bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 617: Apigenin intake regulates Fox ‘O’ signaling in an autochthonous mouse model of prostate cancer
Authors: Shukla Sanjeev , Bhaskaran Natarajan , MacLennan Gregory T. , Fu Pingfu , Gupta Sanjay 
Published: August 2012

Abstract
Forkhead transcription factors of ‘O’ class (FoxOs) are involved in a paradigm that supports proliferation, survival, longevity during multiple cellular environments, and tumor development. Perturbation of FOXO activity leads to altered cellular response which results in cancer development and progression. We previously showed that FOXO signaling is deregulated in human prostate adenocarcinoma and in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model that mimics progressive forms of human disease. In the present study we aimed to demonstrate the potential role of apigenin, a common dietary flavonoid present in fruits and vegetables, in modulating FoxO signaling and its downstream events to suppress cancer progression using in vivo and in vitro models. Apigenin was fed to TRAMP mice at 20- and 50- μg/mouse/day (gavaged in 0.2 ml vehicle containing 0.5% methyl cellulose and 0.025% Tween 20) for six days in a week for 20 weeks; whereas control animals received vehicle only. Apigenin intake by TRAMP mice from 8-28 weeks of age exhibited marked reduction in tumor growth with no signs of metastasis. Apigenin feeding to TRAMP resulted in a significant dose-dependent reduction in Foxo3a, but not Foxo1a protein observed in the dorso-lateral prostates. Foxo3a protein was redistributed more in nuclear than the cytosolic compartments after apigenin feeding. Simultaneously, decreased Foxo3a phosphorylation (Ser253) was observed in the dorso-lateral prostate, which correlated with decreased cytoplasmic retention of Foxo3a with no significant change in 14-3-3 chaperone protein in the cytosol after apigenin feeding. Conversely, TRAMP mice have higher 14-3-3 expression than non-transgenic mice and this higher level accounted for nuclear retention of Foxo3a. A subsequent decrease in p-Akt (Ser473) was noted after apigenin feeding demonstrating that the decreased nuclear presence of p-Akt (ser473) may be restricting Foxo3a phosphorylation and its retention in the nucleus. Furthermore, an increase in the levels of MnSOD and Cu/ZnSOD was observed in TRAMP mice after apigenin intake. Similar findings were recorded in cell culture studies where apigenin treatment to human prostate cancer LNCaP and PC-3 cells resulted in the restoration of FOXO3a in the nucleus. This increase in Foxo3a protein levels in the nucleus may be a decisive factor resulting in the inhibition of prostate cancer. These finding suggests that apigenin has potential role in regulating the FOXO signaling cascade and may be a major therapeutic target in 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 617. doi:1538-7445.AM2012-617
Abstract 641: Prognosis of breast cancer is associated with one-carbon metabolism related nutrients among Korean women
Authors: lee yunhee , Lee Sang-Ah , Choi Ji-Yeob , Sung Hyuna , Jeon Sujee , Park Sue K. , Yoo Keun-Young , Noh Dong-Young , Ahn Sei-Hyun , Kang Daehee 
Published: August 2012

Abstract
The 5-year survival rate for breast cancer has increased from 78% during 1993 to 1995 to 90% during 2004 to 2008 among Korean women. Despite such improvement, breast cancer remains the leading cause of cancer mortality among women. One-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may affect breast cancer prognosis. This study aimed to investigate the associations of dietary intake of vitamin B2, vitamin B6 and folate before diagnosis and breast cancer prognosis. We assessed dietary intake from Food Frequency Questionnaire in 980 women who were newly diagnosed and histopathologically confirmed first primary breast cancer from hospitals located in Seoul, Korea in 2004 to2007 and followed for an average of 5.3 years. Univariate and multivariate analyses were used to investigate association between dietary intake of B-vitamins and disease free survival. There was no association between dietary intake of B vitamins and breast cancer prognosis. However, we found higher dietary intake of vitamin B6 was associated with improved survival in patients with BMI more than 25kg/m2 (harzard ratio (HR), 0.32; 95% confidence intervals (CI), 0.11-0.94) or positive hormone status in estrogen receptor(ER)/progesterone receptor(PR) (HR, 0.39; 95%CI, 0.16-0.97). Our study suggests that the high intake of vitamin B6 is associated with improved breast cancer survival in patients with higher BMI and positive hormone status in ER/PR.
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 641. doi:1538-7445.AM2012-641
Abstract 67: Characterization of the role of KLF9 transcription factor in breast cancer estrogen response
Authors: Pitch Michelle A. , Russell Beth A. , Greene Geoffrey L. 
Published: August 2012

Abstract
Kruppel-like factor 9 (KLF9) is a member of the KLF family of transcription factors. Previous studies report significant KLF member involvement in breast cancer estrogen response, notably KLF4 [1, 2] and KLF5 [3, 4]. KLF9 has been shown in uterine cancer cells to function as an estrogen-dependent regulator of the estrogen response pathway [5]. We aim to evaluate the role of KLF9 in breast cancer cell estrogen response. We have performed studies demonstrating that KLF9 exhibits an early-activated estrogen response. Five sites have been identified upstream of the KLF9 gene that interact with estrogen receptor alpha (ERα) [6-8]; we observe ERα enrichment at three of these sites that is estradiol-dependent. Though KLF9 has been shown to act as an essential element in estrogen response in the uterus, KLF9 response in breast cancer cells has yet to be characterized. To study the role of KLF9 in estrogen-mediated responses in transcriptional and proliferative activity, we have manipulated the level of KLF9 expression in MCF-7 breast cancer cells. These cells have been shown to exhibit a clear transcriptional response to estradiol in luciferase reporter assays. We have optimized RNAi conditions to achieve significant knockdown of the KLF9 gene in MCF-7 cells. Additionally, we have produced and tested a KLF9 overexpression vector construct that significantly upregulates expression of KLF9 in this cell line. These tools will be used to more extensively characterize the role of KLF9 in MCF7 cell estrogen-stimulated transcription and proliferation. We are measuring transcriptional response to estrogen signaling with luciferase reporter assays and estrogen stimulated cell proliferation with BrdU proliferation assays. Elucidating KLF9 involvement in E2-mediated breast cancer cell signaling and response, therefore, is an important component of understanding of the regulatory mechanisms behind estrogen response in breast cancer. 1. Akaogi K et al. (2009). Oncogene 28(32): 2894. 2. Quintana AM et al. (2011). BMC Cancer 11: 30. 3. Guo P et al. (2010). International Journal of Cancer 126(1): 81. 4. Zhao KW et al. (2011). Biochemical Journal 437(2): 323. 5. Velarde MC et al. (2007). Molecular Endocrinology 21(12): 2988. 6. Carroll JS et al. (2006). Nature Genetics 38(11): 1289. 7. Hua S et al. (2008). Molecular Systems Biology 4:188. 8. Fullwood MJ et al. (2009). Nature 462(7269): 58.
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 67. doi:1538-7445.AM2012-67
Abstract 676: Serological levels of folate at birth and risk of childhood acute lymphoblastic leukemia
Authors: Chokkalingam Anand P. , Chun Danielle , Hsu Ling-I , Metayer Catherine , Rabinowitz Daniel J. , Zhang Mindy , Wiemels Joseph L. , Buffler Patricia A. 
Published: August 2012

Abstract
A role for folate in the etiology of childhood acute lymphoblastic leukemia (ALL) has long been suspected due to folate's dual role in control of DNA methylation as well as maintenance of DNA synthesis. Case-control studies examining self-reported maternal folate intake and supplementation during pregnancy have been inconclusive. Furthermore, while studies of children's own folate metabolism and transport genes have identified potential disease loci, the results have been mixed on the whole. A child's exposure to folate in utero is modulated by a number of factors, including maternal intake/supplementation, maternal genes, and child's genes. Therefore, we examined the role of folate in childhood ALL risk more directly by utilizing a quantitative microbiologic assay to measure newborn red blood cell folate levels in archived dried bloodspots collected at birth from 319 incident cases and 413 matched population-based controls who enrolled in the Northern California Childhood Leukemia Study between 1995 and 2002. After adjustment for income, race/ethnicity, gender, and age, we found no difference in newborn folate levels between cases and controls overall (971 vs. 968 nmol/L, p=0.94). In addition, no differences between cases and controls were observed after stratification by birth year to account for the start of folate fortification of grain products in the US (1982-1994: 953 vs. 952 nmol/L, p=0.98; 1995-1998: 1018 vs. 975 nmol/L, p=0.34; and 1999-2002: 878 vs. 990 nmol/L, p=0.23). Children whose mothers reported pre-pregnancy supplement use had somewhat higher newborn folate levels overall, but we observed no case-control differences in folate levels after stratification by supplement use. Our results do not support an association between folate levels at birth and risk of childhood ALL. However, our results do not rule out a role for folate exposures after birth. Future epidemiologic studies of childhood ALL should pay particular attention to post-natal folate exposures.
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 676. doi:1538-7445.AM2012-676
Abstract 680: Loss of miR-34a as measured by quantitative in situ hybridization on a tissue microarray is associated with poor outcome in breast cancer
Authors: Agarwal Seema , Hanna Jason A. , Rimm David L. 
Published: August 2012

Abstract
Introduction: MicroRNAs (miRNAs) have emerged as key regulators in the pathogenesis of cancers as either oncogenes or tumor suppressors. It has been shown that the loss of miR-34a leads to tumor progression and metastasis using cell lines and a limited number of patient samples by RT-PCR. Lack of a robust, reproducible and quantitative method has limited large scale analysis and assessment of miR-34a as tumor suppressor marker in cancer. Herein, we have developed and validated a method for the quantitative analysis of miRNA expression by in situ hybridization (qISH) allowing for the direct assessment of tumor epithelial expression of miR34a in breast cancer. Method: Expression level of miR-34a was measured in a retrospective breast cancer (n=461) cohort with 20 year follow-up using quantitative immunofluorescence (AQUA) technology for ISH in a tissue microarray (TMA) format. The assay was performed in two-fold redundancy with a 40 case index TMA for reproducibility and standardization. Averaged AQUA scores for miR34a were correlated with clinical and pathological characteristics and 10 year disease-free survival in this cohort. Results: Since miR-34a is a tumor suppressor, we determined the threshold at which no specific hybridization was seen (AQUA score =16.89). Reproducibility between two different builds (cores) of the TMA was R*2 = 0.59. Using overall survival as an endpoint in Kaplan Meier analysis with the threshold of expression as the cutpoint, the group with loss of miR-34a had significantly worse survival (log rank p = 0.0264). Cox univariate analysis for miR-34a showed hazard ratio of 1.53 (95% CI: 1.05-2.22, p=0.0276). Cox multivariate analysis including age, nuclear grade, nodal status, ER, PR and Her2 showed miR34a is not an independent marker (p=0.0908). An independent breast cancer cohort will be used to validate this result. Conclusions: The microRNA miR-34a has been proposed to be a tumor suppressor using mechanistic and functional data. This result, showing loss of miR-34a is associated with worse outcome in a large breast cancer cohort provides clinical evidence of the tumor suppressor function of miR-34a.
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 680. doi:1538-7445.AM2012-680
Abstract 682: Increased stearoyl-CoA desaturase 1 expression is associated with shorter survival in breast cancer patients
Authors: Holder Ashley M. , Gonzalez-Angulo Ana M. , Chen Huiqin , Akcakanat Argun , Anh-Do Kim , Symmans Fraser , Pusztai Lajos , Hortobagyi Gabriel , Mills Gordon B. , Meric-Bernstam Funda 
Published: August 2012

Abstract
Stearoyl-CoA desaturase 1 (SCD1) is an essential regulator of fatty acid synthesis that affects cell membrane composition and may play a role in cancer cell metabolism. We have previously shown that SCD1 expression is increased by mTOR signaling and that SCD1 increases breast cancer cell growth in vitro. The purpose of this study was to determine protein levels of SCD1 in breast cancer and to determine whether there is an association between SCD1 levels and survival. Fine needle aspirates were collected from the primary breast cancers of 253 patients with Stage I-III breast cancer and protein lysates were prepared. SCD1 expression was analyzed using reverse phase proteomic array. Patient demographic and clinical characteristics including age, ethnicity, menopausal status, clinical stage, tumor grade, and tumor subtype were reviewed. Samples were divided into high or low SCD1 levels based on a cut-off determined from martingale residual plots and regression tree analysis. SCD1 levels were significantly higher in older patients and lower in triple negative (estrogen, progesterone, and HER2 negative) cancers, After adjusting for tumor subtype, tumor grade, age, and clinical stage, patients who had high SCD1 levels had significantly shorter relapse-free survival (RFS) (p=0.013) and overall survival (OS) (p=0.038). SCD1 level varies by breast cancer subtype and predicts significantly shorter RFS and OS. Future studies are needed to define the role of SCD1 in breast cancer and evaluate its potential as a therapeutic target.
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 682. doi:1538-7445.AM2012-682
Abstract 704: Expression of FOXO1 is associated with GATA3 and Annexin-1 and predicts disease-free survival in breast cancer
Authors: Wu Yan Yuan , Elshimali Yayha , Sarkissyan Marianna , Mohamed Hezla , Clayton Sheila , Vadgama Jay 
Published: August 2012

Abstract
Purpose: To determine the prognostic value of FOXO1, GATA3 and Annexin-1 expression in breast cancer. Methods: Tissue microarray and individual paraffin tissue slides from 131 patients were used for the study. The association of FOXO1, GATA3 and Annexin-1 expression with clinicopathological features of breast cancer and disease outcome was examined in retrospective samples. Kaplan-Meier survival curves and Cox regression with multivariate analysis were used for assessing the relative risk (RR) and disease-free survival (DFS). The expression of FOXO1, GATA3 and Annexin-1 were determined by immunohistochemistry and the association among the three proteins was analyzed by Logistic regression analysis. Results: The nuclear expression of FOXO1 was observed in most of the normal breast tissues and 51.3% of the malignant breast tissues. GATA3 and Annexin-1 were expressed at 73% and 24.6% respectively in breast cancer tissues. The expression of FOXO1, GATA3 and Annexin-1 were all inversely correlated with lymph node-positive tumors. Both FOXO1 and Annexin-1 expression were also inversely associated with HER2-overexpressing tumors. FOXO1 expression was significantly associated with both GATA3 and Annexin-1 expression. In addition, Multivariate analyses confirm that only FOXO1 levels independently predict DFS. Conclusion: FOXO1 expression in breast cancer is regulated by the PI3K/Akt pathway. The expression of FOXO1 is also associated with GATA3 and/or Annexin-1. Restoring or targeting FOXO1 to the cell nucleus in breast cancer tissues may improve response to therapy and disease outcome. Further clinical studies are warranted to test this hypothesis.
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 704. doi:1538-7445.AM2012-704
Abstract 726: Copy number amplification of the PIK3CA gene is associated with poor prognosis in early-stage head and neck squamous cell carcinoma
Authors: Suda Toshihito , Hama Takanori , Urashima Mitsuyoshi , Kato Takakuni , Moriyama Hiroshi 
Published: August 2012

Abstract
Background: Deregulation of the EGFR signaling pathway is one of the most frequently observed genetic abnormalities that drive cancer development. Mutations in downstream components of the EGFR signaling pathway, including KRAS, BRAF and PIK3CA, have been reported in numerous cancers. However, extensive mutation analysis of these genes in clinical samples has not been performed for head and neck squamous cell carcinoma (HNSCC). Patient and methods: We examined mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients. Results: We identified three mutations in K-RAS and two mutations in PIK3CA. Copy number amplification was found in 42 cases (36.4%) for PIK3CA, 12 cases (10.4%) for K-RAS and nine cases (7.8%) for BRAF. Tumor recurrence and death occurred in 49 (42.6%) and in 22 (19.3 %) patients during the median follow-up of 723 days, respectively. Kaplan-Meier survival analysis revealed that in patients with early-stage carcinoma (Stages I-III), copy-number amplification of PIK3CA was drastically associated with cancer relapse. Conclusion: Copy number amplification of the PIK3CA is associated with poor prognosis in early-stage HNSCC. The PIK3CA copy number status will serve as a marker of poor prognosis in patients with HNSCC.
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 726. doi:1538-7445.AM2012-726
Abstract LB-175: β-Escin inhibits NNK-induced lung adenocarcinoma formation in A/J mice by suppressing ALDH1A1 positive cells; and RhoA/Rock induced invasion of human lung cancer cell growth.
Authors: Patlolla Jagan Mohan R. , Qian Li , Barton Laura , Zhang Yuting , Desai Dhimant , Amin Shantu , Lightfoot Stan , Rao Chinthalapally 
Published: August 2012

Abstract
Lung cancer is the leading causes of cancer deaths. β-Escin a triterpene saponin isolated from horse chestnut (Aesculus hippocastanum) seeds, had tested on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung adenoma and adenocarcinoma formation in female A/J mice and its possible mode of action was evaluated using human lung cancer cell lines (H460 and H2126). For bioassay, at 6 weeks of age, mice were randomized and fed control AIN-76A modified diet. At 7 weeks of age (25 mice/group) intended for carcinogen treatment received one dose of 10 μmol NNK /mouse by i.p. injection. Three weeks after the NNK treatment, groups of mice fed either control or experimental diets containing 500 ppm β-Escin. Mice were continued on the respective diets and killed at 20 weeks (10 mice/group) and/or 36 weeks (15 mice/group) after NNK-treatment for lung tumor evaluation by histopathological methods. Administration of 500 ppm β-Escin significantly suppressed lung tumor (adenoma+adenocarcinoma) formation by &gt;40% (p&lt;0.0015), at 20 weeks and 53.3% (p&lt;0.0001), at 36 weeks. Importantly, β-Escin showed NNK-induced lung adenocarcinoma inhibition by 65% (p&lt;0.001), at 20 weeks and by 53% (p&lt;0.0001) at 36 weeks. These results suggest that β-Escin inhibits the NNK-induced lung tumor and more so by suppressing adenocarcinoma formation. Immunohistochemistry analysis revealed that lung tumor harvesting from mice exposed to β-Escin showed significantly reduced ALDH1A1 expression when compared to control lung tumors. Since ALDH1A1 is a putative lung cancer stem cell marker and associated with therapeutic resistance. Furthermore, in Aldefluor assay using FACS analysis of lung cancer cell lines treated with different concentrations of β-Escin (0-40 µM) revealed that the subpopulation of cells with elevated ALDH activity has significantly inhibited by ∼60-85%. Also, β-Escin induced p21 levels and suppressed Rho A and Rock protein expression in H460 and H2126 cell lines and NNK-induced lung tumors. Our findings for the first time suggest that β-escin inhibits tobacco carcinogen-induced lung tumor formation by modulating ALDH1A1 positive cells and RhoA/Rock pathway singling. {Supported by Kerley-Cade Endowment for Cancer Research}
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 LB-175. doi:1538-7445.AM2012-LB-175