tbuckley/cabot-search huggingface dataset:
Abstract 4711: PRMT5 selective inhibitor enhances therapeutic efficacy of cisplatin in lung adenocarcinoma cells
Authors: Khuloud Bajbouj, Rakhee Ramakrishnan, Ahmed M.H.Ihmaid, Suhaib Al Haj Ali, Abdulla Alalool, Reem Abdullah, Maha Saber-Ayad, Qutayba Hamid
Journal: Cancer Research (2019)

Abstract Background: Lung cancer is the most common cancer globally, with an estimate of more than 2 million new cases every year. Protein arginine methyltransferase 5 (PRMT5) is an enzyme that is identified to be involved in multiple cellular events, including gene expression regulation transcriptional regulation and cell division. It has been shown that PRMT5 is highly expressed in cancers including lung adenocarcinoma, hepatocellular carcinoma, and melanoma, raising evidence that PRMT5 might be involved in tumorigenesis. The aim of this study is to examine the potential selective anti-neoplastic activity of AMI-1 and cisplatin on lung adenocarcinoma. Experimental methods: The effect of AMI-1 and subsequent PRMT5 activity inhibition on lung adenocarcinoma (A549 cell line) behavior with the standard chemotherapeutic agent, cisplatin was assessed, by measuring cell viability using MTT assay, PMRT5/β-catenin protein levels via Western Blotting, the extent of cell migration through wound healing assay, and survival of cancer cells by performing cell cycle progression and Annexin-V staining assays along with both drugs combination potential toxicity that was evaluated in human bronchial epithelial cells (HBEC). Results and Discussions: Combination treatment with 10 µM AMI-1 and IC50 of Cisplatin (23.4 µM) significantly reduced viable cell percentages at 24 and 48 hours. Treatment with both drugs at 48 hours led to a decreased cells migration rate. G2/M arrest in A549 cells was evident at 24 hours of AMI-1 addition, which was reinforced after drugs combined treatment. Furthermore, 48 hours of both drug administration hindered the ability of A549 cells to recycle again as they G1 occupying cells percentage was increased after 48 hours of combination treatment. There was a minor cell death induction after 48 hours of treatment with both drugs. Western blot analysis showed that there was no evidence change in total PRMT5 and β-catenin protein levels. Nevertheless, there was a reduction in demethylation Histone 4, a PRMT5- downstream target, after 48 hours treatment with AMI-1 alone or in combination with Cisplatin. Interestingly, as combination approach increased anti-survival effect on lung cancer cells, it exhibited cyto-protective abilities on normal epithelial cells. Conclusion: This study shows a novel selective antitumor activity of AMI-1 and cisplatin in adenocarcinoma cells. Citation Format: Khuloud Bajbouj, Rakhee Ramakrishnan, Ahmed M.H.Ihmaid, Suhaib Al Haj Ali, Abdulla Alalool, Reem Abdullah, Maha Saber-Ayad, Qutayba Hamid. PRMT5 selective inhibitor enhances therapeutic efficacy of cisplatin in lung adenocarcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4711.
Abstract 14755: Progressive Ventricular Dilatation Despite Cardiac Resynchronization Therapy (CRT): Baseline Predictors and Associated Clinical Outcomes
Authors: Daniel J Friedman, Gaurav A Upadhyay, Mary Orencole, Kimberly A Parks, Stephanie A Moore, Michael H Picard, Jeremy N Ruskin, Jagmeet P Singh, E. K Heist
Journal: Circulation (2012)

Introduction While echocardiographic evidence of reverse remodeling has been associated with improved outcomes in CRT, causes of and outcomes associated with progressive remodeling after CRT remain...
Abstract 11005: The Revision of American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Provides Clinical Benefit in Women With Out-of-hospital Cardiac Arrest Undergoing Prehospital Defibrillation
Authors: Sunao Kojima, Kunihiko Matsui, Hisao Ogawa, Naohiro Yonemoto, Hiroshi Nonogi, Ken Nagao, Takeshi Kimura
Journal: Circulation (2012)

Backgrounds: Women are older and have a lower incidence of ventricular fibrillation/pulseless ventricular tachycardia than men when rescuers encounter a victim of sudden adult cardiac arrest. We as...
Increasing Evidence for and a Word of Caution About an Association Between Cancer and Congenital Heart Disease
Authors: Michelle Gurvitz
Journal: JAMA Network Open (2019)

Zacharias Mandalenakis, MD, PhD, FESC; Christina Karazisi, MD; Kristofer Skoglund, PhD; Annika Rosengren, PhD; Georgios Lappas, MSc; Peter Eriksson, PhD; Mikael Dellborg, PhD
Abstract 4227: Salvage genetic testing on buccal swab samples using liquid <i>in situ</i> amplification identifies genetic mutations from previous test failures
Authors: Glen J. Weiss, Andrew Ford, Charmaine Brown, Elizabeth Caver, Matthew Vallejo, Claribel Adeyemi, Forrest Collins, Chen-Hsiung Yeh
Journal: Cancer Research (2019)

Abstract Background: NCCN guidelines version 2.2019 address BRCA1/2 testing for men with a personal history of prostate cancer limited to Gleason ≥7 and specific family history features. Inherited genetic mutations have been identified in up to 12% of metastatic prostate cancer, primarily in DNA repair genes. Here we report liquid in situ amplification (LISA) technique followed by hereditary testing on buccal swab samples that had previously failed to yield a genetic testing result. Methods: Previously failed buccal swab samples from another CLIA-certified laboratory were re-prepared using LISA. Qubit quantification following LISA revealed goodDNA concentrations even for these poor-quality swab samples ranging from 5 to 70 ng/uL, which is sufficient for next-generation sequencing analysis (NGS). Coding regions of ATM, BRCA1, BRCA2, CHEK2, PALB2, and RAD51D genes were amplified by a panel of specific primer pools followed by massively parallel sequencing for the identification of germline mutations. Minimal sequencing coverage was set as 50X, and pathogenic, likely pathogenic, and variants of unknown significance (VUS) were classified and reported. Results: Buccal swab samples from 29 men with at least intermediate-risk prostate cancer were received as low-yield, low-quality DNA (n=12), pre-cut swabs in preservation solution (n=6), and aged swab samples (n=11). LISA and subsequent NGS testing was able to salvage results for 24/29 (82.8%) (failed samples included 4 aged swab and 1 pre-cut swab). 1 patient had a pathogenic BRCA1 mutation (c.4309delT) and 3 patients had VUS (BRCA1 c.4776C&amp;gt;G, BRCA1 c.1846_1848delTCT, and RAD51D c.268G&amp;gt;A). The remaining 20/29 (69.0%) samples have either benign or likely benign variants. Conclusions: LISA applied to these previously failed samples was able to salvage results for over 80% of cases, including the identification of a pathogenic BRCA1 mutation which led cascade hereditary testing for immediate family members. It also provided confirmation for nearly 70% of cases about the absence of hereditary risk for the genes on the panel. Citation Format: Glen J. Weiss, Andrew Ford, Charmaine Brown, Elizabeth Caver, Matthew Vallejo, Claribel Adeyemi, Forrest Collins, Chen-Hsiung Yeh. Salvage genetic testing on buccal swab samples using liquid in situ amplification identifies genetic mutations from previous test failures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4227.
Young endoscopists involvement in national endoscopy societies: the SPEDY example!
Authors: Tiago Cúrdia Gonçalves, Filipe Vilas Boas, Catarina Graça-Rodrigues, Cátia Leitão, Inês Cunha, Paulo Massinha, Richard Azevedo, Rita Barosa, Rui Morais, Sofia Mendes
Journal: Endoscopy (2019)

It was in June 2018, during the Portuguese Digestive Week, that the Portuguese Society of Digestive Endoscopy (SPED) promoted the kick-off meeting of the Young Endoscopists Committee (SPEDY – SPED Young), a working group formed by 4 trainees and 4 Gastroenterology specialists under 35 years of age. It was during this first intensive brainstorming session that the first initiatives and projects were drafted.
Abstract 4574: Combining multimodal biomarkers as an immunogram to guide immunotherapy use: A proof of concept
Authors: Thomas Sbarrato, Lucie Sudre, Laurent Vanhille, Pernelle Outters, Mihaela Angelova, Bernhard Mlecnik, Angela Vasaturo, Gabriela Bindea, Tessa Fredriksen, Lucie Lafontaine, Daniela Bruni, Jérôme Galon, Jacques Fieschi
Journal: Cancer Research (2019)

Abstract Our recent understanding of the immune contribution to fight cancer has deeply modified the standard of care of cancer patients. As an example, immunotherapies by immune checkpoint inhibitors (ICI) anti-PD1/PDL1 are now approved in several cancer indications, such as Non-Small Cell Lung Cancers or melanoma. However, ICI are less effective for other high incidence indications like colorectal cancer (CRC). Here, the heterogeneity as well as the relatively low degree of patient response to those immunotherapies have highlighted that factors, present in the tumor microenvironment (TME), may limit or boost the efficacy of treatment. In this context, the comprehensive assessment of these factors could be key to stratify patients and allow the selection of the optimal treatment. In order to help clinical researchers and biopharmaceutical companies to measure the immune contribution to drug efficacy, HalioDx has developed the Cancer Immunogram, a solution based on Blank CU et al. Science (2016). Our multi-parameter approach encompassing a unique range of immune scoring assays is based on the analysis and the understanding of the immune contexture of tumors and offers a personalized and dynamic “fingerprint” of tumor-immune system interaction. Here, we provide a Proof of Concept for the Cancer Immunogram in the context of CRC by combining the following technologies and biomarkers: Tumor Mutational Burden (Tumour foreignness), DNA mismatch-repair deficiency (MSI), TCR Sequencing (T Cell Clonality), Immunoscore® Colon (Immune Cell Infiltration), Immunosign® (Tumor Sensitivity to Immune Effectors), Halioseek® PDL1/CD8, Brightplex T-Cell Exhaustion Panel (Immune Checkpoints) and Brightplex MDSC Panel and Treg detection (Immune Suppression). We show that the Cancer Immunogram allows to identify patient specific patterns which might improve the prediction of the response to therapy. We believe that the Cancer Immunogram will help researchers and clinicians to personalise treatments in order to improve patients’ outcomes and response to cancer treatment. Citation Format: Thomas Sbarrato, Lucie Sudre, Laurent Vanhille, Pernelle Outters, Mihaela Angelova, Bernhard Mlecnik, Angela Vasaturo, Gabriela Bindea, Tessa Fredriksen, Lucie Lafontaine, Daniela Bruni, Jérôme Galon, Jacques Fieschi. Combining multimodal biomarkers as an immunogram to guide immunotherapy use: A proof of concept [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4574.
Abstract 17976: Functional Correlates and Prognostic Value of Coronary Flow Velocity Reserve by Vasodilator Stress Echocardiography in Hypertrophic Cardiomyopathy
Authors: Quirino Ciampi, Lauro Cortigiani, Milorad Tesic, Branko Beleslin, Fausto Rigo, Ana Djorkievic-Dikic, Eugenio Picano
Journal: Circulation (2016)

Background: A reduction in coronary flow velocity reserve (CFVR) n is a major mechanism for ischemia in hypertrophic cardiomyopathy (HCM). Hypothesis: To assess the functional correlates and progno...
Abstract 4589: SRC drives invasion of luminal, but not basal, bladder cancer
Authors: Bryan Wehrenberg, Andrea Ochoa, Woonyoung Choi, David McConkey
Journal: Cancer Research (2019)

Abstract Preventing progression from non-muscle invasive to muscle invasive bladder cancer (BC) is a major clinical priority. This transition is defined by tumor invasion through the bladder epithelium basement membrane into the lamina propria and muscle wall. Inhibition of SRC, a pro-invasion, non-receptor tyrosine kinase that signals as part of a complex with Focal Adhesion Kinase (FAK), may prevent BC progression. We hypothesize that SRC inhibition will disrupt migration and invasion of BC cells. Using The Cancer Genome Atlas (TCGA) mRNA expression data of human bladder tumors, we generated a classifier to subtype tumors as either “luminal” or “basal” and compared SRC expression between the groups. We then sequenced a panel of 30 bladder cancer cell lines. Each cell line was given a subtype call based on our luminal- basal classifier, and levels of SRC mRNA expression were examined. To determine the impact of SRC inhibition on luminal and basal subtypes, we exposed BC cell lines to the SRC-Family Kinase inhibitor, AZD0530. The impact of SRC inhibition on proliferation was measured by MTT assay. Transwell assays were used to examine the effect of SRC inhibition on migration, collagen invasion, and Matrigel invasion. Phosphorylation of SRC downstream targets after AZD0530 treatment was assessed by western blot. The role of SRC target and signaling partner FAK in migration was determined by siRNA knockdown and transwell assay. Luminal human bladder tumors had significantly greater SRC mRNA expression than basal tumors (p&amp;lt;0.001). SRC expression was also enriched in luminal BC cell lines (p&amp;lt;0.05). Inhibiting SRC with AZD0530 had minimal impact on proliferation with no subtype specific effects. Migration and collagen invasion of all luminal cell lines was significantly reduced by AZD0530 treatment (p&amp;lt;0.05). The majority of luminal models capable of invading Matrigel were also inhibited by AZD0530. In contrast, invasion and migration of the majority of basal cell lines was not significantly reduced by SRC inhibition, and was significantly increased in several cases (p&amp;lt;0.05). Both luminal and basal models exhibited reduced phosphorylation of SRC downstream targets when exposed with AZD0530. siRNA knockdown of FAK had no impact on migration in a basal cell line. Enrichment of SRC expression in luminal tumors and significant reductions in luminal cell line invasion after AZD0530 treatment suggest SRC promotes invasion in luminal BC. These results suggest AZD0530, and other SRC-Family Kinase inhibitors, could serve as effective anti-progression agents in luminal BC. Citation Format: Bryan Wehrenberg, Andrea Ochoa, Woonyoung Choi, David McConkey. SRC drives invasion of luminal, but not basal, bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4589.
Adipose-derived cellular and cell-derived regenerative therapies in dermatology and aesthetic rejuvenation
Authors: Annie Suh, Anthony Pham, Mikel Jean Cress, Thais Pincelli, Sarvam P. TerKonda, Alison J. Bruce, Abba C. Zubair, Joy Wolfram, Shane A. Shapiro
Journal: Ageing Research Reviews (2019)
Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
Authors: Elom K. Aglago, Inge Huybrechts, Neil Murphy, Corinne Casagrande, Genevieve Nicolas, Tobias Pischon, Veronika Fedirko, Gianluca Severi, Marie-Christine Boutron-Ruault, Agnès Fournier, Verena Katzke, Tilman Kühn, Anja Olsen, Anne Tjønneland, Christina C. Dahm, Kim Overvad, Cristina Lasheras, Antonio Agudo, Maria-Jose Sánchez, Pilar Amiano, José Maria Huerta, Eva Ardanaz, Aurora Perez-Cornago, Antonia Trichopoulou, Anna Karakatsani, Georgia Martimianaki, Domenico Palli, Valeria Pala, Rosario Tumino, Alessio Naccarati, Salvatore Panico, Bas Bueno-de-Mesquita, Anne May, Jeroen W.G. Derksen, Sophie Hellstrand, Bodil Ohlsson, Maria Wennberg, Bethany Van Guelpen, Guri Skeie, Magritt Brustad, Elisabete Weiderpass, Amanda J. Cross, Heather Ward, Elio Riboli, Teresa Norat, Veronique Chajes, Marc J. Gunter
Journal: Clinical Gastroenterology and Hepatology (2019)
Triplet chemotherapy plus cetuximab as first-line treatment in RAS wild-type metastatic colorectal carcinoma patients
Authors: E. Samalin, T. Mazard, E. Assenat, M. Rouyer, C. De la Fouchardière, R. Guimbaud, D. Smith, F. Portales, M. Ychou, C. Fiess, H. de Forges, E. Lopez-Crapez, S. Thézenas
Journal: Annals of Oncology (2019)
Compression therapy of both hands is safely applicable for the prevention of oxaliplatin-induced neuropathy
Authors: K. Kawakami, Y. Koyama, M. Morioka, Y. Tobaru, Y. Sakura, M. Fukumoto, A. Nagamine, K. Hattori, I. Taira, N. Shimada, E. Okuno, S. Tsuyuki, A. Kanazawa
Journal: Annals of Oncology (2019)
Percutaneous transgastric endoscopic myotomy for upper esophageal spastic stricture
Authors: Xiang-bin Xing, Yi Cui, Zhen-zi Huang, Yao He, Ying-lian Xiao, Zhi-rong Zeng, Min-hu Chen
Journal: Endoscopy (2019)

Various studies have reported the safety and efficacy of peroral endoscopic myotomy (POEM) for the treatment of esophageal motility spastic disorders, including type III esophageal achalasia, jackhammer esophagus, and distal esophageal spasm [1] [2] [3]. Moreover, there is increasing evidence that the efficacy of POEM for the treatment of nonachalasia esophageal spastic diseases is comparable to laparoscopic Heller myotomy [4] [5]. However, the application of POEM for the treatment of upper esophageal spasm located close to the esophageal introitus is limited, because the POEM procedure involves mucosal incision and submucoal tunneling usually starting at over 5 cm from the oral side of the spastic segment. Here, we describe the case of a patient with upper esophageal spastic stricture, which was successfully treated with percutaneous transgastric endoscopic myotomy (PTEM), a new approach enabling submucoal tunneling myotomy from the anal side of the stricture.
Abstract 3600: Antibiotics suppress growth of breast cancer cells and synergize cytotoxicity of 2-Deoxy-D-glucose: Treating cancer like an infection
Authors: Xianpeng Jiang, Amanda Benoit, Toby Jiang, Robert L. Elliott
Journal: Cancer Research (2019)

Abstract Mitochondria evolved from free-living bacteria via endocytosis within a eukaryotic host cell millions of year ago. We hypothesized that antibiotics might damage mitochondria of human cancer cells and lead to oxidative damage of cancer cells. We examined three classes of antibiotics, azithromycin, doxycycline and ciprofloxacin in the human breast cancer cell lines MCF-7 and MDA-MB-231. The combination of antibiotics and the anti-glycolytic agent, 2-Deoxy-D-glucose (2-DG) was also tested in the cells. Cell growth was measured by MTT [3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide] assay. Mitochondrial membrane potential and reactive oxygen species were tested by fluorescent microscopy. Gene expression and DNA damage were measured by real time polymerase chain reaction (qPCR) and ELISA. All antibiotics suppressed mitochondrial membrane potential and growth of MCF-7 and MDA-MB-231 cells in a dose dependent pattern. The IC50of all three antibiotics were less than clinical patient’s maximum serum concentration (Cmax) or concentrations in tissues. The IC50 of ciprofloxacin in MCF-7 (1.25-2.5µM) and MDA-MB-231 (2.5-3.5µM) are much lower than the Cmax 7.7µM while patients take 500mg every 12 hours orally in clinical practice. The DNA oxidative damage metabolite, 8-OHdG, in the media was significantly increased after cancer cells were cultured in the media containing antibiotics for 24 hours. Three antibiotics upregulated gene expression of glycolytic enzymes including hexokinase 2(HK2), phosphofructokinase 1 (PFKM) and pyruvate kinase muscle isozyme M2 (PKM2), lactate dehydrogenase A (LDHA), and glucose transporters 1 (SLC2A1) and 3 (SLC2A3). The antibiotics increased uptake of 3[H]-2-DG of MCF-7 and MDA-MB-231. These results suggest that cancer cells increase aerobic glycolysis to produce ATP after antibiotic treatment. Thus, we combined 2-DG and antibiotics to treat the breast cancer cell lines. The antibiotics and 2-DG synergistically inhibited growth of the breast cancer cells. MDA-MB-231, a chemo-drug resistant cell line, has similar sensitivity to antibiotics and 2-DG as the MCF-7, a drug sensitive cell line. In summary, azithromycin, doxycycline and ciprofloxacin suppress the growth of breast cancer cells and augment the cytotoxicity of 2-DG to breast cancer cells. These findings suggest we can treat cancer with antibiotics similar to treating an infection. Citation Format: Xianpeng Jiang, Amanda Benoit, Toby Jiang, Robert L. Elliott. Antibiotics suppress growth of breast cancer cells and synergize cytotoxicity of 2-Deoxy-D-glucose: Treating cancer like an infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3600.
Abstract 1892: Dysfunction of resident memory CD8+ T cells facilitates breast cancer lung metastasis
Authors: Erwei Song, Yue Xing, Shicheng Su
Journal: Cancer Research (2019)

Abstract Resident memory T cells (TRM) are generally intraepithelially located and manifesting defence potential in diverse existing virus infection models. However, their roles in cancer development, especially metastasis, are poorly understood. Herein, by using a murine model orthotopically inoculated with 4T1 mammary carcinoma cells, we demonstrated the dynamic distribution and functional changes of lung TRM during the formation of lung pre-metastatic niche. Peri-alveolar accumulation of CD8+ T cells, which constitutively express early activation marker CD69 and epithelial-resident marker CD103, is identified. These draining lymph nodes originated and tumor-specific TRM cells, with high expression of IFN-γ and other cytotoxic cytokines, patrol along blood stream and infiltrate in the pre-metastatic lung. IFN-γ coverts alveolar macrophages in the pre-metastatic lung into a immunosuppressive phenotype with high expression of IDO1, which reciprocally compromises the anti-tumor effects of TRM. In conclusion, our study revealed the alteration of lung TRM during the process of metastasis and its interaction with lung pre-metastatic niche, indicating that by finding possible approaches to enhancing TRM function or strengthening local defenses could decrease breast cancer lung-tropic metastasis. Citation Format: Erwei Song, Yue Xing, Shicheng Su. Dysfunction of resident memory CD8+ T cells facilitates breast cancer lung metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1892.