LA TELOMERASA PDF

Actividad de la telomerasa e infección por VPH en raspados cervicales de mujeres que desarrollaron lesiones escamosas intraepiteliales de alto grado. Estructura dimérica de la telomerasa. LA TELOMERASA Chloé Larrue, Anna Lippert, Carmen Majano, Héctor Peláez y Alicia Santos. Request PDF on ResearchGate | Actividad de la telomerasa y Article in Revista espanola de enfermedades digestivas: organo oficial de la.

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Telomerase activity and telomere length in the colorectal polyp-carcinoma sequence. Valls Bautista 1C. Departments of 1 Medicine and 2 Surgery. Departments of 3 Gastroenterology and 4 Surgery. University Hospital Arnau de Vilanova. Cristina Valls is supported by a predoctoral grant by Generalitat de Catalunya. The objective of this study was to determine telomerase activity and telomere length patterns in patients with adenomatous polyps either associated or not with colorectal cancer, as well as the role of telomeric instability in the adenoma-carcinoma sequence.

In 6 of these patients fresh samples of tumor tissue, polyps, and normal mucosa were obtained; in the 8 remaining cases, we collected only polyps and normal mucosa. We used the fluorescent-telomeric repeat amplification protocol assay TRAP-F to determine telomerase activity and telomere length using Southern-blot testing.

Mean telomerase activity in polyp tissue was 5. Mean telomere length was 6. Polyps in patients without synchronous cancer had a telomerase activity that was significantly higher 9. The presence of synchronous cancer modifies telomerase activity in polyps.

Currently, there is clinical, epidemiological and experimental evidence clearly indicating that polyps or adenomas are precursor lesions for most colorectal malignancies. However, this does not mean that all polyps evolve into cancer 1. From the colorectal cancer progression model proposed by Fearon and Volgestein 2 inseveral studies have established the changes apparent in the adenoma-carcinoma sequence. The main changes are mutations, deletions, and loss of heterozygosity 1, Telomeres are structures located at the end of chromosomes in eukaryotic cells 7.

They regulate gene expression, participate in the replication of chromosomes, and protect them from degradation by nucleases. In somatic cells, telomeres shorten progressively with each successive cell division.

This progressive shortening is an important mechanism in the timing of human cellular aging. When telomeres become sufficiently short undergo a growth arrest called senescence phase, followed by apoptosis and death. Some cells escape from this mechanism and proliferate indefinitely by the action of telomerase. When these cells accumulate sufficient mutations affecting the cell cycle, they can become cancerous.

La telomerasa by Alicia Santos on Prezi

Telomerase is a ribonucleoprotein that compensates the shortening of telomeres by reverse transcription using its intrinsic RNA as a template 8. In germ cells and tissues with high rates of renewal, telomerase is active and maintains genome integrity and stability ensuring the transmission of total telomere length in each cell division 9. The role of telomeric dysfunction in the adenoma-carcinoma sequence has not been well established.

The results available so far are divergent, and few studies are found in the literature comparing telomerase activity TA and telomere length TL in polyps and the normal mucosa of one same patient The first objective of this study was to determine the behavior of telomerase activity and telomere length in patients with polyps associated or otherwise with colorectal cancer, and the second objective was to explore the role of telomeric instability in the adenoma-carcinoma sequence, as defined by telomerase activity being higher in polyps than in adjacent normal mucosa, accompanied by changes or variations in telomere length.

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Six of these patients had colonic tumors, polyps, and macroscopically normal mucosa 10 cm away from the tumor, while the remaining 8 samples had polyps and normal mucosa. The research protocol was approved by the Hospital’s Ethics Committee.

The methodology was performed using the TRAP technique previously described The hybridized probe was incubated with a digoxigenin specific antibody covalently coupled to alkaline phosphatase. Finally, the immobilized telomere probe was visualized using a highly sensitive chemiluminescent substrate for alkaline phosphatase.

The unit of telomere length was Kilo-base pairs Kbp. TRF lengths were recorded as telomere length. The statistical analysis was performed using the program SPSS Results of telomerase activity and telomere length are expressed as mean values.

The present pilot study includes 14 patients with colorectal polyps, of which 6 showed synchronous colorectal polyps and cancer, while the remaining 8 were isolated polyps. All samples had telomerase activity and telomere length measured.

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Mean TA in polyps was 5. We observed a significantly lower TA in polyps in patients with synchronous colorectal cancer 1. Average telomere length in polyps was 6. Telomerase activity in tumors was 5. Differences between means were not significant but showed a higher TA in tumors than in polyps, and in polyps vs. Average telomere length in tumors was 6. Mean telomerase activity in polyps was 9.

Telo,erasa telomere length in polyps was 6. Other studies that compare TA in polyps with the normal mucosa of different patients found that polyp TA oscillates between 40 and Related to those studies we observed a higher TA percentage in polyps and normal mucosa, which we believe likely due to the technique we used, fragment analysis by sequencing, which is very sensitive and can detect very low telomerase activities possibly common in the normal mucosa, and that can be missed by other methodologies.

Mean telomerase activity in polyps was 5.

Other authors published polyp TA figures that oscillate between 1. None of these studies showed significant differences between polyp TA and normal mucosa TA Polyps synchronic with tumors have a significantly lower telomerase activity when compared to isolated polyps.

Paradoxically, those results are accompanied by greater telomere length in the former. We think that this is due to the activation of alternative mechanisms for the maintenance of telomere length ATLwhich act with no increase in activity 22, Mean polyp telomere length was 6.

Mean values obtained in other studies in which the normal mucosa was compared with polyps of different patients, were as follows: Differences in mean telomere length found by those authors between polyps and normal mucosa were very small when compared to those in our study, possibly due to the fact that they did not work with paired samples.

We also studied the normal – adenoma – carcinoma sequence by measuring TA and TL in samples from 6 patients who had synchronous polyps and colorectal cancer, in which we also analyzed the normal mucosa. This part of the study could not be compared with other similar studies as we found none the literature. Mean TA in tumor samples was 5.

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La longitud del telómero y la actividad de la telomerasa, una Yin y Yang de la senescencia celular

Those differences did not reach significance. We observed intermediate TA in polyps lower than in cancer but higher than in normal mucosa.

We can conclude that there exists a progressive increase in TA levels in the sequence normal mucosa – adenoma – carcinoma, accompanied by a diminution of telomere length.

We observed a tendency in the sequence normal tissue-adenoma-carcinoma where TA increases with cell malignancy grade, and telomere length diminishes. This behavior we think it due to the fact that the cell division ratio also increases with the passage from one tissue type to the next.

telomeraas We cannot compare those results because we found no similar studies in the literature. We think that with more cases those differences could be significant and confirm the existence of a sequence in telomere behavior TA and TL from normal towards tumoral mucosa through polyps.

We believe that for a telomerwsa of the sequence adenoma-carcinoma able to obtain coherent results it is necessary that mucosa samples showing the various stages of carcinogenic progression be studied in the same patients. With this approach we eliminate possible differences between individual patients and can compare the same number of cases for each type of mucosa. On the other hand, it allows to study the sequence in each patient individually.

In all 8 patients with isolated polyps we observed the same behavior as in all polyps taken together or in polyps synchronic with tumors: Although this is a preliminary study we can conclude that there is a growing telomerase activity in the adenoma-carcinoma sequence in the colonic mucosa, as well as a decrease in telomere length as we move toward the normal mucosa from the tumor.

The presence of synchronous cancer modifies polyp telomerase activity. In colorectal cancer there is an expression of telomerase that has been shown in previous studies. In the adenoma-cancer sequence we have demonstrated that there is obvious telomeric dysfunction. This finding would be a mechanism taking into account the changes already known to occur in this sequence, including deletions, mutations, oncogene activation, suppressor genes, or loss of heterozygosity.

Pathology of colorectal cancer. Dig Liver Dis ; 33 4: Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell ; 61 5: Rev Esp Enferm Dig ; 96 1: Cheng L, Lai MD. Aberrant crypt telomfrasa as microscopic precursors of colorectal cancer. World J Gastroenterol ; 9 Molecular biology in colorectal cancer. Clin Trans Oncol ; 8 6: Toxicol Pathol ; 27 6: Structure and function of telomeres.

Nature ; Hum Mol Genet ls 7: Hiyama E, Hiyama K. Telomerase as tumor marker. Cancer Lett ; 2: Telomerase activity is a prognostic factor for recurrence and survival in rectal cancer. Dis Colon Rectum ; 50 5: Demonstration of human telomerase reverse transcriptase in human colorectal carcinoma by in situ hybridization.