Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have identified a high frequency of loss of heterozygosity (LOH) on the human chromosome region 8p12-p22 in a panel of microdissected familial (86% LOH) and sporadic (74% LOH) breast tumours. The two most frequently deleted regions were defined around marker D8S133 and in a broader centromeric region bounded by markers D8S137 and D8S339. We cannot unequivocally characterize the 8p12-p22 loss as an early or a late event in breast carcinogenesis. In parallel, we have performed linkage analysis in four German breast cancer families. A location score greater than 13.67 corresponding to a LOD score of 2.97 at the marker D8S137 has been obtained. Our results considerably strengthen the evidence for a breast cancer susceptibility gene(s) located on the short arm of the chromosome region at 8p12-p22.
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PMID:Deletion mapping and linkage analysis provide strong indication for the involvement of the human chromosome region 8p12-p22 in breast carcinogenesis. 937 78

Telomerase activity is generally absent in primary cell cultures and normal tissues. Telomerase is known to be induced upon immortalization or malignant transformation of human cells. In the present study, we analyzed both telomere length and telomerase activity in biopsy samples from mucosa undergoing metaplasia, adenoma and cancer of the stomach. We attempted to estimate the correlation between telomerase activity and telomere length in these tissues. Telomerase activity was estimated using the telomeric repeat amplification protocol and telomere length by Southern blot analysis. Extracts were defined as telomerase-negative when the signals were less intense than those for 10(2) KATO-III cells (positive control). We detected telomerase activity in 15%, 45% and 89% of the examined cases of intestinal metaplasia, adenoma and gastric cancer respectively. However, telomere length in the gastric mucosa became reduced as the mucosa underwent metaplasia and developed into adenoma. Gastric cancers showed a broad range of telomere length among cases. However, gastric adenomas showed the shortest telomere length. These results suggest that telomerase is expressed during the early phase (intestinal metaplasia through adenoma) of gastric carcinogenesis, although the activity at that stage is not high enough to fully restore the reduced telomeric DNA.
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PMID:Telomere length and telomerase activity in carcinogenesis of the stomach. 937 6

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.
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PMID:[Telomerase]. 941 Aug 44

Two regions on chromosome segment 11p15.5 have frequent allele loss in lung cancer. LOH11A is centromeric between loci D11S1758 and D11S12, and LOH11B is telomeric between HRAS and D11S1363. We studied the biological significance of this allele loss using microcell-mediated transfer of human chromosomes 11, 11p, and two radiation-reduced fragments of 11p into human lung adenocarcinoma cell lines. Chromosome 12, which has not been implicated in lung carcinogenesis, was used as a control. All four chromosome 11-containing hybrid clones showed significantly reduced tumorigenicity in nude mice and growth in liquid culture. These findings support the notion of a tumor suppressor gene located in the LOH11A region on chromosome segment 11p15.5.
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PMID:Growth inhibition of a human lung adenocarcinoma cell line by genetic complementation with chromosome 11. 941 55

Many cancer and immortal cells exhibit telomerase activity that stabilizes telomere lengths and may be involved in cell immortality and carcinogenesis. Downregulation of telomerase has been reported during differentiation of hematopoietic, melanoma, glioma, and myelocytic leukemia cells. Moreover, normal human mammary epithelial cells immortalized by a p53 mutant have been reported to exhibit activation of telomerase. However, no information is available about the activity of telomerase during p53-mediated apoptosis of immortalized cells. We investigated the activity of telomerase during p53-induced apoptosis of the immortalized endothelial cell line ECV-304. ECV-304 cells were induced into apoptosis by infection with a recombinant adenovirus that facilitated expression of high levels of wild-type p53. Telomerase activity was measured by a PCR-based telomeric repeat amplification protocol (TRAP). Telomerase activity was found to be unaffected by overexpression of p53 and apoptosis in immortalized endothelial cells.
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PMID:Telomerase activity in immortalized endothelial cells undergoing p53-mediated apoptosis. 943 61

Telomerase, a cellular reverse transcriptase, has been detected in the majority of human malignant tumors, where it provides an escape mechanism from proliferative limitations due to progressive telomere erosion with each cell division. In this study, we used a non-radioactive telomeric repeat amplification protocol (TRAP) with an internal telomerase assay standard for the detection and semiquantitative analysis of 98 single frozen sections of normal breast tissue and benign and malignant breast lesions on an automated laser-fluorescence sequencer. Telomerase activity was detected in 36 of 40 (90%) infiltrating breast carcinomas, whereas no activity was found in nonmalignant breast tissues including blunt duct adenosis, papilloma, ductal hyperplasia and atypical ductal hyperplasia. However, telomerase activity was detected in 59% of ductal in situ carcinomas, suggesting that telomerase reactivation is an early event in breast carcinogenesis. We found a positive correlation between telomerase activity levels and cell proliferation determined by MIB1 immunostaining. No correlation, however, could be demonstrated between telomerase activity and other known breast cancer prognostic indicators. Telomerase activity was also detected in 60% of fibroadenomas indicating that careful interpretation of analysis of telomerase activity in fine needle aspirates is required, since low telomerase activity may not necessarily be an indicator of malignancy in breast tissue.
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PMID:Telomerase activity in human proliferative breast lesions. 947 5

Using the sensitive telomeric repeat amplification protocol assay, we detected telomerase activity in 26 of 35 (74.3%) renal cell carcinomas analyzed. Subdivision of the tumors according to telomerase activity did not reveal an obvious association between the presence of telomerase activity and histomorphological stage, grade, tumor size, or DNA ploidy. Furthermore, no association was found between telomerase activity and a distinct chromosomal aberration pattern; namely, loss of genetic material on the short arm of chromosome 3. Telomerase activity was also detected in 6 of 35 (17.1%) normal corresponding renal tissue samples, which seems interesting in light of the supposed biological role of telomerase expression in carcinogenesis. Interestingly, telomerase activity was detected in three of the four (75%) kidneys bearing non-clear cell tumor types, whereas of the 31 kidneys with clear cell carcinomas, telomerase activity was found in only 3 (9.7%) normal tissue samples. In addition, the two renal angiomyolipomas and one of the two analyzed transitional cell carcinomas of the renal pelvis were telomerase negative.
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PMID:Genetic changes and telomerase activity in human renal cell carcinoma. 951 71

The short arm isochromosome of chromosome 12 and trisomy 12 are well-established chromosomal alterations in human ovarian germ cell tumors. However, numerical aberrations of chromosome 12 in epithelial ovarian tumors (EOTs) are highly controversial; both trisomy 12 and monosomy 12 have been observed. We performed chromosomal in situ hybridization in paraffin-embedded and formalin-fixed tissue sections of 31 EOTs. Twenty-five EOTs could be evaluated statistically (2 mucinous, 11 serous, 5 endometrioid, 3 borderline, and 4 other epithelial-type tumors) to examine the copy number of chromosome 12 and 15. The frequency distribution of hybridization signals with alpha-satellite centromeric DNA probes for chromosome 15 revealed disomy in all cases. However, we found the loss of chromosome 12 in 16 of 25 tumor samples. No correlation was found between the presence of monosomy 12 and the clinical stage of the tumors. Frequent loss of chromosome 12 may indicate that this chromosome is involved in the tumorigenesis of EOTs. Further studies are needed to clarify whether loss of chromosome 12 is an early or late event in ovarian carcinogenesis.
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PMID:Frequent loss of chromosome 12 in human epithelial ovarian tumors: a chromosomal in situ hybridization study. 955 5

We analyzed telomere length and telomerase activity in intestinal metaplasia (IM), adenoma, and cancer of the stomach and studied the stages at which the cells acquire telomerase activity in carcinogenesis and also the correlation between telomerase activity and telomere length. Telomerase activity was detected in 15%, 45%, 89% of IM, adenomas, and cancers. Telomere lengths shortened as normal mucosa changed into IM and more into adenoma. Gastric cancers showed a broad range of telomeric length. The shortest telomere length was found among gastric adenomas. These results suggest that telomerase is expressed during early phase of gastric carcinogenesis but the activity at that stage is not strong enough to fully restore the reduced telomeric DNA.
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PMID:[Telomere length and telomerase activity in intestinal metaplasia, adenoma and well differentiated adenocarcinoma of the stomach]. 961 19

Telomerase is a specialized ribonucleoprotein polymerase that directs the synthesis of telomerase repeats at chromosome ends. Accumulating evidence has indicated that telomerase is stringently repressed in normal human somatic tissues but reactivated in cancers and immortal cells, suggesting that activation of telomerase activity plays a role in carcinogenesis and immortalization. In this work, the status of telomerase activity during the development of human thyroid cancer was determined using telomeric repeat amplification protocol (TRAP) in 14 nodular hyperplasia, 14 adenomas, 23 papillary carcinomas and 11 follicular carcinomas. Positive telomerase activity was detected in 2 of 14 nodular hyperplasias (14%), 4 of 14 adenomas (29%), 12 of 23 papillary carcinomas (52%) and 10 of 11 follicular carcinomas (91%). The cancers that are negative for telomerase activity are mostly in early stage (stage I or II). These results suggest that telomerase reactivation plays a role during the development of thyroid cancer.
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PMID:Telomerase activity in benign and malignant human thyroid tissues. 964 30


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