bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5577: The role of age-related enhancements of IL-17 in prostate cancer initiation and progression
Authors: De Angulo Alejandra , Faris Robert , Cavazos David , Jolly Christopher , deGraffenried Linda A. 
Published: June 2012

Abstract
Background: Age is the single greatest risk factor for prostate cancer development. As men pass age 40, their chance of developing prostate cancer increases exponentially each year. The mechanism by which age influences the risk of prostate cancer remains largely unknown, hindering the development of effective preventive approaches. While local events are known to contribute to age-related prostate tumorigenesis, the role of the aging immune system in prostate cancer development has been largely understudied. The aging process affects the adaptive cell-mediated immune response and at the same time there is a shift to a more inflammatory cytokine profile. Recent studies have shown that age-related enhancements of Th17 might contribute to changes in immune function and prostate cancer development. The age-related shift in T-lymphocyte cytokine profile and the enhancement of TH17 generation might be significant contributing factors to the association between age and prostate tumorigenesis.
Methods: For our studies we have been using a unique animal model, the glycerol-3-phosphate acyltransferase-1 (GPAT-1) knock out mouse. The GPAT-1 KO young mouse T lymphocyte phenotype mimics old (&gt; 18 m) wild type mice. Preliminary data suggested that cytokines secreted from the GPAT-KO aging mimic T-lymphocytes can promote activation of the STAT3/NF-kB pathways. In order to test if IL-17 was responsible for the strong induction of NF-kB and STAT3, we repeated previous experiments that measured the activation of NF-kB and STAT3, but supplemented the experimental sera and conditioned media with depleting antibodies to IL-17. Successful inhibition of the NF-kB and STAT3 pathways was assessed by Western Blot analysis.
Conclusions: Depleting IL-17 in the GPAT-1 KO sera and conditioned media decreased NF-kB activity to the levels of the cells treated with wild-type sera. Sera from the old and GPAT-1 KO mice induced activation of downstream targets of IL-17. These results suggest that circulating factors from the GPAT-1 KO mice mimic those in aging mice and strongly induced signaling pathways involve in the development of prostate cancer. The age-related enhancements of IL-17 may play a key role in prostate cancer initiation and progression.
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 5577. doi:10.1158/1538-7445.AM2011-5577
Abstract 5579: Selenomethionine does not protect against testosterone plus 17 beta-estradiol-induced prostate carcinogenesis and prostatic oxidative stress in NBL rats
Authors: Ozten Nur , Schlicht Michael J. , Bosland Maarten C. 
Published: June 2012

Abstract
Previous studies with selenium and/or vitamin E in prostate carcinogenesis animal models have been negative, but these models may not involve oxidative stress mechanisms. Selenium and vitamin E have been the subject of one of the largest trials ever conducted, SELECT, which was discontinued because there was no difference between the study arms and there were side effects, including an increased chance of developing diabetes mellitus with the use of selenium. We previously found that selenomethionine supplementation did not prevent prostate cancer in NBL rats treated with testosterone plus 17 beta-estradiol (T+E2), a model that does involve sex-hormone induced oxidative stress mechanisms and prostatic inflammation; this result was fully predictive of the outcome of the SELECT trial. Based on the outcomes of SELECT and our NBL rat study, we hypothesized that selenium has no protective effect against T+E2-induced prostate cancer development because it does not protect against oxidative stress. In the present study, we examined the potential of selenomethionine to modulate prostatic oxidative stress and induction of dysplasia and inflammation in the T+E2-treated NBL rat. Nbl/Crl rats were treated for 16 weeks with T+E2 by Silastic implants and were fed a natural ingredient control diet (NIH-07) with or with L-selenomethionine at a concentration of 1.5 or 3.0 mg/kg (as selenium). These diets were initiated one week post hormone implantation. T+E2 significantly increased immunohistochemical staining for 8-hydroxy-deoxyguanosine (8-OHdG) in prostatic ducts, and in the lateral and dorsal prostate which are the main sites of T+E2-induced inflammation and preneoplasia after 16 weeks of hormone treatment, and in the seminal vesicles. However, selenomethionine did not reduce these effects and did not, by itself, change 8OHdG staining. There was a lobe-specific differential response and modulation of antioxidant enzymes. Glutathione peroxidase activity and protein expression level of manganese superoxide dismutase were induced by T+E2, which effects were counteracted by selenomethionine in the dorsolateral prostate, which is the main site of T+E2-induced inflammation and preneoplasia occurring after 16 weeks of hormone treatment. However, selenomethionine did not influence the induction by T+E2 of marked inflammation and dysplasia in the lateral prostate. These findings partially explain the negative outcome of our previous NBL rat study and is consistent with the negative results of the SELECT trial. (Supported in part by Grant No. CA104334)
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 5579. doi:10.1158/1538-7445.AM2011-5579
Abstract 5583: Differential effect of phenethyl isothiocyanate on expression of antioxidant defense genes between normal and cancerous human prostate cells
Authors: Singh Shivendra V. , Powolny Anna A. 
Published: June 2012

Abstract
Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive constituent of cruciferous vegetables (e.g., watercress) as evidenced by efficacy against chemically-induced cancer in experimental rodents. The PEITC is also empowered to inhibit growth of cultured and xenografted human prostate cancer cells, which correlates with apoptotic and autophagic cell death. We have shown previously that reactive oxygen species (ROS) play a critical role in proapoptotic signal transduction by PEITC in human prostate cancer cells. Interestingly, a representative normal human prostate epithelial cell line (PrEC) is significantly more resistant to PEITC-induced apoptosis compared with cancerous prostate cells including PC-3 and LNCaP. However, the mechanism behind this differential response remains elusive. The present study was undertaken to test a hypothesis that differential sensitivity of normal versus cancerous human prostate cells to PEITC-mediated proapoptotic response is determined by differences in ROS production and/or basal or inducible expression of antioxidant defense genes. The PEITC treatment resulted in ROS production in PC-3 human prostate cancer cells as judged by flow cytometry and fluorescence microscopy using a chemical probe (MItoSOX Red) and EPR using a cell permeable sin probe (1-hydroxy-3-methoxy-carbonyl-2,2,5,5-tetramethylpyrrolidine). These effects were not observed in PrEC cells similarly treated with the PEITC. Basal antioxidant defense gene expression signature was strikingly different between PC-3 and PrEC cells. Moreover, PEITC treatment (2.5 μM, 6 h) caused up-regulation of 29 genes and down-regulation of 2 genes in PC-3 cells. Conversely only 4 genes were up-regulated and 10 genes were down-regulated by a similar PEITC treatment in the PrEC cell line. The results of the present study clearly indicate that differential sensitivity of PC-3 versus PrEC cells to proapoptotic effect of PEITC is likely attributable to both differences in ROS production and basal as well as altered expression of antioxidant defense genes. This investigation was supported by the USPHS grant CA101753-07, 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 5583. doi:10.1158/1538-7445.AM2011-5583
Abstract 5590: Role of estrogen receptor-beta in colitis-associated cancer
Authors: Saleiro Diana , Murillo Genoveva , Mutreja Karun , Hawthorne Michael , Mehta Rajendra G. 
Published: June 2012

Abstract
Inflammatory bowel disease has been strongly correlated with colitis-associated cancer (CAC) cases, a subtype of colorectal cancer. Previously, we demonstrated that estrogen receptor-beta (ERβ) exerted protective effects against the development of colonic precancerous lesions in the azoxymethane-induced spontaneous colon cancer in vivo model. In the present study, we investigated whether ERβ could also be protective against CAC. Estrogen receptor-β knockout (βERKO) and wild type (WT) mice were exposed to azoxymethane, followed by dextran sodium sulfate (DSS) treatment. Three days after the DSS treatment two βERKO mice died, suggesting that these mice might be more susceptible to inflammatory inducers than WT mice. Furthermore, six weeks after DSS exposure five mice from each group were sacrificed and morphology and RNA analyses of inflammation markers were performed. All βERKO mice presented polyp-like structures in the colon (3.60 ± 0.81) and greater number of cellular infiltration areas (9.00 ± 1.50), whereas only two WT mice presented polyp-like structures (2.40 ± 1.47) and fewer number of cellular infiltration areas (4.00 ± 2.02). βERKO mice showed 9.8 and 5.6 fold increase in mRNA expression of inducible-nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α), respectively, when compared to WT mice. In both βERKO and WT mice a 2.1 fold increase in cyclooxygenase-2 (COX-2) mRNA expression was observed compared to the respective negative control groups. All together these results suggest that ERβ might be protective against CAC. These data will be compared to the group of mice that will be sacrificed 15 weeks post DSS treatment.
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 5590. doi:10.1158/1538-7445.AM2011-5590
Abstract 5592: Lack of association between AGTR1 (A168G and T825A) and ACE T5529C polymorphisms with breast cancer among Brazilian women
Authors: Correa-Noronha Silvana A Alves , Ribeiro de Noronha Samuel M. , Geraldo Murilo V. , Carvalho Cristina V. , Linhares Jose J. , Silva Fabricio Colacino , Costa Ana Maria M. , Siufi Adalberto A. , Kimura Edna T. , Shimuta Suma I. , Nakaie Clovis R. , da Silva Ismael D.C.G. 
Published: June 2012

Abstract
Background: Angiotensin II (AngII) exerts promitotic, pro-proliferative and angiogenic effects and the administration of angiotensin I-converting enzyme (ACE) inhibitors reduces tumor growth in animal models of cancer. AngII type 1 receptor (AGTR1) is found in a wide variety of normal tissues, increased expression is often found in the corresponding neoplastic tissues, suggesting that its overexpression is involved in carcinogenesis. In a previous study we observed that the ID genotype might be protective against breast cancer and also that the ACE (I/D) polymorphism is a possible target for developing genetic markers for breast cancer. Other authors have also observed the association of the ACE with breast cancer risk. To further test the hypothesis that AngII participates in breast carcinogenesis through AGTR1 and ACE, we examined genetic polymorphisms in the 5’-region of the AGTR1 gene (A-168G and T-825A) and in the ACE (T5529C) in relation to risk of breast cancer among Brazilian women. Methods: Genotyping was performed through Real Time PCR (A168G and T825A) or PCR-RFLP (T5529C) using genomic DNA extracted from buccal cells of subjects with or without breast cancer.Results: Patients with (case) or without (control) breast cancer aging from 30 to 90 years old were genotyped for A168G (n=516), and the following frequencies obtained for AA, AG and GG in % were, among cases: 63, 30, 07 and among controls: 64, 32, 04 (p = 0.89). For T825A (n=562), we determined the frequency of TT, TA and AA (in %, cases: 62, 33, 05; controls: 59, 33, 08; p = 0.68). At last, for ACE (T5529C) (n=272) these are the obtained frequencies for TT, TC and CC genotypes in %, among cases: 65, 23, 12 and among controls: 55, 29, 15 (p = 0.39).
Conclusion: Our results suggest a lack of significant association between AGTR1 polymorphisms (A168G and T825A) with breast cancer risk in the Brazilian population, in contrast to a previous result among Chinese women, where an association of the AGTR1 polymorphisms with breast cancer has been reported. Regarding the ACE T5529C polymorphism, it also did not show any association with breast cancer risk in the present study, differently from the observed for another polymorphism of the same gene, the ACE (I/D). Therefore, the AGTR1 (A168G and T825A) and ACE (T5529C) variant genotypes do not appear to be related to risk of breast cancer among Brazilian women. Support: FAPESP.
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 5592. doi:10.1158/1538-7445.AM2011-5592
Abstract 5597: Evaluation of functional genetic variants for breast cancer risk: Results from the Shanghai Breast Cancer Study
Authors: Zhang Ben , Beeghly-Fadiel Alicia , Zheng Wei 
Published: June 2012

Abstract
In previous studies among 1,144 cases and 1,256 controls recruited in the Stage I Shanghai Breast Cancer Study (SBCS-I), 18 known or potentially functional single nucleotide polymorphisms (SNPs) in 16 genes were found to be associated with breast cancer risk. The authors evaluated these associations among 1,918 cases and 1,819 controls recruited in the Stage II SBCS (SBCS-II) using genetic effect models and subgroup analyses pre-determined from SBCS-I results. Five SNPs showed generally consistent results in SBCS-I and SBCS-II and statistically significant associations with breast cancer risk in combined analyses (AHR rs2066853, ATM rs1003623, ESR1 rs2234693, GSTP1 rs1695, and SHBG rs6259), mostly in subgroups defined by age or menopausal status. Further, the relation between breast cancer risk and SHBG rs6259 was found to vary by body mass index (BMI) (P-value for interaction = 0.003). The strongest reduction in risk associated with SHBG rs6259 was found for postmenopausal lean (BMI&lt;23) minor allele carriers (Odds Ratio=0.6; 95% Confidence Interval: 0.5, 0.8; P-value = 4.6×10−4). This biologically plausible and highly significant finding provides strong evidence for a true association among Asian women. This study also highlights the value of gene-environment interaction analyses in evaluating genetic factors for complex diseases.
Abbreviations: BMI, body mass index; CI, confidence interval; OR, odds ratio; SBCS, Shanghai Breast Cancer Study; SNP, single nucleotide polymorphism.
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 5597. doi:10.1158/1538-7445.AM2011-5597
Abstract 5609: Characteristics of triple-negative breast cancer in patients with a BRCA1 mutation, results from a population-based study of young women
Authors: Lee Eunjung , McKean-Cowdin Roberta , Ma Huiyan , Spicer Darcy , Berg David Van Den , Bernstein Leslie , Ursin Giske 
Published: June 2012

Abstract
BACKGROUND: Triple-negative breast cancers (TNBC) are tumors with low or no expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor-2. These tumors have a poor prognosis, remain a clinical challenge, and are more common among women with BRCA1 mutations. We tested whether there are distinguishing features of TNBC after BRCA1 mutation status has been taken into account. METHODS: We sequenced BRCA1/2 genes in a population-based sample of 1,469 incident breast cancer patients aged 20-49 years from Los Angeles County. Information on tumor receptor status was available for 1,167 women. Clinical, pathologic and hormone-related lifestyle characteristics were compared across patient subgroups defined by BRCA1-mutation status and triple-negative receptor status. RESULTS: Forty-eight percent of BRCA1 mutation carriers had TNBC in contrast with only 12% of non-carriers. Within BRCA1 mutation carriers, as well as within non-carriers, triple-negative receptor status was associated with younger age at diagnosis and higher tumor grade. Among women without a BRCA1 mutation we observed that women with TNBC had higher premenopausal body mass index and earlier age at first full-term pregnancy than those with non-TNBC. Age at menarche and other reproductive factors were not associated with triple-negative status regardless of BRCA1 mutation status. Within BRCA1 mutation carriers, Ashkenazi Jewish women were about 5 times more likely to have TNBC than non-Ashkenazi Jewish women. CONCLUSIONS: Our results suggest that among BRCA1 mutation carriers, as among non-carriers, there are unique characteristics associated with the triple-negative subtype. The finding in Ashkenazi Jewish BRCA1 mutation carriers should be confirmed.
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 5609. doi:10.1158/1538-7445.AM2011-5609
Abstract 564: Resistant to Erlotinib, epidermal growth factor receptor tyrosine kinase inhibitor, is involved in epithelial to mesenchymal transition, cell migration and inflammation in A549, a non-small cell lung cancer cell line
Authors: Yang Seok-Chul , Lee Kyu-Hwa , Lee Sang-Min , Yim Jae-Jun , Yoo Chul-Gyu , Han Sung Koo , Kim Young Whan 
Published: June 2012

Abstract
Background: In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC). A great deal of effort has been focused on identifying specific markers that predict treatment response. The epidermal growth factor receptor (EGFR) pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Erlotinib, a selective EGFR tyrosine kinase inhibitor (EGFR-TKI) is clinically used to treat patients with NSCLC. In this study, we investigated the mechanisms for the drug-resistance of Erlotinib and the cytotoxic effects in NSCLC cell lines treated with Erlotinib.
Methods: In this study, we established an Erlotinib resistant subline (A549/ER) from parental A549 cell line. MTT assay and western blot analysis were used to measure the cell sensitivity to drugs. A549 and A549/ER cells were grown in chamber slide and stained with H&E to observe the cell morphology. The migration ability of A549 and A549/ ER cells was evaluated by transwell experiment. In addition, cDNA microarray was used to analyze gene expression patterns in transcript level, and secretory cytokine patterns were evaluated with multiplex enzyme-linked immunosorbent assay (ELISA) from A549 and A549/ER cell lines.
Results: In the EGFR-TKI-resistant cell line A549/ER, cell growth inhibition by Erlotinib was only mild, and the phosphorylation of this leading target such as EGFR was not inhibited. Phenotypic changes such as a spindle-cell shape and increased pseudopodia formation suggesting epithelial to mesenchymal transition (EMT) was found in A549/ER cells. These changes were accompanied by decreased expression of E-cadherin (ECAD) and cytokeratin-8, which are mesenchymal transition markers. Moreover, the ability of migration was increased in A549/ER cells. Different pattern of gene expression in cDNA microarray reflects changes during resistant progression in A549 cells. In experiment using multiplex ELISA, the secretory cytokines including vascular endothelial growth factor (VEGF), interleukin-6, interleukin-8 known to contribute to pathological inflammation were increased in the medium of A549/ER compared to that of A549 cells.
Conclusions: These results suggest that the mechanism of upstream receptor tyrosine kinase inhibitor, Erlotinib, resistance may be related with EMT, cell migration and inflammation in NSCLC.
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 564. doi:10.1158/1538-7445.AM2011-564
Abstract 573: Ionizing radiation activates IFN signaling in tumor cells
Authors: Khodarev Nikolai , Pitroda Sean , Sood Ravi , Khan Sajid , Filippo Matthew , Gutt Ruchika , Perakis Samantha , Darga Thomas , Malik Renuka , Pederson Aaron , Weichselbaum Ralph 
Published: June 2012

Abstract
Ionizing radiation (IR) uses multiple pathways to mediate killing in tumor cells. We found that fractionated irradiation leads to the constitutive overexpression of Interferon Stimulated Genes (ISGs) which are controlled by Signal Transducer and Activator of Transcription 1 (Stat1). Stat1 mediated IFN signal transduction and at the same time was involved in the production of Type I and Type II IFNs. IR-induced ISGs represent the following groups: 1) mitochondrial-related genes with pro- and anti-apoptotic functions, 2) cell cycle control and regulators of transcription, 3) protein modification and degradation, 4) cytoplasmic sensors of nucleic acids, and 5) anti-viral defense. Fractionated or single-dose IR induced the IFN pathway mediated by activation of Stat1 in breast, colon, prostate and head and neck tumor xenografts. Depletion of tumor-derived IFNs led to the suppression of IR response indicating that IFN production/signaling is a component of anti-tumor IR action. Cell-autonomous experiments indicated that tumor cells up-regulate Stat1 and ISGs and produce IFNα in response to single dose IR (3Gy). Up-regulated Stat1 in irradiated tumor cells was not phosphorylated at Tyr701 position compared to Stat1 activation following interferon stimulation. In a syngeneic tumor model of B16F1, IR-induced activation of IFN signaling in tumors (assessed both by up-regulation of the Stat1-dependent pathway and induction of Type I and Type II IFNs) was dependent on TNFα signaling in the host and was impaired in TNFR1,2-/- mice. We therefore conclude that IR induces IFN signaling in tumor cells as a component of the cytotoxic response. This interferon induction depends on TNFα signaling in host cells.
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 573. doi:10.1158/1538-7445.AM2011-573