bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 586: Withaferin-A inhibits prostate tumor growth by enhancing anti-tumor immune response
Authors: Singh Rajesh , Grizzle William E. , Lillard James W. , Singh Shailesh 
Published: August 2012

Abstract
Indolent nature of prostate cancer provides a ‘large window’ of opportunity for chemopreventive strategies. Most chemopreventive strategies are primarily focused on controlling and/or reversing the mechanisms involved in neoplastic transformation and cancer progression. It is now well accepted that tumors evade the patient's defense system during progression and growth at distant sites. Mounting evidences suggest immunological defects in prostate cancer patients with higher numbers of functionally suppressive CD4+CD25+FOXP3+ T cells (Treg) and lower number of effectors T cells. Furthermore, tumor microenvironment exerts a profound immunosuppressive effect on effectors T cells by secreting TGF-β and IL-10. Therefore, modulating TGF-β and IL-10 using natural and dietary components constitutes an innovative approach for prostate cancer prevention and treatment. In this study, we have shown that Withaferin-A (WA), a bioactive compound isolated from Withania Somnifera also called “Ashwagandha” has the ability to modulate immunosuppressive cytokines (IL-10 and TGF-β) produced by the prostate cancer cells. Additionally, we show selective inhibition of Treg proliferation and induction of apoptosis in Tregs cells in immune competent prostate cancer mouse model treated with WA compared to controls. Our results suggest that WA have potential to fine-tune immunosuppressive phenotype of tumor-associated lymphocytes by modulating immuno-suppressive cytokines. Significant inhibition of tumor growth in immune competent prostate cancer mouse model as compared to immune deficient xenograft suggest potential role of WA on reversal of anti-tumor immune response from immune suppression to immune competence, which is required to fight against prostate 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 586. doi:1538-7445.AM2012-586
Abstract 587: Phenethyl isothiocyanate suppresses inhibitor of apoptosis family protein expression in prostate cancer cells in culture and in vivo
Authors: Sakao Kozue , Desineni Sudhakar , Hahm Eun-Ryeong , Singh Shivendra V. 
Published: August 2012

Abstract
Bioactive food components continue to gain traction for possible chemoprevention of prostate cancer, which is a leading cause of cancer-related death among American men. Phenethyl isothiocyanate (PEITC) is one such compound that is under active investigation for chemoprevention of prostate cancer as well as other types of malignancies, including colon, lung, and breast cancers. PEITC occurs naturally as a thioglucoside conjugate (gluconasturtiin) in a variety of edible cruciferous vegetables (e.g., watercress), and is generated upon cutting or chewing of cruciferous vegetables due to myrosinase-catalyzed breakdown of the gluconasturtiin. Initial evidence supporting prostate cancer protective effect of cruciferous vegetables emerged from population-based case control studies. In vivo chemopreventive efficacy of PEITC against prostate cancer has now been demonstrated in a transgenic mouse model (Transgenic Adenocarcinoma of Mouse Prostate mice; hereafter abbreviated as TRAMP mice). Post-initiation cancer chemopreventive response to PEITC is associated with apoptosis induction but the mechanism of cell death is not fully understood. The present study was undertaken to determine the role of inhibitor of apoptosis (IAP) family proteins in regulation of PEITC-induced apoptosis. The IAP family proteins play critical roles in apoptosis regulation by inhibiting caspases. Elevated expression of IAP proteins, including X-linked inhibitor of apoptosis (XIAP) and Survivin has been reported in human prostate cancers. Exposure of PC-3 and LNCaP human prostate cancer cells to PEITC resulted in downregulation of XIAP and Survivin proteins and suppression of Survivin mRNA expression. PEITC administration to Transgenic Adenocarcinoma of Mouse Prostate mice caused modest but significant downregulation of XIAP and Survivin proteins in the dorsolateral prostate. Proapoptotic response to PEITC was significantly attenuated by ectopic expression of XIAP and Survivin proteins. In addition, Survivin overexpression conferred modest but significant protection against PEITC-mediated inhibition of PC-3 cell migration. In conclusion, these results indicate that cellular responses to PEITC, including apoptosis induction and inhibition of cell migration, in prostate cancer cells are mediated by downregulation of XIAP and/or Survivin, which may serve as valid biomarkers to assess PEITC response in future clinical investigations. This investigation was supported by the USPHS grant RO1 CA101753-08.
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 587. doi:1538-7445.AM2012-587
Abstract 588: Evidence for a role of a P2X7- EHBP1-Akt axis in prostate carcinogenesis and in statin chemo-prevention
Authors: Ghalali Aram , Wiklund Fredrik , Darabi Hatef , Högberg Johan , Stenius Ulla 
Published: August 2012

Abstract
Prostate cancer (PCa) is the most commonly diagnosed cancer (over 30% of all cancer in men) and the second leading cause of cancer death in men. Statins, HMG-CoA reductase inhibitors, are potent cholesterol lowering drugs. Recent epidemiology suggests that statins prevent aggressive PCa development. In previous cell experiments we have shown that statins can down-regulate nuclear Akt responses to insulin (J Biol Chem 2010; 285, 27900). We showed that atorvastatin decreases nuclear phosphorylated Akt (pAkt) levels in pancreatic and lung cancer cell lines within minutes. These effects were mediated by the P2X7 receptor, and its natural ligand, extracellular ATP, induced the same effects as statins. Our published work also implicates PTEN, PHLPP1 and 2 and other phosphatases, which form protein complexes. Akt has oncogene activity in PCa and many other cancer types, and we have now tested the possibility that the P2X7-Akt pathway is of importance for the anticipated anticancer effects of statins in the prostate. We performed SNP analysis of two cohorts of PCa patients (Cgems and Gasp). We found significant associations for SNPs in Akt1, Caveolin1, P2X7, NEDD4-1 and EHBP1 genes. NEDD4-1 negatively regulates PTEN. EHBP1 is a previously shown risk factor for aggressive PCa, and has been implicated in plasma membrane trafficking. A signaling pathway analysis (Hum Hered 2011; 71, 11) also indicated significant associations to PCa (p = 0.043). EHBP1 showed the strongest influence. In additional cell studies we employed PCa cells and found that knock down of EHBP1 or p110α (previously shown to have oncogenic activity in PCa; Nature 2008; 454, 776) prevented depletion of nuclear Akt. In further long term cell experiments (several weeks) we found that high concentrations of statins resulted in a decreased expression of p110α. We also overexpressed a mutated NEDD4-1 and this treatment inhibited the effect of statin on nuclear pAkt in PCa cells (DU145). Taken together this study provides evidence for a role of a putative P2X7-EHBP1-Akt axis in PCa development. As this pathway is negatively regulated by statins it may have a role in the indicated chemo-preventive effect of statins.
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 588. doi:1538-7445.AM2012-588
Abstract 590: Andrographolide suppresses prostate cancer cell migration and alters the expression of vimentin, ZO-1 and MMP-11
Authors: Banerjee Aditi , Casillas Joseph , Sanchez Maria , Rohena Krizia , Martinez-Ferrer Magaly 
Published: August 2012

Abstract
Prostate cancer is the most common cancer and the second cause of cancer-related deaths in males in the United States. The development of novel chemopreventive strategies may be extremely helpful to prevent and arrest the development of this neoplasm. Andrographolide, a labdane diterpenoid that is the main bioactive component of the medicinal plant Andrographis paniculata, has anti-inflammatory and anticarcinogenic properties. In this study, we sought to examine the effect of andrographolide on PC3 and LNCaP prostate cancer epithelial cells. Andrographolide significantly inhibited PC3 cell growth at a concentration of 10µM after 24 h of treatment (P &lt; 0.001), and inhibited LNCaP cell growth at a concentration of 15 µM after 24 h of treatment (P &lt; 0.001). Wound healing assay and boyden chamber experiments were performed in order to determine whether andrographolide had an effect on migration and invasion. When PC3 and LNCaP cells were treated with andrographolide the total number of migrating and invading cells was significantly reduced (P &lt; 0.001) when compared to control. To study possible anti-migration and anti-invasion mechanisms of andrographolide on PC3 and LNCap cells, we examined the expression of various adhesion molecules. Andrograholide significantly decreased the expression of vimentin in PC3 and LNCap treated cells. However, PC3 and LNCaP cells treated with andrographolide had increased expression levels of occludin and ZO-1. In addition, immunofluorescence and western blot analysis showed that PC3 and LNCaP cells treated with andrographolide had decresased expression levels of MMP-11. Our results suggest that the anti-migration and anti-invasion effects of andrographolide in PC3 and LNCaP cells may be associated with alterations in the expression of occluding, ZO-1 and MMP-11.
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 590. doi:1538-7445.AM2012-590
Abstract 593: Mechanisms for inhibition of rodent mammary carcinogenesis by wheel running and/or dietary energy restriction
Authors: Jiang Weiqin , Zhu Zongjian , McGinley John N. , Neil Elizabeth , Thompson Henry J. 
Published: August 2012

Abstract
Our laboratory has reported the inhibitory effects of combined physical activity (PA) and dietary energy restriction (DER) on mammary carcinogenesis while the associated mechanisms are rarely investigated. The objective of this experiment was to determine the cellular regulation of mammary cancer by PA and/or DER. Female Sprague Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter randomized to: 1) sedentary control, 2) PA at wheel running high (WR-HIGH, 3.4 km per day); or the energy balance equivalents of PA: 3) PA at wheel running low (WR-LOW, 1500 revolutions per day + DER), or 4) DER. In order to investigate the effects of physical activity at a constant intensity, rats were given free access to a motorized activity wheel (55 m/min) with reinforcement of running behavior using a food reward system. The duration of this experiment was 8 weeks. Overall, PA and/or DER reduced mammary cancer incidence, cancer multiplicity, and tumor burden and prolonged cancer latency (p&lt;0.05) in comparison to the sedentary control group. PA, DER, or their combination differentially affected host systemic factors including bioavailable IGF-1 and adipokines (leptin and adiponectin) and cell autonomous mechanisms including modulation of FoxO and down regulation of Akt/mTOR signaling. Mediation appears to be via inhibition of cell proliferation and induction of apoptosis. Supported by PHS grant CA100693 from the National Cancer Institute.
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 593. doi:1538-7445.AM2012-593
Abstract 603: Targeted Casp8AP2 methylation increased drug resistance in mesenchymal stem cell and cancer cells
Authors: Leu Yu-Wei , Pai Mei-Yu , Hsu Chia-Chen , Lee Kuan-Der , Chen Chih-Cheng , Chen Yao-Li , Huang Tim H.-M. , Hsiao Shu-Huei 
Published: August 2012

Abstract
Casp8AP2 is a FLASH protein that is critical for the formation of death complex and the relay of death signal into the cells. Genetic defect of Casp8AP2 was found in diseases like acute lymphoblastic leukemia, implying that the miss-expression of Casp8AP2 might cause disease. On the other hand, the promoter of Casp8AP2 is enriched with CpG islands and we observed differential methylation changes within Casp8AP2 promoter during mesenchymal stem cell (MSCs) differentiation. Aberrant DNA methylation was also identified within the Casp8AP2 promoter in vivo like in liver cancers. It was then hypothesized that the abnormal DNA methylation within the Casp8AP2 promoter might contribute to the enhanced survival or drug resistance in cancer development. We determined the epigenetic states within the Casp8AP2 promoter in different cells and confirmed that there are methylation differences between the normal and tumoral samples within the Casp8AP2 promoter. Differential methylation was also observed between the drug resistant cancer cells and primary cancer cells. Global demethylation in drug resistant cell lines reversed the Casp8AP2 methylation, which was correlated with the reversed resistance phenotype. We then target-methylated the Casp8AP2 promoter in normal somatic stem cells and cancer cells like MDA-MB-231 and found increased drug resistance in these cells. These data point out that methylation within the death complex like Casp8AP2 might be able to serve as biomarker and treatment target for drug resistance in cancer cells. (Supported in part by NSC100-2320-B-194-001)
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 603. doi:1538-7445.AM2012-603
Abstract 61: A new serotype chimera Cancer Terminator Virus (Ad.5/3-CTV) expands the efficiency and specificity of prostate cancer gene transfer and therapy
Authors: Azab Belal , Dash Rupesh , Das Swadesh , Bhutia Sujit , Shen Xue-Ning , Quinn Bridget , Dasgupta Santanu , Dent Paul , Dmitriev Igor , Wang Xiang-Yang , Curiel David , Grant Steven , Pellecchia Maurizio , Reed John , Sarkar Devanand , Fisher Paul 
Published: August 2012

Abstract
Conditionally replication-competent adenoviruses (CRCAs) represent potentially useful reagents for treating prostate cancer (PC). We previously constructed a unique CRCA, Cancer Terminator Virus (CTV), in which the E1A gene, necessary for adenoviral replication, is controlled by the cancer-selective Progression Elevated Gene-3 (PEG-3) promoter and which simultaneously expresses melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) from the E3 region of the adenovirus. mda-7/IL-24, a novel member of the IL-10-related cytokine gene family, displays almost ubiquitous antitumor properties in vitro and in vivo, leading to its rapid entry into the clinic, where its safety and clinical efficacy, when administered by adenovirus (Ad.mda-7; INGN 241), was observed in a phase I clinical trial in humans with advanced carcinomas and melanomas. mda-7/IL-24 preferentially induces apoptosis in cancer cells while exerting no discernible toxic effects toward normal cells and it also elicits potent “antitumor bystander activity” in distant cancer cells as a consequence of autocrine and paracrine secretion of MDA-7/IL-24. The CTV was generated on a serotype 5 background (Ad.5-CTV) with infectivity depending on Coxsackie-Adenovirus Receptors (CARs). CARs are frequently reduced in many tumor types, including PCs thereby limiting effective therapy. Using serotype chimerism, a novel CTV (Ad.5/3-CTV) was created by replacing the Ad.5 fiber knob with the Ad.3 fiber knob facilitating infection in a CAR-independent manner. We evaluated Ad.5/3-CTV in comparison with Ad.5-CTV in low CAR human PC cells, demonstrating higher efficiency in inhibiting cell viability in vitro. Moreover, Ad.5/3-CTV potently suppressed in vivo tumor growth in a nude mouse xenograft model and in a spontaneously induced PC in Hi-myc transgenic mice. Ad.5/3.CTV exerted a marked anti-tumor ‘bystander’ effect in vivo confirming therapeutic utility. In these contexts, and considering the significant responses in a Phase I clinical trial of a non-replicating Ad.5-mda-7, the use of Ad.5/3-CTV to administer therapeutic and cytotoxic mda-7/IL24 to selectively induce cytolysis and apoptosis in prostate tumor cells represents a viable treatment options. (Supported by R01 CA097318 and P01 CA104177)
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 61. doi:1538-7445.AM2012-61
Abstract 619: Flavokawain A inhibits urinary bladder carcinogenesis in the UPII-SV40T transgenic mouse bladder cancer model.
Authors: Liu Zhongbo , Li Xuesen , liu Shuman , Xu Xia , Tian Xuejiao , Simoneau Anne R. , Wu Xue-Ru , Zi Xiaolin 
Published: August 2012

Abstract
The UPII-SV40T transgenic model of the mouse bladder reproduces a precursor to recurrent and invasive Transitional Cell Carcinoma (TCC): carcinoma in situ (CIS). This model therefore is useful for testing the potential of agents for preventing bladder cancer recurrence. Flavokawain A is the predominant chalcone identified from the kava plant. We have recently shown that flavokawain A exhibited strong growth inhibitory effects on human bladder cancer cell lines both in vitro in cell cultures and in vivo in a xenograft mouse model. In this study, we examine whether flavokawain A can also inhibit bladder cancer development in the UPII-SV40T transgenic model. The transgenic mice were identified through genotyping using Southern blotting analysis. Both heterozygous and homozygous UPII-SV40T mice were fed orally with vehicle control or 6 g flavokawain A /kg food for 9 months starting at 6 weeks of age. More than 54% control food- fed male mice died of ureter obstruction and nephrohydrosis within 10.5 months of age, while more than 67% of mice fed with 6g flavokawain A /kg food survived beyond 10.5 months of age. The mean bladder weight of male transgenic mice that were fed with 6g flavokawain /kg food for 9 months decreased by about 46% compared to those fed with vehicle control diet (mean bladder weights for vehicle control versus flavokawain A treatments are 0.2031±0.016 versus 0.1108±0.02565, P=0.0037). The mean bladder weights of female transgenic mice that were fed with 6g flavokawain /kg food for 9 months decreased by 31% compared to those fed with vehicle control diet (mean bladder weights for vehicle control versus flavokawain A treatments are 0.0466±0.0052 versus 0.03225±0.004689, p=0.0556). Mouse pathology analysis revealed that vehicle control treated mice exhibited poorly differentiated transitional cell carcinoma in the bladder, while that flavokawain A treated mice presented well differentiated tumors in the bladder. The bladder tissues from flavokawain A treated mice showed a decreased number of Ki67 positive cells compared to those in vehicle control treated mice, which suggested that flavokawain A inhibited cell proliferation in vivo in bladder tumors. These results suggested a potential of flavokawain A in preventing the recurrence of non-muscle invasive urinary bladder cancer by treating CIS.
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 619. doi:1538-7445.AM2012-619
Abstract 623: Prostate cancer and B-vitamins
Authors: Vidal Adriana , Grant Delores , Williams Christina , Allott Emma , Masko Elizabeth , Freedland Stephen J. , Hoyo Cathrine 
Published: August 2012

Abstract
BACKGROUND. Recent reports suggest that excess of nutrients involved in the one-carbon metabolism pathway increases PC risk, however empirical data are lacking. Our hypothesis was to examine whether excessive intake of one carbon nutrients was associated with PC risk and whether this association was similar in LG vs. HG prostate cancer. METHODS. Veteran American men (272 controls and 144 PC cases) who attended the Durham Veteran American Medical Center, between 2004-2011, were enrolled into a case-control study. Intake of folate, vitamin B12, B6 and methionine were measured using a food frequency questionnaire. Regression models were used to evaluate the association among one-carbon cycle nutrients, MTHFR genetic variants and prostate cancer. RESULTS. Higher methionine intake was positively associated with PC risk, OR=2.1 95%CI 1.1-3.9, p=0.02; a risk which increased for low grade PC or Gleason &lt;7, OR=2.75 (95%CI 1.32-5.73), p=0.007. These associations did not vary by MTHFR C677T genotype, however the cross-product term for the association of MTHFR A1298C variant and methionine was statistically significant, compared to non-carriers (p=0.045). Evidence for associations between B vitamins (folate, B12 and B6) and PC risk were less clear. CONCLUSIONS. Our results suggest that high methionine intake increases PC risk. Higher intakes of folate and vitamin B6 may be protective against advanced prostate cancer- however the associations were weak, while vitamin B12 higher intakes showed a trend for significance for higher PC risk. Individuals carrying MTHFR A1298C variants, and consuming more than the recommended levels of methionine, may be at higher risk for PC. Key words: Prostate cancer (PC), folate, vitamins B6, B12, methionine, methylenetetrahydrofolate reductase (MTHFR).
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 623. doi:1538-7445.AM2012-623