tbuckley/cabot-search huggingface dataset:
Comparison of endoscopic papillary large balloon dilation with or without endoscopic sphincterotomy for the treatment of large bile duct stones
Authors: Jin-Seok Park, Seok Jeong, Dong Lee, Sung Jang, Tae Lee, Sang-Heum Park, Jae Hwang, Jin Kim, Byoung Yoo, Shin Park, Don Lee
Journal: Endoscopy (2018)

Abstract Background Endoscopic papillary large balloon dilation (EPLBD) without prior endoscopic sphincterotomy (EST) produces excellent outcomes for the treatment of large common bile duct (CBD) stones. However, it remains unclear how the outcomes of EPLBD alone compare with those of EPLBD with EST. In this study, we assessed the safety and therapeutic outcomes of EPLBD with vs. without EST for the removal of large bile duct stones. Methods This prospective, multicenter study was conducted on 200 patients with bile duct stones of ≥ 10 mm in diameter. Patients were randomly assigned to an EPLBD alone group (n = 100) or an EPLBD with EST group (n = 100). These two groups were compared with respect to overall procedure-related adverse events, overall stone removal success rate, number of endoscopic sessions required for complete stone removal, need for mechanical lithotripsy, and total procedure time. Results The incidence of adverse events was not significantly different between the groups (EPLBD alone vs. EPLBD with EST: overall adverse events 6 % vs. 4 %, P = 0.75; pancreatitis 1 % vs. 3 %, P = 0.62). Overall success (P = 0.35), initial success (P = 0.28), and the need for mechanical lithotripsy (P = 0.39) were also similar between groups. Median total procedure time tended to be greater in the EPLBD alone group (20.5 minutes) than in the EPLBD with EST group (18 minutes; P = 0.08). Conclusion The therapeutic outcomes and adverse events of EPLBD alone for the removal of large bile duct stones were comparable to those of EPLBD with EST.
The clinical outcome of <i>LMNA</i> missense mutations can be associated with the amount of mutated protein in the nuclear envelope
Authors: Rasha A. Al‐Saaidi, Torsten B. Rasmussen, Rune I.D. Birkler, Johan Palmfeldt, Abdelaziz Beqqali, Yigal M. Pinto, Peter H. Nissen, Ulrik Baandrup, Henning Mølgaard, Thomas M. Hey, Hans Eiskjær, Peter Bross, Jens Mogensen
Journal: European Journal of Heart Failure (2018)
Abstract LB-128: The aryl hydrocarbon receptor as driver of cancer immunity
Authors: David Sherr, Jessica Kenison-Whte, Zhongyan Wang
Journal: Cancer Research (2018)

Abstract The Aryl Hydrocarbon Receptor (AHR) has been identified as a driver of cancer progression and cancer immunity in the tryptophan-IDO/TDO-kynurenine-AHR pathway. Over the last 10 years, studies from several laboratories have demonstrated that AHR ligand-mediated immunosuppression is effected, at least in part, through AHR regulation of inflammatory or inhibitory T cell subsets and immune suppressive MDSCs. These results suggest that the AHR is a driver of cancer immunity. To test this hypothesis, we used molecular and pharmacological approaches to regulate AHR activity in multiple murine cancer models and then measured multiple immune phenotypes. The resulting data indicate that a novel, non-toxic AHR inhibitor, HP163 (Hercules Pharmaceuticals), reduces tumor growth in orthotopic models of oral (MOC1), breast (4T1), and skin (B16) cancers in immunocompetent hosts. In the MOC1 model, HP163 significantly reduces the number of CD11b+PD-L1+ or CD11b+CCR2+ cells in the tumor draining lymph node. AHR knockdown in MOC1 cells with CRISPR/Cas9 decreases the percentage of CD11b+PD-L1+ tumor infiltrating cells and increases tumor infiltrating CD4+ and CD8+ T cells. This decrease in cells with an immunosuppressive phenotype is accompanied by a complete lack of orthotopic tumor growth. Furthermore, mice having received AHR- MOC 1 cells are resistant to a second challenge with wildtype AHR+ MOC1 cells several months after the primary inoculation. These data suggest that the presence of the AHR in the tumor itself is sufficient to induce immunosuppression. Preliminary data suggest that AHR+ myeloid cells mediate suppression of tumor immunity. These results collectively suggest that the AHR may be targeted for immunotherapy of several cancers and that HP163 may represent a novel approach to cancer therapy. Citation Format: David Sherr, Jessica Kenison-Whte, Zhongyan Wang. The aryl hydrocarbon receptor as driver of cancer immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-128.
Clinical and Laboratory Markers Associated With Relapse in Cutaneous Polyarteritis Nodosa
Authors: Azusa Kato, Toshihisa Hamada, Tomoko Miyake, Shin Morizane, Yoji Hirai, Osamu Yamasaki, Keiji Iwatsuki
Journal: JAMA Dermatology (2018)

In cutaneous polyarteritis nodosa (CPAN), less aggressive treatments can be selected, because CPAN is not associated with life-threatening or progressive outcomes. Although patients with a recurrent clinical course may require additional immunosuppressive therapies, no pretreatment factors associated with a worse prognosis in CPAN have been reported.To identify clinical or laboratory markers associated with relapse of CPAN.This retrospective case series was performed at a dermatology clinic of a tertiary referral center in Okayama, Japan, from October 1, 2001, through April 30, 2017. Of 30 patients identified with CPAN, the 21 with histopathologic evidence of disease were eligible and enrolled in the study.The medical database was examined for sex, age at diagnosis, affected anatomical sites, type and extent of skin lesion, laboratory data, initial therapies, duration of follow-up, and current status. Relapse was defined as the first reoccurrence or new onset of cutaneous disease that required further escalation of treatment with prednisolone at a dosage of greater than 20 mg/d and/or add-on use of immunosuppressant therapy, more than 6 months after initial treatment. The pretreatment factors were statistically evaluated between the groups without and with relapse.The 21 patients included 5 males and 16 females with a median age of 49 years (range, 11-74 years) at diagnosis. The median follow-up was 42 months (range, 8-374 months). Pretreatment cutaneous ulcer was significantly associated with relapse between the 2 groups (0 of 11 in the nonrelapse group vs 4 of 10 in the relapse group; χ21 = 4.67; P < .05). In the laboratory test results, significantly higher mean (SD) values were observed in the relapse group for C-reactive protein level (0.23 [2.00] vs 6.03 [3.10] mg/dL; standard error of the mean [SEM], 3.40 mg/dL; 95% CI, 0.01-10.8 mg/dL; P = .01), absolute neutrophil count (ANC) (3.4 × 103/μL [1.1 × 103/μL] vs 6.0 × 103/μL [3.2 × 103/μL]; SEM, 2.9 × 103/μL; 95% CI, 1.9 × 103/μL to 14.6 × 103/μL; P = .001), neutrophil-to-lymphocyte ratio (1.4 [0.8] vs 2.8 [0.9]; SEM, 1.2; 95% CI, 1.1-4.9; P = .002), and systemic immune-inflammation index (5.1 × 105 [3.9 × 105] vs 11.7 × 105 [7.7 × 105]; SEM, 7.3 × 105; 95% CI, 3.3 × 105 to 31.1 × 105; P = .007). The estimated 2-year cumulative relapse rate was significantly high in the patients with blood ANC of greater than 4.9 × 103/μL compared with 4.9 × 103/μL or less (9 of 10 [90%] vs 2 of 11 [18%]; 95% CI, 6%-72%).Pretreatment status of cutaneous ulcer, the serum C-reactive protein level, the blood ANC, the neutrophil-to-lymphocyte ratio, and the systemic immune-inflammation index are associated with a worse prognosis in CPAN.
Neuropilin-1 upregulation elicits adaptive resistance to oncogene-targeted therapies
Authors: Sabrina Rizzolio, Gabriella Cagnoni, Chiara Battistini, Stefano Bonelli, Claudio Isella, Jo A. Van Ginderachter, René Bernards, Federica Di Nicolantonio, Silvia Giordano, Luca Tamagnone
Journal: Journal of Clinical Investigation (2018)

Cancer cell dependence on activated oncogenes is therapeutically targeted, but acquired resistance is virtually unavoidable. Here we show that the treatment of addicted melanoma cells with BRAF inhibitors, and of breast cancer cells with HER2-targeted drugs, led to an adaptive rise in neuropilin-1 (NRP1) expression, which is crucial for the onset of acquired resistance to therapy. Moreover, NRP1 levels dictated the efficacy of MET oncogene inhibitors in addicted stomach and lung carcinoma cells. Mechanistically, NRP1 induced a JNK-dependent signaling cascade leading to the upregulation of alternative effector kinases EGFR or IGF1R, which in turn sustained cancer cell growth and mediated acquired resistance to BRAF, HER2, or MET inhibitors. Notably, the combination with NRP1-interfering molecules improved the efficacy of oncogene-targeted drugs and prevented or even reversed the onset of resistance in cancer cells and tumor models. Our study provides the rationale for targeting the NRP1-dependent upregulation of tyrosine kinases, which are responsible for loss of responsiveness to oncogene-targeted therapies.
Immunotherapeutic treatment of metastatic colorectal cancer using ETBX-011.
Authors: Elizabeth Susan Gabitzsch, Michael A. Morse, H. Kim Lyerly, Joseph Balint, Frank Jones
Journal: Journal of Clinical Oncology (2014)

3093 Background: Cell mediated immune (CMI) induction has become a prominent component of potential immunotherapy of cancer. We have reported on a Phase 1/2 single agent clinical trial of the immunotherapeutic ETBX-011 for the treatment of mCRC. We now report on long-tem immunity to CEA and survival data to provide further insight into the responses following treatment with ETBX-011. Methods: Cohorts of patients with advanced colorectal cancer, refractory to prior therapies, received escalating doses from 109 to 5x1011VP of ETBX-011 (Ad5 [E1-, E2B-]-CEA(6D)) subcutaneously every 3 weeks for 3 immunizations. The induction of CEA-specific cell mediated immunity was measured by ELISPOT and overall survival was determined. Also, in a subset of the ETBX-011 treated mCRC patients the number of T-regs as the percent of CD4 cells and the ratio of T-effector cells to Tregs was determined. Results: ETBX-011 was found to be well-tolerated at all doses and there were no drop outs due to treatment. Specific anti-CEA immune responses were observed in the majority of patients and median overall-survival was 11 months. We now report on long term follow-up of the patients. Forty-four percent (48%) of patients still survived at 12 month follow-up and 28% at 18 months following treatments. One patients who developed significant CEA specific cellular immune response also showed a decrease in the Treg:T-effector ratio on follow-up and still survived at 2 years post treatment. Conclusions: These results demonstrate that mCRC patients treated with ETBX-011 immunotherapeutic is safe and can be easily administered to patients. ETBX-011 treatment generated significant CMI induction to the tolerated tumor associated antigen CEA and may experience increased overall survival. A single agent randomized, multicenter Phase 2b trial is being initiated to further evaluate the clinical effectiveness. Clinical trial information: NCT01147965.
Abstract 3455: Biologic functions of BMX/BTK in non-small cell lung cancer
Authors: Wen-Chien Huang
Journal: Cancer Research (2018)

Abstract Non-small cell lung cancer (NSCLC), a leading cause of tumor-related deaths in Taiwan and worldwide, remains not only a health care but also a social burden in Taiwan. EGFR and KRAS mutations and deregulation of the EGFR/KRAS pathways are critical for lung tumorigenesis and progression; however, our knowledge of the genes responsible for the heterogeneity of lung carcinoma is inconclusive. Despite increasing documentation of the role of the Bruton's tyrosine kinase (BMX/BTK) in tumorigenesis, as well as increasing use of BMX/BTK inhibitors as new cancer drugs, to the best of our knowledge, this is the first study on the identification and characterization of BMX/BTK in lung cancer. Our preliminary data show increased expression of BMX/BTK protein in lung cancer cells compared to their nontumor counterparts, using immunohistochemical (IHC) staining and Western blot. Further, using clinicopathologic analyses of large prognoscan database cohorts, we established a negative correlation between BMX/BTK expression and patients' outcome. However, this bioinformatics-based clinical significance of BMX/BTK and its functional mechanisms in the tumorigenesis of NSCLC remains to be verified. In this project, we will comprehensively investigate the role of the BMX/BTK gene in lung tumorigenesis and progression, with its underlying molecular mechanisms. We will also develop and evaluate the therapeutic effect of in-house small-molecule inhibitors of BMX/BTK in lung cancer using animal model. In aim 1, we will explore the expression of BMX/BTK and its related upstream regulators and downstream effectors in lung cancer using IHC staining of primary NSCLC tissue samples. These data will be collated and statistically correlated with patients' clinical data. In aim 2, we will investigate the role of BMX/BTK in lung cancer cell proliferation, epithelial-to-mesenchymal (EMT), and cancer stem cell phenotype, as well as determine the underlying molecular mechanisms, using loss and gain of BMX/BTK function, and functional assays such as the colony formation, invasion, migration and spheroid formation assays in lung cancer tissues and cell lines. In the aim, we will validate the in vitro findings by examining BMX/BTK activities in vivo, evaluate the therapeutic effect of novel BMX/BTK inhibitors and investigate its clinical significance, using tumor xenograft NOD-SCID mice models. We anticipate that this current study will demystify the role and molecular mechanisms of BMX/BTK in the tumorigenesis of lung cancer and provide relevant information for effective anti-lung cancer therapeutic strategy, including combined targeted therapy. Citation Format: Wen-Chien Huang. Biologic functions of BMX/BTK in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3455.
Alternative drug to prevent postpartum bleeding could save many lives in low income countries
Authors: Ingrid Torjesen
Journal: BMJ (2018)

A heat stable formulation of carbetocin is as effective as the current standard of care, oxytocin, for preventing excessive bleeding after vaginal birth, a study led by the World Health Organization has shown.1

WHO currently recommends oxytocin as the first choice drug for preventing excessive bleeding after childbirth, but oxytocin must be stored and transported at 2-8°C, which is hard to do in many low and middle income countries. As a result, women giving birth in such countries may not have access to this lifesaving drug or, if they do, it …
Laboratory medicine in Africa since 2008: then, now, and the future
Authors: John N Nkengasong, Francois-Xavier Mbopi-Keou, Rosanna W Peeling, Katy Yao, Clement E Zeh, Miriam Schneidman, Renuka Gadde, Alash'le Abimiku, Philip Onyebujoh, Deborah Birx, Shannon Hader
Journal: The Lancet Infectious Diseases (2018)
A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses
Authors: Simon Le Gallou, Zhicheng Zhou, Lan-Huong Thai, Remi Fritzen, Alba Verge de los Aires, Jérôme Mégret, Philipp Yu, Daisuke Kitamura, Emmanuelle Bille, Fabiola Tros, Xavier Nassif, Alain Charbit, Sandra Weller, Jean-Claude Weill, Claude-Agnès Reynaud
Journal: The Journal of Experimental Medicine (2018)

To what extent immune responses against the gut flora are compartmentalized within mucosal tissues in homeostatic conditions remains a much-debated issue. We describe here, based on an inducible AID fate-mapping mouse model, that systemic memory B cell subsets, including mainly IgM+ B cells in spleen, together with IgA+ plasma cells in spleen and bone marrow, are generated in mice in the absence of deliberate immunization. While the IgA component appears dependent on the gut flora, IgM memory B cells are still generated in germ-free mice, albeit to a reduced extent. Clonal relationships and renewal kinetics after anti-CD20 treatment reveal that this long-lasting splenic population is mainly sustained by output of B cell clones persisting in mucosal germinal centers. IgM-secreting hybridomas established from splenic IgM memory B cells showed reactivity against various bacterial isolates and endogenous retroviruses. Ongoing activation of B cells in gut-associated lymphoid tissues thus generates a diversified systemic compartment showing long-lasting clonal persistence and protective capacity against systemic bacterial infections.
Consideration of Population-Based <i>BRCA</i> Testing as a Strategy to Reduce Disparities in Genetic Counseling Referrals
Authors: Lisa A. Newman
Journal: JAMA Surgery (2018)

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 Surgery 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 Surgery journal
Elucidating Gene-by-Environment Interactions Associated with Differential Susceptibility to Chemical Exposure
Authors: Michele Balik-Meisner, Lisa Truong, Elizabeth H. Scholl, Jane K. La Du, Robert L. Tanguay, David M. Reif
Journal: Environmental Health Perspectives (2018)

Background: Modern societies are exposed to vast numbers of potentially hazardous chemicals. Despite demonstrated linkages between chemical exposure and severe health effects, there are limited, often conflicting, data on how adverse health effects of exposure differ across individuals. Objectives: We tested the hypothesis that population variability in response to certain chemicals could elucidate a role for gene–environment interactions (GxE) in differential susceptibility. Methods: High-throughput screening (HTS) data on thousands of chemicals in genetically heterogeneous zebrafish were leveraged to identify a candidate chemical (Abamectin) with response patterns indicative of population susceptibility differences. We tested the prediction by generating genome-wide sequence data for 276 individual zebrafish displaying susceptible (Affected) vs. resistant (Unaffected) phenotypes following identical chemical exposure. Results: We found GxE associated with differential susceptibility in the sox7 promoter region and then confirmed gene expression differences between phenotypic response classes. Conclusions: The results for Abamectin in zebrafish demonstrate that GxE associated with naturally occurring, population genetic variation play a significant role in mediating individual response to chemical exposure. https://doi.org/10.1289/EHP2662
Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC): a randomised, open-label trial
Authors: Holly Fisher, Yemi Oluboyede, Thomas Chadwick, Mohamed Abdel-Fattah, Catherine Brennand, Mandy Fader, Simon Harrison, Paul Hilton, James Larcombe, Paul Little, Doreen McClurg, Elaine McColl, James N'Dow, Laura Ternent, Nikesh Thiruchelvam, Anthony Timoney, Luke Vale, Katherine Walton, Alexander von Wilamowitz-Moellendorff, Jennifer Wilkinson, Ruth Wood, Robert Pickard
Journal: The Lancet Infectious Diseases (2018)

Repeated symptomatic urinary tract infections (UTIs) affect 25% of people who use clean intermittent self-catheterisation (CISC) to empty their bladder. We aimed to determine the benefits, harms, and cost-effectiveness of continuous low-dose antibiotic prophylaxis for prevention of recurrent UTIs in adult users of CISC.
STAG2 Is a Biomarker for Prediction of Recurrence and Progression in Papillary Non–Muscle-Invasive Bladder Cancer
Authors: Alana Lelo, Frederik Prip, Brent T. Harris, David Solomon, Deborah L. Berry, Krysta Chaldekas, Anagha Kumar, Jeffry Simko, Jørgen Bjerggaard Jensen, Pritish Bhattacharyya, Ciaran Mannion, Jung-Sik Kim, George Philips, Lars Dyrskjøt, Todd Waldman
Journal: Clinical Cancer Research (2018)

Most bladder cancers are early-stage tumors known as papillary non-muscle-invasive bladder cancer (NMIBC). After resection, up to 70% of NMIBCs recur locally, and up to 20% of these recurrences progress to muscle invasion. There is an unmet need for additional biomarkers for stratifying tumors based on their risk of recurrence and progression. We previously identified
Genetic variants with gene regulatory effects are associated with diisocyanate-induced asthma
Authors: David I. Bernstein, Zana L. Lummus, Banu Kesavalu, Jianbo Yao, Leah Kottyan, Daniel Miller, André Cartier, Maria-Jesús Cruz, Catherine Lemiere, Xavier Muñoz, Santiago Quirce, Susan Tarlo, Joaquin Sastre, Louis Philippe Boulet, Matthew T. Weirauch, Kenneth Kaufman
Journal: Journal of Allergy and Clinical Immunology (2018)
LIFEx: A Freeware for Radiomic Feature Calculation in Multimodality Imaging to Accelerate Advances in the Characterization of Tumor Heterogeneity
Authors: Christophe Nioche, Fanny Orlhac, Sarah Boughdad, Sylvain Reuzé, Jessica Goya-Outi, Charlotte Robert, Claire Pellot-Barakat, Michael Soussan, Frédérique Frouin, Irène Buvat
Journal: Cancer Research (2018)

Textural and shape analysis is gaining considerable interest in medical imaging, particularly to identify parameters characterizing tumor heterogeneity and to feed radiomic models. Here, we present a free, multiplatform, and easy-to-use freeware called LIFEx, which enables the calculation of conventional, histogram-based, textural, and shape features from PET, SPECT, MR, CT, and US images, or from any combination of imaging modalities. The application does not require any programming skills and was developed for medical imaging professionals. The goal is that independent and multicenter evidence of the usefulness and limitations of radiomic features for characterization of tumor heterogeneity and subsequent patient management can be gathered. Many options are offered for interactive textural index calculation and for increasing the reproducibility among centers. The software already benefits from a large user community (more than 800 registered users), and interactions within that community are part of the development strategy.Significance: This study presents a user-friendly, multi-platform freeware to extract radiomic features from PET, SPECT, MR, CT, and US images, or any combination of imaging modalities. Cancer Res; 78(16); 4786-9. ©2018 AACR.