tbuckley/cabot-search huggingface dataset:
Oncolytic Virus and Anti–4-1BB Combination Therapy Elicits Strong Antitumor Immunity against Established Cancer
Authors: Liza B. John, Linda J. Howland, Jacqueline K. Flynn, Alison C. West, Christel Devaud, Connie P. Duong, Trina J. Stewart, Jenny A. Westwood, Z. Sheng Guo, David L. Bartlett, Mark J. Smyth, Michael H. Kershaw, Phillip K. Darcy
Journal: Cancer Research (2012)

Oncolytic virotherapy using vaccinia virus (Vv) has shown some encouraging antitumor responses in mouse models and patients, but the breadth of efficacy in clinical trials has been somewhat limited. Given that antitumor effects have correlated with increased host immune responses, we hypothesized that improved therapeutic outcomes may be achieved by using oncolytic virus (OV) in combination with a potent immune agonist reagent. In this study, we carried out a preclinical evaluation of a genetically engineered strain of oncolytic vaccinia virus (Vvdd) for its capacity to induce antitumor responses when combined with an agonist antibody (Ab) specific for the costimulatory molecule 4-1BB (CD137). In immune-competent syngeneic mouse models of cancer, this combination therapy significantly reduced the growth of established subcutaneous tumors relative to either treatment alone. Importantly, the development of pulmonary metastatic lesions was also reduced. Tumor growth inhibition was associated with increased numbers of CD11b(+) and CD11c(+) myeloid cells in the tumor draining lymph nodes, greater infiltration of CD8(+) effector T and natural killer (NK) cells, and a more sustained presence of neutrophils at the tumor site. Depletion of T or NK cells or neutrophils reduced efficacy, confirming their contribution to an effective therapeutic response. We further extended this conclusion through results from IFNγ-deficient mice. In summary, our findings offered a proof-of-concept for a combinatorial approach to enhance the antitumor efficacy of an OV, suggesting a strategy to improve their use as an immunotherapeutic treatment for cancer.
Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia
Authors: John G. Gribben, David Zahrieh, Katherine Stephans, Lini Bartlett-Pandite, Edwin P. Alyea, David C. Fisher, Arnold S. Freedman, Peter Mauch, Robert Schlossman, Lecia V. Sequist, Robert J. Soiffer, Blossom Marshall, Donna Neuberg, Jerome Ritz, Lee M. Nadler
Journal: Blood (2005)
MiR-185 Targets the DNA Methyltransferases 1 and Regulates Global DNA Methylation in human glioma
Authors: Zuping Zhang, Hailin Tang, Zeyou Wang, Baoxin Zhang, Wei Liu, Hongmei Lu, Lan Xiao, Xiaoping Liu, Rong Wang, Xiaoling Li, Minghua Wu, Guiyuan Li
Journal: Molecular Cancer (2011)

Abstract Background Perturbation of DNA methylation is frequent in cancers and has emerged as an important mechanism involved in tumorigenesis. To determine how DNA methylation is modified in the genome of primary glioma, we used Methyl-DNA immunoprecipitation (MeDIP) and Nimblegen CpG promoter microarrays to identify differentially DNA methylation sequences between primary glioma and normal brain tissue samples. Methods MeDIP-chip technology was used to investigate the whole-genome differential methylation patterns in glioma and normal brain tissues. Subsequently, the promoter methylation status of eight candidate genes was validated in 40 glioma samples and 4 cell lines by Sequenom's MassARRAY system. Then, the epigenetically regulated expression of these genes and the potential mechanisms were examined by chromatin immunoprecipitation and quantitative real-time PCR. Results A total of 524 hypermethylated and 104 hypomethylated regions were identified in glioma. Among them, 216 hypermethylated and 60 hypomethylated regions were mapped to the promoters of known genes related to a variety of important cellular processes. Eight promoter-hypermethylated genes (ANKDD1A, GAD1, HIST1H3E, PCDHA8, PCDHA13, PHOX2B, SIX3, and SST) were confirmed in primary glioma and cell lines. Aberrant promoter methylation and changed histone modifications were associated with their reduced expression in glioma. In addition, we found loss of heterozygosity (LOH) at the miR-185 locus located in the 22q11.2 in glioma and induction of miR-185 over-expression reduced global DNA methylation and induced the expression of the promoter-hypermethylated genes in glioma cells by directly targeting the DNA methyltransferases 1. Conclusion These comprehensive data may provide new insights into the epigenetic pathogenesis of human gliomas.
JUNIOR GYMNASTIC: INCIDENCE AND INJURY PROFILE
Authors: C Bolling, M Leite, D Reis
Journal: British Journal of Sports Medicine (2014)

Background Junior is the transition to senior category reflected by training load increase and element's difficulty. The higher physical demands modify the injury profile. Objective The aim of this study was to describe junior gymnasts' injury profile in the seasons 2011–2012 in a sports club. Design This is an observational study, transversal, about the injuries in 2011–2012 season. Setting This study was developed with national and international level gymnasts, in a Brazilian sports club. Participants The sample was composed of 6 junior male gymnasts, mean age of 15.8 years, exposed to the same training load. Risk factor assessment The physiotherapist reported all injuries during the season. The injury definition was time loss and/or any symptom that result in a training modification. Main outcome measurements The injuries were reported related to type (acute/chronic), location, affected structure and injury mechanism. Results The injury incidence was 37 in 2 years, with an annual average of 3.08 injuries/athlete. According to the injury type, acute lesions were 46% and 54% chronic. The most affected location was the upper limbs (56%), highlighting the shoulder (29%). Shoulder injuries were 18% in 2011 and 21% in 2012, and elbow injuries indicate a decrease from 13% to 4%. In lower limbs (24%), ankle was the more affected joint (10%). Tendon was most common injured structure (32%) followed by muscular (18%). The most frequent mechanism was tendinopathy, especially rotator cuff tendons. Conclusion Gymnastic's injury profile highlights the demand on upper limbs. The higher shoulder injuries incidence are associated to greater difficulty in pommel horse, rings, parallel bars, and horizontal bar. Lower elbow injuries reflect a technique improvement. Ankle injuries incidence are associated to repeated jumps and landings. Junior injury profile is important to guide the prevention strategies for healthy senior athletes.
Effects of Verapamil on the Acute Toxicity of Doxorubicin In Vivo
Authors: R. Sridhar, C. Dwivedi, J. Anderson, P. B. Baker, H. M. Sharma, P. Desai, F. N. Engineer
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Effects of Verapamil on the Acute Toxicity of Doxorubicin In Vivo Get access Rajagopalan Sridhar, Rajagopalan Sridhar Department of Radiation Therapy and Cancer Center, Howard University HospitalWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Chandradhar Dwivedi, Chandradhar Dwivedi College of Pharmacy, South Dakota State UniversityBrookings Search for other works by this author on: Oxford Academic PubMed Google Scholar Jayna Anderson, Jayna Anderson College of Pharmacy, South Dakota State UniversityBrookings Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter B. Baker, Peter B. Baker College of Medicine, The Ohio State UniversityColumbus Search for other works by this author on: Oxford Academic PubMed Google Scholar Hari M. Sharma, Hari M. Sharma College of Medicine, The Ohio State UniversityColumbus Search for other works by this author on: Oxford Academic PubMed Google Scholar Pankaj Desai, Pankaj Desai School of Pharmacy, Northeast Louisiana UniversityMonroe Search for other works by this author on: Oxford Academic PubMed Google Scholar Ferzaan N. Engineer Ferzaan N. Engineer * College of Pharmacy, South Dakota State University, and College of Pharmacy, University of South CarolinaColumbia * Ferzaan N. Engineer, Ph.D., South Dakota State University, College of Pharmacy, Box 2202 C, Brookings, SD 57007. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 21, 4 November 1992, Pages 1653–1660, https://doi.org/10.1093/jnci/84.21.1653 Published: 04 November 1992 Article history Received: 23 January 1992 Revision received: 28 July 1992 Accepted: 13 August 1992 Published: 04 November 1992
Anticancer Chemosensitization and Radiosensitization by the Novel Poly(ADP-ribose) Polymerase-1 Inhibitor AG14361
Authors: C. R. Calabrese, R. Almassy, S. Barton, M. A. Batey, A. H. Calvert, S. Canan-Koch, B. W. Durkacz, Z. Hostomsky, R. A. Kumpf, S. Kyle, J. Li, K. Maegley, D. R. Newell, E. Notarianni, I. J. Stratford, D. Skalitzky, H. D. Thomas, L.-Z. Wang, S. E. Webber, K. J. Williams, N. J. Curtin
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Poly(ADP-ribose) polymerase-1 (PARP-1) facilitates the repair of DNA strand breaks. Inhibiting PARP-1 increases the cytotoxicity of DNA-damaging chemotherapy and radiation therapy in vitro. Because classical PARP-1 inhibitors have limited clinical utility, we investigated whether AG14361, a novel potent PARP-1 inhibitor (inhibition constant <5 nM), enhances the effects of chemotherapy and radiation therapy in human cancer cell cultures and xenografts. Methods: The effect of AG14361 on the antitumor activity of the DNA alkylating agent temozolomide, topoisomerase I poisons topotecan or irinotecan, or x-irradiation or γ-radiation was investigated in human cancer cell lines A549, LoVo, and SW620 by proliferation and survival assays and in xenografts in mice by tumor volume determination. The specificity of AG14361 for PARP-1 was investigated by microarray analysis and by antiproliferation and acute toxicity assays in PARP-1−/− and PARP-1+/+ cells and mice. After intraperitoneal administration, the concentration of AG14361 was determined in mouse plasma and tissues, and its effect on PARP-1 activity was determined in tumor homogenates. All statistical tests were two-sided. Results: AG14361 at 0.4 μM did not affect cancer cell gene expression or growth, but it did increase the antiproliferative activity of temozolomide (e.g., in LoVo cells by 5.5-fold, 95% confidence interval [CI] = 4.9-fold to 5.9-fold; P = .004) and topotecan (e.g., in LoVo cells by 1.6-fold, 95% CI = 1.3-fold to 1.9-fold; P = .002) and inhibited recovery from potentially lethal γ-radiation damage in LoVo cells by 73% (95% CI = 48% to 98%). In vivo, nontoxic doses of AG14361 increased the delay of LoVo xenograft growth induced by irinotecan, x-irradiation, or temozolomide by two- to threefold. The combination of AG14361 and temozolomide caused complete regression of SW620 xenograft tumors. AG14361 was retained in xenografts in which PARP-1 activity was inhibited by more than 75% for at least 4 hours. Conclusion: AG14361 is, to our knowledge, the first high-potency PARP-1 inhibitor with the specificity and in vivo activity to enhance chemotherapy and radiation therapy of human cancer.
Physiological Coupling of Donor and Host Cardiomyocytes After Cellular Transplantation
Authors: Michael Rubart, Kishore B.S. Pasumarthi, Hidehiro Nakajima, Mark H. Soonpaa, Hisako O. Nakajima, Loren J. Field
Journal: Circulation Research (2003)

Cellular transplantation has emerged as a potential approach to treat diseased hearts. Although cell transplantation can affect global heart function, it is not known if this results directly via functional integration of donor myocytes or indirectly via enhanced revascularization and/or altered postinjury remodeling. To determine the degree to which donor cardiomyocytes are able to functionally integrate with the host myocardium, fetal transgenic cardiomyocytes expressing enhanced green fluorescent protein were transplanted into the hearts of nontransgenic adult mice. Two-photon molecular excitation laser scanning microscopy was then used to simultaneously image cellular calcium transients in donor and host cells within the intact recipient hearts. Calcium transients in the donor cardiomyocytes were synchronous with and had kinetics indistinguishable from those of neighboring host cardiomyocytes. These results strongly suggest that donor cardiomyocytes functionally couple with host cardiomyocytes and support the notion that transplanted cardiomyocytes can form a functional syncytium with the host myocardium.
"Grass roots" Sports Medicine
Authors: Kenneth Jones
Journal: British Journal of Sports Medicine (1976)

As one of the members who is not a doctor there is a fundamental point about the Association that I would like to raise and as the AGM is always during the working week I am unable to attend and raise the matter there.The Journal of Sports Medicine is an excellent means of publishing erudite papers on our subject, some of which as a lay person I can wholly or partly follow.When I realise that a paper is fundamental to my sports coaching I obtain the help of a doctor pal of mine.Is there not a great risk that the material that is published after much effort by the contributors is liable never to reach the coaches and benefit British Sportsmen and women?Is there not a case for a synopsis of the most important articles to be published in lay language at regular intervals, possibly with the help of the Sports Council?The isolation of the B.A.S.M. from grassroots level sport in general seems regrettable.We in coaching need scientific medical advice as there are too many witchdoctors about on the fringes of sport.Can the B.A.S.M.
Estimation of Coronary Blood Flow by Washout of Diffusible Indicators
Authors: JAMES B. BASSINGTHWAIGHTE, TORE STRONDELL, DAVID E. DONALD
Journal: Circulation Research (1968)

In 13 canine hearts, 158 disappearance curves for 133 Xe and antipyrine-1 125 I, given by intra-arterial slug injection, were recorded at a wide range of perfusion rates. Flow rates (ml/100 g/min) calculated from these curves by a variety of methods were compared with measured flow rates (F a ) per weight of perfused tissue. Perfusion of isolated, supported hearts and of anterior descending coronary arteries in open-chest dogs provided similar data. The semilogarithmic slope of curves from apex or whole heart decreased with time, particularly at high flow rates. There was a small, consistent difference in shape between antipyrine and xenon curves, suggesting that radioactivity in fat contributed somewhat to this tailing. Estimation of flow rate from the steepest semilog slope yielded an average value of 1.1 F a for all rates; estimation from slope at 30% of peak radioactivity gave 0.9F a . The curves were closely described by a two-exponential equation which gave flow estimates of 0.95F a when collimation limited the observations to the heart apex, and lower values when the whole heart was observed. Peak height/area methods gave values of approximately 0.75F a in spite of various compensations for the impossibility of recording the curve until radioactivity = 0.
Standard versus High-Dose CVVHDF for ICU-Related Acute Renal Failure
Authors: Ashita J. Tolwani, Ruth C. Campbell, Brenda S. Stofan, K. Robin Lai, Robert A. Oster, Keith M. Wille
Journal: Journal of the American Society of Nephrology (2008)

The effect of dosage of continuous venovenous hemodiafiltration (CVVHDF) on survival in patients with acute renal failure (ARF) is unknown. In this study, 200 critically ill patients with ARF were randomly assigned to receive CVVHDF with prefilter replacement fluid at an effluent rate of either 35 ml/kg per h (high dosage) or 20 ml/kg per h (standard dosage). The primary study outcome, survival to the earlier of either intensive care unit discharge or 30 d, was 49% in the high-dosage arm and 56% in the standard-dosage arm (odds ratio 0.75; 95% confidence interval 0.43 to 1.32; P = 0.32). Among hospital survivors, 69% of those in the high-dosage arm recovered renal function compared with 80% of those in the standard-dosage arm (P = 0.29); therefore, a difference in patient survival or renal recovery was not detected between patients receiving high-dosage or standard-dosage CVVHDF.
ON THE EXISTENCE OF A FACTOR INCREASING TISSUE PERMEABILITY IN ORGANS OTHER THAN TESTICLE
Authors: Albert Claude, F. Duran-Reynals
Journal: The Journal of Experimental Medicine (1934)

Many of the organs from animals of both sexes, including the ovary, have been found to contain in various proportion a factor or factors increasing tissue permeability. The potency exhibited by such active extracts was always less than that of extracts from testicle. Blood serum was found to be devoid of any spreading property.
Pneumococcal septic arthritis after splenectomy in Felty's syndrome.
Authors: M Brzeski, L Smart, D Baird, R Jackson, R Sturrock
Journal: Annals of the Rheumatic Diseases (1991)

A patient with Felty's syndrome who developed bilateral knee septic arthritis and septicaemia due to Streptococcus pneumoniae is described. She had had a previous splenectomy for symptomatic thrombocytopenia, having received pneumococcal vaccine before the operation. Measurement of antibody to the 23 vaccine serotypes showed protective concentrations before infection to just two. The infecting serotype was not represented in the vaccine, but a vigorous antibody response to this serotype occurred. The patient also developed glomerulonephritis due to immune complex deposition.
The Hypereosinophilic Syndrome and the Biology of Cancer
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (2003)

Patients with sustained high-grade eosinophilia without an evident cause usually receive the diagnosis of hypereosinophilic syndrome, a high-sounding term that only masks our ignorance. Apart from the consistent presence of hypereosinophilia, the clinical picture of the hypereosinophilic syndrome varies. In some cases, the toxic contents of tissue-invasive eosinophils (see electron micrograph) cause heart failure, pulmonary lesions, and harm to other organs. In other cases, urticaria and itchy nodules in the skin dominate the clinical picture. The hypereosinophilic syndrome is a rare disorder, yet as Cools et al. tell us in this issue of the Journal (pages 1201–1214), it carries a message . . .
The Use of U-500 in Patients With Extreme Insulin Resistance
Authors: Elaine Cochran, Carla Musso, Phillip Gorden
Journal: Diabetes Care (2005)

The Diabetes Control and Complication Trial (1) and the U.K. Prospective Diabetes Study (2,3), as well as other smaller trials (4), have established the benefit of treating type 1 and type 2 diabetes to levels of glycemia as close to normal as possible. These studies have formed the basis for the therapeutic targets set forth in the most recent American Diabetes Association (ADA) guidelines (5).

There is a subset of patients classified by the ADA as having “other specific types of diabetes”; this group represents a major therapeutic challenge in terms of achieving glycemic goals (6). These patients have more extreme forms of insulin resistance than typical type 2 diabetic patients, and many manifest various syndromic classifications (Fig. 1). Furthermore, for the purpose of this discussion, we are including patients with extreme endogenous hyperinsulinemia or hyperglycemic patients who require doses of exogenous insulin of >200 units/day or in pediatric patients doses >3 units · kg−1 · day−1. This includes a subset of obese type 2 diabetic patients. Extreme forms of insulin resistance may also occur as a temporary state with pregnancy, with endocrinopathies and under various other stress conditions such as an infection, or with exogenous steroid use (Fig. 2). The practical issue of insulin management is essentially the same for all of these various patient categories.

While we have defined the more extreme forms of insulin resistance whose requirements are >200 units insulin/day, this is clearly an arbitrary definition. Currently glycemic goals for both type 2 diabetes and “the other specific types of diabetes” are generally not being met. Part of the reason for this is that patients clearly are on insufficient doses of insulin. For instance, the median dose of insulin in a group of Pima Indians under treatment is 70 units/day …
Synergistic inhibition of hepatocellular carcinoma growth by cotargeting chromatin modifying enzymes and poly (ADP-ribose) polymerases
Authors: Jun-Xiang Zhang, Da-Qiang Li, Aiwu Ruth He, Mona Motwani, Vasilis Vasiliou, Jeyanthy Eswaran, Lopa Mishra, Rakesh Kumar
Journal: Hepatology (2011)

Hepatocellular carcinoma (HCC) is a particularly lethal form of cancer, yet effective therapeutic options for advanced HCC are limited. The poly(ADP-ribose) polymerases (PARPs) and histone deacetylases (HDACs) are emerging to be among the most promising targets in cancer therapy, and sensitivity to PARP inhibition depends on homologous recombination (HR) deficiency and inhibition of HDAC activity blocks the HR pathway. Here, we tested the hypothesis that cotargeting both enzymatic activities could synergistically inhibit HCC growth and defined the molecular determinants of sensitivity to both enzyme inhibitors. We discovered that HCC cells have differential sensitivity to the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and PARP inhibitor olaparib, and identified one pair of cell lines, termed SNU-398 and SNU-449, with sensitive versus resistant phenotype to both enzyme inhibitors, respectively. Coadministration of SAHA and olaparib synergistically inhibited the growth of SNU-398 but not SNU-449 cells, which was associated with increased apoptosis and accumulated unrepaired DNA damage. Multiple lines of evidence demonstrate that the hepatic fibrosis/hepatic stellate cell activation may be an important genetic determinant of cellular sensitivity to both enzymatic inhibitors, and coordinate activation or inactivation of the aryl hydrocarbon receptor (AhR) and cyclic adenosine monophosphate (cAMP)-mediated signaling pathways are involved in cell response to SAHA and olaparib treatment. Conclusion: These findings suggest that combination therapy with both enzyme inhibitors may be a strategy for therapy of sensitive HCC cells, and identification of these novel molecular determinants may eventually guide the optimal use of PARP and HDAC inhibitors in the clinic.
V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations
Authors: Anna Villa, Cristina Sobacchi, Luigi D. Notarangelo, Fabio Bozzi, Mario Abinun, Tore G. Abrahamsen, Peter D. Arkwright, Michal Baniyash, Edward G. Brooks, Mary Ellen Conley, Patricia Cortes, Marzia Duse, Anders Fasth, Alexandra M. Filipovich, Anthony J. Infante, Alison Jones, Evelina Mazzolari, Susanna M. Muller, Srdjan Pasic, Gideon Rechavi, Maria Grazia Sacco, Sandro Santagata, Marlis L. Schroeder, Reinhard Seger, Dario Strina, Alberto Ugazio, Jouni Väliaho, Mauno Vihinen, Larry B. Vogler, Hans Ochs, Paolo Vezzoni, Wilhelm Friedrich, Klaus Schwarz
Journal: Blood (2001)