tbuckley/cabot-search huggingface dataset:
Effective Intravenous Therapy of Murine Pulmonary Metastases with an Oncolytic Herpes Virus Expressing Interleukin 12
Authors: Richard J. Wong, Mei-Ki Chan, Zhenkun Yu, Teresa H. Kim, Amit Bhargava, Brendon M. Stiles, Brian C. Horsburgh, Jatin P. Shah, Ronald A. Ghossein, Bhuvanesh Singh, Yuman Fong
Journal: Clinical Cancer Research (2004)

Abstract Purpose: There currently is no therapy that enhances the survival of patients with distantly metastatic squamous cell carcinoma (SCC). Engineered herpes oncolytic viruses are effective therapeutic agents when delivered directly to tumors in animal models, but their efficacy in treating disseminated disease is poorly defined. Experimental Design: We treated disseminated pulmonary SCC in mice with an interleukin (IL)-12-expressing oncolytic herpes virus (NV1042) or with the parent oncolytic virus (NV1023, IL-12 deficient) by i.v. tail vein administration. Results: Lung IL-12 was 16.1 pg/mg and IFN-γ was 4.3 pg/mg at day 1 after a single dose of NV1042 (5 × 107 plaque-forming units); levels of both were undetectable for NV1023. 5-Bromo-4-chloro-3-indolyl-β-d-galactopyranoside histochemistry demonstrated viral infection of disseminated pulmonary tumor nodules by both vectors at day 1, with sparing of adjacent alveolar cells. NV1042-treated lungs showed no surface nodules at day 12, in contrast to NV1023-treated (92 ± 27 surface nodules) and PBS-treated (225 ± 9 surface nodules) lungs. Significantly enhanced survival was observed in NV1042-treated animals compared with NV1023- and PBS-treated animals (log rank &amp;lt; 0.05). In animals with a low tumor burden, 100% of NV1042-treated, 70% of NV1023-treated, and none of the control animals achieved long-term survival. NV1042 efficacy was similar to NV1023 efficacy in animals depleted of CD4/CD8 T lymphocytes, showing that IL-12 expression enhances oncolytic activity through immune effects. Histology showed no cytopathic effects in non-tumor-bearing lung, brain, spleen, liver, and pancreas after completion of viral therapy. No animals demonstrated any visible side effects attributable to viral therapy. Conclusions: The i.v. delivery of an oncolytic herpes virus may achieve effective infection, oncolysis, and transgene expression at distant tumor sites. This approach to systemic therapy combining oncolysis with IL-12 immune stimulation led to significantly improved survival in animals with disseminated SCC.
Hemoglobin Variability Does Not Predict Mortality in European Hemodialysis Patients
Authors: Kai-Uwe Eckardt, Joseph Kim, Florian Kronenberg, Pedro Aljama, Stefan D. Anker, Bernard Canaud, Bart Molemans, Peter Stenvinkel, Guntram Schernthaner, Elizabeth Ireland, Bruno Fouqueray, Iain C. Macdougall
Journal: Journal of the American Society of Nephrology (2010)

Patients with CKD exhibit significant within-patient hemoglobin (Hb) level variability, especially with the use of erythropoiesis stimulating agents (ESAs) and iron. Analyses of dialysis cohorts in the United States produced conflicting results regarding the association of Hb variability with patient outcomes. Here, we determined Hb variability in 5037 European hemodialysis (HD) patients treated over 2 years to identify predictors of high variability and to evaluate its association with all-cause and cardiovascular disease (CVD) mortality. We assessed Hb variability with various methods using SD, residual SD, time-in-target (11.0 to 12.5 g/dl), fluctuation across thresholds, and area under the curve (AUC). Hb variability was significantly greater among incident patients than prevalent patients. Compared with previously described cohorts in the United States, residual SD was similar but fluctuations above target were less frequent. Using logistic regression, age, body mass index, CVD history, dialysis vintage, serum albumin, Hb, angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use, ESA use, dialysis access type, dialysis access change, and hospitalizations were significant predictors of high variability. Multivariable adjusted Cox regression showed that SD, residual SD, time-in-target, and AUC did not predict all-cause or CVD mortality during a median follow-up of 12.4 months (IQR: 7.7 to 17.4). However, patients with consistently low levels of Hb (<11 g/dl) and those who fluctuated between the target range and <11 g/dl had increased risks for death (RR 2.34; 95% CI: 1.24 to 4.41 and RR 1.74; 95% CI: 1.00 to 3.04, respectively). In conclusion, although Hb variability is common in European HD patients, it does not independently predict mortality.
Functional associations of proteins in entire genomes by means of exhaustive detection of gene fusions
Authors: Anton J Enright, Christos A Ouzounis
Journal: Genome biology (2001)

It has recently been shown that the detection of gene fusion events across genomes can be used for predicting functional associations of proteins, including physical interaction or complex formation. To obtain such predictions we have made an exhaustive search for gene fusion events within 24 available completely sequenced genomes. Each genome was used as a query against the remaining 23 complete genomes to detect gene fusion events. Using an improved, fully automatic protocol, a total of 7,224 single-domain proteins that are components of gene fusions in other genomes were detected, many of which were identified for the first time. The total number of predicted pairwise functional associations is 39,730 for all genomes. Component pairs were identified by virtue of their similarity to 2,365 multidomain composite proteins. We also show for the first time that gene fusion is a complex evolutionary process with a number of contributory factors, including paralogy, genome size and phylogenetic distance. On average, 9% of genes in a given genome appear to code for single-domain, component proteins predicted to be functionally associated. These proteins are detected by an additional 4% of genes that code for fused, composite proteins. These results provide an exhaustive set of functionally associated genes and also delineate the power of fusion analysis for the prediction of protein interactions.
Abstract 1238: Apigenin suppresses inhibitor of apoptosis family protein expression and disrupts Ku70-bax interaction in prostate cancer cells in culture and <i>in vivo</i>
Authors: Sanjeev Shukla, Pingfu Fu, Sanjay Gupta
Journal: Cancer Research (2014)

Abstract Apigenin (4′,5,7-trihydroxyflavone), an anticancer agent, selective toxic to cancer cells induces cell cycle arrest and apoptosis. The molecular mechanism(s) of this effect has not been fully elucidated. It is well known that dysfunction of the apoptotic pathway confers apoptosis resistance through inhibitor of apoptosis family protein (IAP) and deregulation of Bax/Bcl2 pathway in prostate cancer cells. In the present study we provide evidence for the mechanisms of apoptosis induction by apigenin. Treatment of androgen-refractory human prostate cancer PC-3 and DU145 cells with 5-40µM apigenin resulted in dose-dependent suppression of XIAP, c-IAP1, c-IAP2 and survivin protein levels. Apigenin treatment (20µM) resulted in significant decrease in cell viability and apoptosis induction with the release of cytochrome C in time-dependent manner. These effects of apigenin were accompanied by decrease in Bcl-xL and Bcl-2 and increase in the active form of Bax protein. The apigenin-mediated increase in Bax was due to dissociation of Bax from Ku70 which is essential for apoptotic activity of Bax. Apigenin treatment resulted in the inhibition of class I histone deacetylases and HDAC1 protein expression, thereby increasing the acetylation of Ku70 and the dissociation of Bax resulting in apoptosis of cancer cells. Furthermore, apigenin significantly reduced HDAC1 occupancy at the XIAP promoter, suggesting that histone deacetylation might be critical for XIAP downregulation. In in vivo studies, per-oral intake of apigenin at doses of 20 and 50µg/mouse/day, two weeks after PC-3 cell implantation, continued for 8 weeks resulted in significant inhibition of tumor volume by 32.5% and 51.3% (P&amp;lt;0.001) and decrease in wet weight tumor by 33.3% and 55.1% (P&amp;lt;0.001), respectively. The animals did not exhibit any signs of toxicity or reduced food consumption. Compared to vehicle-treated controls, induction of apoptosis was significantly increased in tumor xenografts in apigenin fed mice (P&amp;lt;0.001) along with marked reduction in the protein expression of XIAP and survivin in PC-3 tumor xenografts. A dose-dependent decrease in HDAC1 expression, increase in Bax and PARP cleavage was observed in apigenin-treated mice. Taken together, these results suggest that apigenin targets IAP proteins and Ku70-Bax interaction in the induction of apoptosis in prostate cancer cells and in athymic nude mouse xenograft model endorsing its in vivo efficacy. Citation Format: Sanjeev Shukla, Pingfu Fu, Sanjay Gupta. Apigenin suppresses inhibitor of apoptosis family protein expression and disrupts Ku70-bax interaction in prostate cancer cells in culture and in vivo. [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 1238. doi:10.1158/1538-7445.AM2014-1238
A Specific Competitive Antagonist of the Vascular Action of Angiotensin II
Authors: Donald T. Pals, Frederick D. Masucci, Frank Sipos, George S. Denning
Journal: Circulation Research (1971)

The effect of 1-Asn-8-Ala-angiotensin II (Asn-Arg-Val-Tyr-Val-His-Pro-Ala) on the vascular action of angiotensin II was studied with rabbit aortic strips, pithed rats, and conscious rats. Dose-response (contraction) curves for angiotensin II on rabbit aortic strips shifted progressively to the right with increasing bath concentrations of 1-Asn-8-Ala-angiotensin II. The pA 2 value (an indication of the relative affinity of a competitive antagonist for an agonist's receptor site) was 6.84 ± 0.03. Dose-response curves for norepinephtine, serotonin, and histamine were relatively unaffected. No pA 3 values could be obtained with these agonists in the concentration range tested. Partial dose-response (pressor) curves for angiotensin II in pithed rats shifted to the right during infusions of 1-Asn-8-Ala-angiotensin II at 20 and 60 µg/kg min -1 Partial dose-response curves for vasopressin, phenylephririe, and tyramine were unaffected. Infusions of 1-Asn-8-Ala-angiotensin II counteracted the pressor effect of angiotensin II infusions in pithed and conscious rats. Infusions of 1-Asn-8-Ala-angiotensin II (200 µ/ kg min -1 ) effective in reducing the blood pressure of conscious angiotensin II-infused rats caused only small pressor effects in conscious normotensive rats but reduced the blood pressure in 75% of the conscious rats with acute unilateral renal hypertension. The data presented are consistent with the conclusion that 1-Asn-8-Ala-angiotensin II is a specific competitive antagonist of the vascular action of angiotensin II both in vitro and in vivo.
Circulating Leptin in Patients with Chronic Obstructive Pulmonary Disease
Authors: NORIAKI TAKABATAKE, HIDENORI NAKAMURA, SHUICHI ABE, TOSHIHIKO HINO, HIROSHI SAITO, HIDEKI YUKI, SHUICHI KATO, HITONOBU TOMOIKE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Unexplained weight loss is common in patients with chronic obstructive pulmonary disease (COPD). Since leptin, an obesity gene product, is known to play important roles in the control of body weight and energy expenditure, we investigated serum leptin levels, along with circulating tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptor (sTNF-R55 and -R75) levels, in 31 patients with COPD and 15 age-matched healthy controls. The body mass index (BMI) and percent body fat (%fat) were significantly lower in the COPD patients than in the healthy controls (BMI = 18.1 +/- 2.7 kg/m2 versus 22.8 +/- 2.2 kg/m2 [mean +/- SD]; p < 0.0001; %fat = 16.9 +/- 5.8% versus 24.3 +/- 4.9%; p < 0.001). Serum leptin levels were significantly lower in the COPD patients than in the healthy controls (1.14 +/- 1.17 ng/ml versus 2.47 +/- 2.01 ng/ml; p < 0.05). In contrast, serum TNF-alpha levels (6.59 +/- 1.92 pg/ml versus 5.41 +/- 1.60 pg/ml; p < 0.05), plasma sTNF-R55 (1.16 +/- 0.47 ng/ml versus 0.67 +/- 0.13 ng/ml; p < 0.0001) and sTNF-R75 (3.65 +/- 1.29 ng/ml versus 2.25 +/- 0.43 ng/ml; p < 0.0001) levels were significantly higher in the COPD patients than in the healthy controls. Importantly, circulating leptin levels (log transformed) did correlate well with BMI and %fat, but not with TNF-alpha or with sTNF-R levels in the COPD patients. These data suggest that circulating leptin is independent of the TNF-alpha system and is regulated physiologically even in the presence of cachexia in patients with COPD.
Management of refractory early-stage cutaneous T-cell lymphoma (mycosis fungoides) with a combination of oral bexarotene and psoralen plus ultraviolet bath therapy
Authors: Margit A Huber, Karin Kunzi-Rapp, Gyde Staib, Karin Scharffetter-Kochanek
Journal: Journal of the American Academy of Dermatology (2004)
Activation of the p53 pathway by the MDM2 inhibitor nutlin-3a overcomes BCL2 overexpression in a preclinical model of diffuse large B-cell lymphoma associated with t(14;18)(q32;q21)
Authors: E Drakos, R R Singh, G Z Rassidakis, E Schlette, J Li, F X Claret, R J Ford, F Vega, L J Medeiros
Journal: Leukemia (2011)

p53 is frequently wild type (wt) in diffuse large B-cell lymphoma (DLBCL) associated with t(14;18)(q32;q21) that overexpresses BCL2. Nutlin-3a is a small molecule that activates the p53 pathway by disrupting p53-MDM2 interaction. We show that nutlin-3a activates p53 in DLBCL cells associated with t(14;18)(q32;q21), BCL2 overexpression and wt p53, resulting in cell cycle arrest and apoptosis. Nutlin-3a treatment had similar effects on DLBCL cells of activated B-cell phenotype with wt p53. Cell cycle arrest was associated with upregulation of p21. Nutlin-3a-induced apoptosis was accompanied by BAX and PUMA upregulation, BCL-XL downregulation, serine-70 dephosphorylation of BCL2, direct binding of BCL2 by p53, caspase-9 upregulation and caspase-3 cleavage. Cell death was reduced when p53-dependent transactivation activity was inhibited by pifithrin-α (PFT-α), or PFT-μ inhibited direct p53 targeting of mitochondria. Nutlin-3a sensitized activation of the intrinsic apoptotic pathway by BCL2 inhibitors in t(14;18)-positive DLBCL cells with wt p53, and enhanced doxorubicin cytotoxicity against t(14;18)-positive DLBCL cells with wt or mutant p53, the latter in part via p73 upregulation. Nutlin-3a treatment in a xenograft animal lymphoma model inhibited growth of t(14;18)-positive DLBCL tumors, associated with increased apoptosis and decreased proliferation. These data suggest that disruption of the p53-MDM2 interaction by nutlin-3a offers a novel therapeutic approach for DLBCL associated with t(14;18)(q32;q21).
Screening for Breast Cancer
Authors: Lockhart B. McGuire
Journal: Annals of Internal Medicine (1989)

Letters and Corrections15 November 1989Screening for Breast CancerLockhart B. McGuire, MDLockhart B. McGuire, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-111-10-858_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: During the processing of Dr. Eddy's manuscript for publication (1), the American College of Physicians approved new recommendations on screening for breast cancer:1. Screening with breast physical examination is recommended annually for asymptomatic women age 40 and older.2. Screening with breast physical examination and mammography is recommended annually for asymptomatic women age 50 and older.3. Screening with breast physical examination and mammography is recommended annually for women at any age who have a personal history of breast cancer.4. Screening with breast physical examination and mammography is recommended annually for women age 40 and...Reference1. Eddy D. Screening for Breast Cancer. Ann Intern Med. 1989;111:389-99. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Clinical Efficacy Assessment American College of Physicians PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByOversupply of Screening Mammography Units: Why Should Internists Care?Alvin I. Mushlin, MD, ScMIs the Supply of Mammography Machines Outstripping Need and Demand? An Economic AnalysisMartin L. Brown, PhD, Larry G. Kessler, ScD, Fred G. Rueter, DSc 15 November 1989Volume 111, Issue 10Page: 858-859KeywordsBreast cancerCancer screeningMammography Issue Published: 15 November 1989 PDF DownloadLoading ...
Prospective Study of the Frequency and Size Distribution of Polyps Missed by Colonoscopy
Authors: L. J. Hixson, M. B. Fennerty, R. E. Sampliner, D. McGee, H. Garewal
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Prospective Study of the Frequency and Size Distribution of Polyps Missed by Colonoscopy Get access L. J. Hixson, L. J. Hixson Search for other works by this author on: Oxford Academic PubMed Google Scholar M. B. Fennerty, M. B. Fennerty Search for other works by this author on: Oxford Academic PubMed Google Scholar R. E. Sampliner, R. E. Sampliner Search for other works by this author on: Oxford Academic PubMed Google Scholar D. McGee, D. McGee Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Garewal H. Garewal Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 22, 21 November 1990, Pages 1769–1772, https://doi.org/10.1093/jnci/82.22.1769 Published: 21 November 1990 Article history Revision received: 13 April 1990 Received: 20 April 1990 Accepted: 30 August 1990 Published: 21 November 1990
Brain Tumor Mortality Risk Among Men With Electrical and Electronics Jobs: A Case-Control Study
Authors: T L Thomas, P D Stolley, A Stemhagen, E T Fontham, M L Bleecker, P A Stewart, R N Hoover
Journal: JNCI Journal of the National Cancer Institute (1987)

Brain tumor risk associated with electrical and electronics jobs and with occupational exposure to microwave and radiofrequency (MW/RF) electromagnetic radiation was evaluated with the use of data from a death certificate-based case-control study of brain tumors and occupational risk factors in northern New Jersey, Philadelphia, PA, and southern Louisiana. Next-of-kin of 435 white men who died of a primary brain tumor and of 386 controls who died from other causes were interviewed to obtain information on lifetime occupational history and other factors that might be related to excess brain tumor risk. The relative risk (RR) for all brain tumors was elevated among men exposed to MW/RF radiation [RR = 1.6; 95% confidence interval (Cl) = 1.0, 2.4] and was significantly elevated among men exposed for 20 or more years. All of the excess risk for MW/RF radiation-exposed subjects was derived from jobs that involved the design, manufacture, repair, or installation of electrical or electronic equipment (RR = 2.3; 95% Cl = 1.3, 4.2), while risk of brain tumors among MW/RF radiation-exposed subjects who never worked in electrical or electronics jobs was not elevated (RR = 1.0; 95% Cl = 0.5, 1.9). Furthermore, risk was elevated for electronics workers who were considered to have no exposure to MW/RF radiation. Among electrical and electronics workers, risk was highest for engineers, teachers, technicians, repairers, and assemblers combined (RR = 3.9; 95% Cl = 1.6, 9.9) and was limited to excess risk from astrocytic tumors (RR = 4.6; 95% Cl = 1.9, 12.2). Risk of astrocytic tumors among these electronics manufacture and repair workers increased with duration of exposure to tenfold among those employed for 20 or more years. Among electricians and power and telephone linemen combined (electrical tradesmen), the RR for astrocytic tumors was slightly elevated, but not statistically significant (RR = 1.8), and showed no consistent evidence of a duration-response relationship. Electrical tradesmen are exposed to extremely low frequency electromagnetic radiation, while men in some jobs associated with electronics manufacture and repair are exposed to electromagnetic radiation in the very high frequency and ultra-high frequency ranges and also may be exposed to soldering fumes, solvents, and a variety of other chemicals.
Frequency of Severe Hypoglycemia Requiring Emergency Treatment in Type 1 and Type 2 Diabetes
Authors: Graham P. Leese, Jixian Wang, Janice Broomhall, Paul Kelly, Andrew Marsden, William Morrison, Brian M. Frier, Andrew D. Morris
Journal: Diabetes Care (2003)

OBJECTIVE—To determine the incidence, predisposing factors, and costs of emergency treatment of severe hypoglycemia in people with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS—Over a 12-month period, routinely collected datasets were analyzed in a population of 367,051 people, including 8,655 people with diabetes, to measure the incidence of severe hypoglycemia that required emergency assistance from Ninewells Hospital and Medical School (NHS) personnel including those in primary care, ambulance services, hospital accident and emergency departments, and inpatient care. Associated costs with these episodes were calculated. RESULTS—A total of 244 episodes of severe hypoglycemia were recorded in 160 patients, comprising 69 (7.1%) people with type 1 diabetes, 66 (7.3%) with type 2 diabetes treated with insulin, and 23 (0.8%) with type 2 diabetes treated with sulfonylurea tablets. Incidence rates were 11.5 and 11.8 events per 100 patient-years for type 1 and type 2 patients treated with insulin, respectively. Age, duration, and socioeconomic status were identified as risk factors for severe hypoglycemia. One in three cases were treated solely by the ambulance service with no other contact from health care professionals. The total estimated cost of emergency treatment of severe hypoglycemia was ≤£92,078 in one year. CONCLUSIONS—Hypoglycemia requiring emergency assistance from health service personnel is as common in people with type 2 diabetes treated with insulin as in people with type 1 diabetes. It is associated with considerable NHS resource use that has a significant economic and personal cost.
Immediate hemodynamic effects of a dopamine-receptor agonist (fenoldopam) in patients with essential hypertension.
Authors: H O Ventura, F H Messerli, E D Frohlich, I Kobrin, W Oigman, F G Dunn, R M Carey
Journal: Circulation (1984)

Systemic, splanchnic, and renal hemodynamics, intravascular volume, and reflexive and endocrine changes were measured before and after a single dose of fenoldopam, a novel antihypertensive agent that acts through stimulation of specific dopamine receptors. A 13% reduction in mean arterial pressure was mediated by a fall in total peripheral resistance association with an increase in cardiac index, heart rate, stroke volume, left ventricular ejection rate, and circumferential fiber shortening. Renal blood flow increased, thereby reducing the renal vascular resistance by more than 40%. In contrast, splanchnic hemodynamics failed to change. Likewise, there were no changes in intravascular volume, plasma renin activity, or norepinephrine, serum aldosterone, or prolactin levels.