bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4433: RB mediates TGF-β effects on growth inhibition and invasion in pancreatic cancer cells
Authors: Gore Jesse , Korc Murray 
Published: August 2012

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that arises from precursor lesions, termed pancreatic intraepithelial neoplasia (PanIN). PDAC's aggressiveness derives from its advanced stage when patients present clinically, the high frequency of driver mutations (KRAS, INK4A, TP53 and SMAD4) and the heterogeneous distribution of low frequency driver mutations. To study the potential role of RB in PDAC pathobiology, we generated a novel mouse model with pancreatic RB deletion and oncogenic Kras expression (Rb/K mice). These mice rapidly developed highly proliferative PanIN that progress to PDAC with high frequency, underscoring RB's tumor suppressive role in the pancreas. RB deletion alone, however, did not alter pancreatic histology. Previously, we have demonstrated that Smad7-induced loss of TGF-β-mediated growth inhibition is due to functional inactivation of RB. To further examine RB's role in TGF-β action, we established pancreatic cancer cell lines from the Rb/K model. These cells were resistant to TGF-β1-mediated growth inhibition, whereas growth of murine cell lines that retained RB was markedly inhibited. RB loss also abolished TGF-β-induced cell invasion, but did not alter Smad-dependent TGF-β1 signaling since TGF-β1 induced Smad2 phosphorylation, Smad3/4 nuclear translocation, and transactivation of TGF-β1-dependent reporters. By contrast, RB loss did not affect TGF-β1-induced epithelial-to-mesenchymal transition. Array analysis revealed marked alterations in the gene expression profile of Rb/K cells. These data suggest that RB loss contributes to the dysregulation of TGF-β actions in PDAC and suggest that delineation of these perturbations may yield novel therapeutic approaches in this malignancy.
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 4433. doi:1538-7445.AM2012-4433
Abstract 4435: Overexpression of Rhotekin confers gastric cancer cells resistance to interferon-α-mediated growth inhibition
Authors: Yin Tsun-Ying , Hsiao Ya-Wen , Peng Wen-Hsin , Wang Mei-June , Chen Jeou-Yuan 
Published: August 2012

Abstract
Tumor infiltrating lymphocytes (TILs) are frequently detected in a variety of malignancies, including gastric cancer (GC). TILs are known to produce high level of interferon-gamma (IFN-γ) in GC, but fail to suppress tumor growth. We have previously shown that Rhotekin (RTKN), the gene encoding the Rho effector RTKN, is overexpressed in human GC, and its expression is correlated with disease progression. In this study, we show that RTKN expression efficiently blocks IFN-γ-mediated anti-growth and immunologic responses, suggesting a role of RTKN in attenuating tumor immunosurveillance during GC pathogenesis. We show that RTKN attenuates STAT1 phosphorylation in response to IFN-γ, and confers increased resistance to IFN-γ-mediated growth suppression in GC cells through inhibiting the expression of STAT1-dependent downstream target genes, including cyclin-dependent kinase inhibitor p21 and antiapoptotic genes BCL-2 and BCL-xL. Conversely, elimination of RTKN expression by knockdown approach facilitates IFN-γ-mediated STAT1 phosphorylation and promotes IFN-γ-mediated growth arrest and apoptosis. We further show that RTKN-mediated inhibition of STAT1 phosphorylation can be reversed by the treatment of sodium orthovanadate, a tyrosine phosphatase inhibitor, suggesting the involvement of tyrosine phosphatases in RTKN-mediated process. In support, our data show that RTKN suppresses IFN-γ-mediated STAT1 phosphorylation partly through facilitating the interactions of SHP2 and STAT1. In summary, our data suggest that RTKN overexpression confers growth advantages to GC by evading immunosurveillance through suppression of IFN-γ-mediated anti-tumor activity.
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 4435. doi:1538-7445.AM2012-4435
Abstract 4436: Chronic inflammation and gastric carcinogenesis: the role of CD44 variant expression
Authors: Wada Takeyuki , Nagano Osamu , Ishimoto Takatsugu , Yae Toshifumi , Kitagawa Yuko , Saya Hideyuki 
Published: August 2012

Abstract
CD44 is a marker of tumor-initiating cells in gastric cancer. Recently, we have reported that a CD44 variant (CD44v) interacts with xCT, a glutamate-cystine transporter, and manifests enhanced protection against reactive oxygen species (ROS), contributing to tumor growth and resistance to chemo- or radiotherapy. Although an inflammation related metaplasia and/or dysplasia of gastric epithelium is considered as key events in gastric carcinogenesis, the cause or process of these phenomena is not known. We investigated the relationship between CD44v expression and gastric carcinogenesis, using three lineages of gastric cancer mouse models, K19-Wnt1, K19-C2mE, and K19-Wnt1/C2mE mice. We also used CD44-/- K19-Wnt1/C2mE mice and Helicobacter. felis-infected C57BL/6 mice. Chronic inflammation triggered by Helicobactor infection played a major role in CD44v related gastric carcinogenesis. CD44v expression and nuclear factor-kappa B (NF-κB) activation were promoted by inflammatory cytokines, IL-1α and TNF-α, in gastric cancer cell lines. Thus, CD44v+ tumor cell expansion induced by inflammation via NF-κB pathway might contribute to tumor development. Finally, an xCT inhibitor sulfasalazine treatment significantly suppressed tumor growth in K19-Wnt1/C2mE mice. These findings suggest a significant role of CD44v in inflammation-mediated gastric carcinogenesis via ROS defense.
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 4436. doi:1538-7445.AM2012-4436
Abstract 4437: Subsquamous extension of Barrett epithelium is a regular event
Authors: Marx Andreas H. , Rösch Thomas , Sauter Guido 
Published: August 2012

Abstract
Endoscopic resection and/or ablation of Barrett esophagus (BE) is directed by the endoscopic visual impression of pinkish Barrett versus whitish esophageal mucosa; microscopically however, BE may extend underneath squamous epithelium. Aim of the present study is to evaluate subsquamous BE extension in a large cohort of patients with endoscopically resected neoplastic BE. Resection specimens of 97 patients treated by endoscopic mucosal resection (EMR) for suspected or confirmed neoplastic BE (83 men, 14 women, mean age 65 years) were retrospective reanalyzed by two experienced GI histopathologists. Orientation of resected specimens pinned on cork was done prior to histopathological workup with squamous epithelium oriented proximally. Subsquamous extension was measured in all specimens containing squamous epithelium. Endoscopic and other histopathologic data were also analyzed. 442 specimens of the 97 study cases were analyzed and subsquamous BE was found in 42.5% of specimens or 97.9% of patients. Mean length of subsquamous BE extension was 3.5 mm (0.0-9.6 mm) with 27.8% of cases measuring 5 mm or more. In 56 cases (57.7%), subsquamous BE consisted entirely or partially of neoplasia (42 cancers, 12 HGIN, 2 LGIN) with a mean subsquamous tumor extension of 1.2 mm mm (range 0.0-5.2 mm). Subsquamous extension of BE including all forms of neoplasia is a regular event. A minimal safety margin of 1 cm has to be kept with Barrett ablation techniques in order to avoid BE and/or tumor recurrence.
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 4437. doi:1538-7445.AM2012-4437
Abstract 4443: Body weight status predicts pre-treatment risk of PSA failure in men with clinically localized prostate cancer
Authors: Freeman Vincent L. , Flanigan Robert C. , Hollowell Courtney M. , Branch Jeffrey , Deane Leslie , Quek Marcus , Vidal Patricia P. , Friedman Nicholas , Cintron Daisy , Dabbous Firas , Millbrandt Linda , Garabedian Anne , Cleofe Jasmine , Gomez Sandra L. 
Published: August 2012

Abstract
Introduction and Objective: Obesity/excessive adiposity in men with clinically organ-confined prostate cancer is of growing concern, because it associates with an increased risk of cancer recurrence after definitive therapy based on post-treatment prognostic parameters. The objective of this study was to evaluate whether body weight status associates with pre-treatment predictors of cancer recurrence in this patient population. Methods: We performed a cross-sectional study of body weight status and pre-treatment risk of PSA failure in 119 men awaiting radical prostatectomy for clinically localized prostate cancer in four urologic clinics in the Chicago area. Body weight status was assessed using the body mass index (BMI) and dual-energy x-ray absorptiometry (DXA). D'Amico risk scores, which are based on clinical tumor stage, biopsy Gleason sum, and pre-treatment PSA, were used to rank each patient's 5-year risk of PSA failure as low, intermediate, or high. Ordinal logistical regression analyzed the association between BMI quartile and D'Amico risk scores after accounting for age, race, total grams of body fat, and study site. Results: The risk of PSA failure increased with increasing quartile of BMI. Relative to the lowest BMI quartile, the cumulative odds of an intermediate or higher D'Amico risk score vs. a low risk score (the “cumulative odds ratio”) for patients in the second BMI quartile (mean BMI = 27.8 kg/m2) was 3.51 (95% CI = 1.07 to 11.5, p = .038). For patients in the third quartile (mean BMI = 32.0 kg/m2) and forth quartile (mean BMI = 37.0 kg/m2), the cumulative OR was 6.52 (95% CI = 1.72 to 24.6, p = .0057) and 7.74 (95% CI = 1.18 to 50.9, p = .033), respectively (OR trend = 1.98, 95% CI = 1.09 to 3.59, p = .0254). Conclusions: Body weight status predicts pre-treatment risk of PSA failure in men with clinically localized prostate cancer. This provides further support for a mechanistic link between body weight status, which reflects energy balance, and prostate cancer prognosis. The results also highlight the potential for using body weight status and other lifestyle-related factors pertinent to prostate cancer to identify men who are at high risk for unfavorable treatment outcomes.
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 4443. doi:1538-7445.AM2012-4443
Abstract 445: Has k-Ras predictive influence on the kind of metastasis in patients with colon carcinoma
Authors: Falch Claudius , Strohäker Jens , Hann-von-Weyhern Claus , Adam Patrick , Königsrainer Alfred , Fend Falko , Brücher Björn LDM 
Published: August 2012

Abstract
Background: The k-Ras-protein shows in regard to its mutations status a predicitvity of the response after Cetuximab in patients with colon carcinoma. To our knowledge, not much is known, if k-RAS has also a predictivity in regard to different ways of metastasis. The goal of our investigations was the evaluation of k-Ras on primary non-metastatic colon cancer compared to lymphatic, hepatic and peritoneal metastasis. Methods: 98 patients with adenocarcinom of the colon and a postoperative pT2/3-status, who underwent surgical resection between 2006 and 2008 at the University of Tübingen had been included within the study collective. 53 patients had no metastasis (control group), while 45 patients revealed primary metastasis: lymphatic metastasis (n=20), hepatic spread (n=20) and multiple metastasize (n=5). After DNA-extraction, an amplification by ARMS-PCR was performed and the analysis of the mutation status was done by melting point analysis by Light-Cycler. Additionally sequencing of Exons 12 and 13 was performed in individual cases. Results: 29/98 (=30%) revealed a k-Ras-mutation. Out of these, 12 (=41%) had metastasis: 9 hepatic (=75%), 2 lymphatic (=17%) and 1 (=8%) multiple metastasis. Patients with k-Ras-mutation (n=29) showed a significant lower rate of lymphatic metastasis. (90% vs. 10%, p=0.031). The survival in accordance to the k-Ras mutation was not statistically significant (p=0.415). Conclusion: Patients with mutated k-Ras-gene in out patient population revealed no significant higher rate of metastasis (p=0.558), nor in regard to hepatic (p=0.090) or multiple locations (p=0.629). Our preliminary data assume, that the k-Ras mutation status has a predictive function on the rate of lymphatic metastasis in patients suffering from colon carcinoma (p=0.031). Follow-up-studies are demanded, if single mutations status might have an additional influence.
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 445. doi:1538-7445.AM2012-445
Abstract 446: Protein kinase Ciota is a new prognostic factor in gastric cancer
Authors: Kashihara Hideya 
Published: August 2012

Abstract
Background: Protein kinase Ciota (PKCiota) have been reported to be an important effector of oncogenic K-ras. Furthermore, PKCiota is correlated with tumor angiogenesis. The role of PKCiota in gastric cancer remains unclear. The aim of this study is to clarify the role of PKCiota in human gastric cancer. Methods: Twenty-eight patients with gastric cancer who underwent gastrectomy were enrolled. The expression of PKCiota mRNA was determined in clinicopathological factors. Next, the patients were divided into two groups: the PKCiota high expression group (n = 14) and low expression group (n = 14). 5-year survival rate, ERK mRNA, which was the gene of downstream K-ras, and VEGF mRNA were compared between the two groups. The prognostic factors were investigated by multivariate analysis. Results: High expressions of PKCiota mRNA were observed in undifferentiation, deeper tumor invasion (MP≤), advanced stage (Stage III, IV) and peritoneal dissemination (+). The 5-year survival rate in the PKCiota high expression group were lower than that in the PKCiota low expression group. The multivariate analysis revealed that high expression of PKCiota mRNA was an independent prognostic factor. The expressions of ERK mRNA and VEGF mRNA in the PKCiota high expression group were higher than that in the PKCiota low expression group. Conclusion: Our results indicate that PKCiota was correlated with tumor progression and angiogenesis. PKCiota may be a new prognostic factor in gastric 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 446. doi:1538-7445.AM2012-446
Abstract 4464: Genetic variants at chromosome 8q24, colorectal epithelial cell proliferation, and risk for incident, sporadic colorectal adenomas
Authors: Yang Baiyu , Thyagarajan Bharat , Gross Myron D. , Goodman Michael , Sun Yan V. , Bostick Roberd M. 
Published: August 2012

Abstract
Three polymorphic sites at chromosome 8q24 (rs7837328, rs10808555, and rs6983267) have been associated with risk for colorectal adenomas. It was also previously reported that the rs6983267 single nucleotide polymorphism (SNP) may enhance Wnt signaling, which regulates cell proliferation. To investigate associations between the 8q24 variants and colorectal epithelial cell proliferation in the normal-appearing colorectal mucosa, as well as risk for colorectal adenoma, we analyzed data from a previously conducted pilot, colonoscopy-based case-control study of incident, sporadic colorectal adenoma among the White participants (n = 90 cases, 132 controls). Proliferation was measured in biopsies of the normal-appearing mucosa of the rectum, sigmoid colon, and cecum using immunohistochemistry for proliferating cell nuclear antigen (PCNA) and calculated as a labeling index averaged across all three colorectal sites. Each SNP was associated with risk for colorectal adenoma in the same direction as previously reported; the odds ratios (ORs) for those homozygous for the rs7837328, rs10808555, and rs6983267 risk alleles relative to those heterozygous or homozygous for the non-risk alleles combined were, respectively, 2.07 (95% confidence interval [CI] 1.07-3.97), 2.37 (CI 0.97-5.76), and 1.55 (CI 0.86-2.79). Colorectal epithelial cell proliferation tended to be higher among those homozygous for the risk alleles (alleles A, G, and G for SNPs rs7837328, rs10808555, and rs6983267, respectively) compared to those heterozygous or homozygous for the non-risk alleles combined; in the cases and controls combined, for those with the rs7837328 AA genotype proliferation was 6.7% higher (p = 0.40), for those with the rs10808555 GG genotype it was 16.5% higher (p = 0.12), and for those with the rs6983267 GG genotype it was 1.2% higher (p = 0.87). These preliminary findings, which are consistent with previously reported direct associations between genetic variants at chromosome 8q24 and risk for colorectal adenoma, suggest that the genetic variants may also be associated with higher levels of colorectal epithelial cell proliferation in humans, thus providing support for the hypothesis that 8q24 variants may increase risk via enhanced Wnt signaling.
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 4464. doi:1538-7445.AM2012-4464
Abstract 4467: Gene-specific methylation of leukocyte DNA in relation to colorectal cancer among male smokers from a nested case-control study in the ATBC Study
Authors: Gao Ying , Caporaso Neil 
Published: August 2012

Abstract
Gene-specific methylation of Leukocyte DNA in relation to colorectal cancer among male smokers from a nested case-control study in the ATBC Study Recent data suggest a link between leukocyte DNA methylation and cancer risk. However, data on DNA methylation from a prospective study, which may provide evidence for causality, are sparse. We explored the association between methylation in leukocyte DNA and colorectal cancer (CRC) risk in male smokers using the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study. 221 incident CRC cases, and 219 controls, frequency-matched on age and smoking intensity were included. DNA methylation of 1505 CpG sites selected from 807 genes were evaluated using Illumina GoldenGate Methylation Cancer Panel I in pre-diagnostic blood leukocytes of study subjects. Tertiles of methylation level classified according to the distribution in controls for each CpG site were used to analyze the association between methylation level and CRC risk with logistic regression. The time between blood draw to cancer diagnosis (classifying cases according to latency) was incorporated in further analyses using proportional odds regression. We found that methylation changes of 30 CpG sites were associated with CRC risk at P&lt;0.01 level. Taking the latency information into account strengthened some associations, suggesting that the methylation levels of corresponding sites might change over time with tumor progression. This is the first prospective study for CRC risk focusing on gene-specific DNA methylation to date. The results suggest that the methylation level of some genes were associated with cancer susceptibility and some were related to tumor development over time. Further studies are warranted to confirm and refine our results.
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 4467. doi:1538-7445.AM2012-4467
Abstract 4535: CENP-E and c-Myc expression identifies a sensitive population of gastric cancer
Authors: Li Gang , Fan Conglin , Deng Shibing , Xu Jiangchun , Shi Stephanie , Wang Kai , Pascual Bernadette , Kung Pei-Pei , Leung Suet Yi , Yue Siu Tsan 
Published: August 2012

Abstract
Centromere-associated protein E (CENP-E) is expressed during mitosis and plays an essential role in establishing and maintaining stable connections between mitotic chromosomes and the microtubules of the spindle. Previous preclinical studies have shown that inhibition of CENP-E function by small interfering RNA, blocking antibodies or small molecule inhibitors arrested cell cycle before metaphase, and could lead to cell death. In a number of cancers, CENP-E is frequently overexpressed in tumor tissues compared with their normal counterparts. In this study, we showed that CENP-E is overexpressed in about 60% of gastric cancer (intestinal and diffuse-type) tissues. In addition, c-Myc up-regulation was observed in more than 50% of the same samples. Overall, about 40% of all gastric tumor samples harbor both CENP-E and c-Myc upregulation. Using a panel of small molecule inhibitors of CENP-E, we evaluated in vitro anti-proliferation effect in a panel of gastric cancer cell lines. Our data suggested that cells with higher levels of c-Myc transcript were more sensitive to CENP-E inhibition. This preliminary study indicated that c-Myc amplification and/or over-expression could be a potential biomarker for selecting gastric cancer patients more likely to respond to CENP-E inhibition.
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 4535. doi:1538-7445.AM2012-4535