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Biomedical subjects

R C Zenou

Publications and source records attributed to R C Zenou.

7 recordsLinked to original sources

[Gene expression profiling by suppression subtractive hybridization (SSH): a example for its application to the study of lymphomas].

Suppression subtractive hybridization (SSH) was used to isolate genes that were differentially expressed in anaplastic lymphoma kinase (ALK)-positive and ALK-negative anaplastic large cell lymphoma. In addition, this approach was applied to Hodgkin's disease cases with different clinical outcomes. SSH combines a normalization step that equalizes the abundance of cDNAs within the sequences to be tested and a subtraction step that excludes the common sequences between the target and the control. In a model system, the SSH technique enriches for rare sequences up to 5,000-fold in one round. We have isolated several genes whose expression varied significantly with regard to the tumour subtypes. There were different genes with known or unknown functions. We aim to compare the results of the SSH approach with those obtained with high density filters. In a near future, we would like to design DNA chips specific of each pathology that could be used for clinical purposes (evaluation of prognosis and therapeutic response).

Gene Expression Profiling↗

Telomerase activity might persist in the human thymus throughout life.

Telomerase activity has been demonstrated at low levels in peripheral blood lymphocytes but at high levels in germinal centre B cells and thymocyte subpopulations. This study shows that telomerase is activated in the normal human thymus at different times of life. Telomerase activity was detected in thymic protein extracts from two newborn babies and from a 12 year old boy, as well as in extracts from two of six adult patients. The two positive cases were patients aged 54 and 66 years. These results suggest strongly that the thymus can remain functional despite involution in elderly patients.

Adult↗

Telomerase activity in Hodgkin's disease.

Telomerase activity has been demonstrated in various types of cancers including lymphoid neoplasms. The tumour specificity of telomerase activity has been a subject of debate since the description of detectable enzymatic activity in non neoplastic tissues. We and others have demonstrated that such activity was present in non Hodgkin's lymphomas as well as in reactive hyperplastic lymph nodes and tonsils. However, we at the same time were surprised by the absence of telomerase activity in most cases of Hodgkin's disease. We have extended our previous study by adding additional cases and confirm that in the majority of cases, Hodgkin and Reed-Sternberg cells lack telomerase activity (only 2 cases positive out of 20). These results may indicate that the tumour cells of Hodgkin's disease evolve different pathways for maintaining the length of their telomeres during the process of becoming immortal.

Hodgkin Disease↗

Telomerase activity in reactive and neoplastic lymphoid tissues: infrequent detection of activity in Hodgkin's disease.

We used the recently described sensitive and rapid detection assay called telomeric repeat amplification protocol (TRAP) to detect telomerase activity in lymphoblastoid (n = 5) and lymphoma cell lines (n = 7), hyperplastic lymph nodes (n = 6) and tonsils (n = 5), and tissues involved by non-Hodgkin's lymphoma (NHL) (n = 43) and Hodgkin's disease (HD) (n = 14). Clearly evident telomerase activity was found in all lymphoblastoid and lymphoma cell lines, and in 34 of 43 cases (80%) of NHL. These results were expected because of the proliferative and immortal nature of the cell lines and most malignant cells. However, positive results were obtained with the TRAP assay in all hyperplastic lymph nodes and tonsils, which raises the issue of derepression of telomerase activity during an immune response. Telomerase activity alone therefore does not distinguish malignant lymphoid proliferations from reactive states. Telomerase activity was detected in only 1 of 14 cases (7%) of lymphoid tissues involved by HD. Eight of the 13 negative cases were considered to be interpretable because of the lack (3 of 13 cases) or low level (5 of 13 cases) of telomerase inhibition. The five remaining cases could not be evaluated because of their telomerase inhibitor content. The findings imply either transient or very low levels of telomerase activity in HD or that HD for the greater part is a telomerase-independent neoplasm. Microdissection studies are needed to identify subsets of cells carrying telomerase activity in both reactive and neoplastic lymphoid tissues.

Chromosomes, Human↗

Telomerase activity in human thyroid carcinomas originating from the follicular cells.

Telomerase activity is known to be absent from most normal and well-differentiated tissues, although being detectable in the vast majority of malignant tumors. An increasing number of reports demonstrate that telomerase may be activated in benign tumors, such as adenomas. We have investigated a series of normal and neoplastic thyroid tissues for the presence of telomerase activity. As expected, all normal thyroid tissues (n = 20) had no display of telomerase activity. Amongst cancers, the incidence of telomerase activity varied with the histological subtypes. Telomerase activity was present in only 3/15 cases (20%) of papillary carcinomas. Telomerase activity was more frequently detected in follicular (4/6) and in undifferentiated (2/3) carcinomas. Unexpectedly, one case (1/12) of adenoma contained high levels of telomerase activity. Taken together, these results indicate that telomerase may play some role in the pathogenesis of thyroid tumors, in particular in follicular and undifferentiated carcinomas that are known to have the most aggressive behavior.

Adenocarcinoma, Follicular↗

[Techniques for detection of telomerase activity in tissue samples. Diagnostic and prognosis importance].

Telomerase activation has been shown to be an almost universal property of malignant tumors evoking its role in the immortalisation process. We used the recently described sensitive and rapid detection assay called telomeric repeat amplification protocol (TRAP) to detect telomerase activity in neoplastic and non neoplastic tissues. Human telomerase is a ribonucleoprotein which functions as a telomere terminal transferase by adding multiple repeats of the TTAGGG hexamer at the 3'-OH ends of either telomeres or oligonucleotide specifically designed for the TRAP assay. Whenever present, telomerase activity is revealed on acrylamide gel by a six nucleotide ladder of extension products. Detection of telomerase activity may be evaluated for differentiating neoplastic from non neoplastic tissues. In addition, quantitation of telomerase activity may serve as prognostic marker for malignant tumors.

Autoradiography↗