tbuckley/cabot-search huggingface dataset:
Questionable Survival Benefit of Aspirin Use in Patients With Biliary Tract Cancer
Authors: John R. Bergquist, Omair A. Shariq, Brendan C. Visser
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
USE OF MACHINE LEARNING TECHNIQUES TO IDENTIFY RISK FACTORS FOR CARDIAC IMPLANTABLE ELECTRONIC DEVICE (CIED) INFECTION: LESSONS FROM THE WRAP-IT TRIAL
Authors: Khaldoun G. Tarakji, Andrew D. Krahn, Jeanne Poole, Suneet Mittal, Charles Kennergren, G. Ralph Corey, Mauro Biffi, Panaglotls Korantzopoulos, Paolo Dallaglio, Daniel Lexcen, Jeff D. Lande, Reece Holbrook, Bruce Wilkoff
Journal: Journal of the American College of Cardiology (2020)
Cellular responses to lactate in breast cancer.
Authors: Kelly Marie Kennedy, Mark W Dewhirst
Journal: Journal of Clinical Oncology (2012)

e21119 Background: Clinical studies across different tumor types have found that high lactate levels correlate with increased metastases and poor patient prognosis, overall and metastasis-free survival; however, mechanisms are unknown. There is increasing evidence of cancer stem cells (CSC). Lactate inducing a stem-like phenotype may be one explanation for the increased metastases seen in high-lactate solid tumors. We hypothesized that lactate induces EMT in human breast cancer cells and induces/selects for a stem-like phenotype. Methods: We examined lactate levels in locally advanced breast cancer (LABC) biopsies using bioluminescence. Breast cancer cell lines (MCF7, T-47D, MDA-MB-231) were treated acutely (hours) or chronically (weeks) with lactate (0-40mM) and tested for cell viability (Annexin V, clonogenics), EMT markers (Snail-1), cellular detachment, and anchorage-independent cell growth (mammosphere assays). There was one “no treatment” control group. Experimental groups were treated with lactate in the context of complete media or glucose-free conditions (to mimic the typical tumor microenvironment). For the mammosphere assays, cells were treated both prior to (attached as a monolayer) and during sphere formation. Results: Lactate concentrations in the LABC biopsies were between 0-7.5mM. Lactate levels relevant to solid tumors (&lt;40mM) were not toxic to the cell lines tested. Cellular detachment after lactate treatment was not statistically significant; however, the percentage of viable detached cells was significantly increased, and they retained colony-forming abilities. Preliminary data shows a slight increase in Snail-1 levels after chronic lactate treatment. Chronic lactate treatment had a slight but statistically significant effect on secondary mammosphere formation in MCF7s, indicating the important self-renewal properties characteristic of CSCs. Conclusions: The effect of lactate treatment alone on human breast cancer cell lines is subtle but significant. Phenotypic changes elicited by lactate are dependent upon lactate concentration and duration of treatment. Results thus far support the hypothesis that lactate affects expression of stem-like properties in breast cancer cell lines. Supported by BC083154 and R01 CA40355
TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis
Authors: Eric Gracey, Dominika Hromadová, Melissa Lim, Zoya Qaiyum, Michael Zeng, Yuchen Yao, Archita Srinath, Yuriy Baglaenko, Natalia Yeremenko, William Westlin, Craig Masse, Mathias Müller, Birgit Strobl, Wenyan Miao, Robert D. Inman
Journal: Journal of Clinical Investigation (2020)

Spondyloarthritis (SpA) represents a family of inflammatory diseases of the spine and peripheral joints. Ankylosing spondylitis (AS) is the prototypic form of SpA in which progressive disease can lead to fusion of the spine. Therapeutically, knowledge of type 3 immunity has translated into the development of IL-23– and IL-17A–blocking antibodies for the treatment of SpA. Despite being able to provide symptomatic control, the current biologics do not prevent the fusion of joints in AS patients. Thus, there is an unmet need for disease-modifying drugs. Genetic studies have linked the Janus kinase TYK2 to AS. TYK2 is a mediator of type 3 immunity through intracellular signaling of IL-23. Here, we describe and characterize a potentially novel small-molecule inhibitor of TYK2 that blocked IL-23 signaling in vitro and inhibited disease progression in animal models of SpA. The effect of the inhibitor appears to be TYK2 specific, using TYK2-inactive mice, which further revealed a duality in the induction of IL-17A and IL-22 by IL-23. Specifically, IL-22 production was TYK2/JAK2/STAT3 dependent, while IL-17A was mostly JAK2 dependent. Finally, we examined the effects of AS-associated TYK2 SNPs on TYK2 expression and function and correlated them with AS disease progression. This work provides evidence that TYK2 inhibitors have great potential as an orally delivered therapeutic for SpA.
DURATION OF OESTROGEN EXPOSURE DURING REPRODUCTIVE YEARS, AGE AT MENARCHE, AGE AT MENOPAUSE, AND RISK OF CARDIOVASCULAR DISEASE EVENTS, ALL-CAUSE AND CARDIOVASCULAR MORTALITY, A SYSTEMATIC REVIEW
Authors: Shiva Raj Mishra, Hsin-Fang Chung, Michael Waller, Gita D. Mishra
Journal: Journal of the American College of Cardiology (2020)
RUNX1 Is a Driver of Renal Cell Carcinoma Correlating with Clinical Outcome
Authors: Nicholas Rooney, Susan M. Mason, Laura McDonald, J. Henry M. Däbritz, Kirsteen J. Campbell, Ann Hedley, Steven Howard, Dimitris Athineos, Colin Nixon, William Clark, Joshua D.G. Leach, Owen J. Sansom, Joanne Edwards, Ewan R. Cameron, Karen Blyth
Journal: Cancer Research (2020)

Abstract The recurring association of specific genetic lesions with particular types of cancer is a fascinating and largely unexplained area of cancer biology. This is particularly true of clear cell renal cell carcinoma (ccRCC) where, although key mutations such as loss of VHL is an almost ubiquitous finding, there remains a conspicuous lack of targetable genetic drivers. In this study, we have identified a previously unknown protumorigenic role for the RUNX genes in this disease setting. Analysis of patient tumor biopsies together with loss-of-function studies in preclinical models established the importance of RUNX1 and RUNX2 in ccRCC. Patients with high RUNX1 (and RUNX2) expression exhibited significantly poorer clinical survival compared with patients with low expression. This was functionally relevant, as deletion of RUNX1 in ccRCC cell lines reduced tumor cell growth and viability in vitro and in vivo. Transcriptional profiling of RUNX1-CRISPR–deleted cells revealed a gene signature dominated by extracellular matrix remodeling, notably affecting STMN3, SERPINH1, and EPHRIN signaling. Finally, RUNX1 deletion in a genetic mouse model of kidney cancer improved overall survival and reduced tumor cell proliferation. In summary, these data attest to the validity of targeting a RUNX1-transcriptional program in ccRCC. Significance: These data reveal a novel unexplored oncogenic role for RUNX genes in kidney cancer and indicate that targeting the effects of RUNX transcriptional activity could be relevant for clinical intervention in ccRCC.
Favorable outcomes with chemoradiation and surgery for locally advanced non-small cell lung cancer: The BC Cancer Agency Vancouver experience.
Authors: Wen Wen Shan, Sophie Sun, Janessa J. Laskin, Cheryl Ho, Barbara L. Melosky, Hannah Carolan, Karen Goddard, Jonn Wu, Eric Berthelet, Mitchell Liu, Kenneth Evans, Richard Finley, John Yee, Diana Ionescu, Nevin Murray
Journal: Journal of Clinical Oncology (2012)

7020 Background: The role of surgery following concurrent platinum-based chemotherapy and radiation for locally advanced non-small cell lung cancer (NSCLC) remains controversial, with high surgical mortality rates reported in a large randomized clinical trial. In this retrospective study, we evaluated the safety and efficacy of concurrent chemoradiation with or without surgery over an 11 period at the BC Cancer Agency. Methods: Patients were identified by the Vancouver Centre Pharmacy database. Charts were reviewed and data extracted included patient characteristics, weight loss, performance status, and method of mediastinal staging. Outcome measures were overall survival, pathological response rate, and treatment-associated morbidity and mortality. Results: Between January 1999-2010, 177 patients were identified with locally advanced NSCLC (stage IIIA/B) treated with platinum and etoposide and ≥40Gy radiation therapy, with or without surgical resection. The majority of treatment plans were reached by a multidisciplinary conference consensus. 74% (n=131) of patients received chemoradiation alone (bimodality therapy) and 36% (n=46) received chemoradiation followed by surgical resection (trimodality therapy). Among the trimodality therapy group, 16 patients underwent pneumonectomy and 30 lobectomy. Conclusions: In this series, bimodality therapy for patients with locally advanced NSCLC had similar treatment associated mortality and survival outcomes as reported in the literature. Trimodality therapy was associated with low treatment mortality rates and favourable survival. These two groups cannot be directly compared in this retrospective study. However, these results support a multidisciplinary approach to identify and carefully select patients with locally advanced NSCLC to undergo additional surgical resection following concurrent chemoradiation. [Table: see text]
COMPARISON OF OUTCOMES (CORONARY REVASCULARIZATION, LENGTH OF STAY, CARDIOGENIC SHOCK AND IN-HOSPITAL MORTALITY) OF PATIENTS WITH ST ELEVATION MYOCARDIAL INFARCTION WITH VS. WITHOUT SYSTEMIC INFLAMMATORY RESPONSE SYNDROME WITHOUT EVIDENCE OF SEPSIS
Authors: Hassaan B. Arshad, Sara Ayaz Butt, Richard Hajjar, Rehan Umar, Kumar Satya
Journal: Journal of the American College of Cardiology (2020)
INTRAHEPATIC DYNAMIC CONTRAST-ENHANCED LYMPHANGIOGRAPHY IN PATIENTS WITH CONGENITAL HEART DISEASE: A POTENTIAL IMAGING SIGNATURE FOR PROTEIN-LOSING ENTEROPATHY
Authors: Bethan Lemley, David Biko, Aaron Dewitt, Matthew J. Gillespie, Andrew C. Glatz, Michael L. O'Byrne, Erin Pinto, Chitra Ravishankar, Jonathan J. Rome, Christopher Smith, Yoav Dori
Journal: Journal of the American College of Cardiology (2020)
Timeliness of care and stage at diagnosis of non-small cell lung cancer (NSCLC) with the implementation of a cancer care coordination program (CCCP) at a VA medical center.
Authors: Susan Alsamarai, Herta H. Chao, Xiaopan Yao, Yanhong Deng, Michal G. Rose
Journal: Journal of Clinical Oncology (2012)

6033 Background: Timeliness of care improves patient satisfaction and may improve outcomes. A CCCP was established in Nov 2007 to improve timeliness of care of NSCLC patients at the Veterans Affairs Connecticut (VACT) Healthcare System. Methods: We performed a retrospective cohort analysis of patients diagnosed with NSCLC at VACT between 2005-2010. We compared timeliness of care and stage at diagnosis before and after the implementation of the CCCP. Results: Data from 352 patients was analyzed: 163 with initial abnormal imaging between 1/1/2005 and 10/31/2007, and 189 with imaging between 11/1/2007 and 12/31/2010. Variables associated with a longer interval between the initial abnormal image and the initiation of therapy were: (1) earlier stage (mean of 130 days for stages I/II vs. 87 days for stages III/IV, p&lt;0.001),(2) lack of cancer-related symptoms (145 vs 60 days, p&lt;0.001), (3) presence of medical co-morbidities (111 vs 76 days, p=0.01), and (4) depression (127 vs 98 days, p=0.029). Substance abuse increased the interval from initial abnormal image to tissue diagnosis by 29 days (p=0.032) but did not affect the interval from image to treatment. The mean interval between diagnosis and initiation of treatment was 19 days longer in blacks vs. non-blacks (55 vs 36 days, p=0.0118) although the overall time from abnormal image to diagnosis and to treatment was not statistically different. In a multivariate model adjusting for stage, histology, reason for initial imaging, and presence of a primary care provider, implementation of a CCCP resulted in a mean reduction of 25 days in the time between the first abnormal image and initiation of cancer treatment (126 to 101 days, p=0.0154). The percent of patients diagnosed at stages I and II increased from 32% to 48% (p=0.0065) after the implementation of a CCCP. Conclusions: A centralized, multidisciplinary, hospital-based CCCP can improve timeliness of NSCLC care, and may also help ensure that incidental, early stage lung cancers are treated.
Targeting Glycosylated PD-1 Induces Potent Antitumor Immunity
Authors: Linlin Sun, Chia-Wei Li, Ezra M. Chung, Riyao Yang, Yong-Soo Kim, Andrew H. Park, Yun-Ju Lai, Yi Yang, Yu-Han Wang, Jielin Liu, Yufan Qiu, Kay-Hooi Khoo, Jun Yao, Jennifer L. Hsu, Jong-Ho Cha, Li-Chuan Chan, Jung-Mao Hsu, Heng-Huan Lee, Stephen S. Yoo, Mien-Chie Hung
Journal: Cancer Research (2020)

Immunotherapies targeting programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) immune checkpoints represent a major breakthrough in cancer treatment. PD-1 is an inhibitory receptor expressed on the surface of activated T cells that dampens T-cell receptor (TCR)/CD28 signaling by engaging with its ligand PD-L1 expressed on cancer cells. Despite the clinical success of PD-1 blockade using mAbs, most patients do not respond to the treatment, and the underlying regulatory mechanisms of PD-1 remain incompletely defined. Here we show that PD-1 is extensively N-glycosylated in T cells and the intensities of its specific glycoforms are altered upon TCR activation. Glycosylation was critical for maintaining PD-1 protein stability and cell surface localization. Glycosylation of PD-1, especially at the N58 site, was essential for mediating its interaction with PD-L1. The mAb STM418 specifically targeted glycosylated PD-1, exhibiting higher binding affinity to PD-1 than FDA-approved PD-1 antibodies, potently inhibiting PD-L1/PD-1 binding, and enhancing antitumor immunity. Together, these findings provide novel insights into the functional significance of PD-1 glycosylation and offer a rationale for targeting glycosylated PD-1 as a potential strategy for immunotherapy. SIGNIFICANCE: These findings demonstrate that glycosylation of PD-1 is functionally significant and targeting glycosylated PD-1 may serve as a means to improve immunotherapy response.
Platelets from HIV-infected individuals on antiretroviral drug therapy with poor CD4 <sup>+</sup> T cell recovery can harbor replication-competent HIV despite viral suppression
Authors: Fernando Real, Claude Capron, Alexis Sennepin, Riccardo Arrigucci, Aiwei Zhu, Gérémy Sannier, Jonathan Zheng, Lin Xu, Jean-Marc Massé, Ségolène Greffe, Michelle Cazabat, Maribel Donoso, Pierre Delobel, Jacques Izopet, Eliseo Eugenin, Maria Laura Gennaro, Elisabeth Rouveix, Elisabeth Cramer Bordé, Morgane Bomsel
Journal: Science Translational Medicine (2020)

In addition to hemostasis, human platelets have several immune functions and interact with infectious pathogens including HIV in vitro. Here, we report that platelets from HIV-infected individuals on combined antiretroviral drug therapy (ART) with low blood CD4+ T cell counts (<350 cells/μl) contained replication-competent HIV despite viral suppression. In vitro, human platelets harboring HIV propagated the virus to macrophages, a process that could be prevented with the biologic abciximab, an anti-integrin αIIb/β3 Fab. Furthermore, in our cohort, 88% of HIV-infected individuals on ART with viral suppression and with platelets containing HIV were poor immunological responders with CD4+ T cell counts remaining below <350 cells/μl for more than one year. Our study suggests that platelets may be transient carriers of HIV and may provide an alternative pathway for HIV dissemination in HIV-infected individuals on ART with viral suppression and poor CD4+ T cell recovery.
Abstract 15231: Peripheral Gamma-Aminobutyric Acid (GABA) Signaling in Brown Adipose Tissue Induces Metabolic Dysfunction in Obesity
Authors: Ryutaro Ikegami, Ippei Shimizu, Yoko Yoshida, Masaaki Nakao, Takayuki Wakasugi, Goro Katsuumi, Yuka Hayashi, Masayoshi Suda, Tohru Minamino
Journal: Circulation (2018)

Brown adipose tissue (BAT) is a metabolically active organ that contributes to the maintenance of healthy metabolism. Adrenergic signaling is well described as a key regulatory system for BAT, howe...
Clinical response by baseline characteristics in patients (pts) with relapsed and bortezomib (BTZ)-refractory multiple myeloma treated with panobinostat (PAN), BTZ, and dexamethasone (DEX; PANORAMA 2).
Authors: Melissa Alsina, Paul Gerard Guy Richardson, Robert L. Schlossman, Donna M. Weber, Steven E. Coutre, Cristina Gasparetto, Sutapa Mukhopadhyay, Michael S. Ondovik, Mahmudul H Khan, Carole S. Paley, Sagar Lonial
Journal: Journal of Clinical Oncology (2013)

8531 Background: In PANORAMA 2, PAN + BTZ + DEX recaptured responses in heavily pretreated pts with BTZ-refractory MM; overall response rate (ORR), clinical benefit rate (CBR), and progression-free survival (PFS) were 34.5%, 52.7%, and 5.4 months, respectively. Here, we evaluate clinical response per baseline characteristics. Methods: Response was based on European Group of Blood and Marrow Transplantation 1998 criteria. High-risk cytogenetics was defined as del(17p), t(4;14), or t(14;16). Quality of life (QoL) was measured with Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) v4.0 scale. Results: Response rate trended higher in pts whose prior BTZ therapy was not their last line of therapy (Table). Although no trend in response rate was noted, PFS appeared longer in pts progressing within 60 days of their last BTZ-containing regimen than in those progressing on their last BTZ-containing regimen. In the 14 pts with high-risk cytogenetics, ORR was 42.9% and CBR was 71.4%. The mean FACT/GOG-Ntx subscale did not exhibit a clinically meaningful change from baseline (mean ± standard deviation [SD], 114.2 ± 21.1; n = 41) to cycle 9 day 1 (day 169; 104.2 ± 15.4; n = 16) as determined by 50% SD threshold for minimally important difference. Other QoL parameters were similarly unchanged. Conclusions: PAN + BTZ + DEX demonstrated activity regardless of baseline demographics in heavily pretreated pts with BTZ-refractory MM. Clinical trial information: NCT01083602. [Table: see text]
AN 18-YEAR WORLD, EVIDENCE-BASED ANALYSIS COMPARING BIOLOGICAL AND MECHANICAL PROSTHESES FOR ISOLATED AORTIC VALVE REPLACEMENT IN PATIENTS AGED 50 TO 65 YEARS: THE SPANISH AORTIC VALVE MULTICENTRIC STUDY (SPAVALVE)
Authors: Emiliano Rodriguez-Caulo, Oscar Blanco-Herrera, Elisabet Berastegui, Javier Arias-Dachary, Souhayla Souaf, Gertrudis Parody, Gregorio Laguna, Alejandro Adsuar, Manuel Castella, Jose F. Valderrama, Ivana Pulitani, Sergio Canovas, Andrea Ferreiro, Carlota Vigil-Escalera, Antonio Garcia-Valentin, Manuel Carnero, Pilar Pareja, Jose A. Corrales, Jose A. Blazquez, Diego Macias, Delfina Fletcher-Sanfeliu, Daniel Martinez, Elio Martin, Miren Martin, Juan Margarit
Journal: Journal of the American College of Cardiology (2020)
Variation in Adult Outpatient Opioid Prescription Dispensing by Age and Sex — United States, 2008–2018
Authors: Lyna Z. Schieber, Gery P. Guy, Puja Seth, Jan L. Losby
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In 2017, prescription opioids were involved in 36% of opioid-involved overdose deaths in the United States (1). Prescription opioids can be obtained by prescription or through diversion (the channeling of regulated drugs from legal to illegal sources) (2). Among new heroin users, 66%-83% reported that their opioid use began with the misuse of a prescription opioid (3). Misuse is generally defined as drugs taken for a purpose other than that directed by the prescribing physician, in greater amounts, more often, or for a longer duration than prescribed (2). Exposure to prescription opioids can be lessened by ensuring recommended prescribing, thereby potentially reducing the risk for misuse, opioid use disorder, and overdose (4). Sex and age groups with high exposure to prescription opioids are not well defined. Using a retail pharmaceutical database from IQVIA,* nationwide trends in opioid prescription fill rates for adult outpatients by age and sex were examined during 2008-2018. Opioid prescription fill rates were disproportionately higher among men and women aged ≥65 years and women of all ages. For reasons not well understood, these disparities persisted over 11 years even as the opioid fill rate declined for each age group and sex. Interventions to improve prescribing practices by following evidence-based guidelines that include weighing the benefits and risks for using prescription opioids for each patient and adopting a multimodal approach to pain management could improve patient safety while ameliorating pain. These efforts might need to consider the unique needs of women and older adults, who have the highest opioid prescription fill rates.
Targets and Antibody Formats for Immunotherapy of Neuroblastoma
Authors: Jeong A. Park, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2020)

Neuroblastoma (NB) is a malignant embryonal tumor of the sympathetic nervous system that is most commonly diagnosed in the abdomen, often presenting with signs and symptoms of metastatic spread. Three decades ago, high-risk NB metastatic to bone and bone marrow in children was not curable. Today, with multimodality treatment, 50% of these patients will survive, but most suffer from debilitating treatment-related complications. Novel targeted therapies to improve cure rates while minimizing toxicities are urgently needed. Recent molecular discoveries in oncology have spawned the development of an impressive array of targeted therapies for adult cancers, yet the paucity of recurrent somatic mutations or activated oncogenes in pediatric cancers poses a major challenge to the evolving paradigm of personalized medicine. Although low tumor mutational burden is a major hurdle for immune checkpoint inhibitors, an immature or impaired immune system and inhibitory tumor microenvironment can further complicate the prospects for successful immunotherapy. In this regard, despite the poor immunogenic properties of NB, the success of antibody-based immunotherapy and radioimmunotherapy directed at single targets (eg, GD2 and B7-H3) is both encouraging and surprising, given that most solid tumor antibodies that use Fc-dependent mechanisms or radioimmunotargeting have largely failed. Here, we summarize the current information on the immunologic properties of this tumor, its potential immunotherapeutic targets, and novel antibody-based strategies on the horizon.