bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A35: LDL induces prostate cancer cell growth and inhibits growth-reducing effects of simvastatin
Authors: Murtola Teemu J. , Syvälä Heimo , Pennanen Pasi , Bläuer Merja , Ylikomi Timo , Tammela Teuvo L. 
Published: January 2011

Abstract
Background: Several epidemiological studies have reported decreased risk of advanced prostate cancer among men using statins, a widely used group of cholesterol-lowering drugs. The association is possibly linked to serum LDL reduction during statin therapy. We studied in vitro the importance of LDL on growth of normal and cancerous prostate epithelial cells and evaluated its association with growth reducing effect of simvastatin.
Methods: Four normal prostatic epithelial cell lines (P96E, P97E, PWR-1E, RWPE-1) and two cancer cell lines (LNCaP and VCaP) were grown in cholesterol-free conditions. Cells were treated with 1 µg/ml, 15 µg/ml or 50 µg/ml LDL, 100 nM or 10 µM simvastatin and/or 100 µM mevalonate for seven days. Cellular growth rate was measured with crystal violet staining.
Results: In normal epithelial cells, 1 µg/ml and 15 µg/ml LDL did not have marked effect on cell growth, while 50 µg/ml LDL had a growth reducing effect. Conversely, in cancer cells cellular growth was stimulated in direct correlation with LDL concentration. Simvastatin at 100 nM concentration caused clear growth reduction in normal epithelial cells, and 10 µM simvastatin had a cytotoxic effect. Growth reduction by 100 nM simvastatin was attenuated by increasing LDL concentrations, the effect being completely reversed by 15 µg/ml LDL. However, the cytotoxic effect of 10 µM simvastatin could not be reversed by LDL alone, but required combination of 100 µM mevalonate and 15 µg/ml LDL.
Conclusions: Our results demonstrate the importance of LDL for prostate cancer cell growth. The growth reducing effect of simvastatin depends on the level of extracellular LDL. Our study supports the epidemiological studies suggesting that statins’ prostate cancer risk reducing effects depend on LDL reduction. Hypercholesterolemia could be a prostate cancer risk factor.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A35.
Abstract A41: Evaluation of maximum tolerated dose of aerosolized Rapamycin in A/J mice
Authors: Sharma Sheela , Lee Jin , Zhou Jianliang , Wong Brian , Steele Vernon E. 
Published: January 2011

Abstract
Rapamycin, an approved anti-rejection drug for organ transplantation, has shown antitumor activity in preclinical studies and clinical trials. However, concerns regarding the prevalence of pneumanitis in few patients receiving Rapamycin by injection have prompted us to pursue an alternative and hopefully less toxic route of administration. Previously, we have shown that there was a good correlation between the dose-dependent increase in blood levels of Rapamycin and corresponding dose-dependent decrease in the activity of two biomarkers (phospho-AKT and mTOR) in the mouse lung. We have also observed that there was no significant difference between continuous or intermittent dosing regimens in reducing p-AKT and mTOR activity by rapamycin as the activity levels continued to remain suppressed (60 % inhibition) for up to 3 days after the last exposure. The objective of the current study is to assess the maximum tolerated dose (MTD) of aerosolized rapamycin to select optimal doses for subsequent cancer prevention studies. Female A/J mice (8 wks old) were exposed to 3 different doses (0.1, 1 and 10 mg/kg — equivalent to 1.6, 15.8 and 158 mg/m3 of air, respectively) of rapamycin by Nose-Only inhalation for 1 hr/day, 3 days (every other day) per week for 6 weeks. No toxicity was observed during or after the exposure in all dose groups except that the animals exposed to 10 mg/kg of rapamycin showed relatively slow body weight gain compared to other dose groups. Hematology of whole blood showed no significant difference among different dosing groups. Lymphocyte subpopulation evaluated by flow cytometry in blood showed that rapamycin at all doses had no effect on the ratio of T-helper cells/cytotoxic T-cells (CD4+/CD8+). Also, rapamycin did not affect the number of T regulatory cells, which was assessed by measuring FoxP3+/CD3+ ratio (4-5% in all groups) in lungs processed for immunohistochemistry. Pathological evaluation of H&E stained lung sections did not find any dose-related abnormalities in all groups. In conclusion, this study showed that rapamycin did not cause any toxicity in mice exposed to rapamycin by inhalation for 6 weeks at the dose ranges tested, indicating that rapamycin via inhalation route could be a safe candidate as a chemopreventive agent against lung tumors (Supported by NCI #N01-CN-53301).
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A41.
Abstract A45: Berberine acts as an antagonist to estradiol-induced proliferation by inducing apoptosis in cervical cancer cells
Authors: Komal Komal , Sharma Alpana , Deshwal Vishal Kumar 
Published: January 2011

Abstract
Background: Cervical cancer is the most common cancer in Indian females and is associated with infection with high-risk human papillomaviruses (HPVs). Prolonged use of oral contraceptives has been established as a risk factor for cervical cancer which is mediated by elevated estradiol level. Berberine has emerged as a potential anticancer agent in various cancers. The present study investigated the effect of bereberine on estradiol pretreated cervical cancer cell lines HeLa, SiHa and C33A.
Methods: Cervical cancer cells were cultured in DMEM/RPMI/MEM medium supplemented in 10% FBS in a humidified atmosphere of 95% air and 5% CO2 at 37°C and were treated with estradiol for 24 hr followed by 50 µM and 75 µM Berberine for 24 hrs standardized using MTT assay. Apoptosis was measured by flow cytometery. Telomerase activity was studied using PCR ELISA. The expression of various proliferation proteins like PCNA, p16 was assessed by ICC. Expression of viral oncoprotein E6 and E7, Cyclin D1, p53 was assessed by Western blotting.
Results: Treatment of cervical cancer cells with estradiol resulted in increased proliferation after 24 hrs in HPV positive cell lines HeLa and SiHa but no proliferation was observed in HPV negative cell line C33A. Elevation of telomerase activity, viral oncoprotein E6 and E7, PCNA, p16 and cyclin D1 was seen in HPV positive cell lines on pretreatment by estradiol, On the other hand after post treatment by berberine for 24 hrs levels of E6, E7, PCNA and cyclin D1 were reduced while the level of telomerase and p16 were unaltered. Furthermore, estradiol pretreated HPV negative cell line C33A on treatment by berberine shows reduction in level of telomerase, PCNA, p16 and activation of p53 tumor suppressor protein, thus demonstrating the importance of HPV viral proteins in estradiol-induced carcinogenesis.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A45.
Abstract A46: Pseudohypericin in Hypericum perforatum inhibited LPS-stimulated PGE2 and NO in mouse macrophages by potentiating SOCS3 expression
Authors: Huang Nan , Hauck Cathy , Rizshsky Ludmila , Murphy Patricia A. , Nikolau Basil J. , Birt Diane F. 
Published: January 2011

Abstract
Introduction: Hypericum perforatum, also known as ‘St. John's wort’, is one of the most studied medicinal plants. Despite its primary use as an anti-depression agent, certain compounds such as hypericin and hyperforin in H. perforatum extract have been shown to inhibit tumor growth by inducing apoptosis/necrosis and inhibiting angiogenesis. Using hypericin in photodynamic cancer therapy is also being studied. Our previous studies have demonstrated that H. perforatum extract and a group of 4 compounds in it, namely pseudohypericin, amentoflavone, quercetin, and chlorogenic acid, decreased lipopolysaccharide (LPS)-stimulated macrophage inflammatory response, and identified the activation of suppressor of cytokine signaling 3 (SOCS3) as a candidate mechanism for this activity. Given that both inflammation and SOCS3 suppression are associated with tumor progression, we studied the role of SOCS3 activation in the anti-inflammatory activity of H. perforatum extract and its components.
Methods: Specific siRNA was used to knockdown the expression of SOCS3 in RAW 264.7 mouse macrophages. Activation of SOCS3 in macrophages was measured at mRNA and protein levels using qRT-PCR and Western blot. H. perforatum extract at 30 µg/mL, the 4 compounds at the same concentrations as in the extract, and the combinations of individual compounds were applied to macrophages with and without SOCS3 knockdown to reveal whether their inhibition of LPS-stimulated prostaglandin E2 (PGE2) and nitric oxide (NO) was dependent on SOCS3.
Results: SOCS3 expression in the mouse macrophages was activated upon LPS stimulation and further potentiated by H. perforatum extract and the 4 compounds studied. SOCS3 siRNA transfection significantly compromised the activation of SOCS3. H. perforatum extract and the 4 compounds reduced LPS-stimulated PGE2 and NO production, but only the inhibitory effect of the 4 compounds was negated by SOCS3 knockdown. Combinations of two or three of the 4 compounds that include pseudohypericin, the most essential component among the four that act synergistically in reducing macrophage inflammatory response, lost their inhibitory effect on PGE2 and NO production in SOCS3 knockdown cells.
Conclusions: SOCS3 activation was critical for pseudohypericin's independent and interactive anti-inflammatory activity with amentoflavone, quercetin, and chlorogenic acid. H. perforatum extract utilized alternative mechanisms that are SOCS3 independent to inhibit macrophage inflammation. In addition to light-activated cytotoxicity and inhibition of angiogenesis, magnification of SOCS3 activation by H. perforatum extract might contribute to its anti-tumor potential.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A46.
Abstract A49: Verification of two novel phytochemical inducers of phase II metabolic enzyme NQO1 in human lung cells
Authors: Marquardt Gaby , Tan Xianglin , Spivack Simon D. 
Published: January 2011

Abstract
One strategy for lung cancer chemoprevention focuses on the use of agents to modulate the metabolism and disposition of tobacco, environmental and endogenous carcinogens through up-regulation of detoxifying phase II enzymes. However, in studies to date, most candidate agents are not active in human lung cells. Therefore we previously applied a gene expression-based high-throughput screening approach to investigate n=800 plant-derived polyphenolic- and flavenoid- predominant compounds in the MicroSource Natural Products Library as to their effect on inducing the phase II metabolic enzymes glutathione S-transferases (GSTP1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) in primary normal human bronchial epithelial (NHBE) cells and immortalized human bronchial epithelial cells (HBEC). We had identified 2, 3-dihydroxy-4-methoxy-4’-ethoxybenzophenone (DMEBP, putative source arctic sponge) and triacetylresveratrol (TRES, putative source plant myrtle) as new inducers for NQO1 mRNA expression. In the current study, in order to confirm our results, NHBE and HBEC cells in culture were exposed to diet-achievable levels of TRES and DMEBP (0.5, 1.0, 2.0 µM), as well as a panel of conventionally-recognized phytopreventive agents [epigallocatechin gallate (EGCG), resveratrol (RES) and sulforaphane (SFN)] for 24 h, 48 h, and 6 d, respectively. Quantitative RNA-specific RT-PCR showed an up-regulation of NQO1 mRNA expression of up to 10.8 fold in DMEBP-treated NHBE cells and an up-regulation of up to 4.6 fold in TRES-treated NHBE cells. NQO1 protein expression increased up to 3.4 fold in DMEBP-treated and up to 1.8 fold in TRES-treated NHBE cells. HBEC cells showed similar results for mRNA expression — an up-regulation of NQO1 mRNA expression of up to 9.7 fold in DMEBP-treated HBEC cells and an up-regulation of up to 3.1 fold in TRES-treated HBEC cells — whereas none of the tested compounds had an effect on protein expression in HBEC cells. DMEBP had a narrow therapeutic window, and was notably toxic to lung cells at 1-2 µM. We then measured accumulation of reactive oxygen species (ROS) in NHBE cell using DFA, and total GSH assays. Our ROS data so far show a slight anti-oxidant effect for DMEBP, but no effect yet found for TRES. Our data show two new agents have some effect on the up-regulation of the detoxifying enzyme NQO1 at mRNA and protein levels, but the effect was modest, and none was observed for GSTP1. Among the newly discovered agents, TRES is the most plausible candidate resulting from this search, and compares favorably, to conventional plant-derived polyphenolics/flavenoids tested.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A49.
Abstract A51: Acacetin in inhibiting tumor growth and angiogenesis
Authors: Jiang Bing-Hua , Liu Ling-Zhi , Jiang Lisa , Jing Yi , Jiang Xiue 
Published: January 2011

Abstract
Background: Acacetin (5,7-dihydroxy-4′-methoxyflavone) is a member of the flavonoid compound familys, some of which have anti-cancerous effects. Angiogenesis is a key process during carcinogenesis and tumor growth; however, but the effect and the mechanisms of acacetin on angiogenesis and tumor growth remain to be elucidated.
Methods: In order to determine the effect of acacetin on the expression of vascular endothelial growth factor (VEGF) and HIF-1α expression, we tested VEGF expression by reporter assay and HIF-1α expression by Western blotting and RT-PCR assay. To test whether overexpression of active form of AKT increases HIF-1 expression, transient transfection was performed. Tumor angiogenesis and tumor formation in vivo were examined by chicken chorioallantoic membrane (CAM).
Results: Acacetin decreased the steady level of VEGF mRNA under the normoxia and hypoxia conditions while inhibiting, and inhibited VEGF transcriptional activation. To further determine the potential mechanism of acacetin in inhibiting VEGF expression, we showed demonstrated that acacetin inhibited HIF-1α expression and AKT activation. Overexpression of HIF-1α or AKT abolished acacetin-decreasing VEGF transcriptional activation, indicating that AKT and HIF-1 are the essential downstream targets of acacetin for inhibiting VEGF expression in the cells. Moreover, acacetin significantly inhibited ovarian cancer cells-induced angiogenesis and tumor growth in vivo through inhibiting HIF-1α and VEGF expression. Acacetin inhibited HIF-1α protein expression through increasing its degradation and decreasing its stability, but did not alter HIF-1α mRNA levels.
Conclusion: These results indicate that acacetin inhibits tumor agnigenensis and growth by blocking the AKT/HIF-1/VEGF pathway. It may be a useful natural compound for cancer prevention and treatment.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A51.
Abstract A56: Induction of spermine oxidase by enterotoxigenic Bacteroides fragilis contributes to tumorigenesis in a model of colitis-associated colorectal cancer
Authors: Goodwin Andrew , Wu Shaoguang , Huso David , Wu Xinqun , Hicks Jessica , Shields Christina Destefano , Hacker-Prietz Amy , Rabizadeh Shervin , Marzo Angelo De , Sears Cynthia , Casero Robert 
Published: January 2011

Abstract
It is estimated that the etiology of 20-30% of epithelial cancers is directly associated with inflammation, though the molecular events linking inflammation and the necessary carcinogenic mutations remain to be clarified. In the context of gastrointestinal disease, the bacterial pathogens Helicobacter pylori and enterotoxigenic Bacteroides fragilis (ETBF) are significant sources of chronic inflammation and have been implicated as risk factors for the development of gastric and colorectal cancer, respectively. We have previously demonstrated that H. pylori and the cytokine tumor necrosis factor-α (TNF-α) rapidly induce spermine oxidase (SMO), resulting in increased cellular reactive oxygen species (ROS) and DNA damage, in gastric and lung epithelial cells. In addition, tissue microarray studies revealed that increased SMO expression was associated with prostatic intraepithelial neoplasia and prostate cancer lesions and that benign prostate epithelial tissue from men with these diseases exhibits higher SMO expression than normal controls. We now demonstrate that purified B. fragilis toxin (BFT) upregulates SMO in HT29/c1 and T84 colonic epithelial cells, resulting in SMO-dependent induction of γ-H2A.x, a marker of DNA damage. Further, ETBF-induced colitis in wild-type or APC+/− Min C57Bl/6 mice is associated with increased SMO expression. Inhibition of SMO activity by MDL 72,527 in vivo (20 mg/kg i.p. 3 days per week) significantly reduces ETBF-induced chronic inflammation, proliferation, and induction of Th17-associated cytokines. Most importantly, in Min mice, treatment with the SMO inhibitor reduces ETBF-induced colon tumorigenesis by 69% (p&lt;.001). Our studies suggest that SMO is a novel target for chemopreventive or chemotherapeutic drug development.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A56.
Abstract A61: Circulating adiponectin levels as a predictive factor of breast cancer in a double-blind 2x2 phase II trial of low-dose tamoxifen and fenretinide for breast cancer prevention
Authors: Aliana Guerrieri-Gonzaga , Gandini Sara , Johansson Harriet , Macis Debora , Magni Paolo , Dozio Elena , Lazzeroni Matteo , Gulisano Marcella , Latronico Antuono , Bonanni Bernardo , Decensi Andrea 
Published: January 2011

Abstract
Background: The assessment of breast cancer risk is a key step for an effective preventive treatment. Besides the established risk assessment models, independent predictive factors like circulating biomarkers may also be important to better select high risk subjects and to determine efficacy of chemopreventive treatment.
Adiponectin is a peptide hormone secreted from the adipose tissue with anti-inflammatory, anti-atherogenic and anti-diabetic properties. Epidemiological studies have shown that plasma adiponectin level is inversely related to breast cancer risk.
In the present study, we measured plasma adiponectin levels in premenopausal women participating in a phase II trial of low-dose tamoxifen and fenretinide for breast cancer prevention.
Methods: Premenopausal women (n = 235) were randomly assigned in a double-blind 2x2 trial to receive tamoxifen 5 mg/d, fenretinide, a vitamin A derivative, 200 mg/d, both agents, or placebo for 2 years. A total of 181 premenopausal women with ductal intraepithelial neoplasia (DIN) and 54 unaffected women at higher risk according to the Gail model were enrolled.
Mammographic percent density was centrally measured using the computer-assisted method described by Boyd. Plasma adiponectin was measured by use of a commercial enzyme-linked immunosorbent assay kit.
Preliminary results: According to disease status (DIN vs Gail) at baseline, median plasma adiponectin levels were lower in women with a DIN (10 ug/ml; interquartile (IQ) range: 7.1-14) compared to unaffected women with a Gail risk (12 ug/ml; IQ range: 8.7-14.7) (p=0.05).
Importantly, after a median follow-up of 5.5 years, plasma adiponectin levels were lower in women who had a breast cancer event (7.7 ug/mL; IQ range: 6.46-12.78) compared to women without event (11.02 ug/mL; IQ range: 7.8-14.4) (p=0.015). This difference is also maintained after adjusting for BMI and treatment allocation (p=0.011).
Considering the distribution of adiponectin levels at baseline, we observed a 9% reduction in the hazard ratio of breast cancer events by each unit increase of adiponectin levels (95%CI: 0.83-0.96; p=0.02, cox model adjusted for BMI, treatment allocation, mammographic density and disease status at baseline).
Conclusion: We found that subjects with lower plasma adiponectin levels had a significantly higher risk of breast cancer event. The association appeared independent of known risk factors such as BMI and mammographic breast density. Further studies to better understand and confirm the role of adiponectin as independent predictive risk factor are warranted.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A61.
Abstract A85: Fruit and vegetable consumption reduces the risk of pancreatic cancer
Authors: Jansen Rick J. , Robinson Dennis P. , Stolzenberg-Solomon Rachael Z. , Bamlet William R. , de Andrade Mariza , Oberg Ann L. , Hammer Traci J. , Rabe Kari G. , Olson Janet E. , Anderson Kristin E. , Sinha Rashmi , Petersen Gloria M. 
Published: January 2011

Abstract
Pancreatic cancer is a devastating disease for which the role of dietary risk factors remains inconclusive. We evaluated fruit, vegetable, fiber, and grain consumption with pancreatic cancer risk using a clinic-based case-control design, excluding participants who reported changing their diet within 5 years prior to entering the study. Our study included 384 rapidly ascertained cases and 983 non-cases (frequency matched on age at time of recruitment (± 5 years), race, sex, and region of residence) who completed epidemiologic surveys and a 144-item food frequency questionnaire developed by the National Cancer Institute. Logistic regression was used to calculate odds ratios (OR) and 95% CIs, adjusted for age, sex, smoking, body mass index, energy intake, and alcohol consumption. Comparing highest to lowest quintiles, we observed significant (OR &lt; 0.01) inverse associations with significant trends (ptrend &lt; 0.01) for citrus, melon, and berries, other fruit, dark green vegetables, deep yellow vegetables, tomato, other vegetables, dry bean and pea, insoluble fiber, soluble fiber, and whole grains. Adjusting for diabetes or total sugar intake in the multivariate logistic regression model did not significantly affect results. Consuming a diet high in fruits, vegetables, fiber, and whole grains may reduce the risk of developing pancreatic cancer.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A85.
Abstract A86: Higher micronutrient intake is associated with human papillomavirus-positive head and neck cancer: A case-only analysis
Authors: Arthur Anna E. , Duffy Sonia A. , Sanchez Gloria I. , Gruber Stephen B. , Terrell Jeffrey E. , Hebert James R. , Bradford Carol R. , D'Silva Nisha J. , Carey Thomas E. , Wolf Gregory T. , Peterson Karen E. , Rozek Laura S. ,   UM Head and Neck SPORE Program
Published: January 2011

Abstract
While tobacco and concurrent alcohol use account for the majority of head and neck squamous cell carcinomas (HNSCC), human papillomavirus (HPV)-16 contributes to a distinct subtype of the disease. HPV-positive HNSCC cases have better prognoses and typically occur in younger individuals with lower exposure to tobacco and alcohol and higher socioeconomic status (SES) when compared to those with more strongly tobacco-related, HPV-negative HNSCC. As dietary quality is associated with SES, patients with HPV-positive tumors also may have higher intake of micronutrients. This study was conducted to better understand the relationship between diet and HPV status among HNSCC patients. Subjects were recruited from two clinical centers participating in the University of Michigan Head and Neck Specialized Program of Research Excellence (SPORE). HPV genotyping was performed in DNA extracted from micro-dissected tissue and epidemiologic and dietary data collected. Multivariable logistic regression tested whether pretreatment consumption of 12 selected micronutrients was significantly associated with HPV status in 143 patients newly diagnosed with cancer of the oral cavity or pharynx. After controlling for age, sex, body mass index, tumor site, cancer stage, problem drinking, smoking and energy intake, a significant and positive association was observed between HPV-positive status and increasing quartiles of vitamin A, vitamin E, iron, β-carotene and folate intake (Ptrend&lt;0.05). Patients with HPV-positive cancers have higher intakes of selected micronutrients compared to patients with HPV-negative tumors, suggesting that diet may be a factor in the improved prognosis documented in those with HPV-positive HNSCC. Dietary differences by HPV status should be considered in prognostic studies to better understand the influence of diet on HNSCC survival.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A86.