IMAMURA Yuji HIROSHIMA UNIVERSITY MEDICAL HOSPITAL,RESEARCH ASSOCIATE, 医学部・附属病院, 助手 (70274082)
MURAKAMI Yoshiaki HIROSHIMA UNIVERSITY FACULITY OF MEDICINE,RESEARCH ASSOCIATE, 医学部, 助手 (10263683)
YOKOYAMA Takeshi HIROSHIMA UNIVERSITY MEDICAL HOSPITAL,PROFESSOR, 医学部・附属病院, 教授 (60034104)
|Budget Amount *help
¥13,100,000 (Direct Cost : ¥13,100,000)
Fiscal Year 1998 : ¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥10,900,000 (Direct Cost : ¥10,900,000)
Postoperative reoccurrence and metastasis is difficult to be predicted at surgery. To evaluate alterations of telomere length and telomerase activity as biomarkers for postoperative reoccurrence/metastasis, we analyzed the correlation between those parameters and clinical status (stages, prognosis, recurrence, etc) in 653 adult and 164 childhood cancer specimens.
Shortened telomere (length of terminal restriction fragments <less than or equal>8 kb) was detected in 1 9-50% and elongated telomere (<greater than or equal> 15 kb) was in 0-19%. Telomerase activation was detectable in 48-1 00% of these tumors. High telomerase activity was detected in various percentages (17-88%) of each type of these tumors. In pancreatic cancer and rhabdomyosarcoma specimens, high telomerase activity was detected in more than 80%. Significantly high percentages of postoperative reoccurrence/metastasis occurred in the cases with high telomerase activity and shortened telomere, which were considered to be usef
ul markers to predict of postoperative reoccurre
Among these cases, we examined the expression of human telomerase RNA component (hTR) and human telomerase reverse transcriptase (hTERT) mRNA using in situ hybridization or in situ PCR.In the cancers with high telomerase activity, almost all cancer cells showed hTERT and hTR expressions, whereas cancer tissues with low telomerase activity showed heterogeneity of their expressions among composing cells. In the tissue specimens, expression levels of telomerase activity using in situ TRAP were equivalent with the hTERT expression levels. Thus, hTERT expression levels in frozen tissues is considered to be a useful recurrence/metastasis-predicting indicator. Then, we established the method for detecting hTERT expression by RT-PCR.
Among these cases, we obtained liver biopsy and intraperitoneal lavage samples under informed consents. Telomerase activity, telomere length, hTR, and hTERT mRNA expression in these samples was not significantly correlated with postoperative reoccurrence/metastasis. Less