bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5700: Establishing candidate biomarkers for the pharmacodynamic action of sulforaphane in the breast
Authors: Agyeman Abena , Shaw Patrick , Chaerkady Ragohthama , Tran Quynh , Sutter Thomas , Pandey Akhilesh , Visvanathan Kala , Davidson Nancy , Kensler Thomas 
Published: February 2011

Abstract
The goal of this study is the discovery of biomarkers reflecting the pharmacodynamic action of sulforaphane (SFN), initially in the normal human mammary epithelial MCF10A cell line and then in tissue obtained from healthy patients undergoing reduction mammoplasty surgery. SFN is formed by the hydrolysis of glucoraphanin, a water soluble glucosinolate found in cruciferous vegetables with especially high levels measured in 3 day old broccoli sprouts. Chemoprevention by SFN is achieved in part through the upregulation of cytoprotective enzymes via the Keap1/Nrf2 pathway. Preliminary dose response and time course studies in MCF10A cells established that SFN upregulated cytoprotective genes as indicated by increased levels of NQO1 transcripts, protein and activity. NQO1 induction is dependent on the Keap1/Nrf2 pathway since NQO1 transcripts, protein and activity were enhanced by KEAP1 siRNA knockdown in MCF10As. For the biomarker discovery phase isobaric tag for relative and absolute quantitation (iTRAQ) was used to quantify global protein changes using mass spectrometry. Two independent 8-plex iTRAQ experiments determined the pharmacological actions of SFN on protein expression, compared to a vehicle control, and the genetic regulation of protein expression following knockdown of KEAP1 compared to a non targeting control siRNA. In both experiments protein expression was analyzed at 12, 24, 48, and 72 hour time points after SFN treatment or KEAP1 knockdown. In addition to confirming NQO1 to be a good candidate biomarker, the iTRAQ analysis identified other upregulated candidates to be aldo-keto reductase family 1 member C1 (AKR1C1), DJ-1 protein, and thioredoxin. NQO1 and AKR1C1 transcripts were also elevated in the MCF10A cells, as assessed by microarray assay. Candidate biomarkers identified from microarray and iTRAQ studies reflecting the pharmacodynamic action of SFN in human cells will be analyzed by Western blot, qRT-PCR and enzyme assays in tissue from reduction mammoplasty patients. These women have been randomized in a clinical trial to receive either a broccoli sprout preparation containing 100 micomole SFN or a placebo beverage daily for 10 days prior to surgery. Supported by P50 CA088843, U54 RR020839 and BC073262.
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 5700.
Abstract 5707: Effects of non-toxic agents and their combinations on genotoxicity-related endpoints, and mutagenesis induced by dimethylbenzanthracene-dihydrodiol in cultured rat mammary cells
Authors: Sacks Peter G. , Zhao Zhong-Lin , Kosinska Wieslawa , He Zhiming , Vucetic Zeljka , Ngai Alvin , Guttenplan Joseph B. 
Published: February 2011

Abstract
As the annual breast cancer incidence in the US is about 200,000, prevention would be of enormous value. There are many leads from studies in isolated cell systems and experimental animals, but when individual putative protective agents have been tested in humans, results have been equivocal or negative. Levels generally present in foods, beverages or supplements may exert only weak protective effects, and combinations of potential chemopreventives may be necessary for effective cancer prevention. Here we investigated combinations of non-toxic nutraceutical agents dosed at or near physiological levels, for their abilities to modulate xenobiotic metabolism, and mutagenesis induced by the proximate rat mammary carcinogen, 7,12-dimethylbenzanthracene-dihydrodiol (DMBAD), in rat mammary epithelial cells. The agents and their 1x concentrations, were: resveratrol (Res), 2.4 μM; sulforaphane (Sul), 0.015 μM; antioxidant mix (α-, γ-tocopherol, 30 μM, Vitamin C, 68 μM (VCE); α-lipoic acid (LA), 2 μM; epigallocatechin gallate, (EGCG) 0.7 μM; and N-acetylcysteine (NAC), 12 μM). All of the single agents were non-toxic at the 1x doses and had no statistically significant effect on cell proliferation. All combinations of the binary agents were non-toxic and several modestly inhibited cell proliferation: EGCG-NAC, 27% inhibition, EGCG-Res, 21% inhibition, EGCG-VCE, 26% inhibition. For protection against oxidative stress, inhibition of the oxidation of dihydrodichlorofluorescinediacetate (DHDCF) was monitored, and NAC and NAC+Res or EGCG produced small (10-20%) inhibition. The effects of the inhibitors on selected phase I and II gene expression were also examined. EGCG, Sul, VCE and Res alone induced NQO1, (often used as a marker of phase II, detoxification activity) expression and did not induce CYP1A1 or 1B1. In mutagenesis experiments most of the individual agents did not result in statistically significant inhibition of mutagenesis, but some led to minor inhibition (ca. 20%). We also tested several binary combinations of agents, and some of these led to significant inhibition of mutagenesis. The combinations, NAC + Sul, NAC + Res, and NAC + LA inhibited mutagenesis by 25 - 50% at or near physiologic levels. In conclusion, several non-toxic agents favorably affected expression of genes involved in polycyclic aromatic hydrocarbon-induced carcinogenesis, and several combinations of these agents inhibited cell proliferation, and mutagenesis in cultured rat mammary cells by DMBAD. Supported by the Susan Komen Foundation grant # KG080836.
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 5707.
Abstract 5713: Omega-3 fatty acid molecular and cellular modulation of in vitro models of high-risk breast cancer
Authors: Chen Ching Hui , Cavazos David A. , Apte Shruti A. , Fabian Carol , Hursting Stephen , deGraffenried Linda A. 
Published: February 2011

Abstract
Omega-3 (n-3) fatty acids, especially the long-chain polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaonoic acid (DHA), have been shown to have potential antitumor effects for a wide range of cancer types, including breast. Multiple and widely diverse mechanisms have been purported through which n-3 fatty acids act as antitumor agents. Due to this wide range of effects, the n-3 fatty acids EPA and DHA in particular have been extrapolated to be possible chemo-preventive agents. Recent epidemiological studies have demonstrated that high intake of n-3 fatty acids from fish is inversely correlated with breast cancer risk. In this current study, we explore the molecular and cellular effects of EPA and DHA in breast cancer cells demonstrating abnormalities similar to those found in high risk patient populations, including MCF-7 cells with stable suppression of PTEN expression, MDA-MB-231 cells that mimic the triple negative phenotype and mouse epithelial cells that are derived from MMTV-erbB2 mouse breast tumors. Loss of PTEN activity has been reported in as much as 50% of all breast cancers. Triple negative disease exhibits an aggressive and early pattern of metastasis, with limited treatment options and a poor prognosis. ErbB2 is overexpressed in 30% of breast tumors and has been associated with a more aggressive and a pro-inflammatory disease. Based upon the highly inflammatory nature of these three cell types, we hypothesized that omega-3 fatty acids would be effective in modulating cellular processes that promote the more aggressive phenotype associated with these abnormalities. We are investigating the effect of EPA and DHA on survival, proliferation and apoptosis of the three modulated cell lines in comparison to less aggressive cell lines, and the molecular changes that correlate with response. Preliminary data suggest that cell proliferation is not modulated by exposure to either EPA or DHA. However, both EPA and DHA effectively suppressed NF-kB transcriptional activity in these cells. These data suggest that one important mechanism by which omega-3 fatty acids may function as anti-tumor and possibly chemo-preventive agents is through regulation of NF-kB-induced inflammation. Studies are currently on-going to evaluate if modulation of NF-kB is critical for mediating the protective effects of omega-3 fatty acids on breast cancer development and progression and if reduction of inflammatory responses will correlate with a less aggressive disease in these cells that closely reflect high risk 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 5713.
Abstract 5715: Green tea polyphenols implants are more effective than oral dosing in inhibiting benzo[a]pyrene-induced DNA adducts
Authors: Cao Pengxiao , Vadhanam Manicka V. , Gupta Ramesh C. 
Published: February 2011

Abstract
Green tea is drawing increasing attention due to its potential chemopreventive effect. The polyphenols, including epigallocatechin gallate, epicatechin gallate, epigallocatechin and epicatechin in green tea, are believed to be the active components. However, epidemiological and clinical studies have shown mixed results presumably due to lack of bioavailability when given orally. In this study, polyphenon E, a standardized green tea extract, was administered by novel polycaprolactone implants (two, 2-cm implants; 20% drug load) grafted subcutaneously or by drinking water (0.8% w/v) to female S/D rats. Animals were then challenged with subcutaneous benzo[a]pyrene (BP) implants (2 cm; 10% load), and euthanized after 1 week. Analysis of the lung DNA by 32P-postlabeling showed a significant reduction (50%; p=0.023) in BP-induced DNA adducts in the implant group. A modest (34%) but statistically insignificant adduct reduction was also observed in the drinking water group. The dose of polyphenon E administered by implants was found to be &gt;100 times lower than that by oral route (15.7 mg vs. 1,632 mg). No evidence of toxicity associated with either the polymeric materials or the compounds was found in all these groups based on the body weight and tissue weights. To determine possible mechanisms of action of polyphenon E, we analyzed CYP1A1, CYP1B1 and GST at mRNA and protein expression levels and for the enzyme activities. However, no evidence was found for favorable modulation of these phase I and phase II enzymes by polyphenon E. In in vitro studies, reaction of benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) with DNA was found to be strongly inhibited by individual catechins, particularly epigallocatechin gallate, present in polyphenon E, suggesting quenching of the electrophilic metabolite by the catechins. This notion was confirmed by reaction of anti-BPDE with individual catechins by LC/MS/MS. In conclusion, our study demonstrated that i) the effective dose of polyphenon E administered by polymeric implants was over 100-fold lower than the traditional oral route; and ii) polyphenon E exert their chemopreventive effect, at least, in part, due to direct quenching of anti-BPDE (Supported from CA-118114, KLCRP grant and Agnes Brown Duggan Endowment).
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 5715.
Abstract 5718: Convergence of vitamin D and PPARγ signaling in human breast cancer cell lines
Authors: Alimirah Fatouma , Mehta Rajendra G. , Peng Xinjian 
Published: February 2011

Abstract
Previous studies have demonstrated a positive interaction between vitamin D and peroxisome proliferator- activated receptor γ (PPARγ) mediated signaling while other studies have shown an inverse relationship between these two pathways. Therefore, we sought to determine the functional interaction between the vitamin D receptor (VDR) and PPARγ in human breast cancer cells. We report the physical interaction and nuclear colocalization of VDR and PPARγ in the T47D human breast cancer cell line as determined by co-immunoprecipitation and immunofluorescence respectively. Furthermore, 1alpha,25-dihydroxyvitamin D3 (1,25D3) treatment of MCF-7 and T47D cells significantly upregulated PPARγ protein expression in a dose and time dependent manner. Conversely, knockdown of unliganded VDR also upregulated PPARγ protein expression, suggesting that it is a potential VDR target gene. Thus, VDR itself in the absence of ligand, can suppress PPARγ basal expression. This paradoxical effect may be due to the differential binding of VDR to its coactivators or corepressors during the liganded and unliganded state. Consistent with this, the basal expression of PPARγ mRNA was inversely correlated with VDR mRNA expression in several human breast cancer cell lines. Reciprocally, a PPARγ agonist attenuated vitamin D mediated upregulation of vitamin D target genes CYP24 and p21. Similarly, the activity of VDRE, a vitamin D responsive reporter was decreased by 2 fold in the presence of the PPARγ agonist. Together, these observations infer that VDR and PPARγ protein interactions negatively influence their respective pathways. (This work was supported by NCI predoctoral fellowship 1F31CA132619 (F.A.) and NCI R03 CA121365 (X.P).
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 5718.
Abstract 5732: Human papillomavirus infection in Southern Chinese women - a population-based study
Authors: Liu Stephanie S. , Chan Kelvin KY , Leung Rebecca CY , Luk May HM , Lo Sue ST , Fong Daniel YT , Cheung Annie NY , Lin Zhong Qiu , Ngan Hextan YS 
Published: February 2011

Abstract
Cervical cancer is a leading cause of death in women worldwide. Persistent infection of high-risk (HR) type human papillomavirus (HPV) is recognized as a necessary cause of cervical cancer. Additionally, the presence of certain predisposing factors in combination of HPV infection will significantly increase the risk of developing cervical cancer. Previous epidemiological studies showed different HPV genotype prevalence between different geographic regions. The objectives of the present study were to study and compare the prevalence and the spectrum of HPV infection in healthy women living in Hong Kong (HK) and Guangdong (GD) regions of China and the association between the potential risk factors and HPV infection.
This was a cross-sectional study, and 1526 and 1300 healthy women were recruited from HK and GD, respectively. The overall and type-specific HPV prevalence were studied and compared between the two regions. The results showed that healthy women in GD with normal or abnormal cytology had significantly higher HPV prevalence (10% or 54.5%) than those in HK (6.2% or 33%, p≤0.001). The patterns of age-specific HPV prevalence were also different between the two regions. In HK, the highest HPV prevalence was in the youngest (20-30 years) and the eldest (60 and above) age groups, whereas the highest HPV prevalence in GD was observed in the youngest age group (20-30) and declined as the age increased. HPV16 and HPV52 were the most common high-risk type found in HK and GD, respectively. In HK, younger women had significantly higher risk of HPV infection, whereas lifetime number of sexual partner was strongly associated with the risk of HPV infection in GD. Lack of previous cervical screening, current smoker and having previous sexual transmitted diseases had increased risk of HPV infection for women in both regions.
In summary, the overall and type-specific HPV prevalence were found different in healthy women between HK and GD. Together with the understanding of the association between the potential risk factors and HPV infection will be essential for the implementation of effective public health program for prevention of cervical cancer in Southern Chinese women.
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 5732.
Abstract 5738: Spectrum of malignancies in patients with end-stage renal disease
Authors: Shebl Fatma M. , Engels Eric A. 
Published: February 2011

Abstract
Background: Patients with end-stage renal disease (ESRD) are prone to many complications and high mortality. Overall, ESRD patients are at modestly increased cancer risk. Potential mechanisms by which ESRD might induce cancer include underlying medical conditions, altered immune status due to uremia, and medical treatments. Associations with specific cancers have not been widely studied.
Methods: We conducted a population-based case-control study among elderly U.S. adults using Surveillance, Epidemiology, and End Results (SEER) Medicare linked data. After excluding individuals with HIV or history of organ transplant, the study included 1,029,695 cancer cases (identified in SEER) and 99,610 controls, frequency matched by gender, race, age, and calendar year (1992-2007). ESRD was defined by presence of Medicare claims for dialysis in each of the 3 months prior to selection. Logistic regression was used to calculate odds ratios (ORs) adjusted for matching factors.
Results: ESRD was present in 0.33% of cancer cases vs. 0.31% of controls (OR 1.13; 95%CI 1.0-1.27, p=0.04). We observed significant excess risk of cancers of the stomach (OR 1.67; 95%CI 1.34-2.08), small intestine (2.02; 1.31-3.12), colon (1.29; 1.11-1.51), liver (1.72; 1.38-2.15), pancreas (1.35; 1.09-1.68), lung (1.30; 1.13-1.49), cervix (1.94; 1.25-3.00), vagina (3.08; 1.43-6.64), penis (4.81; 2.60-8.91), bladder (1.37; 1.14-1.65), and kidney (2.58; 2.14-3.11), as well as multiple myeloma (1.92; 1.51-2.44), and chronic myeloid leukemia (2.04; 1.26-3.29). Significantly decreased risk was observed for prostate cancer (OR 0.49, 95%CI 0.41-0.59). Of note, risk of cancer of the colon, liver, vagina, penis, and kidney, and chronic myeloid leukemia increased with duration of dialysis (p-trend&lt;0.01). Additional analyses for histologic subtype will be presented.
Conclusions: ESRD was associated with a slight overall elevation in cancer risk but much stronger increases for specific cancers. Increased risks for infection-related cancers (anogenital, liver, and stomach cancers) may reflect immunodeficiency. Excess risks were observed for malignancies (bladder and kidney cancers, myeloma) that could directly lead to ESRD or are related to such conditions. Associations with prostate and colon cancers could reflect cancer screening patterns. Further investigation of the biological pathways underlying the development of cancer in ESRD is needed.
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 5738.
Abstract 574: 1,4-phenylenebis(methylene)selenocyanate (p-XSC) inhibits mammalian target of rapamycin complex 2 (mTORC2) signaling in prostate cancer cells
Authors: Facompre Nicole , Sinha Indu , Pinto John , El-Bayoumy Karam , Sinha Raghu 
Published: February 2011

Abstract
The lack of treatment for worried-well patients with high-grade prostatic intraepithelial neoplasia combined with issues of recurrence and hormone resistance in prostate cancer survivors remains a major public health obstacle. The long latency of prostate cancer development provides an opportunity to intervene with mechanistically-based agents at various stages of disease progression. Preclinical studies and immunohistochemical analyses of human prostate adenocarcinoma tissues have implicated the mammalian target of rapamycin (mTOR) signaling pathway in the progression of prostate cancer and its transition to androgen independence, suggesting mTOR as a potential target for new therapies. Preclinical studies in human prostate cancer cells also show that there is cross-talk between mTOR and androgen receptor signaling, a process critical for prostate cancer growth and survival. We have previously shown that the synthetic organoselenium compound p-XSC effectively inhibits cell viability and down-regulates androgen receptor expression and transcriptional activity in androgen responsive (AR) and androgen independent (AI) human prostate cancer cells; the naturally occurring selenomethionine was either ineffective or weakly active at non-physiological levels. Therefore, we focused our study on the effects of p-XSC and we hypothesized that it inhibits prostate cancer cell growth by interfering with mTOR signaling and that inhibition of this pathway may be linked to down-regulation of androgen receptor signaling in these cells. Here we show that p-XSC inhibits phosphorylation of mTOR in both AR LNCaP and AI LNCaP C4-2 human prostate cancer cells. This inhibition is attenuated by stimulation with androgens in AR LNCaP but not AI C4-2 cells, emphasizing a cross-talk between the two pathways. p-XSC also decreases mTOR binding to mTOR complex 2 (mTORC2) protein Rictor in AR LNCaP and AI C4-2 cells and inhibits the phosphorylation of mTORC2 downstream target Akt. Since p-XSC appears to be inhibiting mTORC2 as well as androgen signaling, we further hypothesized that the combination of p-XSC with rapamycin, which primarily targets mTORC1, may be a superior approach to inhibit prostate cancer cell growth than either agent alone. Our data clearly support this hypothesis. Validation of mTOR as a target of selenium in prostate cancer will provide evidence for its potential role against advanced and hormone refractory prostate disease either individually or in combination with therapies that target other signaling pathways. Support: NIH CA111842, DOD W81XWH-08-1-0297
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 574.