tbuckley/cabot-search huggingface dataset:
Connexin and Pannexin (Hemi)Channels: Emerging Targets in the Treatment of Liver Disease
Authors: Axelle Cooreman, Raf Van Campenhout, Steven Ballet, Pieter Annaert, Bert Van Den Bossche, Isabelle Colle, Bruno Cogliati, Mathieu Vinken
Journal: Hepatology (2018)

Connexin proteins are the building blocks of hemichannels, which dock further between adjacent cells to form gap junctions. Gap junctions control the intercellular exchange of critical homeostasis regulators. By doing so, gap junctions control virtually all aspects of the hepatic life cycle. In the last decade, it has become clear that connexin hemichannels also provide a pathway for cellular communication on their own independent of their role as structural precursors of gap junctions, namely between the cytosol of an individual cell and its extracellular environment. In contrast to gap junctions, connexin hemichannels become particularly active in liver disease by facilitating inflammation and cell death. This equally holds true for cellular channels composed of pannexins, being connexin‐like proteins recently identified in the liver that gather in structures reminiscent of hemichannels. This paper gives an overview of the involvement of connexin‐based and pannexin‐based channels in noncancerous liver disease.
Tumor molecular characteristics in patients (pts) with international metastatic renal cell carcinoma database consortium (IMDC) good (G) and intermediate/poor (I/P) risk
Authors: B. Beuselinck, A. Verbiest, G. Couchy, S. Job, A. de Reyniès, S. Caruso, V. Verkarre, N. Rioux-Leclercq, P. Schöffski, Y. Vano, R.-T. Elaidi, E. Lerut, M. Albersen, S. Oudard, J. Zucman-Rossi
Journal: Annals of Oncology (2018)
P3.16-36 Adjuvant Chemotherapy May Improve the Outcome of Patients with Non-Small-Cell Lung Cancer with Metastasis of Intrapulmonary Lymph Nodes.
Authors: X. Wang, W. Nan, S. Yan, X. Li, C. Lv, S. Li, Y. Wang, J. Wang, Y. Yang
Journal: Journal of Thoracic Oncology (2018)
Abstract P285: Adherence to the Mediterranean Diet is Associated with Longer Telomere Length in Patients with Coronary Artery Disease
Authors: Pratik M Pimple, Kobina Wilmot, Ibhar Al Mheid, Jinying Zhao, Jue Lin, Elizabeth Blackburn, Cherie Rooks, Margarethe Goetz, Yan Sun, J. Douglas Bremner, Arshed A Quyyumi, Viola Vaccarino
Journal: Circulation (2016)

Introduction: The Mediterranean diet pattern has been consistently shown to be beneficial for cardiovascular health in both observation studies and intervention trials. Fruits, vegetables, olive oil and nuts, key components of the Mediterranean diet, have antioxidant and anti-inflammatory properties known to affect biological aging. Leukocyte telomere length (LTL) is a marker of biological aging, and shorter LTL has been associated with CVD and its risk factors. Adherence to the Mediterranean diet has been linked to longer LTL in a community sample, but whether this is also true among patients with established coronary artery disease (CAD) is not known. Methods: Diet was assessed using the Block 2005 food-frequency questionnaire in 270 subjects with pre-existing CAD. A Mediterranean diet score (MDS) ranging from 0 to 8 was calculated using established methodology; a higher score indicates greater adherence to Mediterranean diet. The score was divided into 3 categories: low MDS (score ≤ 2), moderate MDS (score 3-5) and high MDS (score ≥ 6). LTL was measured by quantitative PCR. The association between MDS and LTL was assessed using linear regression models. Results: Mean age was 64 years (SD: 9), 55 (20%) were females and 181 (67%) were whites. After adjusting for age, sex, race, CAD risk factors, and total calorie intake, there was a graded association between MDS categories and LTL. Compared with patients in the low MDS category, those in the moderate MDS category had 0.05 units longer LTL (0.84 vs. 0.79, 95% CI: 0.01, 0.09), and those in the high MDS category had 0.06 units longer LTL (0.85 vs. 0.79, 95% CI: 0.02, 0.10), p for trend = 0.01 (Figure 1). Conclusion: Among subjects with pre-existing CAD, adherence to the Mediterranean diet pattern is associated with longer telomere length. In our sample, patients with at least moderate adherence to the Mediterranean diet were biologically about 10 year younger than their chronological age compared with those in the low MDS category.
Combination of Entecavir/Peginterferon Alfa‐2a in Children With Hepatitis B e Antigen–Positive Immune Tolerant Chronic Hepatitis B Virus Infection
Authors: Philip Rosenthal, Simon C. Ling, Steven H. Belle, Karen F. Murray, Norberto Rodriguez‐Baez, Sarah J. Schwarzenberg, Jeffrey Teckman, Hsing‐Hua S. Lin, Kathleen B. Schwarz
Journal: Hepatology (2018)

The optimal management strategy for children with immune‐tolerant chronic hepatitis B virus (HBV) infection remains unknown. The purpose of this clinical trial was to determine the safety and efficacy of therapy with entecavir and peginterferon in a group of children in the immune‐tolerant phase of HBV infection. Children with immune‐tolerant features of chronic hepatitis B (CHB) received entecavir once‐daily in a dose of 0.015 mg/kg (0.5 mg maximum) for 48 weeks; peginterferon alfa‐2a (180 µg/1.73m 2 subcutaneously) once‐weekly was added at the end of week 8 and continued until week 48. The primary endpoint was lack of detectable hepatitis B e antigen (HBeAg) with HBV DNA levels ≤1,000 IU/mL 48 weeks after stopping therapy. Sixty children (75% female), median age 10.9 (range, 3.4‐17.9) years, were enrolled. All were positive for hepatitis B surface antigen (HBsAg) and HBeAg and had high levels of HBV DNA with normal or minimally elevated levels of alanine aminotransferase (ALT). Fifty‐five children completed the entire 48‐week course of therapy. At 48 weeks after treatment ended (week 96), 2 children (3%) achieved the primary endpoint and were also HBsAg negative and anti–hepatitis B surface antigen antibody (anti‐HBs) positive. One child was HBeAg positive but HBsAg negative at week 60; another was HBeAg negative but HBsAg positive at week 72, which were their last clinic visits. In the remaining children, serum ALT and HBV DNA levels at week 96 were similar to baseline. Thirty‐seven children experienced adverse events (AEs), and 1 had a serious AE (SAE). Conclusion: The combination of entecavir and peginterferon for up to 48 weeks rarely led to loss of HBeAg with sustained suppression of HBV DNA levels in children in the immune‐tolerant phase of HBV infection, and treatment was associated with frequent AEs.
MORPHEUS: A phase Ib/II umbrella study platform evaluating the safety and efficacy of multiple cancer immunotherapy (CIT)-based combinations in different tumour types
Authors: I. Chau, G.M. Haag, O.E. Rahma, T.M. Macarulla, S.L. McCune, D.A. Yardley, B.J. Solomon, M. Johnson, G.A. Vidal, P. Schmid, G. Argiles, K. Dimick, S. Mahrus, H. Abdullah, X. He, P. Sayyed, H. Barak, C. Bleul, E. Cha, A. Drakaki
Journal: Annals of Oncology (2018)
Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline
Authors: Scott C. Morgan, Karen Hoffman, D. Andrew Loblaw, Mark K. Buyyounouski, Caroline Patton, Daniel Barocas, Soren Bentzen, Michael Chang, Jason Efstathiou, Patrick Greany, Per Halvorsen, Bridget F. Koontz, Colleen Lawton, C. Marc Leyrer, Daniel Lin, Michael Ray, Howard Sandler
Journal: Journal of Clinical Oncology (2018)

inclusive of all proper methods of care or exclusive of other methods reasonably directed to obtaining the same results.The physician must make the ultimate judgment regarding any specific therapy
Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series
Authors: Kendall F. Moseley, Jarushka Naidoo, Clifton O. Bingham, Michael A. Carducci, Patrick M. Forde, Geoffrey T. Gibney, Evan J. Lipson, Ami A. Shah, William H. Sharfman, Laura C. Cappelli
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> The use of immune checkpoint inhibitors is increasing in cancer therapy today. It is critical that treatment teams become familiar with the organ systems potentially impacted by immune-related adverse events associated with these drugs. Here, we report adverse skeletal effects of immunotherapy, a phenomenon not previously described. <h3>Case presentations</h3> In this retrospective case series, clinical, laboratory and imaging data were obtained in patients referred to endocrinology or rheumatology with new fractures (<i>n</i>&nbsp;= 3) or resorptive bone lesions (<i>n</i> = 3) that developed while on agents targeting PD-1, CTLA-4 or both. The average age of patients was 59.3 (SD 8.6), and five were male. Cancer types included melanoma, renal cell carcinoma and non-small cell lung cancer. All fracture patients had vertebral compression, and two of the three had multiple fracture sites involved. Sites of resorptive lesions included the shoulder, hand and clavicle. Biochemically, elevated or high-normal markers of bone resorption were seen in five of the six patients. Erythrocyte sedimentation rate was elevated in three of the four patients where checked. <h3>Conclusions</h3> This case series represents the first description of potential skeletal adverse effects related to immune checkpoint inhibitors. These findings are important for providers caring for patients who experience musculoskeletal symptoms and may merit additional evaluation.
Clonal Heterogeneity in Differentiation Response and Resistance to the <i>IDH2</i> Inhibitor Enasidenib in Acute Myeloid Leukemia
Authors: Lynn Quek, Muriel David, Alison Kennedy, Marlen Metzner, Michael Amatangelo, Alan H. Shih, Bilyana Stoilova, Dimitris Karamitros, Cyril Quivoron, Mael Heiblig, Christophe Willekens, Veronique Saada, Andrew Peniket, Olivier Bernard, Sam Agresta, Katharine Yen, Eytan M. Stein, Stephane De Botton, Anjan Thakurta, Ross L. Levine, Virginie Penard-Lacronique, Paresh Vyas
Journal: Blood (2017)
Baseline lymphopenia as a prognostic marker for colorectal carcinoma.
Authors: Dilek Erdem, Idris Yucel, Bahiddin Yilmaz, Guzin Demirag, Yasemin Kemal, Fatih Teker
Journal: Journal of Clinical Oncology (2012)

e14107 Background: Baseline lymphopenia has been proved to be a marker for poor prognosis, chemotherapy-induced toxicity and increased risk of febrile neutropenia, trombocytopenia and anemia in advanced solid neoplasms. This study aims to evaluate the effect of pretreatment lymphopenia on prognosis and hematological toxicity in colorectal cancer patients who received first line systemic chemotherapy. Methods: Lymphocyte count was evaluated in 386 pretreated colorectal cancer patients who do not have a seconder malignancy, HIV infection, bone involvement and primary G-CSF prophylaxis. Overall survival, progression free survival and disease free survival were calculated from date of diagnosis to date of relapse, progression and death. Kaplan-Meier, chi-square and Student-t test were used. Results: Mean follow-up was 30 months (range 1-180 months). Mean age was 57.4±12.5 years. Of all patients, 160 (41 %) were women. Rectum ( 26.2 %) and transvers colon (4.7 %) were the most and the least common anatomic locations, respectively. Mean lymphocyte count before treatment was 1964/µl (170-7000/µl). There were no relationship between lymphopenia and age, sex, performans status, presence of initial metastasis, adjuvant or palliative chemotherapy and hematological toxicity (p&gt;0.05). Grade 3-4 hematological toxicity was found in 40 patients and was significantly higher in patients receiving bi- or tri-chemotherapy regimen (p:0.017). Among 208 patients with relapse or progression, 40 patients had lymphopenia (19.2 %). 1, 3 and 5-year OS were significantly lower in lymphopenic patients (p:0.033). DFS was longer in non-lymphopenic patients but this data didn’t have statistical significance (p&gt;0.05). Conclusions: This study support that lymphocyte number prior to chemotherapy may be a simple but useful prognostic and predictive marker in untreated colorectal cancer patients. Patients with lower pretreatment lymphopenia have lower OS when compared to others (p&lt;0.05). This study has the highest colorectal cancer population in the literature.
Abstract 15062: Heart-Failure Specific MicroRNAs: Comparison Between Patients and Murine Model
Authors: Yuri D’Alessandra, Antonio P Beltrami, MariaCristina Carena, Paolo Devanna, Daniela Cesselli, Maurizio C Capogrossi, Marco Musumeci, Giulio Pompilio, Gualtiero I Colombo
Journal: Circulation (2014)

Purpose: Circulating microRNAs (miRNAs) have been proposed as biomarkers of several cardiac diseases, including myocardial infarction and Heart Failure (HF). In a preliminary expression profile screening, we have identified 10 miRNAs as potentially deregulated in plasma of HF patients. Here, we examined the expression pattern of these miRNAs both in plasma and cardiac samples from a murine model of HF. The aim of the work was to validate these potential biomarkers in a murine model of the disease. Methods: The expression of 10 potentially HF-regulated-miRNAs (miR-1, -124a, -133a, -154, -299-5p, -379, -423-5p, -451, -499-5p, and -654-5p) was examined by qRT-PCR in plasma and heart samples from mice that underwent Thoracic Aortic Constriction (TAC) obtained by banding to induce HF. Disease insurgence was verified by echocardiography. Plasma and left ventricle specimens (n = 5/group) were collected both from operated and sham animals eight weeks after intervention. Results: Among investigated plasmatic miRNA...
Multiple Myeloma
Authors: Susan E Bates
Journal: Clinical Cancer Research (2011)

This article is featured in Highlights of This Issue, p. 1213Nowhere in medical oncology has progress over the past decade been more rewarding than in the treatment of multiple myeloma. Early reports of the characteristic features of myeloma date back to the 1840s and describe patients accumulating an unthinkable number of bone fractures. The classic proteinuria was first described by Dr. Henry Bence Jones in 1847, but the disease itself was not named until 1873. There was no effective therapy until 1958, when clinical benefit was reported following treatment with l-phenylalanine mustard (melphalan). For over four decades, melphalan and prednisone were the mainstay of myeloma therapy; eventually high-dose chemotherapy was adopted as a strategy to improve survival. Major changes began in the late 1990s, when thalidomide was found to be active even in refractory disease. The past decade has been marked by the approval of new agents such as bortezomib and lenalidomide, with many more in the pipeline. As a result, treatment paradigms in this disease are changing, as some of the hard-won treatment strategies have been replaced by newer therapies and combinations. These exciting developments are the subject of this issue of CCR Focus. Guest Editor Kenneth C. Anderson has brought together an outstanding collection of investigators and topics that examine various aspects of myeloma biology and treatment. Munshi and Avet-Loiseau provide an update on the underlying molecular biology; Landgren, Kyle, and Rajkumar examine its premalignant forms and suggest research strategies that could lead to prevention therapies; Palumbo, Attal, and Roussal describe the complexities surrounding selection of upfront therapies; Lonial, Mitsiades, and Richardson present exciting drugs in the pipeline and offer suggestions for combination therapies; and Raje and Roodman discuss the important progress made in averting the bone-related complications of the disease. The Guest Editor's overview highlights the important progress in this field and the challenges involved in rapidly translating this progress to everyday therapy for patients with the disease. As with every issue of CCR Focus, we hope to inform those interested but not expert in cancer drug development and to encourage those already working in the field.
P125 IL-36 axis is an emerging therapeutic target in psoriatic arthritis synovial tissue
Authors: M-A Boutet, A Nerviani, G Lliso-Ribera, K Goldmann, M Lewis, C Pitzalis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> The IL-36 family of cytokines includes three agonists (IL-36α, β and γ) and two established or hypothetical antagonists (respectively IL-36Ra and IL-38). IL-36 agonists are pro-inflammatory cytokines highly expressed in skin, cleaved and activated by neutrophil proteases and involved in the pathogenesis of psoriasis. They have only limited effect in driving synovial inflammation in rheumatoid arthritis (RA) but little is known about the expression and biologic functions of the IL-36 axis in synovial tissue of psoriatic arthritis (PsA). <h3>Objectives</h3> In this study, we aimed to investigate the expression pattern and role of the IL-36 cytokines in early treatment-naïve PsA synovium in comparison with RA. <h3>Methods</h3> Synovial tissue samples were collected from patients with early (disease duration &lt;12 months) RA and PsA DMARDs (Disease Modifying Anti-Rheumatic Drugs) and steroids-naïve. All patients underwent an ultrasound-guided synovial biopsy before starting the treatment and after six months of treatment with conventional DMARDs. The expression of IL-36 family members was investigated in synovial tissue at gene level by RNA-Sequencing (87 RA, 15 PsA), at protein level by immunostaining (20 RA, 26 PsA) and in plasma by ELISA (22 RA, 38 PsA). RA and PsA-fibroblasts-like-synoviocytes (FLS) were treated <i>in vitro</i> to assess their response to IL-36 stimulation. <h3>Results</h3> Gene and protein expression of IL-36 agonists was comparable between RA and PsA synovial tissue; conversely, the antagonists were significantly lower in PsA compared to RA. Accordingly, the agonists/antagonists ratio was considerably higher in PsA synovium, also characterized by a strong neutrophil-signature, suggesting an activation of the IL36 pro-inflammatory pathway. Among the immune cells infiltrating the PsA synovium, macrophages (CD68+) and plasma cells (CD138+) were the primary IL36α-expressing cells. At baseline, the synovial expression of IL-36α was significantly higher in PsA patients who did not respond to DMARDs treatment at 12 months; this differential synovial expression of IL-36α between responders and non-responders was also maintained at six months. In keeping with this observation, we showed that treatment with DMARDs did not reduce the expression of IL-36 in PsA cells <i>in vitro</i>. Finally, we observed that PsA-FLS produced significantly higher levels of IL-8 upon stimulation with IL-36α in comparison with cells isolated from RA patients. <h3>Conclusions</h3> The impaired balance between IL-36 agonists and antagonists observed in PsA synovial tissue might contribute to the persistent inflammation characterising the diseased tissue. The exogenous replacement of the IL-36 antagonists may be a novel promising therapeutic target for PsA patients. <h3>Disclosure of Interest</h3> None declared.
Import of community-associated, methicillin-resistant Staphylococcus aureus to Europe through skin and soft-tissue infection in intercontinental travellers, 2011–2016
Authors: D. Nurjadi, R. Fleck, A. Lindner, J. Schäfer, M. Gertler, A. Mueller, H. Lagler, P.J.J. Van Genderen, E. Caumes, S. Boutin, E. Kuenzli, J. Gascon, A. Kantele, M.P. Grobusch, K. Heeg, P. Zanger, A. Goorhuis, A. Calvo-Cano, C. Hatz, A. Neumayr, J. Blum, B. Friedrich-Jänicke, F. Mockenhaupt, M. Ramharter, S. Gabrysch, M. Schunk, A. Perignon, G. Slesak, A. Stich
Journal: Clinical Microbiology and Infection (2018)
A phase II, multicenter study of the EZH2 inhibitor tazemetostat in adults (INI1-negative tumors cohort) (NCT02601950)
Authors: S. Stacchiotti, J.-Y. Blay, R.L. Jones, G.D.D. Demetri, O. Mir, A. Italiano, D. Thomas, T.W.-W. Chen, P. Schöffski, T. Gil, T. Jahan, G. Cote, R. Ratan, S. Attia, M. Roche, S. Daigle, I. Sapir, A. Clawson, M. Gounder
Journal: Annals of Oncology (2018)
GW29-e1272 ZYZ-803 mitigates endoplasmic reticulum stress-related necroptosis after acute myocardial infarction through down-regulating RIP3-CaMKII signaling pathway
Authors: Lingling Chang, Ba Hieu Tran, Ying Xiong, Yicheng Mao, Yizhun Zhu
Journal: Journal of the American College of Cardiology (2018)
Longitudinal Analysis of Long-Term Air Pollution Levels and Blood Pressure: A Cautionary Tale from the Multi-Ethnic Study of Atherosclerosis
Authors: Sara D. Adar, Yeh-Hsin Chen, Jennifer C. D’Souza, Marie S. O’Neill, Adam A. Szpiro, Amy H. Auchincloss, Sung Kyun Park, Martha L. Daviglus, Ana V. Diez Roux, Joel D. Kaufman
Journal: Environmental Health Perspectives (2018)

Background: Air pollution exposures are hypothesized to impact blood pressure, yet few longitudinal studies exist, their findings are inconsistent, and different adjustments have been made for potentially distinct confounding by calendar time and age. Objective: We aimed to investigate the associations of long- and short-term PM2:5 and NO2 concentrations with systolic and diastolic blood pressures and incident hypertension while also accounting for potential confounding by age and time. Methods: Between 2000 and 2012, Multi-Ethnic Study of Atherosclerosis participants were measured for systolic and diastolic blood pressure at five exams. We estimated annual average and daily PM2.5 and NO2 concentrations for 6,569 participants using spatiotemporal models and measurements, respectively. Associations of exposures with blood pressure corrected for medication were studied using mixed-effects models. Incident hypertension was examined with Cox regression. We adjusted all models for sex, race/ethnicity, socioeconomic status, smoking, physical activity, diet, season, and site. We compared associations from models adjusting for time-varying age with those that adjusted for both time-varying age and calendar time. Results: We observed decreases in pollution and blood pressures (adjusted for age and medication) over time. Strong, positive associations of long- and short-term exposures with blood pressure were found only in models with adjustment for time-varying age but not adjustment for both time-varying age and calendar time. For example, 16-ppb higher annual average NO2 concentrations were associated with 2.7 (95% CI: 1.5, 4.0) and −0.8 (95% CI: −2.6, 1.0) mmHg in systolic blood pressure with and without additional adjustment for time, respectively. Associations with incident hypertension were similarly weakened by additional adjustment for time. Sensitivity analyses indicated that air pollution did not likely cause the temporal trends in blood pressure. Conclusions: In contrast to experimental evidence, we found no associations between long- or short-term exposures to air pollution and blood pressure after accounting for both time-varying age and calendar time. This research suggests that careful consideration of both age and time is needed in longitudinal studies with trending exposures. https://doi.org/10.1289/EHP2966