bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 830: Angiotensin converting enzyme inhibitor and angiotensin receptor blocker suppress obesity-related colonic preneoplastic lesions in male C57BL/KsJ-db/db obese mice
Authors: Kubota Masaya , Shimizu Masahito , Yasuda Yoichi , Sakai Hiroyasu , Tanaka Takuji , Moriwaki Hisataka 
Published: June 2012

Abstract
Obesity and related metabolic abnormalities, including a state of chronic inflammation and oxidative stress, are risk factors for colon cancer. Dysregulation the renin-angiotensin system (RAS) also plays a critical role in obesity-related metabolic disorders and certain types of carcinogenesis. In the present study, we examined the effects of angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB), both of which target RAS, on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were given 4 weekly subcutaneous injections of AOM (15 mg/kg body weight) and then they received drinking water containing captopril (ACE inhibitor, 5 mg/kg/day) or telmisartan (ARB, 5 mg/kg/day) for 7 weeks. At sacrifice, administration of captopril and telmisartan significantly reduced the total number of colonic premalignant lesions, aberrant crypt foci and β-catenin accumulated crypts, compared with the control untreated-group. Both agents decreased the expression levels of TNF-α mRNA on the colonic mucosa of experimental mice. The expression levels of TNF-α, COX-2, IL-1β, IL-6, and PAI-1 mRNAs on the visceral fat were also decreased by administration of these agents. In addition, captopril and telmisartan significantly decreased the levels of urinary 8-OHdG, a surrogate marker of oxidative damage to DNA, in the experimental mice. These findings suggest that both ACE inhibitor and ARB suppress obesity-related colon carcinogenesis by attenuating chronic inflammation and reducing oxidative stress. Targeting the dysregulation of RAS might be, therefore, one of the effective strategies for the chemoprevention of obesity-related colon cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 830. doi:10.1158/1538-7445.AM2011-830
Abstract 838: Suppression of constitutive and interleukin-6-inducible activation of signal transducer and activator of transcription 3 in human prostate cancer cells by diallyl trisulfide, a cancer chemopreventive constituent of garlic
Authors: Chandra-Kuntal Kumar , Singh Shivendra V. 
Published: June 2012

Abstract
Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor implicated in prostate cancer development. The STAT3 is constitutively active in a large fraction of human prostate cancer cells and clinical prostate cancer specimens. Hyperactivity of STAT3 is associated with advanced prostate cancer. Furthermore, STAT3 activation promotes survival and inhibits apoptosis in prostate cancer cells. Agents that are safe but can either suppress activation of STAT3 or overcome STAT3 activation for their anticancer effects are attractive for prevention and treatment of prostate cancer. Natural products have attracted tremendous attention for the discovery of novel agents potentially useful for prevention and treatment of human cancers. The present study demonstrates that diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of processed garlic, inhibits phosphorylation (activation) of STAT3 in prostate cancer cells in culture and in vivo. Exposure of DU145 and LNCaP human prostate cancer cells to growth suppressive and pharmacologically-relevant concentrations of DATS (20 and 40 μmol/L) resulted in suppression of constitutive (DU145) as well as interleukin-6 (IL-6)-induced (LNCaP) phosphorylation of STAT3 (Tyr705). The DATS-mediated suppression of STAT3 activation correlated with inhibition of Janus-activated kinase 2 phosphorylation. Constitutive and/or IL-6-induced nuclear translocation of pSTAT3 as well as STAT3 dimerization was also inhibited markedly on treatment with DATS in both cell lines. Inhibition of prostate cancer development in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice by gavage with DATS correlated with a visible decrease in the levels of pSTAT3. Interestingly, the IL-6-mediated activation of STAT3 failed to confer protection against proapoptotic response to DATS in either cell line. Likewise, the DATS-mediated inhibition of cell migration was either not affected or minimally reversed by the IL-6 treatment or ectopic expression of constitutively active STAT3. In conclusion, the present study indicates that DATS treatment suppresses STAT3 phosphorylation in prostate cancer cells in culture and in vivo, but activation of this oncogenic transcription factor is largely dispensable for cellular responses to DATS. Ability of DATS to overcome STAT3 activation is a therapeutic advantage for this chemopreventive agent. This study was supported by the USPHS grant 2 RO1 CA113363-06, awarded by the National Cancer Institute.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 838. doi:10.1158/1538-7445.AM2011-838
Abstract 848: Prevention of colitis-associated colorectal cancer with 8-hydroxydeoxyguanosine
Authors: Ock Chan Young , Kim Eun-Hee , Hong Kyung Sook , Hahm Ki-Baik , Chung Myung-Hee 
Published: June 2012

Abstract
Colitis-associated colorectal cancer (CAC) is one of clear examples of inflammation-carcinogenesis sequence, based on which strict control of colitis provides the right rationale of the intervention of anti-inflammatory drug on the chemoprevention. We have shown that 8-OHdG, which traditionally has been acknowledged as a marker of oxidative stress-related mutagenesis, could paradoxically exerted potent anti-inflammatory and anti-oxidant action in various inflammation models (Ock CY et al, Biochem Pharmacol, 2010). Based on the fact that Rac1 binds and activates STAT3 which is significantly up-regulated in inflammatory bowel disease (IBD) as well as CAC, we hypothesized that attenuation of Rac1-STAT pathway by exogenous 8-OHdG treatment may block inflammatory bouts in dextran sodium sulfate (DSS) induced colitis and can reduce carcinogenesis promoted by azoxymethane (AOM) followed by DSS ingestion. First we have checked whether exogenous 8-OHdG can ameliorate IBD, for which IL10 knock-out mice, IBD prone mice, are designed to ingest 5% DSS in tap water ad libitum for a week, and 8-OHdG (50, 100, or 150 mg/kg) is given intraperitoneal route daily. Treatment with 8-OHdG significantly reduced complication rates, pathologic grade of inflammation and edema compared with DSS only group. On pathogenic basis, the expressions of various inflammatory mediators such as TNF-α, IL-6, COX-2 and iNOS were decreased, as well as Rac1 activity and phosphorylation of STAT3 in 8-OHdG treated group in a dose-dependent manner. Next, in order to document the chemoprevention effects of 8-OHdG, mice were injected AOM (10 mg/kg) intraperitoneally followed by drinking 2.5% DSS for a week, after which AIN76 diet that contains 0.03 % and 0.06 % 8-OHdG was given for 20 weeks. As results, mice which consumed 8-OHdG-contained diet were significantly reduced tumor incidence and tumor multiplicity. Increased activity of Rac1 and phosphorylation of STAT3 with AOM plus DSS administration were significantly attenuated in 8-OHdG treatment group. These results were further validated with human colorectal adenocarcinoma cell line Caco-2 in vitro model. Conclusively, for the very first time, we clearly showed chemopreventive effect of exogenous 8-OHdG against CAC. Since 8-OHdG, one of well-known by-products generated by oxidative stress, paradoxically blocks inflammation-carcinogenesis sequence in colitis-associated cancer model, 8-OHdG could be a promising chemopreventive drug for the patient suffering from longstanding and extensive IBD, high risk group for CAC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 848. doi:10.1158/1538-7445.AM2011-848
Abstract 850: Selenium compounds activate ATM-dependent DNA damage response via the mismatch repair protein hMLH1 in colorectal cancer cells
Authors: Qi Yongmei , Schoene Norberta W. , Lartey Frederick M. , Cheng Wen-Hsing 
Published: June 2012

Abstract
Epidemiological and animal studies indicate that selenium supplementation suppresses risk of colorectal and other cancers. The majority of colorectal cancers are characterized by a defective DNA mismatch repair (MMR). Here, we have employed the MMR-deficient HCT 116 colorectal cancer cells and the MMR-proficient HCT 116 cells with hMLH1 complementation to investigate the role of hMLH1 in selenium-induced DNA damage response, a tumorigenesis barrier. The ATM (ataxia telangiectasia mutated) protein responds to clastogens and initiates DNA damage response. We show that hMLH1 complementation sensitizes HCT 116 cells to methylseleninic acid, methylselenocysteine, and sodium selenite via reactive oxygen species and facilitates the selenium-induced oxidative 8-oxoguanine damage, DNA breaks, G2/M checkpoint response, and ATM pathway activation. Pretreatment of the hMLH1-complemented HCT 116 cells with the antioxidant N-acetylcysteine or 2,2,6,6-tetramethylpiperidine-1-oxyl or the ATM kinase inhibitor KU55933 suppresses hMLH1-dependent DNA damage response to selenium exposure. Selenium treatment stimulates the association between hMLH1 and hPMS2 proteins, a heterodimer critical for functional MMR, in a manner dependent on ATM and reactive oxygen species. Taken together, the results suggest a new role of selenium in mitigating tumorigenesis by targeting the MMR pathway, whereby the lack of hMLH1 renders the HCT 116 colorectal cancer cells resistant to selenium-induced DNA damage response.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 850. doi:10.1158/1538-7445.AM2011-850
Abstract 900: Tissue CA125 expression levels as a biomarker of endometrial cancer
Authors: Zhou Shu-Feng , He Shu-Ming 
Published: June 2012

Abstract
Serum CA125 has been recognized as a biomarker of gynecological tumors. However, serum CA125 detection is not very sensitive and specific in the diagnosis of cervical and endometrial carcinoma. This study has investigated the endometrial CA125 expression in patients with endometrial polyps, hyperplasia and carcinoma in comparison with normal endometrium. A total of 242 subjects were recruited into this study and they were classified into six groups, namely proliferative phase endometrium (n = 24), secretory phase endometrium (n = 21), non-functional endometrial polyps (n = 24), simple hyperplasia (n = 24), complex hyperplasia (n = 26), and endometrial carcinoma (n = 126). An immunohistochemistry method was used to detect endometrial CA125 expression. The results showed that there were significant differences in CA125 levels between normal and diseased endometrium, with significantly increased CA125 expression in patients with endometrial polyps, complex hyperplasia, and carcinoma compared to those with normal endometrium. There was only a weak CA125 expression in normal endometrium and simple endometrium hyperplasia. There were significant differences in CA125 expression levels between patients with non-functional endometrial polyps, simple hyperplasia, and complex hyperplasia (χ2 = 9.652, p &lt; 0.005). In endometrial carcinoma group, there was a significant difference in CA125 expression among patients with pathological grade I, II and III of endometrial carcinoma (χ2=11.975, p &lt; 0.01), while there was no significant difference in CA125 expression between grade I and grade II carcinoma (χ2=3.698, p &gt; 0.05). These findings indicate that endometrial CA125 expression can be used as a reliable biomarker in the diagnosis and clinical staging of endometrial carcinoma in Chinese women.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 900. doi:10.1158/1538-7445.AM2011-900
Abstract 903: Expression of estrogen receptor beta together with aromatase predicts survival in non-small cell lung cancer
Authors: Mah Vei , Marquez Diana , Alavi Mohammad , Maresh Erin L. , Yoon Nam , Horvath Steve , Bagryanova Lora , Fishbein Michael , Chia David , Pietras Richard , Goodglick Lee 
Published: June 2012

Abstract
Lung cancer continues to be the leading cause of cancer mortality. There is increasing evidence suggesting estrogens and estrogen signaling play a significant role in lung cancer pathophysiology. Estrogen receptors (ER) alpha and beta are expressed in normal lung and many non-small cell lung cancers. Previously we found that in women 65 years and older with non-small cell lung cancer (NSCLC), higher aromatase levels in tumor cells conferred a worse prognosis for survival. Here we examine whether ER alpha and ER beta levels in conjunction with aromatase can further define different patient groups with respect to survival outcomes and possible treatment regimens. Methods: Immunohistochemistry was performed on a high-density tissue microarray with marker data and clinical information available for 378 patients. Patients were subcategorized by gender, age, smoking status and tumor histology. Survival data was determined using the Cox proportional hazards model and Kaplan-Meier curves. Results: Unlike aromatase, neither ER alpha nor ER beta alone were predictors of survival in NSCLC patients or any subset of these patients examined. However, when coupled with aromatase expression, higher ER beta levels predicted poorer survival in those patients whose tumors expressed higher levels of aromatase. Although this survival difference was present in patients of both genders, it was more pronounced in women &gt; 65 years old, where higher expression of both ER beta and aromatase showed a markedly worse survival rate than that determined by aromatase alone. Conclusion: Combined expression of ER beta with aromatase has predictive value for survival in different gender and age subgroups of NSCLC patients. This predictive value is stronger than each individual marker alone. These results suggest that possibly treatment with aromatase inhibitors alone or combined with estrogen receptor modulators may have benefit in some subpopulations of NSCLC patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 903. doi:10.1158/1538-7445.AM2011-903
Abstract 905: Localization of several potential biomarkers in various types of cancer
Authors: Alegre Ballantines F. , Alegre Melissa M. , Hardy Morgan S. , Robison Richard A. , O'Neill Kim L. 
Published: June 2012

Abstract
DNA salvage pathway enzymes are known to be upregulated both within cancer cells and in the serum of cancer patients. These enzymes include TK1, APRT, HGPRT, and dCK. TK1 has been extensively studied and is known to be a cytosolic enzyme. However, relatively few studies have investigated the localization of the other three salvage pathway enzymes in cancer cells. The purpose of this study was to determine the localization of these salvage pathway enzymes in various types of cancer cells. Cancer cells and normal lymphocytes were embedded and prepared for immunolabeling transmission electron microscopy (TEM). Raji cells, a Burkitt's lymphoma cell line known to express high levels of TK1, were used to optimize the TEM protocol. Using rabbit polyclonal antibodies, we were able to determine where the salvage pathway enzymes are localized in cancer cells. Cancer cell lines studied included Raji, Jurkat (acute T cell leukemia), HL60 (acute promyelocytic leukemia), HT29 (colorectal adenocarcinoma), SW620 (colorectal adenocarcinoma from lymph node), and H460 (large cell lung carcinoma). Normal lymphocytes (both unstimulated and stimulated with PHA) were also embedded and prepared for labeling. An antibody control, and anti-Macrophage marker, was used as an isotype control to detect non-specific binding. We observed that DNA salvage pathway enzymes were localized in distinctive parts throughout the cytoplasm, the cell membrane, and the nucleus. The expression of APRT appeared very similar to the expression of TK1 and it was visualized in approximately the same patterns. The same appeared to be true for HGPRT and dCK, but with much lower level of expression than TK1 and ARPT. In several cases, these salvage pathway enzymes appeared to localize near the nuclear pores, as well as other parts of the nuclear membrane. These enzymes also appeared dispersed throughout the cytoplasm, and in some cases formed clusters, especially near the cellular membrane, possibly indicating exocytosis routes. There was no significant difference between the various types of cancer cell lines in the localization of these enzymes Our normal lymphocyte controls show markedly lower expression, while the secondary only and isotype controls showed no staining. Further research is needed to determine the mechanisms of this localization and the role of these enzymes in tumor cell growth.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 905. doi:10.1158/1538-7445.AM2011-905
Abstract 916: BRCA1 mutations impair breast epithelial differentiation through upregulation of the transcriptional repressor Slug
Authors: Proia Theresa A. , Keller Patricia , Gupta Piyush , Klebba Ina , Jones Ainsley , Sedic Maja , Gilmore Hannah , Tung Nadine , Naber Stephen , Schnitt Stuart , Lander Eric , Kuperwasser Charlotte 
Published: June 2012

Abstract
Tumor histopathology is a strong predictor of patient mortality, although the molecular and cellular factors that are responsible for this phenotypic diversity remain poorly understood. Women with inherited mutations in the BRCA1 gene have increased risk for the development of breast cancer, but also exhibit a specific predisposition for the development of aggressive basal-like breast cancers. Here we study the interplay between inherited mutations in BRCA1 and tumor differentiation by examining the regulation of progenitor cell fate in disease-free breast tissues from BRCA1 mutation carriers. We demonstrate for the first time that cell populations derived from patients harboring mutations in BRCA1 (BRCA1mut/+) give rise to tumors with increased basal differentiation, relative to cells obtained from BRCA1+/+ patients. Molecular analysis of disease-free breast tissues from BRCA1mut/+ patients revealed significant defects in epithelial progenitor cells that are present prior to cancer incidence. Moreover, we discovered that the transcriptional repressor Slug is an important functional regulator of human breast progenitor cell lineage commitment and differentiation and that it is aberrantly expressed in BRCA1mut/+ tissues and cells prior to neoplastic transformation. In addition, Slug expression is necessary for the increased basal-like phenotypes prior to and following neoplastic transformation. These findings demonstrate that the genetic background of patient populations, in addition to affecting incidence rates, significantly impacts progenitor cell fate commitment and therefore, tumor phenotype.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 916. doi:10.1158/1538-7445.AM2011-916
Abstract 939: Mechanistic basis of tamoxifen-associated development of endocrine resistance in breast cancer
Authors: Bergamaschi Anna , Katzenellenbogen Benita 
Published: June 2012

Abstract
Many estrogen receptor-positive breast cancers respond well initially to endocrine therapies, but often develop resistance during treatment with SERMs such as tamoxifen. We have reported that the 14-3-3 family member and conserved protein, 14-3-3ζ, is up-regulated by tamoxifen and that high expression correlated with an early time to disease recurrence. However, the mechanism by which tamoxifen up-regulates 14-3-3ζ and may promote the development of endocrine resistance is not known. Our findings reveal that the tamoxifen up-regulation of 14-3-3ζ results from its ability to rapidly down-regulate a microRNA that specifically targets 14-3-3ζ. The levels of 14-3-3ζ and this microRNA were always inversely correlated, with 14-3-3ζ being elevated and the microRNA being at a low down-regulated level in tamoxifen-resistant breast cancer cells. Of note, down-regulation of the microRNA was selectively elicited by tamoxifen but not by other SERMs such as raloxifene or by the estrogen receptor down-regulator ICI182,780 (Fulvestrant). Reducing the cellular level of 14-3-3ζ by either antagomiR blockade of the tamoxifen suppression of the microRNA or by elevation of the intracellular level of the microRNA by over-expression resulted in decreased cell proliferation and colony formation, increased apoptosis, and very importantly, restoration of the growth inhibitory effectiveness of SERMs in endocrine-resistant breast cancer cells. Restoration of responsiveness to endocrine therapy was also accompanied by markedly reduced activation of HER2, EGFR, and MAPK signaling, key components in endocrine resistance. Thus, we identify tamoxifen down-regulation of a microRNA, and consequent elevation of the key survival factor 14-3-3ζ, as a mechanistic basis of tamoxifen-associated development of endocrine resistance. These findings suggest that therapeutic approaches that increase expression of this microRNA should be considered to down-regulate 14-3-3ζ and enhance the effectiveness of endocrine therapies. Furthermore, the observed differential effects of the two SERMs, tamoxifen and raloxifene, in regulation of this microRNA and 14-3-3ζ, may assist in understanding differences in the activities of these SERMs, as seen in the STAR breast cancer prevention trial and in other clinical trials. (Supported by a grant from The Breast Cancer Foundation to BSK and a postdoctoral fellowship from the Department of Defense (W81XWH-09-1-0398) to AB.)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 939. doi:10.1158/1538-7445.AM2011-939