bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 279: Increased Met receptor activation mediates enhanced cell invasion upon mutant p53 expression in esophageal squamous cell carcinoma
Authors: Grugan Katharine D. , Miller Charles G. , Michaylira Carmen Z. , Klein-Szanto Andres J. , Nakagawa Hiro , Rustgi Anil K. 
Published: February 2011

Abstract
Esophageal squamous cell carcinoma (ESCC), a type of squamous cell cancer, is one of the most aggressive forms of human cancer with poor prognosis due to late diagnosis and metastasis. Common genomic alterations in ESCC include p53 mutations and overexpression of oncogenes such as cyclin D1, EGFR, and Met. Using an invasive primary esophageal epithelial cell model system genetically transformed by the overexpression of EGFR and p53R175H, we find novel evidence of cross-talk between p53R175H and the Met receptor tyrosine kinase. Increased Met receptor activation is observed upon expression of p53R175H and is further enhanced upon subsequent overexpression of EGFR. Increased Met activation is observed also in a number of human ESCC cells lines that harbor either p53 genetic mutations or are p53 null. Met phosphorylation can be inhibited using two small molecule compounds (CP31398 and 5-iminodaunorubicin) that have been demonstrated previously to activate wild-type p53 signaling through distinct mechanisms, thereby providing further evidence to a link between these two pathways. Both CP31398 and 5-iminodaunorubicin blocked invasion of the genetically transformed primary esophageal epithelial cells (EPC-hTERT-EGFR-p53R175H) suggesting that the mechanism of increased invasiveness upon EGFR and p53R175H expression may be mediated by Met activation. In aggregate, mutant p53 and Met appear to cooperate to foster tumor invasion and this novel linkage has not been reported previously. These results provide further implications to the use of combinatorial therapeutics directed at Met and mutant p53 in ESCC and other squamous cell cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 279.
Abstract 2793: Folate, B vitamin and methionine intake and risk of colon cancer in relation to BRAF mutation and CpG Island Methylator Phenotype (CIMP)
Authors: Schernhammer Eva S. , Nosho Katsuhiko , Giovannucci Edward L. , Fuchs Charles S. , Ogino Shuji 
Published: February 2011

Abstract
BACKGROUND AND AIMS: One-carbon metabolism appears to play an important role in DNA methylation reaction. Evidence suggests that a low intake of folate or other B vitamins or high alcohol consumption increases colorectal cancer risk. How dietary folate and B vitamins affect the CpG island methylator phenotype (CIMP) and BRAF mutation status in colon cancer remains uncertain.
METHODS: Utilizing 472 colon cancer tissue specimens from a large prospective cohort of women in the Nurses’ Health Study, we sequenced BRAF codon 600 and quantified DNA methylation in eight CpG islands [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1], which have been validated as a CIMP marker panel. In addition, we examined 8 other CpG islands (CHFR, HIC1, IGFBP3, MGMT, MINT-1, MINT-31, p14, WRN). We examined the relationship between intake of folate and other one-carbon nutrients and colon cancer risk, according to BRAF mutation or CIMP status.
RESULTS: We were able to sequence BRAF in 472 incident colon cancers, and determine CIMP status in 462 tumors. Compared with women reporting intake of &lt;200μg of folate per day, the multivariate relative risk (RR) of developing CIMP-low/0 tumors (with &lt;6/8 methylated CIMP-specific markers) was 0.73 (95% confidence interval (CI), 0.53-1.02) for those who took ≥400μg of folate per day. In contrast, total folate intake had no influence on risk for CIMP-high tumors (with ≥6/8 methylated CIMP-specific markers) [multivariate RR, 0.98; 95% CI, 0.54-1.77, comparing ≥400 to &lt;200μg of folate per day]. Vitamin B6 intake did not appear to differentially influence risks for CIMP-high and CIMP-low/0 tumors (Pheterogeneity =0.63). In contrast, a higher methionine intake appeared to lower the risk of CIMP-high cancers (top versus bottom quintile, multivariate RR, 0.68; 95% CI, 0.35-1.31) whereas it had no effect on CIMP-low/0 tumors (multivariate RR, 1.04; 95% CI, 0.71-1.52; Pheterogeneity =0.007). Using the 16-marker CIMP panel did not substantially alter our results. Folate, B vitamin or methionine intake did not differentially affect colon cancer risk by BRAF status.
CONCLUSIONS: Lower levels of folate and vitamin B6 intake were associated with increased risk of CIMP-low/0 colon tumors, whereas higher levels of methionine intake appeared to lower the risk of CIMP-high tumors. These nutrients did not appear to affect BRAF mutation status. Our data support epigenetic alterations as potential mechanisms through which one-carbon nutrients exert their influence on colon carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2793.
Abstract 2797: Measurement of GST-P1 methylation in body fluids and prostate cancer diagnosis: a meta-analysis
Authors: Wu Tianying , Giovannucci Edward , Welge Jeff , Mallick Palash , LeMasters Grace , Tang Wan-yee , Ho Shuk-Mei 
Published: February 2011

Abstract
Prostate-specific antigen (PSA) screening significantly increases the early diagnosis of prostate cancer; however, the specificity of PSA screening is fairly low (20%), leading to many unnecessary biopsies and overtreatment. Hence, the identification of a circulating biomarker with high specificity to complement the traditional PSA test is greatly needed. CpG island promoter hypermethylation may be one of the earliest somatic genome alterations in the development of several types of cancers. Studies have shown that glutathione-s-transferase-π (GST-P1) promoter hypermethylation is the most common somatic genome alteration during prostate cancer development. We have retrieved 22 studies that measured GST-P1 in plasma, urine, buffy coat, ejaculate, or whole blood. In our random effect model, the pooled specificity of measurement of GST-P1 hypermethylation was 89% (95%CI, 71-95%), indicating that GST-P1 has a much stronger specificity than the PSA test. When we stratify the studies by biospecimen type and PCR method, high specificity remains within each stratum. Unlike the PSA test, the pooled sensitivity of the GST-P1 methylation test was 47% (95%CI, 33-61%), relatively low. However, low sensitivity does not downgrade its potential application as a complement to the PSA test, which has a high sensitivity but a poor specificity. Moreover, we have found that the likelihood of GST-P1 methylation tends to increase with prostate cancer pathological stage (stages 3-4 versus 1-2), with an odds ratio of 1.21 (95%CI, 0.99-1.48). However, due to limited sample size (10 studies), this did not reach statistical significance. The current study has several advantages. This is the first study to systemically review GST-P1 methylation as measured in body fluids, and to compare the specificity of GST-P1 to the traditional PSA test; second, this review has rigorously examined specificity by excluding healthy controls, who cannot represent individuals with elevated PSA levels or urological symptoms.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2797.
Abstract 2798: VDR gene polymorphism and risk of prostate cancer in African-American
Authors: Daremipouran Mohammad , Beyene Desta , Nouraie Seyed-Mehdi , Kanaan Yasmine 
Published: February 2011

Abstract
Background: Genetics and epidemiological studies have shown that genes and environment interaction play strong roles in prostate cancer etiology. We have already shown that higher UV exposure, higher serum vitamin D, and lower skin pigmentation inversely associated with the risk of prostate cancer in African-American.
Methods: In order to explore the relationship between Vitamin D receptor (VDR) polymorphisms and prostate cancer risk in African American men; 91 affected African American men with histologically diagnosed adenocarcinoma of the prostate, PSA of &gt; 2.5 ng/ml and a positive digital rectal exam have been recruited. Ninety-one age and ethnicity matched controls have been also recruited.
Genomic DNA was extracted from blood sample of each case and control subjects.
Nine primers were designed for amplification of 9 different axons in VDR gene. DNA fragments from all samples were amplified using PCR reaction. In order to investigate the existence of heteroduplex, PCR products denatured and using denaturing high performance liquid chromatography (DHPLC) technique heteroduplex analysis on the Wave system was performed. Those samples demonstrating heteroduplex peaks were sequenced using an ABI 377 DNA sequencer.
Results: Seven polymorphisms in VDR sequence were confirmed after sequencing. SNPs 132G&gt;A, 332 G&gt;A, 83 G&gt;A, invs9-286C&gt;T, 122 A&gt;G, and invs10-49G&gt;T are located in non-coding region. 209 T&gt;C SNP is located in coding region. However this SNP is anonymous as previously reported. 332G&gt;A, 83G&gt;A, and invs9-286C&gt;T SNPs showed strong negative association with prostate cancer risk (p&lt; 0.05). 132G&gt;A, 209T/C, and IVS10-49G&gt;T showed direct association with risk of prostate cancer but statistically is not significant.
Using Binary Logistic Regression Model confirmed that 332G&gt;A, 83G&gt;A, and invs9-286C&gt;T SNPs are good predictor of protection against prostate cancer. Whereas having SNP 209T&gt;C is strong indicator of risk of prostate cancer.
Conclusion: It is possible that genetic variants may mediate prostate cancer risk via a mechanism involving availability of 1, 25(OH)2 D. Vitamin D protects against risk of prostate cancer. UV exposure, good vitamin D diet, and lighter skin along with advantageous VDR polymorphism as modulators of vitamin D can improve this protection.
We are in the process of assessment of analysis the interaction between other genes involved in vitamin D metabolism and environmental factors.
Our results require further corroboration in large statistically powerful sample collections.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2798.
Abstract 280: Met (the HGF receptor) localizes to the nucleus in wound healing
Authors: Bordeaux Jennifer , Hanna Jason A. , Agarwal Seema , Rimm David L. 
Published: February 2011

Abstract
Background: The hepatocyte growth factor (HGF)/Met signaling pathway has been shown to be important for stimulating cell proliferation, motility, invasion and metastasis. Recent work from our lab has also demonstrated patients with high levels of nuclear Met have a worse prognosis even in lymph node negative breast cancer and has also identified a 60 kDa fragment from the carboxy-terminal domain of Met that localizes to the nucleus.
Methods: We developed a method for quantification of in vitro wounding of epithelial cellular monolayers that we have utilized to further characterize nuclear Met. Nuclear Met was identified by immunofluorescence with the carboxy-terminal Met specific antibody CVD13 (Invitrogen) in H1650, A431 and Caco2 cells. The Met ligand (HGF) was used to stimulate wound healing and the Pfizer Met kinase inhibitor PHA-665752 (PHA) was used to determine the dependence of activated Met for nuclear localization.
Results: As previously observed, stimulating cells with HGF (50 ng/mL) increases overall wound healing and inhibition of Met kinase activity with PHA reduces overall wound healing. Using immunofluorescence we have determined nuclear Met is present at the wound edge of lung (H1650), colon (CaCo2), and skin (A431) cancer cell lines. Additionally, nuclear localization of Met is also observed in H1650 cells by immunofluorescence with a phospho-Met antibody (CST). Nuclear localization of Met is inhibited when cells are pretreated with PHA even in the presence of HGF. However, HGF stimulation alone is not sufficient to induce nuclear Met in the A549 lung cancer cell line. Finally, the 60 kDa Met fragment is absent by Western blot when H1650 cells are grown in serum-starved conditions.
Conclusion: Nuclear Met is observed during the wound healing of cellular monolayers and can be inhibited with Met specific kinase inhibitors. Nuclear Met, as defined by the presence of the 60 kDa fragment, is lost in serum-starved growth conditions. Since, several pharmaceutical companies are currently developing Met-based therapies, the role of Met the nucleus may be important in future targeted cancer therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 280.
Abstract 2825: Red meat and heterocyclic amine intake, metabolic pathway genes, and bladder cancer risk
Authors: Lin Jie , Wang Jianming , Grossman H. Barton , Chen Meng , Dinney Colin P. , Wu Xifeng 
Published: February 2011

Abstract
We analyzed the association between meat intake, heterocyclic amines and bladder cancer (BC) risk using data collected in a large case-control study. The study included 884 histologically confirmed BC cases and 878 healthy controls matched to cases by age (± 5 years), gender and ethnicity. Epidemiologic and dietary data were collected using structured questionnaires via an in-person interview. Dietary intake was reported on the National Cancer Institute- Block 135-item food frequency questionnaire (FFQ). Multivariate unconditional logistic regression was used to estimate odds ratios (ORs) and the 95% confidence intervals (95% CI). Compared to those in the lowest quartile of total red meat intake, the ORs for the second, third and fourth quartiles of total red meat intake were 1.04 (95% CI: 0.78-1.39), 1.58 (95% CI: 1.19-2.10), and 1.49 (95% CI:1.21-1.99), respectively (P-for trend =0.001). Higher intakes of beef steaks, pork chops and bacon were each associated with increased BC risk in a dose-response pattern. For example, the ORs for the second, third and fourth quartiles of beef steak intake were 1.04 (95% CI: 0.78-1.39), 1.19 (95% CI: 0.89-1.57), and 1.54 (95% CI: 1.17-2.04), respectively (P-for trend =0.001). In addition, high intake of fried chicken and fried fish also conferred significantly increased risk. When assessed in doneness level, compared to the rare done level, intakes of red meat with medium done and well done level were associated with 1.46- fold (95% CI: 1.13-1.89) and 1.94-fold (95% CI: 1.52-2.49) increased risk (P for trend&lt;0.001). Intakes of heterocyclic amine (HCA) were available in a subset of 177 cases and 306 controls. Compared to the first quartile (the lowest quartile of intake), the ORs for the second, third, and fourth quartiles were 1.18 (95% CI: 0.63-2.23), 1.64 (95% CI: 0.89-3.00), and 2.58 (95% CI: 1.43-4.66), respectively (P for trend&lt;0.001). We further assessed joint effects of red meat and genetic variants in the pathways relevant to HCA metabolism. We found that the risk associated with high red meat intake was most significant among subjects carrying high number of unfavorable genotypes in the pathway. Compared with subjects in the lowest quartile of red meat intake and who carried low number of unfavorable genotypes (less than 6), subjects carrying seven or more unfavorable genotypes and whose red meat intake was in the highest quartile were at 4.74-fold increased risk (95% CI=2.78-8.10; P&lt;0.001). These results strongly support that red meat intake and genetic variants in the HCA metabolic pathways jointly influence bladder cancer susceptibility.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2825.
Abstract 2832: Genetic variation in TGFB1, TGFBR1, TGFBR2, and prostate cancer risk and recurrence
Authors: Cheng Iona C. , Plummer Sarah , Mefford Joel , Neslund-Dudas Christine , Casey Graham , Rybicki Benjamin , Witte John 
Published: February 2011

Abstract
Background: The transforming growth factor-β (TGF-β) signaling pathway has been reported to play a dual role in prostate carcinogenesis. Initially, TGF-β signaling inhibits tumor growth by its antiproliferative activity, but eventually it promotes tumor development by enhancing tumor cell motility and metastasis. We investigated whether common genetic variation in TGFB1, TGFBR1, and TGFBR2 influences the risk of aggressive prostate cancer and biochemical recurrence.
Methods: Forty-four tag SNPs in TGFB1, TGFBR1, and TGFBR2 were examined in a case-control study of aggressive prostate cancer (501 cases/538 controls) and a follow-up study of biochemical recurrence (824 cases). Aggressive disease was defined as having either having a Gleason score ≥7 or TNM stage ≥ T2c, or PSA at diagnosis &gt;10 ng/ml. Biochemical recurrence was defined as post-treatment prostate specific antigen (PSA) levels &gt;0.3 ng/ml for radical prostatectomy patients or 2 ng/ml increase above the nadir for radiotherpay patients. Odds ratios (OR) and 95% Confidence Intervals (CI) were estimated by unconditional logistic regression to evaluate the association between SNPs and aggressive prostate cancer risk. Hazard ratios (HR) and 95% CI were estimated by Cox proportional hazard regression to examine the association between SNPs and biochemical recurrence.
Results: For risk of aggressive disease, three SNPs were nominally statistically significant (TGFB1-rs4803455; TGFBR1-rs10512263; TGFBR2-rs2276768) with the most compelling polymorphism (TGFBR1-rs10512263) having an OR=1.76; 95% CI: 1.14-2.43 (P = 0.008) per additional minor allele. For risk of biochemical recurrence, seven SNPs were nominally statistical significant (TGFBR1- rs10739778; TGFBR2- rs12493607, rs2082224, rs1346907, rs1431131, rs1835538, rs11129421) with TGFBR2- rs12493607 associated with a HR=1.40; 95% CI: 1.14-1.71; P=0.001 per additional minor allele.
Conclusion: Our study suggests that genetic variation in the TGF-β pathway may be associated with risk of aggressive prostate cancer and biochemical recurrence. Future work will evaluate the cumulative and interactive effects of the associations within this pathway on prostate cancer risk and recurrence.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2832.
Abstract 2834: Genetic variants in TGFβ pathway genes and ovarian cancer risk
Authors: Wu Lei , Lu Karen , Pu Xia , Meyer Larissa , Ye Yuanqing , Wu Xifeng , Liang Dong 
Published: February 2011

Abstract
The transforming growth factor (TGF) β signaling pathway plays a crucial role in cell proliferation, differentiation, apoptosis, extracellular matrix production and other cellular functions. Dysregulation and genetic variations of major genes in this pathway may be involved in the process of carcinogenesis. In this study, 218 single nucleotide polymorphisms (SNPs) in 21 major genes of TGFβ pathway were genotyped in 339 Caucasian ovarian cancer cases and 349 age, gender, and ethnicity matched controls. We analyzed the association between these SNPs and the risk as well as clinical outcomes of ovarian cancer. In the risk analysis, 16 SNPs were found significantly associated with ovarian risk, among these SNPs, a dose-response effect of increased risk for ovarian cancer with increased unfavorable genotype (UFG: defined as the allele related with increased ovarian risk) was observed (P for trend &lt; 0.0001). Compared with individuals carrying ≤ 6 UFGs, subjects carrying ≥ 9 UFGs conferred a 3.7-fold increased risk of ovarian cancer (ORs =3.71, 95%CI=2.52-5.45, P&lt;0.0001). The most significant individual association was found for INHBC: rs2228225. Patients carrying at least one variant allele of this SNP conferred 63% increased risk for ovarian cancer (OR = 1.63, 95%CI= 1.20-2.22, P=0.0018). Potential high-order gene-gene interactions were identified using the classification and regression tree analysis (CART). Eight terminal nodes were identified representing eight groups of patients with different probability for ovarian cancer (ORs ranging from 2.87 to 6.68). In the analysis of clinical outcomes, 13 SNPs were significantly associated with the risk of death. The top two SNPs were from BMP1. Patients carried rare homozygous genotype of either one of the SNP has a nearly two-fold increased risk for death (rs3857979: HR= 1.80, 95%CI= 1.23- 2.65, P=0.0026; rs4075478: HR=1.89, 95%CI=1.22- 2.91, P=0.004). A cumulative effect was also observed (P for trend &lt; 0.0001). The median survival times decreased from 83.3 months for patients with ≤5UFGs to 26.8 months for those with ≥ 9UFGs (log rank P &lt; 0.0001). Survival tree analysis identified eight terminal nodes representing eight groups of patients with different survival probability. Interestingly, the two BPM1 SNPs that were most significant in survival analysis were also significantly associated with poor response for chemotherapy (rs3857979: OR= 1.90, 95%CI= 1.04-3.48, P=0.0375; rs4075478: HR=2.39, 95%CI=1.17-4.86, P=0.0166), indicating that these two SNPs were predictive markers for response. In conclusion, our result demonstrates that genetic variations within TGFβ pathway may have modulate the risk and clinical outcomes of ovarian cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2834.
Abstract 2836: Association between the hypoxia inducible factor-1α polymorphisms and the tumor size of oral squamous cell carcinoma
Authors: Shieh Tzong-Ming 
Published: February 2011

Abstract
Oral squamous cell carcinoma (OSCC) is a common malignancy. The incidence of OSCC is particularly high in some Asian countries due to the popularity of areca chewing habit. Hypoxia inducible factor-1α (HIF-1α) is up-regulated in hypoxic microenvironment to enhance tumor survival. There are five polymorphisms being identified in exon 12 of HIF-1α including C1772T polymorphism causing P582S, and G1790A polymorphism causing A588T of HIF-1α protein. This study investigated the relationship between these functional polymorphisms and the risk or progression of OSCC. PCR and direct sequencing were utilized to compare genotypic polymorphic and allelic frequency of HIF-1α in 96 normal controls and 305 OSCC patients. No statistically significant difference in C1772T and G1790A genotypes and allelic frequency lying between control and OSCC patients was found. However, multivariate analysis indicated that the A carrier of HIF-1α G1790A in OSCC patients was significantly higher in larger tumor than the contrasting group with an adjusted odd's ratio of 2.92. The findings may suggest a potential of HIF-1α G1790A polymorphism in the growth of OSCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2836.