PURPOSE: Our aim was to investigate whether chemotherapy with 5-FU induces an alteration in the levels of topoisomerase I (topo I) in colorectal neoplastic tissues METHODS: Twenty-five colorectal cancer patients were included in our study; these had undergone surgical resection of the primary tumor, received post-operatively 5-FU-based adjuvant chemotherapy and then suffered from recurrences. In a standard three-step immunohistochemical procedure, a monoclonal antibody to topo I was applied in both specimens from each patient (one from the primary location and a second one from the recurrence). Statistical analysis was subsequently performed. RESULTS: Malignant cells from the recurrences displayed a statistical significant increase, concerning the levels of topoisomerase I, by comparison with the primary tumors (P=0.01). The increase in topo I levels did not demonstrate significant correlations with Duke's stage (Fisher's Exact Test P value=0.496), differentiation grade (P value=0.661), localization (P value=0.072), patient sex (P value=0.434), nor with relapse free interval (P value=0.493). There was a statistically significant relationship between the age of patients and increase in topo I levels (P=0.011). CONCLUSIONS: Topo I expression may be part of the malignant cells' phenotype in recurrent colorectal carcinomas, suggesting a potential role for Topo I in the acquisition of a metastatic phenotype. The increase of topo I immunohistochemical status is likely to be attributed to 5-FU and given the fact that high levels of topo I correlate with sensitivity to camptothecin, advanced colorectal cancer patients seem to benefit from topo I targeted anticancer drug therapy.
PURPOSE: Our aim was to investigate whether chemotherapy with 5-FU induces an alteration in the levels of topoisomerase I (topo I) in colorectal neoplastic tissues METHODS: Twenty-five colorectal cancerpatients were included in our study; these had undergone surgical resection of the primary tumor, received post-operatively 5-FU-based adjuvant chemotherapy and then suffered from recurrences. In a standard three-step immunohistochemical procedure, a monoclonal antibody to topo I was applied in both specimens from each patient (one from the primary location and a second one from the recurrence). Statistical analysis was subsequently performed. RESULTS: Malignant cells from the recurrences displayed a statistical significant increase, concerning the levels of topoisomerase I, by comparison with the primary tumors (P=0.01). The increase in topo I levels did not demonstrate significant correlations with Duke's stage (Fisher's Exact Test P value=0.496), differentiation grade (P value=0.661), localization (P value=0.072), patient sex (P value=0.434), nor with relapse free interval (P value=0.493). There was a statistically significant relationship between the age of patients and increase in topo I levels (P=0.011). CONCLUSIONS: Topo I expression may be part of the malignant cells' phenotype in recurrent colorectal carcinomas, suggesting a potential role for Topo I in the acquisition of a metastatic phenotype. The increase of topo I immunohistochemical status is likely to be attributed to 5-FU and given the fact that high levels of topo I correlate with sensitivity to camptothecin, advanced colorectal cancerpatients seem to benefit from topo I targeted anticancer drug therapy.
Authors: C G Leichman; H J Lenz; L Leichman; K Danenberg; J Baranda; S Groshen; W Boswell; R Metzger; M Tan; P V Danenberg Journal: J Clin Oncol Date: 1997-10 Impact factor: 44.544
Authors: Sonal P Sanghani; Sara K Quinney; Tyler B Fredenburg; Zejin Sun; Wilhelmina I Davis; Daryl J Murry; Oscar W Cummings; David E Seitz; William F Bosron Journal: Clin Cancer Res Date: 2003-10-15 Impact factor: 12.531
Authors: Jan Stenvang; Iben Kümler; Sune Boris Nygård; David Hersi Smith; Dorte Nielsen; Nils Brünner; José M A Moreira Journal: Front Oncol Date: 2013-12-25 Impact factor: 6.244