tbuckley/cabot-search huggingface dataset:
Abstract 1790: Caloric restriction can increase the efficacy of radiation in both hormone-sensitive and hormone-resistant prostate cancers by downregulating the IGF-1R pathway
Authors: Sunny Y. Han, Tu D. Dan, Tiziana De Angelis, John Y. Han, Mak Sarich, Peter Carroll, Karen Knudsen, Adam Dicker, Nicole L. Simone
Journal: Cancer Research (2015)

Abstract Locally advanced prostate cancers (LAPC) are aggressive, have poor prognosis, and are associated with high recurrence rates and conversion to castrate resistance. The molecular underpinnings of LAPC are being investigated to identify novel therapeutics. Animal models have shown that caloric restriction (CR) can potentially prevent the initiation of prostate cancer. We propose that CR may be used as a novel therapeutic intervention to enhance outcomes of radiation treatment by altering the molecular profile of prostate tumors. To assess the effect of CR with radiation in vivo, eighty 6 week old male nude mice were injected with LNCaP (hormone sensitive) or PC3 (hormone refractory) tumor cells. Once tumors were palpable, mice were randomized to be treated with one of 4 conditions: ad libitum (AL) diet, 8Gy of radiation (RT), 30% reduction in caloric intake (CR), or CR+RT. CR was associated with significant reduction in tumors. After PC3 tumor injection, compared with AL, the mice had a 22% reduction in tumor size with radiation, 77% with CR (p&amp;lt;0.01 by Student's t-test) and an 80% reduction with CR+RT (p&amp;lt;0.01). After LNCaP tumor injection, compared with ad libitum, the mice had a 49% reduction in tumor size with CR and a 55% reduction with CR+RT (p&amp;lt;0.01). Tissue evaluation of mice treated with CR or CR+RT from both the LNCaP and PC3 models revealed decreased proliferation via Ki-67 and increased apoptosis with cleaved caspase-3 levels. In addition, significant downregulation of multiple members of the IGF-1R pathway was seen, including downregulation of IGF-1R, IRS-1, PI3K and pAKT. Serum evaluation revealed decreased IGF-1:IGF-BP3 in serum. For the first time, we have shown that the efficacy of radiation can be increased by decreasing calories by 30% in both hormone-sensitive and hormone-refractory prostate cancer models. Future clinical trials for both hormone-sensitive and hormone-resistant prostate cancers should consider the innovative use of CR to augment standard cancer therapy as it has the potential to change the biology of tumors and enhance the opportunity for clinical benefit. Citation Format: Sunny Y. Han, Tu D. Dan, Tiziana De Angelis, John Y. Han, Mak Sarich, Peter Carroll, Karen Knudsen, Adam Dicker, Nicole L. Simone. Caloric restriction can increase the efficacy of radiation in both hormone-sensitive and hormone-resistant prostate cancers by downregulating the IGF-1R pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1790. doi:10.1158/1538-7445.AM2015-1790
Abstract 832: The Farnesoid X Receptor (FXR) Antagonizes Oxidized LDL Receptor, LOX-1, Activation
Authors: Douglas Harnish, Ashleigh Hahn, Helen Hartman, Christine Huard, Robert Martinez, Paige Mahaney, Mark Evans, Songwen Zhang
Journal: Circulation (2007)

The nuclear hormone receptor farnesoid X receptor (FXR) plays a critical role in the regulation of enterohepatic circulation and lipid homeostasis and may also positively impact vascular inflammation and endothelial function through the antagonism of oxidized LDL receptor, LOX-1, activation. LOX-1 is a endothelial membrane bound scavenger receptor that upon ligand binding stimulates NF-κB and MAPK pathways leading to adhesion molecule and inflammatory gene expression with subsequent nitric oxide inhibition. Since LOX-1 is activated by oxLDL, LOX-1 expression was monitored in LDLR −/− mice fed a western diet. Hepatic LOX-1 mRNA was significantly induced by 7 days on the western diet compared to chow fed controls. Moreover, this LOX-1 induction was dose dependently inhibited with increasing concentrations of a potent synthetic FXR ligand WAY-362450 (FXR-450; 1–30 mg/kg po) as were downstream LOX-1 dependent genes, VCAM-1 and ICAM-1. The regulation of LOX-1 was FXR-specific since another oxLDL hepatic scavenger receptor, CD36, expression was not affected by FXR-450. To determine whether this signaling pathway was active in other settings, the FXR mediated regulation of LOX-1 was studied in the diabetic mouse strain, KKAy. Both hepatic and renal LOX-1 expression was inhibited by 30 mg/kg FXR-450 after 7 days of dosing on a chow diet and resulted in the reduction of serum soluble LOX-1 levels as well. Renal gene profiling studies indicated that FXR-450 stimulated genes involved in nitric oxide production, including DDAH-1, ASS-1 and GTPCH that were all confirmed to be induced in the KKAy mouse model. Since the nitric oxide synthase antagonist ADMA stimulates LOX-1 expression, we postulated that the positive impact of FXR-450 was due to the decrease in local ADMA concentrations via DDAH-1, ASS-1 and GTPCH inductions. In support of this, ADMA mediated induction of LOX-1 was also inhibited by FXR-450 treatment. Therefore, these results identify a novel cross-talk between FXR and LOX-1 signaling pathways through their co-ordinate modulation of the nitric oxide pathway and suggest that FXR agonists may have a beneficial impact on vascular inflammation and endothelial function.
Abstract 14461: How Does Perhexiline Modulate Myocardial Energetics and Ameliorate Redox Stress?
Authors: Doan T Ngo, Nigel E Drury, Domenico Pagano, Michael P Frenneaux, John D Horowitz
Journal: Circulation (2011)

Introduction: Perhexiline (Perhx) exerts anti-ischemic effects via mechanisms that may include: 1) inhibition of myocardial carnitine palmitoyl transferases, and associated substrate shift with con...
Serum Biomarkers of Inflammation, Fibrosis, and Cardiac Function in Facilitating Diagnosis, Prognosis, and Treatment of Anti-SSA/Ro–Associated Cardiac Neonatal Lupus
Authors: Amit Saxena, Peter M. Izmirly, Sung Won Han, Paraskevi Briassouli, Tania L. Rivera, Hua Zhong, Deborah M. Friedman, Robert M. Clancy, Jill P. Buyon
Journal: Journal of the American College of Cardiology (2015)
Abstract 14005: Body Surface Potential Mapping Improves Diagnosis of ST-Elevation Myocardial Infarction in Patients With Significant Left Main Coronary Artery Stenosis Presenting With Acute Chest Pain
Authors: Michael J Daly, Mark T Harbinson, Jennifer A Adgey
Journal: Circulation (2011)

Non-invasive diagnosis of acute myocardial infarction (AMI) associated with significant left main coronary artery stenosis (LMCAS) is challenging, with characteristic 12-lead ECG abnormalities of S...
Modulation of radiation-induced γH2AX expression by the histone deacetylase inhibitor valproic acid
Authors: David Cerna, Hideaki Dote, Kevin Camphausen, Philip J. Tofilon
Journal: Cancer Research (2005)

5680   A number of histone deacetylase (HDAC) inhibitors have been shown to enhance tumor cell radiosensitivity. In contrast to most other HDAC inhibitors, valproic acid (VPA) crosses the blood brain barrier and can also be chronically administered with minimal toxicity. This suggested that VPA combined with radiotherapy may be of potential as a brain tumor therapy. Exposure of U251 glioma cells to VPA before and after irradiation enhanced their radiosensitivity with a dose enhancement factor of 1.5 as determined by a clonogenic survival assay. However, the mechanism through which VPA and other HDAC inhibitors enhance tumor cell radiosensitivity has not been delineated. To begin to address the mechanism responsible for radiosensitization, we have investigated the effects of VPA on γH2AX expression in irradiated U251 glioma cells. H2AX, a variant of histone H2A, contributes to the regulation of cellular radioresponse. Specifically, after irradiation H2AX is phosphorylated to form γH2AX at the sites of DNA double strand breaks (DSBs). It is generally thought that γH2AX acts to concentrate and retain other repair proteins at the induced DSBs. γH2AX can be detected after irradiation as intranuclear foci. Whereas VPA had no effect on the initial level of radiation-induced γH2AX foci, at 24h after irradiation the number of cells expressing γH2AX was significantly greater in VPA treated cells. VPA exposure also delayed the dispersal of foci containing BRCA1, 53BP1 and NBS1, which associate with γH2AX within the repair foci. To determine whether the delayed dispersal of γH2AX in irradiated cells was associated with VPA-induced histone hyperacetylation, histones were isolated, separated on AUT gels and γH2AX levels determined by immunoblot analysis. In VPA treated cells, irradiation resulted in the formation of both γH2AX and an acetylated form of γH2AX. At 24h, however, essentially only the acetylated form of γH2AX was detectable. These data indicate that the γH2AX foci remaining in the VPA treated cells at 24 h after irradiation are comprised primarily of the acetylated form. Thus, the results of this study suggest that VPA-induced acetylation of γH2AX plays a role in the delayed dispersal of this protein after irradiation, which then may affect the dispersal of other proteins involved in DSB repair. Moreover, these data suggest that altered DSB metabolism is involved in VPA-induced radiosensitization.
Five-Year Follow-Up After Sirolimus-Eluting Stent Implantation
Authors: Giora Weisz, Martin B. Leon, David R. Holmes, Dean J. Kereiakes, Jeffrey J. Popma, Paul S. Teirstein, Sidney A. Cohen, Hong Wang, Donald E. Cutlip, Jeffrey W. Moses
Journal: Journal of the American College of Cardiology (2009)
Abstract 006: Fitness Status Influences the Paradoxical Association Between BMI and Mortality Risk
Authors: Peter Kokkinos, Jonathan Myers, Charles Faselis, Raya Kheirbek, Helen Sheriff, John Peter Kokkinos, Andreas Pittaras, Michael Doumas
Journal: Circulation (2013)

Introduction: In some populations, recent evidence supports a higher mortality risk in individuals with relatively low body mass index (BMI), and lower risk in some overweight or obese individuals. However, the role of fitness in this puzzling relationship, termed as the obesity paradox, has not been fully explored. Hypothesis: We assessed the hypothesis that fitness attenuates the BMI-mortality risk paradoxical association. Methods: The association of exercise capacity and mortality risk in 18,228 individuals (mean age: 58±11) was assessed. Three fitness categories were formed based on the 33 rd and 66 th percentiles of exercise capacity (METs) achieved: Low-Fit (≤6 METs; n=6,072); Moderate-Fit: 6.1-8.5 METs; n=6,158); and High-Fit: &gt;8.5 METs; n=5,998). Individuals were also classified based on BMI as Normal-Wt (BMI 18.5-24.9); Over-Wt (BMI: 25-29.9); Moderate-Obese (BMI: 30-34.9) and Obese (BMI ≥35). Results: There were 4,770 deaths (median follow-up 10.1 years). After controlling for age, risk factors and medications, we observed a paradoxical association between BMI categories and mortality risk (p&lt;0.001 for trend). We also observed an inverse and graded association between fitness status and mortality for the entire cohort and within BMI categories, with reductions in risk ranging from approximately 30% to 60% (p&lt;0.001). We then assessed mortality risk based on fitness status within each BMI category, using the Normal-Wt/High-Fit individuals as the reference group. A paradoxical BMI-mortality risk association was evident in all fitness categories. However, in Low-Fit individuals the risk was significantly increased within each BMI category (hazard ratios (HR): 2.26; 1.7; 1.7 and 1.76 for Normal-Weight, Over-Wt; Moderate-Obese and Obese categories, respectively; p&lt;0.001 for all comparisons). However, in Moderate-Fit individuals, a significantly higher risk was observed only in the Normal-Wt category (HR: 1.58; p&lt;0.001). Finally, in High-Fit individuals, mortality risk was significantly lower in Over-Wt (HR: 0.79; p=0.03) and Moderately Obese categories (HR: 0.58; p&lt;0.001). Conclusions: These findings suggest that the paradoxical association between BMI and mortality risk is strongly modulated by fitness status.
Detection of Compound BCR-ABL Mutations in TKI Resistant CML Patients Including a Novel K245N Mutation Associated with Primary Nilotinib Resistance By Employing a Newly Developed Cost Effective BCR-ABL Sequencing Protocol
Authors: Zafar Iqbal, Tanveer Akhtar, Afia M Akram, Muhammad Khalid, Ijaz Husssain Shah, Aamir Aleem, Muhammad Khalid, Javed Iqbal, Zeba Aziz, Muhammad Absar, Jamil Amjad Hashmi, Mehmood Husssain Qazi, Ahmad Mukhtar Khalid, Muhammad Farooq Sabar, Sajjad Karim, Mahmood Rasool, Aamir Mahmood, Ammara Tariq Gill, Giuseppe Saglio, Mudassar Iqbal
Journal: Blood (2014)
Abstract 3680: Comparison of Intracoronary Stenting Versus Medical Therapy in Patients with Symptomatic Myocardial Bridging
Authors: Subrie Abedallhadi, Prabhakara Kunamneni, Nitin Barman, Michael C Kim, Prakash Krishnan, Samin Sharma, Annapoorna S Kini
Journal: Circulation (2006)
High LYVE-1 positive lymphatic vessel numbers are associated with axillary lymph node metastases and poor outcome in breast cancer
Authors: P. Bono, V.-M. Wasenius, J. Lundin, D. G. Jackson, H. Joensuu
Journal: Journal of Clinical Oncology (2004)

9518 Background: The clinical significance of intratumoral or peritumoral lymph vessel density is not known. LYVE-1, a lymphatic endothelium specific hyaluronan receptor, is a novel lymphatic vessel marker which is expressed on lymph vessel endothelial cells of both normal and neoplastic tissues. Methods: We investigated expression of LYVE-1 by means of immunhistoochemistry in a series of 180 unilateral, invasive ductal breast carcinomas, in order to assess the correlation between the density of lymph vessels, the incidence of lymph node metastases and clinical outcome. Results: A minority (12%) of breast carcinomas had intratumoral lymph vessels, whereas peritumoral lymph vessels were identified in almost all cases (94%). No significant association was found between the number of LYVE-1 positive vessels and the number of CD31 or VEGFR-3 (vascular endothelial growth factor receptor-3) positive vessels. The number of metastatic axillary lymph nodes increased in parallel with increasing lymph vessel counts (P= 0.033). A higher than the median lymph vessel count at the tumor periphery was significantly associated with unfavorable distant disease-free survival (DDFS) and overall survival. Women with high peritumoral lymph vessel density had only 58% (95% CI, 46 to 70%) 5-year DDFS as compared with 74% (66 to 83%) among those with a low peritumoral lymph vessel density (P=0.0088). In contrast, the presence of intratumoral lymph vessels was associated with neither axillary nodal status nor survival. Lymph vessel density was not an independent prognostic factor in a multivariate survival analysis. Conclusions: A high peritumoral lymph vessel density is associated with the presence of frequent axillary node metastases and a poor outcome in invasive ductal breast cancer. No significant financial relationships to disclose.
Clinical Monoclonal B Lymphocytosis (cMBL), Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL): Diagnostic Criteria, Features At Diagnosis and Natural History
Authors: Rodrigo Santacruz, Julio Delgado, Tycho Baumann, Maria Rozman, Martha Aymerich, Magda Pinyol, Arturo Pereira, Cristina Royo, Alba Navarro, Cristina Lopez, Anna Carrió, Emili Montserrat
Journal: Blood (2013)
Inhibition of epidermal growth factor receptor with gefitinib (‘Iressa’, ZD1839) improves the response to ionizing radiation in bladder cancer cell lines
Authors: Alexandra J. Colquhoun, S. Pawel Wozniak, Eugene M. Tulchinsky, Marina Kriajevska, J. Kilian Mellon
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

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Approximately 70% of muscle-invasive bladder cancers express the epidermal growth factor receptor (EGFR) and expression is associated with poor prognosis. Recent evidence suggests that irradiation can stimulate EGFR resulting in activation of intracellular cytoprotective signaling cascades. Thus, inhibition of EGFR function, e.g. using a small molecule tyrosine kinase inhibitor (TKI), may be a means of enhancing the radio-responsiveness of bladder tumors. Six bladder cancer cell lines with variable EGFR expression levels were treated with the EGFR-TKI, gefitinib (‘Iressa’, ZD1839), ionizing radiation (IR) or combined gefitinib/IR. Growth inhibition rates were assessed using both MTT and clonogenic assays. Growth inhibition rates determined with IR alone and combined gefitinib/IR were compared to calculate the dose enhancement ratio (DER) achieved with the use of gefitinib in each cell line. Subsequently, EGFR expression levels in each cell line were determined using Western blotting and related to the previously calculated DER. Treatment with gefitinib and IR alone resulted in dose-dependent growth inhibition in all six cell lines (IC50 gefitinib 0.18-2.48 μM). In all six cell lines assessed using clonogenic assay the combination of gefitinib and IR resulted in significantly greater growth inhibition than treatment with either gefitinib or IR alone (Student’s t-test, p=0.001-0.04; DER 1.19-2.00). The enhancement of growth inhibition achieved using combined gefitinib and IR was significant in five of the six cell lines assessed by MTT assay (Student’s t-test, p=0.001-0.03; DER 1.38-2.08). There was no correlation between EGFR expression levels and DERs (Pearson’s correlation; clonogenic assay, r=0.318, p=0.539; MTT assay, r=0.206, p=0.695). Radiosensitization can be achieved in bladder cancer cell lines by the addition of gefitinib to IR. Repetition of these in vitro findings using an in vivo model (work currently underway) would provide sound justification for translating this work into a clinical trial. ‘Iressa’ is a trademark of the AstraZeneca group of companies.
The Role Of Early TP53 Mutations On The Evolution Of Therapy-Related AML
Authors: Terrence Neal Wong, Giridharan Ramsingh, Andrew Young, Dong Shen, Chris Miller, Tamara Lamprecht, Sharon Heath, Robert S. Fulton, Elaine R. Mardis, Li Ding, Peter Westervelt, John Welch, Matthew J. Walter, Timothy Graubert, John F. DiPersio, Timothy J. Ley, Todd E Druley, Richard K Wilson, Daniel C. Link
Journal: Blood (2013)
Hemoptysis Associated with <i>Paragonimus westermani</i>
Authors: Ashima Sahni, Aiyub Patel
Journal: New England Journal of Medicine (2015)

A 49-year-old man who had recently emigrated from Myanmar presented with a 6-month history of rusty brown sputum with hemoptysis. A tuberculin skin test was positive, but sputum smears were negative for acid-fast bacilli, ova, and parasites.
Jelliffe式により算出されたカルボプラチンのクリアランス推定値における血清クレアチニン値0.6mg/dl未満を0.6mg/dlへと調整することの正誤
Authors: Nagao S, Fujiwara K, Kagawa R, Kozuka Y, Oda T, Maehata K, Ishikawa H, Koike H, Aotani E, Kohno I
Journal: Journal of Clinical Oncology (2006)
Anti-erythropoietin receptor monoclonal antibody: epitope mapping, quantification of the soluble receptor, and detection of the solubilized transmembrane receptor and the receptor-expressing cells
Authors: E Morishita, H Narita, M Nishida, N Kawashima, K Yamagishi, S Masuda, M Nagao, H Hatta, R Sasaki
Journal: Blood (1996)
Inhibition of NF-κB decreases androgen receptor expression and prostate cancer growth
Authors: Liying Zhang, Saleh Altuwaijri, Chawnshang Chang, Lishi Chen, Priti Lal, Ruslan Korets, Hans Lilja, William L. Gerald
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

135 

The mechanisms and biochemical pathways that contribute to the development of androgen independent prostate cancer (AIPC) are not well understood. Enhanced activation of androgen receptor (AR) has been proposed as one important mechanism. Therapy resistance is often associated with a marked increase in AR transcripts without gene amplification and activation of NF-κB, which suggests that increased AR and NF-κB expression is a critical event. In this study, we explored the molecular mechanism and the role of NF-κB in regulating AR expression in prostate cancer. We found that NF-κB activates the AR promoter following transient transfection of LNCaP cells. Overexpression of p65/RelA, the active subunit of NF-κB, significantly increases the AR mRNA and protein level and promotes cell proliferation in prostate cancer cells. Ectopic expression of the dominant mutant inhibitor of NF-κB, IκBαM, decreased AR transactivation activity with inhibited AR protein expression. Furthermore, we demonstrated that Pathenolide, an NF-κB inhibitor, inhibited AR expression, p65 expression, PSA secretion and proliferation of prostate cancer cells in both LNCaP and LAPC-4 cells. Overall, our data suggest that NF-κB is able to activate AR expression in prostate cancer cells. The combination of the inhibition of NF-κB and AR may be a novel therapeutic strategy to battle the prostate cancer.
Abstract 13371: CALM2 Mutations Associated With Atypical Juvenile Long QT Syndrome
Authors: Naomasa Makita, Nobue Yagihara, Lia Crotti, Christopher N Johnson, Britt-Marie Beckermann, Daichi Shigemizu, Hiroshi Watanabe, Taisuke Ishikawa, Takeshi Aiba, Elisa Mastantuono, Tatsuhiko Tsunoda, Hidewaki Nakagawa, Yukiomi Tsuji, Takeshi Tsuchiya, Hirokazu Yamamoto, Yoshihiro Miyamoto, Naoto Endo, Akinori Kimura, Kouichi Ozaki, Hideki Motomura, Kenji Suda, Toshihiro Tanaka, Peter J Schwartz, Thomas Meitinger, Stefan Kaab, Wataru Shimizu, Walter Chazin, Alfred L George
Journal: Circulation (2013)

Background: Congenital long QT syndrome (LQTS) is a monogenic predisposition to lethal cardiac arrhythmias.Despite decades of investigation and discovery of multiple responsible genes, a molecular ...
Abstract 1218: Cardiac-specific Overexpression Of Human Phospholipase D2 Induces Myocardial Hypertrophy In Transgenic Mice
Authors: Thomas Kurz, Ulrich Schafer, Olaf Johren, Christof Burgdorf
Journal: Circulation (2007)

Myocardial phospholipase D (PLD), which is downstream to α1-adrenoceptors, endothelin ET-, and angiotensin II receptors, generates the second messengers phosphatidic acid and diacylglycerol which h...
Near-Roadway Air Pollution and Coronary Heart Disease: Burden of Disease and Potential Impact of a Greenhouse Gas Reduction Strategy in Southern California
Authors: Rakesh Ghosh, Frederick Lurmann, Laura Perez, Bryan Penfold, Sylvia Brandt, John Wilson, Meredith Milet, Nino Künzli, Rob McConnell
Journal: Environmental Health Perspectives (2015)

Several studies have estimated the burden of coronary heart disease (CHD) mortality from ambient regional particulate matter ≤ 2.5 μm (PM2.5). The burden of near-roadway air pollution (NRAP) generally has not been examined, despite evidence of a causal link with CHD.We investigated the CHD burden from NRAP and compared it with the PM2.5 burden in the California South Coast Air Basin for 2008 and under a compact urban growth greenhouse gas reduction scenario for 2035.We estimated the population attributable fraction and number of CHD events attributable to residential traffic density, proximity to a major road, elemental carbon (EC), and PM2.5 compared with the expected disease burden if the population were exposed to background levels of air pollution.In 2008, an estimated 1,300 CHD deaths (6.8% of the total) were attributable to traffic density, 430 deaths (2.4%) to residential proximity to a major road, and 690 (3.7%) to EC. There were 1,900 deaths (10.4%) attributable to PM2.5. Although reduced exposures in 2035 should result in smaller fractions of CHD attributable to traffic density, EC, and PM2.5, the numbers of estimated deaths attributable to each of these exposures are anticipated to increase to 2,500, 900, and 2,900, respectively, due to population aging. A similar pattern of increasing NRAP-attributable CHD hospitalizations was estimated to occur between 2008 and 2035.These results suggest that a large burden of preventable CHD mortality is attributable to NRAP and is likely to increase even with decreasing exposure by 2035 due to vulnerability of an aging population. Greenhouse gas reduction strategies developed to mitigate climate change offer unexploited opportunities for air pollution health co-benefits.