bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 615: Apigenin regulates prostate cancer matrix composition and cell attachment through an integrin alpha 1 dependent pathway
Authors: Franzen Carrie A. , Pelling Jill C. , Bergan Raymond C. 
Published: August 2012

Abstract
Prostate cancer (PCa) mortality is primarily attributed to metastatic rather than primary, organ-confined disease. Acquiring a motile and invasive phenotype is an important step in the development of metastasis. This step involves remodeling of the extracellular matrix (ECM) and of cell-matrix interactions, cell movement mediated by the actin cytoskeleton, and activation of focal adhesion kinase (FAK)/Src signaling. Epidemiologic studies suggest that the metastatic behavior of PCa may be an ideal target for chemoprevention. The natural flavone apigenin is known to have chemopreventive properties against many cancers, including PCa. Building upon our previous findings showing that apigenin inhibits cell motility and invasion of PCa cells through the FAK/Src signaling pathway, here we study the effect of apigenin on integrin receptors, cell attachment, and ECM composition. By using an alpha/beta integrin-mediated cell adhesion array, we found that integrin alpha 1 (ITGA1) was the only integrin subunit to be down-regulated by apigenin in PC3-M cells. ITGA1, whose only binding partner is integrin beta 1, is a receptor for collagen and laminin. Integrin α1α1 gives cells the ability to attach to collagenous substrata. As collagen and laminin are important regulators of PCa cell survival, growth and metastasis to bone, we next elucidated the effect of apigenin on PC3-M cell attachment to laminin 1 and collagen IV. We found that apigenin decreases cell attachment to both of these ECM molecules, suggesting a potential anti-tumorigenic mechanism. It has been shown that integrin α1α1 can regulate the synthesis of collagen. So we next tested whether apigenin can alter the ECM deposited by PC3-M cells. We first tested whether ECM deposited by apigenin-treated cells provided the same adhesive support to PCa cells as the ECM deposited by the untreated cells. Interestingly, even cells not treated with apigenin did not attach and spread well on the ECM deposited by apigenin-treated cells, indicating that apigenin treatment changes the composition of the ECM. Using Western blot to evaluate differences in the composition of matrix deposited by control cells and apigenin-treated cells, we found that apigenin-treated cells produce much less collagen I and IV, thus correlating with the decrease in adhesion and spreading. These results demonstrate that the chemopreventive bioflavonoid apigenin may inhibit PCa cell adhesion through a combined effect on integrin α1α1 cell surface expression and ECM deposition.
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 615. doi:1538-7445.AM2012-615
Abstract 622: Estrogen plus progesterone and colorectal cancer incidence and mortality in the Women's Health Initiative
Authors: Simon Michael S. , Chlebowski Rowan T. , Wactawski-Wende Jean , Johnson Karen C. , Muskovitz Andrew , Kato Ikuko , Young Alicia , Hubbell F Allan 
Published: August 2012

Abstract
Background: During the intervention period in the Women's Health Initiative (WHI) trial, estrogen plus progestin use was associated with lower colorectal cancer incidence but the cancers were diagnosed at substantially higher stage. To assess the long term influence of estrogen plus progestin on this disease, analyses were conducted over the entire follow-up period. Methods: The WHI study is a randomized, double-blind, placebo-controlled, clinical trial involving 16,608 postmenopausal women aged 50-79 years with an intact uterus who were randomly assigned to a once-daily tablet of 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (N=8,506) or matching placebo (N=8,102). We assessed incidence, tumor characteristics, and mortality rates for invasive colorectal cancers. Analyses were by intention to treat. The study is registered with clinical trials CT.gov NCT00000611. Findings: After a mean of 5.6 years (SD 1.03) of therapy and 11.6 (SD 3.1) years of total follow-up, 118 women in the combined hormone therapy group were diagnosed with colorectal cancer vs 145 in the placebo group (incidence/year 0.12% vs 0.16%; hazard ratio [HR] 0.72, 95% confidence interval (CI), 0.56-0.94; P=0.014). Bowel screening exams were comparable between groups throughout. Cancers in the combined hormone therapy group more commonly had positive lymph nodes (53.4% vs 30%, P=0.007) and were at higher stage (regional or distant, 68.8% vs 51.4%, P=0.003). Somewhat more women died from colorectal cancer in the combined hormone therapy group (37 vs 27 deaths; 0.04% vs 0.03%; HR 1.29, 95% CI 0.78-2.11, P=0.320). Interpretation: Although estrogen plus progestin use was associated with lower colorectal cancer incidence, the cancers were at more advanced stage and no trend for colorectal cancer mortality reduction emerged. These findings, suggestive of diagnostic delay, do not support a clinically meaningful benefit for combined hormone therapy on colorectal cancer risk.
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 622. doi:1538-7445.AM2012-622
Abstract 633: Synergistic interplay between long-term overweight and long menstrual years in endometrial cancer
Authors: Lu Lingeng , Lee Shanming , Mayne Susan , Irwin Melinda , Cartmel Brenda , Risch Harvey , Yu Herbert 
Published: August 2012

Abstract
Long-term exposure to estrogen is one of the established mechanisms underlying the development of endometrial cancer. Early menarche, late menopause, low number of pregnancies, and obesity, as risk factors of endometrial cancer, are all linked to this mechanism. However, the synergy among these factors is still less clear. To evaluate the interplay among long-term overweight, menstrual and reproductive features in endometrial cancer, a population-based case-control study was conducted with 668 incident cases and 674 age-matched population controls. Information on menstrual and reproductive features, anthropometric measurements in each decade of adult life as well as hormone replacement therapy was ascertained through a structured questionnaire administered by interviewers. Unconditional logistic regression model was used to examine the associations of these factors with endometrial cancer. As expected, the results show that early menarche, late menopause, low number of pregnancies and live births, and long-term overweight were associated with increased risk. To assess all the menstrual and reproductive factors together, we calculated net menstrual years by subtracting age at menarche from age at menopause, which was further subtracted by the total years of pregnancy. Women with long net menstrual years (&gt; 38 years) had nearly two-fold increases in risk of endometrial cancer (95% CI: 1.43-2.41) compared to those with shorter years (&lt;35 years). Approximately a 3.5-fold increase in risk (95% CI: 2.79-7.04) was observed in those who were overweight since ages 20's or 30's compared to those who maintained BMI under 25 throughout life. Women with both long net menstrual years and long-term overweight combined had over 7-fold increases in risk compared to those with short years and normal weight. These finding suggest that long-term overweight and long menstrual years may have a synergistic effect on endometrial cancer risk.
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 633. doi:1538-7445.AM2012-633
Abstract 652: Reproductive and hormonal factors and ovarian cancer: Case-control study
Authors: ma Seunghyun , Park Sue K. , Yoo Keun-Young , Kim Tae Joong , Kim Byoung-Gie , Kim Yong-Man , Kim Jae Weon 
Published: August 2012

Abstract
Backgrounds: Menstrual, reproductive and hormonal factors have been related to ovarian cancer risk, but further quantification of their role in various populations is required. Patients and methods: Cases were 77 women, below age 79, with incident, histologically confirmed epithelial ovarian cancer, and 117 women with, histologically confirmed benign ovarian tumor and controls 776 women, age matched controls The study was conducted from 2009 to 2010 in five hospitals in Seoul, South Korea. Data were obtained through in-person interviews and analysis was conducted using unconditional logistic regression Results: A statistically significant inverse association was observed between parity and ovarian cancer risk and between parity and benign ovarian tumor (Odds ratio [OR] = 0.18; 95% confidence interval [CI] = 0.06-0.50, OR=0.08, CI (0.02-0.30))No consistent association was observed with time since first or last birth, nor with spontaneous or induced abortions Breastfeeding was associated with a significant reduction in risk of ovarian cancer and benign neoplasm. (OR=0.33, CI (0.17-0.68), OR=0.42 CI(0.34-0.94)) Conclusion: This uniquely asian study confirms and further quantities the relation between hormonal and reproductive factors and ovarian cancer.The pattern of risk observed cannot be totally explained by a role of ovulation in ovarian carcinogenesis.
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 652. doi:1538-7445.AM2012-652
Abstract 659: Intake of fiber and fiber-rich plant foods associated with lower risk of renal cell carcinoma in a large U.S. cohort
Authors: Daniel Carrie R. , Chow Wong-Ho , Park Yikyung , Graubard Barry I I. , Hollenbeck Albert R. , Sinha Rashmi 
Published: August 2012

Abstract
Renal cell carcinoma (RCC) accounts for nearly all adult kidney malignancies. The age-adjusted incidence of RCC has more than doubled over the last three decades in the U.S., mirroring the growing epidemic of obesity, which along with smoking comprise the most well-established RCC risk factors. Plant-based and fiber-rich diets high in vegetables, fruits, and whole grains are recommended for the prevention of cancer, as well as chronic conditions positively associated with RCC incidence, such as hypertension and diabetes. Thus, diet may play a role in RCC etiology directly and/or indirectly. In a large prospective cohort of U.S. men and women, we comprehensively investigated dietary intake of a range of plant foods and their nutritional components in relation to RCC risk. We further examined whether associations varied by history of hypertension or diabetes, body mass index, smoking status, or alcohol intake. At baseline (1995-1996), 492,186 participants of the National Institutes of Health-AARP Diet and Health Study completed a self-administered questionnaire of demographics, diet, lifestyle, and medical history. Over 9 (mean) years of follow-up we identified 1,814 incident cases of RCC. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated within quintiles (Q) using multivariable Cox proportional hazards regression. Intake of legumes, whole grains, and cruciferous vegetables were associated with a statistically significant 16-18% reduced risk of RCC. Conversely, refined grain intake was positively associated with RCC risk [Q5 vs. Q1, HR and 95% CI: 1.19 (1.02-1.39); P-trend =0.04] and we found no association with fruit intake. These findings were consistent with the strong inverse association we observed for total dietary fiber intake [Q5 vs. Q1, HR and 95% CI: 0.81 (0.69-0.95); Ptrend =0.005], as well as fiber derived from various dietary sources. The association between fiber intake and RCC did not vary substantially by smoking status [Q5 vs. Q1, HR and 95% CI: 0.65 (0.49-0.87) and 0.50 (0.25-1.02) in never vs. current smokers, respectively], history of hypertension [0.73 (0.52-1.02) and 0.75(0.57-1.00) in negative vs. positive history, respectively], or other major risk factors. In conclusion, intake of fiber and fiber-rich plant foods was associated with a significantly lower risk of renal cell carcinoma in this large U.S. cohort.
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 659. doi:1538-7445.AM2012-659
Abstract 692: Prognostic indicators associated with breast cancer molecular subtypes in African-American women
Authors: Ricks-Santi Luisel J. , Esnakula Ashwini , Frederick Wayne A.I. , Dunston Georgia M. , Naab Tammey 
Published: August 2012

Abstract
Background: Overexpression of Fascin, Endoglin (CD105), and Beta-Catenin has been found to be associated with unfavorable prognosis and progression in hormone-receptor negative breast carcinomas. Specifically, fascin promotes cell motility, while Beta-catenin is involved in cancer invasion, cellular transformation, and metastasis. CD105 is selectively upregulated in small, immature tumor vessels in malignant tumors. The objective of this study was to correlate fascin, CD105, and Beta-Catenin protein expression with clinicopathological factors including age, grade, tumor size, stage, regional node status, survival, and with the four major molecular breast cancer subtypes (luminal A, luminal B, HER2 positive, and Triple Negative [TN]). Methods: Tissue microarrays (TMAs) were constructed from optimally-fixed formalin-fixed, paraffin-embedded tumor blocks from primary breast carcinomas in 203 African-American females. Sections were stained with antitibodies against fascin, CD105, and beta-catenin. The sections were evaluated for the intensity of reactivity (0-3) and the percentage of reactive cells. Cases were categorized as having negative/weak (score &lt;10) or moderate/strong (score &gt;10) fascin expression, negative (score=0) or positive (score&gt;0) CD105 (in tumor cells only) and beta-catenin (cytoplasmic and nuclear) expression. Bivariate analysis was done via χ2 analysis and survivability data was calculated via the generation of Kaplan-Meier curves (SPSS v19). Statistical significance was assumed if P &lt; 0.05. Results: On the TMA, there were 67 triple negatives, 88 Luminal As, 29 Luminal Bs, and 18 Her2 overexpressing cancers. The mean age for the patients in the study was 57.65. Fascin expression was significantly linked to the triple negative subtype (p&lt;0.0001), ER negativity (p&lt;0.0001), PR negativity (0.0001), and Grade III differentiation (p=0.03). CD105 cytoplasmic expression significantly correlated with HER2 positive subtype (p&lt;0.0001), Luminal B subtype (0.01), HER2 positivity (p&lt;0.0001), tumor size (p&lt;0.01) and was associated with decreased disease-free survival (p=0.038). Cytoplasmic beta-catenin expression was significantly associated with triple negative subtype (p&lt;0.03), HER2+ subtype (p&lt;0.001), ER negativity (p&lt;0.001), PR negativity (p&lt;0.001), and HER2 negativity (p=0.03). Conclusions: Our results indicate that fascin, CD105, and Beta-catenin may be potential markers of aggressive breast cancer subtypes and predictors of recurrence and survival. These data also support pharmacological targets for these aggressive subtypes.
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 692. doi:1538-7445.AM2012-692
Abstract 703: Verification of a novel approach to identify disease mechanisms in breast cancer patient subsets and application of this approach to indicating and characterizing tamoxifen resistance
Authors: Drubin David A. , Thomson Ty M. , Park Jennifer S. , Macoritto Michael , de Graaf David , Kenney Renee D. 
Published: August 2012

Abstract
Breast cancer is a heterogeneous disease that can be divided into distinct clinical and molecular subtypes. Key biomarkers such as the expression of HER2 or ER serve as a basis for subdividing the disease into distinct clinical entities and to distinguish patients who will most likely respond to specific targeted therapies, such as Herceptin and tamoxifen, respectively. Further understanding the molecular mechanistic differences among and within the breast cancer subtypes can facilitate the identification of treatment regimens that can be even more tailored to an individual's disease. If such a strategy is implemented, efficacy rates for cancer treatments can be improved, and more importantly, patients will be spared from any collateral effects of those treatments that will not combat their specific disease. We have taken a systems biology approach to segregate breast cancer patients into subgroups by semi-quantitatively evaluating the literature-derived molecular gene expression footprints of over 2100 mechanisms in our Knowledgebase. This approach effectively enables the stratification of breast cancer patients by their individual levels of signaling amplitude for these mechanisms. Using publicly available breast cancer data sets from GEO, we validated the stratification capability of these inferred mechanism activities against immunohistochemical staining for ER and HER2, and sequencing-based identification of TP53 mutation. In addition, applying this semi-quantitative evaluation of mechanism molecular footprints based on gene expression data from ER+ breast cancer patients before tamoxifen treatment (GSE17705), we developed a tamoxifen-sensitivity classifier a priori of knowledge of clinical outcome. This classifier enabled prediction of 16 of the 19 patients from an independent test set (GSE6532) who had gone on to develop distant metastases. Beyond identifying specific breast cancer sub-groups, which has been well established by clustering sets of genes, the systems biology-based approach presented here enables us to identify the specific mechanisms defining the separation of patient groups, and offers a means of either selecting the right patient population for a drug candidate or indicating additional/alternative disease pathways that could be targeted for clinical efficacy. This strategy is universal and can be applied to a variety of other cancers and diseases.
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 703. doi:1538-7445.AM2012-703
Abstract 705: HER2 assessment to define outcomes for breast cancer patients treated with neoadjuvant therapy
Authors: Cheng Huan , Bai Yalai , Sikov Willliam , Sinclair Natalie , Abu-Khalaf Maysa , Harris Lyndsay N. , Rimm David L. 
Published: August 2012

Abstract
Background: HER2 expression or amplification is now an established companion diagnostic test. Now, as HER2-targeting neoadjuvant therapy for breast cancer increases, the accuracy of the companion diagnostic tests are revisited. Specifically, we seek to determine with the level of expression of the target (HER2 protein) is associated with pathologic response. In this study, we quantitatively assess HER2 expression both before and after the neoadjuvant therapies to breast cancer in the BrUOG BR-211B (NCT00617942) trial. Methods: We evaluated core biopsy samples from breast cancer patients enrolled in a preoperative clinical trial using trastuzumab, nab-paclitaxel and carboplatin combination therapy. Tumor core biopsies were taken before and after 10 days of either trastuzumab or nab-paclitaxel treatment. Combination chemotherapy was given for 6 cycles. Automated quantitative analysis (AQUA), a fluorescent-based method for analysis of in situ protein expression, was used to assess HER2 and phospho-HER2 expression in the BruOG Cohort, a study where patients who serially received Herceptin and Abraxane were biopsied both before and after treatment. This study assesses the HER2 positive patient subset (n=27) Results: Of 18 evaluable patients, the 8 with a PathCR showed a mean HER2 levels of 10251 compared with 4766 in the patients without PathCR (p=0.0047). This is notable in that a HER2 score of 2000 is equivalent to HER2 2+ in previous studies. Measurement of Phospho-HER2 showed no difference in PathCR vs Non-PathCR groups. A small subset (9) cases were measured for HER2 immediately after treatment, but the study has accrued an insufficient number of cases to statistically determine if there is a reduction in HER2 immediately following treatment. Conclusions: High levels of HER2 are associated with PathCR in the neoadjuvant setting. Levels of Phospho-HER2 are not associated with response. Further studies are underway to determine changes in levels of HER2 immediately after treatment.
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 705. doi:1538-7445.AM2012-705
Abstract 716: High viral load is associated with poor postoperative survival in hepatitis B virus-related hepatocellular carcinoma
Authors: Yang Tian , Zhao Ronghua , Zhai Jian , Yu Wei-Feng , Yang Guang-Shun , Wu Meng-Chao , Lu Jun-Hua 
Published: August 2012

Abstract
Background & Aims: The aim of this prospective cohort study was to investigate the impact of preoperative hepatitis B viral load, as well as postoperative antiviral therapy, on the risk of long-term survival after curative resection of hepatitis B virus-related hepatocellular carcinoma (HCC). Methods A prospective cohort of hepatitis B virus-related HCC patients undergoing curative resection from 2001 to 2007 was studied. According to preoperative viral load (using 10,000 copies/mL of hepatitis B virus DNA level as cut-off value), two groups were compared. Prognostic factors for overall survival and recurrence-free survival were evaluated. Additionally, subgroup analysis was conducted in patients with high viral load to investigate prediction of postoperative antiviral therapy on the long-term prognosis. Results With a median follow-up of 49.1 months, patients with high viral load had lower median overall survival (78.3 months vs. 111.4 months, P &lt; 0.001) and RFS (44.6 months vs. 94.8 months, P &lt; 0.001) compared with those with low viral load. Multivariate analysis revealed that preoperative high viral load was an independent risk factor affecting both overall survival and recurrence-free survival (both P &lt; 0.001). The subgroup analysis revealed that postoperative antiviral therapy independently improved recurrence-free survival for patients with high viral load (P = 0.001). Conclusions Hepatitis B virus-related HCC patients with preoperative high viral load led to poorer overall and recurrence-free survival than those with low viral load after curative resection. To prevent postoperative recurrence, antiviral therapy should be initiated in those patients with hepatitis B virus DNA ≤ 10,000 copies/ml.
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 716. doi:1538-7445.AM2012-716