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1.  DNA hypermethylation of tumors from non-small cell lung cancer (NSCLC) patients is associated with gender and histologic type 
Background
We previously identified a number of genes which were methylated significantly more frequently in the tumor compared to the non-cancerous lung tissues from non-small cell lung cancer (NSCLC) patients. Detection of methylation profiles of genes in NSCLC could provide insight into differential pathways to malignancy and lead to strategies for better treatment of individuals with NSCLC.
Methods
We determined the DNA methylation status of 27 genes using quantitative MethyLight assays in lung tumor samples from 117 clinically well-characterized NSCLC patients.
Results
Hypermethylation was detected in one of more of the genes in 106 (91%) of 117 cases and was detected at high levels (Percentage of Methylation Reference (PMR)≥4%) in 79% of NSCLC cases. Methylation of APC, CCND2, KCNH5 and, RUNX was significantly more frequent in adenocarcinomas compared to squamous cell carcinomas (SCC), while methylation of CDKN2A was more common in SCC. Hypermethylation of KCNH5, KCNH8, and RARB was more frequent in females compared to males. Hypermethylation of APC and CCND2 was inversely associated with proliferation score assessed by Ki-67 level.
Conclusions
Our findings of differential gene hypermethylation frequencies in tumor tissues from patients with adenocarcinoma or squamous cell cancers and in females compared to males suggests that further investigation is warranted in order to more fully understand the potential disparate pathways and/or risk factors for NSCLC associated with histologic type and gender.
doi:10.1016/j.lungcan.2009.11.002
PMCID: PMC2888601  PMID: 19945765
hypermethylation; lung cancer; gender; histology
2.  Hypermethylation of CCND2 May Reflect a Smoking-Induced Precancerous Change in the Lung 
Journal of Oncology  2011;2011:950140.
It remains unknown whether tobacco smoke induces DNA hypermethylation as an early event in carcinogenesis or as a late event, specific to overt cancer tissue. Using MethyLight assays, we analyzed 316 lung tissue samples from 151 cancer-free subjects (121 ever-smokers and 30 never-smokers) for hypermethylation of 19 genes previously observed to be hypermethylated in nonsmall cell lung cancers. Only APC (39%), CCND2 (21%), CDH1 (7%), and RARB (4%) were hypermethylated in >2% of these cancer-free subjects. CCND2 was hypermethylated more frequently in ever-smokers (26%) than in never-smokers (3%). CCND2 hypermethylation was also associated with increased age and upper lobe sample location. APC was frequently hypermethylated in both ever-smokers (41%) and never-smokers (30%). BVES, CDH13, CDKN2A (p16), CDKN2B, DAPK1, IGFBP3, IGSF4, KCNH5, KCNH8, MGMT, OPCML, PCSK6, RASSF1, RUNX, and TMS1 were rarely hypermethylated (<2%) in all subjects. Hypermethylation of CCND2 may reflect a smoking-induced precancerous change in the lung.
doi:10.1155/2011/950140
PMCID: PMC3090638  PMID: 21577262
3.  SYNTHESIS AND IN VITRO EVALUATION OF 5-FLUORO-6-[(2-IMINOPYRROLIDIN-1-YL)METHYL]URACIL, TPI(F): AN INHIBITOR OF HUMAN THYMIDINE PHOSPHORYLASE (TP) 
An investigation was conducted to determine if the 5-fluoro analog of TPI (5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]uracil), a potent inhibitor of human thymidine phosphorylase (TP), has an IC50 in a range that might allow to use it labeled for imaging of TP expression in vivo. The previously unreported fluoro analog, TPI(F), was prepared and tested against TPI and TPI(Br) using an inhibition assay of [H-3]thymidine cleavage. An assay, performed in the presence of 0.4 mg/ml of human TP, yielded IC50 values of 2.5 nM, 2.7 nM and 9.0 nM for TPI, TPI(Br) and TPI(F), respectively. The results indicate that further studies to develop 18F-labeled TPI(F) as a potential radiopharmaceutical for PET imaging of TP expression in vivo are warranted.
doi:10.1080/15257770903451603
PMCID: PMC2856128  PMID: 20391192
human thymidine phosphorylase; TP; transition state inhibitor analog; TPI; TPI(F)

Results 1-3 (3)