Study On Adenomatous Polyposis Coli Gene Germline Mutation In Familial Adenomatous Polyposis

Intestine cancer is one of the most common malignant tumors. In recent years the incidence of intestine cancer is increasing in our country. The therapy and genetics of intestine cancer are attracting extensive interest. Although great progress has been made in surgical therapy, the rate of cure of Intestine cancer has not gotten great increase. This thesis discusses the research progress in synthetic treatment of intestine cancer, surgical therapy of chronic emissive intestine inflammation and development of antitumor drugs; studies the genetic factors of enteron cancer, the interaction of between polymorphisms in CYP2E1 Rsa I genotypes and lifestyle with risk of stomach cancer, and the effect of enteral nutrition support on serum free fatty acids in short-bowel syndrome rat.1. A novel APC gene germline mutation in a FAP pedigreeThis work studied the adenomatous polyposis coli (APC) germline mutation in the proband and her family members with familial adenomatous polyposis (FAP), and validated the diagnosis of a patient with FAP by colonscopy, pathology and examining the family history. The systematic screening with multiplex ligation-dependent probe amplification (MLPA), denaturing high-performance liquid chromatography (dHPLC) and DNA sequencing were carried out to detect APC gene germline mutations. The results showed this family occurred a bovel mutation of APC, which led to premature temination of the protein. This mutation manifested an aggressive form of FAP with early onset of colorectal adenocarcinoma and colonic adenoma. The mutation of AOC Q667 is the cause of clinical phenotype of this family with FAP, And prophylactic colectohly for the affected family members should be considered.2. Interaction between polymorphisms in CYP2E1 Rsa I genotypes and lifestyle with risk of stomach cancerThis work evaluated the interaction between polymorphisms in CYP2E1 Rsa I genotypes and lifestyle with risk of Stomach cancer. A case-control study was conducted in 145 cases of stomach cancer and 229 population-based controls in Huai'an city of Jiangsu Province, PRC. The epidemiological data were collected, and DNA of peripheral blood leuocytes was obtained from all of the subjects.CYP2E1 genotypes were identified by PCR amplification followed by digestion with Rsa I. The results indicated no significant difference was observed in the frequency of CYP2E1Rsa I c1/c2 and c2/c2 genotypes between controls (38.9%) and stomach cancer cases (41.4%). Individuals who had CYP2E1Rsa I c1/c2 and c2/c2 genotype and with smoking habit were at greatly higher risk of developing stomach cancer (adjusted OR=2.91, 95% Cl: 1.27-6.69) compared with those who had c1/c2 genotype and no smoking habit. Individuals who had CYP2E1Rsa I c1/c2 or c2/c2 genotype and who had frequenly pickled vegetables intake increases risk of developing stomach cancer (adjusted OR=2.08, 95%CI: 1.00-4.32) compared with those who had c1/c2 genotype and had less pickled vegetables intake. Habits of alcohol drinking or no tea drinking significantly increased the OR for stomach cancer. This phenomena was not influenced by CYP2E1 Rsa I genotype. Therefore, the results suggested that gene-environment interaction between the CYP2E1 polymorphism and smoking, intake of pickled vegetable may influence susceptibility of stomach cancer.3. Effect of enteral nutrition support on serum free fatty acids in short-bowel syndrome ratThe effects of enteral nutrition containing long chain triglycerides (LCT) and long chain triglycerides mixed with 50% medium chain triglycerides (MCT/LCT) or long chain triglycerides supplement L-arginine (LCT/Arg) on serum free fatty acid (FFA) profiles in short bowel syndrome (SBS) rats were studied. Sprague-Dawley rats were randomly assigned to 4 groups with 7 rats each: sham operation fed with LCT as control; 85% small bowel resection fed with LCT, MCT/LCT and LCT/Arg, respectively. Serum FFA profiles were determined by gas chromatography after 14 days. Both total and most of individual serum FFA levels were significantly lower in rats with SBS compared with control group. After treated with MCT or L-arginine, serum FFA levels in rats with SBS were significantly higher than those of LCT. SBS rats fed with enteral nutrition alone showed a deficiency of serum FFA. Enteral nutrition containing MCT obviously increased serum FFA level, but did not inhibit intestinal adaptation. L-arginine-enhanced enteral nutrition was associated with an elevation of serum FFA level due to the enterotrophic effect of L-arginine on remnant small bowel mucosa. L-arginine could stimulate intestinal adaptation.4. Surgical therapy of chronic radioactive intestine inflammationRadioactive treatment as one important treatment technique of malignant tumors has obtained more and more extensive application. However, the side-trauma of radioactive treatment in venter and antrum cannot avoid completely, which leads to the incidence increase of chronic radioactive intestine inflammation. This paper reviews the clinic characters of chronic radioactive intestine inflammation and surgical therapy of its syndrome. 5. Research statue of new target spot for antiache of tumor and related drugsIn recent years the study on antitumor drugs has made quick development. With the elucidation of tumor essence and interaction mechanisms using molecular biological and molecular pharmacological methods, antitumor drugs are developing from traditional exogenous medicine toward novel medicine based on the interaction mechanisms, particularly the design, research and development aiming at the new target spot on cancer cells. A series of novel antitumor drugs have been developed, some of them have been used in clinic or clinical experimentation. This paper reviews the research statue of new target spot for antiache of tumor and related drugs.6. Synthetic treatment of intestine cancerIntestine cancer is one of the most common malignant tumors. Although great progress has been made in surgical therapy in recent 50 years, the rate of cure of Intestine cancer has not gotten great increase. 30% of these cured patients encounter recrudescence, half of the patients die of metastasis. The synthetic therapy based on surgical treatment has become one main way to treat intestine cancer. This paper proposes one strategy for chemical therapy of intestine cancer in details. It is hoped that the synthetic therapy of tumors will play more important role in cure of malignant tumors.