tbuckley/cabot-search huggingface dataset:
Ai-lncRNA EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions in human cancer
Authors: Shouping Xu, Peiyuan Wang, Jian Zhang, Hao Wu, Shiyao Sui, Jinfeng Zhang, Qin Wang, Kun Qiao, Weiwei Yang, Hongbiao Xu, Da Pang
Journal: Molecular Cancer (2019)

The biology function of antisense intronic long noncoding RNA (Ai-lncRNA) is still unknown. Meanwhile, cancer patients with paclitaxel resistance have limited therapeutic options in the clinic. However, the potential involvement of Ai-lncRNA in paclitaxel sensitivity remains unclear in human cancer. Whole transcriptome sequencing of 33 breast specimens was performed to identify Ai-lncRNA EGOT. Next, the role of EGOT in regulation of paclitaxel sensitivity was investigated. Moreover, the mechanism of EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions was investigated in detail. Furthermore, upstream transcriptional regulation of EGOT expression was also investigated by co-immunoprecipitation and chromatin immunoprecipitation. Finally, clinical breast specimens in our cohort, TCGA and ICGC were applied to validate the role of EGOT in enhancing of paclitaxel sensitivity. EGOT enhances autophagosome accumulation via the up-regulation of ITPR1 expression, thereby sensitizing cells to paclitaxel toxicity. Mechanistically, on one hand, EGOT upregulates ITPR1 levels via formation of a pre-ITPR1/EGOT dsRNA that induces pre-ITPR1 accumulation to increase ITPR1 protein expression in cis. On the other hand, EGOT recruits hnRNPH1 to enhance the alternative splicing of pre-ITPR1 in trans via two binding motifs in EGOT segment 2 (324–645 nucleotides) in exon 1. Moreover, EGOT is transcriptionally regulated by stress conditions. Finally, EGOT expression enhances paclitaxel sensitivity via assessment of cancer specimens. These findings broaden comprehensive understanding of the biology function of Ai-lncRNAs. Proper regulation of EGOT may be a novel synergistic strategy for enhancing paclitaxel sensitivity in cancer therapy.
THU-070-The nuclear factor TCF20 regulates the severity of liver fibrosis in mice
Authors: Bernat Cordoba-Jover, Jordi Ribera, Irene Portoles, Silvia Sandalinas, Felix Elortza, Anna Pujol, Wladimiro Jiménez, Manuel Morales-Ruiz
Journal: Journal of Hepatology (2019)
Memorial Sloan Kettering Cancer Center tightens conflict of interest rules after scandals
Authors: Owen Dyer
Journal: BMJ (2019)

One of America’s most famous hospitals, Memorial Sloan Kettering Cancer Center (MSK) in New York, will impose tight new rules on the corporate ties of doctors and executives after six months in which troubling conflicts of interest brought the institution a string of bad headlines.

An independent review by the law firm Debevoise and Plimpton found “a number of instances of serious noncompliance with MSK’s conflict of interest policies,” and concluded that plans to manage executive conflicts of interest were not implemented “because it was felt to be unnecessary.”

The hospital’s troubles began last September when its physician-in-chief Jose Baselga became the subject of a joint report by the New York Times and ProPublica , alleging that he had published dozens of …
Induction Therapy with Everolimus in Combination with DHAP (Dexamethasone, High-Dose AraC, Cisplatinum) in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma: A Randomized, Placebo-Controlled Phase I/II Trial (HD-R3i)
Authors: Bastian von Tresckow, Andreas Hüttmann, Vladan Vucinic, Horst Mueller, Annette Plütschow, Andreas Viardot, Max S. Topp, Carsten Kobe, Boris Böll, Dennis A. Eichenauer, Stephanie Sasse, Heinz Haverkamp, Michael Fuchs, Andreas Engert, Peter Borchmann
Journal: Blood (2018)
The prevalence and prognostic significance of JAK2 mutation subtypes in non-small cell lung cancer from Chinese populations
Authors: W. Wang, C. Xu, Q. Zhang, W. Zhuang, Y. Zhu, Z. Huang, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Annals of Oncology (2019)

Background: Although roles of JAK2 mutations in myeloproliferative neoplasms (MPN) are well established, roles of JAK2 mutations in the pathogenesis of non-small cell lung cancer (NSCLC) remain unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring JAK2 mutations. Methods: A total of 766 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of JAK2 mutations and other genes were detected by next generation sequencing. Results: JAK2 gene mutation rate was 2.35% (18/766) in non-small cell lung cancer, including V617F (3 patients), L43I (2 patients), D768H (1 patient), G1066A (1 patient), W1020C (1 patient), S465R (1 patient), Q21E (1 patient), T842A (1 patient), C452* (1 patient), I404M (1 patient), P708Q (1 patient), S488* (1 patient), S1035L (1 patient), V387L(1 patient) and E575* (1 patient), and median overall survival (OS) for these patients was 19.0 months. Among them, all patients were JAK2 gene with co-occurring mutations. Briefly, patients with (n = 4) or without (n = 14) co-occurring EGFR mutations had a median OS of 23.0 months and 13.0 months respectively (p = 0.05); patients with (n = 11) or without (n = 7) co-occurring TP53 mutations had a median OS of 20.0 months and 7.0 months respectively (p = 0.01); patients with (n = 3) or without (n = 15) co-occurring ARID1A mutations had a median OS of 20.0 months and 13.0 months respectively (p = 0.32); patients with (n = 6) or without (n = 12) co-occurring KRAS mutations had a median OS of 11.5 months and 20.0 months respectively (p = 0.25). Conclusions: TP53 accompanied mutations might play a good prognosis in JAK2 gene mutation NSCLC. Next generation sequencing provides a simplified strategy and reasonably high detection rate for JAK2 mutation, which suggested application of the strategies into clinical molecular diagnostics. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
SAT-012-Alterations in skin microbiota, serum bile acids and autotaxin modulate itching intensity in patients with cirrhosis
Authors: Jasmohan S Bajaj, Andrew Fagan, Masoumeh Sikaroodi, Genta Kakiyama, William Pandak, Hajime Takei, Edith Gavis, Phillip Hylemon, Douglas Heuman, Hiroshi Nittono, Patrick Gillevet
Journal: Journal of Hepatology (2019)
PD-L1 expression affect the efficacy of pemetrexed maintenance therapy in real-world patients with advanced non-squamous NSCLC
Authors: Y. Qin, L. Jiang, Y. Li, L. Ren, Y. Wang, Y. Gong, F. Peng, J. Zhu, Z. Ding, Y. Liu, M. Yu, Y. Lu, M. Huang
Journal: Annals of Oncology (2019)

Background: It has been demonstrated that pemetrexed maintenance therapy is an effective and well tolerated option for patients with advanced non-squamous non-small cell lung cancer (NSCLC). This study aimed to investigate the impacts of clinical features, gene status and PD-L1 expression on the efficacy of pemetrexed maintenance therapy in real-world. Methods: The clinicopathological characteristics and prognostic data of 102 patients with advanced non-squamous NSCLC who received pemetrexed maintenance therapy between May 2011 and October 2017 were retrospectively analyzed. Kaplan-Meier method with Log-rank test was used for survival analysis. Multivariate Cox regression were used to identify variables associated with median progression free survival (mPFS). Results: 102 patients completed 485 cycles of induction chemotherapy and 509 cycles of maintenance chemotherapy, with a mPFS of 11.9 months (95%CI 9.95-13.84). The mPFS of ALK-positive patients was superior to negative patients (18.3 vs. 11.4 months; p = 0.032). Patients with PD-L1 expression ≥50% had significantly prolonged mPFS compared with PD-L1 <50% (17.5 vs. 11.4 months; p = 0.034). Bivariate correlation showed that PFS was significantly positively related to PD-L1 expression (R = 0.359, p = 0.001). No differences were found between EGFR positive and negative patients. The independent beneficial prognostic factors for PFS were age ≥65 years old (HR, 0.328; 95% CI, 0.137-0.787; p = 0.013) and ALK rearrangements (HR, 0.120; 95% CI, 0.027-0.533; p = 0.005). Conclusions: Pemetrexed has been shown to be efficacious in patients with advanced non-squamous NSCLC. ALK rearrangements and high PD-L1 expression are more likely to have longer PFS of pemetrexed maintenance therapy. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract 18758: Dysfunctional Regulatory T-lymphocytes are Pro-inflammatory and Anti-angiogenic in Heart Failure: A Role for TNF-TNFR1 Signaling
Authors: Shyam S Bansal, Mehak Goel, Ameen Ismahil, Tariq Hamid, Sumanth D Prabhu
Journal: Circulation (2017)

Heart failure (HF) is a state of immune cell activation. Regulatory T-lymphocytes (Tregs) are potent immunomodulatory T-cells that suppress inflammatory responses; however, their role in HF is unkn...
THU-470-The mRNA-binding protein tristetraprolin promotes hepatocarcinogenesis but inhibits tumour progression in liver cancer
Authors: Sonja Kessler, Kevan Hosseini, Tarek Kröhler, Ahmad Barghash, Sonika Patial, Jessica Hoppstädter, Katja Gemperlein, Johannes Haybäck, Markus List, Rolf Müller, Volkhard Helms, Marcel Schulz, Stephan Laggai, Perry Blackshear, Alexandra K. Kiemer
Journal: Journal of Hepatology (2019)
SAT-043-Is carvedilol better than propranolol in preventing variceal bleeding
Authors: Muhammad Farooq Hanif, Khalid mahmud Khan, Nooman Gilani, Maria Farooq, Muhammad Adnan Iqbal, Raja Omar Fiaz, Muhammad Osama Butt, Ommara Jamil, Muhammad Omer Qureshi, Amjad Khan
Journal: Journal of Hepatology (2019)
FRI-470-External beam radiotherapy as an effective and safe treatment in all stages of hepatocellular carcinoma with cirrhotic liver disease : A single institution experience
Authors: Clémence Hollande, Nhu Hanh To, Gokoulakrichenane Loganadane, Sahar Ghith, Noémie Grellier, Aziz Cherif, Laurianne Colson Durand, Maryse Fayolle, Marie-Laure Hervé, Edouard Herin, Julia Chalaye, Hélene Regnault, Giuliana Amaddeo, Alain Luciani, Christophe Duvoux, Yazid Belkacemi
Journal: Journal of Hepatology (2019)
Detection and clinicopathologic features of ctDNA in T790M-positive advanced lung adenocarcinomas patients after failure of treatment with first- and second-generation EGFR-TKIs
Authors: W. He, Z.S. Zhou, T.Q. Yu, H.W. Zhao, Y.C. Su, P.A. Zeng
Journal: Annals of Oncology (2019)

Background: We aimed to detect ctDNA in patients with advanced lung adenocarcinomas after failure of treatment with first- and second-generation EGFR-TKIs and to analyze it's clinicopathologic features in a subset of patients harbouring the T790M mutation. Methods: We retrospectively collected data from November 2016 to October 2018 in patients with lung adenocarcinomas who had been analysed by Next-Generation Sequencing or ddPCR after progression on EGFR-TKIs at GuangXi Medical University Affiliated Tumor Hospital. Statistical analyses were performed to examine the associations between clinicopathologic features and acquired T790M mutation in patients. Results: A total of 72 plasma samples were collected, of which 17 had matched tissue biopsies. Of these patients, 48 were analysed by NGS and the rest by ddPCR. The T790M mutation was detected in 43 cases (59.7%). We found this mutation was higher than that of mPFS>11.5 months (79% vs. 44%; odds ratio, 4.516; 95%CI, 1.53 to 13.30; p=0.006), and in which longer median PFS (13.0 months vs. 9.0 months; p = 0.042). Those who received chemotherapy before EGFR-TKIs were more likely to have the T790M mutation (80% vs. 53%, p=0.03) compared to those who received EGFR-TKIs in the first-line. In this study, the occurrence of T790M mutation in patients with L858R mutation was higher than seen in patients with 19-del (65% vs.57%; p=0.809). Among 17 patients who were sequenced by NGS in both samples, 7 had T790M positive blood samples and 8 were T790M positive in tissue biopsies. The coincidence rate was 94%.10 cases after the progression of the third generation TKI treatment. Three cases of T790M with C797S cis-mutation were detected and 3 cases with PIK3CA, BRAF V600E and MAP2K1 mutations, respectively. Secondary resistance mutations were not detected by NGS in 4 cases. Conclusions: Patients with advanced lung adenocarcinomas harbouring the T790M mutation who failed with first- or second-generation EGFR-TKIs were more likely to have longer mPFS. In this study, NGS testing using ctDNA was a feasible means for monitoring acquired resistance mutations during or after progression on targeted therapy. Legal entity responsible for the study: Cancer Hospital of Guangxi Medical University. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Serum inhibition of massively calcified endosomal death (MCED) in endothelial cells is a putative mechanism of resistance to bevacizumab (BEV) and other anti-angiogenic (anti-angio) agents.
Authors: Larry M. Weisenthal, Summer Williamson, Esther Moon, Cindy Brunshwiler, Constance Rueff-Weisenthal
Journal: Journal of Clinical Oncology (2015)

e22005 Background: Bähr et al reported that 22 of 36 glioblastoma (GBM) patients treated with BEV showed tumor (TUM) calciﬁcations (CALC) on 8 wk follow up post therapy. Early TUM CALC strongly predicted for response, time to progression, and overall survival: Neuro-Oncology, 13:1020, 2011. At the 13th International Anti-Angio Symposium (2011), we presented our discovery of the phenomenon of massive calcium accumulation death, wherein MCAD occurred in endothelial cells in response to VEGF depletion by BEV and other anti-angio agents, but not in response to non-speciﬁc cytotoxins http://dx.doi.org/10.1038/npre.2011.6647.1 At the 14th International Anti-Angio Symposium (2012) we documented marked MCAD to occur in primary microcluster cultures from fresh human GBM biopsies, following 96 hours of VEGF depletion in vitro by BEV. http://dx.doi.org/10.1038/npre.2012.7069.1 We later reported that BEV and other anti-angiogenics (but not non-speciﬁc cytotoxins) produce highly-calciﬁed microparticles, in a process termed massively calcified endosomal death (MCED). http://biorxiv.org/content/early/2014/07/15/007112. We presently attempted to document the ability of different human sera to inhibit MCED, as a putative biomarker for resistance to anti-angio therapy. Methods: Human umbilical vein endothelial cells (HUVEC), circulating EC, and EC present in microclusters of primary cultures of human TUM cells were incubated with BEV and small molecule anti-angio for 96-120 hr, in the presence of 10% human serum from 30 different pts. Massively calcified microparticles were quantified by alizarin staining and microscopic image analysis. Results: Sera from different pts reproducibly varied markedly with regard to ability to inhibit MCED occurring in HUVEC, circulating EC, and EC in primary tumor microclusters. Conclusions: Effectiveness of anti-angio therapy may be influenced the the presence of endogenous inhibitors of MCED. Testing serum for MCED inhibition may provide a biomarker for clinical activity for anti-angio agents. Circumvention of MCED inhibition may enhance the effectiveness of anti-angio therapy.
A Tale of Two Complications of Obesity: NASH and Hepatocellular Carcinoma
Authors: Renumathy Dhanasekaran, Dean W. Felsher
Journal: Hepatology (2019)

Dhanasekaran, Renumathy M.D.; Felsher, Dean W. M.D., Ph.D.Editor(s): Corey, Kathleen E.3; Malhi, Harmeet4 Author Information
Vibrational spectroscopy of serum to detect brain metastases in patients with melanoma.
Authors: Ruth Board, Benjamin Willis, Matthew Baker
Journal: Journal of Clinical Oncology (2015)

e22151 Background: 44% of patients with metastatic melanoma develop symptomatic brain metastases. These lesions cause considerable morbidity, and prognosis in these patients is poor. A rapid diagnostic method based upon blood serum samples would allow for a relatively non-invasive test that can be easily and regularly repeated in contrast to radiological imaging. Attenuated Total Reflection – Fourier Transform Infrared Spectroscopy (ATR-FTIR) is a vibrational spectroscopic technique ideally suited for the analysis of biofluids. Recent studies have shown the ability of FTIR to discriminate between blood serum of high grade gliomas patients and healthy patients. We have applied the same principles to analyse serum samples from patients with metastatic melanoma, with and without brain metastases to see if a spectroscopic ‘melanoma fingerprint’ exists. Methods: Serum was collected from patients with metastatic melanoma attending the oncology clinic. Serum was analysed by ATR-FTIR (3 x 1μl serum spots per patient were analysed 3 times from 4000 – 400 cm-1) from 55 patients with metastatic melanoma (n = 34 with radiologically proven brain metastases, n = 21 without) and n = 122 normal controls. Spectra were then pre-processed using principal component based noise reduction and vector normalisation and analyses using principal component discriminant function analysis (PC-DFA). Results: The PC-DFA analysis achieved sensitivities and specificities between 83 and 92 %. Analysis of the spectral signature per grouping (metastatic vs normal control) identified discriminatory regions correlated to Amide I (α – helix protein structures) and the CH3/CH stretching of lipids. Conclusions: This proof of principle study demonstrates that spectrospcopic analysis of serum can detect a ‘melanoma fingerprint’ and distinguish patients with melanoma with and without brain metastases. Future studies will concentrate on improving the sensitivity and specificity of this work and identifying the salient features of the spectrum to enable targeted molecular analysis.
Cutaneous Melanoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology
Authors: Daniel G. Coit, John A. Thompson, Mark R. Albertini, Christopher Barker, William E. Carson, Carlo Contreras, Gregory A. Daniels, Dominick DiMaio, Ryan C. Fields, Martin D. Fleming, Morganna Freeman, Anjela Galan, Brian Gastman, Valerie Guild, Douglas Johnson, Richard W. Joseph, Julie R. Lange, Sameer Nath, Anthony J. Olszanski, Patrick Ott, Aparna Priyanath Gupta, Merrick I. Ross, April K. Salama, Joseph Skitzki, Jeffrey Sosman, Susan M. Swetter, Kenneth K. Tanabe, Evan Wuthrick, Nicole R. McMillian, Anita M. Engh
Journal: Journal of the National Comprehensive Cancer Network (2019)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.
Blood DNA Methylation and Breast Cancer: A Prospective Case-Cohort Analysis in the Sister Study
Authors: Zongli Xu, Dale P Sandler, Jack A Taylor
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Peripheral blood DNA methylation may be associated with breast cancer, but studies of candidate genes and global and genome-wide DNA methylation have been inconsistent. Methods We performed an epigenome-wide study using Infinium HumanMethylation450 BeadChips with prospectively collected blood DNA samples from the Sister Study (1552 cases, 1224 subcohort). Differentially methylated cytosine-phosphate-guanine sites (dmCpGs) were identified using case-cohort proportional hazard models and replicated using deposited data from European Prospective Investigation into Cancer and Nutrition in Italy (EPIC-Italy) (n = 329). The correlation between methylation and time to diagnosis was examined using robust linear regression. Causal or consequential relationships of methylation to breast cancer were examined by Mendelian randomization using OncoArray 500 K single-nucleotide polymorphism data. All statistical tests were two-sided. Results We identified 9601 CpG markers associated with invasive breast cancer (false discovery rate = q &amp;lt; 0.01), with 510 meeting a strict Bonferroni correction threshold (10–7). A total of 2095 of these CpGs replicated in the independent EPIC-Italy dataset, including 144 meeting the Bonferroni threshold. Sister Study women who developed ductal carcinoma in situ had methylation similar to noncases. Most (1501, 71.6%) dmCpGs showed lower methylation in invasive cases. In case-only analysis, methylation was statistically significantly associated (false discovery rate = q &amp;lt; 0.05) with time to diagnosis for 892 (42.6%) of the dmCpGs. Analyses based on genetic association suggest that methylation differences are likely a consequence rather than a cause of breast cancer. Pathway analysis shows enrichment of breast cancer-related gene pathways, and dmCpGs are overrepresented in known breast cancer susceptibility genes. Conclusions Our findings suggest that the DNA methylation profile of blood starts to change in response to invasive breast cancer years before the tumor is clinically detected.
Endoscopic drainage using a lumen-apposing metal stent under contrast-enhanced harmonic endoscopic ultrasonography guidance
Authors: Yasuki Hori, Michihiro Yoshida, Kazuki Hayashi, Itaru Naitoh, Akihisa Kato, Katsuyuki Miyabe, Hiromi Kataoka
Journal: Endoscopy (2019)

Endoscopic ultrasonography-guided transmural drainage (EUS-TMD) is an effective treatment for collections of infected peripancreatic fluid [1]. A novel one-step device consisting of a combined lumen-apposing metal stent (LAMS) and an electrocautery-enhanced delivery system (Hot AXIOS; Boston Scientific, Marlborough, Massachusetts, USA) was recently developed [2] [3]. The stent flange interval is 10-mm long; therefore, the recommended indication for this stent is a fluid collection with a wall of < 10 mm. Evaluating the precise thickness of the cavity wall before this procedure is crucial, and a LAMS should not be used if the operator cannot be certain. Here, we report a case of successful drainage of an infected hematoma using the Hot AXIOS under contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) guidance.
THU-337-Cardiovascular risk factors and fibrosis severity in NAFLD: is there a link?
Authors: Davide Roccarina, Laura Iogna Prat, Marta Guerrero, Elena Buzzetti, Anna Mantovani, Atul Goyale, Francesco Arico, Francesca Saffioti, Massimo Pinzani, Emmanuel Tsochatzis
Journal: Journal of Hepatology (2019)
SAT-252-Long-term effect of direct-acting antivirals therapy in patients with hepatitis C-related decompensated cirrhosis: Russian single academic center experience
Authors: Ekaterina Nabatchikova, Dzhamal Abdurakhmanov, Teona Rozina, Elena Nikulkina, Elena Tanashchuk, Sergey Moiseev
Journal: Journal of Hepatology (2019)