tbuckley/cabot-search huggingface dataset:
Association between early promoter methylation changes and outcome in older acute myeloid leukemia patients treated on SWOG S0703 (NCT0065884).
Authors: Sucha Nand, Nicholas Achille, Megan Othus, Kathleen Wren Phelan, Shubin Zhang, Kathrine A. Cooper, John E. Godwin, Frederick R. Appelbaum, Jerald P. Radich, Harry Paul Erba, Nancy Zeleznik-Le
Journal: Journal of Clinical Oncology (2015)

7060 Background: Treatment of acute myeloid leukemia (AML) in older patients remains a therapeutic challenge. Current treatment options range from supportive care alone to full-dose chemotherapy. Identifying factors that predict response to therapy may help increase efficacy and avoid toxicity. Methods: The phase II SWOG S0703 study investigated the use of hydroxyurea and azacitidine with gentuzumab ozogamicin in the elderly AML population. This regimen appeared to have efficacy similar to the standard AML regimens, with less toxicity in the poor risk population. Here we report the laboratory findings of samples accrued as part of this study. Global DNA methylation, promoter DNA methylation of six candidate genes (CDKN2A, CDKN2B, HIC1, RARB, CDH1 and APAF1), and expression analysis of these same genes were determined at several time points before and during therapy. Results: The goal of this study was to investigate whether DNA methylation or gene expression changes predict clinical response. Global DNA methylation was not associated with a clinical response. Samples from days 3 or 4 of treatment showed significantly decreased CDKN2A promoter DNA methylation in patients achieving complete remission (CR) compared to those who failed to achieve CR. Samples from day 7 of treatment showed significantly decreased RARB, CDKN2B and CDH1 promoter DNA methylation in patients achieving CR and/or complete remission with incomplete blood count recovery (CRi) compared to those who failed to achieve CR. Of the genes assessed in this study, there was a significant negative correlation (R2= -0.47) between APAF1 promoter methylation and APAF1 gene expression between pre-study and day 3 or 4 samples among patients who later went on to achieve CR. Conclusions: These findings offer a potentially important early insight that may inform clinicians about the likelihood of success with demethylating agents in the treatment of older patients with AML. Such information may help to decrease toxicity and improve therapeutic efficacy in these patients. Support: NIH/NCI/NCTN CA180888, CA180819 and in part by Celgene Corporation and Pfizer, Inc.
Abstract 21022: Increasing Cav1.2 in Smooth Muscle Cells Induces Both Systemic and Pulmonary Hypertension via Inhibiting Endothelium-Dependent Relaxation
Authors: Jian Zhou, Xiaoying Zhang, Ying Zhang, Zhongjian Chen, Hong Wang, Xiongwen Chen
Journal: Circulation (2017)

Introduction: Local activation of the L-type Ca 2+ channel (Cav1.2) in smooth muscle cells (SMCs) may activate big- and small- conductance K + channels, leading to hyperpolarization of the cell and vascular relaxation; however, large-scale activation of Cav1.2 increases cytosolic Ca 2+ to enhance muscle contraction. Hypothesis: We are testing if and how increasing Cav1.2 in SMCs causes systemic and pulmonary hypertension. Methods: Systemic blood pressure in conscious mice were measured with telemetric blood pressure system. Intra-ventricular hemodynamics of the LV and RV were determined in 6-month old SMC-specific Cavβ2a transgenic and control mice. Whole heart, LV and the right ventricular (RV) hypertrophy was assessed by heart weight (HW)/body weight (BW), LV weigth/BW, RV weight/BW, and RV-to-left ventricle+septum (RV/LV+S) ratio. Lung and heart sections were stained with H&amp;E. Mesenteric arteries were isolated for evaluating small arterial contractility and relaxation. Results: SMCs from the cerebral iddle arteries of TG mice had increased ICa (by 98.5±5.4%) vs. control. Conscious TG mice had significantly higher systemic systolic (TG vs. control: 145.4±12.1mmHg, n=45 vs. 115.2±7.4mmHg, n=16 ) and diastolic (TG vs control: 116.7±9.1mmHg, n=45 vs. 87.8±8.2mmHg, n=16) pressure (telemetry). Intra-ventricular hemodynamics (anesthestized) showed significantly increased systolic and diastolic pressure in both the LV (systolic: TG vs control: 120.2±7.3mmHg, n=17 vs. 82.3±7.2mmHg, n=16) and RV (systolic: TG vs control: 60.5±6.8mmHg, n=10 vs. 20.4±4.9mmHg, n=9). HW/BW, LV/BW, RV/BW, and RV/LV+S was higher in TG mice than in control mice. Small arteries in the lungs and the heart had increased wall thickness. Mesenteric arteries from TG mice had similar maximum contractility upon 40mM KCl stimulation. Acetylcholine induced relaxation but not NO-depedent relaxation was impaired in TG mesenteric arteries. Western blot and immunostaining showed less small- and large-conductance Ca 2+ -activated K + channels in the TG endothelium. Conclusions: Excessive calcium ion (Ca 2+ ) influx through L-type Ca 2+ channels can lead to both systemic and pulmonary arterial hypertension due to impairment of endothelium-dependent relaxation.
Treatment patterns and long-term survival for unresected stage III non-small cell lung cancer patients: A nationwide register study in Denmark
Authors: A. Green, K.E. Olsen, M. Bliddal, H.N. Christensen, E. Jakobsen
Journal: Annals of Oncology (2019)

Background: Patients with stage III non-small cell lung cancer (NSCLC) is a heterogeneous population with resectable or unresectable tumors. Current standard of care for unresectable disease has since long been either curatively intended chemoradiotherapy (CRT) followed by active surveillance, or palliative treatment for CRT ineligible patients. Recently, published data have shown survival benefit of CRT followed by immunotherapy (durvalumab). The aim was to investigate long-term survival, treatment patterns, and characteristics for unresected stage III NSCLC patients in a real-life setting. Methods: This nationwide study identified all stage III NSCLC patients diagnosed in Denmark during 2006-2015 in the Danish Cancer Registry. Patient and tumor data were linked with data on resection, CRT, radiotherapy only [RT], chemotherapy only [CT] and comorbidity from the National Patient Registry. Survival rates were estimated from date of diagnosis until death, migration, or end of study (2016) using Kaplan-Meier curves. Results: During the study period, 33,747 patients were diagnosed with NSCLC, of which 7390 (22%) had stage III disease. Of these, 5919 (80%) patients were unresected, and they were older (mean age 69.2 vs. 65.8 years), more frequently men (55.0% vs. 51.5%), and had more comorbidity (39.8% vs. 33.6% ≥one comorbidity) compared to the resected patients. Among the unresected patients, 40.5% received CRT, 15.1% RT, 15.6% CT, and 28.8% had no treatment. Patients receiving CRT were younger and had less comorbidity than patients receiving RT or CT only. The 5-year overall survival rates in the unresected group were: 10.6% CRT, 4.5% RT, and 3.6% for patients treated with CT. Among the resected stage III NSCLC patients, 42% survived ≥5 years. Conclusions: The poor long-term survival rates observed among unresected stage III NSCLC patients indicate a high unmet need for more effective therapy. New treatment strategies, including CRT followed by immunotherapy, might improve long-term outcomes for these patients. Increased utilization of biomarkers and correctly targeted therapies has the potential to personalize and improve treatment of stage III NSCLC. Legal entity responsible for the study: Institute of Applied Economics and Health Research Aps, Copenhagen, Denmark. Funding: AstraZeneca. Disclosure: H.N. Christensen: Employed: AstraZeneca. All other authors have declared no conflicts of interest.
Concordance, decision impact, and satisfaction for a computerized clinical decision support system in treatment of lung cancer patients
Authors: K.A. Lee, W. Felix, G. Jackson
Journal: Annals of Oncology (2019)

Background: Treatment options for lung cancer patients are progressing rapidly. A clinical decision support system (CDSS) which affords first-line treatment recommendations for cancer patients was implemented at Jupiter Medical Center, on March 1, 2017. This pilot analysis studied system performance and its impact on patients and providers. Methods: Lung cancer cases managed in the CDSS between October 2017 and November 2018 were incorporated. CDSS results were viewed by providers, discussed in tumor board, and shared with the patients. Navigators directed a survey about CDS impact and user satisfaction to clinician and patients at conclusion of visits. Summary responses were calculated. Results: Thirty cases were processed by the CDSS; 23 surveys were completed. The treatment team agreed completely with CDSS recommendations for 18 cases (78.3%) and partly for 4 (17.4%). Clinicians reported that the CDSS impacted the treatment decision 9 (39.1%) cases and saved time in treatment design for 17 (73.9%). The CDSS confirmed the treatment plan for 16 cases (69.6%), recommended an option that was designated for 5 (21.7%), and offered a useful option not chosen for 1 (4.3%). For most cases, clinicians conveyed they were pleased with the CDSS results (n = 22; 95.7%), realized the system easy to use (n = 21; 91.3%), and would use it again (n = 22; 95.7%). For most cases, clinicians responded that they strongly agreed or agreed that the CDSS provided information that was relevant (n = 22, 95.7%), easy to understand (n = 21, 95.6%), and actionable (n = 21, 95.6%). Most patients answered that they were pleased with the CDSS analysis of their treatment plan (n = 19; 82.6%) and would want their provider to use the system in the future (n = 19; 82.6%). Conclusions: This study provides initial evidence that a CDSS can positively support and influence the care of lung cancer patients. Treatment teams agreed with CDSS recommendations in most cases, and the CDSS impacted treatment conclusions. Providers and patients were pleased with the CDSS and reported being willing to use it again. Legal entity responsible for the study: Jupiter Medical Center. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
THU-068-Alcoholic and non-alcoholic fatty liver disease and liver-related mortality: A cohort study
Authors: Yong Kyun Cho, Keonhwa Kim, Yoosoo Chang, Juhee Cho, Hyun-Suk Jung, Kyung Eun Yun, Jiin Ahn, Seungho Ryu
Journal: Journal of Hepatology (2019)
WHERE IS UREA FORMED?
Authors: J Cleghorn
Journal: JAMA (1922)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
RETRACTED ARTICLE: Exosome-transmitted miR-128-3p increase chemosensitivity of oxaliplatin-resistant colorectal cancer
Authors: Tong Liu, Xin Zhang, Lutao Du, Yunshan Wang, Xiaoming Liu, Hui Tian, Lili Wang, Peilong Li, Yinghui Zhao, Weili Duan, Yujiao Xie, Zhaowei Sun, Chuanxin Wang
Journal: Molecular Cancer (2019)

Abstract Background Oxaliplatin resistance is a major challenge for treatment of advanced colorectal cancer (CRC). Both acquisition of epithelial-mesenchymal transition (EMT) and suppressed drug accumulation in cancer cells contributes to development of oxaliplatin resistance. Aberrant expression of small noncoding RNA, miR-128-3p, has been shown to be a key regulator in tumorigenesis and cancer development. However, its roles in the progression of CRC and oxaliplatin-resistance are largely unknown. Methods Oxaliplatin-resistant CRC and normal intestinal FHC cells were transfected with a miR-128-3p expression lentivirus. After transfection, FHC-derived exosomes were isolated and co-cultured with CRC cells. miR-128-3p expression in resistant CRC cells, FHC cells, and exosomes was quantified by quantitative real-time PCR (RT-qPCR). The mRNA and protein levels of miR-128-3p target genes in resistant CRC cells were quantified by RT-qPCR and western blot, respectively. The effects of miR-128-3p on CRC cell viability, apoptosis, EMT, motility and drug efflux were evaluated by CCK8, flow cytometry, Transwell and wound healing assays, immunofluorescence, and atomic absorption spectrophotometry. Xenograft models were used to determine whether miR-128-3p loaded exosomes can re-sensitize CRC cells to oxaliplatin in vivo. Results In our established stable oxaliplatin-resistant CRC cell lines, in vitro and vivo studies revealed miR-128-3p suppressed EMT and increased intracellular oxaliplatin accumulation. Importantly, our results indicated that lower miR-128-3p expression was associated with poor oxaliplatin response in advanced human CRC patients. Moreover, data showed that miR-128-3p-transfected FHC cells effectively packaged miR-128-3p into secreted exosomes and mediated miR-128-3p delivery to oxaliplatin-resistant cells, improving oxaliplatin response in CRC cells both in vitro and in vivo. In addition, miR-128-3p overexpression up-regulated E-cadherin levels and inhibited oxaliplatin-induced EMT by suppressing Bmi1 expression in resistant cells. Meanwhile, it also decreased oxaliplatin efflux through suppressed expression of the drug transporter MRP5. Conclusion Our results demonstrate that miR-128-3p delivery via exosomes represents a novel strategy enhancing chemosensitivity in CRC through negative regulation of Bmi1 and MRP5. Moreover, miR-128-3p may be a promising diagnostic and prognostic marker for oxaliplatin-based chemotherapy.
Upregulation of <i>SNAI2</i> and <i>SOX9</i> mRNA versus downregulation of eight other EMT/stemness related genes in basal cell carcinoma
Authors: F. Vand‐Rajabpour, P. Noormohammadpour, M.R. Ahmadifard, S. Panjeh‐Shahi, R. Ahmadi‐Beni, J. Rahmati, M. Daneshpazhooh, K. Kamyab‐Hesari, M. Yaseri, M. Tabrizi
Journal: British Journal of Dermatology (2019)
Donation of mitochondria by iPSC-derived mesenchymal stem cells protects retinal ganglion cells against mitochondrial complex I defect-induced degeneration
Authors: Dan Jiang, Guoyin Xiong, Hong Feng, Zhao Zhang, Peikai Chen, Bin Yan, Ling Chen, Kesavamoorthy Gandhervin, Chuiyan Ma, Cheng Li, Shuo Han, Yuelin Zhang, Can Liao, Tin-Lap Lee, Hung-Fat Tse, Qing-Ling Fu, Kin Chiu, Qizhou Lian
Journal: Theranostics (2019)

Rationale: Retinal ganglion cell (RGC) degeneration is extremely hard to repair or regenerate and is often coupled with mitochondrial dysfunction. Mesenchymal stem cells (MSCs)-based treatment has been demonstrated beneficial for RGC against degeneration. However, underlying mechanisms of MSC-provided RGC protection are largely unknown other than neuroprotective paracrine actions. In this study, we sought to investigate whether mitochondrial donation from induced pluripotent stem cell-derived MSC (iPSC-MSCs) could preserve RGC survival and restore retinal function. Methods: iPSC-MSCs were injected into the vitreous cavity of one eye in NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) knockout (KO) and wild type mice. Phosphate buffer saline (PBS) or rotenone treated iPSC-MSCs were injected as control groups. Retinal function was detected by flash electroretinogram (ERG). Whole-mount immunofluorescence (IF), morphometric analysis, confocal microscopy imaging, polymerase chain reaction (PCR) of the retinas were conducted to investigate mitochondrial transfer from human iPSC-MSCs to mouse retina. Quantitative mouse cytokine arrays were carried out to measure retinal inflammatory response under difference treatments. Results: RGC survival in the iPSC-MSC injected retina of Ndufs4 KO mice was significantly increased with improved retinal function. GFP labelled human mitochondria from iPSC-MSC were detected in the RGCs in the retina of Ndufs4 KO mice starting from 96 hours post injection. PCR result showed only human mitochondrial DNA without human nuclear DNA could be detected in the mouse retinas after iPSC-MSC treatment in Ndufs4 KO mice eye. Quantitative cytokine array analysis showed pro-inflammatory cytokines was also downregulated by this iPSC-MSC treatment. Conclusion: Intravitreal transplanted iPSC-MSCs can effectively donate functional mitochondria to RGCs and protect against mitochondrial damage-induced RGC loss.
FRI-147-Gradual restoration of HCV-specific CD8+ T cell frequency but persistence of altered phenotype in cirrhotic HCV-infected patients after successful direct-acting antiviral therapy
Authors: Elena Perpiñan, Sofía Pérez-del-Pulgar, Maria Carlota Londoño, Patricia González, Zoe Mariño, Sabela Lens, Concepció Bartres, Mireia García-López, Xavier Forns, Georgios Koutsoudakis
Journal: Journal of Hepatology (2019)
PS-099-PP100-01 (calmangafodipir) for overdose of paracetamol (The POP trial): Principal results
Authors: Emma Morrison, Katherine Oatey, Polly Black, Bernadette Gallagher, Julia Grahamslaw, Rachel O’Brien, Wilna Oosthuyzen, Robert Lee, Christopher Weir, Dennis Henriksen, James Dear
Journal: Journal of Hepatology (2019)
Association of Domestic Responsibilities With Career Satisfaction for Physician Mothers in Procedural vs Nonprocedural Fields
Authors: Heather G. Lyu, Jennifer S. Davids, Rebecca E. Scully, Nelya Melnitchouk
Journal: JAMA Surgery (2019)

Physicians who are mothers face challenges with equal distribution of domestic duties, which can be an obstacle in career advancement and achieving overall job satisfaction.To study and report on the association between increased domestic workload and career dissatisfaction and if this association differed between proceduralists and nonproceduralists.Data for this study were gathered from April 28 to May 26, 2015, via an online survey of 1712 attending physician mothers recruited from the Physician Moms Group. Statistical analysis was performed from August 25, 2017, to November 20, 2018.Univariate analysis was performed for respondents who reported sole responsibility for 5 or more vs fewer than 5 main domestic tasks. Independent factors associated with career dissatisfaction or a desire to change careers were identified using a multivariate logistic regression model.Of the 1712 respondents, most were partnered or married (1698 [99.2%]), of which 458 (27.0%) were in procedural specialties. Overall, respondents reported having sole responsibility for most domestic tasks, and there were no statistically significant differences between procedural and nonprocedural groups. Physician mothers in procedural specialties primarily responsible for 5 or more domestic tasks reported a desire to change careers more often than those responsible for fewer than 5 tasks (105 of 191 [55.0%] vs 114 of 271 [42.1%]; P = .008). This difference was not noted in physician mothers in nonprocedural specialties. In multivariate analysis of the proceduralist cohort, primary responsibility for 5 or more tasks was identified as a factor independently associated with the desire to change careers (odds ratio, 1.5; 95% CI, 1.0-2.2; P = .05).Physician mothers report having more domestic responsibilities than their partners. For proceduralist mothers, self-reported higher levels of domestic responsibility were associated with career dissatisfaction. Increasing numbers of mothers in the medical workforce may create a demand for more equitable distribution and/or outsourcing of domestic tasks.
The benefit of adjuvant radiotherapy in high-grade retroperitoneal sarcoma: A SEER analysis.
Authors: James Edward Bates, Ali Mazloom, Sughosh Dhakal, Louis S. Constine
Journal: Journal of Clinical Oncology (2015)

10559 Background: There is significant controversy surrounding the use of adjuvant radiotherapy (RT) in patients with retroperitoneal sarcoma (RPS). Grade is a prognostic factor in RPS and high-grade disease is associated with decreased local control (LC) and overall survival (OS). Adjuvant RT has been demonstrated to improve LC but not OS. In extremity sarcomas, recent evidence suggests that the benefit of RT is most significant for high-grade sarcomas. We hypothesized that any benefit in OS for RPS would most likely exist in those with high-grade tumors. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with pathology-confirmed retroperitoneal soft tissue sarcoma from 1973 to 2010. Clinical characteristics and outcomes were investigated via Kaplan-Meier and Cox proportional hazards analyses. OS was defined as time to death or last follow-up. Results: A total of 483 patients with RPS were identified; 144 (29.8%) of who received post-operative radiation, the rest received surgery alone. Patients who received adjuvant RT had improved median OS (36 mo) compared to those who did not (27 mo, HR = 0.79, p = 0.023). On multivariate analysis the use of adjuvant RT (HR = 0.80, 95% CI: 0.65 – 0.97, p = 0.025), male gender (HR = 1.33, 95% CI: 1.10 – 1.60, p = 0.003), patient age greater than 65 years (HR = 1.34, 95% CI: 1.11 – 1.62, p = 0.002), and increasing SEER historical stage (HR = 1.45, 95% CI: 1.21 – 1.75, p < 0.001) were all statistically significant prognostic factors for OS. Conclusions: In a retrospective analysis of a large national cancer database, post-operative RT improved OS in high-grade RPS patients. As such, adjuvant RT should be strongly considered in all patients with high-grade RPS. The current standard of care is to administer radiation prior to surgery in order to minimize potential radiation morbidities. A multi-national EORTC study is currently accruing patients to validate this approach in a prospective manner.
SAT-330-Whole metabolome profiling identifies the combination of an eicosanoid, a bile acid and an androgen as a highly accurate marker of liver fibrosis in patients with non-alcoholic fatty liver disease
Authors: Felix Stickel, Silke Schulze Pellengahr, Sebastian Neuber, Antje Wagner-Golbs, Nicole Christiansen, Beate Kamlage, Philipp Schatz, Holger Hinrichsen, Clemens Schafmayer, Matteo Montani, Witigo von Schönfels, Christoph Röcken, Markus Lerch, Thomas Berg, Christian Datz, Ursula Huber-Schönauer, Mario Brosch, Jochen Hampe
Journal: Journal of Hepatology (2019)