bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4908: Detection of bladder tumor by quantitative methylation specific real time PCR from urine sediment DNA
Authors: Chung Woonbok , Bondaruk Jolanta , Kim Daniel D. , Czerniak Bogdan , Issa Jean-Pierre J. 
Published: February 2011

Abstract
Bladder cancer is the fifth most frequent human cancer and causes approximately 3% of all cancer-related deaths. DNA hypermethylation is a common epigenetic abnormality in cancer and may serve as a useful marker to clone new cancer-related genes as well as a marker of the disease activity. Recently, we developed a high throughput genome wide methylation assay, Methylated CpG Island Amplification Microarray (MCAM). Using MCAM, we investigated methylation changes in about 8,000 genes in bladder tumors. Through this screening method and validation by bisulfite pyrosequencing, we have developed novel biomarkers for diagnosis and prognosis of bladder tumor. We characterized a group of genes that was found to be methylated in 80-90% of the tested bladder tumor samples. These candidate genes (DBC1, MYO3A, SOX11, SLC16A12, NPTX2, NKX6-2, A2BP1, PENK and CA10) were used to screen for bladder cancer in urine samples by quantitative methylation specific real time PCR, thus representing a non-invasive method for early detection. Based on these data, we established a panel of 6 biomarkers (MYO3A, SOX11, NKX6-2, PENK, CA10 and quantity of DNA in test urine) that can be used for bladder tumor screening in urine samples. The method showed 89.1 % sensitivity and 91.4 % specificity for detection of bladder tumor urines (n=128) compared to normal control urine (n=105) by 3 or more than 3 positive out of 6 biomarkers. Analyzing by stage of bladder tumors, 5 out of 5 (100 %) in Tis, 21 out of 29 (72 %) in Ta, 18 out of 19 (95 %) in T1, 57 out of 60 (95 %) in T2, 6 out of 6 (100 %) in T3 and 2 out of 2 (100 %) in T4 showed 3 or more than 3 positive out of 6 biomarkers. Thus, 83% of Tis-Ta-T1 stages and 95.6 % of T2-T3-T4 stages were detected in analyzed bladder tumor urines. This DNA methylation biomarkers panel will help the early detection and monitoring of bladder tumor patients.
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 4908.
Abstract 4909: The role of CpG island methylator phenotype 2 (CIMP2) in early onset colorectal cancer patients
Authors: Li Carmen , Yuen Siu Tsan , Anthony  , Chan Kin Wang , Tsui Wendy Wai Yin , Chan Annie Suk Yee , Leung Suet Yi , Chan Tsun Leung 
Published: February 2011

Abstract
CpG Island Methylator Phenotype (CIMP), characterized by methylation at various promoter sites, has been reported as a subgroup in colorectal cancer. CIMP1 is often associated with microsatellite instability (MSI) as well as BRAF mutation while CIMP negative enriched with P53 mutant. Besides, a CIMP2 classification has also been established and indicated to be associated with KRAS mutation. Most of these experiments related to CIMP were carried out on tumor samples from late onset patients with a mean or median age of at least 60. Thus it was of interest to observe any deviation of such pattern among early onset colorectal cancer population. Bisulfite conversion of the extracted DNA from 73 tumor samples with MSS status were examined via pyrosequence for their methylation status among loci MINT1, MINT2 and MINT27, the most frequently methylated sites reported in CIMP 2 phenomenon. These samples were free from MLH1 methylation and BRAF mutation to exclude conditions of CIMP1. The age group ranged from 29 to 68 years old with a mean age of 50.7 years old. Sequencing of its genomic DNA for KRas mutation was also screened as per se to previous studies. It was found that CIMP2 appeared more frequently in patients over the age of 50 (p=0.04) when compared with patients below 50 years old. Furthermore, methylation of the CIMP 2 loci examined (MINT1, MINT2 and MINT27) were most likely accompanied with the mutation of KRas in patients over 50 years old (p=0.05) while there was no observed correlation of CIMP 2 loci and KRas mutation in patient samples under 50 years of age. Since the CIMP2 phenotype is not seen in early-onset CRC samples, our data suggests that an alternative pathway, but not CIMP, may be responsible for the tumorigenesis of early-onset MSS CRC. Moreover, current studies proposed chromosomal instability may be a distinct mechanism in the pathogenesis of CRC, thus investigation would be carried on this aspect.
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 4909.
Abstract 4910: Identification of putative epigenetic markers for head and neck squamous cell carinoma recurrence
Authors: Rettori Marianna M. , de Carvalho Ana Carolina , Maia Danielle C. C. , Carvalho Andre L. , Kowalski Luiz Paulo , Vettore Andre L. 
Published: February 2011

Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent types of cancer but the lack of early detection and high incidence of local-regional recurrence lead to high mortality. Therefore, it is important to develop new molecular markers to be used as diagnostic and prognostic indicators. An important mechanism for gene transcriptional inactivation is hypermethylation at the CpG islands within the promoter regions. The presence of hypermethylation might be useful as a molecular marker for tumor cell detection which could be useful for early detection of tumor recurrence. The aim of this study was to evaluate promoter hypermethylation of suppressor genes via quantitative methylation-specific PCR (Q-MSP) in tumor and body fluid samples (saliva) as a means to detect epigenetic alterations specific to HNSCC. Tumor samples and salivary rinse were collected before and after the last curative treatment from 180 consecutive HNSCC cases and every 6 months during the patient follow-up. The pattern of aberrant methylation of 24 genes was analyzed and allowed the selection of a panel of 5 genes that have a specificity of 95% and a sensitivity of 38% in the detection of hypermethylated cells in saliva samples from recently diagnosed HNSCC patients. The efficacy of this panel may be useful in early diagnosis of HNSCC recurrence is being evaluated.
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 4910.
Abstract 4916: MAL, a frequently methylated gene marker for early detection of breast cancer
Authors: Hillocks Yolanda M.N. , Lo Pang-Kuo , Teo Wei Wen , Fackler Mary Jo , Sukumar Saraswati 
Published: February 2011

Abstract
Hypermethylation of CpG islands in the promoter region of tumor suppressor genes is a common event in cancer, and often results in transcriptional silencing. Computational searches of existing large databases for genes underexpressed in multiple cancers, combined with CpG island analysis of those genes, identified a novel methylation marker gene in breast cancer called MAL (Maturation-Associated protein for T-Lymphocyte). MAL encodes a 17kD lipid raft protein that is found in mature T-cells and participates in T-cell differentiation and T-cell receptor signaling. Two previous studies have reported gene promoter hypermethylation of MAL in primary breast tumors and breast cancer cell lines. Furthermore, Horne et al found MAL inactivation is predictive of benefit from adjuvant chemotherapy. We propose that alteration of MAL expression is functionally important in breast cancer. In addition, we propose that MAL has the potential to serve as a serum methylation marker for early detection of breast cancer. MAL gene methylation as assessed in breast cancer cell lines and primary tumors by quantitative multiplex methylation specific PCR (QM-MSP) showed that it is frequently methylated in cell lines (40/48; 83%), in primary tumors (11/20; 55%) and in distant metastasis (18/35; 51%), but not in normal breast tissues. Hypermethylation of MAL resulted in its decreased expression in the majority of the samples tested. Treatment of breast cancer cell lines with demethylating agents and histone deacetylase inhibitors restored MAL expression, thus establishing epigenetic alterations as the major mechanism of silencing. The function of MAL is being deciphered at both the biological and biochemical level by performing overexpression and knockdown studies in breast cells using already constructed expression vectors. The characterization and validation of MAL, a lipid raft protein, as a potential DNA methylation marker in breast cancer, particularly in serum, could provide a valuable early detection and prediction tool for breast 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 4916.
Abstract 492: Esophageal administration of manganese superoxide dismutase plasmid liposomes (MnSOD-PL) reverses thoracic irradiation sensitivity of nitric oxide synthase one homologous recombinant negative (NOS1 -/-) mouse
Authors: Epperly Michael W. , Rajagopalan Malolan S. , Rwigema Jean-Claude , Stone Brandon , Goff Julie , Dixon Tracy M. , Franicola Darcy , Greenberger Joel S. 
Published: February 2011

Abstract
NOS1 -/- mice are more sensitive to 29 Gy thoracic or 9.5 Gy total body irradiation (TBI) than control C57BL/6NHsd, or NOS2 -/- or NOS3 -/- mice (p &lt; 0.0001 and p = 0.0006). Histological examination of the esophagus, lungs, heart and intestine revealed no explanation of the rapid death of NOS1 -/- mice. Blood and bone marrow isolates six days after TBI (1 day before the NOS1 -/- mouse death) showed similar decrease in blood counts for all the mouse strains. NOS1 -/- mouse marrow irradiated to doses ranging from 0 to 8 Gy showed CFU-GM, BFU-E and CFU-GEMM radiosensitivity similar to that from control mice. There were also no differences in serum electrolytes, liver or renal function tests in irradiated NOS1 -/- compared to C57BL/6NHsd mice. RNA extracted from esophagus, stomach or intestine at day 0, 1 or 6 following 9.5 total body irradiation showed by qualitative RT-PCR analysis of TNF-σ, NF-κβ, and INF-γ similar cytokine expression between NOS1 -/- and C57BL/6NHsd mice. NOS1 -/- and C57BL/6NHsd mice were irradiated to 9.5 Gy total body or 20 Gy to the thoracic cavity and observed by video camera. NOS1 -/- mice had seizures before death following both TBI or thoracic irradiation, while no seizures were detected in dying C57BL/6NHsd mice. NOS1 -/- mice irradiated to 9.5 Gy to the brain (with the remainder of the body shielded) did not produce death from seizures. NOS1 -/- were intraesophageally administered MnSOD-PL (100 µg plasmid DNA) and irradiated to 20 Gy to the upper body 24 hr later. NOS1 -/- mice administered MnSOD-PL had normalized survival compared to control irradiated NOS1 -/- mice: 50% survival at 12 days for irradiated control NOS1 -/- mice compared to 128 days for MnSOD-PL treated NOS1 -/- mice (p = 0.0311). The data indicate that esophageal neuronal abnormalities which cause pyloric stenosis in the strain may be responsible for both the rapid thoracic irradiation sensitivity leading to seizure and its reversal by intraesophageal MnSOD-PL gene therapy.
Supported by NIAID grant U19AI068021, and NIH grant T32AG21885
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 492.
Abstract 4920: Effects of PMEPA1 in prostate tumor cell growth and tumor formation
Authors: Li Hua , Li Hongyun , Raymundo Eliza , Thangapazham Rajesh , Sreenath Taduru , Dobi Albert , Srivastava Shiv 
Published: February 2011

Abstract
Introduction: PMEPA1 is an androgen-induced gene. We have shown that androgen receptor transcriptionally activates PMEPA1 and PMEPA1 negatively regulates androgen receptor by recruiting the E3 ubiquitinatin ligase NEDD4 to AR, therefore promoting proteasome-dependent AR degradation, thus, forming a remarkably tight feedback loop between AR and PMEPA1. Moreover, PMEPA1 mRNA was found in decreased amounts in prostate carcinoma. Previous data in cell culture models of prostate cancer have shown that DNA Methylation of the PMEPA1 gene may play a role in decreased PMEPA1 expression in human prostate cancer cells.
Experimental procedures: We generated stable PMEPA1 shRNA expressing LNCaP cells and analyzed this cell line by cancer biological assays including cell counting, soft agar and cell invasive assays. To evaluate the Methylation status of PMEPA1 promoter genomic DNA from primary human prostate tumors was examined by Methylation sensitive PCR method.
Results: PMEPA1 is successfully knocked down in the PMEPA1 shRNA expressing LNCaP cell line as detected at the mRNA and protein levels. The PMEPA1 knockdown cell line expressed AR protein at elevated levels and consistent elevation of AR signaling was evident in the study. Interestingly, the size of PMEPA1 knockdown cell showed altered morphology when compared to stale transfectant non-targeted shRNA LNCaP cells. In the PMEPA1 knockdown cell line we found higher number of cells in the S phase of the cell cycle compared with the control. In agreement with this observation the cellular proliferations were also enhanced under both androgen dependent and independent conditions. Moreover, the PMEPA1 knockdown cells have stronger invasive activity compared to control cells. The promoter methylation study of human prostate tumor derived genomic DNA revealed DNA Methylation within the PMEPA1 promoter downstream region in 20% of the examined samples.
Conclusions: PMEPA1 knockdown may enhance proliferation and invasiveness of prostate cancer cell by the elevation of AR levels. Thus PMEPA1 gene may act as a tumor suppressor gene in human prostate cancer cells. DNA methylation may play a role in silencing PMEPA1 gene expression in a subset of patients with lost or decreased PMEPA1 expression.
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 4920.
Abstract 4922: KRAS and BRAF mutations influence correlation structure of locus-specific CpG island methylation and CIMP in colorectal cancer
Authors: Ogino Shuji , Tanaka Noriko , Nosho Katsuhiko , Huttenhower Curtis , Quackenbush John , Haigis Kevin , Fuchs Charles 
Published: February 2011

Abstract
Background: The CpG island methylator phenotype (CIMP-high or CIMP1) is a distinct phenotype associated with microsatellite instability (MSI) and BRAF mutation in colon cancer. Recent investigations suggested that a separate KRAS mutation-associated CIMP subtype (CIMP-low or CIMP2) exists. However, no study has deciphered the interrelationship between KRAS, BRAF, CIMP and locus-specific CpG island methylation, utilizing causal modeling by structure equation model (SEM) analysis.
Design: Utilizing the database of 861 colorectal cancers, DNA methylation at 16 CpG islands [CACNA1G, CDKN2A (p16), CHFR, CRABP1, HIC1, IGF2, IGFBP3, MGMT, MINT-1, MINT-31, MLH1, NEUROG1, p14 (CDKN2A/ARF), RUNX3, SOCS1, and WRN] was quantified by real-time PCR (MethyLight). We also examined MSI status and DNMT3B expression. To evaluate the effect of KRAS and BRAF mutation on the correlation structure of the CpG island markers and MSI, we categorized tumors into 4 groups; Group 1 (N=440) with wild-type KRAS and BRAF; Group 2 (N=308) with mutant KRAS and wild-type BRAF; Group 3 (N=107) with wild-type KRAS and mutant BRAF; and Group 4 (N=6) with mutant KRAS and BRAF, which was excluded from further analyses. We analyzed data using clustering analysis, principal component analysis (PCA) and SEM.
Results: In unsupervised disjoint clustering analysis of the methylation markers, only 4 markers (CACNA1G, IGF2, RUNX3, SOCS1), were clustered with CIMP-high regardless of KRAS or BRAF mutation. In Groups 1 and 2, two latent CIMP classes, CIMP-low and CIMP-high, were assumed. However, in Group 3, CIMP-high status and CIMP-low status were clustered together so that only one latent class, “CIMP”, was assumed. PCA yielded similar findings to clustering. Based on the results of the cluster analysis and PCA and the literature data, we applied causal modeling by SEM analysis. In SEM analyses, the correlation structures between CIMP, locus-specific CpG island methylation and MSI differed according to KRAS and BRAF status, which was in agreement with results by PCA analyses. Differences between Group 1, Group 2 and Group 3 were highly significant p&lt;0.0001).
Conclusions: KRAS and BRAF mutations influence correlation structures between locus-specific CpG island methylation, and CIMP status in colorectal cancer. Our data suggest the role of KRAS and BRAF mutations in modifying propensity of CpG island methylation in a locus-specific manner.
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 4922.
Abstract 4927: MGMT promoter methylation is enriched in glioblastoma derived spheres as compared to respective original tumor tissue and is associated with loss of expression
Authors: Sciuscio Davide , Diserens Annie-Claire , Martinet Danielle , Vlassenbroeck Ilse , Hamou Marie-France , Janzer Robert-Charles , Pollo Claudio , Stupp Roger , Levivier Marc , Hegi Monika E. 
Published: February 2011

Abstract
Epigenetic silencing of the O6-methylaguanine DNA methyl transferase (MGMT) gene by promoter hypermethylation blunts repair of O6-methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma. Quantitative methylation specific PCR (Q-MSP) suggests that not all cells in a glioblastoma exhibiting MGMT methylation carry a methylated MGMT allele, even after adjustment for tumor cell content. This raises the question of the clinically relevant methylation threshold for predicting response to therapy for treatment stratification. There are several potential reasons: heterogeneity of glioblastoma; contaminating normal tissue; a heterogenous methylation pattern not correctly detectable by the assay, or presence of MGMT methylation in distinct subpopulations of cells, namely tumor initiating cells. In order to address the question we investigated the degree and pattern of MGMT promoter methylation in 10 paired samples of glioblastoma and spheres derived thereof using Q-MSP and methylation specific clone sequencing. We observed that in MGMT methylated glioblastoma, the percentage of methylated alleles ranged from 10 to 90%. In contrast, in most of the respective glioblastoma derived spheres, cultured under stem cell conditions, methylated alleles were highly enriched (10/10 clones), even if both MGMT-alleles were retained. The methylation pattern was conserved in the spheres, even when passing them in nude mice. Most importantly, this hypermethylation was associated with complete loss of MGMT expression. For one case we observed only 50% methylated clones in the sphere fraction, associated with low expression of MGMT.
Taken together, our data suggest that in MGMT methylated glioblastoma, cells with MGMT promoter hypermethylation are enriched in the sphere fraction which supposedly comprises cancer initiating cells. Thus, even a low percentage of MGMT methylation in a glioblastoma could be predictive marker for a benefit from alkylating agent 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 4927.
Abstract 4937: Hypermethylation of semaphorin 3B promoter in malignant pleural mesothelioma
Authors: Koyama Nobuyuki , Zhang Jialing , qun Hu , Goto Yoshiya , Ishikawa Yuichi , Shimizu Yoshihiko , Sakaguchi Kozo , Kobayashi Kunihiko , Hagiwara Koichi 
Published: February 2011

Abstract
Semaphorin 3B (SEMA3B) is a putative tumor suppressor gene that is inactivated by promoter hypermethylation and allelic loss on chromosome 3p21.3 in lung cancer. While malignant pleural mesothelioma (MPM) is associated with poor outcome, its pathogenic mechanism remains unclear. The purpose of this study is to elucidate a novel molecular pathogenesis of MPM from the investigation of the methylation status of SEMA3B promotor. After informed consent, we used surgically resected specimens of 28 MPM cases. The methylation was detected by methylation-specific PCR for genomic DNA extracted from individual specimens, and then correlation between the methylation status and clinicopashological features was analyzed. While 17 of 28 MPM cases harbored SEMA3B methylation (60.7%), there was no significant difference in any factors including survival time. SEMA3B promotor is frequently hypermethylated in MPM compared to lung cancer, and might be associated with the pathogengesis of MPM.
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 4937.