cr-2945 and Adenocarcinoma

The potential role of gastrin and the cholecystokinin-B (CCK-B)/gastrin receptor in the genesis of colon cancer is debated. Aberrant crypt foci (ACF) are considered to be preneoplastic lesions of colon cancer. We aimed to assess whether the CCK-B/gastrin receptor antagonist, CR2945, may prevent the development of ACF and adenocarcinoma in the experimental model of dimethylhydrazine (DMH)-induced colorectal cancer.. 226 CD1 mice were randomized into 3 groups (sham, control and treated) and received intraperitoneal injections of NaCl 0.9%, DMH, and DMH + CR2945, respectively, for 5 weeks. 168 mice were sacrificed at 15, 38, 45 and 52 weeks after the first injection day. The colon and rectum were investigated for frequency, multiplicity and distribution of ACF as well as for adenocarcinoma at histology. The expression of gastrin was assessed in tumor samples at histology by immunohistochemistry.. ACF frequency and multiplicity significantly increased with time in both controls and treated mice with no difference between groups except that at week 45. 38.8% of controls and 14.3% of treated mice developed cancer (p = 0.004). No cancer was positive for gastrin at immunohistochemistry. The mean number of cancers per mouse and the proportion of mice with cancer increased with time with statistically significant difference between controls and treated mice at week 38 only but not afterwards. A significant correlation between cancer and ACF frequency (r = 0.35) and multiplicity (r = 0.25) was observed.. Our findings support the preneoplastic significance of ACF and indicate that CR2945 treatment does not interfere with the DMH-induced carcinogenic process.

Topics: Adenocarcinoma; Animals; Benzodiazepines; Colonic Neoplasms; Male; Mice; Mice, Inbred Strains; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Time Factors

This study tested the effect of a new gastrin receptor antagonist, CR2945, on colorectal cancer induced by 1,2-dimethylhydrazine (DMH) in mice. 75 CD1 male mice were divided into 3 groups: group 1 received 1 weekly injection of 20 mg/kg of DMH and 2 daily intraperitoneal injections of 0.5 ml of NaCl 0.9% solution for 5 weeks; groups 2 and 3 received the same weekly dose of DMH and 2 daily injections of CR2945 at the respective doses of 2.5 and 7.5 mg/kg for 5 weeks. The animals were sacrificed 25 and 38 weeks after the first injection. No tumours were found at the 25th week. A lower cancer frequency (4%) was observed in treated animals compared to controls (37.4%) at the 38th week (p = 0.002). These data show that CR2945 could prevent chemically induced colon cancer development in mice.

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Adenoma; Animals; Benzodiazepines; Carcinogens; Colorectal Neoplasms; Incidence; Male; Mice; Mice, Inbred Strains; Receptors, Cholecystokinin