MX1 expression was indeed decreased in PCa as compared to normal, indicating that MX1 could be transcriptionally down-regulated. Literature studies indicated that MX1 down-regulation could be due to a specific polymorphism in the proximal MX1 promoter. In the promoter region of MX1 at position -88, a single nucleotide polymorphism G&amp;gt;T (rs2071430) is involved in modifying the gene expression. Interestingly, the rs2071430 harbors an interferon-stimulated response element (ISRE) that is required for MX1 expression in response to interferons. The “T” allele restores whereas the “G” allele attenuates ISRE binding resulting in increased or decreased MX1 expression respectively. Based on these observations we hypothesized that decreased expression of MX1 in prostate cancer could be due to the rs2071430 polymorphism. DESIGN METHODS: We investigated MX1 rs2071430 polymorphism in genomic DNA from equal number of disease free and prostate cancer samples (N=305). The sample size required to achieve statistically significant associations were calculated using the power calculator for case control genetic association studies. Polymorphism was detected by sequencing the PCR amplicon through SNPdetector to ensure that the SNP was due to heterozygous allelic variations and not due to sequencing artifacts. RESULTS: The data suggests that the GG genotype (low promoter activity) is higher in PCa (72%) as compared to normal (58.6%). The TT genotype (high activity) was higher in normal (5.7%) compared to PCa (2.4%). No TT genotype was observed in Caucasian normal samples. The results were statistically significant at P&amp;lt;0.05. Our results, for the first time demonstrate that MX1 is down-regulated in prostate cancer possibly at the transcriptional level due to ISRE polymorphism in the promoter region. ACKNOWLEDGEMENTS: This research is supported by NIH/NCMHD grant 1P20MD002285-01. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-282. doi:1538-7445.AM2012-LB-282
PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH INSULIN TREATED DIABETES MELLITUS: INSIGHTS FROM THE TUXEDO TRIAL
Authors: Upendra Kaul, Ajit Bhagwat, Brian Pinto, Praveen K. Goel, Prashant Jagtap, Shireesh Sathe, Priyadarshini Arambam
Journal: Journal of the American College of Cardiology (2016)
Abstract 3437: Epithelial-mesenchymal transition spectrum characterized by an ovarian cancer cell line library defines an aggressive metastable state
Authors: Ruby YJ Huang, Meng Kang Wong, Vin Yee Chung, Aloysius Ng, You Fei Lee, Elke Pietschmann, Seiichi Mori, Noriomi Matsumura, Jean Paul Thiery
Journal: Cancer Research (2011)

Abstract Epithelial-mesenchymal transition (EMT) has been implicated to be one of the driving mechanisms of carcinoma progression in many solid tumours, such as breast, colorectal, and ovarian cancer. It explains how carcinoma cells invade and metastasize by transforming an epithelial state via a metastable state to a mesenchymal state. Many studies have addressed the epithelial and mesenchymal states. However, understanding of the metastable state is still limited. In this study, we describe a model system for appraising the spectrum of EMT by using 42 well-characterized ovarian cancer cell lines. Phenotypic EMT characterization reveals 4 subgroups which represent different epithelial-mesenchymal compositions on the EMT spectrum. Genome-wide transcriptional characteristics and recurrent genomic alterations specific for each subgroup are also described. We also demonstrate that this EMT spectrum can be used to refine the analysis of data generated in cell-based functional studies. Ovarian cancer cells harbouring intermediate phenotypes are more migratory, invasive, anoikis resistant, and more spheroidogenic. This ovarian cancer cell line EMT spectrum allows fine tuning of the EMT process by further characterizing the metastable state, which can help reduce heterogeneity. Several candidate genes were applied in a human ovarian carcinoma collection to determine the EMT status by using methods such as quantitative PCR. We conclude that this EMT spectrum library can contribute to the identification of molecular features that serve as predictive diagnostic markers or therapeutic targets associated with EMT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3437. doi:10.1158/1538-7445.AM2011-3437
The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice
Authors: Elizabeth C. Townsend, Mark A. Murakami, Alexandra Christodoulou, Amanda L. Christie, Johannes Köster, Tiffany A. DeSouza, Elizabeth A. Morgan, Scott P. Kallgren, Huiyun Liu, Shuo-Chieh Wu, Olivia Plana, Joan Montero, Kristen E. Stevenson, Prakash Rao, Raga Vadhi, Michael Andreeff, Philippe Armand, Karen K. Ballen, Patrizia Barzaghi-Rinaudo, Sarah Cahill, Rachael A. Clark, Vesselina G. Cooke, Matthew S. Davids, Daniel J. DeAngelo, David M. Dorfman, Hilary Eaton, Benjamin L. Ebert, Julia Etchin, Brant Firestone, David C. Fisher, Arnold S. Freedman, Ilene A. Galinsky, Hui Gao, Jacqueline S. Garcia, Francine Garnache-Ottou, Timothy A. Graubert, Alejandro Gutierrez, Ensar Halilovic, Marian H. Harris, Zachary T. Herbert, Steven M. Horwitz, Giorgio Inghirami, Andrew M. Intlekofer, Moriko Ito, Shai Izraeli, Eric D. Jacobsen, Caron A. Jacobson, Sébastien Jeay, Irmela Jeremias, Michelle A. Kelliher, Raphael Koch, Marina Konopleva, Nadja Kopp, Steven M. Kornblau, Andrew L. Kung, Thomas S. Kupper, Nicole R. LeBoeuf, Ann S. LaCasce, Emma Lees, Loretta S. Li, A. Thomas Look, Masato Murakami, Markus Muschen, Donna Neuberg, Samuel Y. Ng, Oreofe O. Odejide, Stuart H. Orkin, Rachel R. Paquette, Andrew E. Place, Justine E. Roderick, Jeremy A. Ryan, Stephen E. Sallan, Brent Shoji, Lewis B. Silverman, Robert J. Soiffer, David P. Steensma, Kimberly Stegmaier, Richard M. Stone, Jerome Tamburini, Aaron R. Thorner, Paul van Hummelen, Martha Wadleigh, Marion Wiesmann, Andrew P. Weng, Jens U. Wuerthner, David A. Williams, Bruce M. Wollison, Andrew A. Lane, Anthony Letai, Monica M. Bertagnolli, Jerome Ritz, Myles Brown, Henry Long, Jon C. Aster, Margaret A. Shipp, James D. Griffin, David M. Weinstock
Journal: Cancer Cell (2016)
Erlotinib as First-Line Treatment for Patients with Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Phase Iiib Study
Authors: B. Zaric, B. Perin, M. Cekic, M. Rancic, V. Kovcin, Z. Andric, Z.H. Murtezani, D. Jovanovic, M. Velinovic, M. Markovic
Journal: Annals of Oncology (2015)
Have we found how to identify candidates for thrombolysis among normotensive patients with acute pulmonary embolism?
Authors: Piotr Pruszczyk
Journal: European Respiratory Journal (2016)

Acute pulmonary embolism (PE) results in a wide spectrum of haemodynamic compromise and in hospital PE-related mortality. It is generally accepted that haemodynamically unstable patients with systolic blood pressure <90 mmHg at presentation form a high-risk group (∼5% of all PE patients), with short-term mortality exceeding 15%. They require urgent primary revascularisation performed mostly with systemic thrombolysis. In contrast, only a few patients without shock or hypotension are at risk of an adverse early outcome [1]. Thus, clinically stable, non-high risk patients require further risk stratification in order to optimise their management, including selection of the therapeutic strategy and the duration of the hospitalisation. Current European Society of Cardiology (ESC) guidelines introduced the simplified Pulmonary Embolism Severity Index (sPESI) [2], used for identification of the low-risk group [1]. Patients with sPESI of 0 are at the "benign" end of the risk spectrum; mostly, they have uncomplicated clinical courses and are candidates for very short hospitalisation or can even be managed as outpatients without any further risk stratification. If prospectively validated, modified FAST could identify normotensive patients with PE for primary thrombolysis <http://ow.ly/WTZIs>
A novel HER2 inhibitor TAK-285 overcomes trastuzumab resistance of HER2-over-expressing breast cancer.
Authors: A Hayashi, T Tamura, T Yusa, S Takagi, Y Ohta
Journal: Cancer Research (2009)

Abstract Abstract #3143 Background: The anti-HER2 antibody trastuzumab has been proven highly effective in the treatment of HER2-expressing breast cancers clinically. However, the continuous administration often leads to drug resistance, the mechanism of which is not well understood. Here we present a new mechanism for trastuzumab-resistance. We also show TAK-285, a novel small molecule HER2/EGFR kinase inhibitor under clinical evaluation, overcomes the resistance to trastuzumab.&amp;#x2028; Methods: A trastuzumab-resistant sub-clone (BT-474TR) of the HER2-positive human breast cancer line, BT-474, was established in house by serial passage in the presence of 5 μg/mL trastuzumab for over 5 months. Gene expression profiles of the clones were assessed using Affymetrix HG-U133 plus 2.0 human gene arrays and confirmed by real-time PCR. Target genes were depleted by siRNA-mediated knockdown and confirmed by real time-PCR and immunoblot. Effects on cell growth were assessed by the CellTiter-Glo luminescent cell viability assay (Promega).&amp;#x2028; Results: BT-474TR cells exhibited modified expression of several genes including cofilin, compared to the parental BT-474 cells. Although immunoblotting using anti-cofilin antibody revealed no clear change in protein level, BT-474TR displayed significant increase in phosphorylation of cofilin. Gene-specific knockdown of cofilin-1 led to re-sensitization of BT-474TR to trastuzumab, though the cofilin-2 knockdown did not. Likewise, knockdown of either LIMK1 or PAK1, known to regulate cofilin-phosphorylation, resulted in similar re-sensitization of BT-474TR to trastuzumab. BT-474TR also exhibited increase in phosphorylation of both LIMK1 and PAK1. TAK-285 showed almost equivalent inhibitory activity against both BT-474 and BT-474TR proliferation in cell culture and in xenograft study, while trastuzumab did not affect the proliferation of BT-474TR in either condition&amp;#x2028; Conclusions: These data suggest that activation of cofilin signaling pathway is a probable mechanism of trastuzumab resistance. PAK1/LIMK1/cofilin-1 inhibitors might therefore be useful in preventing or reversing trastuzumab resistance. The phosphorylation status of PAK1/LIMK1/cofilin might also serve as a biomarker of Trastuzumab-sensitivity. Moreover a novel HER2 inhibitor, TAK-285, might show benefit in the treatment of trastuzumab-resistant HER2-expressing breast cancers. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3143.
Abstract 1452: mTOR inhibition radiosensitizes bladder cancer tumor cells <i>in vitro</i> and <i>in vivo</i>: A novel strategy for treatment
Authors: Roland Nassim, Jose Mansure, Simone Chevalier, Fabio Cury, William Parker, Stephen Davis, Joice Cury, Wassiim Kassouf
Journal: Cancer Research (2012)

Abstract Background: Radiation therapy for invasive bladder cancer allows for organ preservation but systemic toxicity and local control remain problematic. As such, there is a need to increase radiosensitization of tumor cells to improve efficacy. The aim of this study was to investigate if mTOR (mammalian target of rapamycin), a downstream kinase of the PI3K/Akt survival pathway, may be a target for combined bladder cancer therapy. Methods: Clonogenic assays were performed using 6 bladder cancer cell lines in order to address the effects of ionizing radiation (IR) on growth, when tested alone and in combination with RAD001, a potent mTOR inhibitor. Cell cycle analysis was performed using flow cytometry. In the in vivo study, nude mice were subcutaneously injected with KU7 and 253J-BV cells. Treatment with RAD001 (1.5 mg/kg, daily), fractionated IR (total 9 Gy), and the combination of RAD001 and IR was followed over 4 weeks. Tumor growth kinetics was measured and tumor weight at the experimental endpoint. Results: In vitro, a significant decrease in colony formation was observed in the combined treatment when compared to RAD001 or radiation alone (p&amp;lt;0.05) in all cell lines. A G0/G1 as well as a significant increase in G2 arrest was observed in the combined treatment compared to either treatment alone. Changes in the levels of Cyclin D1, p27 and p21 correlated with the observed changes in the cell cycle. Moreover, IR rapidly activated AKT whereas RAD001 effectively inhibited the mTOR downstream signaling as shown by the inhibition of the phosphorylation of S6. Furthermore, autophagy was induced following the treatment with RAD001 and in combination as indicated by the conversion of LC3-I to LC3-II, a protein marker for autophagy. Our in vivo data confirmed our in vitro data, wherein a significant decrease in tumor weight was observed in the combined treatment arm (90% decrease, p&amp;lt;0.001) compared to either treatment alone (60% decrease for RAD001, p&amp;lt;0.05; 77% decrease for IR, p&amp;lt;0.05). These findings point to additive and possibly synergistic beneficial effects of the combined on bladder cancer. Conclusions: The inhibition of mTOR signaling appears promising as a therapeutic modality for bladder cancer, especially in the context of combination with radiation therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1452. doi:1538-7445.AM2012-1452
Rotavirus Vaccines — Balancing Intussusception Risks and Health Benefits
Authors: Roger I. Glass, Umesh D. Parashar
Journal: New England Journal of Medicine (2014)

In January 2006, the Journal published two landmark articles reporting the safety and efficacy of two different vaccines — RotaTeq (Merck), a pentavalent vaccine (RV5),1 and Rotarix (GlaxoSmithKline), a monovalent vaccine (RV1)2 — to prevent rotavirus, the most common cause of severe childhood diarrhea worldwide and of deaths from diarrhea in low-income countries. Each trial enrolled more than 60,000 infants to determine whether these live oral vaccines caused intussusception, the rare complication that in 1999 forced the withdrawal of the first licensed rotavirus vaccine, RotaShield (Wyeth Lederle), less than a year after it was recommended for routine immunization of U.S. . . .
Abstract B37: A DNA polymerase beta gene harboring the colon cancer-associated G231D variant increases the sensitivity of cells to chemotherapeutic agents and induces cellular transformation
Authors: Antonia A. Nemec, Katherine A. Donigan, Drew L. Murphy, Joachim Jaeger, Joann B. Sweasy
Journal: Cancer Research (2011)

Abstract Rapidly advancing technology has resulted in the generation of the genomic sequences of several human tumors. These studies have revealed that tumors are heterogeneous and contain many mutations, supporting the mutator phenotype hypothesis of human cancer. Drivers of carcinogenesis are thought to be mutated genes that occur at high frequencies in large numbers of human tumors. However, functional characterization of many of the somatic mutations is lacking. We have identified several mutations of the DNA polymerase beta (POLB) gene in human colorectal cancer. Pol beta is the main polymerase involved in the base excision repair (BER) pathway and aberrant expression of Pol beta has been linked to a cancerous phenotype. In this study, we characterized the homozygous G231D mutation that was identified in a Stage 3 colorectal tumor. We have demonstrated that its expression in epithelial cells induced cellular transformation and increased the rate of proliferation. The transformed phenotype persisted in the cells even once the expression of G231D was extinguished. These data indicated that the expression of G231D caused an inheritable change; this change is most likely due to an increase in genomic instability caused by unfilled gaps proceeding through replication. Expression of G231D was insufficient to rescue Pol beta-deficient cells treated with chemotherapeutic agents suggesting that these agents may be effectively used to treat tumors harboring this mutation. Biochemical analysis of G231D revealed that it was 100-fold slower than WT Pol beta as determined by pre-steady state kinetics. The slow rate was a result of the decreased binding affinity of nucleotides by G231D. Residue 231 of Pol beta lies in close proximity to the template strand of the DNA. Molecular modeling showed that the change from a glycine to a negatively charged amino acid caused a repulsion between the template and residue 231 leading to the disruption of the dNTP binding pocket. Together, these data indicate that a person harboring the G231D Pol beta mutation may have an increased risk of cancer. Moreover, the altered sensitivity to chemotherapeutic drugs in cells carrying the G231D variant may have further implications in how to better improve the therapeutic outcome in patients with this mutation and supports the need for personalized cancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B37.
Abstract 1158: Clinical significance of p53 codon 72 polymorphism in hepatocellular carcinomas
Authors: Leona N. Council, Chandrakumar Shanmugam, Venkat R. Katkoori, Meenakshi Sthanam, Alex Hanna, Upender Manne
Journal: Cancer Research (2012)

Abstract Purpose: We recently demonstrated that, in colorectal carcinomas, the presence of a single nucleotide polymorphism (SNP) at codon 72 of the p53 gene was associated with a poor outcome for African American (AA) patients. Since such studies have not been performed for hepatocellular carcinomas (HCCs), we determined, for AAs and non-Hispanic Caucasians (NHCAs), the prevalence of p53 SNPs in codon 72 of HCCs and its association with adverse clinical and pathological features. Methods: DNA samples extracted from 48 archived, formalin-fixed, paraffin-embedded HCC tissues and from matching, uninvolved liver were analyzed for the mutational status of the p53 gene by sequencing exon 4 through exon 9. The results obtained were correlated with the demographic and clinicopathological features of the HCCs and with patient survival. Results: Overall, the frequency of missense point mutations in p53 of HCCs was low (6 of 48, 12%). Missense point mutations, however, were common in NHCAs (4 of 6). Genotyping of codon 72 of p53 demonstrated that the Arg/Arg phenotype had the highest frequency (27 of 48; 56%), followed by Arg/Pro (16 of 48; 33%) and Pro/Pro (5 of 48; 11%). Four of five patients with the Pro/Pro phenotype were AAs (χ2 p = 0.028). Of these, three of the four tumors had high proliferative (ki67) indices; two of the four were poorly differentiated. In contrast, poorly differentiated tumors were few in Arg/Arg (1 of 27, 4%) and Arg/Pro (1 of 16; 6%) (χ2p = 0.016) phenotype groups. For all patients, the Pro/Pro phenotype were associated with hepatitis C virus (HCV) infection (χ2 p = 0.048). Furthermore, AAs with the Pro/Pro phenotype had lower median survival (15.5 months) compared to those with the Arg/Arg and Arg/Pro (32 months) phenotypes. NHCA patients with missense point mutations had shorter median survival (22.5 months) relative to NHCAs with wild-type p53 (34 months).Conclusion: These preliminary findings suggest that, in AAs, the Pro/Pro phenotype at codon 72 of the p53 gene is associated with aggressive tumor behavior, shorter median survival, and HCV infection. These pilot studies were supported jointly by a Charles Barkley Award through the UAB Minority Health Disparities Research Center (MHRC) and the UAB Center for Clinical and Translational Science (5UL1 RR025777-04). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1158. doi:1538-7445.AM2012-1158