Objective To investigate the mechanism and clinical significance of vincristine (VCR) inhibiting gastrinproliferation effects on human colon cell line SW480. Methods Effects of VCR on the viable cell count (A value), myoinositol triphosphate (IP3, CPM value), 〔Ca2+〕i and protein kinase C (PKC) activity of human colon cell line SW480 were evaluated in vitro by MTT assay,3Hmyoinositol incorporation, fluorescence measurements and γ-32P-ATP incorporation.Results A value of VCR+PG group was lower than that of PG or control group (P<0.01 vs control, P<0.01 vs PG). The concentration of IP3 or 〔Ca2+〕i in VCR+PG group was lower than that in PG group (P<0.01 vs PG); and the PKC activity of membrane was lower than that in PG group (P<0.05 vs PG, P>0.05 vs control). Conclusion Effects of vincristine may be through the phosphoinositide signaling pathway on gastrinstimulating cell proliferation in human colon cell line SW480. It has provided an experimental evidence for antisignaling therapy for patients with colon cancer.
Objective To study the earlier and later clinic results of 64 chronic duodenal ulcer patients treated with high selective vagotomy and mucosal antrectomy (HSV+MA). Methods The clinic results of the patients and the changes of gastrin, motilin and somatostatin in the blood were prospectively investigated. Results Fifty nine (92.2%) patients after 3-6 months of follow-up and 26 (92.9%) patients after 5-8 years of follow-up achieved Visick grates Ⅰ-Ⅱ. No patients died. Gastric acid secretion and infection rate of helicobacter pylori in antral mucosa were significantly reduced after operation. No significant difference was showed in bile acids and total bacterial counts of gastric juice before and after operation. No ulcer recurrence was found by barium meal and endoscopy. There was no significant difference in serum gastrin and plasma motilin before and after operation. The level of somatostatin in the blood of patients after 5-8 years of follow-up was decreased. Conclusion HSV+MA is the better operative treatment for duodenal ulcer, since it can not only effectively and lastingly decrease acid secretion and rates of ulcer recurrence, but also preserve the function of the antrum and pylorus and keep the gastric milieu interne relatively stable.
Objective To study the relationship between gastrin and c-myc, c-fos expression in colorectal cancerous tissue and the mechanism of gastrin effect on colorectal cancer.Methods The gastrin and c-myc, c-fos expression in 48 cases of colorectal cancerous tissue and canceradjacent mucosa were detected with immunohistochemistry techniques.Results The positive rate of gastrin in colorectal cancerous tissue was 39.58%. The rate of the well differentiated adenocarcinoma was higher than that of the poorly differentiated and mucinous adenocarcinoma(P<0.05). The positive rates of c-myc and c-fos in colorectal cancerous tissue were higher than those in canceradjacent and normal mucosa. The positive rate of c-myc and c-fos in the group with gastrin positive expression were 78.94% and 73.68%, higher than those in the group with negative gastrin expression(37.93% and 31.04%). Conclusion Some of colorectal cancer cells formed and secreted gastrin through autocrine. The increase of cmyc, c-fos etc oncogene expression probably stimulate the cancer cells proliferation.
Human SW480 colonic cancer cell line was evaluated for its growth response to pentagastrin, gastrin receptor antagonist proglumide (PGL) in vitro by MTT assay and flow cytometry. The results showed that gastrin possessed a proliferative effect on SW480 cell, PGL alone had no obvious effect on SW480 cell, but it inhibited gastrin-induced growth of SW480 cell with dosage dependent when it was used with gastrin, its inhibitive effect did not steadly increase at a dose>32μg/ml. This suggests that effect of gastrin is achieved via gastrin receptor. Gastrin promoted the sythesis of DNA, protein and triggered the cancer cell shifting from phase G0/G1 to phase S, G2M. PLG inhibited the effect of gastrin, it suggests that gastrin possessed a proliferation on SW480 cell at post receptor is achieved by the effect of gastrin on cell cycle.
Forty-two patients with duodenal ulcer underwent highly selective vagotomy and mucosal antrectomy (HSV+MA) and were followed up for 3 years. Two weeks, 1 year and 3 year after operation, serum gastrim level and gastric emptying capacity were tested. The results show that he postoperative levels of serum gastrin were lower than the preoperative ones, but wih no significant difference (P>0.05). Only a few patients had delayed gastric emptying 2 weeks and 1year after operation,but it returned to normal in 3 years .The authors conclude that HSV+MA is a better operative treatment for duodenal ulcer since it can abolish the factors of postoperative ulcer recurence and perserve the functions of the antrum and the pylorus.
Objective To study ultrastructure and clinical significance of gastrin secretory granule in colorectal carcinoma cells. Methods The gastrin expression in colorectal carcinoma tissue and blood of 10 cases was examined by using radioimmunity analysis and immunohistochemistry. The ultrastructure of gastrin secretory granule of 10 cases, the positive of gastrin immunohistochemistry of colorectal carcinoma were examined by using immunoelectron microscopic technique. Results The gastrin concentration of the colorectal cancer group 〔(130.75 ±21.34) pg/ml〕 was significantly higher than that of control group 〔(95.63± 12.26) pg/ml〕,Plt;0.05. In 10 specimens of colorectal cancer, 5 cases were gastrin immunohistochemistry positive (+++), 4 moderate positive (++) and 1 weak positive (+). Cells in colorectal cancer were polyshaped, with unusual nucleoli different in size, concentrating on the edge, the cytoplasm mitochondrion was plentiful with vacuolates, and more secretion granules could be seen, 400-1500 nm in diameter with a clear border of membrane. There were two types of granular appearance: type A was largest in bulk size, low electrodensity was welldistributed, granular core appeared loose; type B was smaller in bulk size, high electrodensity was welldistributed, nucleus was usually compact.protein A gold (pAg) positive granules were located partially in secreting granules. pAg positive granules in highly differentiated cancer were mainly located in secreting granules of type A. pAg positive granules in low differentiated cancer were mainly located in secreting granules of type B. A part of cancer cell membrane, and inside and outside of microvillus membrane, adhering to pAg granules in line could be seen. Conclusion The colorectal carcinoma cells may synthesize and secrete gastrin themselves, which may be the mechanism of high gastrin levels in colorectal cancer. The use of gastrin antagonist and receptor antagonist may treat the patents with colorectal carcinoma.
Gastrin(G) concentration in fasting blood, cancer tissues and its adjacent mucosas sampled from fourty-three patients with large intestine carcinoma (LIC) were measured. The results showed fasting G levels in patients with LIC were significantly higher than those in the normal surum controls (P<0.05),and dropped to normal value after resection of the cancers. Surum G levels were correlated with cell differentiations of the cancer.The cancer tissues and its adjacent mucosas contained higher levels of G than the normal mucosas (P<0.05). The results provided a laboratory evidence that the growth of LIC in vivo were regulated by G and G level might be an indicative parameter for selection of patients with LIC to be treated with hormone therapy and the study of biological character of LIC.
Objective To study the neuropathological changes of gastrin and substance P(SP) in the intermuscular and submucous nerve plexus of the colonic walls in patients with delayed motor constipation(DMC).MethodsGastrin and rabbit SP polyclonal antibiotics were used to make an immunohistochemical staining of the samples of different segments obtained from 10 patients with DMC and 8 normal subjects(control group) for a comparative observation as well as a relative semi-quantitative analysis.Results The immune positive nerve cells of gastrin and SP in the intermuscular nerve plexus of colon with DMC were markedly reduced; no differences in the immune response of gastrin and SP in the mucous nerve plexus were found between the two groups(P<0.01). With routine HE staining, focal inflammation occurred in the mucous membrane of DMC colon and that the neuronal vacuolus of the intermuscular nerve plexus degenerated, reduced and even disappeared. Conclusion The abnormal changes of the neural structure in the immune reponse of gastrin and SP in the intermuscular nerve plexus of colon with DMC might be related to reduction of gastrin and SP peptide neuron or dysfunctional.