Relationship between telomerase activity and its subunit expression and inhibitory effect of antisense hTR on pancreatic carcinoma

Abstract

The expression of telomerase activity has a significant relationship to carcinogenesis. A strong correlation exists between telomerase activity and hTERTmRNA expression. The up-regulation of hTERTmRNA expression may play a critical role in human carcinogenesis. The expression of telomerase activity and its subunit level in pancreatic carcinoma significantly correlate with the clinical stage of pancreatic carcinoma and hence, may be helpful in its diagnosis and prognosis. The anti-hTR complementary to the template region of hTR is sufficient to inhibit P3 cell telomerase activity and cell proliferation in vitro, and can lead to a profound induction of programmed cell death.

Telomerase Activity as a Marker for Differential Diagnosis of Pancreatic Adenocarcinoma: A Systematic Review and Meta-Analysis

“…Some studies showed no obvious link between telomere length and pancreatic cancer (21,34). Others (11,26,34) found that increased telomerase activity was related to clinical manifestation of pancreatic cancer, a finding that was contradicted by yet other studies (25,27,45). With regard to the diagnostic value, a larger number of studies have indicated that positive telomerase activity is found in pancreatic adenocarcinoma and that detecting telomerase activity can help diagnose pancreatic adenocarcinoma (14,30).…”

“…After the screening of titles and abstracts, 172 articles were excluded and 35 potentially eligible articles were retrieved for analysis of the full text. Among them, 19 eligible articles (8,10,11,14,15,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) qualified for the meta-analysis. Of the 16 excluded, 9 were not appropriate in their design (12,(36)(37)(38)(39)(40)(41)(42)(43), 3 were duplicated publications (9, 44, 45), 2 included fewer than 20 cases (46,47), and 2 were review articles (48,49) (Fig.…”

“…Figure 2 shows the quality of the 19 eligible articles assessed by QUADAS-2 criteria. Thirteen studies (8,14,(22)(23)(24)(25)(26)(27)(28)(29)(33)(34)(35) were regarded as being at high risk of patient selection bias due to the case-control design; 9 studies (8, 11, 14-15, 25-28, 35) enrolled nonconsecutive patients; and 1 study (29) was classified as high risk in the index test domain due to the lack of the pre-specified threshold. All patients of 7 studies (8, 25, 29-33) received more than one reference standard and therefore these studies were classified as high risk in the flow and timing domain.…”

“…Of the 19 studies, 14 (8,10,11,15,(21)(22)(23)(24)(25)(27)(28)(29)(30)(31) involved 678 subjects in whom pancreatic cancer was differentiated from chronic pancreatitis; β = -0.38 (95% CI, -1.89-1.13), Z = -0.49, p = 0.62>0.1. Compared with the above results in studies differentiating pancreatic cancer from benign lesions, the λ value (5.30, 95% CI, 3.37-7.24) was slightly lower.…”

The expression of hTR and hTERT in human breast cancer: correlation with clinico-pathological parameters

“…Our observation that hTR expression was associated with younger age (patients aged ≤ 40 years) is a very interesting one. This has implication regarding telomerase gene based therapy or cancer treatment strategies in young patients with breast cancer such as targeting the template region of hTR with anti hTR (such as oligonucleotides) which may inhibit cell telomerase activity and cell proliferation and can lead to a profound induction of programmed cell death [ 41 , 42 ]…”