Telomerase Activity In Tumors Research Articles

Indomethacin suppresses the growth of colon 26, Meth-A and FM3A tumors in mice by reducing the prostaglandin E2 content and telomerase activity in tumor tissues.

The antitumor effect of indomethacin on Colon 26, Meth‐A and FM3A tumors was investigated in mice. The prostaglandin E2 content in tumor tissues was assayed to find out if indomethacin acts on tumors, and the telomerase activity in tumors and somatic tissues (testis, liver, spleen and colon) was also monitored during indomethacin treatment. Growth of Colon 26, Meth‐A and FM3A tumors was significantly (P < 0.001‐0.05) suppressed by indomethacin compared to the untreated controls. The prostaglandin E2 content in the three tumors was markedly (P < 0.001) reduced by indomethacin. Telomerase activity in Colon 26 and FM3A tumors was significantly (P < 0.001) lower than that of untreated tumors (80% and 45% decrease versus the controls, respectively), and the activity in Meth‐A tumor was slightly decreased (10% decrease versus the control) by indomethacin. Telomerase activity in the somatic tissues was not significantly affected by indomethacin. In summary, this study shows the effectiveness of indomethacin as an antitumor agent against three types of tumors, and suggests that indomethacin affects telomerase activity in tumors in vivo.

Suppression of cell proliferation and telomerase activity in 4-(hydroxyphenyl)retinamide-treated mammary tumors.

The detection of telomerase activity has been proposed as a biomarker of breast cancer development and progression. In this study, we used cell proliferation and telomerase in MNU (N-methyl-N-nitrosourea)-induced mammary carcinomas as targets for assessing the response of tumor cells to 4-(hydroxyphenyl)retinamide (4-HPR), a known inhibitor of mammary carcinogenesis in animal models and premenopausal women. In mammary tumors of rats treated for 1, 2, 4 or 6 weeks with 4-HPR, we observed that telomerase activity decreased progressively with the extension of 4-HPR administration. A marked reduction in telomerase activity was already observed by 2 weeks after treatment and the lowest level was found at 6 weeks after initiation of 4-HPR treatment. The changes in telomerase activity were preceded and accompanied by a significant decrease in the percentage of proliferating cells as evaluated by 5-bromodeoxyuridine (BrdU)-labeling. However, when the values of telomerase activity in the individual tumors were compared with the percentage of proliferating cells, no significant correlation was found. These data suggest that the decreased telomerase activity in the animals treated with 4-HPR is not a simple consequence of the changes in cell proliferation, but a more complex phenomenon involving different cellular mechanisms and pathways. The time-dependent and consistent decrease of telomerase activity in the tumors treated with 4-HPR suggests that, in addition to the percentage of proliferating cells, telomerase activity could also be used as an endpoint in breast cancer chemotherapy studies.

Measurement of telomerase activity in dog tumors.

Telomeres are specific structures present at the end of liner chromosomes. DNA polymerase can not synthesize the end of liner DNA and, as a result, the telomeres become progressively shortened by successive cell divisions. To overcome the end replication problem, telomerase adds new telomeric sequences to the end of chromosomal DNA. The enzyme activity is undetectable in most normal human adult somatic cells, in which shortening of the telomere is thought to limit the somatic-cell life span. In contrast to normal somatic cells, many human tumors possess telomerase activity. The present study looked at whether telomerase activity might serve as a marker for canine tumors. Telomerase activity was measured using the telomeric repeat amplification protocol assay. Normal dog somatic tissues showed little or no telomerase activity, while normal testis exhibited a high level of telomerase activity. We measured telomerase activity in tumor samples from 45 dogs; 21 mammary gland tumors, 16 tumors developed in the skin and oral cavity, 7 vascular tumors and 1 Sertoli cell tumor. Greater than 95% of the tumor samples contained telomerase activity (3-924 U/2 micrograms protein). The results obtained in this study indicated that telomerase should be a useful diagnostic marker for a variety of dog tumors, and it may serve as a target for antitumor chemotherapy.

Evaluation of an assay for detecting telomerase activity in neoplastic tissues of dogs

Abstract Objective To determine feasibility of using the telomere repeat amplification protocol (TRAP) assay to detect telomerase activity in tumors of dogs. Sample Population Samples of tumor or normal tissue were obtained from client-owned dogs that underwent surgical biopsy during the period of January 1996 through December 1997. Procedure The TRAP assay was used to detect telomerase activity in malignant or benign tumors of dogs. Telomerase status (positive or negative) was compared with results of histologic examination for each sample to estimate specificity and sensitivity of this assay for the diagnosis of malignancy. Results Of 26 malignant tumors, 24 were telomerase positive on TRAP assay, whereas 3 of 4 benign tumors and 3 of 3 normal tissues were telomerase negative. Analysis of these results indicated an estimated sensitivity of 92% and specificity of 86% for tumor analysis, using the TRAP assay. Conclusion The TRAP assay can be used to measure telomerase activity in malignant tumors of dogs. Clinical Relevance Because telomerase activation may be required for indefinite longevity of cells, it may also serve as a tumor marker and therapeutic target. The TRAP assay can be used to detect telomerase in samples of fluid as well as tissues obtained from solid tumors. Therefore, it may have considerable clinical value in rapid and noninvasive diagnosis of neoplasia in dogs. Additional studies must be completed to more accurately determine sensitivity and specificity of the assay. (Am J Vet Res 1998;59:1526-1529)

Telomerase activity in renal cell carcinoma

Telomerase activity has been shown to be increased in numerous tumors and cell lines, although to the authors' knowledge there has been no previous assessment of telomerase activity in renal cell carcinoma (RCC). To examine whether telomerase activity could be used as a biochemical parameter for predicting the behavior of RCC, telomerase activity was quantified in RCC samples and correlated with clinicopathologic findings. Telomerase activity was quantified in 50 RCC samples and 21 samples of normal renal tissue using fluorescence-based telomeric repeat amplification. Telomerase activity was detected in 28 of 50 RCC samples (mean +/- standard deviation, 35.03 +/- 18.47 U/microg protein), whereas there was no telomerase activity in 21 normal renal tissue specimens. Telomerase activity in tumors classified as pT4 was significantly higher than in tumors classified as pT1 to pT3. Telomerase activity also correlated with patient age. Telomerase activity was increased in RCC samples compared with normal renal tissues. Although significant associations were observed between telomerase activity and clinicopathologic parameters, further study is required to determine whether telomerase activity affects the biologic and clinical behavior of RCC.

A non-isotopic method for the detection of telomerase activity in tumour tissues: TRAP-silver staining assay.

Telomerase activity has been observed in a high proportion of specimens from a wide variety of human malignant tumours, but not in non-neoplastic tissues. Measurement of telomerase activity is a...

Telomerase

Telomerase is an enzyme that elongates telomeric repeats, the specialized structures at the ends of chromosomes that provide genomic stability and compensate for the physiologic process of telomere shortening. It has been implicated in cellular senescence, immortalization, and carcinogenesis. Over 85% of human tumours, and 95% of nonmelanocytic skin cancers, show telomerase activity, in contrast to the corresponding normal tissues. This suggests that telomerase activity may play an important role in carcinogenesis. Recent evidence shows that telomerase is active not only in embryonal and germ line tissues, but also in some normal tissues. In the skin, this activity has been traced to the stem-cell-bearing epidermal basal cell layer, possibly reflecting the presence of telomerase-competent stem cells. These findings require a reconsideration of our interpretation of telomerase activity in tumours of the skin and other tissues. As a causal relationship linking telomerase activity and cancer has yet not been demonstrated, some caution is warranted.

Development of a novel in vitro chemosensitivity assay: telomerase as a possible marker of tumor cell survival.

Telomerase is a ribonucleoprotein enzyme which is involved in the maintenance of chromosome ends. Telomerase activity (TLMA) is required for cell immortality and can be considered a ubiquitous tumor marker. In this study we describe a new approach for developing in vitro chemosensitivity assays based on the assessment of TLMA in tumors, upon treatment with antineoplastic agents. The results of preliminary studies on in vitro cultured tumor cell lines indicate that TLMA inhibition can be used as a marker of tumor cell killing by anticancer drugs. Therefore the present investigation provides the rational basis for an in vitro chemosensitivity assay based on TLMA evaluation.