bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4684: Autophagy blockade sensitizes prostate cancer cells towards Src family kinase inhibitors
Authors: Wu Zhaoju , Chang Pei-Ching , Yang Joy C. , Chu Cheng-Ying , Wang Ling-Yu , Chen Nien-Tsu , Ma Ai-Hong , Desai Sonal J. , Lo Su Hao , Evans Christopher P. , Lam Kit S. , Kung Hsing-Jien 
Published: February 2011

Abstract
There is overwhelming evidence that tyrosine kinases play an important role in cancer development. As a prototype of targeted therapy, tyrosine kinase inhibitors are now successfully applied to cancer treatment. However, as single agents, tyrosine kinase inhibitors have not achieved satisfactory results in the treatment of prostate cancer, principally due to their inability to efficiently kill tumor cells. Our lab has been interested in the role of the Src complex in prostate cancer progression including the induction of androgen independence and metastasis. Previously, we reported that Src inhibitors such as saracatinib and PP2 caused G1 growth arrest and diminished invasiveness in prostate cancer cells, but rarely apoptosis. Here, we have shown that Src family kinase (SFK) inhibitors can induce a high level of autophagy, which protects treated cells from undergoing apoptosis. Src siRNA knockdown experiments confirmed that autophagy was indeed caused by the lack of Src activity. The SFK inhibitor-induced autophagy is accompanied by the inhibition of PI3K (type I)/Akt/mTOR signaling pathway. To test whether autophagy blockade could lead to enhanced cell death, pharmacological inhibitors (3-methyladenine and chloroquine) and a genetic inhibitor (siRNA targeting Atg7) were used in combination with SFK inhibitors. The results showed that autophagy inhibition effectively enhanced cell killing induced by SFK inhibitors. Importantly, we showed a combination of saracatinib with chloroquine in mice significantly reduced prostate cancer (PC3) xenograft growth, compared with the control group. Taken together, these data suggest that 1) autophagy serves a protective role in SFK inhibitor-mediated cell killing; 2) clinically acceptable autophagy modulators may be used beneficially as adjunctive therapeutic agents for SFK inhibitors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4684.
Abstract 4730: Exploring the nature of prostate cancer SNP associations: Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)
Authors: Lindstrom Sara , Kraft Peter ,   BPC3
Published: February 2011

Abstract
Genome-wide association studies have identified more than 35 single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. In order to characterize the associations by disease aggressiveness (stage and tumor grade) and to investigate gene-environment and gene-gene interactions that might increase our understanding of prostate cancer etiology, we genotyped 29 SNPs in 9,067 prostate cancer cases and 9,188 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We confirmed prostate cancer associations for all SNPs (P-values ranging from 0.03 to 10−26) and found no evidence that the SNPs are differentially associated with aggressive and non-aggressive disease.
We further tested each SNP for effect modification by age and family history. One SNP, rs6983267, showed a significant non-multiplicative interaction with age (P=7.3[[Unable to Display Character: &#8729;]]10−5) where a stronger risk association was observed in younger men. We observed no interaction between SNPs and family history. The prospective nature of cohorts allowed us to explore possible gene-environment interactions with environmental factors such as smoking, alcohol and BMI that have been inconsistently related to prostate cancer, and we hypothesized that hidden gene-environment interactions might explain previous weak associations. We observed no interaction between the SNPs and these factors. In addition, we found no evidence of SNP-SNP interactions (epistasis).
Our findings for established prostate cancer SNPs did not differ across prostate cancer clinical subtypes, and we observed no significant gene-environment interactions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4730.
Abstract 4734: Validation of genome-wide colorectal cancer genetic risk factors in African- and European-Americans
Authors: Kupfer Sonia , Anderson Jeffrey , Hooker Stanley , Henderson Cory , Kittles Rick , Kim Karen , Keku Temitope , Sandler Robert S. , Ellis Nathan A. 
Published: February 2011

Abstract
Background: Genome-wide association studies have identified several colorectal cancer (CRC) genetic risk factors. However, these studies have been performed primarily in individuals of European descent and none include African Americans (AAs). Determining CRC genetic risk factors in AAs is important because CRC incidence and mortality rates are highest of all US populations.
Aim: To validate genome-wide CRC genetic risk factors, we tested single nucleotide polymorphism (SNP) associations in ten chromosome (chr) regions in AAs and European-Americans (EAs).
Methods: We genotyped 22 SNPs in 1725 AA and 883 EA CRC cases and controls using Sequenom iPLEX. Ancestry estimates were obtained using STRUCTURE 2.1. We tested for allelic association and calculated odds ratios and confidence intervals using logistic regression adjusting for ancestry, age and gender.
Results: Association results are shown in the Table. In AAs, rs10795668 (chr 10) and rs10318 (chr 15) were significantly associated with CRC. rs7014346 (chr 8) and rs355527 (chr 20) trended toward significant associations. In EAs, three SNPs on chr 8 were significantly associated with CRC. In addition, two chr 11 SNPs (rs3802842 & rs1074997) and rs1862748 (chr 16) were significantly associated with disease in EAs. SNPs on chr 15 and chr 16 are located in or near genes GREM1 and CDH1 respectively. SNPs on chr 8, 10, 11 and 20 are in gene deserts.
Conclusion: This is the first study to validate genome-wide SNP associations in AAs. We also confirm several associations in EAs. SNPs on chr 15 & 16 are located in genes involved in TGFβ signaling (GREM1 & CDH1) which has been implicated in CRC pathogenesis, while those on chr 8, 10, 11 and 20 are in gene deserts. Future fine-mapping in these regions is warranted to identify functional variants.Genome-wide SNP associations in African- and European-AmericansChr (gene)SNPReference alleleAllele frequency casesAllele frequency controlsOR [95% CI]p*African Americans 8rs7014346A0.420.391.14 [0.99-1.31]0.0710rs10795668A0.080.061.41 [1.07-1.87]0.0415 (GREM1)rs10318T0.050.031.45 [1.02-2.05]0.0520rs355527A0.180.200.87 [0.73-1.04]0.09European Americans 8rs6983626T0.120.091.38 [1.00-1.91]0.058rs6983267G0.520.471.24 [1.01-1.51]0.048rs7837328A0.430.371.30 [1.06-1.60]0.0111rs3802842C0.330.281.26 [1.02-1.57]0.0211rs10749971G0.410.331.42 [1.15-1.74]0.000216 (CDH1)rs1862748T0.280.320.80 [0.64-0.99]0.04
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4734.
Abstract 4735: Examining known diabetes risk variants for association with prostate cancer in a multiethnic population
Authors: Waters Kevin M. , Stram Daniel O. , Cheng Iona , Schumacher Frederick R. , Wilkens Lynne R. , Monroe Kristine R. , Kolonel Laurence N. , Henderson Brian E. , Marchand Loïc Le , Haiman Christopher A. 
Published: February 2011

Abstract
Epidemiologic studies have found evidence of an inverse association between diabetes status and prostate cancer risk. Recently genome-wide association studies of these two diseases have identified a single risk allele at the HNF1B locus that is associated with both diseases along with two risk loci (JAZF1 and THADA) that have been associated with both diseases through distinct unlinked variants. We, as part of the Population Architecture using Genomics and Epidemiology (PAGE) Study, explored the hypothesis that common genetic variation may explain, in part, the inverse association between type II diabetes and prostate cancer, by examining known diabetes risk variants for their association with prostate cancer. Our study consists of men from a prostate cancer case-control set of 2,707 cases and 2,438 controls from five racial-ethnic groups (African American, European American, Latino, Japanese American, and Native Hawaiian) of the Multiethnic Cohort. The allelic discrimination assay was used to genotype 21 diabetes risk variants from 18 loci identified by genome-wide association studies. Unconditional logistic regression was used to examine these alleles for association with prostate cancer risk. In ethnic-pooled analysis, we did not find evidence of an association with prostate cancer for the diabetes risk alleles in either of the two loci previously associated with prostate cancer (JAZF1, rs864745, OR 1.01, 95% CI 0.92-1.10; THADA, rs7578597, OR 1.11, 95% CI 0.97-1.27). An allele (rs7961581) in the TSPAN8 locus, which has been shown to be positively associated with diabetes risk had a protective association with prostate cancer at a nominally statistically significant level (OR 0.88, 95% CI 0.80-0.97, p=7.8×10-3). Except for the risk allele at HNF1B (allele G of rs4430796), which we previously reported to be associated inversely with prostate cancer, we found no evidence of an association with prostate cancer for the diabetes risk loci at JAZF1 and THADA despite other independent alleles at these loci being associated with prostate cancer. In summary, we found an association between the TSPAN8 allele and prostate cancer risk that needs to be replicated in larger populations. Resequencing and fine-mapping studies to identify causal alleles in large association studies will be important in exploring the role of common risk variants in the inverse association between diabetes and prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4735.
Abstract 4739: Interactions between variants of angiogenesis pathway genes and reflux symptom, BMI, and smoking in esophageal adenocarcinoma susceptibility
Authors: Zhai Rihong , Chen Feng , Liu Geoffrey , Ter-Minassian Monica , Su Li , Asomaning Kofi , Wang Zhaoxi , Kulke Matthew H. , Lin Xihong , Heist Rebecca S. , Sheu Chau-Chyun , Wain John C. , Hooshmand Susanne H. , Nishioka Norman S. , Christiani David C. 
Published: February 2011

Abstract
Esophageal adenocarcinoma (EA) is a complex malignancy that involves multiple genetic and environmental risk factors. Genetic polymorphisms in angiogenesis pathway, gastroesophageal reflux symptoms (reflux), higher body mass index (BMI), and tobacco smoking have been individually associated with EA development. However, interactions among multiple factors in EA risk have not been well characterized. We conducted a case-only study to investigate gene-environment interactions among 145 functional/tagging SNPs of angiogenesis pathway genes, reflux, smoking, and BMI in 335 patients with EA. We used a two-stage approach to detect interactions: first, we applied random forest (RF) approach to select important interacting markers based on mean decrease in accuracy and mean decrease in GINI index; then we estimated the interaction odds ratios (ORinter) of RF selected interaction markers by case-only logistic regression, adjusting for covariates and false discovery rate (FDR). We identified twelve interaction markers that were significantly associated with EA risk (all FDR_Ps&lt;0.05). Among them, six interaction markers, including reflux*rs2295778 (HIF1AN) (ORinter=2.27; 95% CI, 1.44-3.57), reflux*rs996999 (MMP1) (ORinter=1.80; 95%CI, 1.12-2.89), reflux*rs13337626 (TSC2) (ORinter=2.18; 95%CI, 1.15-4.12), BMI*rs2114039 (PDGFRA) (ORinter=2.06; 95%CI, 1.29-3.30), BMI*rs6554164 (PDGFRA) (ORinter=1.92; 95% CI, 1.20-3.08), and BMI*rs17708574 (PDGFRB) (ORinter=1.89; 95%CI, 1.12-3.18) were significantly associated with increased risk of EA. On the other hand, six interaction markers, including reflux*rs2519757 (TSC1) (ORinter=0.43; 95% CI, 0.21-0.83), smoking*rs2295778 (HIF1AN) (ORinter=0.45; 95%CI, 0.26-0.79), smoking*rs2296188 (FLT1) (ORinter=0.50; 95%CI, 0.28-0.87), BMI*rs2296188 (FLT1) (ORinter=0.41; 95%CI, 0.24-0.73), BMI*rs11941492 (KDR) (ORinter=0.52; 95%CI, 0.32-0.85), and BMI*rs17619601 (FLT1) (ORinter=0.26; 95%CI, 0.09-0.75) were significantly associated with decreased risk of EA. These findings suggest that variants in angiogenesis pathway genes, reflux, smoking, and BMI jointly contribute to EA development through gene-environment interactions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4739.
Abstract 4743: Genome-wide gene-centric discovery of disease variants in neuroblastoma
Authors: Nguyen Le B. , Diskin Sharon , Hakonarson Hakon , Maris John M. , Li Hongzhe 
Published: February 2011

Abstract
Genome-wide associations studies (GWAS) have been increasingly utilized to identify novel genetic variants for complex human diseases. As we are interested in disease causal variants that have a high likelihood of impacting protein encoding genes, we developed a gene-centric genome-wide association approach. This method computes the aggregated effect of all SNPs mapped on a gene normalized by the number of SNPs on this gene. Therefore, this method is able to identify genes whose SNPs have marginal effect size by conventional statistical methods because the Bonferroni correction criteria are relaxed since the number of genes in the human genome is far less than the number of SNPs on the array. We applied this gene-centric method to both high-risk and low-risk neuroblastoma, a cancer of early childhood with less than 40% cure rate in high-risk patients and more than 95% survival rate in low-risk patients. We utilized a discovery set of 1627 cases and 2575 control subjects, and an independent replication set with 398 cases and 1507 control subjects. First, we provided proof of concept by replicating each prior association study result reported by our lab, including the hypothetical gene FLJ44180 at chromosome band 6p22, BARD1 at 2q35 and LMO1 at 11p15 (P=9.92×10−11, &lt;1.00×10−30, and 1.80 ×10−7, respectively). Additionally, we also discovered two new association signals that robustly replicated in low-risk cases only: DUSP12 at 1q23 (P=3.03 ×10−6) and DDX4 at 5q11 (P=2.39×10−6). These data suggest that a gene-centric statistical approach to GWAS data can identify causal variants in relatively rare phenotypic subsets.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4743.
Abstract 4761: The iCD40. MyD88 combo-vector: A new platform for enhanced DC tumor immunotherapy
Authors: Narayanan Priyadharshini , Lapteva Natalia , Kemnade Jan O. , Slawin Kevin M. , Spencer David M. 
Published: February 2011

Abstract
Introduction: Given the pre-eminent role of dendritic cells (DCs) as antigen-presenting cells, their exploitation as natural adjuvants in vaccination protocols for the treatment of various malignancies and infectious diseases is not surprising. Nevertheless, inadequate or unsustained activation has likely limited response rates in clinical trials. We previously reported a potent synthetic dimerizer drug-inducible CD40 (iCD40) receptor that permits temporally controlled DC-specific activation within the context of an immunological synapse (Hanks et al, Nat Med, 2005). We showed that when combined with Toll-like Receptor (TLR) adjuvants, iCD40-modified DCs (iCD40-DCs) have enhanced survival, co-stimulatory marker expression, migration, IL-12 production, antigen (Ag)-specific T cell stimulatory capacity and anti-tumor responses (Lapteva et al, Cancer Res, 2007). A phase I/II clinical trial based on iCD40-DCs to treat castration-resistant, metastatic prostate cancer began enrolling patients in August 2009.
Procedures: To simplify this approach, we have developed a unified, inducible DC switch, called “iCD40. MyD88”, which combines signaling elements from costimulatory molecule, CD40, and TLR adapter, MyD88, fused to tandem FK506-binding binding proteins (FKBP12v36). Activation is initiated in vitro or in vivo by lipid-permeable dimerizing ligands (i.e. AP1903 or AP20187).
Results: Both murine and human iCD40. MyD88-DCs secrete high (ng) levels of IL-12 and maturation markers in a ligand-dependent fashion without the need for exogenous adjuvants. iCD40. MyD88 activation is associated with synergistic activation of IKK&#945;/&#946; and p38. Moreover, tumor-bearing mice treated with antigen-pulsed, iCD40. MyD88-DCs show a potent anti-tumor immune response, consistent with expansion of antigen-specific CTLs in vivo. Bicistronic vectors combining iCD40. MyD88 along with tumor-associated antigens are underway.
Conclusion: This “combo-switch” permits potent, targeted activation of antigen-pulsed DCs in vivo, leading to improved anti-tumor immunity with a high likelihood for reduced side effects. Production of a single vector that combines a potent DC switch with tumor antigen is the first requisite step leading to economically viable, “off-the-shelf”, vaccine therapies for cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4761.
Abstract 4762: Dendritic cell therapy delays disease progression in hepatocellular carcinoma
Authors: Khan Jamal A. , Yaqin Sharmin B. 
Published: February 2011

Abstract
Hepatocellular carcinoma(HCC) has a poor outcome with all known conventional treatment plans. In advanced stage disease, surgery and ablation are also not done. In such situations, patients look for alternative therapies and accept them without even oncologists opinion. Dendritic cell therapy is one of the options in such cancers and HCC is said to be immunoresponsive. We have treated 12 patients of advanced stage HCC in our center with this approach. Patients were informed about the experimental nature of the protocol and gave their written consent. The protocol was isolation of peripheral blood mononuclear cells from about 25 ml of patient's blood and culture them in RPMI-1640, GM-CSF and IL-4. After 6 days of culture, immature dendritic cells were exposed to Tumor Associated Antigen(TAA) and cultured for additional 2 days. The final product was evaluated by immunocytochemistry (CD83/86+ve) and confirmed free of microbial and mycoplasma contamination. It is administered to the same patient by mixing it in 100 ml of dextrose-normal saline. The adverse effects observed were fever, fever with shivering and rigors and lethargy for a day or two. No patient required hospitalization during treatment. The process is repeated by taking fresh blood sample every 23 days and is continued till the patient kept showing clinical benefits. 5 patients have shown radiological stabilization of disease for more than 2 years including improvement in performance status from 3/2 to 1 (ECOG scale). 3 patients showed no response and 4 patients showed partial response with mean survival of 7 months. We conclude that early stage patients of HCC should be given an option of dendritic cell therapy after completion of their primary conventional treatment plan.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4762.
Abstract 4765: Treatment with anti - IL 17 A coupled with COX-2 inhibitor significantly decreases breast cancer associated secondary metastasis in a model of autoimmune arthritis
Authors: Roy Lopamudra Das , Schettini Jorge L. , Gruber Helen E. , Sahraei Mahnaz M. , Mukherjee Pinku 
Published: February 2011

Abstract
Introduction: Inflammation is a critical hallmark of autoimmune arthritis (AA) and cancer. We have previously shown that the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. We have identified IL-17, a critical pro-inflammatory cytokine involved in osteoclastic bone resorption in AA as the underlying mechanism for increased metastasis. In addition, high levels of cyclooxygenase 2 (COX-2) is linked to both AA and breast cancer metastasis. We report that blocking the IL-17 and COX-2 pathways simultaneously significantly reduces the development of breast cancer associated metastasis in a spontaneous model of AA.
Methods: 4T1 mammary gland tumors were generated in mice genetically prone to develop AA (designated SKG mice). When tumors reached &gt; 0.2 gms, anti-IL17 antibody treatment was injected intraperitoneally once a week for three weeks. Celecoxib, a specific COX-2 inhibitor was orally administered starting at the same time as the anti-IL-17 antibody but was given daily until sacrifice. One week after the last injection, mice were sacrificed. Secondary metastasis and the associated inflammatory milieu were evaluated.
Summary of Results: Data demonstrated that compared to the untreated mice or mice treated with isotype control antibody, survival was significantly enhanced and primary tumor burden was significantly decreased in the anti-IL-17+celecoxib treated mice. Importantly, we observed significant decrease in lung and bone metastasis as compared to the control group. The contributing factor was recognized to be the low neutrophilic and granulocytic infiltration and therefore low inflammation in the lungs as well as reduced severity of arthritis with low cellular infiltration and low osteoclast formation in the bones of mice treated with anti-IL-17+celecoxib.
Conclusion: We report that treatment with anti-IL 17 and celecoxib significantly reduced primary tumor burden, reduced metastasis to the lungs and bones, and increased survival in SKG mice.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4765.