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To measure the concentrations of TRF1 and the relationships among telomere length, telomerase activity, and TRF1 levels in tumor and normal colorectal mucosa, from normal and tumoral samples of patients who underwent surgery for colorectal cancer we analyzed TRF1 protein concentration, and telomerase activity were analysed.
In most multicellular eukaryotic organisms, telomerase is active only in germ cells, some types of stem cells such as embryonic stem cells, and certain white blood cells. [9] Telomerase can be reactivated and telomeres restored to the embryonic state by somatic cell nuclear transfer. [18]
90% of cancers are characterized by increased telomerase activity. [28] Lung cancer is the most well characterized type of cancer associated with telomerase. [29] There is a lack of substantial telomerase activity in some cell types such as primary human fibroblasts, which become senescent after about 30–50 population doublings. [28]
If a drug can inhibit telomerase in cancer cells, the telomeres of successive generations will progressively shorten, limiting tumor growth. [56] Telomerase is a good biomarker for cancer detection because most human cancer cells express high levels of it. Telomerase activity can be identified by its catalytic protein domain .
Two concerns with applying telomerase inhibitors in cancer treatment are that effective treatment requires continuous, long-term drug application and that off-target effects are common. [30] For example, the telomerase inhibitor imetelstat, first proposed in 2003, [31] [32] has been held up in clinical trials due to hematological toxicity. [30]
Alternative Lengthening of Telomeres (also known as "ALT") is a telomerase-independent mechanism by which cancer cells avoid the degradation of telomeres.. At each end of the chromosomes of most eukaryotic cells, there is a telomere: a region of repetitive nucleotide sequences which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes.
Human chromosomes (grey) capped by telomeres (white). A telomere (/ ˈ t ɛ l ə m ɪər, ˈ t iː l ə-/; from Ancient Greek τέλος (télos) 'end' and μέρος (méros) 'part') is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see Sequences).
Levels or presence of biomarker should readily distinguish between normal, cancerous, and precancerous tissue; Effective treatment of the cancer should change the level of the biomarker; Level of the biomarker should not change spontaneously or in response to other factors not related to the successful treatment of the cancer