tbuckley/cabot-search huggingface dataset:
Abstract 222: Inhibition Of Class I But Not Class IIb Lysine Deacetylases Is Responsible For Cardioprotection From Ischemia-Reperfusion.
Authors: Sverre E Aune, Santhosh K Mani, Donald R Menick
Journal: Circulation Research (2013)

Background: While dual inhibition of class I/IIb KDACs protects the mammalian heart from ischemia-reperfusion (IR) injury, class-specific effects have not been examined. Hypothesis: We hypothesized that specific inhibition of class I KDACs would preserve left ventricular (LV) function following IR in isolated hearts. Methods: Male Sprague-Dawley rats (n=4 per group) were injected with vehicle, the class I KDAC inhibitor entinostat, the class IIb inhibitor tubastatin A, or the class I/IIb inhibitor trichostatin A (TSA). After 18 h, hearts were isolated and perfused in Langendorff mode. A saline-filled balloon was placed in the LV to monitor contractile function. Following IR (30/120 min), LV free wall tissue was assayed for activation of pro-survival proteins. Group results are reported vs vehicle as mean±SE. Results: There were no differences between groups in LV function before ischemia. At the end of reperfusion, rate pressure product (mm hg/min) was improved with entinostat (27392±3474, p&lt;0.001) and TSA (22980±3226, p&lt;0.05) vs vehicle (11,352±1977), as were +dP/dt max and -dP/dt max . Most notably, entinostat alone blunted the rise in end diastolic pressure (mm Hg) during reperfusion (18.6±1.4 vs. 45.3±4.1, p&lt;0.001), and completely prevented diastolic contracture (mm Hg) in reperfusion for up to one hour (12.4±2.0 vs pre-ischemia=8.7±1.7, p=0.21). Contractile function was not significantly preserved in hearts treated with tubastatin A. Entinostat reduced phosphorylation at the eNOS inhibitory site, and increased phosphorylation at the eNOS activation site, and Src activation was dramatically reduced. TSA increased activation of Src, p38, and ERK 1/2, and increased phosphorylation of eNOS at both the activation (Ser1177) and inhibition site (Thr495). Tubastatin A reduced activation of p38, ERK 1/2, and eNOS, but not Src. Conclusions: Inhibition of class I KDACs was most effective at preserving contractile function following IR in isolated hearts, notably through prevention of LV contracture during reperfusion. Class I KDAC inhibition may preserve LV function by differentially modulating Src and eNOS activities. These results suggest that the protective effects of KDAC inhibitors in IR can be ascribed to specific inhibition of class I KDACs.
Use of changes in CA125 doubling time to detect activity of cytostatic agents in women relapsing with ovarian carcinoma. Study 1 - tamoxifen
Authors: D. M. Patterson, G. J. Rustin, P. D. Nathan, T. S. Ganesan, J. M. Evans, W. Qian, A. M. Swart
Journal: Journal of Clinical Oncology (2005)

5119 Background: Many new targeted-therapy agents with potential anti-cancer activity could be cytostatic rather than cytotoxic. Therefore standardised radiological response criteria such as RECIST may not detect activity of these agents in phase II trials. There is an urgent need for a method to screen for activity of these agents before embarking on large randomised trials. The main purpose of this study was to determine whether there is a predictable log-linear rise of CA125 levels in asymptomatic relapsing ovarian cancer patients and if so, whether a change in rate of rise of CA125 can be used to demonstrate activity of a cytostatic agent. For proof of principle, we used tamoxifen in this trial which has modest clinical activity, and so one would expect some changes in CA125 doubling time. Methods: Ovarian cancer patients with previously elevated CA125 levels that had successfully completed first relapse chemotherapy were eligible. Patients consented to monthly CA125 measurements, which became fortnightly once there was any rise in levels. Tamoxifen 20mg once daily was commenced once CA125 was either four times its upper limit of normal, or four times the nadir level if this was elevated at baseline. Log CA125 levels were plotted to look for linear trends. Results: So far out of the first 15 patients that have entered the study, 12 have had rising CA125 levels, out of whom 6 patients demonstrated a log-linear rise. The median number of samples from the start of the linear rise to start of tamoxifen was 5. A change in the slope of log linear CA125 levels was observed in 2 out of 6 patients started on Tamoxifen. Conclusions: Early results suggest that this approach to assessing new cytostatic agents in phase II trials does look feasible. A log linear rise was seen in 50% of patients. We aim to recruit 200 patients to reliably assess whether Tamoxifen has activity based on a change in slope of CA125. No significant financial relationships to disclose.
Wheezing Patterns in Early Childhood and the Risk of Respiratory and Allergic Disease in Adolescence
Authors: Meghan B. Azad, Moira Chan-Yeung, Edmond S. Chan, Amy M. Dytnerski, Anita L. Kozyrskyj, Clare Ramsey, Allan B. Becker
Journal: JAMA Pediatrics (2016)

This study applied the Tuscon Children's Respiratory Study wheeze phenotypes to the high-risk Canadian Asthma Primary Prevention Study cohort and evaluated associations with pulmonary function, asthma, and allergic disease in adolescence.
PHYSICAL FACTORS IN THE ANALYSIS OF THE ACTIONS OF DRUGS ON MYOCARDIAL CONTRACTILITY
Authors: JOHN R. BLINKS, JAN KOCH-WESER
Journal: Pharmacological Reviews (1963)

In most areas of pharmacology knowledge about the mechanism of action of drugs has advanced in pace with the understanding of the systems in which the drugs act. Despite great progress toward an understanding of the nature of muscular contraction, however, practically nothing is known about the mechanisms of action of drugs that affect myocardial contractility. The heart is a muscle, and much can be gained by applying the concepts of muscle physiology to the study of its function. The effects of drugs can then be defined in terms more precise than simply the direction and magnitude of the change produced in the strength of contraction. Similar changes in the strength of contraction can result from quite different changes in the fundamental mechanical properties of the muscle. An understanding of the effects of drugs in terms of their actions upon these properties seems essential for further progress.

The influence of physical factors on the contractions of the heart must be given careful consideration in the design and interpretation of experiments on the inotropic actions of drugs. Such actions vary quantitatively or even qualitatively with the physical conditions of the experiment: the frequency of contraction is particularly important in this regard [see companion review (258a)]. In some cases, the actions of physical and chemical determinants of contractility are so closely related that they cannot profitably be studied separately. Interactions of this sort challenge explanation; they may furnish a valuable approach to the study of the mechanisms of action of both factors concerned.
Green tea extract does not protect against prostate cancer induction by MNU and testosterone in WU rats
Authors: Maarten C. Bosland, Lori Horton, Rachael Weir
Journal: Cancer Research (2005)

6071  The low prostate cancer rates in countries where consumption of green tea is high suggests green tea may be protective against this human cancer. Green and black tea and some tea catechins, including epigallocatechin gallate (EGCG), have shown anticancer properties in vitro and in vivo. Inhibition of prostate tumor development in the TRAMP model by administration of a green tea polyphenolic fraction in drinking water has been reported (2001, PNAS 98:10350-5). However, we observed that green tea extract does not affect the in vivo growth of rat prostate cancer cells and a human prostate xenograft (Proc AACR 44, Abstract #3895, 2003). In this study, we examined the effect of a green tea extract developed by Unilever Bestfoods for human clinical trials on the induction of prostate cancer in a rat model. Hormone-dependent prostate cancers were induced in male Wistar-Unilever (Hsd:WU) rats by the following treatment. To stimulate prostatic cell proliferation, rats were first treated with Flutamide (20 mg/day for 21 days by gavage) followed one day later by testosterone propionate (100 mg/kg/day by single s.c. injection). Sixty hours after this androgen injection, rats (34 per group) received a single intravenous injection of N-methyl-N-nitrosourea (MNU [NCI Carcinogen Repository]; 30 mg/kg body weight). Beginning one week post-MNU, low dose chronic androgen stimulation was provided by two 3 cm-long subcutaneous Silastic tubing capsules containing crystalline testosterone; capsules were replaced once after 9 months. One week post-MNU, animals began receiving drinking water supplemented with either a 1.5% solution of green tea extract (735 mg/L EGCG, 1656 mg/L total catechins, and 300 mg/L caffeine) or a solution of 300 mg/L caffeine, or they continued to receive plain drinking water. Growth and survival were not affected by the treatments, but rats on the tea extract drank 16% less than rats on caffeine or control rats which drank identical amounts. The two treatments did not affect prostate cancer induction. In comparison to a total cancer incidence of 64% (all accessory sex glands) in control rats, total cancer incidences of 60% and 58% were observed in groups given the tea extract or caffeine, respectively. Similarly, cancers that were clearly confined to the dorsolateral/anterior prostate were found in 55% of controls versus 40% and 42% of rats in groups given the tea extract or caffeine, respectively. Adding data on carcinoma in situ to this did not change the observed lack of a protective effect. Using cyproterone acetate in stead of Flutamide or MNU from Ash Stevens did not substantially change prostate cancer incidence in parallel groups given drinking water. Cancer incidence in only the seminal vesicle was less than 15% in all groups. These data do not support the hypothesis that green tea is an inhibitor of prostate carcinogenesis and they are in line with our previous observations. (Supported by NIH Grant CA76426)
Karnofsky Memorial Lecture. The immunotherapy and gene therapy of cancer.
Authors: S A Rosenberg
Journal: Journal of Clinical Oncology (1992)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1992.10.2.180 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1732421 Karnofsky Memorial Lecture. The immunotherapy and gene therapy of cancer. S A RosenbergxS A RosenbergSearch for articles by this author Show More National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. https://doi.org/10.1200/JCO.1992.10.2.180 First Page PDF © 1992 by American Society of Clinical Oncology
Effects of bisphosphonates on human osteoblasts as an important constituent of the bone marrow microenvironment.
Authors: T. Kaiser, K. Geiger, D. Wallwiener, G. Klein, T. N. Fehm
Journal: Journal of Clinical Oncology (2010)

e13620 Background: Bisphosphonates (BPs) are widely used for the treatment in bone metastatic disease and for the management of osteoporosis. Their antiresorptive effects can be explained by inhibition of osteoclastic resorption, promoting osteoclast apoptosis. However, recent evidence also points to a direct action of bisphosphonates on bone-forming osteoblasts. Despite its clinical importance, the mechanisms of BPs on osteoblast function still remain poorly characterized. Methods: In this study, the influence of BPs zoledronate (zol), ibandronate (iban), and pamidronate (pam) on molecular and cellular functions of human osteoblasts was assessed by focusing on osteogenic marker gene expression, cell proliferation and viability. Results: The regulation of osteogenic markers was analyzed by quantitative real-time RT-PCR after exposure of primary osteoblasts (pOB) to different concentrations (0.01-100 μM) of zol and iban for 48 h and 72 h. The gene-expression analyses revealed an important increase in osteopontin and in osteocalcin expression with 100 μM, decrease in type I collagen alpha-2 with 0.01-100 μM zol and iban and an unchanged expression of bone sialoprotein, runt-related transcription factor 2 and osteonectin after 48 h and 72 h. Further, exposure of pOB to different zol but not to iban concentrations for 72 h resulted in a significant overexpression of alkaline phosphatase relative to control cells, except for the treatment with 100 μM. Proliferation assays demonstrated that treatment with iban and pam for 72 h did not affect the osteoblast number at concentrations of 0.01-10 μM, whereas 100 μM resulted in a notably cell growth reduction. Zol showed an inhibitory proliferation action already by 1 μM. Moreover, a significant decrease of osteoblast viability was noted after treatment with ≥ 1 μM zol after 48 h, which could be enhanced after 72 h. Conclusions: Our results demonstrated that bisphosphonates revealed prominent differences in the mode of action on human osteoblast functions. Zol, recognized as the most potent BP, reduced both the expression of osteogenic markers and the proliferation as well as the viability of human osteoblasts at concentrations in the low micro-molar range. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Correlation Between the Ability of Tumor Cells To Incorporate Specific Fatty Acids and Their Sensitivity to Killing by a Specific Antibody Plus Guinea Pig Complement
Authors: Seymour I. Schlager, Sarkis H. Ohanian, Tibor Borsos
Journal: JNCI Journal of the National Cancer Institute (1978)

Line-1 diethylnitrosamine-induced guinea pig tumor cells can be rendered sensitive to killing by rabbit anti-Forssman IgM antibody plus guinea pig complement (GPC) or antitumor antibody plus GPC following prolonged incubation (17 hr ) of the cells with one of several metabolic inhibitors. Compared to control cells, these cells have been shown to be inhibited in their ability to incorporate fatty acids into complex cellular lipids, which suggested that lipid synthesis is of fundamental importance for the ability of the tumor cells to resist humoral immune killing. In this study, drug-treated cells that were rendered sensitive to killing by anti-Forssman antibody plus GPC, but not antitumor antibody plus GPC, were inhibited in their incorporation of saturated (palmitic or stearic acid), but not an unsaturated, fatty acid (linoleic acid). These data suggested that the fatty acid composition of specific lipids may also be important for the resistance of these tumor cells to killing by antibody and complement.
Axillary lymph node nanometastases are prognostic factors for metastatic relapse in breast cancer patients
Authors: S. Alberti, P. Querzoli, M. Pedriali, R. Rinaldi, E. Biganzoli, P. Boracchi, M. Piantelli, S. Iacobelli, E. Marubini, I. Nenci
Journal: Journal of Clinical Oncology (2006)

610 Background: Early breast cancer presents with a remarkable and largely unaccounted for heterogeneity of outcomes. Undetected, microscopic lymph node tumor deposits may account for a significant fraction of this prognostic diversity. Thus, we systematically evaluated the presence of lymph node tumor cell deposits &lt;0.2 mm in diameter [pN0(i+), nanometastases], and analysed their prognostic impact. Methods: Seven hundred and two single institution, consecutive patients with 8 years of median follow-up were studied. To maximize the chances of detecting micro and nanometastases, whole-axilla dissections were analysed. pN0 cases were systematically reevaluated by step sectioning and anti-cytokeratin immunohistochemical analysis of 6676 corresponding dissected lymph nodes. The risk of first adverse events and of distant relapse of bona fide pN0 patients was compared with that of pN0(i+), pN1mi and pN1 cases. Crude cumulative incidence (CCI) curves were used to estimate the cumulative probability of occurrence of adverse events. CCI curves were compared by the Gray’s test. A proportional sub distribution hazard (SDH) regression model was utilized to assess the difference among CCI curves of pN0(i+) versus pN0(i-), and of pN1mi versus pN0(i+). Competing risks were accounted for and regression models were adjusted for established breast cancer prognostic factors, i.e. grading, pathological T stage and age. Proportional SDH assumptions were checked using Schoenfeld-type residuals. Results: A pN0(i+) status was shown to be a strong risk factor for event-free survival (P&lt;0.0005) and for metastatic relapse in both univariate and multivariate analyses accounting for competing risks and adjusted for grading, pathological T stage and age. Conclusions: Our findings demonstrate that nanometastases are an important risk factor in breast cancer. These results support the inclusion of procedures for nanometastasis detection in TNM pathological staging. No significant financial relationships to disclose.
Natural History of Renal Angiomyolipoma (AML): Most Patients with Large AMLs &gt;4 cm Can Be Offered Active Surveillance as an Initial Management Strategy
Authors: Jaimin R. Bhatt, Patrick O. Richard, Nicole S. Kim, Antonio Finelli, Karthikeyan Manickavachagam, Laura Legere, Andrew Evans, York Pei, Jenna Sykes, Kartik Jhaveri, Michael A.S. Jewett
Journal: European Urology (2016)
MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production
Authors: Heather H. Pua, David F. Steiner, Sana Patel, Jeanmarie R. Gonzalez, Jorge F. Ortiz-Carpena, Robin Kageyama, Ni-Ting Chiou, Antonia Gallman, Dimitri de Kouchkovsky, Lukas T. Jeker, Michael T. McManus, David J. Erle, K. Mark Ansel
Journal: Immunity (2016)
Angel's Trumpet psychosis: a central nervous system anticholinergic syndrome
Authors: R C Hall, M K Popkin, L E Mchenry
Journal: American Journal of Psychiatry (1977)

The authors warn physicians that intoxication by Angel's Trumpet (Datura sauveolens) is becoming more frequent due to its use by adolescents and young adults as a legal, readily available hallucinogen. Ingestion of Angel's Trumpet flowers or a tea brewed from them results in an alkaloid-induced central nervous system anticholinergic syndrome characterized by symptoms such as fever, delirium, hallucinations, agitation, and persistent memory disturbances. Severe intoxication may cause flaccid paralysis, convulsions, and death. Treatment with intravenous physostigmine reverses the toxic effects of Angel's Trumpet.
Abstract 12805: Calcific Aortic Stenosis and Marfanoid Habitus
Authors: Nina N Parfenova, Svetlana I Khasanova, Ekaterina V Dubova, Eduard V Zemtsovsky
Journal: Circulation (2012)

Calcific aortic stenosis (CAS) stands on top among the acquired heart diseases nowadays. Of all the known risk factors for CAS there is no evidence of correlation with the inherited connective tiss...
Abstract 12365: Are there Sympathetic Nerve Fibers in Human Cervical and Thoracic Vagus Nerves?: Implications for Therapeutic Vagal Stimulation
Authors: Atsuko Seki, Peng-Sheng Chen, Jian Tan, Michael C Fishbein
Journal: Circulation (2013)

Introduction: Cervical vagal nerve stimulation has been used to treat resistant partial-onset seizures and is being evaluation in clinical trials for treatment of heart failure and cardiac arrhythm...
The Human Alzheimer Disease Project
Authors: Steven T. DeKosky, John H. Growdon
Journal: JAMA Neurology (2016)

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대간간학회지 제6차 춘계학술대회 초록집 : 구연 ; 비멘틴과 시토케라틴을 동시에 발현하는 상피-진피 전이 간세포주의 확립
Authors: 김홍표 ( Kim Hong Pyo ), 윤정환 ( Yun Jeong Hwan ), 이효석 ( Lee Hyo Seog ), 김정룡 ( Kim Jeong Lyong )
Journal: Clinical and Molecular Hepatology (2000)
Controlled-release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation.
Authors: A Khojasteh, W Evans, R D Reynolds, G Thomas, J J Savarese
Journal: Journal of Clinical Oncology (1987)

The bioavailability and clinical effects of an oral controlled-release morphine sulfate tablet, MS-contin (MSC; Purdue-Frederick, Norwalk, CT) in comparison to an immediate-release (IRMS) preparation were evaluated in normal subjects and cancer patients, respectively. The inherent slow-release character of MSC was confirmed by 2 1/2 X T1/2 absorption rate, one-half Cmax, and twice Tmax relative to IRMS. The T1/2 elimination of the two morphine preparations was similar, demonstrating insignificant risk of MSC accumulation. The difference in the mean number of side effects experienced by the control group per subject was significant (.70 for MSC and 1.26 for IRMS, P = .05) and was consistent with peak plasma morphine attenuation. The cancer patients were initially switched from their previous analgesic to four hourly IRMS and then to MSC at double the dose every eight hours. The majority had their MSC dosing interval lengthened to every 12 hours with a decrease in the total daily morphine requirement. While the mean duration on MSC was 20.5 days, many patients were followed poststudy for an extended period with no appreciable development of tolerance. Overall, MSC analgesia and side effects were perceived by the patients as superior compared with prestudy opioids. The advantage of less frequent dosing may lead to improvement of the quality of life of cancer patients.
Commentary concerning demonstration of safety and efficacy of investigational anticancer agents in clinical trials.
Authors: J A O'Shaughnessy, R E Wittes, G Burke, M A Friedman, J R Johnson, J E Niederhuber, M L Rothenberg, J Woodcock, B A Chabner, R Temple
Journal: Journal of Clinical Oncology (1991)

Expeditious clinical development and approval of new drugs that are beneficial to patients are matters of high priority. There has been a great deal of discussion within the oncology community about what should constitute evidence of effectiveness of new anticancer agents for purposes of drug approval. This commentary is intended to illustrate a variety of end points that can lead to approval of new anticancer agents for specific clinical situations. Although the ultimate hope of antineoplastic therapy is prolongation of life, there are other effects of anticancer drugs that constitute clear clinical benefit and represent evidence of effectiveness. The guiding principle is that the beneficial effects obtained from a new drug should sufficiently outweigh the adverse effects such that the potential risk:benefit ratio achieved by an individual patient is favorable. The assessment of a new drug should flexibly evaluate safety and efficacy in the context of the specific clinical condition being treated. Early discussions with the Food and Drug Administration (FDA) and the National Cancer Institute (NCI) are recommended to identify prospectively the end points and trial designs needed to demonstrate effectiveness of a new drug. The general principles discussed will likely apply to the drug approval process for other medical disciplines as well.