bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2640: Risk of cytochrome P450 1B1 missense polymorphisms in renal cell carcinoma
Authors: Tanaka Yuichiro , Chang Inik , Majid Shahana , Saini Sharanjot , Zaman Mohd S. , Yamamura Soichiro , Chiyomaru Takeshi , Arora Sumit , Singh Kamaldeep , Shahryari Varahram , Dahiya Angela V. , Deng Guoren 
Published: August 2012

Abstract
In male kidney, 4-hydroxy-estradiol has been shown to play a role in the carcinogenesis process. This metabolite is formed from estradiol and due to the hydroxylation activity of the cytochrome P450 1B1 (CYP1B1) enzyme. Prior reports show polymorphisms of CYP1B1 to result in higher catalytic activity and thus, we hypothesize that single nucleotide polymorphisms of the CYP1B1 gene are involved in the malignant transformation of the renal cell. To test this hypothesis, the genetic distributions of four missense CYP1B1 polymorphisms were analyzed in 383 normal healthy subjects and 384 sporadic renal cell carcinoma (RCC) cases by sequence-specific PCR and sequencing. All subjects were men and from a Caucasian population. The polymorphic sites evaluated were at codons 48 (ArgαGly, rs10012), 119 (AlaαSer, rs1056827), 432 (LeuαVal, rs1056836), and 453 (AsnαSer, rs1800440). Results of these experiments demonstrate a trend for the codon 119 Ser/Ser genotype to be a risk for RCC (χ2, P=0.09). Odds ratio for the Ser/Ser genotype was calculated as 1.85 with 95% confidence interval of 1.07-3.20 as compared to the Ala/Ala genotype. The Leu allele on codon 432 was also found to approach significance as a risk for RCC as compared to Val (χ2, P=0.09). Codons 119 and 432 were observed to be linked (R2=0.25) and haplotype analyses show Ala and Val, representing non-risk alleles at these sites, respectively, to be significantly reduced in RCC cases (P=0.06). No association was found however, when analyzing polymorphic sites with clinical stage of RCC. These results demonstrate missense polymorphisms of CYP1B1 to be associated with renal carcinogenesis and are of importance in understanding their role in the pathogenesis of RCC.
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 2640. doi:1538-7445.AM2012-2640
Abstract 2642: Dietary intake is associated with tumor suppressor DNA methylation in head and neck squamous cell carcinomas
Authors: Arthur Anna E. , Colacino Justin A. , Duffy Sonia A. , Dolinoy Dana C. , Terrell Jeffrey E. , Sartor Maureen A. , Chepeha Douglas B. , McHugh Jonathan B. , Bradford Carol R. , Wolf Gregory T. , Carey Thomas E. , Peterson Karen E. , Rozek Laura S. 
Published: August 2012

Abstract
Background: Diet is associated with prognosis in several cancers, including head and neck, and has been hypothesized to influence epigenetic state by determining the availability of moieties involved in the modification of DNA and histone proteins. Tumor DNA methylation patterns are also hypothesized to be a prognostic factor in cancer, however, the link between diet and HNSCC tumor DNA methylation has not been characterized. Methods: Pretreatment data on usual food and nutrient consumption was collected via food frequency questionnaire (FFQ) on 49 cases identified through the UM Head and Neck SPORE. Tumor DNA methylation was assessed with the Illumina Goldengate Methylation Cancer Panel, which measures methylation at 1505 CpG sites across 807 genes related to cancer. To identify if dietary intake was associated with stochastic methylation in tumor suppressor genes, we calculated a “methylation score,” the sum of the individual hypermethylated tumor suppressor associated CpG sites. Gene specific analyses using linear modeling coupled with an empirical Bayes method of variance estimation were conducted to identify if methylation at individual CpG sites is associated with dietary intake. Results: Intake of antioxidant and methyl donor nutrients tended to be inversely associated with tumor suppressor methylation score. Individuals reporting the highest quartile of dietary folate, vitamin B12 and cruciferous vegetable intake, compared to those with lowest intake, had significantly less tumor suppressor gene methylation (p=0.04 and p=0.01, respectively), as did patients reporting the highest intake of cruciferous vegetables (p=0.04). In gene specific analyses, HPV positive individuals with the highest quartile of vitamin B12 intake were found to have significantly decreased methylation of four genes, RARB, PTHLH, SNRPN, and DCC. Conclusions: These preliminary results suggest that dietary intake may influence the tumor DNA methylation profile in HNSCC and that intake of specific micronutrients may enhance tumor suppression and possibly contribute to survival. Further studies will be needed to explore the effect of diet on head and neck cancer prevention and 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 2642. doi:1538-7445.AM2012-2642
Abstract 2645: Genomic deletions and point mutations in the STK11 gene in Peutz-Jeghers Chilean families
Authors: Orellana Paulina , Alvarez Karin , Heine Claudio , Suazo Cristobal , Pinto Eliana , Carvallo Pilar , López-Kostner Francisco 
Published: August 2012

Abstract
Background: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant hereditary disease characterized by mucocutaneous pigmentation and gastrointestinal hamartomatous polyposis. Individuals with PJS are at increased risk for development of various neoplasms. The genetic susceptibility for PJS has been associated with germline mutation in the serine/threonine kinase 11 (STK11) gene. The aim of the present study was to characterize the genotype and phenotype of Chilean PJS patients. Methods: Mutation screening of 13 patients from 8 PJS families was performed by using single strand conformation polymorphism (SSCP) analysis and DNA sequencing, covering the entire coding region and the splice-site boundaries. In addition, multiplex ligation-dependent probe amplification (MLPA) assay was used for the identification of large exonic deletions or duplications. Results: We identified seven different pathogenic mutations in STK11 gene in 7 unrelated families. Point mutations correspond to a small deletion (c.109delC) in exon 1 that generates a premature stop codon and two intronic mutations localized in splice site of intron 4 (c.597+2 T&gt;A) and intron 6 (c.862-2 A&gt;G). The pathogenic effect on splicing of intronic changes was demonstrated in mRNA of STK11 from lymphocytes of patients. By MLPA, we identified four large deletions ranging from one exon to the whole gene. Breakpoints were identified in two of these patients. Three point mutations (43%, 3/7) may be considered as novel. Conclusions: Different germline mutations in STK11 were detected. A combination of sensitive techniques may improve a high STK11 mutation detection frequency (88%) in PJS Chilean families. Funded by Clinica Las Condes
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 2645. doi:1538-7445.AM2012-2645
Abstract 2646: Genetic determinants of PAH-DNA adduct level and nucleotide excision repair among non-smokers in a high risk area for esophageal squamous cell carcinoma
Authors: Etemadi Arash , Islami Farhad , van Schooten Frederik-Jan , Phillips David H. , Godschalk Roger , Golozar Asieh , Kamangar Farin , Fazel-Tabar Akbar , Pourshams Akram , Boffetta Paolo , Abnet Christian C. , Malekzadeh Reza , Dawsey Sanford M. 
Published: August 2012

Abstract
Background: Polycyclic aromatic hydrocarbons (PAHs) play a role in esophageal squamous cell carcinoma in high risk areas where even non-smokers are highly exposed to these compounds. Their early biological effect is the formation of DNA adducts, mediated by phase 1 and 2 pathways and nucleotide excision repair (NER). We aimed at finding a genetic model to explain inter-individual variations in PAH-DNA adduct level among people with similar exposures. Methods: In 111 randomly-selected female non-smokers from the Golestan Cohort Study in Iran, 21 SNPs in 14 genes related to xenobiotic metabolism and 13 SNPs in 9 DNA repair genes were studied (Table). NER capacity was evaluated by a comet assay, and DNA adduct level was measured by 32p-postlabelling. Multivariate regression was used to assess the effects of the number of risk alleles, NER capacity, and environmental exposures on the log-transformed PAH-DNA adduct levels. Models were compared by Akaike's information criterion (AIC). Results: Mean PAH-DNA adduct level was 5.76+3.13 per 108 nucleotides (range: 1.71 - 18.57). The level of PAH-DNA adducts was significantly lower in homozygotes for N-acetyltransferase 2 (NAT2) slow alleles and excision repair cross-complementing (ERCC)-5 T/T genotype, and higher in individuals with myeloperoxidase (MPO) G/G genotype. The sum of risk alleles in these genes had a significant correlation with the log-adduct level (r=0.4, p&lt;0.001). The table shows gene level coefficients for multivariate analysis. The model including environmental exposures, phase 1 SNPs and NER capacity had the best fit (AIC=93.7). NER capacity itself was affected by a polymorphism in the methylenetetrahydrofolate reductase gene. Conclusion: We observed a high level of PAH-DNA adducts with great inter-individual variation, which could be best explained by a combination of environmental factors, number of polymorphisms in phase 1 genes and DNA repair capacity.

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 2646. doi:1538-7445.AM2012-2646
Abstract 2647: Influence of quercetin-rich foods intake on microRNA expression in EAGLE lung cancer tissues
Authors: Lam Tram K. 
Published: August 2012

Abstract
Background: Lung cancer is one of the most common cancers worldwide and has the highest cancer-related mortality rate. Dietary factors may contribute to lung carcinogenesis. Epidemiologic studies, including the Environment and Genetics in Lung Cancer Etiology (EAGLE) study, have reported increased consumption of quercetin-rich foods to be inversely associated with lung cancer incidence. Although experimental studies suggest that quercetin might affect microRNA (miRNA) expression, this mechanism has not been fully examined. We investigated this hypothesis in quercetin-related lung carcinogenesis using lung cancer tissues. Methods: miRNA expression data were derived from formalin-fixed paraffin-embedded tissue samples in 264 lung (144 adenocarcinoma and 120 squamous cell carcinoma) cases from EAGLE using a custom-made, two-channel oligo array. Quercetin-rich foods were derived from food frequency questionnaire. Individuals were categorized into high and low consumers based on sex-specific tertiles of quercetin-rich food intake. We compared the expression of miRNAs (n=198) between lung cancer cases consuming high-versus-low quercetin-rich food intake using multivariate ANOVA test. We identified miRNAs whose expression differentiated high and low consumption (p-value&lt;0.05), and further grouped them based on their biological function using MiRBase release 17.0. miRNA families were analyzed using Functional Class Scoring (FCS). All analyses were conducted for adenocarcinoma and squamous cell carcinoma separately. Further analyses included stratification by smoking status (former and current smokers only). Results: We found that miRNA expression of 56 miRNAs significantly distinguished lung cancer cases who consumed high-versus-low quercetin-rich foods in tumor tissue within smoking-specific histological subtypes (p-value&lt;0.05). FCS analyses of these miRNAs identified the let-7 family to strongly differentiate between high-versus-low quercetin-rich cases (p-value&lt;0.001), followed by miR-146, miR-125, miR-26, and miR-17 (p-value&lt;0.05). Conclusions: We observed differential expression of key biologically functional miRNAs between high-versus-low consumers of quercetin-rich foods. Our findings, the first of this kind, warrant confirmation from larger studies.
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 2647. doi:1538-7445.AM2012-2647
Abstract 2696: Modulation of intracrine androgen signaling in bone metastatic castrate resistant prostate cancer (bmCRPC) by MDV3100
Authors: Efstathiou Eleni , Titus Mark , Tsavachidou Dimitra , Wen Sijin , Hoang Anh , Ashe Robynne , Karlou Maria , Berman Craig , Troncoso Patricia , Mohler James , Logothetis Christopher J. 
Published: August 2012

Abstract
Background Androgen signaling is a central driver in CRPC. We performed a study to determine the effect of the antiandrogen MDV 3100 on bone marrow infiltrating CRPC. Methods From February 2010 to June 2011, we performed an open-label, observational study of 60 bmCRPC patients (pts), who underwent transilial bone marrow biopsy (BMB) at baseline and 8 weeks of treatment. Pts received MDV3100 160mg orally once daily. The primary objective was to evaluate androgen signaling in bone marrow infiltrating cancer and testosterone in blood (BT) and bone marrow (BMT) and correlate findings with clinical observations. Androgen receptor (AR), CYP17 and phospho Src (pSrc) expression were assessed by immunohistochemistry, and BT and BMT by liquid chromatography mass spectrometry. Findings Maximal PSA decline of Δ50% occurred in 29 (48%) of 60 pts, and α90% in 13 (22%). Tumor involvement in BMB was detected in 28 (47%) pretreatment BMBs. Paired tumor infiltrated BMBs were found in 23 (38%) pts. Pretreatment androgen signaling and pSrc tumor expression is shown in Table 1. Pretreatment intense nuclear AR expression combined with α10% CYP17 tumor expression or increased BMT correlate with Δ50% PSA decline (p value 0.02). AR subcellular localization shift from dominant nuclear to cytoplasmic correlate with Δ50% PSA decline (p value 0.05). Increased pretreatment p-Src expression is associated with lack of PSA decline (p value 0.002). Increase in BMT and BT is observed after 8 weeks of MDV3100. (Mean Pretreatment BMT 0.03 ng/ml, Wk8 BMT 0.04 in 33pts, p value 0.0009) (Pretreatment BT 0.05, wk8 BT 0.066 in 37 pts, p value 0.0001) Interpretation Pretreatment expression profile is consistent with persistent androgen signaling in bmCRPC. MDV3100 induces ‘pharmacodynamic’ changes in Androgen Signaling. AR changes likely account for the reported therapeutic effect of MDV3100. These data prompt exploratory combinations of MDV3100 with Androgen Biosynthesis Inhibitors and src inhibitors.

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 2696. doi:1538-7445.AM2012-2696
Abstract 270: Compensatory and non-compensatory alterations in LNCaP gene expression following antisense therapy directed against bcl-2
Authors: Rubenstein Marvin , Hollowell Courtney MP , Guinan Patrick 
Published: August 2012

Abstract
Antisense oligonucleotides (oligos) have been employed against in vivo and in vitro prostate cancer models targeting proteins associated with growth and programmed death (apoptosis). In LNCaP cells we evaluated monospecific (directed towards bcl-2) and bispecific (directed towards bcl-2 and the epidermal growth factor receptor [EGFR]) oligos which targeted and comparably suppressed the expression of bcl-2, an apoptosis inhibitory protein. Antisense oligos directed against bcl-2 are entering clinical trials and it was of interest to see: 1) Whether such therapy would produce non-specific effects which could compromise its’ efficacy; and 2) To identify genes whose activity, if diminished, may have to be either maintained or replaced for this type of therapy to be effective. Cells were evaluated for the expression of non-targeted genes associated with apoptosis (caspase-3, clusterin); androgen regulation (androgen receptor [AR], p300), cytokines (IL-2, IL-4, interferon [IFN]); antigen expression (prostate specific antigen [PSA], prostate specific membrane antigen [PSMA], prostatic acid phosphatase [PAP]); and autocrine growth (insulin like growth factor [IGF1]). As expected in this type of specific gene therapy, most non-targeted proteins were unaffected. However, the expression of several non-targeted genes were altered. Following the suppression of bcl-2 activity by both mono- and bispecific oligos, LNCaP cells compensated by both suppression of caspase-3 activity (an apoptosis promoter) and enhanced expression of both AR and its’ p300 co-activator. This suggests both an ability to reverse the effects of bcl-2 suppression on apoptosis through decreased expression of the apoptosis promoter and a possible stimulation of growth due to increased androgen sensitivity. It also identifies caspase-3 as an essential gene whose expression must be either maintained or replaced when bcl-2 activity is therapeutically suppressed. Among the differentiation antigens, cell surface PSMA expression was increased by bispecific oligos, whereas secretory PSA and PAP were unchanged. This PSMA increase was associated with an increased IFN expression induced by a unique double strand conformation (intrastrand hybridization) of the bispecific oligos not seen in the monospecific oligo. Increased PSMA expression could make LNCaP cells more recognizable to cytotoxic T cells and/or potentiate prostate cancer vaccines. If gene therapy is truly to be effective, the mechanisms for compensatory changes which contribute to tumor resistance must be further identified and controlled.
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 270. doi:1538-7445.AM2012-270
Abstract 2705: In search of a cost effective sentinel node biopsy technique: A randomized trial comparing the use of methylene blue and patent blue violet to identify sentinel node in breast cancer
Authors: vuthaluru seenu , Srivastava Anurag , Misra Mahesh 
Published: August 2012

Abstract
One of the most significant breakthroughs in breast cancer management in recent times has been in the area of sentinel lymph node biopsy (SLNB), which is now an established staging technique for assessing regional lymph node status while minimizing the morbidity associated with conventional axillary lymph node dissection. Recommended technique of SLNBis the combination of blue dye (isosulfan blue or patent blue violet) and radiotracer. However, neither of the blue dyes are currently marketed in India & are expensive. Thus, SLNB technique as practiced in the West is unlikely to be used widely in economically less developed nations. In India, some surgeons use methylene blue (MB) for identification of sentinel node in breast cancer with variable success rates. However, there are no large randomized trials comparing the efficacy of MB vis a vis isosulfan blue or patent blue violet (PBV) in identifying sentinel node in literature Objective To compare the sentinel node (SN) identification rate using patent blue violet (PBV) and methylene blue (MB) in combination with radiotracer in breast cancer. Sample size Assuming that MB identified SN in 60% cases and PBV in 85% of cases, a two group continuity corrected X2 test with 0.05 two sided test will have 80% power to detect the difference when the sample size is 57. Inclusion criteria Clinically axillary lymph node negative (N0) patients with breast cancer with tumor (T) stage T1, T2, Tx. willing to participate TechniqueCombination technique. Sentinel node: Any LN that is blue/ hot/ hot and blue is defined as SN. Any lymph node to which a blue stained lymphatic leads/ends will also be considered as SN. Results Study Period: Feb 2010-Nov 2011 No of Pts: 102 Age range: 31-82 yrs (mean: 41.4 yrs) Menopausal Status: Pre: 46 Post: 56 Side: R:L:: 50:52 T status: T1: 34; T2: 64; Tx SN identification rates: PBV: 46/49 MB: 51/53 (p value: NS) Conclusions Sentinel node can be identified with equal success rates using MB & PBV. Methylene blue can be used as a cost effective sentinel node biopsy technique in breast cancer in economically less developed countries
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 2705. doi:1538-7445.AM2012-2705
Abstract 2788: GTx-230: an orally available novel tubulin inhibitor that disrupts tumor vasculature and displays single-agent antitumor efficacy in multidrug-resistant prostate cancer with less neurotoxicity
Authors: Ahn Sunjoo , Li Chien-Ming , Barrett Christina M. , Chen Jianjun , Li Wei , Lu Yan , Miller Duane D. , Dalton James T. 
Published: August 2012

Abstract
A novel indole antimitotic compound, GTx-230, was identified in cell-based screening assays that binds to the colchicine site in tubulin and destabilizes microtubules. In this study, the pharmacokinetics, antitumor efficacy, neurotoxicity, and vascular disrupting ability of GTx-230 were evaluated. GTx-230 inhibited the in vitro growth of a number of human cancer cell lines including DU-145, LNCaP, PC-3, and PPC-1 prostate cancer cells with low nanomolar IC50 values. Following a 10 mg/kg intravenous (i.v.) dose to mice, the plasma clearance (CL), volume of distribution at steady state (Vdss), and terminal half-life (T1/2) of GTx-230 were 19 ml/min/kg, 2.9 l/kg, and 1.7 h, respectively. Oral bioavailability of GTx-230 was 36% in mice. In vivo, GTx-230 (6.7 mg/kg, qd, p.o.) was effective with near 100% tumor growth inhibition in xenograft models using PC-3/TXR cells over-expressing P-glycoprotein. In contrast, docetaxel, a known antimitotic agent, was not effective in the PC-3/TXR xenograft model. In vivo studies of mouse performance on an accelerating rotarod and hotplate showed that GTx-230 did not induce any symptoms of peripheral neuropathy. In addition, we evaluated the effect of GTx-230 on in vitro vascular permeability using a transwell system with confluent HUVEC monolayers. GTx-230 resulted in increased permeability after 1 h incubation and showed potency similar to CA4. In summary, the potent in vitro and in vivo antitumor activities of GTx-230 suggest that it may represent a new antimitotic agent for management of solid malignancies, particularly for patients with drug resistant 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 2788. doi:1538-7445.AM2012-2788