Effects ofm perioperative cimetidine administration on tumor cell nuclear morphology and DNA content in patients with gastric and colorectal cancer

Objective To explore the effects of perioperative cimetidine administration on tumor cell nuclear morphometric parameters and DNA content in patients with gastric and colorectal adenocarcinoma (GCRA) Past studies have attributed the antitumor effect of cimetidine to its immunomodulatory property, which led to an increase of cellular immunity Whether there are other possible mechanisms by which cimetidine exerts its antitumor function is unknown 49 patients with GCRA were randomized into treatment group (n=25) and control group (n=24) based on whether cimetidine was applied to them during the perioperative periold The treatment group started oral cimetidine intake 400mg, tid, 7-10d before oiperation, followed by curative surgery 'The control group did not receive cimetidine Tumor specimens were paraffin embedded for 4μm thick microsection and stained with (1) hematoxylin and eosin (HE) for the morphometric measurements of tumor cell nuclear area (NA), nuclear perimeter (NP), maximal nuclear diameter (MMND) and minimal nuclea4r diameter (MNND); (2) feulgen stain for tumor nuclear DNA content analysis by IBAS Image Analyzer The percentages (%) of diploidy (2C), tripletetraploidy (3C 4C), quintuple ploidy (5C) and >quintuple ploidy (>5C) tumor cells were calculated, using the mean value of DNA content of 50 lymphocytes as normal 2C control 3C 5C cells were designated as law aneuploid cells and >5C cells as high aneupoid cells Results The clinicopathological variables between the two groups were balanced and comparable There were no statistically significant differences between bthe treatment and control groups in regard of the following parameters: age, gender, tumor location, pathological type, TNM stage, and degree of differentiation The NA (μm 2), NP (μm), MMND (μm) and MNND (μm) for treatm ent group/control group were 23 54±5 08/34 698±10 18 ( P <0 001), 22 06±4 43/24 88±4 05 ( P <0 05),7 84±1 64/8 62±1 24 ( P >0 05), and 4 42±0 61/5 41±0 89 ( P <0 001), respectively The percentages (%) of 2C, 3C 4C, 5C and >5C tumor cells for treatment group/control group were 16 64±2 58/5 35±2 14 ( P <0 002), 39 84±2 28/35 70±3 58 ( P >0 50), 12 42±5 00/14 48±0 74 ( P >0 20), 31 11±6 86/45 97±3 82 ( P <0 005), respectively In the treatment group, there was a tendency tiowards low aneuploid tumor cells from high an euploid tumor cells However, high aneuploid tumor cells predominated in the control group Conclusion Perioperative administration of cimetidine to GCRA patients could decrease the size of tumor cell nuclei, raise the percentage of diploid tumor cells, and partially convery high aneuploid tumor cells into low aneuploid tumor cells All of these effects may in turn help reduce the proliferative potential and invasiveness of tumor cells The direct inhibitory functions on tumor cell nuclei may be a new antitumor mechanism of cimetidine, in addition to its immunomodulatory action