ABSTRACT
The isomeric yield ratios of 99m,gRh, 101m,ggRh, and 102m,gRh isomeric pairs produced from the natPd(γ,pxn) reactions were measured with the bremsstrahlung end-point energies of 50-, 55-, 60-, 65-, and 70-MeV at the 100MeV electron linac of the Pohang Accelerator Laboratory, Korea. The measurements were carried out with the activation method in combination with off-line γ-ray spectrometry. In order to improve the accuracy of the activity measurements, the separation of the overlapping γ-rays and the necessary corrections for the counting losses were made. The new experimental results are compared with the theoretical values of the TALYS-1.6 code.
ABSTRACT
CDH13 encodes a cell adhesion molecule, H-cadherin. In this study, we examined CDH13 methylation in nasopharyngeal carcinoma (NPC). Methylation specific PCR results showed that CDH13 was methylated in 20% (1/5) NPC cell lines, 100% (2/2) NPC xenografts and 89.7% (52/58) of the NPC primary tumors, while only methylated in 10% (1/10) normal nasopharyngeal epithelia (P<0.05). CDH13 expression in NPC cell lines and NPC xenografts analyzed by RT-PCR showed that expressions of CDH13 were reversely correlated with their methylation status. In CDH13-silenced cell line, demethylating agent 5-aza-deoxycytidine could dramatically restore CDH13 expression. Taken together, CDH13 promoter is aberrantly methylated in NPC both in vitro and in vivo, and promoter methylation plays a pivotal role in the silencing of H-cadherin expression. Furthermore, the high sensitivity (81%) and specificity (0% false positives) of detecting CDH13 methylation from nasopharyngeal swabs suggest it could be utilized as a tool for early diagnosis.
Subject(s)
Cadherins/genetics , Carcinoma, Squamous Cell/genetics , DNA Methylation , Nasopharyngeal Neoplasms/genetics , Biomarkers, Tumor/metabolism , Cadherins/metabolism , Carcinoma, Squamous Cell/metabolism , Humans , Nasopharyngeal Neoplasms/metabolism , Promoter Regions, Genetic , Reverse Transcriptase Polymerase Chain Reaction , Sulfites/chemistryABSTRACT
RASSF2 can bind directly to K-Ras and function as a negative effector of Ras protein. RASSF2A is the only isoform of RASSF2 that contains CpG islands in its promoter and it has been reported to be inactivated by its promoter methylation in several human cancers. In the present study, we investigated the correlation of RASSF2A expression with its promoter methylation in nasopharyngeal carcinoma (NPC). Expression of RASSF2A was down-regulated in 80% (4/5) of NPC cell lines. Decreased RASSF2A expression was also observed in NPC primary tumors compared with normal nasopharyngeal epithelia. Promoter methylation of RASSF2A could be detected in all the RASSF2A-silenced cell lines (4/5) of the NPC cell lines and 50.9% (27/53) of primary tumors, but not in any of the normal epithelia. RASSF2A-methylated cases showed a significantly lower level of RASSF2A expression than unmethylated cases. Loss of RASSF2A expression can be greatly restored by the methyltransferase inhibitor 5-aza-dC in NPC cell lines. In addition, patients with methylated RASSF2A presented a higher frequency of lymph node metastasis (p < 0.05). Ectopic expression of RASSF2A in RASSF2A-silenced and -methylated NPC cell line CNE2 shows that RASSF2A could inhibit cell cycle progression, colony formation and cell migration, which provided further evidence that RASSF2A is a candidate tumor suppressor gene. In conclusion, RASSF2A, a candidate tumor suppressor gene (TSG), is frequently inactivated by its promoter methylation and this aberrant methylation correlates with lymph node metastasis in NPC.
