tbuckley/cabot-search huggingface dataset:
Factors Affecting the Polynuclear Hydrocarbon Level in Rat Mammary Glands
Authors: Fred G. Bock, Thomas L. Dao
Journal: Cancer Research (1961)

The levels of 3-methylcholanthrene (MCA) in rat mammary and fat tissues after feedings were measured. After a single feeding, the amounts which were found in the mammary tissue and fat were proportional to the amount fed. In contrast, multiple feedings did not result in higher tissue levels. MCA levels after feeding were lower in pregnant rats than in normal rats, whereas those of either castrated or hypophysectomized rats were higher. There was little difference between results found for normal males and normal females.

The amount of hydrocarbon found in the mammary gland and fat after feeding depended upon the nature of the hydrocarbon fed. Very little, if any, phenanthrene was found in these tissues 24 hours after a phenanthrene meal. Benzo[ a ]pyrene was localized in the mammary tissue and fat better than was MCA, whereas 7,12-dimethylbenz[ a ]anthracene behaved similarly to MCA.

The data suggest that hydrocarbons reached the mammary glandular cells because of their intimate association with the mammary fat pads. This mechanism appears to account for much of the sensitivity of mammary glands to oral feeding of polycyclic hydrocarbons.
Abstract P4-11-09: Comparison of immunohistochemical residual risk panels to predict risk in early breast cancers treated with endocrine therapy
Authors: Jacqueline Stephen, Gordon Murray, David Cameron, Jeremy Thomas, Ian Kunkler, Wilma Jack, Gill Kerr, Tammy Piper, Cassandra Brookes, Daniel Rea, Cornelis van de Velde, Annette Hasenburg, Christos Markopoulos, Luc Dirix, Caroline Seynaeve, John Bartlett
Journal: Cancer Research (2015)

Abstract Background: We compare two residual risk models combining immunohistochemical (IHC) biomarkers, IHC4 and Mammostrat, in the Edinburgh Breast Conservation Series (BCS) and in the Tamoxifen versus Exemestane Adjuvant Multinational (TEAM) trial. Materials and Methods: The primary cohorts comprised 831 and 2,513 estrogen receptor (ER)-positive patients who did not receive adjuvant chemotherapy from the Edinburgh BCS and TEAM cohorts respectively. We evaluated prognostic scores for distant recurrence-free survival (DRFS). Results: Low scores for both IHC4 and Mammostrat are associated with better DRFS. In multivariate Cox regression analyses the addition of both scores to clinical factors provided independent information on residual risk (p&amp;lt;0.05). In the larger TEAM cohort, IHC4 was the stronger predictor of DRFS but additional information was gained from including the Mammostrat score for all ER-positive patients (p&amp;lt;0.001). Conclusion: The results showed that the scores have different capabilities in predicting DRFS depending on the study and subgroup of patients. However, significant benefit in estimating residual recurrence risk after treatment was observed from a combined use of both marker panels. This provides support for investigating their combined use for risk stratification of ER-positive early breast cancer patients. Citation Format: Jacqueline Stephen, Gordon Murray, David Cameron, Jeremy Thomas, Ian Kunkler, Wilma Jack, Gill Kerr, Tammy Piper, Cassandra Brookes, Daniel Rea, Cornelis van de Velde, Annette Hasenburg, Christos Markopoulos, Luc Dirix, Caroline Seynaeve, John Bartlett. Comparison of immunohistochemical residual risk panels to predict risk in early breast cancers treated with endocrine therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-09.
Cardiac transplantation and aspergillosis.
Authors: E K Massin, B J Zeluff, C L Carrol, B Radovancević, R S Benjamin, M S Ewer, T L Bransford, L M Buja
Journal: Circulation (1994)

A 31-year-old female heart transplant recipient was admitted to the hospital for a recent history of progres- sively worsening headaches.Her past medical history included doxorubicin (Adriamycin)-induced cardiomyopathy and cisplatin-induced nephropathy secondary to a nonrecurrent osteosarcoma that occurred in 1982; in 1991, she underwent orthotopic heart transplantation.After transplantation (at age 29), she was admitted on several occasions for organ rejection and for onset of moderate-to-severe headaches after an uneventful preg- nancy.In September 1992, a complete neurological evaluation for the headaches was unrevealing, and she was treated symptomatically.The patient was admitted to another hospital for worsening headaches in January 1993; her WBC count was 0, and a lumbar puncture indicated a pressure of 450 mm H20.She was diagnosed with pseudotumor cerebri and given acetazolamide (Diamox).While hos- pitalized, she developed a low-grade fever, and empiric antibiotic therapy was begun with defervescence.She was subsequently transferred to the intensive care unit for acute worsening of liver and renal function with hepatic encephalopathy.Cyclosporine and azathioprine were discontinued, and prednisone was converted to solumedrol.Her neurological condition worsened with coma and seizures.Computed tomography (CT) scans of the brain were normal.Because of hepatic failure, she was transferred to another hospital for a possible liver transplant.A new CT scan of the brain (3 days after the previous scan) showed multiple, circumferen- tial, low-density lesions.The lesions were considered representative of a possible infectious process, perhaps Nocardia, tuberculosis, septic emboli, toxoplasmosis, or fungus.Shortly thereafter, the patient's pupils became
Healthy Lifestyle and Decreasing Risk of Heart Failure in Women
Authors: Golareh Agha, Eric B. Loucks, Lesley F. Tinker, Molly E. Waring, Dominique S. Michaud, Randi E. Foraker, Wenjun Li, Lisa W. Martin, Philip Greenland, JoAnn E. Manson, Charles B. Eaton
Journal: Journal of the American College of Cardiology (2014)
Methylenetetrahydrofolate Reductase Gene and Coronary Artery Disease
Authors: A. Mager, Petah Tiqva
Journal: Circulation (2000)

To the Editor:Brattstro ¨m et al 1 performed a meta-analysis of the results of 13 studies on plasma homocysteine concentrations in the 3 genotypes of the C677T mutation of the enzyme methylenetetrahydrofolate reductase (MTHFR) and of 23 case-control studies on this mutation in cardiovascular disease.They found that the TT (homozygous mutant) genotype was associated with mildly elevated plasma homocysteine concentrations but with a relative risk of vascular disease of only 1.12.They concluded that although the C677T mutation of MTHFR is a major cause of mild hyperhomocysteinemia, it is not a risk factor for cardiovascular disease.We are greatly concerned by this meta-analysis, particularly by the inclusion of different populations.The impact of the C677T mutation on plasma homocysteine and its association with coronary artery disease (CAD) reflect a gene-environment interaction.However, Brattstro ¨m et al pooled data from populations that differed in their ethnic origin, geographic location, and probably nutritional status.A review of the pooled studies on MTHFR polymorphism in CAD and of more recent works, including a preliminary report from our institution, 2 shows that almost all the negative studies included populations of Anglo-Saxon origin, whereas all the positive studies included populations of other ethnic origins: Dutch, 3 Irish, 4 Japanese, 5 and Israeli Jews. 2 This suggests that the association between MTHFR polymorphism and CAD is population specific and cannot be subjected to meta-analysis.Although it is not yet clear why the role of MTHFR C677T as a risk factor for CAD varies among populations, differences in plasma homocysteine levels in homozygotes may provide at least a partial answer.For example, in some populations, hyperhomocysteinemia is confined to those TT homozygotes with plasma folate levels in the lowest quartile, 1 whereas in other populations it also occurs with higher folate levels.Other factors may also be important in this context, including differences in folate intake and in plasma folate, in itself a possible coronary risk factor, and in concomitant genetic disturbances in the clotting system.Moreover, there is strong evidence that the role of this mutation also varies within populations and among phenotypes.In our population, 2 for example, the TT genotype was overrepresented only among patients with early-onset (Ͻ45 years of age) CAD and not among those with later CAD onset.A similar association with premature CAD was found in 2 other positive case-control studies. 3,4Since early onset characterizes only a minority of CAD patients, the role of MTHFR polymorphism in this setting could have eluded authors who did not specifically address this issue.Therefore, it is much too early for a verdict to be rendered on the role of MTHFR in CAD, and much more evidence is necessary.
Nilotinib reduces muscle fibrosis in chronic muscle injury by promoting TNF-mediated apoptosis of fibro/adipogenic progenitors
Authors: Dario R Lemos, Farshad Babaeijandaghi, Marcela Low, Chih-Kai Chang, Sunny T Lee, Daniela Fiore, Regan-Heng Zhang, Anuradha Natarajan, Sergei A Nedospasov, Fabio M V Rossi
Journal: Nature Medicine (2015)
Carboxyl-Terminal Repressor Domain of MBP-1 is Sufficient for Regression of Prostate Tumor Growth in Nude Mice
Authors: Asish K. Ghosh, Robert Steele, Ratna B. Ray
Journal: Cancer Research (2005)

Abstract Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of male cancer death in the United States. Early detection and improved procedures for surgical intervention and radiation therapy have reduced the fatalities; however, there is no effective cure for men with advanced disease and additional therapy is urgently needed. We have previously shown that MBP-1 acts as a general transcriptional repressor and exerts an antiproliferative effect on several human cancer cells. MBP-1 possesses two repressor domains, located at the amino and carboxyl termini. In this study, we have examined the potential of the repressor domains of MBP-1 as a gene therapeutic candidate in regression of prostate tumor growth. Our results suggested that replication-deficient adenovirus-mediated delivery of amino-terminal (MBP-AR) or carboxyl-terminal (MBP-CR) repressor domain of MBP-1 exerted an antiproliferative effect, like the full-length MBP-1, and induced caspase-independent apoptosis in prostate cancer cells. Next, we investigated the therapeutic effectiveness of MBP-1 repressor domain on prostate tumors. When tested in human tumor xenografts in nude mice, MBP-CR suppressed prostate tumor growth more effectively than full-length MBP-1, whereas MBP-AR delayed prostate tumor growth. Together, these results suggested that MBP-CR expression has an antiproliferative effect in human prostate cancer cells, being more effective than the full-length MBP-1 in preventing tumor growth.
630. In Vivo h- VEGF165 Gene Transfer Improves Early Endothelialisation and Patency in Synthetic Vascular Grafts
Authors: Mika Lahtinen, Vitas Zemgulis, Pontus Blomberg, Giedrius Baliulis, Fredrik Carlsson, Harry Khamis, David Bergqvist
Journal: Molecular Therapy (2005)

Top of pageAbstract
Background: Synthetic vascular graft performance is inferior to autologous vein grafts. This study investigated if 1) local administration of plasmids encoding for human vascular endothelial growth factor (pNGVL3-VEGF165) or h-VEGF165/FGF-2 combination or 2) graft design affect synthetic graft endothelialisation and patency.

Methods and Results: Rat abdominal aorta (n=132) was replaced with 60 microns ePTFE graft and pNGVL3-VEGF165, pNGVL3-VEGF165/FGF-2 combination or control plasmid were administered. In rabbits (n=90), polyester, 60 microns ePTFE, hybrid ePTFE, or 30 microns ePTFE grafts and pNGVL3-VEGF165 or control plasmids were used. Rats were sacrificed after 1, 2, 4 or 77 weeks and rabbits after 2, 4, 12 or 43 weeks. In dogs, 60 microns ePTFE (n=10) or polyester grafts (n=10) were inoperated to carotid and hybrid ePTFE grafts (n=15) to femoral position, followed by injection of pNGVL3-VEGF165 or control plasmid. Dogs were sacrificed at 6 weeks. Endothelialisation was determined in the midgraft area with scanning electron microscopy (SEM). pNGVL3-VEGF165 enhanced endothelialisation at every time point in rats, whereas plasmids encoding h-VEGF165/FGF-2 combination had worst outcome at 1 week (NS), 2 weeks (p=0.01) and at 4 weeks (p=0.02). In rabbits, polyester grafts had a trend for faster endothelialisation (p=0.08) and pNGVL3-VEGF165 enhanced endothelialisation at 2 weeks (p=0.06) but the effect reversed at 4 weeks (p=0.03). pNGVL3-VEGF165 improved hybrid ePTFE patency in dogs (p=0,103).

Conclusions: Improved early endothelialisation and patency with local administration of pNGVL3-VEGF165 reveal a new concept for enhancement of synthetic vascular graft performance with gene therapy.

Was founder of the Company but has no indirect, direct or other businesses with buyer of the IP assets Fit Biotech Oyj.
Lineage-specific regulation of the murine RAG-2 promoter: GATA-3 in T cells and Pax-5 in B cells
Authors: Hiroyuki Kishi, Xing-Cheng Wei, Zhe-Xiong Jin, Yoshiyuki Fujishiro, Takuya Nagata, Tadashi Matsuda, Atsushi Muraguchi
Journal: Blood (2000)
Abstract 20406: Stimulation of Glucagon-Like-Peptide-1 Receptor Elicits the Protection Through Akt-1 in Infarcted Hearts
Authors: Jian Feng Du, Yu Zhao, Youfang Chen, Ting C Zhao
Journal: Circulation (2014)

Background: We have demonstrated that GLP-1 protects the heart against ischemia and reperfusion injury. However, it remains unknown whether the stimulation of GLP-1 receptor (GLP-1R) that initiates cardioprotection is mediated by Akt-1 pathway.

Objectives: The goal of this study is to elucidate the functional roles of Akt-1 in mediating GLP-1 receptor-elicited protection in infarcted hearts.

Methods: Adult mouse myocardial infarction (MI) was created by ligation of the left descending artery. Both wild type (C57BL/6) and Akt-1-/- mice were divided into one of three groups as following: 1) Sham: Animals underwent thoracotomy without ligation; 2) MI: Animals underwent MI and received a daily dose of intraperitoneal injection (i.p.) of vehicle (saline); 3) MI + Exendin-4: MI mice received daily injections of exendin-4, a GLP-1 receptor agonist (0.1mg/kg, i.p.). Echocardiography was employed to measure ventricular function prior to and after myocardial infarction. Histological analysis was conducted to assess cardiac hypertrophy and interstitial fibrosis. Western blot was used to examine the levels of Akt-1 and apoptotic signaling pathway.

Results: Echocardiography showed a reduction in left ventricular ejection fraction (EF) and fraction shortening (FS) (41.8% ± 3.5; 17.1% ± 2.1) in WT after MI as compared to sham (81.7% ± 2.2; 44% ± 3.6, p<0.05, respectively). Exendin-4 improved both EF and FS (67.7% ±2.4; 32.3% ±1.5, p<0.05 vs MI), respectively. The improvement induced by Exendin-4 in EF and FS in MI mice was diminished in Akt-1-/- mice (35.5% ±4.4; 15.1% ± 3.3, p<0.05). Exendin-4 treatments suppressed cardiac hypotrophy and reduced scar size and cardiac interstitial fibrosis in the MI hearts, but these beneficial effects were absent in infarcted mice by elimination of Akt-1. GLP-1R stimulated angiogenesis in infarcted hearts, which were also mitigated by deletion of Akt-1. Furthermore, GLP-1R stimulation increased phosphorylation of Akt-1, decreased active-caspase 3, PARP and annexin V. Anti-apoptotic effects of Exendin-4 were diminished in Akt-1-/- mice.

Conclusion: GLP-1R stimulation improves cardiac function, attenuates remodeling, and promotes angiogenesis in the infarcted myocardium through the Akt-1 pathway.
Long-Term Outcomes Of Ruxolitinib Therapy In Patients With Myelofibrosis: 3-Year Update From COMFORT-I
Authors: Srdan Verstovsek, Ruben A. Mesa, Jason Gotlib, Richard S. Levy, Vikas Gupta, John F. Dipersio, John V. Catalano, Michael W. Deininger, Carole B. Miller, Richard T. Silver, Moshe Talpaz, Elliott F. Winton, Jimmie H. Harvey, Murat O. Arcasoy, Elizabeth Hexner, Roger M. Lyons, Ronald Paquette, Azra Raza, Kris Vaddi, William Sun, Wei Peng, Victor A. Sandor, Hagop M. Kantarjian
Journal: Blood (2013)
Bisindolylmaleimide and indolocarbazole protein kinase (PK) inhibitors reverse ABCG2-mediated drug transport and resistance
Authors: Robert W. Robey, Suneet Shukla, Kenneth Steadman, Suresh V. Ambudkar, Susan E. Bates
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Protein kinases have emerged as attractive targets in cancer treatment and several PK inhibitors are currently in development. Most PK inhibitors are based on the structure of stauropsporine and are bisindolylmaleimides or indolocarbazoles. Bisindolylmaleimide I and the indolocarbazoles staurosporine and UCN-01 are known to inhibit the ATP-binding cassette (ABC) transporter ABCB1. We previously demonstrated that UCN-01 is a substrate and inhibitor of the ABC half-transporter ABCG2. Thus, we examined the ability of commercially available bisindolylmaleimides or indolocarbazoles (BIM I, II, III, IV, V, VII, IX, X, XI, Go6983, arcyriaflavin a, KT5720, KT5823, Go6976, Go7874, K252a, K252c) to inhibit ABCG2. At 10 μM, all of the compounds tested increased intracellular fluorescence of the ABCG2-specific substrate pheophorbide a as measured by flow cytometry in ABCG2-transfected HEK-293 cells by 2- to 7-fold. The ABCG2-specific inhibitor fumitremorgin C increased intracellular pheophorbide a fluorescence by 8-fold at a concentration of 10 μM. Four-day cytotoxicity assays showed that, compared to empty-vector transfected HEK-293 cells, wild-type ABCG2-transfected cells were not more than 2-fold resistant to any of the compounds suggesting their ability to inhibit ABCG2 is primarily non-competitive. At concentrations shown to inhibit ABCG2, four compounds–BIM IV, V, arcyriaflavin a or K252c–were not toxic to cells. These four compounds reduced the relative resistance of ABCG2-transfected cells to SN-38 2- to 34-fold. The four compounds were also able to inhibit [125I]iodoarylazidoprazosin labeling of ABCG2 by 65 to 80% at 10μM, compared to a 55% reduction by 10 μM fumitremorgin C. Bisindolylmaleimides and indolocarbazoles represent novel classes of ABCG2 inhibitors. The results presented here suggest that these PK inhibitors can overcome drug resistance in ABCG2-overexpressing cells and may be able to increase the oral bioavailability of ABCG2 substrates. Studies are underway to determine potency and in vivo activity in animal models.
Abstract 14483: Strain Analysis by 2D Speckle Tracking Imaging Sensitively Identifies Early Dystrophin Cardiomyopathy in Murine Duchenne Muscular Dystrophy Model: An Ultrasound Biomicroscopy and Histology Correlation Study
Authors: Minjuan Zheng, Zhenzhou Li, Mingxing Xie, Jiangbo Qu, Manli Fu, Yuxin Fan, Xiaodong Zhou, Yong-Jian Geng, Xiongwen Chen, Shuping Ge
Journal: Circulation (2010)

Introduction: Cardiomyopathy is a significant cause of mortality and morbidity in Duchenne muscular dystrophy (DMD). To develop novel safe and efficacious therapy for dystrophin cardiomyopathy in m...
Abstract 15029: Ticagrelor Versus Clopidogrel in Patients with Acute Coronary Syndromes and History of Stroke or Transient Ischemic Accident: Results from the Platelet Inhibition and Patient Outcomes Trial
Authors: Stefan K James, Robert F Storey, Cheryl Bushnell, Jay Horrow, Steen Husted, Kenneth W Mahaffey, Juan Maya, Richard C Becker
Journal: Circulation (2011)

Background: Despite current therapy, patients with acute coronary syndrome (ACS) and history of stroke or transient ischemic attack (TIA) have both a high risk of recurrent cardiac events and bleed...
338. Non-Viral Gene Transfer into Hematopoietic Cells of Artemis Deficient ScidA Mice Using the Sleeping BeautyTransposon System
Authors: Andy Wilber, Shannon Buckley, Uma Lakshmipathy, Joel Frandsen, Morton J. Cowan, R. Scott McIvor
Journal: Molecular Therapy (2005)

The Sleeping Beauty (SB) transposon system has been shown to mediate gene insertion into mouse and human chromosomes, which is favored for cells where molecular therapies seek to provide durable gene expression. Although conditions have been established for non-viral delivery of DNA into cultured hematopoietic cells, no conclusive result has been published showing stable in vivo expression following non-viral delivery into mouse hematopoietic cells. Here we describe studies designed to test the ability of the SB system to mediate gene transfer into mouse total bone marrow (TBM) for the purpose of achieving stable gene expression in hematopoietic stem cells. Experiments were conducted in normal mice and in a model of T-B-NK+ SCID (ScidA) resulting from deficiency of Artemis for which selective engraftment of normal cells has been observed.
Correspondence re: K. S. Crump, D. G. Hoel, C. H. Langley, and R. Peto. Fundamental Carcinogenic Processes and Their Implications for Low-Dose Risk Assessment. Cancer Res., 36: 2973–2979, 1976, and H. Guess, K. Crump, and R. Peto. Uncertainty Estimates for Low-Dose-Rate Extrapolations of Animal Carcinogenicity Data. Cancer Res., 37: 3475–3483, 1977.
Authors: Kenny S. Crump
Journal: Cancer Research (1978)
Comparison of efficacy of respiratory rehabilitation in patients with COPD and interstitial lung disease
Authors: Atsuhito Nakazawa, Takeshi Shinohara, Eri Hagiwara, Kaori Tsuruta, Takuma Sasaki, Takashi Ogura, Hiroshi Takahashi
Journal: European Respiratory Journal (2011)

Objectives:  There are few reports describing the efficacy of pulmonary rehabilitation (PR) in patients with interstitial lung disease (ILD). We studied whether PR could improve functional status and dyspnea in a group of patients with ILD in comparison with patients with COPD.   Methods:  Seventy three outpatients (mean age 71y, male: female = 57:16, ILD: COPD: others = 22: 36: 15) joined a 12-week PR program including exercise training, physiotherapy and education. Six-minute walking test, lung function test and evaluation of health-related quality of life (St George9s Respiratory Questionnaire: SGRQ, Short Form questionnaire: SF-36) were performed before and after the program and retrospectively analyzed.   Results:  We found substantial decrease in SGRQ score from 42.1 to 33.9 (p   Conclusions:  Our results show that PR improves both functional status and dyspnea in patients with ILD to the same extent as with COPD. PR should be considered as a standard of care for ILD patients.