tbuckley/cabot-search huggingface dataset:
lncRNA <i>THAP9-AS1</i> Promotes Pancreatic Ductal Adenocarcinoma Growth and Leads to a Poor Clinical Outcome via Sponging miR-484 and Interacting with YAP
Authors: Nan Li, Guohua Yang, Liyun Luo, Li Ling, Xiaorong Wang, Lejuan Shi, Junsong Lan, Xiaoting Jia, Qiong Zhang, Ze Long, Jinbao Liu, Weimin Hu, Zhimin He, Haiying Liu, Wanqing Liu, Guopei Zheng
Journal: Clinical Cancer Research (2019)

Long noncoding RNAs (lncRNA) have been observed in various cancer types. Our bioinformatic analysis of existing databases demonstrated overexpression of lncRNA THAP9-AS1 in pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the roles and mechanisms of THAP9-AS1 in PDAC.The overexpression of THAP9-AS1 in samples of patients with pancreatic cancer was characterized and was associated with clinical outcomes. The nonprotein coding property of the THAP9-AS1 was verified. Various in vitro and in vivo experiments were performed to investigate the interaction between THAP9-AS1 and YAP signaling.We demonstrated that lncRNA THAP9-AS1 is overexpressed in PDAC in multiple patient sample sets, which is significantly associated with poor outcome of patients with PDAC. THAP9-AS1 promotes PDAC cells growth both in vitro and in vivo. THAP9-AS1 exerts its effects via enhancing YAP signaling. Ectopic YAP expression overcame the effects of THAP9-AS1 knockdown. Inversely, YAP knockdown diminished the effects of THAP9-AS1 overexpression. THAP9-AS1 acts as a competing endogenous RNA for miR-484, leading to YAP upregulation. Moreover, THAP9-AS1 binds to YAP protein and inhibits the phosphorylation-mediated inactivation of YAP by LATS1. Reciprocally, YAP/TEAD1 complex promotes THAP9-AS1 transcription to form a feed-forward circuit. Importantly, THAP9-AS1 level positively correlates with YAP expression in PDAC tissues. YAP overexpression also predicts a poor outcome in patients with PDAC.Our findings indicate that THAP9-AS1 plays an important role in PDAC growth via enhancing YAP signaling, which in turn also modulates THAP9-AS1 transcription. THAP9-AS1/YAP axis may serve as a potential biomarker and therapeutic target for PDAC treatment.
The Proteomic Landscape of Pancreatic Ductal Adenocarcinoma Liver Metastases Identifies Molecular Subtypes and Associations with Clinical Response
Authors: Henry C.-H. Law, Dragana Lagundžin, Emalie J. Clement, Fangfang Qiao, Zachary S. Wagner, Kimiko L. Krieger, Diane Costanzo-Garvey, Thomas C. Caffrey, Jean L. Grem, Dominick J. DiMaio, Paul M. Grandgenett, Leah M. Cook, Kurt W. Fisher, Fang Yu, Michael A. Hollingsworth, Nicholas T. Woods
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease that can be separated into distinct subtypes based on molecular signatures. Identifying PDAC subtype-specific therapeutic vulnerabilities is necessary to develop precision medicine approaches to treat PDAC. Experimental Design: A total of 56 PDAC liver metastases were obtained from the UNMC Rapid Autopsy Program and analyzed with quantitative proteomics. PDAC subtypes were identified by principal component analysis based on protein expression profiling. Proteomic subtypes were further characterized by the associated clinical information, including but not limited to survival analysis, drug treatment response, and smoking and drinking status. Results: Over 3,960 proteins were identified and used to delineate four distinct PDAC microenvironment subtypes: (i) metabolic; (ii) progenitor-like; (iii) proliferative; and (iv) inflammatory. PDAC risk factors of alcohol and tobacco consumption correlate with subtype classifications. Enhanced survival is observed in FOLFIRINOX treated metabolic and progenitor-like subtypes compared with the proliferative and inflammatory subtypes. In addition, TYMP, PDCD6IP, ERAP1, and STMN showed significant association with patient survival in a subtype-specific manner. Gemcitabine-induced alterations in the proteome identify proteins, such as serine hydroxymethyltransferase 1, associated with drug resistance. Conclusions: These data demonstrate that proteomic analysis of clinical PDAC liver metastases can identify molecular signatures unique to disease subtypes and point to opportunities for therapeutic development to improve the treatment of PDAC.
Preclinical Evaluation of a Novel SHIP1 Phosphatase Activator for Inhibition of PI3K Signaling in Malignant B Cells
Authors: Elizabeth A. Lemm, Beatriz Valle-Argos, Lindsay D. Smith, Johanna Richter, Yohannes Gebreselassie, Matthew J. Carter, Jana Karolova, Michael Svaton, Karel Helman, Nicola J. Weston-Bell, Laura Karydis, Chris T. Williamson, Georg Lenz, Jeremy Pettigrew, Curtis Harwig, Freda K. Stevenson, Mark Cragg, Francesco Forconi, Andrew J. Steele, Jennifer Cross, Lloyd Mackenzie, Pavel Klener, Graham Packham
Journal: Clinical Cancer Research (2019)

PI3K signaling is a common feature of B-cell neoplasms, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), and PI3K inhibitors have been introduced into the clinic. However, there remains a clear need to develop new strategies to target PI3K signaling. PI3K activity is countered by Src homology domain 2-containing inositol-5'-phosphatase 1 (SHIP1) and, here, we have characterized the activity of a novel SHIP1 activator, AQX-435, in preclinical models of B-cell malignancies.
Increased Frequency of Expression of Elevated Dihydrofolate Reductase in T-Cell Versus B-Precursor Acute Lymphoblastic Leukemia in Children
Authors: Larry H. Matherly, Jeffrey W. Taub, So C. Wong, Pippa M. Simpson, Rachenii Ekizian, Steve Buck, Michael Williamson, Michael Amylon, Jeannette Pullen, Bruce Camitta, Y. Ravindranath
Journal: Blood (1997)
Synchronous 3D Bioprinting of Large‐Scale Cell‐Laden Constructs with Nutrient Networks
Authors: Lei Shao, Qing Gao, Chaoqi Xie, Jianzhong Fu, Meixiang Xiang, Yong He
Journal: Advanced Healthcare Materials (2019)

Abstract Maintaining an adequate supply of nutrients/oxygen is a major challenge in the biofabrication of large tissue constructs. However, building preformed nutrient networks may be an effective strategy for engineering thick tissues. Here, a novel way for bioprinting large‐scale tissue constructs with intentional nutrient networks is presented. A special nozzle is developed which can print bioink and sacrificial ink half and half synchronously in a single filament. Nutrient networks of these bioprinted constructs are formed by subsequently dissolving away gelatin, which allows for effective oxygen, nutrient, and waste diffusion, facilitating the cell activity and the generation of functional tissues. Due to the cell‐laden bioink and sacrificial ink working together and promoting each other's printability to support themselves, complex soft cell‐laden constructs with nutrient networks can easily be printed. Furthermore, two different cell types (osteoblast, human umbilical vein endothelial cells) encapsulated in the bioprinted large‐scale constructs (≥1 cm) with nutrient networks show enhanced cell viability and spreading within a period of culture. It is envisioned that the advanced bioprinting technology may have significant potentials in facilitating the engineering of complex structures for tissue‐specific needs, and bioprinting large‐scale tissue constructs with nutrient networks toward applications in organ transplantation and repair.
Myelodysplastic syndromes and the risk of cardiovascular disease in older adults: A SEER-medicare analysis
Authors: Diego Adrianzen Herrera, Kith Pradhan, Rose Snyder, Siddharth Karanth, Murali Janakiram, Ioannis Mantzaris, Ira Braunschweig, Anjali Budhathoki, Urvi A. Shah, Amit K. Verma, Santosh B. Murthy, Aditi Shastri
Journal: Leukemia (2019)
Personalized Medicine for Primary Treatment of Serous Ovarian Cancer
Authors: Dan L. Longo
Journal: New England Journal of Medicine (2019)

The introduction of “personalized medicine” has spurred major changes in oncology, but success has been spread unevenly across the spectrum of solid tumors. Although prognoses for adenocarcinoma of the lung and melanoma have been profoundly altered, other diseases, such as colon cancer and ovarian cancer, have lagged behind owing to differences in genetics and biology. One of the earliest classes of targeted therapies in ovarian cancer has been the PARP (poly[adenosine diphosphate–ribose] polymerase) inhibitors.1-3 In this issue of the Journal, investigators report the results of three randomized trials of three different PARP inhibitors for maintenance therapy in patients with ovarian . . .
CRISPR/Cas9 Mediated ELANE Knock-out Restores Survival and Granulocytic Differentiation of HL60 Cells Expressing Mutant Neutrophil Elastase: Is Neutrophil Elastase a Dispensible Granulocyte Protease?
Authors: Vahagn Makaryan, Isabella N. Archibald, Merideth L. Kelley, Breanna Fletcher, David C. Dale
Journal: Blood (2019)
Functional Genomics Identifies Hepatitis-Induced STAT3–TYRO3–STAT3 Signaling as a Potential Therapeutic Target of Hepatoma
Authors: Chia-Liang Tsai, Jeng-Shou Chang, Ming-Chin Yu, Chern-Horng Lee, Tse-Ching Chen, Wen-Yu Chuang, Wei-Liang Kuo, Chen-Chun Lin, Shi-Ming Lin, Sen-Yung Hsieh
Journal: Clinical Cancer Research (2019)

Hepatitis promotes the development and recurrence of hepatocellular carcinoma (HCC). Receptor tyrosine kinases (RTK) play critical roles in the development of many cancers. We explored the potential roles of RTKs in hepatitis-related liver cancers.We conducted loss-of-function screening to elucidate the roles of RTKs in the development of HCC in vitro and in vivo.Many RTKs were coexpressed in HCC and were involved in tumor development and growth. Of these, TYRO3 promoted tumor growth and was clinically associated with hepatitis activity and poor prognosis. In mice, chemical-induced hepatitis transcriptionally activated Tyro3 expression via IL-6/IL6R-STAT3 signaling. Moreover, hepatitis-associated apoptotic cells facilitated the presentation of GAS6, a TYRO3 ligand, to further activate TYRO3-mediated signaling. Furthermore, TYRO3 activation elicited intracellular SRC- and STAT3 signaling. In mice, hepatitis and Tyro3 synergistically promoted HCC development. Silencing TYRO3 expression or inhibiting its kinase activity suppressed xenograft HCC growth in nude mice.Many RTKs are simultaneously involved in HCC development. Hepatitis exerts dual effects on the activation of TYRO3-mediated signaling in HCC cells, which further elicits the "TYRO3-STAT3-TYRO3" signaling loop to facilitate tumor growth. Our findings unveil a previously unrecognized link between RTKs and hepatitis-associated HCC and suggest TYRO3 as a marker and therapeutic target for the HCCs with higher hepatitis activity.
Abstract 14094: Relative Wall Thickness of the Left Ventricle is an Independent Risk Factor of Stroke or Systemic Embolism in Patients With Atrial Fibrillation in Japan: The Fushimi AF Registry
Authors: Yuji Tezuka, Moritake Iguchi, Kousuke Doi, Yoshimori An, Mitsuru Ishii, Nobutoyo Masunaga, Masahiro Esato, Yeong-Hwa Chun, Hiromichi Wada, Koji Hasegawa, Hisashi Ogawa, Mitsuru Abe, Masaharu Akao
Journal: Circulation (2017)

Introduction: It remains unclear which echocardiographic parameters are associated with stroke/ systemic embolism (SE) in atrial fibrillation (AF) patients. Methods: The Fushimi AF Registry, a comm...
The expression of PD-1 alone by T cells is associated with cell activation while the co-expression of TIM-3 indicates exhausted subsets both in peripheral blood and bone marrow of multiple myeloma patients
Authors: E. Batorov, V. Sergeevicheva, T. Aristova, S. Sizikova, G. Ushakova, A. Maximova, A. Morenkova, E. Shevela, A. Ostanin, E. Chernykh
Journal: Annals of Oncology (2019)
The Inherited Platelet Disorder of RUNX1 Haploinsufficiency (Familial Platelet Disorder with Associated Myeloid Malignancy (FPDMM)) Has a Marked Deficiency of Megakaryocyte-Biased Hematopoietic Progenitor Cells: Mechanistic Studies and Drug Correction
Authors: Brian Estevez, Sara Borst, Danuta Jadwiga Jarocha, Varun Sudunagunta, Michael Gonzalez, Peng Gao, Kai Tan, Deborah L French, Paul Gadue, Mortimer Poncz
Journal: Blood (2019)
Circulating tumor DNA as an early cancer detection tool
Authors: Andrea Campos-Carrillo, Jeffrey N. Weitzel, Prativa Sahoo, Russell Rockne, Janet V. Mokhnatkin, Muhammed Murtaza, Stacy W. Gray, Laura Goetz, Ajay Goel, Nicholas Schork, Thomas P. Slavin
Journal: Pharmacology & Therapeutics (2019)
Outcomes of bendamustine‐ or cyclophosphamide‐based first‐line chemotherapy in older patients with indolent B‐cell lymphoma
Authors: Adam J. Olszewski, James N. Butera, John L. Reagan, Jorge J. Castillo
Journal: American Journal of Hematology (2019)

Abstract Clinical trials comparing bendamustine/rituximab (BR) with cyclophosphamide‐based regimens (RCHOP/RCVP) have pooled various histologies of indolent B‐cell lymphomas. We examined real‐life outcomes of older patients with follicular (FL), mantle cell (MCL), or marginal zone/lymphoplasmacytic lymphoma (MZL/LPL), treated with these first‐line regimens. We identified Medicare beneficiaries with FL, MCL, or MZL/LPL, who received either first‐line BR or RCHOP/RCVP in 2009‐2016, and matched groups using a propensity score. Outcomes of claims‐based event‐free survival (EFS), overall survival (OS), toxicity, secondary cancers, and costs were compared in the aggregate cohort (N = 2736), and in separately matched histology‐specific subcohorts. In the aggregate cohort, EFS was better with BR than with RCHOP/RCVP (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.70‐0.87). Acute toxicity was lower with BR, including rates of hospitalizations (33% vs 45%), infections (21% vs 30%), cardiovascular events, and transfusions, yet OS did not differ (HR, 1.03; 95% CI, 0.91‐1.17) and Medicare spending was higher. There was no difference in the cumulative incidence of secondary cancers (subhazard ratio, 1.11; 95% CI, 0.83‐1.48). The EFS advantage of BR was pronounced in MCL (N = 690; HR, 0.64; 95% CI, 0.54‐0.76), but less so in FL (N = 1330; HR, 0.83; 95% CI, 0.69‐0.98) and absent in MZL/LPL (N = 574; HR, 0.92; 95% CI, 0.73‐1.17). Despite improved EFS and lower toxicity, the shift from RCHOP/RCVP to BR in clinical practice did not improve OS for older patients with indolent B‐cell lymphomas. Frequent infections and hospitalizations underscore the need for safer treatment approaches in this population. Secondary cancers do not appear to be increased after BR compared with RCHOP/RCVP.
Global burden of breast cancer and attributable risk factors in 195 countries and territories, from 1990 to 2017: results from the Global Burden of Disease Study 2017
Authors: Na Li, Yujiao Deng, Linghui Zhou, Tian Tian, Si Yang, Ying Wu, Yi Zheng, Zhen Zhai, Qian Hao, Dingli Song, Dai Zhang, Huafeng Kang, Zhijun Dai
Journal: Journal of Hematology & Oncology (2019)

Abstract Background Statistical data on the incidence, mortality, and burden of breast cancer and the relevant risk factors are valuable for policy-making. We aimed to estimate breast cancer incidence, deaths, and disability-adjusted life years (DALYs) by country, gender, age group, and social-demographic status between 1990 and 2017. Methods We extracted breast cancer data from the 2017 Global Burden of Disease (GBD) study from 1990 through 2017 in 195 countries and territories. Data about the number of breast cancer incident cases, deaths, DALYs, and the age-standardized rates were collected. We also estimated the risk factors attributable to breast cancer deaths and DALYs using the comparative risk assessment framework of the GBD study. Results In 2017, the global incidence of breast cancer increased to 1,960,681 cases. The high social-development index (SDI) quintile included the highest number of breast cancer death cases. Between 2007 and 2017, the ASDR of breast cancer declined globally, especially in high SDI and high middle SDI countries. The related DALYs were 17,708,600 in 2017 with high middle SDI quintile as the highest contributor. Of the deaths and DALYs, alcohol use was the greatest contributor in most GBD regions and other contributors included high body mass index (BMI) and high fasting plasma glucose. Conclusion The increasing global breast cancer burden is mainly observed in lower SDI countries; in higher SDI countries, the breast cancer burden tends to be relieving. Therefore, steps against attributable risk factors should be taken to reduce breast cancer burden in lower SDI countries.
Genetic instability as a driver for immune surveillance
Authors: Guim Aguadé-Gorgorió, Ricard Solé
Journal: Journal for ImmunoTherapy of Cancer (2019)

*: BackgroundGenetic instability is known to relate with carcinogenesis by providing tumors with a mechanism for fast adaptation. However, mounting evidence also indicates causal relation between genetic instability and improved cancer prognosis resulting from efficient immune response. Highly unstable tumors seem to accumulate mutational burdens that result in dynamical landscapes of neoantigen production, eventually inducing acute immune recognition. How are tumor instability and enhanced immune response related? An important step towards future developments involving combined therapies would benefit from unraveling this connection. *: MethodsIn this paper we present a minimal mathematical model to describe the ecological interactions that couple tumor adaptation and immune recognition while making use of available experimental estimates of relevant parameters. The possible evolutionary trade-offs associated to both cancer replication and T cell response are analysed, and the roles of mutational load and immune activation in governing prognosis are studied. *: ResultsModeling and available data indicate that cancer-clearance states become attainable when both mutational load and immune migration are enhanced. Furthermore, the model predicts the presence of well-defined transitions towards tumor control and eradication after increases in genetic instability numerically consistent with recent experiments of tumor control after Mismatch Repair knockout in mice. *: ConclusionsThese two main results indicate a potential role of genetic instability as a driver of transitions towards immune control of tumors, as well as the effectiveness of increasing mutational loads prior to adoptive cell therapies. This mathematical framework is therefore a quantitative step towards predicting the outcomes of combined therapies where genetic instability might play a key role.
Current trends and new developments in HIV research and periodontal diseases
Authors: Mark I. Ryder, Caroline Shiboski, Tzy‐Jyun Yao, Anna‐Barbara Moscicki
Journal: Periodontology 2000 (2019)

Abstract With the advent of combined antiretroviral therapies, the face of HIV infection has changed dramatically from a disease with almost certain mortality from serious comorbidities, to a manageable chronic condition with an extended lifespan. In this paper we present the more recent investigations into the epidemiology, microbiology, and pathogenesis of periodontal diseases in patients with HIV, and the effects of combined antiretroviral therapies on the incidence and progression of these diseases both in adults and perinatally infected children. In addition, comparisons and potential interactions between the HIV‐associated microbiome, host responses, and pathogenesis in the oral cavity with the gastrointestinal tract and other areas of the body are presented. Also, the effects of HIV and combined antiretroviral therapies on comorbidities such as hyposalivation, dementia, and osteoporosis on periodontal disease progression are discussed.
Double Environmental Injustice — Climate Change, Hurricane Dorian, and the Bahamas
Authors: James M. Shultz, Duane E. Sands, James P. Kossin, Sandro Galea
Journal: New England Journal of Medicine (2019)

Double Environmental Injustice The escalating effects of hurricanes on population health represent a double environmental injustice: disadvantaged populations sustain disproportionate harm, and tho...
Letter to the Editor: Some TIPS for Future Decompensations!
Authors: Achintya Dinesh Singh, Agrima Mian
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: In the September 12, 2019 issue of Hepatology, Billey et al. published a study assessing the laboratory, echocardiographic, and right heart catheter–based parameters to predict cardiac decompensation in patients undergoing a transjugular intrahepatic porto systemic shunts (TIPS) procedure.1 A total of 100 patients who were evaluated with serum N‐terminal b‐type natriuretic peptide (NT‐proBNP) levels and echocardiography were included. Prior underlying cardiac diseases like aortic stenosis and cardiomyopathy, the presence of echocardiographic features of diastolic dysfunction, and a raised pulmonary capillary wedge pressure predicted post‐TIPS cardiac decompensation. These findings emphasize the importance of evaluation of diastolic function in patients with cirrhosis, especially if they have an elevated NT‐proBNP at the time of hospital admission. We would like to bring forth some more points that require due consideration. Of the 100 patients who were included in the study, 20 (20%) had cardiac decompensation. In a similar study of 882 patients with cirrhosis from our center, only 8 (0.9%) developed cardiac decompensation during the first week.2 Our findings concurred with the present study that diastolic dysfunction was associated with higher rates of post‐procedure cardiac decompensation. As most of the fluid shift–related cardiac decompensation in TIPS should happen immediately after the procedure, it would be important to know the proportion of patients who had early heart failure (within the first week) in this study. It would also be interesting to compare the clinical parameters of these patients with those who had late decompensation. The impact of goal‐directed therapy for heart failure in this patient population has not been reported. Understanding the differences in drug therapies, especially beta blockers and diuretics, can be useful. We suggest performing a regression analysis to evaluate the treatment differences between patients who decompensated and those who did not. In addition, studies have shown that reduction of cardiac reserve precedes the onset of diastolic or systolic dysfunction.3 It would have been interesting to assess the cardiac reserve volume in these patients by a formal stress testing in those with elevated NT‐proBNP, as it may likely influence post‐TIPS cardiac decompensation. We commend Billey et al. for the rigorously performed study. The evaluation and management of cirrhotic cardiomyopathy and cardiac dysfunction in cirrhosis has many unanswered questions, and this study is a step in the right direction.
Re: Malte W. Vetterlein, Jakob Klemm, Philipp Gild, et al. Improving Estimates of Perioperative Morbidity After Radical Cystectomy Using the European Association of Urology Quality Criteria for Standardized Reporting and Introducing the Comprehensive Complication Index. Eur Urol 2019;77:55–65
Authors: Liang Sun, Yi Feng
Journal: European Urology (2019)