tbuckley/cabot-search huggingface dataset:
Abstract 3613: Lipid Biomarkers, Hormone Therapy, and the Risk of Unprovoked Venous Thromboembolism in Women
Authors: Brendan M Everett, Robert J Glynn, Julie E Buring, Paul M Ridker
Journal: Circulation (2007)

Background : Published reports of a relationship between lipid biomarkers and venous thromboembolism (VTE) are inconsistent and controversial, and many do not account for potential effect modifiers such as hormone therapy (HT). Methods and Results : Among 27,082 initially healthy women followed prospectively (median, 11.4 years) for incident unprovoked VTE, we measured a full panel of lipid biomarkers, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, triglycerides, and apolipoproteins A-I (apo A-I) and B100. In analyses adjusted for age and body mass index (kg/m 2 ), only HDL-C and apo A-I showed any association with VTE (N=158; hazard ratio (95% CI) per 1 unit SD, 1.17 (1.00 –1.37) and 1.29 (1.11–1.51), respectively). However, after stratifying by HT use at the time of blood collection, none of the lipid biomarkers was associated with future VTE (N=80) in non-users, while higher levels of HDL-C and apo A-I were associated with increased risk of VTE (N=78) among users. Specifically, among HT users the adjusted hazard ratios for future VTE were 1.29 (1.05–1.58) and 1.41 (1.13–1.75) per 1 unit SD increase in HDL-C and apo A-I, respectively (each P≤0.01; Table ). In models further adjusted for factor V, prothrombin, and methylenetetrahydrofolate reductase genotypes, risk estimates did not change substantially, suggesting that the differences seen with HT were not due to any confounding by these genotypes. Conclusions : We observed little evidence that any lipid marker predicted risk of future VTE among non-users of HT. The observation that among HT users high levels of HDL-C and apo A-I relate to risk of VTE likely reflects concomitant prothrombotic effects of hormone therapy, rather than direct effects of HDL-C or apo A-I. Table. Risk of Future Unprovoked Venous Thromboembolism
Abstract 13865: Cardiac Specific Deletion of Endothelin-1 Receptor a Rescues the Heart from High-Fat Diet-Induced Cardiac Dysfunction via Regulating Autophagy
Authors: Asli Ceylan-Isik, Haoyu Zhao, Jun Ren, Sreejayan Nair
Journal: Circulation (2011)

Obesity is a major health concren worldwide and is an important risk factor for heart diseases. The objective of this study was to evaluate the role of endothelin-1 receptor A (ETA) in obesity-associated cardiac dysfunctions. Cardiac specific ETA receptor knock-out (ETAKO) mice and their age- and gender-matched controls (C57BL/6J mice) were randomly assigned to receive either high- fat (45% fat) diet (HFD) or low-fat (10% fat) diet (LFD) starting from their 5-6 weeks of age for 24 weeks. After 24 weeks of feeding, oral glucose tolerance test performed to ensure insulin-resistance. Mice were subjected to echocardiography and cardiomyocyte function assessment. Our data revealed that HFD-feeding compromised myocardial contractile function (fractional shortening, cardiomyocyte peak shortening, maximal velocity of shortening/relengthening and duration of relengthening) and intracellular Ca2+ handling, which were significantly attenuated in the ETAKO. Echocardiography revealed increased left ventricular mass an...
Abstract 12248: B Lymphocyte Deficiency Attenuates Cold-Induced Elevation of Blood Pressure
Authors: Xiuqing Wang, Ryan Stormont, Zhongjie Sun
Journal: Circulation (2011)

Background & Objective. The major function of B lymphocytes is to produce antibodies and cytokines. The purpose of this study was to determine if B cells play a role in the pathogenesis of cold-ind...
Improved Survival In Adults With Mixed-Phenotype Acute Leukemia Following Stem Cell Transplantation (SCT): A Single Centre Experience
Authors: Mallikarjun Kalashetty, Bakul I. Dalal, Kristine J Roland, Yasser Abou Mourad, Michael J. Barnett, Raewyn Broady, Donna L. Forrest, Donna E. Hogge, Alina S. Gerrie, Stephen H. Nantel, Maryse Power, Kevin W. Song, Heather J. Sutherland, Cynthia L. Toze, Thomas J. Nevill, John D. Shepherd, Sujaatha Narayanan
Journal: Blood (2013)
Abstract 1747: Acute Effect of Oral Flavonoid-Rich Dark Chocolate Intake on Coronary Circulation by Transthoracic Doppler Echocardiography in Healthy Adults
Authors: Yumi Shiina, Kwangho Lee, Miyuki Kawakubo, Yukiko Sekine, Maiko Takahashi, Rei Yajima, Yu Wakatsuki, Taichi Murayama, Koki Nakamura, Masao Daimon, Nobusada Funabashi, Issei Komuro
Journal: Circulation (2007)

Purpose: To assess the acute effects of the oral intake of flavonoid-rich dark chocolate on coronary circulation, we measured coronary flow velocity reserve (CFVR) by noninvasive transthoracic Doppler echocardiography (TTDE) in healthy adult subjects in comparison to no-flavonoid white chocolate intake.  Materials and Methods: The study was a randomized, single-blind design conducted for 2 weeks in 39 healthy adults (mean age 29.7±3.9 years, range 23– 40 years). Subjects were randomly assigned a daily intake of either flavonoid-rich dark chocolate (Cacao polyphenol 550 mg/day, 200 kcal) or no-flavonoid white chocolate (Cacao polyphenol 0 mg/day, 140 kcal) as a control. CFVR was recorded by TTDE, and assessed at baseline and after 2 weeks of intake. At the same time, we also assessed serum asymmetric dimethylarginine (ADMA), 8-isoprostanes, and malondialdehyde-modified low density lipopro-tein (MDA-LDL) as markers of oxidative stress, in addition to blood pressure, and blood lipids. We evaluated the acute effect of oral flavonoid-rich dark chocolate intake on coronary circulation by multiple regression analysis considering these parameters.  Results: Flavonoid-rich dark chocolate consumption significantly improved CFVR (3.38±0.49 before intake, 4.28±0.85 after intake; p  Conclusion: Flavonoid-rich dark chocolate intake had acute effects in improving coronary circulation in healthy adults, as compared with no-flavonoid white chocolate, independent of changes in oxidative stress parameters, blood pressure and lipid profile.
Abstract A105: Mechanisms of overcoming intrinsic resistance to gemcitabine in pancreatic ductal adenocarcinoma through redox modulation
Authors: Huaiqiang Ju, Takshi Gocho, Mitzi Aguilar, Zhuo-Nan Zhuang, Jie Fu, Min Wu, Katsuhiko Yanaga, Peng Huang, Paul Chiao
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) usually develops intrinsic and extrinsic resistances to gemcitabine, and the mechanisms are not well understood. Here we found gemcitabine treatment induced NOX-derived ROS generation through the increase of p22-phox expression via NF-kappaB activation. As ROS levels increased, nuclear translocation of Nrf2 stimulated transcription of cytoprotective antioxidant genes, specially, those encoding enzymes that catalyze glutathione production to reduce elevated ROS as one of intrinsic resistance counter measures. RNAi depletion of Nrf2 enhanced the sensitivity to gemcitabine in multiple PDAC cells. The addition of beta–phenylethyl isothiocyanate (PEITC) inhibited the ROS detoxification process by reducing glutathione levels; this, in turn, increased the efficacy of gemcitabine in vitro and in vivo. Thus, our results provide novel pre-clinical knowledge in pancreatic cancer chemoresistance, and combination with a redoxmodulating compound to deplete antioxidants can overcome intrinsic gemcitabine resistance. Our study suggests that a redox-mediated pathway that contributes to the intrinsic resistance of PDAC to gemcitabine and provides a basis for developing strategies to preferentially kill PDAC cells through ROS-mediated mechanism. The combination of gemcitabine and PEITC demonstrates a coordinated and selective cytotoxic effect against pancreatic cancer cells and a new avenue for further clinical studies of this deadly disease. Thus, this combination strategy could prove valuable as a cancer treatment. Note: These results were published in Molecular Cancer Therapeutics as a full-length article before the online publication of this abstract. Citation information: Mechanisms of Overcoming Intrinsic Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma through the Redox Modulation. Huai-Qiang Ju, Takeshi Gocho, Mitzi Aguilar, Min Wu, Zhuo-Nan Zhuang, Jie Fu, Katsuhiko Yanaga, Peng Huang, and Paul J. Chiao. Mol Cancer Ther March 2015 14:788-798. doi:10.1158/1535-7163.MCT-14-0420. Citation Format: Huaiqiang Ju, Takshi Gocho, Mitzi Aguilar, Zhuo-Nan Zhuang, Jie Fu, Min Wu, Katsuhiko Yanaga, Peng Huang, Paul Chiao. Mechanisms of overcoming intrinsic resistance to gemcitabine in pancreatic ductal adenocarcinoma through redox modulation. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A105.
Abstract 15923: Indoxyl Sulfate Increases Ly6Chigh Inflammatory Monocytes and Enhanced Neointima Formation in Response to Vessel Injury
Authors: Shunsuke Ito, Yoko Yagi, Sumie Goto, Hideyuki Yamato, Mizuko Osaka, Masayuki Yoshida
Journal: Circulation (2012)

[Background] Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. Indoxyl sulfate, a uremic toxin, is associated with vascular disease and mortality in CKD patient...
Abstract B115: PD0332991 induces epithelial to mesenchymal transition in pancreatic cancer
Authors: I. E. Imasuen, A. Jesse Gore, M. Korc
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains the fourth leading cause of cancer-related death among both men and women in the United States, with an overall survival rate of 6%. Moreover, the median survival in PDAC is only five to six months, underscoring the need for improved therapies. Cancer cell proliferation and cell cycle dysregulation is a major target in cancer treatment. Cyclin-dependent kinase (CDK) and cyclin inhibitors act as anti-proliferative agents that target upregulated cell-cycle progression proteins in various tumors. The efficacy of PD0332991, a CDK4/6 inhibitor, is currently being investigated in clinical trials in patients with retinoblastoma protein (Rb)-positive breast, ovarian, and non-small-cell lung cancers, but has not yet been examined for treatment in PDAC. We have recently shown that PD0332991 inhibits cell proliferation in PDAC cell lines but initiates epithelial to mesenchymal transition (EMT) and induces cancer cell invasion in some of these cells. Using human PDAC tissues and tissues from genetically engineered mouse models (GEMMs) of PDAC, we also recently showed that loss of RB function is common in PDAC. To further assess the therapeutic potential of PD0332991 in PDAC, we now compared its effects in PANC-1 human PDAC cells (wild-type RB1 gene) and in murine PDAC cells devoid of RB that were derived from a GEMM expressing mutant KRASG12D (KRC mice). In PANC-1 cells, PD0332991 (1 μM) inhibited proliferation and induced EMT. By contrast, in KRC 1022-4 murine PDAC cells, the same concentration of PD0332991 induced EMT without altering proliferation. Moreover, removal of PD0332991 from the incubation medium reversed its growth inhibitory actions in PANC-1 cells, but did not reverse its effects on EMT in either PANC-1 or KRC 1022-4 cells. Taken together, these findings suggest that PD0332991 may exert long-term deleterious effects in patients with PDAC limiting its potential therapeutic use in this deadly cancer, except in conjunction with agents that target EMT. This study was supported, in part, by NCI grant R37-075059 to MK. Citation Format: I. E. Imasuen, A. Jesse Gore, M. Korc. PD0332991 induces epithelial to mesenchymal transition in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B115.
Structural and functional insights into sclerostin-glycosaminoglycan interactions in bone
Authors: Juliane Salbach-Hirsch, Sergey A. Samsonov, Vera Hintze, Christine Hofbauer, Ann-Kristin Picke, Martina Rauner, Jan-Philip Gehrcke, Stephanie Moeller, Matthias Schnabelrauch, Dieter Scharnweber, M. Teresa Pisabarro, Lorenz C. Hofbauer
Journal: Biomaterials (2015)
Abstract 14813: eNOS induced Oxidative Stress exacerbates Pressure-Overload induced LV Hypertrophy and Dysfunction and masks Beneficial Effects of eNOS Overexpression
Authors: Elza D van Deel, Martine de Boer, Rio P Juni, Daphne Merkus, Rien van Haperen, Rini de Crom, An L Moens, Dirk J Duncker
Journal: Circulation (2011)

Although initiated as a compensatory mechanism, pressure-overload induced left ventricular hypertrophy (LVH) increases the risk for heart failure. Previously, we showed endothelial Nitric Oxide syn...
A Phase I Study Of The Oral Btk Inhibitor ONO-4059 In Patients With Relapsed/Refractory B-Cell Lymphoma
Authors: Simon Rule, Nimish Shah, Gilles Andre Salles, Lionel Karlin, Franck Morschhauser, Louis Terriou, Martin JS Dyer, Claire Hutchinson, Chris Fegan, Guillaume Cartron, Tomasz Knurowski, James G Wright, Andrew J Saunders, Hideyuki Honda, Andrew Mazur, Toshio Yoshizawa, Kazuhito Kawabata, Joseph TP Birkett
Journal: Blood (2013)
Antibody to the Rheumatoid Arthritis Nuclear Antigen
Authors: Michael A. Catalano, Dennis A. Carson, James C. Niederman, Paul Feorino, John H. Vaughan
Journal: Journal of Clinical Investigation (1980)

Most patients with seropositive rheumatoid arthritis, and a variable but lesser percentage of normal subjects, have precipitating antibodies to a nuclear antigen, rheumatoid arthritis nuclear antigen, present in Epstein-Barr virus-infected human B lymphoblastoid cells. We have used a sensitive indirect immunofluorescence assay for antibody to rheumatoid arthritis nuclear antigen in a study of patients with infectious mononucleosis and healthy control subjects. Of 110 sera from normal, college-age cadets, 58 were from individuals without prior Epstein-Barr virus infection, as indicated by the lack of antibody to viral capsid antigen. All of these also lacked activity to rheumatoid arthritis nuclear antigen. 52 sera were positive for antibody to viral capsid antigen, and antibody to rheumatoid arthritis nuclear antigen was present in 26 (50%) of these. In 67 sequential sera from 11 college-age students with infectious mononucleosis who became positive for antibody to rheumatoid arthritis nuclear antigen, only 2 were positive during the 1 mo. Thereafter the incidence and titers increased progressively through the 1st yr after infection. This time-course resembled that for the development of antibody to Epstein-Barr nuclear antigen, another transformation antigen in Epstein-Barr virus-infected B lymphocytes. The development of positivity for both was much later than that of antibody to the structural viral capsid antigen, which in the current study was always positive by 1 wk. Thus, antibody to rheumatoid arthritis nuclear antigen is present in a large proportion of normal individuals and can now be clearly ascribed, from both in vivo and in vitro studies, to prior infection with Epstein-Barr virus.
Gastric Stump Carcinoma Following Billroth II Resection for Peptic Ulcer Disease
Authors: G. Schnapka, F. Hofstaedter, K. Schwamberger, H. Reissigl
Journal: Endoscopy (1984)

40 gastric stump carcinomas have been investigated. The results are compared with 72 gastric carcinomas without preceding Billroth II resection. The aim of this study was to contribute to our knowledge about the pathogenesis of gastric stump carcinoma. The mean age of patients with gastric stump carcinoma and with carcinoma without preceding Billroth II resection is identical. The age distribution, too, is similar in both groups. Furthermore the time of the Billroth II resection for benign peptic ulcer shows no correlation with the appearance of the gastric stump carcinoma, which suggests that there is no constant time lag between Billroth II resection and stump carcinoma. The histological investigation of the tumor-free gastric mucosa shows similar alterations in the two groups compared. Intestinal metaplasia and cystic dilatation seems to be more common in the gastric mucosa after Billroth II resection as compared with the non-tumorous mucosa of patients without preceding Billroth II resection. But the grade of nuclear atypia in non-tumorous mucosa is identical in both groups. Interestingly enough, the frequency of the main types of gastric cancer, intestinal carcinoma and diffusely infiltrating carcinoma is very similar. Thus, both the epidemiological and histological data seem to indicate that the pathogenesis of gastric carcinoma is very similar to that of gastric carcinoma without preceding gastric surgery. The Billroth II resection does not seem to be a main factor in pathogenesis, but may have co-factorial significance.
Drug discovery: Screening natural products and synthetic libraries by cell based assays
Authors: Geetanjali Sachdeva, Gardella Roberta, James McMahon, Suresh Arya
Journal: Clinical Cancer Research (2007)

B14  To reiterate the present day mantra, one way to discover new drug-like molecules is to screen libraries of natural products or synthetic compounds, followed by optimization. . For rational screening, it is important to design mechanism-based assays that allow for simple interpretation and provide guidance for further validation. As a start, we have elected to screen libraries with transcriptional apparatus as the target. More specifically and as a proof of principle, the search is designed to find drug-like lead molecules that modulate a viral promoter (HIV LTR) and a cellular promoter (hTERT). The mechanism of activation of the HIV promoter and regulation of the hTERT promoter are known in sufficient detail to design mechanism-based assays. For transcription as the target, the assays must meet the following criteria: no or low basal promoter activity, inducibility or suppression with known inducers or suppressors, and stability of the indicator or responder cell line. To accomplish these goals we created genetic clones with the indicator GFP gene linked to a viral or the cellular promoter, each in turn linked to the puromycin resistance gene for selection. Human HeLa cells were transfected with the genetic clones and cells selected in puromycin to obtain stable tranfectants. Several cell clones of each set derived from limiting dilution selection were tested for basal activity and response to the viral transactivator Tat (viral LTR set) and to c-Myc transcriptional factor (hTERT set). The cell clones that had low basal activity and responded to the activators were selected. Selected clones were maintained in culture for several generations and checked for stable integration and expression of the transgene. Some of these cell clones have been adapted for growth and responsiveness in 96-well formats and now are ready for screening NCI’s natural products and synthetic libraries. The intent is to find molecules that will up regulate the HIV promoter for over expression in gene therapy with lentiviral vectors or down regulate it for HIV suppression. Similarly, upregulators of the hTERT promoter will be useful in aging and down regulators in cancer. Combining the two is our model of cancer cell selective expression of pro-apoptotic gene and anti-survival shRNA where Bax gene and Bcl2 shRNA are driven by the viral LTR (silent without Tat) and Tat is driven the hTERT promoter.
Claudin 4 overexpression in serous ovarian cancer is mediated by promoter hypomethylation and is a potential therapeutic target.
Authors: Babak Litkouhi, Margarita Aponte, James G. Smedley, Bruce McClane, Joseph Kwong, Samuel C. Mok, Elizabeth I. Garner
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5504 

Objectives: Microarray analysis demonstrated that claudin 4 ( CLDN4 ) was significantly overexpressed in serous ovarian cancers (SOC). This study sought to validate the overexpression of CLDN4 , determine the mechanism behind its overexpression, and demonstrate that CLDN4 is a potential therapeutic marker for targeted treatment of SOC. Methods: CLDN4 overexpression in SOC tissue and cell lines was compared to normal ovarian surface epithelium (NOSE) using quantitative reverse-transcription PCR (qRT-PCR ), immunohistochemistry (IHC), and Western blotting. The methylation status of the CLDN4 promoter was identified using methylation-specific PCR (MS-PCR). Cell cultures not expressing CLDN4 were treated with 5-Aza-2′-deoxycytidine (AZA) (a demethylating agent) and CLDN4 expression was compared to non-treated cultures. Five SOC cell lines were treated with purified CPE ( clostridium perfringens enterotoxin - a specific ligand for CLDN4) alone and in combination with paclitaxel, and dose-response curves and IC50 values were generated. Results: CLDN4 was significantly overexpressed in SOC tissue (p=0.02) and cell lines (p=0.02). qRT-PCR expression correlated with Western blot intensity (r=0.71, p=0.003) and with IHC scores (p=0.03). MS-PCR demonstrated that the CLDN4 promoter was unmethylated in all eight OC cell cultures expressing CLDN4. Similarly, the CLDN4 promoter was unmethylated in 12 OC tissue samples, all of which overexpressed CLDN4. Conversely, the CLDN4 promoter was methylated in all three NOSE and in all five SOC cell cultures not expressing CLDN4. Furthermore, treatment with AZA increased CLDN4 expression in cell lines not expressing CLDN4. CPE exhibited rapid cytotoxic activity in cell cultures expressing CLDN4. The degree of its cytotoxic effect is inversely related to the level of CLDN4 expression. Conclusions: CLDN4 is overexpressed in serous ovarian cancer and this has promising potential for targeted therapy using CPE. As in other cancers, CLDN4 overexpression in SOC is due to promoter hypomethylation, another potential treatment target. Ongoing investigation is examining the activity of CPE in xenograft mice with SOC. Additional work is focusing on the ability of C-CPE (the non-cytotoxic receptor-binding terminus of CPE) to behave as a chemosensitizing agent in SOC cell lines.
Abstract 3687: Long-term Clinical and Hemodynamic Performance of the Medtronic Hancock II versus the Carpentier-Edwards Perimount Aortic Bioprostheses
Authors: Vincent Chan, Alexander Kulik, Anthony Tran, B-Khanh Lam, Paul Hendry, Fraser Rubens, Thierry Mesana, Marc Ruel
Journal: Circulation (2009)