bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4486: Mitochondrial DNA copy number is associated with colorectal cancer risk
Authors: Thyagarajan Bharat , Wang Renwei , Barcelo Helene , Koh Woon-Puay , Yuan Jian-Min 
Published: August 2012

Abstract
Background: Mitochondrial DNA (mtDNA) copy number variation is common in colorectal tumors and one case control study showed mtDNA copy number to be associated with increased colorectal cancer risk. Data on mtDNA copy number and colorectal cancer risk in prospective cohorts is lacking. Objectives: We evaluated the association between mtDNA copy number in peripheral blood and colorectal cancer risk among participants of the Singapore Chinese Health Study. Methods: We conducted a nested case-cohort study of 422 colorectal cancer cases (168 incident cases with pre-diagnostic blood and 254 prevalent cases with post-diagnostic blood) and 880 controls who were free of colorectal cancer at blood draw. The relative mtDNA copy number was measured using real time PCR. Analysis of covariance and logistic regression methods were employed to examine the association between mtDNA copy number and colorectal cancer risk. Results: mtDNA copy number was significantly higher among colorectal cancer cases than controls (geometric mean: 0.62 vs. 0.50, p&lt;0.0001). There was a U shaped relationship between the mtDNA copy number and colorectal cancer risk. Individuals in the low and high mtDNA copy numbers were at increased risk of colorectal cancer; odds ratios (95% confidence interval) for developing colorectal cancer for the lowest and highest quartile of mtDNA copy numbers were 1.83 (1.16-2.90) and 3.54 (2.25-5.55), respectively, compared to those in the second quartile of mtDNA after adjustment for potential confounders (p for curvilinear trend &lt;0.001). The lowest mtDNA copy number quartile was associated with colorectal cancer only in the pre-diagnostic blood samples (OR=3.22, 95% CI:1.51-6.85) but not in the post-diagnostic blood samples (OR=1.36, 95% CI:0.80-2.32), implying that cancer status impacts the mtDNA copy number-colorectal cancer risk association. Conclusions: This is the first study to show a prospective association between mtDNA copy number and colorectal cancer risk. Further studies are needed to confirm this association and understand the biological significance of these observations.
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 4486. doi:1538-7445.AM2012-4486
Abstract 4491: Transforming growth factor (TGF) ≤ pathway and clinical outcome of pancreatic cancer
Authors: Javle Milind M. , Dong Xiaoqun , Tan Dongfeng , Li Yanan , Kar Siddhartha P. , Baladandayuthapani Veera , Weatherly Jacqueline , Krishnan Sunil , J Tzu-chuan , Huang  , Fogelman David R. , Abbruzzese James L. , Wolff Robert A. , Li Donghui 
Published: August 2012

Abstract
Background: TGFβ acts both as a tumor suppressor or tumor promoter depending upon cellular context and stage of tumor progression. TGFβ exerts its effects through the TGFβR1/ R2 receptors and the SMAD transcription regulators. We investigated the prognostic value of TGFβ signaling biomarkers in pancreatic cancer. Methods: We measured plasma TGFβ1 level using Meso Scale Discovery Multi-array® Human TGFβ1 Assay in 643 pancreatic cancer patients. TGFβR2 (Novus) and SMAD4 (Proteintech) protein expression were measured in 86 biopsies using immunohistochemisty (IHC). IHC intensity was scored 0-3. Percentage IHC-positive cancer cells were 0-3 (0: 0%+, 1: 1-10%+, 2: 10-25%+, 3: &gt;25%+). Final IHC score was measured as intensity × percentage. We also genotyped 3 SNPs of TGFB1 gene using the Taqman assay. Kaplan-Meier and log-rank tests were used to analyze overall survival (OS) by TGFβ1 level. Multivariate Cox proportional hazards models with relevant clinical covariates were used to assess the relationship between IHC score and OS. Results: In patients with locally advanced and metastatic disease (n = 355), there was a significant association of plasma TGFβ1 with OS. OS of the top quartile of TGFβ1 levels (&gt;19.05 ng/mL) vs. those with low level was 27.7 weeks vs. 40 weeks, respectively [log-rank p = 0.0125, adjusted for baseline CA 19-9 and performance status (PS)]. No significant association between plasma TGFβ1 and OS was noted in surgical patients (n = 288). In the multivariate Cox model, after adjusting for baseline stage, CA 19-9, PS, age and TGFβR2 expression, complete loss of SMAD4 expression (IHC score 0) was significantly associated with lower OS [HR (95% CI): 1.85 (1.06-3.23), p = 0.03]. Progressive disease on gemcitabine-based therapy was more likely in SMAD4 IHC 0 group as compared with higher score (46.5% vs. 38.1% progressed; chi square p = 0.069). TGFB1 –1346T&gt;C CT/TT genotype correlated with shorter OS [HR (95% CI): 1.21 (1.02-1.45), p = 0.03] after adjusting for clinical variables. Conclusions: This large retrospective study suggests an important stage-dependant role of the TGFβ pathway in pancreatic cancer. Targeting this pathway in advanced pancreatic cancer may have therapeutic relevance.
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 4491. doi:1538-7445.AM2012-4491
Abstract 4493: Serum X-linked inhibitor of apoptosis protein (XIAP) predictive recurrence of renal cell carcinoma
Authors: Hongo Fumiya , Takaha Natsuki , Kimura Yasunori , Nakamura Terukazu , Mikami kazuya , Miki Tsuneharu 
Published: August 2012

Abstract
Purpose: The X-linked Inhibitor of Apoptosis (XIAP) is associated with cell survival by blocking caspase-mediated apoptosis. The expression and prognostic significance of XIAP in renal cell cancer (RCC) has been rarely studied. To our knowledge, no report on the serum XIAP levels from RCC patients has been published. In this study, we examined serum XIAP levels of RCC patients and normal individuals and evaluated its utility as biomarker. Methods: Peripheral blood samples were obtained from 84 patients (59 men and 25 women, median age; 63 years [36-85]) with RCC before surgery. All the patients underwent radical or partial nephrectomy. Blood samples were also collected from 52 healthy controls. The serum TRAIL levels were measured by a sandwich enzyme-linked immunosorbent assay (Gencompare, TiterZyme®). Cut off value was calculated by ROC analysis. Results: The serum XIAP levels in patients with RCC were higher than those of normal control individuals (328.3 pg/ml vs 156.2 pg/ml, P&lt;0.001). The progression free survival rate of the RCC patients with high serum XIAP was shown to be significantly lower than that of those with low serum XIAP in Grade 1-2 group (P &lt; 0.05). Conclusions: Serum XIAP level is higher in renal cell cancers compared to normal control. High XIAP expression is not directly associated with tumor stage. These results suggest that it may be used as a novel prognosticator and a potential target for renal cell cancer diagnosis and therapy.
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 4493. doi:1538-7445.AM2012-4493
Abstract 4498: Prognostic significance of nuclear factor kappa B expression in human papillomavirus-associated oropharyngeal cancer
Authors: Zhang Hongzheng , Hu Zhongliang , Phelan Vanessa , Liu Yuan , Müller Susan , Saba Nabil F. , Beitler Jonathan J. , Khuri Fadlo R. , Chen Georgia Z. , Shin Dong M. 
Published: August 2012

Abstract
Nuclear factor kappa B (NFκB) has been implicated in the development of head and neck squamous cell carcinoma (HNSCC) from premalignant changes to tumor progression and recurrence. However, the prognostic significance of cytoplasmic or nuclear localization of NFκB expression in human papillomavirus (HPV)-associated HNSCC has not been investigated largely due to limited patient samples. We hypothesized that cytoplasmic and/or nuclear expression of NFκB may be a poor prognostic factor for tumor recurrence and overall survival (OS) regardless of p16 status. We conducted a retrospective study with archival formalin-fixed paraffin-embedded tumor biopsies collected from 188 patients with oropharyngeal SCC between October 1994 and February 2008 from Emory University Department of Pathology. Median follow-up was 21.7 and 58.0 months for p16- and p16+ patients, correspondingly. Tumors were evaluated for p16 expression (a surrogate marker for HPV) by immunohistochemistry (IHC). Cytoplasmic expression of NFκBp65 by IHC or total expression combining cytoplasmic and nuclear localization were significantly greater in p16- patients (N=58) than p16+ patients (N=130), p&lt;0.05. High cytoplasmic expression of NFκBp65 was significantly associated with poor OS (p=0.0276) and the total expression was associated with recurrence (p=0.0081) by log rank test, whereas nuclear NFκBp65 displayed weak association. Positive nuclear expression significantly correlated with smoking history (p=0.025). In conclusion, p16+ and low total NFκBp65 expression is associated with the best while p16- and high total NFκBp65 is associated with the worst OS in this patient cohort (Table I). (The study was supported by Head and Neck SPORE Grant P50CA128613).

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 4498. doi:1538-7445.AM2012-4498
Abstract 45: The clinical significance of CD163 in patients with hepatocellular carcinoma who underwent curative resection
Authors: Hui-Chuan Sun , Kong Ling-Qun , Zhu Xiao-Dong , Chai Zong-Tao , Tang Zhao-You 
Published: August 2012

Abstract
Background We have found that the abundance of peritumoral CD68+ macrophages was associated with patients’ prognosis after curative resection of hepatocellular carcinoma (HCC). However, the role of the pro-tumoral or tumoricidal macrophages is still not clear. Methods In this study, the clinical significance of immunostaining of CD163, a marker of alternatively activated macrophages (M2), in tumor and peritumoral liver tissue from a cohort of 295 Chinese HCC patients who underwent curative resection was evaluated and compared with that of the immunostaining of CD68. The clinical significance of soluble form of CD163 (sCD163) in peripheral blood was also evaluated in another cohort of 107 HCC patients. Results The count of CD163+ cells was well correlated with and much higher than that of CD68+ cells in both tumors and peritumoral liver tissues respectively, which was consistent with the observation from immunostaining by CD68 or CD163 antibody on the consecutive sections. Patients with a higher count of peritumoral CD68+ cells was associated with poor recurrence-free survival and overall survival (P = 0.004 and, P = 0.001, respectively), whereas the counts of tumor and peritumoral CD163+ cells did not. Plasma sCD163 level was associated with active hepatitis-related factors (e.g. serum alanine aminotransferase, serum aspartate aminotransferase, γ-glutamyl transpeptidase and serum alkaline phosphatase). Conclusions CD163+ cell count is of limited significance to predict patients’ prognosis in HCC. Plasma sCD163 was more likely a factor related with active hepatitis rather than tumor related features.
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 45. doi:1538-7445.AM2012-45
Abstract 4500: Clinical significance of survivin expression in urothelial carcinoma of the bladder
Authors: Wang Yuan-Hung , Hsieh Hsiao-Yen , Hsu Cheng-Da , Tung Chun-Liang , Shen Kun-Hung , Shen Cheng-Hung 
Published: August 2012

Abstract
Objective: Survivin is one of the inhibitors of apoptosis protein family and plays an important role in carcinogenesis. Survivin also has been reported to be related with poor clinical outcome in various malignancies. The aim of this study is to examine the association between survivin expression and clinical outcome in urothelial carcinoma of the bladder. Materials and methods: A total of 56 histopathologically confirmed urothelial carcinoma of bladder (UCB) patients were recruited from the Department of Urology of Chiayi Christian Hospital and Chi-Mei Medical Center from August 2006 to May 2007. Immunohistochemistry (IHC) analysis was performed to determine the expression level of survivin in tumor and adjacent normal tissues. One normal human urothelial cell: HUC4449 and nine urothelial carcinoma cell lines which are TSGH8301, 5637, BFTC905, BFTC909, HT1376, TCC SUP, J82, T24 and HT1197 for survivin mRNA analysis by quantitative real-time PCR. The –31 C/G polymorphism in survivin gene was determined using PCR-RFLP method. The effects of a higher expression level of survivin on disease-free survival (DFS) and overall survival (OS) were estimated using Cox proportional hazard models. Results: The frequency of low, moderate and higher expression of survivin in tumor tissues of UCB were 16.1%, 39.3% and 44.6%, respectively. The frequency of high expression of survivin was significantly higher in muscle-invasive tumors (66.6%) than in non-muscle invasive tumors (34.2%) (P=0.042). The frequency of high expression of survivin was significantly higher in poor-differentiated (85.7%) than in moderate- differentiated tumors (30.8%) (P= 0.0014). The survivin mRNA expression (Log2 fold change were 3.41∼5.30) in various grade (G2-G4) urothelium carcinoma cell lines were all higher than normal human urothelial cell. Moreover, the higher frequency of risk genotypes (C/C+C/G) was observed in median and high survivn expression groups. In a multivariate analysis, high survivin expression was predictive of inferior OS (HR= 12.3, P=0.02). Conclusion: These findings suggest that the high expression of survivin is not only associated with tumor stage and grade of tumors but also may be predictive of inferior overall survival of urothelail carcinoma of the bladder. Keywords: survivin; bladder; urothelial carcinoma; immunohistochemistry, disease-free survival; overall survival
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 4500. doi:1538-7445.AM2012-4500
Abstract 4501: Energetic risk and prostate cancer-specific and all-cause mortality in two large cohorts of men with localized prostate cancer
Authors: Ma Jing , Giovannucci Edward , Nguyen Paul L. , Qiu Weiliang , Chavarro Jorge , Rosner Bernard , Cook Nancy R. , Platz Elizabeth A. , Gaziano J. Michael , Pollak Michael , Stampfer Meir J. 
Published: August 2012

Abstract
Objective: To examine whether high energetic risk predisposes men with localized prostate cancer (PC) to higher risk of PC-specific mortality or all-cause mortality. Methods: Among men with localized PC, prediagnostic body mass index (BMI) and plasma C-peptide (a marker of insulin production) were available for 691 men (301 overall deaths, 78 PC deaths) in the Physicians’ Health Study (discovery set) and 1111 men (262 overall deaths, 56 PC deaths) in the Health Professionals Follow-up Study (validation set). High energetic risk was defined as BMI 25-29.9 kg/m2 and C-peptide in the highest quartile or BMIα30 kg/m2. We used the Cox-regression model to estimate risk, adjusting for age, smoking, diabetes, and D'Amico risk defined by stage, Gleason grade and prostate-specific antigen (PSA). Results: Results were similar in both cohorts; the combined hazard ratio (HR)s (95% confidence interval, CI) associated with high energetic risk (25% of study population) were 2.2 (1.5-3.3) for PC-specific mortality and 1.4 (1.1-1.7) for all-cause mortality. The risk of PC-specific mortality according to low- intermediate-, or high-D'Amico risk were 1.0 (reference), 2.6, 6.4 for low energetic risk, and 5.0, 6.1, 9.4 for high energetic risk. The corresponding HRs for all-cause mortality were 1.0 (reference), 1.3, 2.1, 2.1, 2.1, and 2.3. Compared to D'Amico risk alone, incorporating energetic risk significantly improved the predictability of PC-specific mortality (C-statistic from 0.72 to 0.78, P&lt;0.001). Conclusion: Adding energetic risk to D'Amico risk groups significantly improved prediction of PC-specific and all-cause mortality, and identifies 20% D'Amico “low-risk” patients who may be poor candidates for active surveillance.
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 4501. doi:1538-7445.AM2012-4501
Abstract 4502: DNA ploidy in tumor correlates with age, and explains some of the poor prognostic impact of age in endometrial carcinomas
Authors: Mauland Karen K. , Wik Elisabeth , Werner Henrica MJ , Trovik Jone , Salvesen Helga B. 
Published: August 2012

Abstract
Background: Endometrial cancer incidence is increasing in industrialized countries, and the demand for better prognostic markers in order to individualize treatment is emerging. DNA ploidy has previously shown independent prognostic impact in smaller studies. In this study, we wanted to investigate the prognostic impact of ploidy in primary endometrial tumors, and the link between DNA ploidy and patient age at diagnosis in relation to traditional clinicopathologic prognostic variables. Study design: 663 patients treated for endometrial carcinoma at Haukeland University Hospital, Norway, from 1981 through 2010 were included. DNA ploidy in fresh tumor specimens was measured by flow-cytometry. Comprehensive clinical and histopathologic data, treatment and complete follow-up were collected. The software PASWStatistics18 was used for statistical analysis. Results: DNA aneuploidy was significantly correlated to high patient age at diagnosis (p&lt;0.001). It was also correlated to non-endometrioid histology and high-grade tumors (p&lt;0.001) and high FIGO stage (p=0.012). In univariate survival analysis (Kaplan Meier), the 5-year disease specific survival of patients with diploid tumors was 89%, versus 65% for aneuploid tumors (p&lt;0.001). In Cox regression analysis, aneuploidy was significantly associated with poor survival (HR=2.4, 95%CI 1.6 - 3.8, p&lt;0.001), adjusted for FIGO stage, age, grade, and histologic subtype. Interestingly, the prognostic impact of patient age diminished when ploidy status was included in the Cox analysis. Conclusion: DNA ploidy estimation in endometrial carcinoma tumor tissue is highly associated with patient age at diagnosis, as well as prognosis. The prognostic impact of age decreases when adjusting for ploidy status in tumor.
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 4502. doi:1538-7445.AM2012-4502
Abstract 4505: Polymorphisms in vascular endothelial growth factor (VEGF) and associated receptors as prognostic and predictive factors in advanced solid tumors
Authors: Eng Lawson , Amir Eitan , Azad Abul Kalam , Habbous Steven , Pang Vincent , van der Zee Anke-Hilse Maitland , Savas Sevtap , Mackay Helen , Liu Geoffrey 
Published: August 2012

Abstract
Introduction: Angiogenesis is an important host factor that is utilized by cancer cells to both grow and metastasize. In an attempt to halt the progression of cancer growth, new agents, such as bevacizumab, have been developed to target VEGF. Host genetic variability in the VEGF pathway may influence angiogenesis-dependent signalling during cancer development, cancer biology and therefore may impact on sensitivity to various therapies and survival. Here, we conducted a systematic review of the predictive and prognostic significance of polymorphisms in VEGF and VEGF receptor (VEGFR) and their isoforms. Materials and Methods: We performed a literature search of PubMed in July 2011 using the keywords and MeSH terms: {“angiogenesis,” “VEGF,” “VEGFR1,” “FLT1,” “KDR,” “VEGFR2,” “VEGFA,” “VEGFB,” “bevacizumab”} and “cancer” and “polymorphism”. Eligible studies were those comparing wild-type and variant polymorphisms and reporting one or more of the following outcomes: overall survival (OS), progression free survival, time to progression, time to recurrence, disease free survival, response rate or drug toxicities. Meta-analysis was performed for studies reporting identical outcome data for pre-specified polymorphisms. Results: We identified 44 prognostic studies and 12 predictive studies. There was marked inter and intra-disease site heterogeneity in the effect of polymorphisms on both outcome and response to therapy. Meta-analysis was possible for six polymorphisms (VEGF +936C&gt;T, VEGF –460T&gt;C, VEGF +405G&gt;C, VEGF –1154G&gt;A, VEGF –2578C&gt;A and VEGF –634G&gt;C) each of which reported the effect of wild-type and variant forms on OS. VEGF –634G&gt;C showed a statistically significant improvement in OS (HR: 0.75, 95% CI: 0.57-0.98, p=0.03). There were non-significant associations between VEGF +936C&gt;T with worse OS and VEGF +405G&gt;C with improved survival (HR: 1.38, 95% CI: 0.96-1.97, p=0.08 and HR: 0.85, 95% CI: 0.72-1.01, p=0.07, respectively). There were no significant differences between homozygosity and heterozygosity for these polymorphisms. Conclusions: VEGF –634G&gt;C appears to predict for improved outcome while VEGF +936C&gt;T and +405G&gt;C both show non-significant associations with outcome. These polymorphisms should be investigated in prospective studies to ensure standardization of measurement and reporting.
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 4505. doi:1538-7445.AM2012-4505