bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3674: Chemoprevention of endometrial cancer with urolithin A, a metabolite of berry ellagitannins.
Authors: Huang Yi-Wen , Kuo Chieh-Ti , Siddiqui Jibran , Chen Jo-Hsin , Shiau Chung-Wai , Stoner Gary D. 
Published: August 2014

Abstract
Berries have been reported to elicit chemopreventive effects in cell culture, in animal model systems and in humans. Bio-fractionation studies indicate that the chemopreventive effects of berries can be ascribed to their component anthocyanins, ellagitannins and compounds in the non-alcohol soluble (fiber) fraction. In the present study, 17 berry-related compounds were evaluated at concentrations ranging from 1- 50 μM for their anti-proliferative effects on cultured human endometrial cancer cell lines (ECC-1, Ishikawa and HEC1A). These compounds include the anthocyanins; cyandin-3-glucoside and cyanidin-3-rutinoside and their metabolite, protocatechuic acid; ellagic acid and its metabolites, urolithins A and B; and three oligosaccharides, four short-chain carboxylic acids and four lignans present in the fiber fraction. Cell proliferation assays indicated that urolithin A was the most effective inhibitor of the growth of all three endometrial cancer cell lines. Cell cycle analysis by flow cytometry revealed that urolithin A induced cell cycle arrest at the G2/M phase. This was associated with up-regulation of the protein expression of cyclins B1 and E2, p21, phospho-cdc2 and myt1 as determined by western blot analysis. Endometrial cells depend on progesterone to limit cellular growth because it is antagonistic to estrogen-mediated cell proliferation. It is of importance therefore, that urolithin A was found to reduce estrogen receptor alpha and induce progesterone receptor expression in all three cell lines. In summary, our findings suggest that urolithin A may be chemopreventive for endometrial cancer through modulating genes that control the G2/M phase of the cell cycle and that regulate steroid receptor expression. This research was supported, in part, by MCW Startup Funds to Y-W Huang.
Citation Format: Yi-Wen Huang, Chieh-Ti Kuo, Jibran Siddiqui, Jo-Hsin Chen, Chung-Wai Shiau, Gary D. Stoner. Chemoprevention of endometrial cancer with urolithin A, a metabolite of berry ellagitannins. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3674. doi:10.1158/1538-7445.AM2013-3674
Abstract 3680: Targeting IGF-1R for inhibition of pancreatic cancer metastasis by pomegranate fraction.
Authors: Vadhanam Manicka V. , Gupta Ramesh C. , McNally Lacey R. 
Published: August 2014

Abstract
Patients with pancreatic adenocarcinoma have the lowest 5-year survival rate with more than 95% of the patients dying within 5 years and median survival of &lt;6 months. The incidence of pancreatic cancer is also increasing by 1.5% per year since 2004. At present, there are limited treatment options and no early detection strategies for the disease. Although ∼ 20% of patients are eligible for surgical and chemotherapy intervention, these patients typically die of metastasis. Therefore, the prevention of these metastases would greatly improve patient care. Insulin-like growth factor receptor 1 (IGF-1R) is commonly over-expressed in metastases as compared to primary tumor. The aggressive forms of tumors overexpress the receptor when compared to less aggressive, non-metastatic tumors. In order to test this concept, we tested two metastatic pancreatic cell lines, S2VP10 and S2CP9 and three non-metastatic cell lines, Panc-1, AsPc-1 and MiaPaCa-2. Immunoblotting revealed the overexpression of IGF-1R specifically in the metastatic pancreatic cell lines. Pomegranate has recently gained much attention for its chemopreventive efficacy. We had previously demonstrated that the less-polar pomegranate component of the peel target IGF-1R signaling pathway in prostate cells. To test the efficacy of the pomegranate component against pancreatic cancer cells, we treated the highly aggressive S2VP10 cells with fractions derived from different parts of pomegranate. The water-insoluble fraction of pomegranate peel was most efficacious with an IC50 of 62 μg/ml. Molecules related to IGF-1R signaling were analyzed by immunoblotting. IRS-1, a docking protein for the receptor decrease significantly in a dose-dependent manner. A dose-dependent decrease of phosphorylation of the IGF-1R receptor was also observed. Dose-dependent decreased protein levels of BCL2 and increased levels of caspase 9 confirmed the effect of pomegranate fraction on apoptosis; and increased levels of p21 protein and decreased levels of cyclin D1 confirmed the effect on cell proliferation. Thus, we hypothesize that targeting IGF-1R signaling axis with pomegranate fraction will decrease survival of pancreatic tumor cells and decrease metastasis. Studies are currently underway to assess the anti-metastatic effect in vivo.
Citation Format: Manicka V. Vadhanam, Ramesh C. Gupta, Lacey R. McNally. Targeting IGF-1R for inhibition of pancreatic cancer metastasis by pomegranate fraction. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3680. doi:10.1158/1538-7445.AM2013-3680
Abstract 3682: Differential effect of withaferin A treatment on activation of Notch1 and Notch2 in human breast cancer cells.
Authors: Lee Joomin , Sehrawat Anuradha , Singh Shivendra V. 
Published: August 2014

Abstract
Withaferin A (WA), a constituent of the Ayurvedic medicine plant Withania somnifera, exhibits in vivo efficacy against human breast cancer xenografts in athymic mice as well as spontaneous mammary cancer development in MMTV-neu transgenic mice. However, the mechanism underlying anticancer effect of WA is not fully understood. The present study was undertaken to determine the role of Notch family of transcription factors in anticancer effects of WA using human breast cancer cells as a model. Notch activation is linked to mammary carcinogenesis as evidenced by the following observations: (a) overexpression of activated Notch1 and Notch3 in transgenic mice blocks mammary gland development but induces tumorigenesis of the breast; (b) high level expression of Notch1 and its ligands is associated with poor outcome in breast cancer; (c) expression of Notch ligand Jagged1 is associated with recurrence in lymph node-negative breast cancer; and (d) Notch1 is involved in migration and invasion of human breast cancer cells. The present study reveals differential effect of WA treatment on activation of Notch1 versus Notch2 in human breast cancer cells. Exposure of MDA-MB-231 (an estrogen-independent cell line with mutant p53) and MCF-7 (an estrogen-responsive cell line with wild-type p53) human breast cancer cells to pharmacological concentrations of WA (2 and 4 μM) resulted in cleavage (suggesting activation) of Notch2, which was accompanied by transcriptional activation of Notch as evidenced by RBP-Jk, HES-1A/B, and HEY-1 luciferase reporter assays. On the other hand, WA treatment caused a decrease in levels of both transmembrane and cleaved (active) Notch1. The WA-mediated activation of Notch2 was associated with induction of γ-secretase complex components presenilin1 and/or nicastrin. Inhibition of MDA-MB-231 and MDA-MB-468 cell migration resulting from WA exposure was statistically significantly augmented by knockdown of Notch2 using siRNA and shRNA. Activation of Notch2 was not observed in cells treated with withanone or withanolide A, which are structural analogs of WA. Moreover, withanone and withanolide A were practically inactive against MDA-MB-231 cell migration. The results of the present study suggest that anti-metastatic effect of WA may be augmented in the presence of Notch2 inhibitors. This study was supported by the grant CA142604 awarded by the National Cancer Institute.
Citation Format: Joomin Lee, Anuradha Sehrawat, Shivendra V. Singh. Differential effect of withaferin A treatment on activation of Notch1 and Notch2 in human breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3682. doi:10.1158/1538-7445.AM2013-3682
Abstract 3688: Leptin contributes to prostate cancer progression.
Authors: De Velasco Marco A. , Yamamoto Yutaka , Hatanaka Yuji , Kura Yurie , Ando Naomi , Fukushima Emiko , Nozawa Masahiro , Shimizu Nobutaka , Yoshimura Kazuhiro , Yoshikawa Kazuhiro , Nishio Kazuto , Uemura Hirotsugu 
Published: August 2014

Abstract
Obesity is a complex chronic disorder that can result in a number of metabolic and endocrine disturbances and may thus account for the disparity seen in epidemiologic studies investigating the association between obesity and prostate cancer. Although the association between dietary factors and the occurrence of prostate cancer has been studied extensively, there is yet to be a published study on the relationship between diet and disease progression among prostate cancer patients. Circulating levels of most adipokines are positively correlated with obesity and exert a variety of biologic effects on prostate cancer cells modulating a variety of cellular processes. This would suggest that the presence of obesity may promote the progression of established prostate cancer rather than being a risk factor for the development of prostate cancer; however, a direct link has yet to be established. Recognizing adipose tissue as a metabolically active endocrine organ and identifying tumor promoting adipokines would support such an association.
To better understand the effects of increased dietary fat in prostate cancer, we used the prostate-specific PTEN conditional knockout mouse model to show that consumption of a high-fat diet (HFD) promoted prostate-specific cancer progression and decreased survival. Molecular analysis identified elevated levels of leptin as a likely molecule involved in driving tumor progression. In this study we provide data from in vitro experiments show that leptin promoted invasiveness, motility and adhesion of PC3, human prostate cancer cells. Together, our findings show that increased levels of leptin, induced by dietary fat, contributes to promote prostate cancer progression by upregulating STAT3 signal cascades.
Citation Format: Marco A. De Velasco, Yutaka Yamamoto, Yuji Hatanaka, Yurie Kura, Naomi Ando, Emiko Fukushima, Masahiro Nozawa, Nobutaka Shimizu, Kazuhiro Yoshimura, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura. Leptin contributes to prostate cancer progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3688. doi:10.1158/1538-7445.AM2013-3688
Abstract 3690: p53 stabilizing agent CP-31398 prevents urinary bladder tumor growth and invasion in transgenic UPII-SV40T mice.
Authors: Madka Venkateshwar , Zhang Yuting , Li Qian , Mohammed Altaf , Lightfoot Stan , Xue Wu Re , Kopelovich Levy , Rao Chinthalapally V. 
Published: August 2014

Abstract
The United States will have approximately 73,510 new cases of bladder cancer in 2012 with 14,880 deaths. More than 50% of the invasive (lamina and muscularis) bladder tumors have mutations in p53 and/or pRB. p53 appears to play a major role in the etiology of human bladder cancer, particularly in the high grade invasive type. Structural and functional defects in p53 are found in majority of human transitional cell carcinomas (TCC). The high prevalence of bladder cancer and the frequency of tumor recurrence make it an important target for chemoprevention. In UPII-SV40T transgenic mice, induced bladder TCC bears strong resemblance to that of human TCC in phenotype and in the mode of progression. In the present study, we determined the chemopreventive efficacy of a p53 stabilizing agent, CP-31398, using transgenic UPII-SV40T mouse model. After genotyping, six-week old UPII-SV40T mice (n=32/group) were fed control (AIN-76A) or experimental diets containing 150 or 300 ppm CP-31398 for ∼34 weeks. Progression of bladder cancer was monitored by MRI imaging. At 40 weeks of age, all mice were euthanized; urinary bladders were collected to determine weights, tumor incidence and multiplicity; and histopathology. There was a significant increase in bladder weights of transgenic vs. wild type mice (male 140.2 mg vs. 27.3 mg, p&lt;0.0001; female 34.2 mg vs, 14.8 mg p&lt;0.0001, respectively). A significant decrease in the tumor growth as evidenced by decreased bladder weights (by 52-65%, p&lt;0.000 in males; by 32 %, p&lt;0.001 in females) was observed in CP-31398 treated mice. Invasive papillary TCC incidence was 100 % in transgenic mice fed with control diet. The mice exposed to 150 and 300 ppm CP-31398 showed dose dependent inhibition (29%, p&lt;0.01; 57%, p&lt;0.005) of invasive TCC with 28% and 53% carcinoma In situ, respectively, suggesting suppression of invasive tumor growth. Kidney abnormalities like ureter obstruction and nephrohydrosis were observed in almost all control mice but significantly less frequent in CP-31398-fed mice. Molecular analysis of the bladder tumors showed an increase in apoptosis markers (p53, p21, Bax) with a decrease in angiogenic markers (CD31 and VEGF) in transgenic mice fed with CP-31398. These results suggest that p53 modulating agents can serve as potential chemopreventive for bladder TCC. (Supported in part by NCI-CN53300)
Citation Format: Venkateshwar Madka, Yuting Zhang, Qian Li, Altaf Mohammed, Stan Lightfoot, Wu Re Xue, Levy Kopelovich, Chinthalapally V. Rao. p53 stabilizing agent CP-31398 prevents urinary bladder tumor growth and invasion in transgenic UPII-SV40T mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3690. doi:10.1158/1538-7445.AM2013-3690
Abstract 3706: Intervention of human breast cell carcinogenesis chronically induced by 3, 4, 4’-trichlorocarbanilide.
Authors: Sood Shilpa , Choudhary Shambhunath , Wang Hwa-Chain R. 
Published: August 2014

Abstract
The purpose of this study was to investigate the ability of antimicrobial agent 3,4,4’-trichlorocarbanilide (TCC) to induce breast cell carcinogenesis, and then identify preventive agents to intervene in TCC-induced breast cell carcinogenesis. TCC is widely used in personal care products such as bath soaps, detergents, and cleansing lotions. Recent studies suggest that TCC acts as an endocrine disruptor to enhance the ability of steroid hormones (estrogen or testosterone) to induce estrogen and androgen receptor-mediated gene expression. Due to its environmental persistence and wide use, there are concerns about TCC's possible impact on human health. To determine whether TCC exposure may contribute to the development of breast cancer, we used our chronically-induced breast cell carcinogenesis model to determine the ability of TCC to induce progressive carcinogenesis of human breast epithelial MCF10A cells to acquire cancer-associated properties. We found that chronic exposure of MCF10A cells to TCC at physiologically-achievable nanomolar levels resulted in cellular acquisition of the cancer-associated properties of reduced dependence on growth factors, anchorage independent growth, and increased cell proliferation. These cellular changes were accompanied by upregulation of the ERK pathway, Nox1-induced ROS production, and DNA damage. We also found that curcumin, a component of turmeric extracted from the rhizome of the Indian herb Curcuma longa, was able to suppress TCC-induced cellular carcinogenesis. Our study revealed, for the first time, that chronic exposure to TCC was able to induce breast cell carcinogenesis, and TCC-induced cellular carcinogenesis was preventable by curcumin.
Citation Format: Shilpa Sood, Shambhunath Choudhary, Hwa-Chain R. Wang. Intervention of human breast cell carcinogenesis chronically induced by 3, 4, 4’-trichlorocarbanilide. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3706. doi:10.1158/1538-7445.AM2013-3706
Abstract 3708: Effects of black raspberry and related components on DB[a,l]P-induced DNA adduct formation in mouse oral tissues.
Authors: Chen Kun-Ming , Zhang Shang-Min , Aliaga Cesar , Sun Yuan-Wan , Berg Arthur , Sharma Arun , Amin Shantu , Stoner Gary , El-Bayoumy Karam 
Published: August 2014

Abstract
Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck region; in the USA, over 45,000 cases and about 11,000 deaths from the disease occur annually. Progress in the prevention and control of OSCC has been hampered by the lack of appropriate animal models that would reflect human exposure. Tobacco smoking is considered a major etiological factor in the development of oral cancer. Previous studies have demonstrated the ability of diets containing 5-10% freeze-dried black raspberry (BRB) powder to inhibit the development of chemically-induced cancers in multiple organ sites in rodents including 7,12-dimethylbenz(a)anthracene (DMBA) induced squamous cell carcinomas (SCC) in the hamster cheek pouch. DMBA, however, is not present in the environment and the hamster cheek pouch model may not be applicable to humans. Recently, we developed a relevant animal model (Int. J. Cancer, 2012, 2783-90) and showed that dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and a tobacco smoke component, induces SCC in oral tissues of mice. In the current study, we evaluated the effects of BRB and related components including kaempferol and resveratrol on DNA adducts induced by DB[a,l]P in mouse oral cavity as an initial step to explore the potential preventive activity of BRB and its related components on DB[a,l]P-induced oral cancer. The DB[a,l]PDE-DNA adduct levels were quantified by our recently developed LC-MS/MS method (Chem. Res. Toxicol. 2011, 1297-303). We demonstrated that the administration of BRB (5%), kaempferol (0.025%) or resveratrol (0.002%) in the diet, starting 2 weeks before DB[a,l]P (24 nmol, 3 times a week for 5 weeks) resulted in 27%, 36% or 65% reduction of the level of (-)-anti-trans-DB[a,l]PDE-dA in murine oral tissues, respectively. In conclusion, our results support that dietary consumption of BRB and its related components can inhibit the metabolic activation of DB[a,l]P, and may prevent the subsequent mutagenesis and carcinogenesis resulting from exposure to DB[a,l]P.
Citation Format: Kun-Ming Chen, Shang-Min Zhang, Cesar Aliaga, Yuan-Wan Sun, Arthur Berg, Arun Sharma, Shantu Amin, Gary Stoner, Karam El-Bayoumy. Effects of black raspberry and related components on DB[a,l]P-induced DNA adduct formation in mouse oral tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3708. doi:10.1158/1538-7445.AM2013-3708
Abstract 371: PGI2 analog enhances endothelial-pericyte interactions and suppresses lung metastasis.
Authors: Minami Yoshinori , Sasaki Takaaki , Endo Satoshi , Shibukawa Kiyoko , Ohsaki Yoshinobu 
Published: August 2014

Abstract
Background: Endothelial cells (ECs) express IP (prostaglandin I2 (PGI2) specific receptor) and are playing important role in tumor angiogenesis. We have reported that the PGI2-IP system is necessary for vascular remodeling and angiogenesis. Additionally, we have reported that the knockdown of IP increases tumor metastasis in mouse models.
Objectives: In this study, we examined whether the activated PGI2-IP signaling could enhance EC-PC interactions and suppress tumor metastasis.
Materials & Methods: Mouse-derived Lewis lung carcinoma (LLC) cells were used for a mouse lung metastatic model, and were injected from the tail vein of mice (c57BL/6J). Beraprost sodium (BPS; PGI2 analog) was continuously administered for 3 weeks. Tumor metastasis to lung was assessed by using hematoxylin-eosin staining. The a-SMA and the NG2 as a pericyte marker and the endomucin as an endothelial cell marker were analyzed by immunofluorescence to evaluate angiogenesis in metastatic lung tumors. The structure of the tumor blood vessels was analyzed by scanning electron microscopy (SEM).
Results: The size and number of lung metastatic nodules were significantly decreased in BPS group compared with in control group assessed by the mice lung metastatic model. Immunofluorescence analysis revealed that the number of vessel-associated a-SMA+ cells was significantly increased by BPS administration. Scanning electron microscopy revealed that pericytes covering the tumor blood vessels increased in BPS group.
Conclusions: The present study demonstrated that BPS suppresses lung metastasis in our model. These results also suggested that the maturation of tumor blood vessels by pericytes may decrease tumor metastasis. Finally, we propose that BPS would be a novel therapeutic target in lung metastasis.
Citation Format: Yoshinori Minami, Takaaki Sasaki, Satoshi Endo, Kiyoko Shibukawa, Yoshinobu Ohsaki. PGI2 analog enhances endothelial-pericyte interactions and suppresses lung metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 371. doi:10.1158/1538-7445.AM2013-371