tbuckley/cabot-search huggingface dataset:
Abstract B33: Beyond apoptosis, Bcl-xL in metastasis
Authors: Soyoung Choi, Zhengming Chen, Laura Tang, Yuanzhang Fang, Yi Li, Xuejun Jiang, Yi-Chieh Nancy Du
Journal: Cancer Research (2016)

Abstract Bcl-xL, a negative regulator of mitochondria-mediated apoptosis, is frequently overexpressed in cancer to promote survival. Bcl-xL can also promote migration and/or metastasis. However, it is unclear whether this metastatic function is mediated via – or independent of – its anti-apoptotic activity and its residence at mitochondria. Here, we show that Bcl-xL promotes migration of cells defective in mitochondria-mediated apoptosis. Importantly, Bcl-xL mutants lacking anti-apoptotic activity still induce epithelial-mesenchymal transition (EMT), upregulate TGFβ, and increase metastasis of pancreatic neuroendocrine tumor (panNET) cells. In the RIP-Tag; RIP-tva mouse model, infection of pancreatic lesions with avian retroviruses carrying such Bcl-xL mutants promotes metastasis as potently as wild-type Bcl-xL does. Furthermore, engineered Bcl-xL targeted to the nucleus, but not mitochondria or outside of nucleus, promotes EMT and alters EMT-associated factors. In addition, nuclear Bcl-xL can be found in human metastatic panNET samples. Taken together, these data demonstrate that the metastatic function of Bcl-xL is independent of its anti-apoptotic activity and its residence at mitochondria. Citation Format: Soyoung Choi, Zhengming Chen, Laura Tang, Yuanzhang Fang, Yi Li, Xuejun Jiang, Yi-Chieh Nancy Du. Beyond apoptosis, Bcl-xL in metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B33.
Cuprous oxide nanoparticles trigger ER stress-induced apoptosis by regulating copper trafficking and overcoming resistance to sunitinib therapy in renal cancer
Authors: Qiwei Yang, Ye Wang, Qing Yang, Yi Gao, Xiaopeng Duan, Qingcheng Fu, Chuanmin Chu, Xiuwu Pan, Xingang Cui, Yinghao Sun
Journal: Biomaterials (2017)
Strengthening laboratory surveillance of antimicrobial resistance in South East Asia
Authors: Aparna Singh Shah, Kumudu Karunaratne, Geeta Shakya, Ismael Barreto, Shashi Khare, Wantana Paveenkittiporn, Sonam Wangchuk, Htay Htay Tin, Milza Abdul Muhsin, Lin Aung, Rajesh Bhatia, Rahul Srivastava, Dwi Adi Maryandi
Journal: BMJ (2017)

Aparna Shah and colleagues call on South East Asian countries to invest in national networks of laboratories for robust and standardised surveillance of antimicrobial resistance
CD19 Target Activated Natural Killer (CD19.TaNK) Cellular Therapy: A Novel immunotherapeutic Approach to the Treatment of Non-Hodgkin Lymphoma (NHL)
Authors: Ravi Dashnamoorthy, Afshin Beheshti, Saheli Sarkar, Pooja Sabhachandani, Frank C. Passero, Sneha Purvey, Laurent Boissel, Tania Konry, Andrew M Evens
Journal: Blood (2016)
Elemental Sulfur Use and Associations with Pediatric Lung Function and Respiratory Symptoms in an Agricultural Community (California, USA)
Authors: Rachel Raanan, Robert B. Gunier, John R. Balmes, Alyssa J. Beltran, Kim G. Harley, Asa Bradman, Brenda Eskenazi
Journal: Environmental Health Perspectives (2017)

Background: Elemental sulfur, "the oldest of all pesticides," is the most heavily used agricultural pesticide in California and Europe. Sulfur is considered relatively safe and is used in both conventional and organic farming systems. Adverse respiratory effects have been reported in applicators and animals, but the effect on residential populations, and especially on children living in proximity to fields treated with elemental sulfur, is not known. Objectives: We evaluated associations between residential proximity to elemental sulfur applications and respiratory symptoms and spirometry of children living in an agricultural community. Methods: Participants were enrolled in the CHAMACOS longitudinal birth cohort. We collected respiratory symptomatology for 347 children at 7 y of age and measured spirometry on a subset of 279. Of these, estimations of proximity to sulfur application and relevant covariate data were available for 237 and 205 children for whom we had symptomatology information and FEV1 measurements, respectively. Data from the California Pesticide Use Reporting System were used to estimate the amount of elemental sulfur applied within 0.5, 1, and 3km of a child's residence during the week, month, and 12 mo prior to pulmonary evaluation. Regression models controlled for maternal smoking during pregnancy; season of birth; PM2.5 (particulate matter ≤2.5mm in aerodynamic diameter); breast feeding duration; child's sex, age, and height; technician; and other covariates. Results: Adverse associations with respiratory outcomes were found for sulfur applications within 0.5- and 1-km radii. Specifically, asthma medication usage and respiratory symptoms increased [OR=3.51; 95% confidence interval (CI): 1.50, 8.23, p=0.004; OR=2.09; 95% CI: 1.27, 3.46, p=0.004, respectively] and FEV1 decreased (β=−0.143; 95% CI: −0.248, −0.039, p=0.008) per 10-fold increase in the estimated amount of sulfur used within 1km of child residence during the year prior to pulmonary evaluation. Conclusions: This study suggests that elemental sulfur use, allowed in both organic and conventional farming, in close proximity to residential areas, may adversely affect children's respiratory health. https://doi.org/10.1289/EHP528
Heterogeneity Within and Between Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder
Authors: Stephanie H. Ameis
Journal: JAMA Psychiatry (2017)

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 Psychiatry 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 Psychiatry journal
In vitro and in vivo footprinting of the promoter region of the human vascular endothelial growth factor gene is consistent with G-quadruplex formation
Authors: Kexiao Guo, Daekyu Sun, Jadrian J. Rusche, Laurence H. Hurley
Journal: Cancer Research (2005)

6118   The proximal promoter region of the vascular endothelial growth factor (VEGF) gene consists of a polypurine (guanine)/polypyrimidine (cytosine) tract, which is known to be very dynamic in its conformation. We hypothesize that there could be a conformational transition between B-type DNA, melted DNA, and G-quadruplex structures within this polypurine/polypyrimidine tract present in the human VEGF promoter. To probe the possible transition from B-type DNA structures to alternate structures at the promoter region of the VEGF gene, we carried out in vitro and in vivo footprinting experiments on the VEGF promoter region with DNase I, S1 nuclease, and dimethyl sulfate (DMS) in this study. In vitro footprinting of the VEGF promoter region with DNase I and S1 nuclease revealed a long protected region including G-rich sequences, indicating the possible transition from B-DNA to unusual types of DNA structures at the VEGF promoter region. Interestingly, a striking hypersensitivity to both nucleases was found in the presence of KCl and telomestatin at the 3′-side residue of the predicted G-quadruplex-forming region, which could be the junction site separating the G-quadruplex from adjacent normal B-DNA. Footprint changes by both DNase I and S1 nuclease were significantly enhanced after the addition of KCl and telomestatin, indicating altered conformation of the VEGF proximal promoter region surrounding G-rich sequences under the conditions that favor the transition of B-type DNA structure to the G-quadruplexes. Our DMS-based genomic footprinting analysis of the VEGF promoter also provides strong evidence for possible alterations in DNA conformation with changes in this gene expression after exposure to TMPyP4 using A498 cells. The VEGF promoter is not well protected prior to TMPyP4 treatment, but following TMPyP4 treatment at the concentration that effectively inhibits the VEGF gene expression, most DMS-protected sites fall within (or close to) G-rich sequences consisting of four sets of 3-5 guanine repeats, forming a stable G-quadruplex structure in in vitro studies. Collectively, our results provide evidence that specific G-quadruplex structures can be formed in the VEGF promoter region, and that the transcription of these genes can be controlled by ligand-mediated G-quadruplex stabilization.
Sex Difference in Liver Tumorigenesis in Rats Ingesting &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenylacetamide
Authors: Sidransky, Herschel, Wagner, Billie P., Morris, Harold P.
Journal: JNCI Journal of the National Cancer Institute (1961)

Journal Article Sex Difference in Liver Tumorigenesis in Rats Ingesting N-2-Fluorenylacetamide Get access Herschel Sidransky, Herschel Sidransky Laboratories of Pathology and Biochemistry, National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Billie P. Wagner, Billie P. Wagner Laboratories of Pathology and Biochemistry, National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold P. Morris Harold P. Morris Laboratories of Pathology and Biochemistry, National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 26, Issue 1, January 1961, Pages 151–187, https://doi.org/10.1093/jnci/26.1.151 Published: 01 January 1961 Article history Received: 26 July 1960 Published: 01 January 1961
Reduced generation of lung tissue–resident memory T cells during infancy
Authors: Kyra D. Zens, Jun Kui Chen, Rebecca S. Guyer, Felix L. Wu, Filip Cvetkovski, Michelle Miron, Donna L. Farber
Journal: The Journal of Experimental Medicine (2017)

Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRMs, and heterosubtypic protection was reduced compared with adults. Impaired TRM establishment was infant–T cell intrinsic, and infant effectors displayed distinct transcriptional profiles enriched for T-bet–regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression after activation, and reduction of T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses, and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage.
Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587
Authors: Javier Figueroa, Lynette M. Phillips, Tal Shahar, Anwar Hossain, Joy Gumin, Hoon Kim, Andrew J. Bean, George A. Calin, Juan Fueyo, Edgar T. Walters, Raghu Kalluri, Roel G. Verhaak, Frederick F. Lang
Journal: Cancer Research (2017)

Tumor-stromal communications impact tumorigenesis in ways that are incompletely understood. Here, we show that glioma-associated human mesenchymal stem cells (GA-hMSC), a newly identified stromal component of glioblastoma, release exosomes that increase the proliferation and clonogenicity of tumor-initiating glioma stem-like cells (GSC). This event leads to a significantly greater tumor burden and decreased host survival compared with untreated GSCs in orthotopic xenografts. Analysis of the exosomal content identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via downregulation of the tumor-suppressive nuclear receptor corepressor NCOR1. Our results illuminate the tumor-supporting role for GA-hMSCs by identifying GA-hMSC-derived exosomes in the intercellular transfer of specific miRNA that enhance the aggressiveness of glioblastoma. Cancer Res; 77(21); 5808-19. ©2017 AACR.
注射可能なヒドロゲルからのフェルラ酸の徐放によるCisd2欠損心筋細胞における酸化ストレス誘発性損傷の回復【Powered by NICT】
Authors: Cheng Yung-Hsin, Lin Feng-Huei, Wang Chien-Ying, Hsiao Chen-Yuan, Chen Hung-Ching, Kuo Hsin-Yu, Tsai Ting-Fen, Chiou Shih-Hwa
Journal: Biomaterials (2016)
Abstract P019: Exosomes from Human CD34+ Cells: Critical Mediators of Proangiogenic Paracrine Effect of EPCs
Authors: Susmita Sahoo, Sol Misener, Tina Thorne, Meredith Millay, Kathryn M Schultz, Ting Liu, Aiko Ito, Christine Kamide, Ekaterina A Klyachko, Douglas W Losordo
Journal: Circulation Research (2011)

Local transplantation of human CD34+ hematopoietic stem cells has been shown to promote neovascularization in pre-clinical studies in models of myocardial and limb ischemia. In early phase clinical trials, transplantation of CD34+ cells has been associated with reduced angina, improved exercise time and reduced amputation rates. Several studies have suggested that paracrine effects by these pro-angiogenic cells mediate the effects induced by cell transplantation. We hypothesized that CD34+ cells secrete exosomes (Exo), which mediate at least a part of the therapeutic function of the cells. Methods and Results: We isolated Exo from the conditioned media of adult human peripheral blood (PB) CD34+ cells. The angiogenic and therapeutic potency of CD34+ Exo was compared with the intact CD34+ cells and also with PB mononuclear cell (MNC) Exo. Exo from both CD34+ cells and MNC are 50–90nm in size, have cup shaped morphology, and carry known Exo-marker proteins such as CD63, TSG101 and Annexin V as shown by electron microscopy, Western blot and flow cytometry. Compared to CD34+ cells or MNC Exo, CD34+ Exo significantly induces in vitro angiogenic activities such as viability, proliferation and tube formation of HUVECs on matrigel- in a dose dependent manner. In vivo, CD34+ Exo stimulated significant neovascularization in mouse corneal angiogenesis assay (14±4 mm v MNC Exo, 4±1 mm, p&lt;0.01) and incorporation of endothelial (CD31+) cells in mouse matrigel-plug assay (6±1.7% v CD34+ cells, 2±0.8%, p&lt;0.01). Finally, in a mouse model of hind limb ischemia (HLI), CD34+ Exo significantly improved perfusion (ratio: 1.01±0.04 v 0.57±0.1, P&lt;0.05), increased capillary density (1.8±0.3/HPF v 0.9±0.1/HPF, p&lt;0.001) and prevented ischemic leg amputation (16% v 100%), as compared with MNC Exo. Conclusions: These data demonstrate that CD34+ Exo induce angiogenic activity and ischemic tissue repair in the absence of CD34+ cells, and suggest that Exo represent important mediators of the therapeutic effects associated with CD34+ cell therapy. We speculate that Exo derived from CD34+ cells may represent a significant component of the paracrine effect of progenitor-cell transplantation for therapeutic angiogenesis.
Survival benefit of tumor treating fields plus stereotactic radiosurgery for recurrent malignant gliomas.
Authors: Anand Mahadevan, Loretta Barron, Scott R. Floyd, Ekkehard Kasper, Eric T. Wong
Journal: Journal of Clinical Oncology (2015)

e13036 Background: Tumor Treating Fields (TTFields) is a noninvasive antimitotic therapy that uses intermediate frequency (200 kHz) alternating electric fields for the regional treatment of recurrent glioblastoma. At a higher electromagnetic frequency, stereotactic radiosurgery (SRS) treats tumors by delivering a highly conformal and extremely intense dose of ionizing radiation. It is known that interruption of mitosis by chemotherapy and ionizing radiation can have a synergistic anti-tumor effect. Hence, we evaluated our patients with recurrent malignant gliomas when treated with TTFields with or without SRS. Methods: A retrospective review was performed of patients with malignant gliomas who were treated at our institution with TTFields. All had failed initial temozolomide chemo-irradiation with or without subsequent salvage treatments. A subset of these patients also received SRS and their outcome was compared to those without SRS. TTFields were applied using standard treatment protocol as previously described while SRS was performed utilizing the frameless Cyberknife. Tumors < 3 cm received radiosurgery in a single fraction (22 Gy for those < 2 cm and 18 Gy for those > 2 cm) while larger lesions received 24 Gy in 3 fractions. All patients were followed clinically after treatment and with head MRI at 2-month intervals. Results: Forty patients (24 men and 16 women) who received TTFields in 2013-14 were included in the study. The mean age was 57 (range 47-79). Twelve received SRS plus TTFields. The median overall survival for the entire group from the initiation of TTFields was 8 months. Compared to those who did not receive SRS, patients who were treated with SRS in addition showed an increase in median overall survival, 4 (95%CI 2-6) versus 12 (95%CI 4-20) months (p = 0.0036). There was no additional treatment-related toxicity other than fatigue. Conclusions: Synergism between antimitotic treatment and radiation is well known. We have shown that clinical benefit may exist when both antimitotic effect of TTFields and ionizing radiation of SRS are used together for patients with recurrent malignant gliomas. The benefit of this combined treatment will need further confirmation in future prospective studies.
Impact of immune-related adverse events (irAE) on overall survival (OS) in patients treated with immunotherapy for non-small cell lung cancer (NSCLC).
Authors: Dwight Hall Owen, Lai Wei, Miguel Angel Villalona-Calero, Erin Marie Bertino, Kai He, Peter G. Shields, David P. Carbone, Gregory Alan Otterson
Journal: Journal of Clinical Oncology (2017)

9080 Background: Immunotherapy (IO) has brought dramatic clinical benefit to patients with NSCLC. Most patients tolerate IO, but serious irAE have been reported. In melanoma, a correlation between development of irAE and clinical benefit has been suggested. For NSCLC, the risk of irAE including pneumonitis has been described in clinical trials but not for the wider population. Risk factors for irAE and the impact of irAE on OS are unknown. Methods: A retrospective review of patients with NSCLC treated with single-agent IO between September 2014 and June 2016 was carried out at The Ohio State University. Patients had confirmed pathologic disease and received IO either on clinical trial or as standard of care. IrAE were assessed based on the treating physician diagnosis. OS was calculated from the date of initiation of IO to death from any cause or date or last follow-up. Results: A total of 90 patients met criteria. Median age was 67. Histology was nonsquamous in 58 (64%) and squamous in 32 (35%). Most patients received nivolumab (n = 87). Median months of IO was 2.6 (95% CI 1.9 – 4.2). IrAE occurred in 24 patients (26.67%). The most common irAE were pneumonitis (n = 8), thyroid dysfunction (n = 6), and rash/pruritus (n = 5). Other irAE included colitis in 2 patients and new onset diabetes and autoimmune hepatitis in 1 patient each. Development of pneumonitis did not have a statistically significant impact on overall survival (median OS 5.8 vs 8.1 months, p = 0.11). Prior thoracic radiation (TR) was not associated with pneumonitis (11.54% vs 8.33%, p = 0.69), but was associated with shorter survival (median OS 3.9 vs 8.7 months, p = 0.018). Development of irAE was not associated with histology (p = 1.00), KRAS mutation (p = 0.10), TP53 mutation (p = 0.09), or recent flu vaccination (p = 1.00). Patients with irAE had longer median OS (13.2 vs 5.8 months, p = 0.018). Conclusions: The incidence of irAE and pneumonitis match that seen in published clinical trials. The development of irAE was associated with better prognosis, whereas patients with prior TR had worse outcomes. Further prospective research is warranted to investigate the correlation of irAE with clinical benefit from IO in patients with NSCLC.
Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis
Authors: Cynthia S Crowson, Silvia Rollefstad, Eirik Ikdahl, George D Kitas, Piet L C M van Riel, Sherine E Gabriel, Eric L Matteson, Tore K Kvien, Karen Douglas, Aamer Sandoo, Elke Arts, Solveig Wållberg-Jonsson, Lena Innala, George Karpouzas, Patrick H Dessein, Linda Tsang, Hani El-Gabalawy, Carol Hitchon, Virginia Pascual Ramos, Irazú Contreras Yáñez, Petros P Sfikakis, Evangelia Zampeli, Miguel A Gonzalez-Gay, Alfonso Corrales, Mart van de Laar, Harald E Vonkeman, Inger Meek, Anne Grete Semb
Journal: Annals of the Rheumatic Diseases (2017)

Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA.In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions.5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics).In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.