bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5435: Tolcapone inhibits catechol-O-methyl transferase-mediated methylation of (-)-epigallocatechin-3-gallate in vivo
Authors: Forester Sarah C. , Lambert Joshua D. 
Published: August 2012

Abstract
Green tea polyphenols (GTP) have been shown to exert anti-cancer effects in vitro and in vivo. Studies suggest that (-)-epigallocatechin-3-gallate (EGCG) is largely responsible for these anti-cancer effects. EGCG reduces lung cancer cell viability in vitro and reduces tumor incidence, multiplicity, and size in vivo. EGCG, however, is rapidly methylated by catechol-O-methyl transferase (COMT), a transformation that may limit its effectiveness in lung cancer prevention. The nitrocatechol drug tolcapone is a potent inhibitor of COMT and is used to mitigate the symptoms of Parkinson's disease. In this study, we examined the effect of tolcapone on the bioavailability of EGCG in male CF-1 mice. Plasma and tissue levels of EGCG and its major methyl metabolites in mice (n = 6) were determined by LC-MS following oral administration of EGCG (100 mg/kg b.w.), tolcapone (30 mg/kg b.w.), or the combination (100 mg/kg b.w. + 30 mg/kg b.w., respectively). In mice treated with EGCG for 720 min, plasma EGCG accounted for 34.6 % of the total (EGCG + methylated metabolites), whereas in mice treated with EGCG plus tolcapone this increased to 65.7 %. In urine, EGCG accounted for 9.4 % of the total, whereas in mice treated with EGCG plus tolcapone this increased to 100 % (metabolites not detected). Similar effects were observed in the organ samples. For example, tolcapone extensively inhibited COMT- mediated methylation of EGCG in the lungs of mice. In conclusion, tolcapone effectively increased the bioavailability of unmethylated EGCG in vivo. The combination, may therefore increase the cancer preventive effects of EGCG. Future work will test the effect of tolcapone on the bioavailability of other GTP, and also determine the effect of tolcapone/GTP combination in animal models of cancer. Funded by NIH grant AT004678.
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 5435. doi:1538-7445.AM2012-5435
Abstract 5437: Blueberries: Conventional cancer prevention
Authors: Kraus Ryan D. , Martinez Andres , Measom Kylie , Gill Matthew , Gaytri Gupta , Garrett Andrew , Robison Richard , O'Neill Kim L. 
Published: August 2012

Abstract
Coronary heart disease and cancer, besides remaining the two leading causes of death in the United States, share another common trait: they can both be attributed to lifestyle choices that increase their risk. Epidemiological studies suggest that the consumption of both an antioxidant and phytochemical-rich diet contribute towards the reduction of heart disease and several cancer types. There has been a substantial amount of interest in Vaccinium corymbosum, also known as blueberries, due to their high antioxidant levels which have been show to help prevent cancer of the colon, breast, and prostate. Blueberries exhibit a high content of both phytochemicals such as flavonoids and tannins; and antioxidants such as phenolic acid and resveratrol. Antioxidants provide protection against oxidative stress, a condition that has been suggested to contribute to a variety of diseases, including atherosclerosis, Parkinson's disease, and cancer. The purpose of this study was to explore the health benefits of organic vs. conventional blueberry consumption by comparing the antioxidant content of their individual components, including pulp, skin, seed, and juice using both the Hydrophilic Oxygen Radical Absorbance Capacity (H-ORAC) and the Lipophilic Oxygen Radical Absorbance Capacity (L-ORAC) assay. High-Performance Liquid Chromatography (HPLC) was also used to identify and quantify the amount of Vitamin C in both the organic and conventional blueberries. Blueberry samples were obtained from local distributors and the assays were replicated with five different lots of blueberries. Results indicated that conventional blueberries (33,388 TE/100g pulp, seed, skin and 607,700 TE/L juice) have higher antioxidant levels than organic blueberries (25,800 TE/100g pulp, seed, skin and 415,608 TE/L juice) across all samples. Conversely, HPLC determined a slightly higher Vitamin C content in the organically grown blueberries (592.879 μg/g) compared to conventional blueberries (386.947 μg/g). These results suggest that conventional blueberries may have a higher health benefit potential in preventing cancer and many other degenerative diseases that plague the world.
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 5437. doi:1538-7445.AM2012-5437
Abstract 5446: Green tea catechin intervention of reactive oxygen species-mediated ERK pathway activation, DNA damage, and chronically-induced breast cell carcinogenesis
Authors: Wang Hwa-Chain R. , Rathore Kusum , Choudhary Shambhunath 
Published: August 2012

Abstract
Long-term exposure to low doses of environmental carcinogens contributes to sporadic human breast cancers. Epidemiologic and experimental studies indicate that green tea catechins (GTCs) may interfere with breast cancer development. We have been developing a chronically-induced breast cell carcinogenesis model wherein we repeatedly expose non-cancerous, human breast epithelial MCF10A cells to physiologically-achievable pico-molar concentrations of environmental carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P), to progressively induce cellular acquisition of cancer-associated properties, as measurable endpoints. The model is then used as a target to identify non-cytotoxic preventive agents effective in suppressing cellular carcinogenesis. Here, we report a two-step strategy that initially used short-term endpoints that were transiently-induced by a single exposure to NNK and B[a]P. These short-term endpoints were used as targets to detect the ability of individual GTC components to block carcinogenesis. We subsequently used long-term endpoints that were constantly-induced by cumulative exposures to carcinogens as targets to verify and compare the activity of individual GTC components in suppressing carcinogenesis. We detected that a single exposure to NNK and B[a]P resulted in elevation of reactive oxygen species (ROS), leading to ERK pathway activation and induction of cell proliferation and chromosomal DNA damage. GTC components, at non-cytotoxic levels, were able to suppress chronically-induced cellular carcinogenesis by blocking carcinogen-induced ROS elevation, ERK activation, cell proliferation, and DNA damage in each exposure cycle. Our model may help accelerate the identification of agents to prevent carcinogenesis induced by long-term exposure to environmental carcinogens, thereby safely and effectively reducing the health risk of sporadic breast cancer.
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 5446. doi:1538-7445.AM2012-5446
Abstract 545: Autocrine growth regulation by PEDF is mediated by ovarian steroid hormones: Implications in the pathogenesis of endometrial carcinoma
Authors: Huang Kuang-Tzu , Pavlides Savvas C. , Mittal Khushbakhat , Blank Stephanie V. , Crawford Susan E. , Gold Leslie I. 
Published: August 2012

Abstract
The angiogenic inhibitor and neurotrophic factor, pigment epithelium-derived factor (PEDF) was first shown in the eye and is now shown to be expressed in a number of tissues and to function in apoptosis and growth inhibition. The importance of PEDF in growth regulation of the endometrium is reflected in PEDF null mice, which develop endometrial hyperplasia. Therefore, we hypothesized that PEDF is decreased in human endometrial carcinoma with loss of growth inhibition. We show by immunostaining (n=44) that PEDF expression is decreased in both stromal and epithelial cells in atypical endometrial hyperplasia (AEH), the precursor to type I endometrial carcinoma (ECA; 80% of all ECAs) and ECA. Whereas PEDF is highly expressed by primary endometrial epithelial cells (EECs) and stromal cells, ECA cells synthesize less protein and stromal cells isolated from malignant endometrium (cancer associated fibroblasts; CAFs) synthesize 80% less PEDF mRNA (n=35) by quantitative real time PCR and less PEDF protein. In addition, whereas exogenous recombinant PEDF inhibits proliferation of ECA cell lines (e.g. HEC-1B by 40%; peak response at 4nM), PEDF antibodies and PEDF siRNA stimulate proliferation suggesting PEDF inhibits cell proliferation in an autocrine manner in the endometrium. Estrogen (E2) stimulates and progesterone (Pg) inhibits proliferation of the endometrium in a cyclical manner. Due to these hormonal growth regulatory effects, E2 induces AEH and Type I ECA and Pg is a successful therapeutic agent for these diseases. Therefore, we further hypothesized that E2 decreases PEDF causing dysreglated growth and conversely, that Pg might inhibit growth by increasing PEDF. Indeed, we show that treatment of the ECA cell lines, HEC-1A, HEC-1B, KLE and primary EECs with E2 decreased PEDF mRNA and protein expression, which was blocked by the estrogen receptor (ER) antagonist, ICI 182,780. In direct contrast, Pg increased PEDF mRNA and protein, which was blocked by the antagonist, RU486. It is notable that the PEDF promoter contains two putative PREs and one ERE thereby justifying these responses. Taken together, our data implicate PEDF as an autocrine hormone-regulated inhibitor of endometrial growth and suggest that the E2-driven decrease in PEDF leads to dysregulated endometrial growth as an important molecular target in the pathogenesis of type I ECA.
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 545. doi:1538-7445.AM2012-545
Abstract 5452: In utero exposure to bisphenol A promotes mammary tumor development in MMTV-erbB-2 transgenic mice
Authors: Ma Zhi-Kun , Cao Xia , Yang XiaoHe 
Published: August 2012

Abstract
Increasing evidence indicates that environmental exposure plays a critical role in breast cancer etiology. Bisphenol A (BPA), the building block of polycarbonate plastics with estrogenic activity, is one of the most common chemicals exposed in daily life. Recent studies suggest a link between BPA exposure and increased breast cancer risk. However, specific conditions and the underlying mechanisms of BPA exposure associated breast cancer risk remain unclear. This study aimed to investigate the effects of in utero exposure to BPA on mammary tumor development in MMTV-erbB-2 transgenic mice, which exemplifies a scenario of gene-environmental interaction. Since erbB-2 is amplified/overexpressed in approximately 30% of breast cancer, which has been associated with poor prognosis and therapeutic resistance, use of this clinically relevant mammary tumor model is of high translational value. In this study, pregnant MMTV-erbB-2 mice were subcutaneously injected with 0, 25 ng, 250 ng and 250 µg/Kg body weight BPA daily between day 13 and day 19 of gestation. We found that in utero exposed mice in the low dose (25 and 250 ng) groups, but not the high dose group (250 µg), displayed earlier vaginal opening and prolonged estrous phase, suggesting a dose dependent pro-estrogenic effect of in utero exposure to BPA. Whole mount analysis showed that mammary glands of mice with in utero exposure to low dose BPA had a longer ductal extension at 6 weeks and increased lateral branching/alveolar structures at 10 weeks, which was more significant in the 250 ng group but less evident in the high dose group. Molecular analysis of mammary tissues at 10 weeks indicated that in utero exposure to BPA increased phosphorylation/activation of erbB-2, EGFR, erbB-3 Erk1/2 and Akt, and expression of erbB-3 and EGFR. Signaling of estrogen receptor (ER) pathway was upregulated concomitantly, as reflected by increased expression and phosphorylation of ERα and upregulation of cyclin D1 and c-myc. More importantly, mice in the 250 ng group but not the high dose group, developed tumor earlier than the mice in the control group, suggesting that dose is a critical factor affecting the outcomes. These data demonstrated that in utero exposure to BPA may promote mammary tumor development in erbB-2 transgenic mice in a dose dependent manner. Concomitant activation of the erbB-2 and ER pathways in the premalignant tissues suggests that induction of ER-erbB-2 crosstalk may play a critical role in mammary tumorigenesis promoted by in utero exposure to BPA, which underscores the significance of gene-environment interaction in early exposure to BPA associated breast cancer risk.
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 5452. doi:1538-7445.AM2012-5452
Abstract 5464: Genotoxicity of multi-walled carbon nanotubes at occupationally relevant doses
Authors: Sargent Linda M. , Reynolds Steven H. , Lowry David , Kashon Michael L. , Benkovic Stanley A. , Salisbury Jeffery L. , Hubbs Ann F. , Young Shih-Houng , Siegrist Katelyn J. , Keane Michael J. , Mastovich John , Bunker Kristin , Sturgeon Jacqueline , Cena Lorenzo , Dinu Cerasela-Zoica 
Published: August 2012

Abstract
Carbon nanotubes represent a creative alternative for applications in medicine as therapeutic vectors, imaging and controlled release of active molecules. Although the low density and small size of carbon nanotubes makes respiratory exposures to workers likely during the production or use of commercial products, the potential genotoxicity of multi-walled carbon nanotubes has not been investigated. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In order to investigate whether genetic damage was unique to SWCNT, we examined mitotic spindle aberrations following dosing of cells to multi-walled carbon nanotubes (MWCNT) at concentrations anticipated in the workplace. Immortalized and primary respiratory epithelial cells were exposed to 0.024, 0.24, 2.4, and 24μg/cm2 carbon nanotubes. The minimal dose of MWCNT considered for this research was based on the permissible exposure limit for particles with an aerodynamic diameter of less than 5 microns (Occupation Safety and Health Administration). MWCNT induced a dose response of disrupted centrosomes, mitotic spindles and aneuploid chromosome number. The data further showed that monopolar mitotic spindles comprised 95% of the disrupted mitoses. The monopolar phenotype of the disrupted mitotic spindles is in sharp contrast to the multi-polar spindle of SWCNT-induced disruption. Three-dimensional reconstructions showed carbon nanotubes integrated with the microtubules, the DNA and within the centrosome structure. The lower doses did not cause cytotoxicity or apoptosis 24 hours after exposure; however, after 72 hours, significant cytotoxicity was observed in the MWCNT-exposed cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is a key event in the progression of cancer and is correlated with tumor stage. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant doses. These results suggest caution should be used in the handling and processing of carbon nanotubes.
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 5464. doi:1538-7445.AM2012-5464
Abstract 5558: Interplay between BRAF, p16, p53, and MIB1 in pediatric low grade gliomas
Authors: Horbinski Craig , Nikiforova Marina N. , Hagenkord Jill , Hamilton Ronald L. , Pollack Ian F. 
Published: August 2012

Abstract
BRAF rearrangements and BRAF V600E point mutations are recurring events in pediatric low-grade gliomas. However, their clinical significance, including possible interactions between these markers and other glioma biomarkers, is unclear. In this study a retrospective cohort of 198 pediatric low-grade gliomas (including 40 treated with adjuvant therapy) was analyzed for BRAF rearrangements, BRAF V600E, p16/CDKN2A deletion, p53 expression, and MIB1 proliferation index. In tumors with BRAF rearrangement, homozygous p16 deletion correlated with shorter PFS (P = 0.04). High MIB1 proliferation index strongly trended toward correlating with worse response to adjuvant therapy (P = 0.06). On multivariate analyses, the two most consistently powerful independent adverse prognostic markers were midline location (P = 0.0001) and p16 deletion (P = 0.03). Tumors with BRAF V600E had a strong trend toward an increased risk for progression (hazard ratio = 2.48, P = 0.07), whereas those with BRAF rearrangement had a milder trend toward reduced risk (hazard ratio = 0.54, P = 0.15). These data suggest that p16 deletion adversely impacts the outcomes of BRAF-driven gliomas; that high proliferation index may be a better marker of progression risk than BRAF; that BRAF rearrangement and BRAF V600E might not necessarily produce comparable outcomes; and that none of these markers is stronger than tumor location in determining prognosis in pediatric low-grade gliomas.
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 5558. doi:1538-7445.AM2012-5558
Abstract 5572: Prognostic significance of TS, TK, OPRT and DPD activities in renal cell carcinoma
Authors: Mizutani Yoichi , Uehara Hiroshi , Fujisue Yutaka , Takagi Shizuko , Nishida Takeshi , Inamoto Teruo , Ubai Takanobu , Nomi Hayahito , Azuma Haruhito 
Published: August 2012

Abstract
Introduction: Thymidylate synthase (TS) and thymidine kinase (TK) are the key enzymes in the de novo and salvage DNA synthetic process, respectively. Orotate phosphoribosyltransferase (OPRT) plays an important role in the de novo pathway of DNA and RNA synthesis. In contrast, dihydropyrimidine dehydrogenase (DPD) is a key enzyme involved in degradation of DNA and RNA. We examined the activities of TS, TK, OPRT and DPD in 83 renal cell carcinomas and normal kidneys and evaluated the clinical significance. Methods: TS, TK, OPRT and DPD activities in non-fixed fresh frozen renal cell carcinomas and normal kidneys were determined enzymatically by the FdUMP binding assay, the DEAE cellulose disc method, the 5-FU phosphorylation assay and the 5-FU degradation assay, respectively. Results: TS activity was 5-fold higher in renal cell carcinoma compared to normal kidney. TS activity in Stage III/IV renal cell carcinoma was 3-fold higher than that in Stage I/II renal cell carcinoma. In addition, the level of TS activity in Grade 3 renal cell carcinoma was 2-fold higher than that in Grade 1 and Grade 2 carcinomas. TK activity was approximately 4-fold higher in normal kidney compared with renal cell carcinoma. TK activity in Stage IV renal cell carcinoma was 2-fold higher than that in Stage I-III renal cell carcinoma. Furthermore, the level of TK activity in Grade 3 renal cell carcinoma was 2-fold higher than that in Grade 1 and Grade 2 carcinomas. OPRT activity was approximately 7-fold higher in renal cell carcinoma compared to normal kidney. OPRT activity in Stage III/IV renal cell carcinoma was 2-fold higher than that in Stage I/II renal cell carcinoma. The level of OPRT activity in Grade 3 renal cell carcinoma was 3-fold higher than those in Grade 1 and Grade 2 carcinomas. DPD activity was approximately 2-fold higher in normal kidney compared to renal cell carcinoma. The higher stage and grade of renal cell carcinoma was, the lower DPD activity was observed. The level of OPRT activity correlated with those of TS and TK activities. However, DPD activity was not associated with TS activity. High TS, TK, OPRT activities and low DPD activity predicted worse prognosis in patients with renal cell carcinoma.Conclusions: The present study has demonstrated that TS, TK, OPRT and DPD activities in renal cell carcinoma correlated with the stage/grade status of renal cell carcinoma. In addition, the levels of TS, TK, OPRT and DPD activities were prognostic parameters in patients with renal cell carcinoma.
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 5572. doi:1538-7445.AM2012-5572
Abstract 5584: Disregulation of phosphorelated Amplified In Breast Cancer3 (AIB3) contributes to poor prognosis and mediates trastuzumab efficacy in breast cancer patients
Authors: Zhang Hao , Dong Hongmei , Chen Yuping , Zhong Xueyun 
Published: August 2012

Abstract
Trastuzumab (Herceptin) is the first line HER2 (ErbB2)/neu-directed therapy for the treatment of patients with metastatic breast cancer. Although the efficacy of trastuzumab depends on the HER2/neu status of the tumour, the single-agent response rate ranges from 12 to 30% and ew patients respond to trastuzumab monotherapy largely due to various resistance mechanisms. Amplifeid In Breast Cancer3 (AIB3) is a transcriptional coactivator. AIB3 plays an important role in embryonic development, adipocyte differentiation, metabolism. AIB3 was initially found to be amplified in subgroup of breast cancer patients. Our previous data using knockout mouse mode combined cell culture indicate that AIB3 plays important role in breast tumorigenesis. Here we report that AIB3 can be phosphorylated by MAPK at S884 site and phosphorylation at S884 of AIB3 dramatically reduced ligand-dependent AIB3 interactions with estrogen receptors when compared with the wild-type unphosphorylated form, although there was a significant increase of interactions with the unliganded receptor. Misexpression of phosphorylated AIB3 was observed in human breast cancer tissues and disregulation of phosphorylated AIB3 was associated with patients’ poor prognosis. Breast cancer is a heterogeneous disease and intrinsic subtypes play an extremely important role in improve on current standards for breast cancer prognosis and prediction of chemotherapy. Noticeably, phosphorylated AIB3 was highly expressed in Her2-enriched subtype of human breast cancer patients, as well as in the mammary tumor of MMTV-Her2 transgenic mice. Mechanism studies reveal that phosphorylated AIB3 alters trastuzumab efficacy in cultured breast cancer cells. The association between pAIB3 and important clinical outcomes confers pAIB3 a significant prognostic marker in breast cancer. Phosphorylated AIB3 as a modulator in ErbB2-MAPK regulating loop represents a potentially novel mechanism for trastuzumab (herceptin) efficacy. The implied interaction between pAIB3 and Her2 suggests the potential of dual targeting of Her2 and pAIB3 as a promising therapeutic approach for personalized breast cancer therapy.
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 5584. doi:1538-7445.AM2012-5584