tbuckley/cabot-search huggingface dataset:
Predictors of Locoregional Recurrence After Failure to Achieve Pathologic Complete Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Authors: Prashant Gabani, Emily Merfeld, Amar J. Srivastava, Ashley A. Weiner, Laura L. Ochoa, Dan Mullen, Maria A. Thomas, Julie A. Margenthaler, Amy E. Cyr, Lindsay L. Peterson, Michael J. Naughton, Cynthia Ma, Imran Zoberi
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: This study evaluated factors predictive of locoregional recurrence (LRR) in women with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy who do not experience pathologic complete response (pCR). Methods: This is a single-institution retrospective review of women with TNBC treated with neoadjuvant chemotherapy, surgery, and radiation therapy in 2000 through 2013. LRR was estimated between patients with and without pCR using the Kaplan-Meier method. Patient-, tumor-, and treatment-specific factors in patients without pCR were analyzed using the Cox proportional hazards method to evaluate factors predictive of LRR. Log-rank statistics were then used to compare LRR among these risk factors. Results: A total of 153 patients with a median follow-up of 48.6 months were included. The 4-year overall survival and LRR were 70% and 15%, respectively, and the 4-year LRR in patients with pCR was 0% versus 22.0% in those without ( P &lt;.001). In patients without pCR, lymphovascular space invasion (LVSI; hazard ratio, 3.92; 95% CI, 1.64–9.38; P =.002) and extranodal extension (ENE; hazard ratio, 3.32; 95% CI, 1.35–8.15; P =.009) were significant predictors of LRR in multivariable analysis. In these patients, the 4-year LRR with LVSI was 39.8% versus 15.0% without ( P &lt;.001). Similarly, the 4-year LRR was 48.1% with ENE versus 16.1% without ( P =.002). In patients without pCR, the presence of both LVSI and ENE were associated with an even further increased risk of LRR compared with patients with either LVSI or ENE alone and those with neither LVSI nor ENE in the residual tumor ( P &lt;.001). Conclusions: In patients without pCR, the presence of LVSI and ENE increases the risk of LRR in TNBC. The risk of LRR is compounded when both LVSI and ENE are present in the same patient. Future clinical trials are warranted to lower the risk of LRR in these high-risk patients.
Evaluation of safety and efficacy of minocycline combined with tyrosine kinase inhibitors in patients of EGFR mutated metastatic lung cancer
Authors: A.G.F. Thottian, G.K. Babu, L. Dasappa, L.A. Jacob, S.M. Babu, K.N. Lokesh, A.H. Rudresha, S. Saldanha, G. Gv, R. Lk
Journal: Annals of Oncology (2019)

Background: Tyrosine Kinase Inhibitors (TKI) are used in the first line management of metastatic Non-Small cell lung cancer in the presence of EGFR activating driver mutations. Skin rash is one of the most common side effects associated with the use of TKIs and Minocycline is recommended for prophylaxis and treatment of TKI induced skin rash. An exploratory analysis of a Phase III study evaluating the role of Minocycline with regard to skin rash showed a trend toward improved survival in such patients. This finding can be backed by appropriate biologic rationale as Minocycline has been shown to inhibit PARP-1 in in-vitro studies and EGFR mutated lung cancers are deficient in BRCA1 leading to a synthetic lethality in tumor cells exposed to both these drugs. This study is intended to assess the safety and efficacy of minocycline in patients of metastatic Non-Small Cell Lung cancer treated with a combination of TKIs and Minocycline. Trial design: Objectives Primary To assess and compare Response rates in patients receiving TKIs and minocycline versus those receiving TKI alone To assess the toxicity with addition of minocycline to TKIs Secondary To assess and compare PFS and OS in patients receiving TKIs and minocycline versus those receiving TKIs alone Materials and Methods Type of Study - A phase 2 randomized study Patients – Metastatic NSCLC with EGFR mutations sensitive to Gefitinib Arms – Gefitinib 250mg/day alone Gefitinib 250mg/day + Minocycline 100mg/day Study site and duration Kidwai Cancer Institute; July 2018 to June 2020 Inclusion Criteria Patients of Metastatic Biopsy Proven NSCLC with an EGFR sensitising mutation to Gefitinib Age 18 – 80 Exclusion Criteria Any other Synchronous / Metachronous cancer or any uncontrolled co-morbidities Sample size n = 50 in each arm Randomization – Simple Random Method, Lottery Method Statistical Analysis - The Mann-Whitney U test and the χ2 test will be used to determine statistically significant differences between the two groups, Kaplan-Meier method to assess survival curves, Log-rank test to evaluate the statistical significance of differences and Cox proportional hazards model for multivariate analysis of the effect of clinicopathological factors on survival. Legal entity responsible for the study: Kidwai Cancer Institute. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
THU-072-N-ras protects against experimental liver fibrosis by maintaining hepatocyte homeostasis
Authors: Kang Zheng, Fengjie Hao, Yulia Nevzorova, Sandra Medrano, Javier Vaquero, Manuel Gómez del Moral, Rafael Bañares, Jose Ramón Regueiro, Eduardo Martínez-Naves, Edgar Fernández-Malavé, Francisco Javier Cubero
Journal: Journal of Hepatology (2019)
HHLA2 in intrahepatic cholangiocarcinoma: an immune checkpoint with prognostic significance and wider expression compared with PD-L1
Authors: Chu-Yu Jing, Yi-Peng Fu, Yong Yi, Mei-Xia Zhang, Su-Su Zheng, Jin-Long Huang, Wei Gan, Xin Xu, Jia-Jia Lin, Juan Zhang, Shuang-Jian Qiu, Bo-Heng Zhang
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Intrahepatic cholangiocarcinoma (ICC) is a highly mortal malignancy with limited therapeutic options. Immunotherapies targeting PD-1/PD-L1 pathway represent a promising treatment for ICC. However, PD-L1 expression and microsatellite instability are not common in ICC. This study aimed to investigate whether HHLA2, a newly identified B7 family immune checkpoint for T cells, could be a therapeutic target next to PD-L1 in ICC. <h3>Methods</h3> Expression levels of PD-L1 and HHLA2 as well as infiltrations of CD3+, CD8+, CD4 + Foxp3+, CD68+, CD163+ and CD20+ cells were evaluated by immunohistochemistry in 153 resected ICC samples. Comprehensive comparisons were made between PD-L1 and HHLA2 in terms of the expression rates, clinicopathological features and infiltrations of different immune cells. The expression level and prognostic significance of HHLA2 were further validated in an independent cohort. <h3>Results</h3> Expression of HHLA2 is more frequent than PD-L1 in ICC (49.0% vs 28.1%). Co-expression of both immune checkpoints was infrequent (13.1%) and 50% PD-L1 negative cases were with elevated HHLA2. HHLA2 overexpression was associated with sparser CD3+ tumor infiltrating lymphocytes (TILs), CD8+ TILs and a higher CD4 + Foxp3+/CD8+ TIL ratio, whereas PD-L1 expression was associated with prominent T cells and CD163+ tumor associated macrophages infiltrations. PD-L1 failed to stratify overall survival (OS) but HHLA2 was identified as an independent prognostic indicator for OS in two independent cohorts. <h3>Conclusions</h3> Compared with PD-L1, HHLA2 is more prevalent and possesses more explicit prognostic significance, which confer the rationale for HHLA2 as a potential immunotherapeutic target next to PD-L1 for ICC patients.
Detection of NRG1 Gene Fusions in Solid Tumors
Authors: Sushma Jonna, Rebecca A. Feldman, Jeffrey Swensen, Zoran Gatalica, Wolfgang M. Korn, Hossein Borghaei, Patrick C. Ma, Jorge J. Nieva, Alexander I. Spira, Ari M. Vanderwalde, Antoinette J. Wozniak, Edward S. Kim, Stephen V. Liu
Journal: Clinical Cancer Research (2019)

Abstract Purpose: NRG1 gene fusions are rare but potentially actionable oncogenic drivers that are present in some solid tumors. Details regarding the incidence of these gene rearrangements are lacking. Here, we assessed the incidence of NRG1 fusions across multiple tumor types and described fusion partners. Experimental Design: Tumor specimens submitted for molecular profiling at a Clinical Laboratory Improvement Amendments (CLIA)–certified genomics laboratory and that underwent fusion testing by anchored multiplex PCR for targeted RNA sequencing were retrospectively identified. The overall and tumor-specific incidence was noted, as was the specific fusion partner. Results: Out of 21,858 tumor specimens profiled from September 2015 to December 2018, 41 cases (0.2%) harbored an NRG1 fusion. Multiple fusion partners were identified. Fusion events were seen across tumor types. The greatest incidence was in non–small cell lung cancer (NSCLC, 25), though this represented only 0.3% of NSCLC cases tested. Other tumor types harboring an NRG1 fusion included gallbladder cancer, renal cell carcinoma, bladder cancer, ovarian cancer, pancreatic cancer, breast cancer, neuroendocrine tumor, sarcoma, and colorectal cancer. Conclusions: NRG1 fusions can be detected at a low incidence across multiple tumor types with significant heterogeneity in fusion partner. See related commentary by Dimou and Camidge, p. 4865
TCTAP A-136 Safety and Clinical Performance of Biodegradable Polymer Coated Ultra-thin Everolimus-eluting Stents in ‘Real-world' Patients: A Multicentre Registry (Perform-ever)
Authors: Sridhar Kasturi, Shailender Singh, Vijay Kumar Reddy Shanivaram
Journal: Journal of the American College of Cardiology (2019)
Dialysis initiation, modality choice, access, and prescription: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Authors: Christopher T. Chan, Peter J. Blankestijn, Laura M. Dember, Maurizio Gallieni, David C.H. Harris, Charmaine E. Lok, Rajnish Mehrotra, Paul E. Stevens, Angela Yee-Moon Wang, Michael Cheung, David C. Wheeler, Wolfgang C. Winkelmayer, Carol A. Pollock, Ali K. Abu-Alfa, Joanne M. Bargman, Anthony J. Bleyer, Edwina A. Brown, Andrew Davenport, Simon J. Davies, Frederic O. Finkelstein, Jennifer E. Flythe, Eric Goffin, Thomas A. Golper, Rafael Gómez, Takayuki Hamano, Manfred Hecking, Olof Heimbürger, Barnaby Hole, Daljit K. Hothi, T. Alp Ikizler, Yoshitaka Isaka, Kunitoshi Iseki, Vivekanand Jha, Hideki Kawanishi, Peter G. Kerr, Paul Komenda, Csaba P. Kovesdy, Ed Lacson, Maurice Laville, Jung Pyo Lee, Edgar V. Lerma, Nathan W. Levin, Monika Lichodziejewska-Niemierko, Adrian Liew, Elizabeth Lindley, Robert S. Lockridge, Magdalena Madero, Ziad A. Massy, Linda McCann, Klemens B. Meyer, Rachael L. Morton, Annie-Claire Nadeau-Fredette, Hirokazu Okada, Jose Perez, Jeff Perl, Kevan R. Polkinghorne, Miguel C. Riella, Bruce M. Robinson, Michael V. Rocco, Steven J. Rosansky, Joris I. Rotmans, María Fernanda Slon Roblero, Navdeep Tangri, Marcello Tonelli, Allison Tong, Yusuke Tsukamoto, Kriang Tungsanga, Tushar J. Vachharajani, Ismay van Loon, Suzanne Watnick, Daniel E. Weiner, Martin Wilkie, Elena Zakharova
Journal: Kidney International (2019)

Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied "country-specific" factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a "one-size-fits-all" approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions.
FRI-434-Role of next generation sequencing in the etiological diagnosis of splanchnic venous thrombosis
Authors: Marta Magaz, Alberto Álvarez-Larrán, Dolors Colomer, Mónica López, Gabriel Mezzano, Fanny Turon, Anna Baiges, José Ferrusquia, Michel Ble, Lara Orts, Claudia Berbel, Francisco Cervantes, Virginia Hernandez-Gea, Juan-Carlos Garcia-Pagan
Journal: Journal of Hepatology (2019)
TCTAP A-003 Sex Differences in Instantaneous Wave-free Ratio (iFR) or Fractional Flow Reserve (FFR) Guided Strategy
Authors: Chee Hae Kim, Joo Myung Lee, Hakim-Moulay Dehbi, Joon Hyung Doh, Chang-Wook Nam, Eun-Seok Shin, Ricardo Petraco, Sayan Sen, Iqbal S. Malik, Sukhjinder Nijjer, Javier Escaned, Justin E. Davies, Bon-Kwon Koo
Journal: Journal of the American College of Cardiology (2019)
Author Correction: Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma
Authors: Junfei Zhao, Andrew X. Chen, Robyn D. Gartrell, Andrew M. Silverman, Luis Aparicio, Tim Chu, Darius Bordbar, David Shan, Jorge Samanamud, Aayushi Mahajan, Ioan Filip, Rose Orenbuch, Morgan Goetz, Jonathan T. Yamaguchi, Michael Cloney, Craig Horbinski, Rimas V. Lukas, Jeffrey Raizer, Ali I. Rae, Jinzhou Yuan, Peter Canoll, Jeffrey N. Bruce, Yvonne M. Saenger, Peter Sims, Fabio M. Iwamoto, Adam M. Sonabend, Raul Rabadan
Journal: Nature Medicine (2019)
Abstract 16708: Data Driven Phenotyping of Patients With Heart Failure using a Deep-learning Cluster Representation of Echocardiographic and Electronic Health Record Data
Authors: Alvaro E Ulloa Cerna, Gregory Wehner, Dustin N Hartzel, Christopher Haggerty, Brandon Fornwalt
Journal: Circulation (2017)

Introduction: Heart failure (HF) is a common condition with a significant clinical burden. Despite numerous etiologies that lead to HF, the most common clinical classification is solely based on he...
SAT-463-Albumin-bilirubin grade-based nomogram to predict tumor recurrence in patients with hepatocellular carcinoma
Authors: Teh-Ia Huo, Shu Yein Ho, Po-Hong Liu, Chia-Yang Hsu, Yi-Hsaing Huang, Chien-Wei Su, Ming-Chih Hou
Journal: Journal of Hepatology (2019)
Abstract 23928: Microrna-125b-5p Protects The Heart From Acute Myocardial Infarction By Repressing Pro-apoptotic Bak1 And Klf13 In Cardiomyocytes
Authors: Tatsuya Aonuma, Ahmed S Bayoumi, Il-man Kim
Journal: Circulation (2017)

Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy and has been proposed as a biomarker of heart failure. We previously showed using the β-arrestin-biased β-blocker, carvedilol that β1-adrenergic receptor-mediated cardioprotective signaling through β-arrestin1 stimulates processing of miR-125b-5p in the mouse heart (Figure A-C). We hypothesize that β1-adrenergic receptor/β-arrestin1-responsive miR-125b-5p confers cardioprotection against acute myocardial infarction. Using cultured cardiomyocyte (CM) and in vivo approaches, we show that miR-125b-5p is an ischemic stress-responsive protector against CM apoptosis. CMs lacking miR-125b-5p exhibit an increased sensitivity to stress-induced apoptosis, while CMs overexpressing miR-125b-5p have increased phospho-AKT pro-survival signaling. Moreover, we demonstrate that loss-of-function of miR-125b-5p in the mouse heart causes abnormalities in cardiac structure and function after acute myocardial infarction. Mechanistically, cardioprotection elicited by miR-125b-5p is in part attributed to repression of the pro-apoptotic genes Bak1 and Klf13 in CMs (Figure D). In conclusion, these findings reveal a pivotal role for miR-125b-5p in regulating CM survival during acute myocardial infarction.
Low-dose naltrexone therapy in benign chronic pemphigus (Hailey-Hailey disease): A case series
Authors: Constanza Riquelme-Mc Loughlin, José Riera-Monroig, Daniel Morgado-Carrasco, Priscila Giavedoni, Sebastian Podlipnik, Pilar Iranzo, José M. Mascaró
Journal: Journal of the American Academy of Dermatology (2019)
SAT-496-Circulating cell-free HBV-human chimera DNA as new marker for HCC recurrence and clonality after curative resection
Authors: Chiao-Ling Li, Ming-Chih Ho, You-Yu Lin, Sheng-Tai Tzeng, Yun-Ju Chen, Hsin-Yung Pai, Ya-Chun Wang, Shiou-Hwei Yeh, Pei-Jer Chen
Journal: Journal of Hepatology (2019)
Orchestrated biomechanical, structural, and biochemical stimuli for engineering anisotropic meniscus
Authors: Zheng-Zheng Zhang, You-Rong Chen, Shao-Jie Wang, Feng Zhao, Xiao-Gang Wang, Fei Yang, Jin-Jun Shi, Zi-Gang Ge, Wen-Yu Ding, Yu-Chen Yang, Tong-Qiang Zou, Ji-Ying Zhang, Jia-Kuo Yu, Dong Jiang
Journal: Science Translational Medicine (2019)

Anisotropic meniscus engineered using biomechanical, biochemical, and structural cues demonstrates long-term knee chondroprotection in rabbits.
PS-074-A first-in-class orally available HBV cccDNA destabilizer ccc_R08 achieved sustainable HBsAg and HBV DNA suppression in the HBV circle mouse model through elimination of cccDNA-like molecules in the mouse liver
Authors: Li Wang, Qihui Zhu, Jing Zeng, Zhipeng Yan, Andrew Feng, John Young, Lu Gao
Journal: Journal of Hepatology (2019)
Abstract 216: Causal Role of Oxidized Lipids in Pulmonary Hypertension Development
Authors: Gregoire Ruffenach, Soban Umar, Mylene Vaillancourt, Victor Grijalva, Ellen I O’Connor, Shayan Moazeni, Christine Cunningham, Abbas Ardehali, Aman Mahajan, Srininivasa T Reddy, Mansoureh Eghbali
Journal: Circulation Research (2017)

Pulmonary arterial hypertension (PAH) is a deadly disease characterized by increased pulmonary arterial pressure and pulmonary vascular occlusion. Recently, we and others demonstrated a robust increase in oxidized lipids, including 15-hydroxyeicosatetraenoic acids (15-HETE), in the lungs and plasma of PAH patients and animal models of pulmonary hypertension (PH). We hypothesized that diets rich in 15-HETE are sufficient to cause PH in wild type mice. We also examined whether 15-HETE or its metabolites are required to cause PH by comparing the effect of 15-HETE with 15-HETE methyl ester, which is a stable form of 15HETE that is not easily metabolized. C57BL/6 male mice were fed for 3 weeks with 15-HETE diet (5μg/day), 15-HETE methyl ester (15-HETE-ME, 5μg/day), or regular chow diet (n=8-21 mice/group). PH development was followed via weekly serial echocardiography. Right ventricular systolic pressure (RVSP) was measured via direct heart catheterization. RV hypertrophy index (RV/[IVS+LV]) was measured. Lung morphology and lipid accumulation were assessed using H&amp;E and Oil red O staining. Echocardiography revealed the first sign of PH in mice on 15HETE diet as early as one week and a significant decrease in the pulmonary arterial acceleration time after 2 weeks of treatment (16.6±1.9 vs. 21.2±1.4 msec, p&lt;0.05). Mice on 15HETE diet also had significantly higher RVSP (31.3±1.1 vs. 38.4±2.3 mmHg, p&lt;0.05). Increase in RVSP was concomitant with significantly higher RV hypertrophy index (0.26 ± 0.02 vs. 0.33 ±0.02, p&lt;0.05). Pulmonary arteriolar thickness was also significantly increased in mice on 15-HETE diet compared to regular diet (35.1±0.8 vs 53.4±1, p&lt;0.05). Our new model of PH is not a model of atherosclerosis as there was no detectable plaque in aorta of the mice on 15-HETE diet. Finally, mice on 15-HETE-ME diet also developed PH as RVSP was significantly higher compared to control (31.3±1.1 vs. 39±3 mmHg, p&lt;0.05). The severity of PH was similar in 15HETE-ME and 15HETE, confirming 15HETE itself and not its metabolites is sufficient to cause PH in wild type mice. We have developed a new and physiologically relevant animal model to study PH as a consequence of oxidized lipids overload as it occurs in humans with PAH.
Identification of novel prognostic markers of glioblastoma using computational strategies on four genomic datasets.
Authors: Haruka Itakura, Olivier Gevaert
Journal: Journal of Clinical Oncology (2015)

11045 Background: We sought to discover novel biomarkers using computational strategies on four genomic/epigenomic datasets to improve prognostication in glioblastoma (GBM). Methods: We obtained survival, clinical, gene expression, copy number variation (CNV), microRNA, and methylation data from The Cancer Genome Atlas on GBM subjects. Our study design was to fit Cox proportional hazards regression models using penalized maximum likelihood on the four datasets to predict overall survival, our analysis endpoint. We trained and tested our Cox models using 10-fold cross-validation on combined datasets created by three different integration strategies: concatenation, partial integration with double penalized maximum likelihood, and combination of weighted predictions from each dataset. We compared three, final Cox regression models using: 1) molecular features selected by the highest-performing integration strategy, 2) established risk factors (age, performance status (KPS), IDH1, MGMT, CIMP), and 3) combined molecular and established features. Results: 243 subjects, who possessed survival and all four genomic datasets, were included for analysis. Selecting the top 25% varying genes, gene expression data contained 4453, CNV 5770, microRNA 534, and methylation data 4643 features. The integration strategy based on weighted predictions produced the highest performing prediction model (p = 0.0006). The final molecular feature-only model yielded a multivariate combination of 17 prognostic features (p = 3.89x10-10). The established features model produced three prognostic features (p = 5.0x10-08): age, gender, and KPS. In the combined molecular-established risk model, 11 molecular features (one gene expression, three CNV, four microRNA, and three methylation features) and three clinical features (age, CIMP status, and KPS) were prognostic (p = 1.79x10-08). Conclusions: Using four genomic datasets and novel computational strategies, we identified 11 molecular features that could improve GBM prognostication beyond the current set of established risk factors. These features warrant closer investigation as novel markers for disease prognostication and targets for therapy.