tbuckley/cabot-search huggingface dataset:
Clinical significance of serum transforming growth factor beta 1 (TGFB1) level in breast cancer.
Authors: Rumeysa Ciftci, Faruk Tas, Leyla Kilic, Sezai Vatansever, Senem Karabulut
Journal: Journal of Clinical Oncology (2014)

e11526 Background: The transforming growth factor beta 1 (TGFB1) is a regulatory cytokine with both tumor supressor and tumor promoting effects in breast cancer (BC) cell lines and tissue. Data about level of circulating TGFB1 and its prognostic significance in BC patients is conflicting. The objective of this study was to determine the clinical significance of the serum TGFB1 levels in BC patients. Methods: We enrolled 96 female patients with histopathologically diagnosed BC who did not receive chemotherapy (CT) or radiotherapy. Serum TGFB1 levels were measured by ELISA method and compared with 30 healthy controls. Results: The median age at diagnosis was 48 (range: 29-80) years. Thirty-nine percent of the patients had metastatic disease. The rates of patients with estrogen receptor positive, HER2 positive and triple negative disease were 71%, 32% and 8%, respectively. CT response rate of patients with locally advanced or metastatic disease was 78%. The mean serum TGFB1 level of BC patients was significantly higher than controls (0.08 vs 0.04 ng/ml, p<0.001). There was no significant difference according to known disease-related clinicopathological or laboratory parameters. The 2-year survival rates of patients with high (>mean) and low (<mean) TGFB1 levels were 97%(±3) and 67%( ±8), respectively. Serum TGFB1 level had a significant impact on overall survival in both univariate (p=0.01) and multivariate analysis (p=0.013). Conclusions: Serum TGFB1 level is elevated in BC patients and has a favorable prognostic value. However, it has no predictive role on CT response.
Improved dissolution and oral absorption by co-grinding active drug probucol and ternary stabilizers mixtures with planetary beads-milling method
Authors: Fang Li, Linsen Li, Shaoning Wang, Yan Yang, Jia Li, Dongchun Liu, Sijie Zhang, Siling Wang, Hui Xu
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The objective of this work is to construct a nanosuspension drug delivery system of probucol, a BCS II drug, in order to improve its dissolution and oral bioavailability. The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process. Cellulose derivatives of different substitution groups and molecular weights, including HPMC, HPC, and MC, were evaluated as the primary stabilizer of probucol nanosuspension. Ternary stabilizers system composed of a primary stabilizer (cellulose derivative, i.e. HPC), a nonionic surfactant (Pluronic® F68), and an anionic surfactant (SDS) was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media. The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4 °C or 25 °C. The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate (> 60% at 2 h) compared to other cryoprotectant. The in vivo pharmacokinetic evaluation indicated about 15-folds higher AUC value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats. The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.
Endoscopic treatments for gastrointestinal bleeding: a story of cleverness and success
Authors: Klaus Mönkemüller, Nib Soehendra
Journal: Endoscopy (2018)

In the early 1970 s, various endoscopists in Germany and Japan began utilizing various through-the-scope utensils to treat gastrointestinal bleeding (GIB), including clips and electrocoagulation devices. In this editorial, we evaluate a landmark paper published in 1976 by Dr. Nib Soehendra, who had designed a new needle inserted through a simple polyvinyl chloride (PVC) sheath to treat bleeding gastric ulcers. The paper describes two patients with bleeding gastric ulcers [1]. The first patient was found to have a bleeding ulcer at the level of the cardia. The second patient was a patient who had undergone a Whipple's operation and presented with pulsating bleeding from an anastomotic ulcer. In the latter patient, therapy by electrocoagulation failed; in the first patient, electrocoagulation was deemed too dangerous because of the shape and location of the ulcer. Therefore, Soehendra proceeded to inject the ulcers with Ethoxysclerol using the new needle inside the PVC sheath, which led to rapid and successful hemostasis in both patients. He named the technique "transendoscopic submucous infiltration."
Immunotherapy 2.0: Improving the Response to Checkpoint Inhibitors
Authors: M.J. Friedrich
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Sofosbuvir–velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a single-arm, open-label, phase 3 trial
Authors: Lai Wei, Seng Gee Lim, Qing Xie, Kính Nguyen Văn, Teerha Piratvisuth, Yan Huang, Shanming Wu, Ming Xu, Hong Tang, Jun Cheng, Hung Le Manh, Yanhang Gao, Zhuangbo Mou, Abhasnee Sobhonslidsuk, Xiaguang Dou, Satawat Thongsawat, Yuemin Nan, Chee Kiat Tan, Qin Ning, Hoi Poh Tee, Yimin Mao, Luisa M Stamm, Sophia Lu, Hadas Dvory-Sobol, Hongmei Mo, Diana M Brainard, Yong-Feng Yang, Long Dao, Gui-Qiang Wang, Tawesak Tanwandee, Peng Hu, Pisit Tangkijvanich, Lunli Zhang, Zhi Liang Gao, Feng Lin, Thi Tuyet Phuong Le, Jia Shang, Guozhong Gong, Jun Li, Minghua Su, Zhongping Duan, Rosmawati Mohamed, Jin Lin Hou, Jidong Jia
Journal: The Lancet. Gastroenterology & hepatology (2018)
C-Src confers resistance to mitotic stress through inhibition DMAP1/Bub3 complex formation in pancreatic cancer
Authors: Jingjie Li, Bin Hu, Ting Wang, Wenhua Huang, Chunmin Ma, Qin Zhao, Lingang Zhuo, Tao Zhang, Yuhui Jiang
Journal: Molecular Cancer (2018)

Chromatin modification at mitosis is closely related to transcriptional reactivation in the subsequent cell cycle. We reasoned this process is deregulated by oncogenic signals, which would contribute to mitotic stress resistance in pancreatic cancer. Here, we show DMAP1/Bub3 complex mediates mitotic stress-induced cellular apoptosis, while this effect is counteracted by c-Src in pancreatic cancer cells. Our study aims to uncover an unidentified mechanism underlying the distinct response to mitotic stress between normal cells and pancreatic cancer cells. The interaction between Bub3 and DMAP1 upon mitotic stress signaling was determined through molecular and cell biological methods. The inhibitory effect of c-Src on DMAP1/Bub3-mediated DNA methylation and gene transcription profile was investigated. The association between c-Src-mediated DMAP1 phosphorylation and paclitaxel activity in vivo and clinicopathologic characteristics were analyzed. Mitotic arrest induced p38-dependent phosphorylation of Bub3 at Ser211, which promotes DMAP1/Bub3 interaction. DMAP1/Bub3 complex is recruited by TAp73 to the promoter of anti-apoptotic gene BCL2L1, thus mediates the DNA methylation and represses gene transcription linked to cell apoptosis. Meanwhile, DMAP1 was highly phosphorylated at Tyr 246 by c-Src in pancreatic cancer cells, which impedes DMAP1/Bub3 interaction and the relevant cellular activites. Blocking DMAP1 pTyr-246 potentiates paclitaxel-inhibited tumor growth. Clinically, DMAP1 Tyr 246 phosphorylation correlates with c-Src activity in human pancreatic cancer specimens and poor prognosis in pancreatic cancer patients. Our findings reveal a regulatory role of Bub3 in DMAP1-mediated DNA methylation upon mitotic stress and provide the relevance of DMAP1 pTyr-246 to mitotic stress resistance during pancreatic cancer treatment.
Transplantation for Alcoholic Hepatitis: Are We Achieving Justice and Utility?
Authors: Steven F. Solga, Marina Serper, Rebecca A. Young, Kimberly A. Forde
Journal: Hepatology (2018)

Early liver transplantation for alcoholic hepatitis is a potentially life‐saving treatment. As this practice becomes increasingly common, however, the liver transplant community is taking a fresh look at a familiar challenge: best stewardship of donor organs. Herein, we examine a few basic, necessary ethical and practical concerns relevant to this indication.
Engineering Nanoparticles for Targeted Remodeling of the Tumor Microenvironment to Improve Cancer Immunotherapy
Authors: Shan Gao, Dongjuan Yang, Yan Fang, Xiaojie Lin, Xuechao Jin, Qi Wang, Xiyan Wang, Liyuan Ke, Kai Shi
Journal: Theranostics (2018)

Owing to the fast-paced growth and cross-infiltration of oncology, immunology and molecular biology, tumor immunotherapy technology represented by immune checkpoint blockade and chimeric antigen receptor (CAR) T cell therapy has lately made remarkable advancements.In comparison with traditional chemotherapy, immunotherapy has the potential to elicit a stronger sustained antitumor immune response in those patients who have advanced malignant malignancies.In spite of the advancements made, a significant number of clinical research works have validated that an extensive proportion of cancer patients still manifest insensitivity to immunotherapy, primarily because of the immunomodulatory interactions between tumor cells and the immunosuppressive tumor microenvironment (TME), together mediating the immune tolerance of tumors and accordingly impacting the positive response to immunotherapy.The intricate immunosuppressive networks formed by stromal cells, inflammatory cells, vasculature, extracellular matrix (ECM), and their secreted cytokines in the TME, play a pivotal role in tumor immune escape.Specific blocking of inhibition pathways in the TME is expected to effectively prevent immune escape and tolerance of tumor cells in addition to their metastasis, accordingly improving the antitumor immune response at various phases of tumor growth.Emerging nanoscale targeted drug carriers truly suit this specific requirement due to their specificity, biocompatibility, and convenience of production.This review emphasizes recent attempts to remodel the tumor immune microenvironment using novel nanoparticles, which include specifically eliminating immunosuppressive cells, reprogramming immune regulatory cells, promoting inflammatory cytokines and blocking immune checkpoints.Targeted remodeling of the immunosuppressive TME using well-designed and fabricated nanoparticles provides a promising strategy for improving the effectiveness of current immunotherapy and is greatly significant.
Abstract MP027: Gene-environment Interaction Analysis Reveals Evidence for Independent Influences of Physical Activity and Sedentary Behavior on Obesity: Results From the Hispanic Community Health Study/study of Latinos (HCHS/SOL)
Authors: Jee-Young Moon, Tao Wang, Tamar Sofer, Kari E North, Carmen R Isasi, Jianwen Cai, Marc D Gellman, Ashley E Moncrieft, Daniela Sotres-Alvarez, Maria Argos, Robert Kaplan, Qibin Qi
Journal: Circulation (2017)

Background: Studies using self-reported data support gene-physical activity interaction on obesity, yet the influence of sedentary behavior, distinct from lack of physical activity, on genetic associations with obesity remains unclear. Methods: We examined interactions of accelerometer-measured physical activity and sedentary behavior with genetic variants on BMI/obesity risk in 9,645 participants aged 18-74 years from the HCHS/SOL, a population-based cohort of US Hispanics/Latinos (2008-2011). A genetic risk score (GRS) was calculated by summing the BMI-increasing alleles of known 97 SNPs (identified primarily in European-ancestry in the GIANT BMI GWAS; P &lt;5х10 -8 ). Specific GRSs were also calculated based on the possible biological categories of these SNPs. Results: The overall GRS was significantly associated with BMI in the HCHS/SOL (β=0.65 per SD [~6-allele increase]; P=1.0х10 -39 ). The genetic effect on BMI was stronger in participants with lower moderate-to-vigorous physical activity (MVPA) (1 st tertile, &lt;8min/day) compared to those with higher MVPA (3 rd tertile, &gt;23min/day) (0.78 [0.10] vs 0.39 [0.10]; P int =0.005), as well as in participants with more sedentary time (3 rd tertile, &gt;13h/day) compared to those with less sedentary time (1 st tertile, &lt;11h/day) (0.73 [0.1] vs 0.44 [0.1]; P int =0.005). The genetic effects on obesity risk were stronger in participants with lower MVPA (P int =0.016) or more sedentary time (P int =0.016). Interactions of GRS with MVPA and sedentary behavior remained significant after further adjustment for each other. Of note, 4 biological category-specific GRSs showed nominally significant interactions with both MVPA and sedentary behavior, while a number of different GRSs interacted with only MVPA or sedentary behavior, in relation to BMI ( Figure ). Conclusions: Our data suggest that both increasing physical activity and reducing sedentary behavior may attenuate the genetic association with obesity, possibly through interacting with shared and different genetic pathways.
AB0719 Close temporal association between silicone cosmetic surgery and systemic sclerosis onset
Authors: A. Sulli, S. Paolino, E. Alessandri, B. Ruaro, M. Pendolino, M. Cutolo, C. Pizzorni
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The pathogenesis of systemic sclerosis (SSc) still remains unclear, however It is increasingly thought to result from interactions between environmental factors and epigenetic features leading to the onset and progression of SSc in genetically susceptible patients.<sup>1</sup> Case reports of women with silicone breast implants who developed SSc have been published, but several case–control series and prospective studies in connective tissue diseases (including SSc) failed to find an increased risk of SSc associated with silicone cosmetic surgery.<sup>2</sup> However, several byas may be recognised in these studies, i.e. heterogeneous cohorts of enrolled patients not selective for SSc, non homogeneous either disease duration or disease stage at study entry. For these reason the possible effect of silicone implants as immune adjuvants is not clear.<sup>3</sup> <h3>Objectives</h3> Retrospective study to find out patients who developed SSc after cosmetic surgery. <h3>Methods</h3> The clinical files of 110 female patients with systemic sclerosis were retrospectively evaluated. Among these, four patients showing a history of silicone cosmetic surgery (3.6%) were identified, and clinical data collected. <h3>Results</h3> The clinical data of the four patients are below reported. 1. LS 28 year old female who underwent cosmetic breast prosthesis: two years later she complained of Raynaud' phenomenon (RP), and one more year later aggressive diffuse cutaneous SSc, along with anticentromere antibodies (ACA) positivity. 2. PJ 38 year old female who underwent cosmetic breast prosthesis: one year later she experienced RP and one more year later aggressive diffuse cutaneous SSc; antinuclear antibodies were positive with a speckled patter, but specific SSc-related autoantibodies negative. 3. BS 33 year old female who underwent cosmetic breast prosthesis: two years later she complained of RP and one more year later limited cutaneous SSc with ACA positivity; SSc clinical condition partially improved and its progression stopped after breast prosthesis removal. 4. CM 58 year old female who underwent cosmetic lip silicone application: one year later she complained simultaneous onset of RP and aggressive diffuse cutaneous SSc with anti-Topoisomerase positivity; she died during follow-up. <h3>Conclusions</h3> This study reports a prevalence of 3.6% of silicone cosmetic surgery before SSc onset. The close temporal association between silicone implant and disease development suggests a possible role of silicone in SSc pathogenesis. Specifically addressed clinical studies or big-data studies need to rule out this matter. <h3>References</h3> [1] Denton C, et al. Lancet2017; 390: 1685–99. [2] Marie I, et al. Semin Immunopathol2015; 37:463–473. [3] Watad A, et al. Lupus. 2017; 26:675–681. <h3>Disclosure of Interest</h3> None declared
Abstract 18589: The Impact of a Door-to-Balloon Time of Less Than 30 Minutes on the In-Hospital Prognosis of Patients With ST Elevation Myocardial Infarction
Authors: Takeshi Yamada, Akihiko Takahashi, Yukio Mizuguchi, Hiroki Shibutani, Sho Hashimoto, Norimasa Taniguchi, Shunsuke Nakajima, Tetsuya Hata
Journal: Circulation (2016)

Introduction: Several recent studies suggested that the door-to-balloon time (DTBT) for patients with ST elevation myocardial infarction (STEMI) should be as short as possible, even in centers curr...
Dose Reduction of First and Second Generation TKIs Is Effective in the Maintenance of Major Molecular Response and May Predict Successful Tfr in CML Patients
Authors: Simone Claudiani, Jane Apperley, Afzal Khan, Richard Szydlo, George Nesr, George Adams, Letizia Foroni, Jamshid S Khorashad, Dragana Milojkovic
Journal: Blood (2018)
Impact of Breast Cancer Subtypes on Prognosis of Women with Operable Invasive Breast Cancer: A Population-based Study Using SEER Database
Authors: Ki-Tae Hwang, Jongjin Kim, Jiwoong Jung, Ji Hyun Chang, Young Jun Chai, So Won Oh, Sohee Oh, Young A. Kim, Sung Bae Park, Kyu Ri Hwang
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To determine the prognostic roles of breast cancer subtypes in females with operable invasive breast cancer. Experimental Design: Data of 321,958 patients from Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Breast cancer subtypes were classified into four categories according to the status of hormone receptor (HRc) and HER2: HRc(+)/HER2(−), HRc(+)/HER2(+), HRc(−)/HER2(+), and HRc(−)/HER2(−). Results: Proportions of HRc(+)/HER2(−), HRc(+)/HER2(+), HRc(−)/HER2(+), HRc(−)/HER2(−), and unknown subtype were 70.3%, 9.4%, 3.9%, 10.4%, and 6.0%, respectively. HRc(+)/HER2(−) showed the highest 5-year breast cancer–specific survival (BCSS) rate (95.5%), followed by HRc(+)/HER2(+) (94.1%), HRc(−)/HER2(+) (89.3%), and HRc(−)/HER2(−) (83.1%). HRc(+)/HER2(−) and HRc(+)/HER2(+) showed higher 5-year overall survival (OS) rates (88.4% and 88.2%, respectively) than HRc(−)/HER2(+) and HRc(−)/HER2(−) (83.9% and 76.5%, respectively). HRc(−)/HER2(−) showed the worst BCSS irrespective of race, age, or stage. Although proportions of HRc(−)/HER2(−) in the subgroup with negative event regarding BCSS and OS were 10.4% and 10.2%, respectively, they were 34.2% and 22.7%, respectively, in the subgroup with positive event. Subtype was a significant factor in both univariable and multivariable analyses regarding both BCSS and OS (all P &amp;lt; 0.001). Conclusions: Breast cancer subtype was a significant independent prognostic factor regarding both BCSS and OS in multivariable analyses. HRc(+) subtypes showed better prognosis compared with HRc(−) subtypes regarding both BCSS and OS. HRc(−)/HER2(+) showed better prognosis than HRc(−)/HER2(−) but worse prognosis than HRc(+) subtypes regarding both BCSS and OS. The triple-negative subtype showed the worst BCSS compared with the other subtypes irrespective of race, age, or stage.
Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways
Authors: Christopher D. Steele, Maxime Tarabichi, Dahmane Oukrif, Amy P. Webster, Hongtao Ye, Matthew Fittall, Patrick Lombard, Iñigo Martincorena, Patrick S. Tarpey, Grace Collord, Kerstin Haase, Sandra J. Strauss, Fitim Berisha, Heli Vaikkinen, Pawan Dhami, Marnix Jansen, Sam Behjati, M. Fernanda Amary, Roberto Tirabosco, Andrew Feber, Peter J. Campbell, Ludmil B. Alexandrov, Peter Van Loo, Adrienne M. Flanagan, Nischalan Pillay
Journal: Cancer Cell (2019)

Undifferentiated sarcomas (USARCs) of adults are diverse, rare, and aggressive soft tissue cancers. Recent sequencing efforts have confirmed that USARCs exhibit one of the highest burdens of structural aberrations across human cancer. Here, we sought to unravel the molecular basis of the structural complexity in USARCs by integrating DNA sequencing, ploidy analysis, gene expression, and methylation profiling. We identified whole genome duplication as a prevalent and pernicious force in USARC tumorigenesis. Using mathematical deconvolution strategies to unravel the complex copy-number profiles and mutational timing models we infer distinct evolutionary pathways of these rare cancers. In addition, 15% of tumors exhibited raised mutational burdens that correlated with gene expression signatures of immune infiltration, and good prognosis.
Abstract 19248: Altered Cytoskeletal Mechanics in Cardiomyocytes Treated With Pediatric Heart Failure Serum
Authors: Thomas Lanzicher, Anastacia M Garcia, Xuan Jiang, Shelley D Miyamoto, Brian L Stauffer, Luisa Mestroni, Matthew R Taylor, Orfeo Sbaizeero, Carmen C Sucharov
Journal: Circulation (2017)

Introduction: Heart Failure (HF) in children is poorly understood with most clinical treatment paradigms extrapolated solely from adult practice. Emerging experimental and epidemiologic data suggest that the pediatric HF population is distinct from adult patients. We have recently developed an innovative primary cell culture model to investigated pediatric HF that treats primary neonatal rat ventricular myocytes (NRVMs) with serum from pediatric HF patients, specifically idiopathic dilated cardiomyopathy (IDC) and single ventricle heart disease (SV). We showed that serum treatment results in changes in gene expression suggestive of pathologic remodeling. Hypothesis: Serum treatment resulted in changes in gene expression suggestive of alteration in actin polymerization. We hypothesized that serum treatment would affect cellular elasticity of the cytoskeleton resulting in altered whole-cell biomechanical behavior. Methods: We combined atomic force microscopy (AFM), molecular and cellular biology methodologi...
Abstract 12921: Hematopoietic Stem/progenitor Cells Contribute to Atherosclerotic Progression Via Integrin aMβ2
Authors: Mingming Gao, Sarah Schouteden, Anton Roebroek, Kristel Eggermont, Paul Holvoet, Paul Van Veldhoven, George Liu, Catherine Verfaillie, Yingmei Feng
Journal: Circulation (2013)

Objectives: Inflammatory cells in atherosclerotic plaque are exclusively derived from hematopoietic stem/progenitor cells (HSPC) in bone marrow (BM). Recently, we and others reported HSPC prolifera...