tbuckley/cabot-search huggingface dataset:
Abstract 126: The KISS1 metastasis suppressor appears to integrate glycolysis, mitochondrial biogenesis and metastasis via regulation of a PGC1α pathway
Authors: Wen Liu, Benjamin Beck, Kedar S. Vaidya, Kevin T. Nash, Scott W. Ballinger, Danny R. Welch
Journal: Cancer Research (2014)

Abstract Considering the enormous energy requirements and stresses of the metastatic cascade, an interrelationship with aerobic glycolysis seems intuitive, but has not been definitively established. The purpose of these studies was to determine whether there is a relationship between KISS1 metastasis suppression and metabolism. Wild-type KISS1 expressed in human melanoma cells were metastasis suppressed and took up less glucose and produced less lactate, corresponding to higher pH[Ex]. Metabolism and metastasis changes did not occur when KISS1 was missing the secretion signal peptide (ΔSS). Changes in glucose transport and key glycolytic enzymes did not consistently correlate with metabolic changes; however, V-ATPase, which promotes extracellular acidification, invasion and metastasis, appears to be involved in KISS1-mediated metabolic changes. Also corresponding with the shift from glycolysis to oxidative phosphorylation, KISS1-expressing cells have 30-50% more mitochondrial mass accompanied increased higher expression of PPARγ co-activator 1α (PGC1α), a master regulator of mitochondrial biogenesis. PGC1α-mediated downstream pathways (i.e. fatty acid synthesis and β-oxidation) are differentially regulated by KISS1, apparently reliant upon direct KISS1 interaction with Nuclear Respiratory Factor 1 (NRF1), a major transcription factor involved in mitochondrial biogenesis. KISS1 does not affect PGC1α mRNA expression but stabilizes the protein through interaction with the ubiquitin-like protein, UBQLN1. To test whether a KISS1- PGC1α axis is critical for metastasis suppressor function, shRNA to KISS1 or PGC1α was introduced into KISS1-expressing cells. Metabolic changes and suppression of invasion and migration were reversed. Importantly, knock-down of PGC1α abolished KISS1-mediated metastasis suppression in vivo, strongly suggesting that PGC1α is an essential downstream mediator of KISS1 as a metastasis suppressor. Taken together, these data define a novel signaling pathway controlling metabolism and metastasis. Moreover, these data appear to directly connect changes in aerobic glycolysis, mitochondrial metabolism, and cancer metastasis. Citation Format: Wen Liu, Benjamin Beck, Kedar S. Vaidya, Kevin T. Nash, Scott W. Ballinger, Danny R. Welch. The KISS1 metastasis suppressor appears to integrate glycolysis, mitochondrial biogenesis and metastasis via regulation of a PGC1α pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 126. doi:10.1158/1538-7445.AM2014-126
CXCL1 gene silencing in skin using liposome-encapsulated siRNA delivered by microprojection array
Authors: Oscar Haigh, Alexandra C.I. Depelsenaire, Stefano C. Meliga, Sally R. Yukiko, Nigel A.J. McMillan, Ian H. Frazer, Mark A.F. Kendall
Journal: Journal of Controlled Release (2014)
Abstract 1769: Significant in vivo activity of an APE1/Ref-1 redox inhibitor, E3330, alone and in combination with Bevacizumab in a glioblastoma mouse model analyzed by a whole slide digital imaging system and quantitative immunohistochemistry
Authors: Krishan Kumar, Jessica L. Jackson, Mark R. Kelley, Mircea Ivan, George Sandsuky
Journal: Cancer Research (2012)

Abstract Human apurinic endonuclease/redox factor 1 (APE1/Ref-1) mediates the repair of baseless sites in DNA caused by alkylation and oxidative DNA damage as well as regulates the function of various transcription factors (TF) under redox signaling control (p53, NFkB, HIF-1, AP-1, and others). High levels of APE1 expression have been reported in numerous cancers (glioblastoma, ovarian, pancreatic, prostate, and others) such that APE1 is an emerging target for a variety of novel anticancer drugs. E3330 targets the redox signaling function of APE1 and its activity was studied in vivo using a glioblastoma xenograft mouse model. This preclinical xenograft model evaluated the use of dual anti-angiogenic agents, Bevacizumab (Bev) and E3330, in glioblastoma implanted Nude mice. Four mice groups were used to determine drug effects: E3330, Bev, a combination of E3330 and Bev, and an untreated vehicle control group. Immunohistochemistry (IHC) was used to predict the effectiveness of treatment for glioblastoma based on caspase-3, Ki67, and CD31 biomarker expression. IHC slides were quantified using both a traditional pathology hand count and an image system analysis. The positive pixel data closely mirrored the hand count for all three biomarkers. At the combined dosage, hand count data demonstrated that CD31 levels decreased significantly from the vehicle control group. Ki67 decreased slightly, and caspase-3 was not increased in any of the drug treatment groups. While each drug independently had anti-angiogenic effects, the combined drug group, E3330 and Bev, had anti-angiogenic effects that were greatly enhanced. These results support previous studies demonstrating the anti-angiogenic activity of E3330 and its enhancement of Bevacizumab. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1769. doi:1538-7445.AM2012-1769
Folate Receptor–Specific Antitumor Activity of EC131, a Folate-Maytansinoid Conjugate
Authors: Joseph A. Reddy, Elaine Westrick, Hari K.R. Santhapuram, Stephen J. Howard, Michael L. Miller, Marilynn Vetzel, Iontcho Vlahov, Ravi V.J. Chari, Victor S. Goldmacher, Christopher P. Leamon
Journal: Cancer Research (2007)

Abstract EC131, a new folate receptor (FR)–targeted drug conjugate, was prepared by covalently attaching the vitamin folic acid (FA) to a potent microtubule-inhibiting agent, maytansinoid DM1, via an intramolecular disulfide bond. When tested on cells in culture, EC131 was found to retain high affinity for FR-positive cells and to provide FR-specific cytotoxicity with an IC50 in the low nanomolar range. The activity of EC131 was completely blocked in the presence of an excess of free FA, and no activity was detected against FR-negative cells. When evaluated against s.c. FR-positive M109 tumors in BALB/c mice, EC131 showed marked antitumor efficacy. Furthermore, this therapeutic effect occurred in the apparent absence of weight loss or noticeable organ tissue degeneration. In contrast, no significant antitumor activity was observed in EC131-treated animals that were codosed with an excess of FA, thus demonstrating the targeted specificity of the in vivo activity. EC131 also showed marked antitumor activity against FR-positive human KB tumors, but not against FR-negative A549 tumors, in nude mice with no evidence of systemic toxicity during or after the therapy. In contrast, therapy with the free maytansinoid drug (in the form of DM1-S-Me) proved not to be effective against the KB model when administered at its maximum tolerated dose (MTD). Taken together, these results indicate that EC131 is a highly potent agent capable of producing therapeutic benefit in murine tumor models at sub-MTD levels. [Cancer Res 2007;67(13):6376–82]
A Prospective Study of Sugar Intake and Risk of Type 2 Diabetes in Women
Authors: Sok-Ja Janket, JoAnn E. Manson, Howard Sesso, Julie E. Buring, Simin Liu
Journal: Diabetes Care (2003)

OBJECTIVE—To investigate prospectively whether intake of total or type of sugar is associated with the risk of developing type 2 diabetes. The contribution of sugar intake to the pathogenesis of type 2 diabetes has not been settled in the context of primary prevention because of limited prospective data. RESEARCH DESIGN AND METHODS—The Women’s Health Study is a randomized controlled trial of aspirin and vitamin E in the prevention of cardiovascular disease and cancer. A validated semiquantitative food frequency questionnaire was completed by 39,345 women aged 45 years and older. The main outcome was the incidence of type 2 diabetes. The predictor was sugar intake, including sucrose, glucose, fructose, and lactose. Using Cox proportional hazard models, multivariate RRs of type 2 diabetes for increasing quintiles of sugar intake compared with the lowest quintile were estimated. RESULTS—Compared with the lowest quintile of sugar intake, the RRs and 95% CIs for the highest quintiles were 0.84 (0.67–1.04) for sucrose, 0.96 (0.78–1.19) for fructose, 1.04 (0.85–1.28) for glucose, and 0.99 (0.80–1.22) for lactose, after adjustment for known risk factors for type 2 diabetes. Similar findings of no association were obtained in subgroup analyses stratified by BMI. CONCLUSIONS—Intake of sugars does not appear to play a deleterious role in primary prevention of type 2 diabetes. These prospective data support the recent American Diabetes Association’s guideline that a moderate amount of sugar can be incorporated in a healthy diet.
Gastrointestinal bleeding in adult patients with Henoch–Schönlein purpura
Authors: Eon Nam, Gun Kim, Jong Kang, Churl Im, Seong Jeon, Chang-Min Cho, Ji Jeong, Ji Park, Yun Jang, Young Kang
Journal: Endoscopy (2014)

We investigated the clinical and endoscopic features of gastrointestinal lesions in adults with Henoch–Schönlein purpura (HSP) causing gastrointestinal bleeding. The study included 24 adult HSP patients with gastrointestinal hemorrhage who underwent both upper gastrointestinal endoscopy and colonoscopy. The controls were 27 adult HSP patients without gastrointestinal hemorrhage. Patients with gastrointestinal bleeding showed higher frequencies of purpura on the upper extremities and trunk, and of elevated serum C-reactive protein (CRP). The rate of concurrent lesions in both the upper and lower gastrointestinal tracts was 91.7 %. The second portion of duodenum and terminal ileum were most frequently and severely involved. Leukocytoclastic vasculitis was detected in severe lesions and was significantly associated with mucosal ischemic changes. Most lesions (95.7 %) dramatically improved after corticosteroid therapy. This study suggests that both upper and lower gastrointestinal examinations are necessary for proper evaluation of gastrointestinal bleeding in patients with HSP.
Structural and functional implications of the phospholamban hinge domain: impaired SR Ca2+ uptake as a primary cause of heart failure
Authors: A SCHMIDT, J ZHAI, A CARR, M GERST, J LORENZ, P POLLESELLO, A ANNILA, B HOIT, E KRANIAS
Journal: Cardiovascular Research (2002)

Objective: The role of sarcoplasmic reticulum (SR) in the onset and progression of heart failure is controversial. We tested the hypothesis that impairment of SR Ca2+ sequestration may be a primary cause for progressive left ventricular (LV) dysfunction and the phospholamban hinge domain may be critical in this process. Methods: A phospholamban hinge domain mutant (PLB/N27A) was introduced in the cardiac compartment of the phospholamban null mouse. An integrative approach was used to characterize the resulting cardiac phenotype at a structural, cellular, whole organ and intact animal level. Results: NMR analysis revealed a defined alteration in the α-helical configuration between residues Q22 to F35 in mutant phospholamban. Transgenic lines expressing similar levels of mutant compared to wild-type phospholamban exhibited super-inhibition of the SR Ca2+ ATPase affinity for Ca2+ (EC50 0.52 μM) in oxalate-supported Ca2+ uptake measurements, which translated into impaired relaxation and attenuated responses to β-adrenergic stimulation. Importantly, a blunted force–frequency relation was observed in mutant hearts preceding left ventricular dilation. Upon aging to 10 months, the predominantly diastolic dysfunction progressed to congestive heart failure, characterized by induction of a fetal gene program, cardiac remodeling, lung congestion, depressed systolic function and early mortality. Conclusion: Increased inhibition of Ca2+ sequestration may be a causative factor in the development of left ventricular dysfunction and myocyte remodeling leading to heart failure. Furthermore, the hinge domain may play an important role in transmitting PLB's regulatory effects on SERCA.
Presinusoidal Portal Hypertension in Non–Alcoholic Cirrhosis
Authors: Gilles Pomier-Layrargues, Daniel Kusielewicz, Bernard Willems, Jean-Pierre Villeneuve, Denis Marleau, Jean Côté, P.-Michel Huet
Journal: Hepatology (1985)

The simultaneous measurement of wedged hepatic vein pressure (WHVP) and portal vein pressure (PVP) was performed in 156 cirrhotic patients. In the 110 alcoholic cirrhotic patients (97 micronodular and 13 macronodular cirrhosis), WHVP and PVP were closely related (25.8 +/- 6.3 vs. 25.9 +/- 6.3 mm Hg; p = not statistically significant). The difference between the two parameters was greater than 4 mm Hg in only six patients. In the 46 patients with nonalcoholic cirrhosis (41 macronodular and 1 micronodular cirrhosis; 4 primary biliary cirrhosis), PVP was significantly higher than was WHVP (25.8 +/- 6.2 vs. 21.7 +/- 6.8 mm Hg; p less than 0.001); in 20 patients, PVP exceeded WHVP by more than 4 mm Hg, and the mean difference was 7.5 mm Hg. There was no correlation between the porto-hepatic gradient and total hepatic blood flow measured by the indocyanine green single injection method or the portal fraction of total hepatic blood flow measured by indicator dilution curves. It is concluded that: (i) measurement of WHVP in alcoholic cirrhosis provides a reliable estimate of the severity of the portal hypertension, and (ii) hemodynamic evaluation of nonalcoholic cirrhosis should include PVP measurement in order to avoid underestimation of the porto-hepatic gradient.
The Nonallergic Asthma of Obesity. A Matter of Distal Lung Compliance
Authors: Ali Al-Alwan, Jason H. T. Bates, David G. Chapman, David A. Kaminsky, Michael J. DeSarno, Charles G. Irvin, Anne E. Dixon
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

The pathogenesis of asthma in obesity is poorly understood, but may be related to breathing at low lung volumes.To determine if lung function in obese patients with asthma and control subjects would respond differently to weight loss.Lung function was evaluated by conventional clinical tests and by impulse oscillometry in female late-onset, nonallergic patients with asthma and control subjects before, and 12 months after, bariatric surgery.Patients with asthma (n = 10) had significantly lower FEV1 (79.8 ± 10.6 vs. 95.5 ± 7.0%) and FVC (82.4 ± 13.2 vs. 93.7 ± 8.9%) compared with control subjects (n = 13). There were no significant differences in FRC or TLC at baseline. Twelve months after surgery, control subjects had significant increases in FEV1 (95.5 ± 7.0 to 100.7 ± 5.9), FVC (93.6 ± 8.9 to 98.6 ± 8.3%), FRC (45.4 ± 18.5 to 62.1 ± 15.3%), and TLC (84.8 ± 15.0 to 103.1 ± 15.3%), whereas patients with asthma had improvement only in FEV1 (79.8 ± 10.6 to 87.2 ± 11.5). Control subjects and patients with asthma had a significantly different change in respiratory system resistance with weight loss: control subjects exhibited a uniform decrease in respiratory system resistance at all frequencies, whereas patients with asthma exhibited a decrease in frequency dependence of resistance. Fits of a mathematical model of lung mechanics to these impedance spectra suggest that the lung periphery was more collapsed by obesity in patients with asthma compared with control subjects.Weight loss decompresses the lung in both obese control subjects and patients with asthma, but the more pronounced effects of weight loss on lung elastance suggest that the distal lung is inherently more collapsible in people with asthma.
Gastric cancer in patients with benign dyspepsia
Authors: K E L McCOLL
Journal: Gut (2001)

Editor,—There is an ongoing debate regarding the value of endoscopy in younger patients presenting with dyspepsia. One important consideration is the likelihood of detecting an underlying cancer which might be cured by early treatment. The large retrospective study by Breslin and colleagues in the January issue of Gut (

 Gut 2000; 46:93–97



) indicates that underlying cancer will be diagnosed in about 1 in 1000 patients presenting with uncomplicated dyspepsia under 45 years of age. However, the …
Hallucinogenic drug reaction-MDA
Authors: C. D. Leake
Journal: JAMA (1972)

ABSTRACT To the Editor.— In their report on near fatal reaction to ingestion of the hallucinogenic drug methylenedioxyamphetamine (MDA), Richards and Borgstedt (218:1826, 1971) state that they could find little information upon it. Gordon Alles (1901-1963), who first made and developed amphetamine, reported quite fully on structure and action of phenethylamines with discussion of MDA Neuropharmacology: Transactions of the Fourth Conference. (Abramson HA, Macy J Jr [eds]: New York, Foundation Press, 1959, pp 181-268).In this, Alles says that on injection of MDA into small animals it was determined that its toxicity is not significantly different from the lethal dosage of phenethylamine or of amphetamine. He fully described the effects on himself of taking a total divided dose by mouth of 1.4 mg/kg in two hours. These effects included visual and auditory distortions, with a tendency to neck-muscle tension, pupil dilatation, and the peculiar phenomenon of seeing himself hit a
SOME TYPHOID EPIDEMICS STUDIED BY LABORATORY METHODS.
Authors: WM. ROYAL STOKES
Journal: JAMA (1905)

2 cases; March 15, 3 cases; March 16, 1 case; March 18, 1 case; March 19, 2 cases; March 21, 2 cases.This whole group all took their meals at the institute inn, except one teacher and his child of 2 years, and a young woman visitor of 26 years.No servants were attacked
Expanding and Understanding Risk Factors for Coronary Heart Disease-Reply
Authors: Jeffrey M. Hoeg
Journal: JAMA (1997)

In Reply.  —More than 100 potential risk factors for CHD have been reported. My article focused on 17 promising new risk factors that have therapeutic implications. I agree with Drs Stetson and Schrodt that psychosocial risk factors are promising as is the association of OSA with cardiovascular disease risk as outlined by Dr Davidson. However, the status of these candidate risk factors is not as advanced in establishing either the independence of other factors or the therapeutic efficacy of risk factor modulation on the development of coronary artery disease.  Whether the statistically significant changes in the homocysteine concentrations that Dr DeRose and colleagues have observed with lifestyle alterations are physiologically meaningful requires further study.
Underage Drinking—A Report From the Inspector General
Authors: Antonia C. Novello
Journal: JAMA (1992)

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
(35) Diabetes, necrobiosis lipoidica and granuloma annulare
Authors: M.L. Wood, S.S. Bleehen, J.D. Ward
Journal: British Journal of Dermatology (1986)

Journal Article (35) Diabetes, necrobiosis lipoidica and granuloma annulare Get access M.L. Wood, Drs, M.L. Wood, Drs Search for other works by this author on: Oxford Academic Google Scholar S.S. Bleehen, S.S. Bleehen Search for other works by this author on: Oxford Academic Google Scholar J.D. Ward J.D. Ward Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Pages 81–82, https://doi.org/10.1111/j.1365-2133.1986.tb07730.x Published: 01 July 1986
Drinking water treatment and risk of cancer death in Wisconsin.
Authors: M S Kanarek, T B Young
Journal: Environmental Health Perspectives (1982)

A case control study of drinking water treatment practices and female cancer mortality was conducted in Wisconsin. Cancer deaths for 1972-1977 from 28 Wisconsin counties and noncancer deaths matched to cancer deaths on age, year of death and county of residence, were compared for characteristics of drinking water supplied to their places of residence. Using logistic regression, estimates of relative risk associated with chlorinated water were examined allowing for the influence of indicators of water organics and the potential confounders of occupation, marital status and urbanicity. Only colon cancer appeared to be related significantly to chlorination in all models explored. A dose-response relationship was found between crude indicators of trihalomethane level (chlorination X organic contamination) and colon cancer death. The odds ratio for chlorinated surface water for colon cancer was 2.81 (p less than 0.01); approximately half this risk was found for chlorinated ground water. Consequently, a case control study of colon cancer and drinking water quality utilizing newly diagnosed patients is being conducted in Wisconsin.
Plan to stimulate research in developing countries is put on hold
Authors: A. Gulland
Journal: BMJ (2012)

Health officials have failed to come to an agreement on a binding convention on stimulating research and development focusing on the health problems of developing countries.

Last week’s World Health Assembly, the World Health Organization’s decision making body, saw negotiations throughout the week on a report published by WHO in April. A key recommendation of that report was that all countries—developing and developed—should commit around 0.01% of their gross domestic product to research into and development of treatments for the health problems of developing countries.

The United States (despite the fact that it already meets this target), the European Union, and Japan blocked this recommendation, and instead member states agreed on the final day of the assembly that the report would be …
Effects of diacylglycerol administration on serum triacylglycerol in a patient homozygous for complete lipoprotein lipase deletion
Authors: Kunio Yamamoto, Hideki Asakawa, Katsuto Tokunaga, Shinichi Meguro, Hiroyuki Watanabe, Ichiro Tokimitsu, Noriko Yagi
Journal: Metabolism (2004)