tbuckley/cabot-search huggingface dataset:
Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial
Authors: Shankar Siva, Mathias Bressel, Declan G. Murphy, Mark Shaw, Sarat Chander, John Violet, Keen Hun Tai, Cristian Udovicich, Andrew Lim, Lisa Selbie, Michael S. Hofman, Tomas Kron, Daniel Moon, Jeremy Goad, Nathan Lawrentschuk, Farshad Foroudi
Journal: European Urology (2018)
Price Setting for Physician Services—Reply
Authors: Austin B. Frakt, Michael E. Chernew
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
Abstract 366: Association of <i>MLL2/KMT2D</i> and <i>MLL3/KMT2C</i> with chronic myeloid leukemia
Authors: Doralina do Amaral Rabello Ramos, Vivian D'Afonseca da Silva Ferreira, Maria Gabriela Berzoti-Coelho, Sandra Mara Burin, Cíntia Leticia Magro, Maira da Costa Cacemiro, Belinda Pinto Simões, Felipe Saldanha-Araujo, Fabíola Attié Castro, Fábio Pittella-Silva
Journal: Cancer Research (2018)

Abstract Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm linked to the Philadelphia chromosome presence that generates the BCR-ABL1 fusion oncogene. Tyrosine kinase inhibitors (TKI) such as imatinib mesylate (IM) dramatically improved the treatment efficiency and survival of CML patients by targeting BCR-ABL tyrosine kinase. Although patients in the chronic phase respond well to treatment, patients in the accelerated phase or blast crisis usually show therapy resistance and CML relapse. It is crucial, therefore, to identify biomarkers to predict CML genetic evolution and resistance to TKI therapy, considering not only the effects of genetic aberrations but also the role of epigenetic alterations during the disease. Although dysregulations in epigenetic modulators such as histone methyltrasnferases have already been described for some hematologic malignancies, to date very limited data is available for CML, especially when considering the MLL2/KMT2D and MLL3/KMT2C genes of histone methyltrasnferases. Here we investigated the expression profile of both genes in CML patients in different stages of the disease, in patients showing different responses to therapy with IM and in non-neoplastic control samples. Imatinib sensitive and resistant CML cell lines were also used to investigate whether treatment with other tyrosine kinase inhibitors interfered in their expression. Both genes were either upregulated or with basal expression level during the chronic phase compared to controls. Interestingly, MLL3/KMT2C and specially MLL2/KMT2D levels decreased during disease progression correlating with distinct clinical stages. Furthermore, MLL2/KMT2D was decreased in patients resistant to IM treatment. Our results established a new association between MLL2/KMT2D and MLL3/KMT2C genes with CML and suggest that MLL2/KMT2D is associated with disease evolution and may be a potential marker to predict the development of therapy resistance. Citation Format: Doralina do Amaral Rabello Ramos, Vivian D'Afonseca da Silva Ferreira, Maria Gabriela Berzoti-Coelho, Sandra Mara Burin, Cíntia Leticia Magro, Maira da Costa Cacemiro, Belinda Pinto Simões, Felipe Saldanha-Araujo, Fabíola Attié Castro, Fábio Pittella-Silva. Association of MLL2/KMT2D and MLL3/KMT2C with chronic myeloid leukemia [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 366.
Loss of Estrogen-Regulated <i>MIR135A1</i> at 3p21.1 Promotes Tamoxifen Resistance in Breast Cancer
Authors: Weijie Zhang, Mingming Wu, Qing-Yun Chong, Min Zhang, Xiao Zhang, Lan Hu, Yanghao Zhong, Pengxu Qian, Xiangjun Kong, Sheng Tan, Gaopeng Li, Keshuo Ding, Peter E. Lobie, Tao Zhu
Journal: Cancer Research (2018)

The dysregulation of miRNAs has been increasingly recognized as a critical mediator of cancer development and progression. Here, we show that frequent deletion of the MIR135A1 locus is associated with poor prognosis in primary breast cancer. Forced expression of miR-135a decreased breast cancer progression, while inhibition of miR-135a with a specific miRNA sponge elicited opposing effects, suggestive of a tumor suppressive role of miR-135a in breast cancer. Estrogen receptor alpha (ERα) bound the promoter of MIR135A1 for its transcriptional activation, whereas tamoxifen treatment inhibited expression of miR-135a in ERα+ breast cancer cells. miR-135a directly targeted ESR1, ESRRA, and NCOA1, forming a negative feedback loop to inhibit ERα signaling. This regulatory feedback between miR-135a and ERα demonstrated that miR-135a regulated the response to tamoxifen. The tamoxifen-mediated decrease in miR-135a expression increased the expression of miR-135a targets to reduce tamoxifen sensitivity. Consistently, miR-135a expression was downregulated in ERα+ breast cancer cells with acquired tamoxifen resistance, while forced expression of miR-135a partially resensitized these cells to tamoxifen. Tamoxifen resistance mediated by the loss of miR-135a was shown to be partially dependent on the activation of the ERK1/2 and AKT pathways by miR-135a-targeted genes. Taken together, these results indicate that deletion of the MIR135A1 locus and decreased miR-135a expression promote ERα+ breast cancer progression and tamoxifen resistance.Significance: Loss of miR-135a in breast cancer disrupts an estrogen receptor-induced negative feedback loop, perpetuating disease progression and resistance to therapy.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/17/4915/F1.large.jpg Cancer Res; 78(17); 4915-28. ©2018 AACR.
Protective effects of antimalarials in Chinese patients with systemic lupus erythematosus
Authors: Fan Wang, Wei Zhang, Shiying Wang, Wenyou Pan, Lin Liu, Min Wu, Fuwan Ding, Huaixia Hu, Xiang Ding, Hua Wei, Yaohong Zou, Xian Qian, Meimei Wang, Jian Wu, Juan Tao, Jun Tan, Zhanyun Da, Miaojia Zhang, Jing Li, Xuebing Feng, Lingyun Sun
Journal: Annals of the Rheumatic Diseases (2018)

In conclusion, our data show that the use of antimalarials could improve long-term outcome of Chinese patients with SLE.These drugs possess protective effects on a wide range of clinical aspects.Patients with vital organ involvements, especially cardiopulmonary, gastrointestinal, renal or haematological impairments, may gain more benefits from antimalarial treatments.
Geographic variation in molecular subtype for gastric adenocarcinoma
Authors: Ping Liao, Feifei Jia, Jamie K Teer, Todd C Knepper, Hong-Hao Zhou, Yi-Jing He, Howard L McLeod
Journal: Gut (2018)

The presence of distinct molecular subgroups of gastric cancer (GC) has been recently highlighted in Gut .1 2 However, there has been little focus on the geographic distribution of molecular subgroups. Differences in GC molecular subtypes were assessed using data from The Cancer Genome Atlas (TCGA). Razvan et al established four clinically relevant molecular subtypes, which are MSS (microsatellite stable)/TP53−, MSS/TP53+, MSI (microsatellite instability) and MSS/EMT (epithelial–mesenchymal transition), further delineating GC.3 The clinical significance has been evaluated in a recent study using the TCGA proposed comprehensive molecular classification of patients with GC into four subtypes: Epstein-Barr virus (EBV), chromosomal instability (CIN), MSI and genomically stable (GS). Sohn et al reported that CIN and MSI subtypes had better overall survival than GS, but worse than EBV subtypes.4 Identification of molecular subtypes of GC may offer improved ways to monitor the progression, and predict prognosis …
Abstract 10634: Impact of Pulmonary Hypertension on Surgical Outcomes after Restrictive Mitral Annuloplasty in Patients with Ischemic Cardiomyopathy and Mitral Regurgitation
Authors: Satoshi Kainuma, Kazuhiro Taniguchi, Koichi Toda, Takashi Daimon, Toshihiro Funatsu, Shigeru Miyagawa, Haruhiko Kondoh, Shigeaki Otake, Masayuki Sakaki, Takafumi Masai, Takayoshi Ueno, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2012)

Background:  Pulmonary hypertension (PH) in patients with left ventricular dysfunction is a predictor of operative mortality, but its impact on long-term outcome has not been sufficiently established.   Methods:  We classified 156 patients undergoing RMA for end-stage ischemic cardiomyopathy (ejection fraction ≤40%) and functional mitral regurgitation into 3 groups on the basis of Doppler-derived systolic pulmonary artery pressure (PAP) at baseline: systolic PAP    Results:  The actual operative mortality was 2.4% [95% confidential interval (CI), 0.4%-13%], 1.4% (95% CI, 0.2%-7.6%), and 2.4% (95% CI, 0.4%-12%) for mild, moderate, and severe PH group, respectively (p=0.90), which was lower than that estimated by the New EuroSCORE II models (9±8%, 12±10% and 14±11%, respectively). During the follow-up period, there were 44 mortality and 51 readmissions for heart failure. Actuarial survival at 5 years after surgery was 89%, 65%, and 56%, for mild, moderate, and severe PH, respectively (p=0.005). Freedom from adverse events (all cause mortality/readmission for heart failure) at 5 years was 86%, 47%, and 7%, respectively, which were related to the degree of preoperative PH (p   Conclusions:  The operative mortality after RMA was relatively low in patients with varying degrees of preoperative PH, but patients with severe PH showed high rate of mortality and adverse events. New medical treatment strategy should be established to expect improved long-term survival after RMA in patients with severe PH.
von Willebrand factor enhances microvesicle-induced vascular leakage and coagulopathy in mice with traumatic brain injury
Authors: Yingang Wu, Wei Liu, Yuan Zhou, Tristan Hilton, Zilong Zhao, Wei Liu, Min Wang, Jason Yeon, Katie Houck, Perumal Thiagarajan, Fangyi Zhang, Fu-Dong Shi, Xiaoping Wu, Min Li, Jing-fei Dong, Jianning Zhang
Journal: Blood (2018)
3D organizational mapping of collagen fibers elucidates matrix remodeling in a hormone-sensitive 3D breast tissue model
Authors: Zhiyi Liu, Lucia Speroni, Kyle P. Quinn, Carlo Alonzo, Dimitra Pouli, Yang Zhang, Emily Stuntz, Carlos Sonnenschein, Ana M. Soto, Irene Georgakoudi
Journal: Biomaterials (2018)
Effects of orally administered sunitinib malate (SU11248) on embryo-fetal development in the rat and rabbit
Authors: Shem Patyna, Diann Morris, Karen Freshwater, Geoffrey Peng, Diane Matsumoto, Gary Chmielewski
Journal: Cancer Research (2007)

1561    Introduction:  Angiogenesis plays a critical role in many physiological processes, including embryo-fetal development. Accordingly, most of the targeted antiangiogenic agents used in oncology are not recommended for use during pregnancy based on existing nonclinical safety data. Sunitinib is an oral, multitargeted RTK inhibitor of VEGFRs, PDGFRs and other RTKs with direct antitumor and antiangiogenic activity. We report the results of three nonclinical studies investigating the effects of orally administered sunitinib on embryo-fetal development in female rats and rabbits.   Methods:  Sunitinib was administered orally, once daily, to pregnant Sprague-Dawley rats and New Zealand White rabbits for 12 and 14 consecutive days, respectively, during the major period of organogenesis. Sunitinib was administered as a solution in vehicle at doses ranging from 0 (control) to 0.3-30 mg/kg/day in rats, and to 0.5-20 mg/kg/day in rabbits. Body weights, food consumption and clinical observations were recorded throughout gestation. Animals were humanely euthanized and a cesarean section was performed on gestation days 20 or 21 (rats) and 29 (rabbits). Each uterus was weighed intact and a gross necropsy was performed on each female. The numbers of live and dead fetuses, early and late resorptions, corpora lutea and total implantations were recorded. Fetuses were examined grossly (externally), weighed, and euthanized. Rat fetuses were sexed and, in the case of the embryo-fetal development study, were processed for visceral and skeletal examination.   Results:  Mortality was observed in rats at the highest dose of sunitinib, 30 mg/kg/day. In rats, sunitinib ≥5 mg/kg/day resulted in decreased gravid uterine weights, number of viable fetuses, and fetal body weight, as well as an increased number of resorptions (post-implantation loss), and complete litter loss (in all litters at ≥15 mg/kg/day). Fetal malformations were observed at doses >3 mg/kg/day and consisted primarily of an increased incidence of skeletal malformations, although acephalostomia also occurred in 2 fetuses in the 5 mg/kg/day group. Mortality was observed in rabbits at the highest dose of sunitinib, 20 mg/kg/day, and treatment in this group was terminated early due to overt toxicity and escalating weight loss. At 5 mg/kg/day, reductions in gravid uterine weights and number of live fetuses were due to increases in the number of resorptions (post-implantation loss), and complete litter loss (4 of 6 females). Cleft lip and/or cleft palate were observed at doses ≥1 mg/kg/day. No other treatment-related fetal malformations or variations were observed.   Conclusions:  As expected for a VEGF signaling inhibitor, sunitinib was associated with embryo-fetal developmental toxicity in female rats and rabbits. These developmental effects were observed at or below the estimated human systemic exposure to sunitinib at 50 mg/day.
Abstract 20620: The Relationship Between Thyroid-Related Antibodies and Atrial Fibrillation in Euthyroid Patients
Authors: Dong Hyun Park, Bong Joon Kim, Ga In You, Tae Joon Cha
Journal: Circulation (2016)

Objective:  Hyperthyroidism is an important cause of atrial fibrillation (AF). However, the prevalence of thyroid-related antibodies in a normal thyroid function state has not yet been thoroughly documented. Therefore, we aim to identify the relationship between thyroid-related antibodies and AF in euthyroid AF patients compared with age-matched control patients.   Methods:  A cross-sectional survey of 1,294 patients (mean age 57.09±14.27 years, 476 males, 818 females) who were euthyroid without anti-thyroid medication was performed. Serum Thyroid- stimulating hormone(TSH) receptor antibodies, anti-microsomal antibodies and anti-thyroglobulin antibody level were measured in 844 non-AF control patients and 450 AF patients using a radioimmunoassay kit.   Results:  TSH receptor antibodies were significantly increased in euthyroid AF patients. TSH receptor antibodies were present at 4.23±21.85 u/L and 10.15±45.07 u/L (control vs. AF, respectively; p=0.029). Anti-thyroglobulin antibody levels were 64.31±105.59 u/mL and 71.53±114.51 u/mL (control vs. AF, respectively; p=0.282). Anti-microsomal antibodies were present at 155.53±352.35 u/mL and 198.67±404.50 u/mL (p=0.068, control vs. AF, respectively). Seropositivity was defined as a TSH receptor antibody level exceeding 10 u/L and seropositivity was compared between groups using the chi-square test. In total, 26/569 (4.6%) of control patients and 35/278 (11.2%) of AF patients were seropositive, representing a significant difference (odds ratio, 2.629; p   Conclusion:  Patients seropositive for TSH receptor antibody were at high risk of AF even when in the euthyroid state.
Abstract 3738: Three-dimensional treatment-resistant breast cancer spheroids as a predictive model of <i>in vivo</i> response to endocrine therapy
Authors: Carlo I. Rosales, Jiong Zhao, Lauren M. Gutgesell, Rui Xiong, Debra A. Tonetti, Gregory R. Thatcher
Journal: Cancer Research (2018)

Abstract 1 out of every 8 U.S. women will develop invasive breast cancer during her lifetime, making it the second most common form of cancer affecting women. Breast cancer is also a leading cause of cancer related deaths for women in the U.S., second only to lung cancer. Activation of estrogen receptor alpha (ERα) is the primary proliferative mechanism of breast cancer cells, making it a logical target for therapy. ER ligands with antiestrogenic activity, such as the selective estrogen receptor modulator (SERM), tamoxifen, and selective estrogen receptor degrader (SERD), fulvestrant, have proven clinically successful as treatments for breast cancer; however, resistance in up to 50% of patients provides a therapeutic challenge. Once resistant, breast cancer cells become endocrine-independent, because of this, there is an urgent need for both novel therapy and improved models of resistant breast cancer. Our lab has created a panel of various endocrine-independent cell lines to mimic SERM and SERD resistance. Along with traditional 2D cell culturing, 3D spheroids have also been utilized to gain a better understanding of resistance. Importantly, the response to therapeutic agents, of cell lines in 2D versus 3D cultures is not identical. We observe that 3D cultures better replicate observations in mouse xenograft models, demonstrating that elements of the spheroid microenvironment, such as cell-cell interactions and the presence of extracellular matrix (EM), mimic aspects of the tumor microenvironment in vivo. Cells cultured as spheroids are therefore a suitable in vitro model for drug discovery, predictive of response in preclinical animal models, in contrast to 2D monolayer cell cultures. Citation Format: Carlo I. Rosales, Jiong Zhao, Lauren M. Gutgesell, Rui Xiong, Debra A. Tonetti, Gregory R. Thatcher. Three-dimensional treatment-resistant breast cancer spheroids as a predictive model of in vivo response to endocrine therapy [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 3738.
Abstract LB-192: 2,2'-Methylenebis (6-tert-butyl 4-methylphenol) enhances the antitumor efficacy of belotecan, a derivative of camptothecin, by inducing autophagy
Authors: Junsoo Park, Eun-Ju Lee
Journal: Cancer Research (2018)

Abstract Autophagy regulation is important for tumor cell survival. Activation and inhibition of autophagy can sensitize tumor cells to anticancer drugs. However, few autophagy-regulating small molecules are available to increase the efficacy of anticancer drugs. Here, we report that 2,2'-methylenebis (6-tert-butyl 4-methylphenol), hereafter referred to as methylenebis, is a novel autophagy-regulating small molecule that sensitizes tumor cells to belotecan, which is a derivative of camptothecin, a topoisomerase I inhibitor. Methylenebis activates autophagic flux by increasing the level of LC3-II and forming autolysosome puncta. Moreover, methylenebis enhances the antitumor efficacy of belotecan by activating both autophagy and apoptosis. Interestingly, methylenebis increased the level of LC3-II and belotecan independently decreased the level of p62, suggesting that methylenebis and belotecan target different steps of autophagy. Finally, we searched for compounds that are structurally similar to methylenebis. Our results imply that the specific structure of methylenebis contributes to its ability to activate autophagy. Citation Format: Junsoo Park, Eun-Ju Lee. 2,2'-Methylenebis (6-tert-butyl 4-methylphenol) enhances the antitumor efficacy of belotecan, a derivative of camptothecin, by inducing autophagy [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-192.
Parallel Accumulation of Tumor Hyaluronan, Collagen, and Other Drivers of Tumor Progression
Authors: Xiaoming Li, H. Michael Shepard, Jessica A. Cowell, Chunmei Zhao, Ryan J. Osgood, Sanna Rosengren, Barbara Blouw, Sheryl A. Garrovillo, Mark D. Pagel, Clifford J. Whatcott, Haiyong Han, Daniel D. Von Hoff, Darin M. Taverna, Michael J. LaBarre, Daniel C. Maneval, Curtis B. Thompson
Journal: Clinical Cancer Research (2018)

Purpose: The tumor microenvironment (TME) evolves to support tumor progression. One marker of more aggressive malignancy is hyaluronan (HA) accumulation. Here, we characterize biological and physical changes associated with HA-accumulating (HA-high) tumors.Experimental Design: We used immunohistochemistry, in vivo imaging of tumor pH, and microdialysis to characterize the TME of HA-high tumors, including tumor vascular structure, hypoxia, tumor perfusion by doxorubicin, pH, content of collagen. and smooth muscle actin (α-SMA). A novel method was developed to measure real-time tumor-associated soluble cytokines and growth factors. We also evaluated biopsies of murine and pancreatic cancer patients to investigate HA and collagen content, important contributors to drug resistance.Results: In immunodeficient and immunocompetent mice, increasing tumor HA content is accompanied by increasing collagen content, vascular collapse, hypoxia, and increased metastatic potential, as reflected by increased α-SMA. In vivo treatment of HA-high tumors with PEGylated recombinant human hyaluronidase (PEGPH20) dramatically reversed these changes and depleted stores of VEGF-A165, suggesting that PEGPH20 may also diminish the angiogenic potential of the TME. Finally, we observed in xenografts and in pancreatic cancer patients a coordinated increase in HA and collagen tumor content.Conclusions: The accumulation of HA in tumors is associated with high tIP, vascular collapse, hypoxia, and drug resistance. These findings may partially explain why more aggressive malignancy is observed in the HA-high phenotype. We have shown that degradation of HA by PEGPH20 partially reverses this phenotype and leads to depletion of tumor-associated VEGF-A165. These results encourage further clinical investigation of PEGPH20. Clin Cancer Res; 24(19); 4798-807. ©2018 AACR.
Osteoporosis Screening—2 Steps May Be Too Much for Women Younger Than 65 Years
Authors: Margaret L. Gourlay
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal