bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3705: Deguelin suppresses epithelial to mesenchymal transition (EMT) in pancreatic cancer cells by Snail repression and RKIP induction: Pivotal role of NF-kB
Authors: Boreddy Srinivas Reddy , Srivastava Sanjay K. 
Published: June 2012

Abstract
Metastatic disease is a primary cause of death for most cancer patients and is associated with the loss of epithelial features and the acquisition of mesenchymal characteristics, a process known as epithelial to mesenchymal transition (EMT). Hence, targeting EMT would be a novel therapeutic modality in cancer prevention. Previous reports have shown that deguelin, a derivative of rotenone induces apoptosis in cancer cells by inhibiting AKT but its potential as anti-metastatic agent remained elusive. In the present study we investigated the anti-metastatic (EMT) properties of deguelin in PanC-1 and MIA PaCa-2 pancreatic cancer cells. Our results show that deguelin significantly (P&lt;0.0001) suppressed the migration of PanC-1 and MIA PaCa-2 cells in a wound healing assay. Further, deguelin treated PanC-1 and MIA PaCa-2 cells show reduced expression of E-cadherin and cytokeratin 18, the markers of epithelial cell phenotype. On the other hand, the expression of mesenchymal markers N-cadherin and vimentin were up regulated by degulin treatment in both the cell lines. Furthermore, deguelin significantly reduced the expression of Snail, a known EMT inducer, and increased the expression of RKIP, a tumor suppressor gene in both the cell lines. Since NF-kB hyperactivation is associated with tumor metastasis via regulation of EMT, we evaluated whether deguelin inhibit the phosphorylation of NF-kB in PanC-1 and MIA PaCa-2 cells. Our results show that deguelin significantly suppressed the constitutive phosphorylation of NF-kB at Ser-536. Inhibition of NF-kB activation by deguelin was further confirmed by DNA binding activity and EMSA. IL-1β has been shown to activate NF-κB and its transcriptional target Snail leading to increase in the expression of E-cadherin. Treatment of PanC-1 cells with IL-1β significantly attenuated deguelin induced E-cadherin repression and N-cadherin induction, indicating the involvement of NF-kB in deguelin mediated anti-metastatic activity. Ectopic expression of either Snail or NF-kB completely abolished EMT protection offered by deguelin in PanC-1 cells confirming the role of NF-kB and Snail in deguelin induced EMT inhibition. Taken together our results provide convincing evidence on the anti-metastsis properties of deguelin in pancreatic cancer. [Supported in part by R01 grants CA106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute].
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3705. doi:10.1158/1538-7445.AM2011-3705
Abstract 3706: Novel analogs of dietary thymoquinone with superior bioavailability and anti-tumor activity against GI cancers
Authors: Azmi Asfar S. , Padhye Subhash , Banerjee Sanjeev , Aboukameel Amro , Sarkar Fazlul H. , Mohammad Ramzi M. 
Published: June 2012

Abstract
Alterations in multiple signaling pathways are a hallmark of most epithelial cancers, including pancreatic (PC) and colon cancers (CC). In principle, agents such as dietary bioactive compounds that affect multiple pathways should exhibit superior effectiveness due to their pleiotrophic actions compared to single pathway targeted therapies. Earlier we had shown that thymoquinone (TQ), a bioactive agent derived from edible black seed plant Nigella Sativa exerts anticancer activity against PC and CC alone or can enhance the effects of chemotherapeutics through mechanisms involving down-regulation of multiple pathways [such as NF-kB, cell cycle, inflammation, anti-apoptosis and angiogenic signaling (Cancer Research 69(13) 2009)]. However, due to poor bioavailability the anti-tumor effects of TQ that are observed at pharmacological high doses (&gt;25 µM in vitro that translates to ∼7.4 g/kg in humans) cannot be considered clinically relevant. To address this problem we have developed a series of potent TQ analogs and among them two (TQ-THB and TQ-TFB patent pending) were found to have greater potency (growth inhibition and apoptosis) than parent TQ (IC50s 5 and 7µM respectively). TQ-THB and TQ-TFB not only show superior in vitro activity against PC, they also demonstrate greater anti-tumor activity in a highly metastatic BxPC-3 pancreatic xenograft model. The analogs are well tolerated and can be given i.v. Most interestingly, these analogs synergize with gemcitabine and FOLFOX that are the standard care for pancreatic and colon cancer respectively. The synergy was found both in cell culture and animal tumor models. Molecular Docking studies revealed that both TQ-THB and TQ-TFB binds very strongly to Cox-2 and NF-kB. This suggests that the analogs work by inhibiting the tumor survival and angiogenic pathways. Based on our novel findings we believe that these dietary analogs hold promise as anticancer agents that warrant further clinical development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3706. doi:10.1158/1538-7445.AM2011-3706
Abstract 3720: Obesity and mortality among black women and white women with invasive breast cancer
Authors: Lu Yani , Ma Huiyan , Malone Kathleen E. , Norman Sandra A. , Sullivan-Halley Jane , Strom Brian L. , Marchbanks Polly A. , Spirtas Robert , Burkman Ronald T. , Deapen Dennis , Folger Suzanne G. , Simon Michael S. , Press Michael F. , McDonald Jill A. , Bernstein Leslie 
Published: June 2012

Abstract
PURPOSE To evaluate the effect of obesity on survival among black and white women with invasive breast cancer; and determine whether different distribution of obesity accounts for the poorer survival of black women.
METHODS 4538 (1604 black, 2934 white) women ages 35 to 64 years when diagnosed with first incident invasive breast cancer between 1994 and 1998, who participated in the Women's Contraceptive and Reproductive Experiences Study, were followed up for a median of 8.6 years. Multivariate Cox regression models were used to examine height, body mass index (BMI, kg/m2) at different ages on the risk of all-cause mortality and breast cancer-specific mortality.
RESULTS During follow-up, 1053 (519 black, 534 white) women died, 828 (412 black, 416 white) from breast cancer. Compared to women with a recent (5 years before diagnosis) BMI of 20-24.9 kg/m2, those who were obese (BMI≥30 kg/m2) had a greater risk of all-cause mortality (relative risk [RR], 1.23; 95% confidence interval [CI], 1.04-1.47) and breast cancer-specific mortality (RR, 1.20; 95% CI, 0.99-1.46). However, these risk patterns were only observed among white women (all-cause RR, 1.54; 95% CI, 1.21- 1.96; breast cancer RR, 1.46; 95% CI, 1.11-1.92), but not among black women (all-cause RR, 1.03; 95% CI, 0.81-1.29; breast cancer RR, 1.02; 95% CI, 0.79-1.33).Similar risk patterns were observed in different strata of estrogen receptor(ER) status, tumor stage, menopausal status, and education level.
CONCLUSION Obesity may play an important role in mortality among white but not black breast cancer patients. It is unlikely that differences in obesity distributions between black and white women account for the poorer survival of black women.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3720. doi:10.1158/1538-7445.AM2011-3720
Abstract 3734: Alcohol consumption and breast cancer risk among Nigerian women
Authors: Hou Ningqi , Ogundiran Temidayo O. , Adebamowo Clement A. , Olopade Olufunmilayo I. , Huo Dezheng 
Published: June 2012

Abstract
Background: Alcohol consumption has been reported as a risk factor for breast cancer. However, little is known about its importance for indigenous African population, among whom the prevalence of breast cancer is relatively low. The purpose of this study was to investigate the relationship between alcohol drinking and breast cancer risk in Nigerian women.
Methods: The study was based on the Nigerian Breast Cancer Study, a case-control study of breast cancer conducted in Ibadan, Nigeria, between 1998 and 2010. In-person interviews were conducted with 1355 invasive breast cancer cases and 1132 community controls, using structured questionnaires to collect detailed epidemiologic data including alcohol drinking. Multivariate logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI), controlling for age, ethnicity, and type of questionnaire (we revised the questionnaire in the middle of study), with potential effect measure modifications tested.
Results: 5.8% controls and 11.3% cases reported drinking alcohol every week for at least 6 months, with crude OR=2.08 (95% CI: 1.54-2.82, p&lt;0.0001). After adjusting for potential confounding variables, alcohol drinking remained statistically associated with breast cancer risk but the strength of association was attenuated (adjusted OR=1.56, 95% CI: 1.11-2.19, p=0.01). Among women who drink weekly, the average drinks per week were 1.7±0.8 in controls and 3.4±5.8 in cases, and there was a dose-response trend: the crude OR was 1.86 for women who had 1-2 drinks per week and 3.27 for those who had ≥ 2 drinks per week, compared with non-drinkers (p-trend=0.08). The age- and ethnicity-adjusted ORs for 1-2 drinks and ≥ 2 drinks per week were 1.20 (95% CI: 0.49-2.93) and 1.80 (95% CI: 0.36-8.87), respectively. The association between alcohol drinking and breast cancer was particularly stronger in overweight or obese women who have BMI ≥ 25 kg/m2 (adjusted OR=1.92, 95% CI: 1.23-3.01, p=0.004) than in normal weight women (adjusted OR=1.20, 95% CI: 0.71-2.02, p=0.5). Similar association was observed in pre-menopausal and post-menopausal women.
Conclusions: Our study showed that regular alcohol intake is uncommon among Nigerian women. However, regular alcohol drinking may increase breast cancer risk among the Nigerians, particularly overweight women.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3734. doi:10.1158/1538-7445.AM2011-3734
Abstract 3736: Correlates of vitamin D: A measurement pilot study
Authors: Steffen Alana D. , Gies Peter , Cooney Robert 
Published: June 2012

Abstract
Vitamin D has protective effects for colorectal cancer and possible benefits for breast and ovarian cancers yet the determinants of vitamin D status are not fully understood. This study measured sun exposure, sun protection, diet, body mass index, and skin color and correlated them with serum 25(OH)D to understand better the impact of these factors on vitamin D status. Women (n=28) ages 18-30 residing in Hawaii attended small group sessions where they completed questionnaires about diet, supplement use, and skin type and had skin color measured by reflectance spectrophotometry. Participants wore polysulphone dosimeters mounted on wristbands, photographed clothing outfits and kept daily diaries for the 7 days before their blood draw. Results: Participants were, on average, 24.6 (3.3) years old, had BMI of 23.6 (range 17.7 – 34.7), consumed 308 IU vitamin D daily (range 10 – 1202), used sunscreen on 12% of their body (range 0 to 44%), were 44% covered by clothing (range 22 – 79%), received 2.3 standard erythemal doses (range .1 to 5.9) of UVB and had 34.7 ng/mL of 25(OH)D3 (range 17.7 – 90.5). Personal UVB dose accounted for 22% of the variance in 25(OH)D, and the addition of clothing and sunscreen coverage increased the R2 value to 0.33. Skin color and diet were not associated with 25(OH)D. While BMI was showed an association 25(OH)D, it did not improve the model and was inversely related to UVB exposure. While the measured sun-related variables were useful for predicting 25(OH)D, the majority of variance in vitamin D status is unexplained. More research is needed to understand how this hormone is regulated in the body.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3736. doi:10.1158/1538-7445.AM2011-3736
Abstract 3746: Prostate stem cell antigen is associated with gastric cancer in Caucasians: Results from the EPIC-EURGAST study
Authors: Sala Nuria , Muñoz Xavier , Travier Noemie , Agudo Antonio , Duell Eric J. , Moreno Victor , Garcia Nadia , Capella Gabriel , Riboli Elio , Gonzalez Carlos A. 
Published: June 2012

Abstract
Background. A genome-wide study performed in a Japanese population identified a strong association between SNP rs2294008 (Met1Thr) in the Prostate Stem Cell Antigen gene (PSCA) and diffuse-type gastric cancer (GC). This association has been validated in different Asian populations but no study has yet been conducted in Caucasians. Objective. To analyze the association between PSCA variants and gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods. As part of a wider study in which we used the Illumina GoldenGate technology to genotype 1287 SNPs in 249 candidate genomic regions, we genotyped six tagSNPs covering the PSCA gene region in 411 incident gastric adenocarcinoma cases and 1530 matched controls from a nested case-control study in the European EPIC cohort. Among GC cases, 28% were in the cardia or in the gastroesophageal junction, 48% were noncardia and 24% were unspecified. Regarding the histological type, 36% were intestinal, 35% were diffuse and 29% were unspecified. After quality control analysis and data filtering, association was analyzed by unconditional logistic regression, adjusting for age, sex and country. Results. The T allele of rs2294008 in PSCA (frequency of 0.44 in controls and 0.53 in cases) was found to be a significant risk factor for GC (per allele OR=1.42, 95%CI:1.23-1.6; uncorrected p-value=6.5×10-6; Bonferroni adjusted p-value=0.0126). The A allele of rs12155758 also appeared to increase GC risk, while the C allele of rs9297976, in LD with rs2294008, was inversely associated with GC. These 3 SNPs jointly cover 92% of the common variation (MAF≥0.05) within 10 kb around PSCA in Caucasians. Haplotype analysis did not provide additional information. No statistically significant differences were observed in the effect of rs2294008 between diffuse (OR=1.54, 95%CI:1.20-1.96; p-value=0.0005) and intestinal-types (OR=1.52, 95%CI:1.20-1.93; p-value=0.0005), or between cardia (OR=1.19, 95%CI:0.91-1.56; p-value=0.20) and noncardia (OR=1.47, 95%CI:1.19-1.81; p-value=0.0003) sub-sites, although the associations were stronger in noncardia GC. Conclusions. Variation in the promoter region of PSCA, specifically the functional rs2294008 variant, is associated with GC risk in Caucasians.
Supported by “LaCaixa” (BM06-130-0); Spanish Ministry of Health (PI070130 and PI081420); European Commission FP5 (ref.QLG1-CT-2001-01049).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3746. doi:10.1158/1538-7445.AM2011-3746
Abstract 3750: Body mass index and obesity- and diabetes-associated genotypes and risk for pancreatic cancer
Authors: Tang Hongwei , Dong Xiaoqun , Hassan Manal M. , Abbruzzese James L. , Li Donghui 
Published: June 2012

Abstract
Background: There is accumulating evidence that obesity and diabetes are modifiable risk factors for pancreatic cancer. However, the genetic factors predispose individuals with obesity or diabetes to pancreatic cancer has not been identified.
Aims: To investigate the hypothesis that obesity- and diabetes-related genes modify the risk of pancreatic cancer.
Methods: We genotyped 15 single nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO), peroxisome proliferators-activated receptor gamma (PPARγ), nuclear receptor family 5 member 2 NR5A2 (aka liver receptor homolog 1), AMP-activated protein kinase (AMPK), and adiponectin (ADIPOQ) gene in 1,070 patients with pancreatic cancer and 1,175 cancer-free controls that are enrolled in a case control study conducted at MD Anderson Cancer Center during 2000-2008. Information on risk factors was collected by personal interview. Genotypes were determined using the Taqman method. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated using multivariable unconditional logistic regression.
Results: The PPARγ P12A (rs1801282) GG genotype was inversely associated with risk of pancreatic cancer (AOR: 0.21, 95%CI: 0.07−0.62). Three NR5A2 variants (rs12029406, rs3790844 and rs3790843) that were previously identified in a genome-wide association study were significantly associated with reduced risk of pancreatic cancer, AORs ranging 0.57-0.79. Two FTO gene variants (rs8050136 and rs9939609) and one ADIPOQ variant (rs17366743) were differentially associated with pancreatic cancer according to levels of body mass index (BMI) (P interaction = 0.0001, 0.0015, and 0.03). The variant alleles were associated reduced risk of pancreatic cancer among individuals with normal weight but increased risk among those with excess body weight. For example, the AOR (95%CI) for FTO IVS1-2777 AC/AA genotype (rs8050136) was 0.72 (0.55-0.96) and 1.54 (1.14-2.09) in participants with a BMI &lt;25 or ≥ 25 kg/m2, respectively. We observed no significant association between AMPK genotype and pancreatic cancer and no genotype interactions with diabetes or smoking.
Conclusion: Our findings suggest a protective effect of PPARγ P12A GG genotype and NR5A2 variants on pancreatic cancer. A positive association of FTO and ADIPOQ gene variants with pancreatic cancer may be limited to persons who are overweight.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3750. doi:10.1158/1538-7445.AM2011-3750
Abstract 3753: Genome wide association study of HCV-induced hepatocellular carcinoma
Authors: Matsuda Koichi , Kumar Vinod , Nakamura Yusuke 
Published: June 2012

Abstract
To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), a genome-wide association study (GWAS) was conducted using 432,703 autosomal SNPs in 721 HCV-induced HCC cases and 2,890 HCV-negative controls of Japanese origin. Eight SNPs which showed possible association (P &lt; 1 × 10-5) in the GWAS were further genotyped in 673 cases and 2,596 controls. We found a novel locus in the 5 prime flanking region of HCRSP (hepatocellular carcinoma related soluble protein) gene (Pcombined = 4.21×10-13, odds ratio (OR) = 1.39) to be strongly associated with HCV-induced HCC. Subsequent analyses using patients with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61), but significantly associated with progression from CHC to HCC (P=3.13 × 10-8). We also found that risk allele of SNP was associated with lower level of HCRSP protein in HCV-induced HCC patients (P = 1.38 × 10-13). Thus, our results highlight the importance of genetic variations of HCRSP as a predictive biomarker for HCV-induced HCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3753. doi:10.1158/1538-7445.AM2011-3753
Abstract 376: Development of nanosuspension formulation of diethylstilbestrol and effect of particle size on the in vitro drug release
Authors: Samant Tanay , Tu Shi-Ming , Chow Diana S-L 
Published: June 2012

Abstract
Purpose: To develop a sustained release nanosuspension formulation of diethylstilbestrol (DES) for subcutaneous delivery, in recurrent prostate cancer, to by-pass the first pass hepatic metabolism and potentially reduce the adverse effects of DES.
Methods: Three nanosuspension formulations of DES were prepared by the wet milling technique with sizes of 160 (A), 300 (B) and 500 (C) nm, respectively. The formulations were characterized by particle size, zeta-potential and release kinetics. The release study was performed by adding each formulation, equivalent to 1mg of DES, to a dialysis bag (M.W cut off, 6000-8000). The bag was placed in 20 ml of PBS to simulate the subcutaneous conditions. The tubes were shaken at 100 rpm in a water bath at 37°C. The drug release was monitored for 14 days. DES concentrations were quantified by a validated HPLC assay.
Results: Sizes of the nanosuspensions were 162.5±1.5 nm, 287.1±2.7 nm and 492.5±8.3 nm, and the polydispersity was 0.18±0.01, 0.15±0.01, 0.20±0.03 for formulations A, B and C, respectively. The time of milling required for A, B and C was 30, 8 and 6 hours respectively. The zeta potential was -18.11±0.65, -19.49±0.49, -18.08±0.45 mV for formulations A, B and C, respectively. The release profiles showed a biphasic pattern, with an initial rapid release in 4 days followed by a slower release and reaching plateau after 6 days. Formulations A and B showed a significantly higher release than the formulation C by using ANOVA and Tukey's Multiple Comparison Test (p&lt;0.05). However, there was no statistically significant difference between the release profiles of A and B. Formulation A had a much faster initial release rate of 25.06%/day than B and C with an initial release rate of 15.68%/day and 15.51%/day respectively (p&lt;0.05). The extents of release were 65.76% (A), 67.38% (B) and 55.42% (C) at 6 days and 67.77% (A), 70.53% (B) and 64.79% (C) at 14 days.
Conclusion: Stable nanosuspension formulations were successfully formulated for DES with particle sizes of 162.5 nm, 287.1 nm and 492.5 nm. The particle size depends on the duration of milling. The 162.5 nm and 287.1 nm formulations achieved a much higher release than the 492.5 nm nanosuspension indicating that the particle size has a profound effect on the release of the drug. A sustained and extended release of DES was achieved over a period of 14 days in simulated subcutaneous conditions indicating that these formulations definitely warrant further preclinical evaluations.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 376. doi:10.1158/1538-7445.AM2011-376