tbuckley/cabot-search huggingface dataset:
β‐catenin deficiency in hepatocytes aggravates hepatocarcinogenesis driven by oncogenic β‐catenin and MET
Authors: Yan Liang, Yun Feng, Min Zong, Xu‐Fu Wei, Jin Lee, Yukuan Feng, Hairi Li, Guang‐Shun Yang, Zhong‐Jun Wu, Xiang‐Dong Fu, Gen‐Sheng Feng
Journal: Hepatology (2017)

Both activating and inactivating mutations in catenin β1 ( ctnnb1 ), which encodes β‐catenin, have been implicated in liver tumorigenesis in humans and mice, although the underlying mechanisms are not fully understood. Herein, we show that deletion of endogenous β‐catenin in hepatocytes aggravated hepatocellular carcinoma (HCC) development driven by an oncogenic version of β‐catenin (CAT) in combination with the hepatocyte growth factor receptor MET proto‐oncogene receptor tyrosine kinase (MET). Although the mitogenic signaling and cell cycle progression was modestly impaired after CAT/MET transfection, the β‐catenin‐deficient livers displayed changes in transcriptomes, increased DNA damage response, expanded Sox9 + cells, and up‐regulation of protumorigenic cytokines, including interleukin‐6 and transforming growth factor β1. These events eventually exacerbated CAT/MET‐driven hepatocarcinogenesis in β‐catenin‐deficient livers, featured by up‐regulation of extracellular signal‐regulated kinase (Erk), protein kinase B (Akt), and Wnt/β‐catenin signaling and cyclin D1 expression. The resultant mouse tumors showed similar transcriptomes to human HCC samples with concomitant CTNNB1 mutations and MET overexpression. Conclusion : These data argue that while dominantly activating mutants of β‐catenin are oncogenic, inhibiting the oncogenic signaling pathway generates a pro‐oncogenic microenvironment that may facilitate HCC recurrence following a targeted therapy of the primary tumor. An effective therapeutic strategy must require disruption of the oncogenic signaling in tumor cells and suppression of the secondary tumor‐promoting stromal effects in the liver microenvironment. (H epatology 2018;67:1807‐1822)
Inhibition of the Epigenetic Modifier EZH2 Upregulates Cell Cycle Control Genes to Inhibit Myeloma Cell Growth and Overcome High-Risk Disease Features
Authors: Charlotte Pawlyn, Michael Bright, Amy Buros, Caleb K. Stein, Zoe Walters, Lauren Aronson, Fabio Mirabella, Martin F Kaiser, John R Jones, Brian A Walker, Graham H Jackson, Paul Clarke, Leif Bergsagel, Paul Workman, Marta Chesi, Gareth J Morgan, Faith E Davies
Journal: Blood (2016)
PDGFR-β gene expression relates to recurrence in colorectal cancer
Authors: N. Miyoshi, S. Fujino, M. Ohue, Y. Takahashi, M. Yasui, H. Takahashi, N. Haraguchi, J. Nishimura, T. Hata, C. Matsuda, T. Mizushima, Y. Doki, M. Mori
Journal: Annals of Oncology (2017)
Employment status at time of first hospitalization for heart failure is associated with a higher risk of death and rehospitalization for heart failure
Authors: Rasmus Rørth, Emil L. Fosbøl, Ulrik M. Mogensen, Kristian Kragholm, Anna‐karin Numé, Gunnar H. Gislason, Pardeep S. Jhund, Mark C. Petrie, John J.V. McMurray, Christian Torp‐Pedersen, Lars Køber, Søren L. Kristensen
Journal: European Journal of Heart Failure (2017)
Investigation of the Relationship Between Radiation Dose and Gene Mutations and Fusions in Post-Chernobyl Thyroid Cancer
Authors: Alexey A Efanov, Alina V Brenner, Tetiana I Bogdanova, Lindsey M Kelly, Pengyuan Liu, Mark P Little, Abigail I Wald, Maureen Hatch, Liudmyla Y Zurnadzy, Marina N Nikiforova, Vladimir Drozdovitch, Rebecca Leeman-Neill, Kiyohiko Mabuchi, Mykola D Tronko, Stephen J Chanock, Yuri E Nikiforov
Journal: JNCI Journal of the National Cancer Institute (2017)

Exposure to ionizing radiation during childhood is a well-established risk factor for thyroid cancer. However, the genetic mechanisms of radiation-associated carcinogenesis remain not fully understood.In this study, we used targeted next-generation sequencing and RNA-Seq to study 65 papillary thyroid cancers (PTCs) from patients in the Ukrainian-American cohort with measurement-based iodine-131 (I-131) thyroid doses received as a result of the Chernobyl accident. We fitted linear regression models to evaluate differences in distribution of risk factors for PTC according to type of genetic alteration and logistic regression models to evaluate the I-131 dose response. All statistical tests were two-sided.Driver mutations were identified in 96.9% of these thyroid cancers, including point mutations in 26.2% and gene fusions in 70.8% of cases. Novel driver fusions such as POR-BRAF, as well as STRN-ALK fusions that have not been implicated in radiation-associated cancer before, were found. The mean I-131 dose in cases with point mutations was 0.2 Gy (range = 0.013-1.05 Gy), statistically significantly lower than 1.4 Gy (range = 0.009-6.15 Gy) for cases with fusions (P < .001). No driver point mutations were found in tumors from individuals who received more than 1.1 Gy of radiation. Relative to tumors with point mutations, the proportion of tumors with gene fusions increased with radiation dose, reaching 87.8% among individuals exposed to 0.3 Gy or higher. With a limited study sample size, the estimated odds ratio at 1 Gy was 20.01 (95% confidence interval = 2.57 to 653.02, P < .001). In addition, after controlling for I-131 dose, we found higher odds ratios for gene fusion-positive PTCs associated with several specific demographic and geographic features.Our data provide support for a link between I-131 thyroid dose and generation of carcinogenic gene fusions, the predominant mechanism of thyroid cancer associated with radiation exposure from the Chernobyl accident.
Palliative versus nonpalliative patients’ perceptions of the effect of alcohol consumption on clinical outcomes.
Authors: Graham McFarlane, Karmugi Balaratnam, Peter Selby, Shabbir Alibbhai, M. Catherine Brown, Jennifer M. Jones, Doris Howell, Dan Pringle, Wei Xu, Geoffrey Liu, Lawson Eng
Journal: Journal of Clinical Oncology (2017)

199 Background: Little is known about the perceptions of palliative patients on the impact of continued alcohol consumption after a cancer diagnosis and whether they are similar to the perceptions of patients who are considered potentially curative. Methods: Patients with diverse cancer subtypes were surveyed at a comprehensive cancer centre, cross-sectionally. Specifically, palliative and non-palliative cancer patients were asked about their perceptions on the benefits/harms of continued drinking on cancer-related quality of life, fatigue, and overall survival, and whether they had received information on their alcohol consumption from their health care providers. Palliative status was established by chart review. Results: Of 1049 patients, 48% were male, with median age of 58 (18-98) years; cancer sites included gastrointestinal, genitourinary, breast, thoracic, hematologic, and others; 16% were classified as being palliative at the time of survey; and 14% reported receiving counselling information on alcohol use sometime after their cancer diagnosis. Compared to curative patients, palliative patients were more likely to perceive continued alcohol consumption as harmful to their fatigue (OR=1.39, P=0.05) and survival (OR=1.45, P=0.03), but less so on quality of life (OR=1.16, P=0.35). When compared to those who had not been counselled, informed patients were twice as likely (OR=2.01, P&lt;0.01) to perceive continued drinking as harmful to their levels of fatigue, although there was less of a difference in their perception of quality of life (OR =1.39, P=0.20) and survival (OR=1.40, P=0.19). Conclusions: Palliative patients are more likely to perceive continued alcohol consumption as harmful to their fatigue and overall survival, when compared to non-palliative patients, especially after receiving counselling. Given the lack of data on the benefits or harm of mild-moderate alcohol use and a strong emphasis on quality of life, future research should focus on effects of alcohol in palliative patients, and there should be improved education to both providers and patients on regarding the current lack of information.
Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma
Authors: Thierry Facon, Meletios A. Dimopoulos, Angela Dispenzieri, John V. Catalano, Andrew Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar J. Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie D. Cavenagh, Catarina Geraldes, Je-Jung Lee, Christine Chen, Albert Oriol, Javier De La Rubia, Darrell White, Daniel Binder, Jin Lu, Kenneth C. Anderson, Philippe Moreau, Michel Attal, Aurore Perrot, Bertrand Arnulf, Lugui Qiu, Murielle Roussel, Eileen Boyle, Salomon Manier, Mohamad Mohty, Herve Avet-Loiseau, Xavier Leleu, Annette Ervin-Haynes, Guang Chen, Vanessa Houck, Lotfi Benboubker, Cyrille Hulin
Journal: Blood (2017)
Decitabine enhances targeting of AML cells by CD34+ progenitor-derived NK cells in NOD/SCID/IL2Rgnull mice
Authors: Jeannette Cany, Mieke W. H. Roeven, Janneke S. Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M. A. Blijlevens, Walter J. van der Velden, Gerwin Huls, Joop H. Jansen, Nicolaas P. M. Schaap, Harry Dolstra
Journal: Blood (2017)
Hybrid-capture based comprehensive genomic profiling of hepatocellular carcinoma identifies patients who may benefit from targeted therapies and immune checkpoint blockade
Authors: J. Suh, E. Severson, J. Hechtman, G. Frampton, D. Fabrizio, J. Sun, S. Ali, P. Gu, S. Klempner, V. Miller, P. Stephens, J. Ross
Journal: Annals of Oncology (2017)
Multi-institutional competing risks analysis of distant brain failure and salvage patterns after upfront radiosurgery without whole brain radiotherapy for brain metastasis
Authors: E. McTyre, D. Ayala-Peacock, J. Contessa, C. Corso, V. Chiang, C. Chung, J. Fiveash, M. Ahluwalia, R. Kotecha, S. Chao, A. Attia, A. Henson, J. Hepel, S. Braunstein, M. Chan
Journal: Annals of Oncology (2017)
Abstract 19164: Cell Free DNA Levels is Associated With Inflammation and Thrombosis Following Pediatric Cardiopulmonary Bypass
Authors: Alejandro Floh, Cedric Manlhiot, Brian McCrindle, Gustavo La Rotta, Glen Van Arsdell, Steven Schwartz
Journal: Circulation (2017)

Introduction: Cell free DNA (cfDNA) is released into the circulation in the setting of various pathological states and is linked with morbidity, including systemic inflammation (SIRS) and thrombosi...
Placental growth factor inhibition alleviates hepatopulmonary syndrome in mice
Authors: Sarah Raevens, Annelies Paridaens, Sander Lefere, Bart Jonckx, Xavier Verhelst, Hans Van Vlierberghe, Christophe Van Steenkiste, Anja Geerts, Lindsey Devisscher, Isabelle Colle
Journal: Hepatology (2016)
Structural priming supports grammatical networks
Authors: Richard Hudson
Journal: Behavioral and Brain Sciences (2017)

Abstract As Branigan &amp; Pickering (B&amp;P) argue, structural priming has important implications for the theory of language structure, but these implications go beyond those suggested. Priming implies a network structure, so the grammar must be a network and so must sentence structure. Instead of phrase structure, the most promising model for syntactic structure is enriched dependency structure, as in Word Grammar.
A dynamic managed care platform for palliative care.
Authors: Briant Fruth, Tom R. Fitch, Robert P. Shannon, Ryan Uitti, Elise Carey, Cory Ingram, Angelina D. Tan, Alex Alexander, Rahma M. Warsame, Margot Melanson-Arnold, Jeff A. Sloan
Journal: Journal of Clinical Oncology (2017)

32 Background: The link between patient concerns and clinical systems delivery is often suboptimal. We developed a case management system for palliative care which transforms the patient’s greatest concerns into actionable clinical pathways. Methods: The system collects patients’ single greatest and second greatest concern plus Quality of Life (QOL) data (pain, fatigue and overall QOL single-items scored 0-10 with 10 representing worst pain/fatigue, or best QOL) and produces a report to guide the physician and patient. The system presents ten “buttons” in a xylophone-like grid: Personal Relationships, Monitoring Health, Emotional Health, Money, Health Behaviors, Medication Troubles, Care Access, Work Worries, Physical Health and Care Planning. We performed a quality improvement study at Mayo Clinic sites. Results: 409 patients participated in at least one survey from 11/04/2015 to 9/22/2016 (620 total surveys). The most common Main Concern was Physical Health 265/620 (43%) followed by Monitoring Health (17%), Medication (8%), and Emotional Health, Money, and Health Behaviors (7% each), Personal Relationships (6%). Future Care Planning, Work, and Care Access/Coordination were rarely chosen ( &lt; 5%). The most common Second greatest concern was Health Behaviors 73/409 (18%) followed by Physical Health (17%). 93/122 (67%) patients changed their greatest concern from baseline to subsequent visits. The mean QOL, fatigue and pain at baseline were 4.8, 6.0 and 4.8 respectively, indicating substantial clinically significant deficits. Post baseline mean scores improved by a maximum of 0.8, 1.1, and 0.9 points respectively, representing clinically meaningful effects. On average it took 8 minutes for patients to use the system. Conclusions: The system was quick and easy to utilize. The personal impact concerns (physical/emotional health, medications) were most often cited as the greatest concern, while care issues were de-emphasized by patients. Patients and physicians praised the system for making visits more efficient and raising issues that otherwise might not have been addressed. This system has the potential to improve patient well-being and clinical outcomes, as well as to reduce burden on clinicians and optimize case management activities.
Suppression of FIP200 and autophagy by tumor-derived lactate promotes naïve T cell apoptosis and affects tumor immunity
Authors: Houjun Xia, Wei Wang, Joel Crespo, Ilona Kryczek, Wei Li, Shuang Wei, Zhaoqun Bian, Tomasz Maj, Mingxiao He, Rebecca J. Liu, Youwen He, Ramandeep Rattan, Adnan Munkarah, Jun-Lin Guan, Weiping Zou
Journal: Science Immunology (2017)

Naïve T cells are poorly studied in cancer patients. We report that naïve T cells are prone to undergo apoptosis due to a selective loss of FAK family-interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This results in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. Mechanistically, loss of FIP200 disables the balance between proapoptotic and antiapoptotic Bcl-2 family members via enhanced argonaute 2 (Ago2) degradation, reduced Ago2 and microRNA1198-5p complex formation, less microRNA1198-5p maturation, and consequently abolished microRNA1198-5p-mediated repression on apoptotic gene
Abstract 16131: Certified Basic Life Support Instructors Assess Cardiopulmonary Resuscitation Skills Poorly
Authors: Camilla Hansen, Stinne E Rasmussen, Mette A Nebsbjerg, Mathilde Stærk, Bo Løfgren
Journal: Circulation (2016)

Introduction: High-quality cardiopulmonary resuscitation (CPR) improves survival from cardiac arrest. During basic life support (BLS) training, instructors assess CPR skills to enhance learning out...
Alectinib (ALC) vs crizotinib (CRZ) in treatment-naïve ALK+ non-small-cell lung cancer (NSCLC): Asian vs non-Asian subgroup analysis of the ALEX study
Authors: T.S.K. Mok, S. Peters, D.R. Camidge, S-H I Ou, J.S. Ahn, E.H. Tan, Z. Li, J-S Lee, B.C. Cho, S.L. Geater, V. Sriuranpong, J. Ho, O S-H Chan, A. Zeaiter, B. Balas, E. Nueesch, E. Mitry, P.N. Morcos, D-W Kim
Journal: Annals of Oncology (2017)
Abstract 2343: Analysis of the Tachycardia Circuit in Patients With Slow-Fast Form of Atrioventricular Nodal Reentrant Tachycardia Using the Right and Left Atrial Single Extrastimulation
Authors: Kenji Morihisa, Hiroshige Yamabe, Yasuaki Tanaka, Takashi Uemura, Koji Enomoto, Hisao Ogawa
Journal: Circulation (2009)

Background: Radiofrequency catheter ablation of the slow pathway is an establish treatment for slow-fast form of atrioventricular nodal reentrant tachycardia (AVNRT). However, rare cases of the slo...
Regulation of EGFR activity through N-glycan fucosylation and effect on the sensitivity of EGFR-TKI
Authors: Kazuko Matsumoto, Hideyuki Yokote, Kaoru Tanaka, Mari Maegawa, Tokuzo Arao, Yoshihiko Fujita, Kazuto Nishio
Journal: Cancer Research (2007)

2068   The glycosylation of cell surface proteins is important for cancer biology processes like cell proliferation and metastasis. Receptor tyrosine kinases are usually modified by glycosylation at the cell membrane, and the glycosylation status often regulates the receptors’ activities. α1,6-fucosyltransferase (Fut8) catalyzes the transfer of a fucose residue to N-linked oligosaccharides on glycoproteins via an α1,6-linkage to form core fucosylation in mammals. Here, we studied the fucosylation of EGFR protein by FUT8 and its effect on receptor activity. First, we constructed HEK293 cells expressing Flag-tagged FUT8 at its c-terminus (293/FUT8) and found that the level of EGFR fucosylation in the 293/FUT8 cells increased, compared with that in the control cells. Furthermore, we found that highly fucosylated EGFR was more responsive to EGF ligand stimulation, as determined using an XTT assay, than the control. Next, we constructed 293/EGFR/FUT8 cells by the additional introduction of the FUT8 gene into 293/EGFR and studied the relationship between EGFR fucosylation and sensitivity to EGFR-TKI using an MTT assay. As expected, the 293/EGFR/FUT8 cells were more sensitive to gefitinib than the 293/EGFR cells. In conclusion, FUT8-fucosylated EGFR regulated its responsiveness to ligand stimulation, and therefore affected the sensitivity to EGFR-TKI.
Review: Defining a Unified Vascular Phenotype in Systemic Sclerosis
Authors: Yannick Allanore, Oliver Distler, Marco Matucci‐Cerinic, Christopher P. Denton
Journal: Arthritis & Rheumatology (2017)

Microcirculation impairment and related vasculopathy are hallmarks of systemic sclerosis (SSc). Digital ulceration is second only to Raynaud's phenomenon as a vascular complication occurring in patients with SSc. Digital ulcers are painful and generate disability. Furthermore, patients may develop recurrent digital ulcers, and it is reasonable to question whether the outcomes of such patients might be different from those of patients who are not affected. Recently, several registries have provided relevant information about digital ulcers. Male sex and severe skin disease appear to be the main associated factors observed in several registries. However, limitations of those studies are the differences in the definitions of digital ulcers and organ involvement. Few longitudinal studies are available, and the more robust data from the European League Against Rheumatism Scleroderma Trial and Research cohort suggested worse outcomes in patients with a history of digital ulcers but could not demonstrate that a history of digital ulcers can predict additional vascular complications such as pulmonary arterial hypertension, heart failure, or renal crisis. Nevertheless, the autopsy studies published many years ago and the more recent longitudinal biomarker studies support the concept of generalized vasculopathy and a potential association between various cardiovascular complications. It is expected that with the availability of several structured registries, identification of a vascular profile or vascular phenotype will be addressed using more robust data in the near future.
A description of cancer directed therapy within 14 days of death in a community cancer institute.
Authors: Kristina Newport, Rachel Holliday, Caitlyn McNaughton, Emily Gehron, Michael Horst, Shanthi Sivendran
Journal: Journal of Clinical Oncology (2017)

73 Background: It is recommend that no more than 10% of patients receive chemotherapy within 14 days of death. Aggressive end of life interventions like chemotherapy and hospitalization are used as measures of quality. However, cancer care now includes immunotherapy and targeted therapies. It is therefore important to understand how all cancer directed treatments are utilized at end of life, to better define the group of patients for whom they are indicated. Therefore, we sought to describe the people in our institution who received cancer directed therapy in the last two weeks of life. Methods: Adult patients who received cancer directed therapy for any malignancy in a single community cancer institute and died from July 2016-April 2017 were included. Retrospective data collection included clinical cancer stage and type, ECOG performance status (ECOG), last cancer therapy, date of death, dates of treatment, type of treatment, treatment goal, demographics and utilization of ED, hospital, palliative care and hospice. Results: A total of 218 patients were included. 13.7% (30/218) received cancer directed therapy within 14 days of death. Of those patients, only four had ECOG of 3, while 26 had ECOG 0-2. The average duration from treatment to death in this group was eight days, with one patient dying on the day of treatment. The average duration from treatment to death for all patients was 166 days (median 59). 20 patients receiving cancer directed therapy at end of life received chemotherapy, while the remaining 10 received targeted therapy (8) or immunotherapy (2). 40% (8/20) of patients in the chemotherapy group died in hospital as did 50% (5/10) of the remaining patients. Most patients in the overall sample (83%) were being treated with palliative intent. 20% (6/30) of the patients who died within 14 days of treatment were being treated with curative intent. Conclusions: Recommendations regarding cancer directed treatment near end of life need to include non-chemotherapy treatments such as immunotherapy and targeted treatments. Although a small sample size, our data suggest that patients on these treatments receive aggressive end of life care at a similar frequency as those who receive chemotherapy.