tbuckley/cabot-search huggingface dataset:
Abstract LB-300: Development of an orally-administrative MELK (maternal embryonic leucine zipper kinase)-targeting small molecule inhibitor that suppresses the growth of various types of human cancer.
Authors: Suyoun Chung, Hanae Suzuki, Takashi Miyamoto, Naofumi Takamatsu, Ayako Tatsuguchi, Koji Ueda, Kyoko Kijima, Yo Matsuo, Yusuke Nakamura
Journal: Cancer Research (2013)

Abstract Breast cancer is the most common malignancy among women worldwide. Treatment for breast cancer acting on molecular targets in critical signaling pathways in cancer cells have successfully reduced the motility rate in a subset of breast cancer patients, but a significant portion of patients expect to have little benefit from these treatments. Therefore, development of new therapeutics for those patients is urgently required. We previously reported MELK (maternal embryonic leucine zipper kinase) as a novel therapeutic target for breast cancer. MELK was highly upregulated in multiple types of human cancer including breast, prostate and lung cancers, and plays indispensable roles in cancer cell survival, particularly in the maintenance of tumor-initiating cells. Although several substrates of MELK were reported, we still do not understood fully how MELK contributes to breast cancer development and/or progression. To elucidate the MELK signaling pathway in breast cancer cells, we screened and identified two novel MELK substrates, DBNL and PSMA1, which were also found to play critical roles in human carcinogenesis and mammary tumor-initiating cells. Furthermore, we conducted a high-throughput screening of a compound library followed by structure-activity relationship studies, and successfully obtained a highly potent MELK inhibitor OTSSP167 with IC50 of 0.41 nM. OTSSP167 inhibited the phosphorylation of these two substrates by MELK as well as mammosphere formation of breast cancer cells, and exhibited significant tumor growth suppression in xenograft studies using breast, lung, prostate, and pancreas cancer cell lines in mice by both intravenous and oral administration. Here, we report the biological function of novel substrates of MELK and the first MELK inhibitor OTSSP167 that is a promising compound to treat various types of human cancer. Citation Format: Suyoun Chung, Hanae Suzuki, Takashi Miyamoto, Naofumi Takamatsu, Ayako Tatsuguchi, Koji Ueda, Kyoko Kijima, Yo Matsuo, Yusuke Nakamura. Development of an orally-administrative MELK (maternal embryonic leucine zipper kinase)-targeting small molecule inhibitor that suppresses the growth of various types of human cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-300. doi:10.1158/1538-7445.AM2013-LB-300
The Convergence of Science and Governance: Research, Health Policy, and American States
Authors: Samuel Y. Sessions
Journal: JAMA (2010)

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
Relationship between the time of sustained ethyl acrylate forestomach hyperplasia and carcinogenicity.
Authors: B I Ghanayem, I M Sanchez, R R Maronpot, M R Elwell, H B Matthews
Journal: Environmental Health Perspectives (1993)

Chronic administration of ethyl acrylate (EA) by gavage at 100 or 200 mg/kg/day resulted in a significant dose-dependent increase in the incidence of forestomach (FS) squamous cell papillomas and carcinomas in both sexes of F344 rats and B6C3F1 mice. Subsequent work in this laboratory was designed to investigate the relationship between EA-induced FS hyperplasia and carcinogenicity. Current studies have focused on determining the time required for sustained FS hyperplasia to produce neoplastic transformation. Results of these studies demonstrated that gavage administration of EA to male F344 rats at 200 mg/kg/day for 6 or 12 months caused a sustained increase in FS epithelial hyperplasia for as long as exposure to EA continued. However, FS hyperplasia regressed, and no neoplasms developed when animals receiving EA for 6 months were allowed to recover until they were sacrificed at 24 months of age. In contrast, rats treated for 12 months and allowed 9 months recovery developed FS squamous cell carcinomas (3/13) and papillomas (1/13) for a combined incidence of 4/13. No gross lesions were detected in the liver of any of the rats treated with EA or corn oil vehicle, confirming the tissue specificity in the relationship between EA-induced FS hyperplasia and carcinogenesis. In conclusion, the present work has demonstrated that FS hyperplasia is selectively sustained at the site of EA-induced carcinogenicity for as long as EA is administered and has also demonstrated a temporal relationship between FS mucosal hyperplasia and the development of FS neoplasia by EA.(ABSTRACT TRUNCATED AT 250 WORDS)
Aortic Valve Replacement for Aortic Stenosis With Severe Left Ventricular Dysfunction
Authors: Heidi M. Connolly, Jae K. Oh, Thomas A. Orszulak, Sara L. Osborn, Veronique L. Roger, David O. Hodge, Kent R. Bailey, James B. Seward, A. Jamil Tajik
Journal: Circulation (1997)

Aortic valve replacement for aortic stenosis (AS) carries an increased risk in the presence of left ventricular (LV) systolic dysfunction. Few data are available on the outcome of such patients.Between 1985 and 1992, 154 consecutive patients (107 men and 47 women) with LV systolic dysfunction (ejection fraction [EF] < or = 35%) underwent aortic valve replacement for AS. The mean preoperative characteristics included EF, 27 +/- 6%; aortic valve mean gradient, 44 +/- 18 mm Hg; aortic valve area, 0.6 +/- 0.2 cm2; and cardiac output, 4.1 +/- 1.5 L/min. Simultaneous coronary artery bypass graft surgery was performed in 78 patients (51%). Perioperative (30-day) mortality was 9% (14 of 154 patients). Fifty patients died during follow-up. Coronary artery disease (P = .002) and a reduced preoperative cardiac output (P = .03) were significantly related to reduced overall survival rate by multivariate analysis. Postoperative improvement occurred in most patients; 88% were New York Heart Association class III or IV before surgery versus 7% after surgery. Postoperative EF was assessed in 76% of survivors; 76% of these demonstrated improvement. By multivariate analysis, change in EF was inversely related to coronary disease (P = .002) and preoperative aortic valve area (P = .03).Despite LV dysfunction, the risk of aortic valve replacement for AS was acceptable and related to coronary artery disease and mean aortic gradient, and long-term survival was related to coronary disease and cardiac output. Improvement in symptoms and EF occurred in most patients.
Differentiated properties of hepatocytes induced from pancreatic cells
Authors: David Tosh, Chia-Ning Shen, Jonathan M. W. Slack
Journal: Hepatology (2002)

Transdifferentiation of pancreas to liver is a well-recognized phenomenon and has been described in animal experiments and human pathology. We recently produced an in vitro model for the transdifferentiation (or conversion) of the pancreatic cell line AR42J-B13 to hepatocytes based on culture with dexamethasone (Dex). To determine whether the hepatocytes express markers of hepatic intermediary metabolism and detoxification, we investigated the patterns of expression of glucokinase, cytochrome P450s CYP3A1 and CYP2B1/2, testosterone/4-nitrophenol uridine diphosphate glucuronosyltransferase (UDPGT), and aryl sulfotransferase. All were expressed. We also determined the expression of 2 enzymes involved in ammonia detoxification: carbamoylphosphate synthetase I (CPS I) and glutamine synthetase (GS). These enzymes are normally strictly compartmentalized in liver in a wide periportal pattern and the last downstream perivenous hepatocytes, respectively. Following culture with Dex, CPS I and GS are expressed in 2 different cell populations, suggesting that both periportal and perivenous hepatocytes are induced. We also produced a reporter assay based on the activation of green fluorescent protein (GFP) by the transthyretin (TTR) promoter or glucose-6-phosphatase (G6Pase) promoter. After culture with Dex, transfected cells begin to express GFP, showing that hepatic promoters are activated in concert with the induction of the hepatocyte phenotype. Lastly, we examined the stability of the hepatic phenotype and found that some cells still express liver markers (transferrin or albumin) up to 14 days after removal of Dex. In conclusion, these results suggest that pancreatic hepatocytes produced by this method may offer an alternative model to primary cultures of hepatocytes for the study of liver function.
Headaches from cellular telephones: are they real and what are the implications?
Authors: A H Frey
Journal: Environmental Health Perspectives (1998)

There have been numerous recent reports of headaches occurring in association with the use of hand-held cellular telephones. Are these reported headaches real? Are they due to emissions from telephones? There is reason to believe that the answer is "yes" to both questions. There are several lines of evidence to support this conclusion. First, headaches as a consequence of exposure to low intensity microwaves were reported in the literature 30 years ago. These were observed during the course of microwave hearing research before there were cellular telephones. Second, the blood-brain barrier appears to be involved in headaches, and low intensity microwave energy exposure affects the barrier. Third, the dopamine-opiate systems of the brain appear to be involved in headaches, and low intensity electromagnetic energy exposure affects those systems. In all three lines of research, the microwave energy used was approximately the same--in frequencies, modulations, and incident energies--as those emitted by present day cellular telephones. Could the current reports of headaches be the canary in the coal mine, warning of biologically significant effects?
The Medical Cost-Containment Crisis: Fears, Opinions, and Facts
Authors: Bruce Stuart
Journal: JAMA (1990)

Four pages into this volume there is a figure that compares health care spending in the United States to that in seven other industrialized countries. Five of the seven are shown to spend more than the United States on a per capita basis—Canada a whopping 48% more! Were it true, there would be no need for this book or any of the dozens of others published on the same topic over the last decade. Errors of this sort abound in the introductory chapter of this loosely edited collection of 18 essays, which, as the title indicates, put fears and opinions before facts. It would have helped had the editor provided standard documentation for his figures and charts. As it is, the reader has no idea where the numbers actually came from. For example, Figure 2 (p 7), which is attributed simply to the "Health Care Financing Administration," is a pie
Surgical vs Conventional Therapy for Weight Loss Treatment of Obstructive Sleep Apnea
Authors: John B. Dixon, Linda M. Schachter, Paul E. O’Brien, Kay Jones, Mariee Grima, Gavin Lambert, Wendy Brown, Michael Bailey, Matthew T. Naughton
Journal: JAMA (2012)

Obstructive sleep apnea (OSA) is strongly related to obesity. Weight loss is recommended as part of the overall management plan for obese patients diagnosed with OSA.To determine whether surgically induced weight loss is more effective than conventional weight loss therapy in the management of OSA.A randomized controlled trial of 60 obese patients (body mass index: >35 and <55) with recently diagnosed (<6 months) OSA and an apnea-hypopnea index (AHI) of 20 events/hour or more. These patients had been prescribed continuous positive airway pressure (CPAP) therapy to manage OSA and were identified via accredited community sleep clinics. The trial was conducted between September 2006 and March 2009 by university- and teaching hospital-based clinical researchers in Melbourne, Australia. Patients with obesity hypoventilation syndrome, previous bariatric surgery, contraindications to bariatric surgery, or significant cardiopulmonary, neurological, vascular, gastrointestinal, or neoplastic disease were excluded.Patients were randomized to a conventional weight loss program that included regular consultations with a dietitian and physician, and the use of very low-calorie diets as necessary (n = 30) or to bariatric surgery (laparoscopic adjustable gastric banding; n = 30).The primary outcome was baseline to 2-year change in AHI on diagnostic polysomnography scored by staff blinded to randomization. Secondary outcomes were changes in weight, CPAP adherence, and functional status.Patients lost a mean of 5.1 kg (95% CI, 0.8 to 9.3 kg) in the conventional weight loss program compared with 27.8 kg (95% CI, 20.9 to 34.7 kg) in the bariatric surgery group (P < .001). The AHI decreased by 14.0 events/hour (95% CI, 3.3 to 24.6 events/hour) in the conventional weight loss group and by 25.5 events/hour (95% CI, 14.2 to 36.7 events/hour) in the bariatric surgery group. The between-group difference was -11.5 events/hour (95% CI, -28.3 to 5.3 events/hour; P = .18). CPAP adherence did not differ between the groups. The bariatric surgery group had greater improvement in the Short Form 36 physical component summary score (mean, 9.3 [95% CI, 0.5 to 18.0]; P = .04).Among a group of obese patients with OSA, the use of bariatric surgery compared with conventional weight loss therapy did not result in a statistically greater reduction in AHI despite major differences in weight loss.anzctr.org Identifier: 12605000161628.
A pRb-responsive, RGD-modified, and Hyaluronidase-armed Canine Oncolytic Adenovirus for Application in Veterinary Oncology
Authors: Eduardo Laborda, Cristina Puig-Saus, Alba Rodriguez-García, Rafael Moreno, Manel Cascalló, Josep Pastor, Ramon Alemany
Journal: Molecular Therapy (2014)

Human and canine cancer share similarities such as genetic and molecular aspects, biological complexity, tumor epidemiology, and targeted therapeutic treatment. Lack of good animal models for human adenovirotherapy has spurred the use of canine adenovirus 2-based oncolytic viruses. We have constructed a canine oncolytic virus that mimics the characteristics of our previously published human adenovirus ICOVIR17: expression of E1a controlled by E2F sites, deletion of the pRb-binding site of E1a, insertion of an RGD integrin-binding motif at the fiber Knob, and expression of hyaluronidase under the major late promoter/IIIa protein splicing acceptor control. Preclinical studies showed selectivity, increased cytotoxicity, and strong hyaluronidase activity. Intratumoral treatment of canine osteosarcoma and melanoma xenografts in mice resulted in inhibition of tumor growth and prolonged survival. Moreover, we treated six dogs with different tumor types, including one adenoma, two osteosarcomas, one mastocitoma, one fibrosarcoma, and one neuroendocrine hepatic carcinoma. No virus-associated adverse effects were observed, but toxicity associated to tumor lysis, including disseminated intravascular coagulation and systemic failure, was found in one case. Two partial responses and two stable diseases warrant additional clinical testing.
Prediction of Long-Term Mortality in Patients with Rheumatoid Arthritis according to Simple Questionnaire and Joint Count Measures
Authors: Theodore Pincus
Journal: Annals of Internal Medicine (1994)

Objective: To describe mortality over 15 years in a cohort of patients with rheumatoid arthritis, according to a simple questionnaire and joint count. Design: A cohort study with 15 years of follow-up. Setting: University hospital outpatient clinic. Patients: A cohort of 75 patients with rheumatoid arthritis. Measurements: Quantitative baseline measures: demographic, articular (joint counts), clinical, questionnaire, and physical measures, including modified questionnaire and joint count measures with substantially fewer items. Results: Although few deaths were seen in the first 3 years after baseline, the standard mortality ratio over 15 years was 1.62, similar to findings in other series. Significant predictors of mortality included age, formal education level, joint count, activities-of-daily-living questionnaire scores, disease adjustment scores, morning stiffness, comorbid cardiovascular disease, grip strength, modified walking time, and button test. Five-year survival in patients with the poorest status according to these quantitative measures was 40% to 60%, comparable to expected survival at that time of patients with three-vessel coronary artery disease or with stage 4 Hodgkin disease. Simplified measures, including a count using only 28 joints and a questionnaire using only 8 activities of daily living, were similar to the more elaborate traditional measures for predicting mortality. Conclusion: Higher mortality rates in patients with rheumatoid arthritis are predicted by more severe clinical disease, as in other chronic diseases. Severe rheumatoid arthritis may be identified using quantitative functional status questionnaires and joint counts, which can be ascertained in about 10 to 15 minutes in any clinical setting.
HHS Secretary Louis Sullivan speaks out for improved health
Authors: D. L. Breo
Journal: JAMA (1991)

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 Journals 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
Composite scaffolds of nano-hydroxyapatite and silk fibroin enhance mesenchymal stem cell-based bone regeneration via the interleukin 1 alpha autocrine/paracrine signaling loop
Authors: Hua Liu, Guo Wei Xu, Ya Fei Wang, Hong Shi Zhao, Si Xiong, Yan Wu, Boon Chin Heng, Cheng Rui An, Gang Hua Zhu, Ding Hua Xie
Journal: Biomaterials (2015)
Mechanisms and pathology of occupational asthma
Authors: CE Mapp, M Saetta, P Maestrelli, A Di Stefano, P Chitano, P Boschetto, A Ciaccia, LM Fabbri
Journal: European Respiratory Journal (1994)

Since the pathogenesis and the pathological features of occupational asthma are similar to those of nonoccupational asthma, the former represents a very useful model for the investigation of the pathogenesis of asthma in general. More than one mechanism may be operative in occupational asthma. Among the mechanisms proposed, immunological mechanisms and airway inflammation play an important role. There is evidence to confirm that T-lymphocyte activation and local accumulation in the bronchial wall of activated eosinophils occurs in asthma of diverse aetiology, i.e. immunoglobulin E (IgE)-mediated, occupational and intrinsic. Neurogenic pathways should be further investigated as a potential mechanism of modulation and amplification of airway inflammation in occupational asthma.
294 Safety and antiviral effect of BILN 2061, a novel HCV serine protease inhibitor, after oral treatment over 2 days in patients with chronic hepatitis C, genotype 1, and liver cirrhosis
Authors: H WEDEMEYER, A ERHARDT, W SCHMIEGEL, H HINRICHSEN, R CHAVES, C YONG, G NEHMIZ, G STEINMAN, B INGELHEIM
Journal: Hepatology (2003)
On Bedside Teaching
Authors: Elise A. Olsen
Journal: Annals of Internal Medicine (1997)

Letters15 July 1997On Bedside TeachingElise A. Olsen, MDElise A. Olsen, MDDuke University Medical Center; Durham, NC 27710Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-2-199707150-00044 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I was touched by the recent article on bedside teaching [1]. As a harried academic physician, I long to get back to basics and spend more time doing bedside teaching but have not been able to do so. The article correctly captured both the costs and rewards of effective bedside teaching. I thank the author for gently reminding all of us what we are missing.References1. LaCombe MA. On bedside teaching. Ann Intern Med. 1997; 126:217-20. Google Scholar Author, Article, and Disclosure InformationAffiliations: Duke University Medical Center; Durham, NC 27710 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1997Volume 127, Issue 2Page: 173 Issue Published: 15 July 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Report of the Health Care Delivery Work Group
Authors: Russell E. Glasgow, Roland G. Hiss, Robert M. Anderson, Neal M. Friedman, Rodney A. Hayward, David G. Marrero, C. Barr Taylor, Frank Vinicor
Journal: Diabetes Care (2001)

As one of four work groups for the November 1999 conference on Behavioral Science Research in Diabetes, sponsored by the National Institute on Diabetes and Digestive and Kidney Diseases, the health care delivery work group evaluated the status of research on quality of care, patient-provider interactions, and health care systems' innovations related to improved diabetes outcomes. In addition, we made recommendations for future research. In this article, which was developed and modified at the November conference by experts in health care delivery, diabetes and behavioral science, we summarize the literature on patient-provider interactions, diabetes care and self-management support among underserved and minority populations, and implementation of chronic care management systems for diabetes. We conclude that, although the quality of care provided to the vast majority of diabetic patients is problematic, this is principally not the fault of either individual patients or health care professionals. Rather, it is a systems issue emanating from the acute illness model of care, which still predominates. Examples of proactive population-based chronic care management programs incorporating behavioral principles are discussed. The article concludes by identifying barriers to the establishment of a chronic care model (e.g., lack of supportive policies, understanding of population-based management, and information systems) and priorities for future research in this area needed to overcome these barriers.