bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5447: Breast cancer chemoprevention by ‘Jamun’, the Indian blackberry: Potential mechanisms
Authors: Aqil Farrukh , Jeyabalan Jeyaprakash , Munagala Radha , Ravoori Srivani , Sharma Ramjee , Sidana Jasmeen , Singh Inder P. , Gupta Ramesh C. 
Published: August 2012

Abstract
Dark-colored berries are gaining increasing attention lately for their chemopreventive and chemotherapeutic activities. Jamun (Syzygium cumini L.), the Indian blackberry is perhaps the only berry that has the diversity of anthocyanins of blueberry and abundance of ellagic acid present in black raspberry. We previously reported chemoprotective activities in jamun pulp extract and powder in vitro and short-term in vivo studies (Aqil et al. AACR 2010, Vol. 51, Abst. # 5688). Here we report anti-cancer potential of jamun pulp powder against estrogen mediated breast cancer and the role of miRNAs and other targets in the disease inhibition. Groups of female ACI rats were given AIN-93M diet or diet supplemented with jamun pulp powder (5%, w/w). Two weeks later, animals from each group were treated with subcutaneous silastic implants of 17β-estradiol (1.2 cm; 9 mg). Additional groups of animals received control or experimental diet in the absence of estrogen. Diet and water were provided ad libitum. Twelve weeks later animals were palpated weekly for the mammary tumors, and all groups were euthanized when tumors incidence reached over 90% in control group. Compared to control, jamun-supplemented diet delayed the first tumor appearance by 21 days, and significantly reduced the tumor incidence (65% vs 96%), tumor burden (313±95 vs 661±123 mm3) and tumor multiplicity (1.8±0.3 vs 4.2±0.4 tumors/rat). The experimental diet also significantly reduced the estrogen-associated growth of pituitary prolactinomas, circulating prolactin and estradiol levels and the mammary cell proliferation (PCNA) markers. Mechanistically, the jamun diet significantly offset estrogen-associated increases in mammary cell proliferation, ER-α and cyclin D1 as determined by western blot analysis. We have recently identified ‘miRNA signature’ associated with estrogen treatment (Munagala et al. AACR 2011, Vol. 52, Abst. # 155). All miRNAs that were either significantly overexpressed (miR-182 and miR-375) or underexpressed (miR-127 and miR-206) as a result of estrogen treatment were significantly protected by intervention with the jamun diet. Targets for these miRNAs remain to be identified. Together, our data show that jamun significantly offset estrogen-mediated alterations in i) mammary cell proliferation; ii) ER-α; iii) cyclin D1, and iv) candidate miRNAs, and that the modulation of these biomarkers correlated with the reduction in mammary carcinogenicity. (Supported by CA-125152, CA-118114 and Agnes Brown Duggan Endowment).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5447. doi:1538-7445.AM2012-5447
Abstract 5448: Common targets of epigenetic dysfunction in distinct target tissues of arsenic and cadmium induced malignant transformation
Authors: Severson Paul L. , Tokar Erik J. , Vrba Lukas , Waalkes Michael P. , Futscher Bernard W. 
Published: August 2012

Abstract
Arsenic and cadmium are known human carcinogens and rank as number one and seven respectively on the Agency for Toxic Substances and Disease Registry (ATSDR) substance priority list. Accumulating evidence suggests that long-term exposure to arsenic or cadmium induces epigenetic dysfunction and this effect may be an important aspect of their carcinogenic activity. To this end we analyzed the epigenetic dysfunction associated with arsenic or cadmium induced malignant transformation of immortalized urothelial and prostate epithelial cells. Using methyl-DNA immunoprecipitations coupled to human promoter microarrays as well as Sequenom MassArray, we found that arsenic and cadmium mediated malignant transformation of immortalized urothelial and prostate epithelial cells produced thousands of DNA methylation changes. Many of the DNA hypermethylation events appear to be localized to individual genes whereas others cluster into groups that are within large genomic regions on the order of 100kb. Significant aggregates of DNA hypermethylation events occur within the protocadherin and HOX gene clusters. Intersecting the arsenic induced hypermethylation events from the two distinct models results in an overlap of 113kb of DNA which represents roughly 100 genes. This overlap is significantly more than expected by chance, suggesting these genes are targeted for aberrant DNA methylation in both models of arsenic induced malignant transformation. A similar result is seen in the cell lines transformed by cadmium, and the cadmium induced DNA hypermethylation events are highly concordant with the hypermethylation profiles induced by arsenic. Most of the DNA hypermethylated regions found in the arsenic or cadmium transformed cells are also targets of aberrant DNA hypermethylation in human bladder tumors. Comparing the hypermethylated regions from our models to publicly available H3K27me3 ChIP-seq data from embryonic stem cells revealed that the targets of DNA hypermethylation fall disproportionately within H3K27me3 domains of human stem cells. H3K27me3 chromatin immunoprecipitations coupled to real-time PCR confirmed that the promoters of candidate genes NPR3 and LTK are marked with H3K27me3 in normal and immortalized cells before becoming DNA hypermethylated in the arsenic transformed cells. This H3K27me3 data supports the previously discovered association between H3K27me3 marked regions of normal cells and DNA hypermethylation in malignant cells. All together, these observations suggest commonality in the mechanisms of epigenetic change induced by carcinogenic metals.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5448. doi:1538-7445.AM2012-5448
Abstract 5453: The effect of ovarian hormones on the induction of mammary tumors induced by the environmental pollutant 6-nitrochrysene
Authors: Sun Yuan-Wan , Krzeminski Jacek , Aliaga Ceser , Manni Andrea , Amin Shantu , El-Bayoumy Karam 
Published: August 2012

Abstract
Exposure to ovarian hormones is the most widely recognized risk factors for breast cancer. However, hormones alone do not fully address the majority of the risk for this disease. Increasing data have linked environmental factors such as radiation, chemical pollutants and diet to the incidence of breast cancer. Humans are often exposed to a combination of multiple risk factors. Thus, the potential of the interaction between the environment and hormones is critical to assess the risk of breast cancer. The goal of the present study is to examine the role of ovarian hormones on the induction of mammary tumors by 6-nitrochrysene (6-NC), a representative environmental pollutant. We have previously demonstrated that 6-NC is one of the most potent mammary carcinogen in the rat. Thus, 6-NC (25 µmol in 500 µL trioctanoin) was administered orally to both female intact and ovariectomized (ovax) Sprague-Dawley rats at age of 30 days once a week for 8 weeks. Tumors in the intact animals was first detected at week 4 (incidence 8%) and tumor incidence reached 50% at week 18 after the last administration of 6-NC. On the contrary, in the group of ovax rats tumors were first observed at week 8 (4% incidence) and the incidence remained the same at week 22 after the last dose of 6-NC administration. Further evidence to support this hormone dependence is also observed in a separate group of ovax rats which received both 6-NC at the same dose described above and estradiol (E2) pellet implantation (twice, 5 mg/90 days); mammary tumor incidence was comparable to that observed in intact animals treated with 6-NC. No tumors were found in vehicle (trioctanoin) treated intact and ovax control groups. In this study, we showed for the first time that ovarian hormones are essential in the development of mammary tumors induced by this environmental pollutant; the molecular mechanisms are being explored. Support: NCI RO1 35519.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5453. doi:1538-7445.AM2012-5453
Abstract 5454: Genotoxic consequences of exposure to mixtures of food-derived chemical carcinogens
Authors: David Rhiannon M. , Gooderham Nigel J. 
Published: August 2012

Abstract
It has been shown that mutagenic chemicals can form naturally in foods during cooking. Examples include Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon generated by incomplete combustion of organic substances such as lipids, leading to contamination of numerous foodstuffs (Lijinski and Shubik, Science 1964, 145, 53), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine that is formed during the cooking of meat (Murray, et al. J Chromatog 1993, 616, 211), and glycidamide (GA) is the ultimate genotoxic metabolite of acrylamide (AC), which forms when foods, such as potatoes and cereals, are cooked at temperatures exceeding 100°C, in a reaction between the amino acid asparagine and reducing sugars that are naturally present in these foods (Tornqvist, Adv Exp Biol Med 2005, 561, 1). These chemicals have individually been shown to be genotoxic but the biological consequences of exposure to mixtures of these chemicals have not been systematically examined. The aim of the current study was to examine the biological response of MCL-5 cells (a metabolically competent human lymphoblastoid cell line) to mixtures of these genotoxic chemicals at concentrations that are relevant to human exposure (mM to sub-nM). Cells were exposed to the chemicals individually or in mixtures for 24h and mutagenicity was assessed through resistance to trifluorothymidine at the thymidine kinase (TK) locus and 6-thioguanine at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus. The mixture exposures gave modified dose-response curves from the individual chemicals, with increased mutation frequency (MF) at some low concentration combinations that were not mutagenic individually, and decreased MF at some combinations of higher concentrations that did produce a mutation response individually. Responses also differed between the TK and HPRT loci, with a higher MF observed for high concentration combinations at HPRT compared to TK. Ethoxyresorufin-O-deethylase (EROD) activity was measured and was found to correspond to the MF at the TK locus suggesting the involvement of CYP1A family in the mutation response. These data suggest that mixtures of genotoxic chemicals produce different mutation responses to the individual chemicals. The increase in MF at some low concentration combinations where the individual chemicals are not genotoxic is of significance when considering the carcinogenic potential of food.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5454. doi:1538-7445.AM2012-5454
Abstract 5457: Chlorinated drinking water alters carcinogenesis in a mice model of colon cancer
Authors: Sasada Tatsunari , Hinoi Takao 
Published: August 2012

Abstract
Purpose: The gastrointestinal tract is constantly exposed to vast numbers of commensal bacteria and inflammatory product. The diet and enteric environment has been implicated in the pathogenesis of enterocolitis and colon cancer. Probiotic Lactbacilli modify the enteric microflora and are thought to have a beneficial effect on enterocolitis, eventually on colon cancer. We conducted this study to evaluate the effects of chlorinated drinking water which was used in general institutions. Experimental design: Mouse stains carrying colon epithelium-preferential Apc mutation (CPC;Apc mice), that show sporadic colorectal adenomas and carcinomas are used in this study. Nine of Eighteen CPC;Apc mice were consumed chlorinated drinking water (chlorinate concentrations of 10.0 mg/L) and 9 consumed tap water (chlorinate concentrations of 0.7 mg/L) for 25 week. Body weight was measured weekly. Faecal microbial analysis was performed. At sacrifice, the small and large bowel were histologically assessed. Results: Chlorinated drinking water strongly prevented intestinal tumorigenesis in terms of polyps formation in distal portion of small intestine. However, in colon we observed an increase in numbers and volumes of tumors. Body weight gain was more favorable by chlorine treated. Conclusions: These results show for the first time the efficacy and associated mechanisms of chlorinated drinking water feeding against spontaneous intestinal tumorigenesis in the CPC;Apc mice suggesting its chemopreventive potential against intestinal cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5457. doi:1538-7445.AM2012-5457
Abstract 5460: Effects of ethanol exposure during involution on mouse mammary gland
Authors: Garofalo Jennifer-Marie , Bowers Dawn , Browne Richard , MacQueen Brian , Mashtare Terry , Masso-Welch Patricia A. 
Published: August 2012

Abstract
Mammary gland involution represents a discrete developmental time point when the breast may be particularly susceptible to risk factors associated with mammary carcinogenesis. One dietary carcinogen which has been shown to affect breast cancer risk in women is ethanol; as little as one drink per day can increase breast cancer risk by 10%. The purpose of the current study was to determine if ethanol exposure during involution affects mammary tumor development or progression in the FVB-MMTV-Her2/Neu transgenic mouse. Dams were fed isocaloric liquid diets containing 0, 0.5, 1 or 2% ethanol from day 1 of involution (weaning at day 21 of lactation) until day 4, 9 or 14 post-weaning. Short-term effects of ethanol on the progression of involution were assessed. No significant difference in mouse weight, or organ weights (spleen, liver or kidney), was seen between groups. Lobular regression (decrease in ducts per lobule) occurred similarly in all dietary groups, in parallel with an increase in average adipocyte size. No difference in leukocyte infiltration was seen between dietary groups. Proteomic analysis and tumor studies are ongoing.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5460. doi:1538-7445.AM2012-5460
Abstract 5461: Role of the NLRP3 inflammasome in the development and drug resistance of malignant mesothelioma
Authors: Shukla Arti , Miller Jill M. , Hillegass Jedd M. , MacPherson Maximilian B. , Beuschel Stacie L. , Pass Harvey I. , Mossman Brooke T. 
Published: August 2012

Abstract
Inflammation plays an important role in development of various cancers including malignant mesothelioma (MM). We have shown that asbestos activates NOD-like receptor protein 3 (NLRP3), a component of the inflammasome in human macrophages. As chronic asbestos exposure is a key risk factor for the development of MM, we hypothesized that inflammasome-mediated inflammation might underlie the pathogenesis of this cancer. To show the involvement of NLRP3 in asbestos-induced mesothelioma, we demonstrated that exposure of asbestos to immortalized human mesothelial cells (LP9/hTERT), a cell type responsible for origin of MM, caused mRNA increase and activation of NLRP3 as measured by caspase-1 activation and IL-1β release. Inhibition of NLRP3 by siRNA caused significant decreases in NLRP3 mRNA levels as well as asbestos-induced IL-1β release in medium. On the other hand, human MM lines and tumor tissues showed significantly decreased levels of NLRP3 and caspase-1 as compared to LP9 or matching normal tissues respectively. Our findings suggest that initial exposure to asbestos causes increased mRNA levels and activity of NLRP3, which may help in MM development by promoting mesothelial cell transformation. However, tumor development culminates in MM with decreased NLRP3 protein and increased drug resistance which may be due to caspase-1 inactivation. Thus NLRP3 may be an appropriate target for therapy of MM, especially in combination with cytotoxic chemotherapeutic drugs and IL-1 receptor antagonists. This study is supported by a Meothelioma Applied Research Foundation (MARF) grant (AS) and by NIEHS grants T32 ES07122 (BM).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5461. doi:1538-7445.AM2012-5461
Abstract 5463: Serum aminotransferases and alkaline phosphatases as biomarkers of hepatotoxicity in sprague-dawley rats exposed to silver nanoparticles
Authors: Patlolla Anita K. , Tchounwou Paul B. 
Published: August 2012

Abstract
Nanoparticles are small scale substances (&lt;100 nm) used in biomedical applications, electronics, and energy production. Increased exposure to nanoparticles being produced in large scale industry facilities elicits concerns for the toxicity of certain classes of nanoparticles. In particular, the oral toxicity of silver nanoparticles is of concern to ensure public and consumer health. Due to the intensive commercial application of silver nanoparticles (Ag-NPs), health risk assessment of this nanoparticle is of great importance. The previous in vitro studies demonstrated that Ag-NPs caused toxicity in various cell-lines. However, toxicity of Ag NPs in vivo is largely lacking. This study evaluated the effect of Ag-NPs on the activities of specific liver enzymes such as aminotransferases (GOT/GPT), and alkaline phosphatases (ALP) which may be useful as biomarkers of hepatotoxicity. Four groups of five male rats each weighing approximately 80 + 2 g were orally administered once a day for five days with doses of 5, 25, 50 and 100 mg/kg BW of silver nanoparticles. A control group was also made of 5 rats. At the end of the experiment, serum samples were collected following standard protocols. The data obtained from the hepatotoxicity study clearly show that highest two dose 50 and 100 mg/kg of silver nanoparticles has statistically significantly increased the activity of serum aminotransferases (GOT and GPT) and alkaline phosphatases (ALP) when compared to control. The results demonstrate that Ag-NPs have the potential to induce hepatotoxicity in Sprague-Dawley rats. Our result does not imply that silver nanoparticles should be banned from use but more in vivo studies with histopathological characterization should be designed to confirm the results of this study.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5463. doi:1538-7445.AM2012-5463
Abstract 555: A role for XMRV in prostate tumor promotion in vivo
Authors: Comeaux Brennen P. , Zolochevska Olga , Figueiredo Marxa 
Published: August 2012

Abstract
Xenotropic murine leukemia virus-related virus (XMRV) is a retrovirusclosely related to murine leukemia viruses, which cause a variety of cancersand immunological and neurological diseases in mice. Whether XMRV plays a rolein cancer and other diseases remains controversial; some studies show apossible association, but there is currently no evidence that the virus is acausal agent for disease. Our hypothesis was that the 3′ long terminal repeat(LTR) from the XMRV genome is responsible for its oncogenic activity inprostate cells. We chose three regions from the XMRV 3′ LTR and tested thepotential of these regions in transactivating a cellular gene promoter whosehomolog is transactivated by MMLV in mouse cells. We examined thetransactivation potential in pre-cancerous and a panel of cancerous prostateepithelial cells. Our results showed that for certain 3′LTR regions inducenearly full transactivating activity, while others might comprise inhibitoryregions. Therefore, to better understand the mechanism by which the XMRV 3′ LTRregions might be inducing or inhibiting transactivation, we tested theirability to transactivate cellular genes related to transformation. We used asreporters plasmids containing binding sites for cellular transcription factors.The results showed several similarities in transactivation, suggesting commonactivation pathways for 3′LTR transactivating activity. Finally, we tested ifXMRV infection could enhance oncogenicity potential of prostate precancerousand cancerous cell lines. We examined this in vitro by assessing the rate of colonyformation in soft agar, and in vivo, using xenograft assays. The resultssuggested that cell lines infected with XMRV had enhanced in vitro colonyformation, as well as enhanced in vivo growth, however, addition of anothertumorigenic genetic alteration was required in conjunction with XMRV-infectionto induce enhanced tumor growth. Our data suggests that the XMRV 3′LTR may havea transactivating activity on cellular genes, and that XMRV stimulatepromotion/progression and not ‘initiation’ of tumorigenesis. These results arenovel since they represent for the first examinations of the role of XMRV intumorigenesis of prostate epithelial cell lines in vitro and in vivo andexaminations of the 3′LTR context of the virus upon transactivation of cellulargenes as a potential mechanism of cellular transformation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 555. doi:1538-7445.AM2012-555