Objective To investigate the effect of a selective cyclooxygenase-2 inhibitor on tumor metastasis,tumor angiogenesis,and vascular endothelial growth factor(VEGF)of orthotopic implanted human gastric carcinoma in non.obesity diabetes(NOD)severe combined immune deficiency(SCID)mice.Methods Human gastric cancer SGC-7901 tissues were orthotopically implanted into the stomach of the NOD SCID mice.Forty mice were randomly divided into two groups which received either intravenous injections of 0.9% Nacl solution (0.9% NaCL solution group)or 50mg/kg.d Nimesulide(Nimesulide group)twice weekly for two weeks.Mice were sacrificed in the 5th week after implantation.Tissues from stomach and other organs were obtained for histopathologieal evaluation.The intratumoral microvessel density(MVD)and VEGF protein expression in tumor were evaluated by immunochemical method.Results The tumor metastasis rates were 18/20 in 0.9% Nacl solution group and 5/20 in Nimesulide group(P＜0.05).MVD was 9.5±2.9 in 0.9% NaCl solution group and 3.9±2.1 in Nimesulide group(P＜0.01).VEGF protein expression was 90% in 0.9%NaCl solution group and 25% in Nimesulide group(P＜0.01).Conclusions Nimesulide can inhibit the metastasis or gastric cancer through inhibiting tumor VEGF expression and tumor angiogenesis with no obvious anticoagulant activity.

OBJECTIVETo detect putative suppressor loci involved in tumor progressing or metastases.

METHODSThirty microsatellite marker primers were employed to amply the corresponding loci of the genome DNA from 83 patients with sporadic colorectal cancer. The PCR products were electrophoresed on a 377 PRISM sequencer and the fluorescent signals were analyzed by Genotyper and Genescan software.

RESULTSThe data were obtained from 24 loci, with an average LOH frequency of 15.16%. The LOH at D2S206 and D2S364 was more frequent than 30%, and was less than 20% at the rest loci. Significant difference was observed between the percentage of LOH and tumor staging or differentiation at D2S142 (2q24.1), D2S126 (2q35), D2S2211 (2p24.2), D2S305 (2p23.3). Occarrence of deletion at the later two loci was correlative.

CONCLUSIONSFrequent LOH was not observed at the loci around known mismatch repair genes on chr. 2. The region between D2S305 (2p23.3) and D2S2211 (2p24.2) deleted holistically, and was correlated to the stage and differentiation of tumor attended by D2S142 (2q24.1) and D2S126 (2q35) on 2q. It is suggested that unknown genes associated with tumor progressing or metastases reside in the two loci on 2q or the region on 2p.

Adult ; Aged ; Aged, 80 and over ; Cell Differentiation ; Chromosome Mapping ; Colorectal Neoplasms ; genetics ; pathology ; Female ; Humans ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged ; Neoplasm Metastasis

OBJECTIVETo evaluate and map the putative tumor suppressor loci on chromosome 5 involved in tumor progress or metastasis.

METHODSChromosome 5 of 83 patients with sporadic colorectal cancer was systemically screened. Fifteen microsatellite marker primers labeled with 3 different fluorescents were used to amplify the corresponding loci of the genome DNA. The PCR products were electrophoresed on a 377 PRISM sequencer and the fluorescent signals were analyzed with Genotyper and Genescan software.

RESULTSThe highest loss of heterozygosity (LOH) ratio was found at D5S416 (48.15%) on 5p and at D5S471 (38.71%) on 5q. The region (5q13.3 - 31), where D5S471 and 3 neighboring loci (D5S428, D5S2027 and D5S2115) reside, presented high frequent LOH.

CONCLUSIONThe deletion of APC, MCC, CTNNA1 and IL cluster in the 5q 13.3 - 31.1 area play important role in the tumorogenesis of colorectal cancer, and the expected existence of another novel tumor suppressor gene on 5p is possible.

Adult ; Aged ; Aged, 80 and over ; Alleles ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; Colorectal Neoplasms ; genetics ; Female ; Genes, Tumor Suppressor ; Humans ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; genetics ; Middle Aged

OBJECTIVETo analyze the loss of heterozygosity (LOH) of chromosome 20 in patients with sporadic colorectal cancer to identify additional loci involved in colorectal tumorigenesis.

METHODSPolymorphic microsatellite markers were analyzed in 83 colorectal cancer patients' tumor and normal DNA by PCR. PCR products were electrophoresed on an 377 DNA sequencer. Genescan 2.1 and Genotype 2.1 software were used in the LOH scanning and analysis. Comparisons between LOH frequency and clinicopathological data were performed by chi(2) test. P < 0.05 was considered statistically significant.

RESULTSThe average LOH frequency in the long arm, short arm and whole chromosome 20 was 21.1%, 26.7% and 22.8%, respectively. Chromosome 20 exhibited relatively high LOH frequency, particularly in the regions of 20p and 20q11.1-q13.1.

CONCLUSIONThere is notable genetic instability on chromosome 20 in sporadic colorectal carcinoma patients; that is, mutation on chromosome 20 is closely associated with sporadic colorectal carcinogenesis. Also, there may be tumor suppressor genes related to sporadic colorectal carcinoma near the region 20q11.1-q13.1.

Adult ; Aged ; Aged, 80 and over ; Chromosomes, Human, Pair 20 ; Colorectal Neoplasms ; genetics ; pathology ; Female ; Humans ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged