bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 601: PPARδ mediated p21 induction in aerodigestive preneoplastic cell lines
Authors: Miller Wendy , Wuertz Beverly , Ondrey Frank G. 
Published: August 2012

Abstract
PPARδ activating strategies are currently being tested preclinically and clinically in aerodigestive cancer prevention. Thiazolidinedione drugs like pioglitazone are clinically used for the treatment of diabetes and activate PPARδ as a primary target. P21/WAF1 is a cell cycle protein that is a cyclin dependent kinase inhibitor that reguylates cell cycle progression at the G1 phase; therefore its induction may be associated with cell cycle downregulation in precancerous cells experiencing increased proliferation. In our present study we examined the effects of pioglitazone on proliferation in human leukoplakia cells (MSK 1) and transformed lung (BEAS 2B) cells. We found that pioglitazone significantly inhibited cell proliferation in both cell lines in a dose dependent fashion at concentrations between 0 and 40 uM, as judged by MTT assays from 1-5 days. We found p21/WAF 1 induction by western blot within the first eight hours after the intitiation of treatment with pioglitazone, which were preceded by measureable increases in p21 induction on q PCR. In an analysis of an Affymetrix database of human head and neck tumors (41 tumors compared to 13 normal oral mucosa samples), we found significant dysregulation in several p21 activated kinases. We conclude the PPARδ activator, pioglitazone, can activate p21, which is associated with decreased proliferation in 2 aerodigestive preneoplastic cell lines. We also conclude that this gene may be a potential hypothesis driven biomarker in translational studies of pioglitazone as a chemoprevention agent for aerodigestive 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 601. doi:1538-7445.AM2012-601
Abstract 607: Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea
Authors: Wang Piwen , Heber David , Henning Susanne M. 
Published: August 2012

Abstract
The chemopreventive activity of green tea (GT) and green tea polyphenols (GTPs) in prostate cancer has been demonstrated in preclinical cell culture and animal models. However, extensive methylation of GTPs in vivo to less active methyl-metabolites may be limiting the anti-cancer activity of GT. The objective of the present study was to investigate whether quercetin (Q), a natural inhibitor of catechol-O-methyltransferase (COMT), will increase tissue concentrations of non-methylated GTPs and enhance the inhibition of xenograft tumor growth in severe combined immune deficient (SCID) mice. Androgen-sensitive LAPC-4 prostate cancer cells were injected subcutaneously into SCID mice (n=12 per group). SCID mice were randomly assigned to four groups: control, GT, Q, and GT + Q treatment. The interventions were initiated when tumors reached volume of 10mm3. The final concentration of GTPs in brewed tea administered as drinking water was 0.07% and Q was supplemented in AIN-93G diet at a concentration of 4g/kg diet. There were no differences in food intake, body weight or water consumption during the intervention. Tissue bioavailability of GTPs was increased significantly by 2 to 3-fold in lung, kidney and xenograft tumors and showed a trend to increase by 1.3-fold in liver tissue by GT and Q treatment compared to GT alone. Methylation of epigallocatechin gallate (EGCG), the main polyphenol in green tea, was decreased in tissues from mice in the GT+Q group. After 6 weeks, tumor growth was inhibited by 16% (Q alone), 21% (GT alone), and 45% (GT+Q) compared to the control group. Western blot analysis demonstrated a significant inhibition of methyl transferases such as COMT (31%) and DNA methyltransferase (DNMT) (52%) in tumors from the GT+Q group compared to the control. It has been demonstrated previously that EGCG can act as androgen receptor (AR) antagonist as well as inhibit angiogenesis via inhibition of the vascular endothelial growth factor (VEGF). Together Q+GT inhibited protein expression of AR (35%), prostate-specific antigen (PSA) (39%), and VEGF (25%) more than either GT or Q alone. This study demonstrates an enhanced inhibition of prostate tumor growth when GT and Q are co-administered and this is likely due to inhibition of methylation resulting in enhanced anti-tumor activity of EGCG via effects on angiogenesis, and androgen-mediated tumor growth. This study sets the stage for future human interventions to confirm the increase in bioavailability and chemoprevention using GT in combination with Q. This project was supported by DOD grant W81XWH-10-1-0298 and NIH grant RO3 CA150047-01.
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 607. doi:1538-7445.AM2012-607
Abstract 609: Benzyl isothiocyanate inhibits prostate cancer development in the transgenic adenocarcinoma mouse prostate model
Authors: Cho Han Jin , Kim Ji Hee , Park Jung Han Yoon 
Published: August 2012

Abstract
Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has also been shown to have anti-tumor properties. In the present study, we attempted to determine whether BITC inhibits the development of prostate cancer using the transgenic adenocarcinoma mouse prostate (TRAMP) model. Male TRAMP mice and their nontransgenic (normal) littermates at 5 wk of age were randomly divided into control and BITC-treatment groups and gavage-fed with 0 (vehicle), 5, or 10 mg/kg of BITC every other day. At the time of sacrifice (24 wk of age), BITC did not affect body weight of normal or transgenic animals. The genitourinary tract weight of TRAMP mice was increased markedly as compared to normal mice, and this increase was suppressed significantly via the oral administration of 5 or 10 mg/kg of BITC. H&E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the 24 week old vehicle-fed TRAMP mice, whereas number of lobes with WDC was reduced and the number of lobes with prostatic intraepithelial neoplasia was increased by feeding with 5 or 10 mg/kg of BITC. BITC feeding reduced the number of cells expressing the Ki67 (a proliferation marker) in the prostatic tissue. Additionally, BITC feeding reduced the expression of cyclin E, cyclin D1, cyclin A, and cyclin-dependent kinase (CDK)2. Our in vitro cell culture results revealed that BITC decreased DNA synthesis and CDK2 activity in TRAMP-C2 mouse prostate cancer cells. However, BITC did not affect apoptosis either in transgenic mice in vivo or in TRAMP-C2 cells in vitro. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in animals treated with BITC.
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 609. doi:1538-7445.AM2012-609
Abstract 611: Alpha-santalol, a chemopreventive agent induces apoptosis in human prostate cancer cells by causing caspase-3 activation
Authors: Bommareddy Ajay , Rule Brittny , VanWert Adam L. , Santha Sreevidya , Dwivedi Chandradhar 
Published: August 2012

Abstract
The anticancer effects of α-santalol, a major component of sandalwood oil, have been reported against the development of certain cancers such as skin cancer both in vitro and in vivo. The primary objectives of the current study were to investigate the cancer preventive properties of α-santalol on human prostate cancer cells PC-3 (androgen independent and P-53 null) and LNCaP (androgen positive and P-53 wild-type), and determine the possible mechanisms of its action. The effect of α-santalol on cell viability was determined by trypan blue dye exclusion assay. Apoptosis induction was confirmed by analysis of cytoplasmic histone-associated DNA fragmentation using both an apoptotic ELISA kit and a DAPI fluorescence assay. Caspase-3 activity was determined using caspase-3 (active) ELISA kit. PARP cleavage was analyzed using Immunoblotting. α-santalol at 25-75 µM decreased cell viability in both cell lines in a concentration and time dependent manner. Treatment of prostate cancer cells with α-santalol resulted in induction of apoptosis as evidenced by DNA fragmentation and nuclear staining of apoptotic cells by DAPI. α-santalol treatment also resulted in activation of caspase-3 activity and PARP cleavage. The α-santalol-induced apoptotic cell death and activation of caspase-3 was significantly attenuated in the presence of pharmacological inhibitors of caspas-8 and caspase-9. In conclusion, the present study reveals the apoptotic effect of α-santalol in inhibiting the growth of human prostate cancer cells.
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 611. doi:1538-7445.AM2012-611
Abstract 616: A cumulative molecular model for the mechanisms of green tea catechins in the chemoprevention of prostate cancer
Authors: Connors Shahnjayla K. , Kumar Nagi B. 
Published: August 2012

Abstract
Background: Prostate cancer (CaP) is the most commonly diagnosed cancer in men. It's long latency, slow progression, and high incidence rates make it ideal for targeting chemoprevention therapies. Studies suggest that green tea may be suitable candidate for CaP chemoprevention. The green tea catechin (GTC) chemopreventive mechanisms against CaP cells, however, are not completely clear. Understanding and refining models of the fundamental molecular pathways by which GTCs modulate prostate carcinogenesis is essential to most appropriately utilize green tea for CaP prevention in clinical settings. Objective: The objective of the study was to review the current literature and develop a model that attempts to recreate the molecular mechanisms and pathways by which GTCs modulate prostate carcinogenesis. Methods: Laboratory studies, clinical studies, and clinical trials focused on GTC chemoprevention of CaP were critically analyzed and reviewed for mechanisms of GTC chemoprevention. The most prevalent mechanisms were combined into a multi-mechanistic model that attempts to recreate the cumulative events that occur as GTCs exert anti-cancer activity on prostate cancer cells and tissues. Results: GTCs exert anti-cancer actions on CaP cells and tissue through six major mechanisms: proteasome inhibition, cell cycle arrest, inhibition of cell proliferation, induction of apoptosis, suppression of carcinogenesis/progression, and inhibition of metastasis. We have proposed a novel model in which GTCs exert chemopreventive effects on CaP though these six major mechanisms that work simultaneously and dependently, largely driven by proteasome inhibition-induced regulation of the NFκB pathway. The cumulative effect of these mechanisms ultimately leads to the inhibition of CaP cell growth, progression, and metastasis. Conclusions: Several mechanisms of GTC chemopreventive activity on CaP cells and tissues have been identified in laboratory and clinical studies. Although GTCs act through distinct cell cycle regulative pathways, the cumulative chemopreventative effect appears to be attributed to their well-coordinated ensemble, rather than a single pathway. Additionally, transitioning to the use of standardized GTC preparations may more accurately reflect human tea consumption, deliver the maximum amount of GTCs, and allow for more generalizable results in epidemiological, laboratory, and clinical studies. We are currently testing and refining our novel cumulative model to fully elucidate the complex mechanism of GTC chemoprevention of prostate cancer in its entirety.
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 616. doi:1538-7445.AM2012-616
Abstract 618: Rhodiola rosea L. extract, SHR-5, and metformin exhibit potent activity against bladder carcinogenesis in the UPII-mutant Ha-ras transgenic model.
Authors: Liu Zhongbo , Li Xuesen , Liu Shuman , Xu Xia , Tian Xuejiao , Simoneau Anne R. , Zi Xiaolin 
Published: August 2012

Abstract
The incidence of human urinary bladder cancer increases markedly with age, suggesting a mechanistic connection between aging and bladder carcinogenesis and a potential use of anti-aging agents in bladder cancer chemoprevention. Rhodiola rosea, growing in high altitude or cold regions of the world, has been reported to have anti-aging effects in Drosophila. Metformin, a popular anti-diabetics drug, has also shown anti-aging effect in mice. In addition, both agents have been shown to inhibit the mTOR pathway. Therefore, we examined the effect of SHR-5 and Metformin on bladder carcinogenesis in the UPII-mutant Ha-ras transgenic mouse bladder model. This model mimics human papillary transitional cell carcinoma and exhibits enhanced mTOR activity in the bladder tumors. The homozygous mutant Ha-ras transgenic mice were identified through genotyping using Southern blotting analysis. 0.625% SHR-5 or 0.1% Metformin in drinking water was given to the mice starting at 6 weeks of age and ending at 6 months of age. About 42% of homozygous mutant Ha-ras male transgenic mice which drank normal water died of urinary tract obstruction and hydronephrosis within 6 months of age, while more than 93% and 89% of mice which drank SHR-5 or Metformin containing water survived. The mean bladder weights in male mice drinking SHR-5 or Metformin decreased by 69% and 62%, respectively, compared to control group (Bladder weights for mice drinking normal water versus SHR-5 or Metformin are 0.3382± 0.061versus 0.1278± 0.02 or 0.1053±0.015 gram, P=0.0197 or 0.0082). The mean bladder weights in female mice which drank SHR-5 or Metformin containing water also decreased by about 40% or 39.8 %, respectively, compared to those which drank normal water (Bladder weights for normal water versus SHR-5 or Metformin: 0.07149 ±0.0036 versus 0.04301 ±0.0032 or 0.04295±0.0115 gram, P&lt;0.0001 or =0.0007). Chemstrip tests showed that mice which drank SHR-5 or metformin water developed less hematurine than those which drank normal water. Histological analysis of H&E staining bladder sections from SHR-5 and Metformin treated mice demonstrated more differentiated tumors compared to those from the transgenic mice which drank normal water. Immunohistochemistry staining revealed that SHR-5 and Metformin treatments decreased cell proliferation in the urothelium. Taken together, our results suggest a potential new method for bladder cancer prevention by drinking SHR-5 or Metformin.
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 618. doi:1538-7445.AM2012-618
Abstract 639: The effect of grapefruit intake on endogenous serum estrogen levels in postmenopausal women
Authors: Monroe Kristine R. , Stanczyk Frank Z. , Besinque Kathleen , Pike Malcolm C. 
Published: August 2012

Abstract
The inhibitory effect of grapefruit juice on the intestinal cytochrome P450 3A4 system interacts with more than 60% of orally administered drugs leading to elevation of their serum concentrations. While grapefruit has been shown to lead to elevated serum levels of estrogens when hormones are administered orally, there are no published data on the effect of grapefruit intake on endogenous levels. To begin to address that data gap, we conducted a dietary intervention study among healthy postmenopausal volunteers to determine whether endogenous estrogen levels are significantly affected by grapefruit consumption. We tested 4 grapefruit products: whole fresh grapefruit, fresh squeezed juice “not from concentrate,” shelf-stable juice from concentrate, and grapefruit soda. The majority of volunteers were recruited through the Love/Avon Army of Women. The six-week study consisted of a run-in period of three weeks, a two-week period of grapefruit consumption, and a one-week wash-out period. Eight fasting blood samples were collected during the study. An additional 5 samples drawn at 1, 2, 4, 8 and 10 hours after initial grapefruit intake were collected during an acute-phase study. Serum assays for estrone (E1), estradiol (E2), estrone-3- sulfate (E1S), and sex hormone-binding globulin (SHBG) were conducted. Sixty-two women participated in the study, 10 of whom also participated in the acute phase. Only the whole grapefruit had statistically significant effects on endogeneous estrogen levels. The largest increases were seen in the women with the highest BMI. The changes were evident at 24 hours and remained relatively constant over the 2 week period. With whole grapefruit at the average BMI of 26.6 kg/m2, E1S increased overall by 10.6% (p=0.031), and at a BMI of 30 kg/m2 this increased to 16.4% (p=0.003). Approximately double the effects were seen around 10 hours after whole grapefruit consumption. The effects of fresh juice consumption were around 25% of these increases but were not statistically significant. Small increases in E1 were seen with whole grapefruit, but no increase was seen in E2. The findings of the present study suggest an important interaction between grapefruit consumption and serum levels of endogenous E1S. The increase in E1S is difficult to interpret in term of risk of breast cancer as we found only a small increase in E1 and failed to find any increase in E2. More detailed studies are needed to gain an understanding how the increased levels of E1S are not reflected in similar increases in E1 and E2, and whether the increased E1S levels are reflected in an increase in E1 and E2 levels in the breast itself.
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 639. doi:1538-7445.AM2012-639
Abstract 642: Body fat distribution and prostate cancer risk: A UK case-control study
Authors: Robinson Fredie , Lophatananon Artitaya , Rahman Aneela A. , Brown Sarah S. , Parker Terence L. , Easton Douglas , Jarai Zsofia K. , Pocock Richard , Dearnaley David , Guy Michelle , Wilkinson Rosemary A. , awyer Emma S , Page Elizabeth , Liu Jo-Fen , Grabowska Anna , Walker David , Hall Amanda L. , Eeles Rosalind A. , Muir Kenneth R. ,   The UK Genetic Prostate Cancer Study Collaborators and British Association of Urological Surgeons
Published: August 2012

Abstract
Background: Prostate cancer is the most common cancer among males in the UK and in 2007 accounted for almost a quarter of all male cancers diagnosed. Previous studies have shown some associations between body size/obesity and prostate cancer risk. However body fat distribution in terms of perceived “body shape” and its association with prostate cancer risk has never been described. Methods: In the UK data from 1343 cases and 817 controls with age ranged between 38 and 85, with mean age 62.4 (SD 6.2) were collected between 2007 -2009 as part of the UKGPCS Prostate Cancer Study. The data on subjects’ body fat distribution type including “apple” (body fat mostly around the waist and upper trunk), “pear” (body fat around hips), “oval” (body fat generalised on whole body) and “symmetrical” were obtained through self report diagrams in questionnaires after consent from the subjects. Unconditional logistic regression analysis, with adjustment for age, education, ethnic, family history and lifetime body shape size as potential confounders, were carried out to obtain odds ratios and confidence intervals for different types of body fat distribution to assess their possible association with risk of prostate cancer. Results: A “symmetrical” body shape was used as the reference category. Subjects with an “apple” shape were at a significantly 30% reduced risk (adjusted OR 0.70 with 95% CI: 0.55-0.89). Subjects with an “oval” or “pear” shapes did not show any statistically significant association. Conclusion: An “apple” body fat distribution was associated with reduced prostate cancer risk when compared to symmetrical shape.
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 642. doi:1538-7445.AM2012-642
Abstract 643: Vitamin D deficiency increases breast cancer risk: A population based case-control study in the Chinese population
Authors: Chen Peizhan , Gu Xiaoli , Liu Yanling , Li Xiaoguang , Li Chenglin , Hu Pingting , Wang Yuan , Ou Zhouluo , Wang Hui 
Published: August 2012

Abstract
Vitamin D plays an important role in metabolism, cellular function and reproduction. Vitamin D has also been suggested to have potential protective effects against many cancers including breast cancer; however, the data from the epidemiological studies have been inconclusive. Our previous meta-analysis have found high dietary vitamin D intake significantly decreased breast cancer risk (RR = 0.91, 95% CI = 0.85-0.97) and women with higher circulating 25(OH)D level showed about 45% (95% CI = 0.38-0.80) decrease in breast cancer risk (Breast Cancer Res Treat. 2010;121(2):469-77). In a population-based case control study with 593 cases and 580 controls from Shanghai area, we have found that 80% of the normal women with severe vitamin D deficiency (less than 20ng/mL), 15.2% were of deficiency status (20 to 30ng/mL). Only 4.8% of women had sufficient vitamin D level (&gt; 30ng/mL). However, in the breast cancer patients, nearly 96.1% were of vitamin D severe deficiency, 3.2% were of vitamin D deficiency and only 0.7% had sufficient levels. Based on a logistic regression analysis, compared to those with the lowest quintile of plasma 25(OH)D level, women with higher level had significant lower breast risk (Q2 vs. Q1, OR = 0.45, 95% CI = 0.33-0.63; Q3 vs. Q1, OR = 0.25, 95% CI = 0.17-0.36; Q4 vs.Q1, OR = 0.09, 95% CI = 0.06-0.15) showing a significant dose-effect relationship (p-trend &lt; 0.001) after adjusted for the co-variants. We also found a seasonal distribution of vitamin D. Significantly lower vitamin D levels were found for the cases and controls in spring and summer (p &lt; 0.01). In the controls the mean level of vitamin D was higher in the summer (17.76ng/ml) and autumn (16.25ng/ml), and lower in the spring (15.67ng/ml) and winter (10.75ng/ml). However, in the breast cancer patients, the plasma level of vitamin D was highest in the autumn (14.38ng/ml) and lowest in the spring (10.16ng/ml). These results provide a strong evidence that vitamin D may have a chemo-preventive effect against 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 643. doi:1538-7445.AM2012-643