Investigation of ABCB1 1236 and 2677 SNPs in patients with peptic ulcer.

OBJECTIVE: P-gp, encoded by ABCB1 gene, is an ATP-binding membrane pump, which exports substrates from the cell including drugs and xenobiotics. Changes in the function of P-gp as a result of polymorphism could have an impact in some diseases' risks and treatment outcomes. The aim of the study was to determine the significance of the ABCB1 gene SNPs: 1236 and 2677 for peptic ulcer risk and development of Helicobacter pylori infection in peptic ulcer patients. MATERIAL AND METHODS: One hundred and ninety-five biopsy specimens obtained from peptic ulcer patients (investigated group) were genotyped using sequencing for common SNPs of ABCB1: 1236 and 2677. Genotyping data were compared with the results from healthy subjects (control) and with the presence of H. pylori infection, which was estimated by urease test. RESULTS: No statistically significant difference in frequency of genotypes and alleles for the SNPs were found between the investigated group and the control. However, in the peptic ulcer patients, mutant TT homozygotes and those who carried at least one allele T for the polymorphisms 1236 and 2677 were observed more frequently than the control group. In the peptic ulcer group, there were no significant dependences between the presence of H. pylori infection and the investigated polymorphisms other than more frequent occurrence of TT 1236 homozygous in the group of infected women (p = 0.0298). CONCLUSIONS: The TT genotype and the mutated allele T for the polymorphisms 1236 and 2677 could increase peptic ulcer risk. ABCB1 1236 polymorphism may also be associated with an increased likelihood of H. pylori infection development, especially in women.

[Paliative procedures in cholangiocarcinomas--experience of 5 centers]. / Zabiegi paliatywne w raku pecherzyka i/lub dróg zólciowych--doswiadczenia 5 osrodków.

UNLABELLED: Cholangiocarcinomas have been often met in daily practice. Biliar tract neoplasmas are the most important group in adenomas and papillomas. There is the medical and social problem with cancer patients because they call doctor too late when cancer changes reach a high level and only paliative procedures are recommended. In the most cases the prothesis implanted by ERCP and surgical digestive bypasses are applied. AIM OF THE STUDY: was to evaluate some therapeutic methods in paliative treatment applied in patients with biliary tract cancer. MATERIAL AND METHODS: From 01.2003 to 12.2007 (5 years experience) in 4 departments of general surgery and departments of digestive tract diseases the medical treatment of 430 patients with biliary tract cancer was analyzed. All patients were divided into 3 groups: G1--prosthesis by ERCP; G2--percutaneously, transhepatic drainage of biliary tract; G3--surgical digestive bypass. RESULTS: G1 techniques were applied in 75 patients, G2 in 14 cases and G3 in 74 cases. In the last group of patients the following procedures have been performed: triple bypass (TB) in 45 cases (62%), choledochoduodenostomy (ChD) in 7 cases (9%), gastroenterostomy (GE) in 10 patients (13%) and laparotomy with Kehr drainage in 12 patients (16%). The number of complications in G1 group was observed in 31%, in G2--42%, and in G3--63%. 30 days death rate was 14% in G1, 28% in G2 and 18% in G3. Over 12 months survival rate was in G1, 3 months in G2 and 15 months in G3. Differences are statistically sagnificant (p < 0.05). CONCLUSIONS: From all applied methods of paliative treatment the best results were noticed in surgical digestive bypass and implantation of prosthesis by ERCP. After surgical treatment survival rate was higher, but the number of complications was higher in relation to another methods.

[Treatment of cholecysto- and choledocholithiasis--own experiences]. / Leczenie kamicy dróg zólciowych--doswiadczenia wlasne.

UNLABELLED: Cholecystolithiasis is a serious problem of contemporary medicine. The most common operations in gastroenterologic surgery are gallbladder operations because of calculosis. The most common complications after gallbladder operations are bleeding from site of the gallbladder and bile leakage, but the most serious complication is a bile ducts injury. THE AIM: The assessment of complications quantity after cholecystectomy due to cholecystolithiasis. Observation of operation's profile changes during last 10 years. MATERIAL AND METHODS: From January 1997 to December 2006 in Department of Surgery in MSWiA Hospital in Lodz and in Departments of Surgery in Leczyca and Piotrkow Trybunalski 6845 cholecystectomy were made including 4215 laparoscopic operations. RESULTS: Complications were observed in 12.6% patients. Suppuration of the wound and postoperative hernias occurred more often after classic operations, in the other hand blood and bile leakage from site of the gallbladder were more often observed after laparoscopic operations. The ratio of complications after classic operations to laparoscopic operations was about 15.4% to 6.1%. Conversion was made in 11.5%. During first 5 years conversion was made in 17.6%, in the next 5 years average number of complications drop to 5.4%. CONCLUSIONS: Nowadays laparoscopic cholecystectomy is a standard procedure in symptomatic and asymptomatic cholecystolithiasis. It's a safe operation, burden with a little amount of complications made during acute as well as chronic course of disease. Laparoscopic technique requires a lot of care and in the event of operator's doubts should be replace with classic operation.

ABCG2 in peptic ulcer: gene expression and mutation analysis.

The aim of this study was to evaluate the participation of polymorphism at position C421A and mRNA expression of the ABCG2 gene in the development of peptic ulcers, which is a very common and severe disease. ABCG2, encoded by the ABCG2 gene, has been found inter alia in the gastrointestinal tract, where it plays a protective role eliminating xenobiotics from cells into the extracellular environment. The materials for the study were biopsies of gastric mucosa taken during a routine endoscopy. For genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at position C421A, DNA was isolated from 201 samples, while for the mRNA expression level by real-time PCR, RNA was isolated from 60 patients. The control group of healthy individuals consisted of 97 blood donors. The dominant genotype in the group of peptic ulcer patients and healthy individuals was homozygous CC. No statistically significant differences between healthy individuals and the whole group of peptic ulcer patients and, likewise, between the subgroups of peptic ulcer patients (infected and uninfected with Helicobacter pylori) were found. ABCG2 expression relative to GAPDH expression was found in 38 of the 60 gastric mucosa samples. The expression level of the gene varies greatly among cases. The statistically significant differences between the intensity (p = 0.0375) of H. pylori infection and ABCG2 gene expression have been shown. It was observed that the more intense the infection, the higher the level of ABCG2 expression.

[HMGA proteins and their genes as a potential neoplastic biomarkers]. / Bialka HMGA i ich geny jako potencjalne biomarkery nowotworowe.

HMGA proteins and their genes are described in this article. HMGA proteins reveal ability to bind DNA in AT-rich regions, which are characteristic for gene promoter sequences. This interaction lead to gene silencing or their overexpression. In normal tissue HMGA proteins level is low or even undetectable. During embriogenesis their level is increasing. High HMGA proteins level is characteristic for tumor phenotype of spontaneous and experimental malignant neoplasms. High HMGA proteins expression correlate with bad prognostic factors and with metastases formation. HMGA genes expression can be used as a marker of tumor progression. Present studies connected with tumor gene therapy based on HMGA proteins sythesis inhibition by the use of viral vectors containing gene encoding these proteins in antisence orientation, as well as a new potential anticancer drugs acting as crosslinkers between DNA and HMGA proteins suggest their usefulness as a targets in cancer therapy.

ABCB1 expression in peptic ulcer patients and its connection with H. pylori Infection.

Glycoprotein P, encoded by the ABCB1 gene, plays an important role in gastric mucosa homeostasis and can influence the eradication therapy outcome in H. pylori-infected individuals. In the study we examined the ABCB1 expression level in 128 peptic ulcer patients by real-time PCR. There was no correlation between gene expression and the presence of H. pylori or the H. pylori infection intensity. The expression level did not differ between women and men. However, the levels were higher in patients who were over 54 years old than those who were aged up to 54 years old. As ABCB1 expression is largely determined by genetic polymorphisms, in the future, expression data will be related to the patients' ABCB1 genotypes.

C3435T polymorphism of the ABCB1 gene: impact on genetic susceptibility to peptic ulcers.

The functional single nucleotide polymorphism (SNP) C3435T in exon 26 of the ABCB1 gene encoding the xenobiotic transporter P-glycoprotein (P-gp) may influence susceptibility to several diseases, as well as the clinical outcome of treatment with P-gp substrates. Exposure to environmental chemicals is thought to be involved in peptic ulcer pathogenesis and then later in stomach cancer development. About 80% of ulcers are associated with Helicobacter pylori infection, one of the risk factors of stomach cancer. P-gp-transported drugs are used in treatment of H. pylori. Therefore, a lack of effectiveness in eradication therapy can lead to chronic stomach inflammation and promote cancerogenesis. In this study, 196 patients with peptic ulcers divided into two groups with and without H. pylori infection and combined with 96 healthy controls were genotyped for the ABCB1 C3435T SNP. A trend towards higher incidence of the 3435TT genotype among peptic ulcer patients than in controls (p = 0.0983) was observed. Likewise, the 3435T allele was more frequent in groups suffering from peptic ulcers. The association was near to statistical significance (p = 0.0538). Between analyzed genotypes and H. pylori infection, statistically significant dependence was found (p = 0.0372). In addition, the CT genotype was associated with 1.56 times and the TT with 2.45 times higher prevalence of infection compared to the CC genotype. Asimilar association was present in a subgroup of peptic ulcer men (p = 0.0090). The isolated C3435T ABCB1 SNP is not a major factor for genetic susceptibility to peptic ulcer, but in a group of men who suffered from peptic ulcer, this polymorphism seemed to be a risk factor for H. pylori infection development.