BACKGROUND & AIMS:Cyclooxygenase-2 (COX-2) is a potential target for chemotherapy of colorectal cancer (CRC). We tested the antineoplastic activity of the selective COX-2 inhibitor rofecoxib on human CRC liver metastases by measuring surrogate markers of tumor growth and angiogenesis in a randomized, double-blind, placebo-controlled trial. METHODS:Patients undergoing liver resection surgery for metastatic disease were randomized to receive rofecoxib 25 mg daily or placebo before surgery (duration, >14 days). The apoptosis index (AI; neocytokeratin 18), proliferation index (PI; Ki-67), and microvessel density (MVD; CD31) were measured in metastases by immunohistochemistry. The effect of rofecoxib on COX-2-positive HCA-7 human CRC cell PGE(2) synthesis, proliferation, and apoptosis in vitro was also investigated. RESULTS: Patients who received rofecoxib (n = 23) and placebo (n = 21) were well matched regarding clinical and metastasis characteristics. The mean (range) duration of rofecoxib therapy was 26 (14-46) days. Rofecoxib-treated metastases had a 29% decrease in MVD (mean, 25.1 [SEM, 2.7] per hpf) compared with placebo-treated tissue (32.5 [SEM, 4.5] per hpf; P = 0.15). There was little difference in AI (rofecoxib mean, 2.03% [SEM, 0.43%] vs. placebo 1.39% [SEM, 0.39%]) or PI (rofecoxib 54.7% [SEM, 5.1%] vs. placebo 52.6% [SEM, 5.6%]). Rofecoxib-induced growth arrest and apoptosis of HCA-7 cells occurred only at concentrations (>10 micromol/L), which were significantly higher than the IC(50) for COX-2 inhibition. CONCLUSIONS:Rofecoxib may negatively regulate angiogenesis in human CRC liver metastases. The absence of a significant, direct effect of rofecoxib on epithelial cells in liver metastases in vivo mirrors the lack of activity on human CRC cells at pharmacologically relevant concentrations in vitro.
RCT Entities:
BACKGROUND & AIMS:Cyclooxygenase-2 (COX-2) is a potential target for chemotherapy of colorectal cancer (CRC). We tested the antineoplastic activity of the selective COX-2 inhibitor rofecoxib on human CRC liver metastases by measuring surrogate markers of tumor growth and angiogenesis in a randomized, double-blind, placebo-controlled trial. METHODS:Patients undergoing liver resection surgery for metastatic disease were randomized to receive rofecoxib 25 mg daily or placebo before surgery (duration, >14 days). The apoptosis index (AI; neocytokeratin 18), proliferation index (PI; Ki-67), and microvessel density (MVD; CD31) were measured in metastases by immunohistochemistry. The effect of rofecoxib on COX-2-positive HCA-7 human CRC cell PGE(2) synthesis, proliferation, and apoptosis in vitro was also investigated. RESULTS:Patients who received rofecoxib (n = 23) and placebo (n = 21) were well matched regarding clinical and metastasis characteristics. The mean (range) duration of rofecoxib therapy was 26 (14-46) days. Rofecoxib-treated metastases had a 29% decrease in MVD (mean, 25.1 [SEM, 2.7] per hpf) compared with placebo-treated tissue (32.5 [SEM, 4.5] per hpf; P = 0.15). There was little difference in AI (rofecoxib mean, 2.03% [SEM, 0.43%] vs. placebo 1.39% [SEM, 0.39%]) or PI (rofecoxib 54.7% [SEM, 5.1%] vs. placebo 52.6% [SEM, 5.6%]). Rofecoxib-induced growth arrest and apoptosis of HCA-7 cells occurred only at concentrations (>10 micromol/L), which were significantly higher than the IC(50) for COX-2 inhibition. CONCLUSIONS:Rofecoxib may negatively regulate angiogenesis in human CRC liver metastases. The absence of a significant, direct effect of rofecoxib on epithelial cells in liver metastases in vivo mirrors the lack of activity on human CRC cells at pharmacologically relevant concentrations in vitro.
Authors: Peter C Konturek; Kazimierz Rembiasz; Grzegorz Burnat; Stanisław J Konturek; Marcin Tusinela; Władysław Bielanski; Jens Rehfeld; Danuta Karcz; Eckhart Hahn Journal: Dig Dis Sci Date: 2006-04 Impact factor: 3.199
Authors: Yuyi Wang; Chi Du; Nan Zhang; Mei Li; Yanyang Liu; Maoyuan Zhao; Feng Wang; Feng Luo Journal: Oncol Lett Date: 2018-02-14 Impact factor: 2.967
Authors: Alastair L Young; Claire R Chalmers; Gillian Hawcroft; Sarah L Perry; Darren Treanor; Giles J Toogood; Pamela F Jones; Mark A Hull Journal: BMC Cancer Date: 2013-02-26 Impact factor: 4.430