Investigation of possible associations between tryptophan/kynurenine status and FOXP3 expression in colorectal cancer.

Tryptophan metabolism in the tumor microenvironment exerts immunosuppressive effects by affecting the anti-tumor functions of immune cells. The immunosuppressive roles of tryptophan and tryptophan metabolites and their effects on the FOXP3 gene, highly expressed in regulatory T cells (Tregs), are remarkable. Our study aimed to investigate the relation between tryptophan metabolism and the transcription factor FOXP3 gene in colorectal cancer (CRC). Patients with CRC (n = 159) and controls (n = 112) were included in the study. The FOXP3 rs3761548 variant genotyping from the isolated genomic DNA was performed by PCR-RFLP. FOXP3 gene expression was determined by Q-PCR in RNAs isolated from resected tissues at the same time. Serum tryptophan, kynurenine, kynurenic acid levels of the cases were determined by HPLC. In serum samples with CRC, tryptophan level was 14.32 ± 1.09 µmol/L, kynurenine level was 1.33 ± 0.02 µmol/L, and the kynurenic acid level was 0.01 ± 0.001 µmol/L. The level of tryptophan was found to be low in CRC compared to control (p < .001). In cases with CRC, CC genotype (p = .048) and C allele (p = .012) frequency for FOXP3 rs3761548 were higher than the control group. It was found that the expression level of the FOXP3 gene was approximately 44 times higher in the advanced tumor stage (T3 + T4) than in the early tumor stage (T1 + T2) (p = .021).We suggest that there may be a possible relationship among serum TRP, TRP metabolites (KYN, KYNA) levels, FOXP3 gene expression, and FOXP3 gene variants in CRC pathogenesis.

Morgagni's Hernia: Analysis of 21 Patients with Our Clinical Experience in Diagnosis and Treatment.

A Morgagni's hernia is a congenital defect found in the anterior aspect of the diaphragm between the costal and the sternal portions of this muscle. This defect is also referred to as the space of Larrey. It has been reported that 70% of patients with Morgagni's hernia are female, 90% of the hernias are right-sided, and 92% of the hernias have hernia sacs. This type of hernia is a rare clinical entity and accounts for 3% of all surgically treated diaphragmatic hernias. There are no large retrospective or prospective studies on this topic. This type of hernia is a rare type among adults without a well-described prevalence and without well-established definitive management strategies. There are also few clinical reports about this clinical entity and its surgical treatment. We treated 21 patients with Morgagni's hernia in a 12-year period, and we report our experience while discussing the surgical treatment of this disease. We performed a retrospective review of the 21 patients who were operated between 2003 and 2015. These patients had undergone surgical repair of Morgagni's hernia. For each subject, demographic data, symptoms of presentation, physical examination findings, preoperative imaging studies and diagnosis, and surgical procedures were documented. Location of the hernia sac and its contents, postoperative complications, and duration of hospital stay were recorded and evaluated. Twelve patients were females and nine were males. The mean age of patients was 63.85 years. Dyspnea was the most prominent symptom in our patients. Morgagni's hernias were located on the right side in 19 patients and on the left side in 2 patients. Chest X-ray in 10 patients and abdominal computerized tomography in 17 patients were the major diagnostic tools. Four patients were operated as emergency while others underwent elective surgery (17 patients). Twelve patients were operated with laparoscopy and the remaining nine were operated with the conventional open abdominal technique. Hernia sacs were observed in all of the patients and removed except in four of them. The omentum and the transverse colon were the most commonly seen organs in hernia sacs. Hernia defects were repaired with primary sutures in four patients (all open cases) and primary closure supported with mesh in six patients (four laparoscopic, two open cases). In the remaining 11 patients, hernia defects were closed with synthetic meshes (eight laparoscopic, three open cases). Mean postoperative hospital stay was 9.8 days. No recurrence was observed in any patients. Only one of our patients died during follow-up. In Morgagni's hernias, surgical intervention is necessary as the hernia may cause complications such as strangulation of the colon or intestines. A laparoscopic approach has increased its popularity in recent years because of the well-known advantages of laparoscopy.

Association of CTLA4 and CD28 Gene Variants and Circulating Levels of Their Proteins in Patients with Breast Cancer.

BACKGROUND/AIM: Breast cancer is one of the most common and lethal types of cancer among women. We focused on the importance of the immune system in the etiology of breast cancer by investigating critical polymorphisms of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and cluster of differentiation 28 (CD28) gene, and circulating levels of these proteins. MATERIALS AND METHODS: A total of 79 patients with breast cancer and 76 healthy controls were enrolled. Molecular assessment of CTLA4 (rs231775&rs5742909) and CD28 (rs3116496) variants were determined with polymerase chain reaction restriction fragment length polymorphism techniques. Circulating levels of soluble forms of CTLA4 and CD28 were analyzed by ELISA. RESULTS: Although no significant association was found between study groups, CTLA4 +49AA genotypic frequency, and sCTLA4 and sCD28 levels were higher in patients. Some clinicopathological features were also related with CTLA4 and CD28 variants and blood levels. CONCLUSION: While CTLA4 +49AA genotype is increased in patients with breast cancer, the CTLA4 -318T allele may have a prognostic value. In addition, sCTLA4 and sCD28 can be used for diagnostic purposes in patients with breast cancer.

LGALS3 and AXIN1 gene variants playing role in the Wnt/ ß-catenin signaling pathway are associated with mucinous component and tumor size in colorectal cancer.

The Wnt pathway alterations have been identified in colorectal and many other cancer types. It has been reported that galectin-3 (which is encoded by the LGALS3 gene) alters the signaling mechanism in the Wnt/ ß-catenin pathway by binding to ß-catenin in colon and other cancers. AXIN1 is mainly responsible for the assembly of the ß-catenin destruction complex in the Wnt pathway. This study investigated the relationship of rs4644 and rs4652 variants of the LGALS3 gene and rs214250 variants of the AXIN1 gene to histopathological and clinical properties. Our study included a total of 236 patients, of whom 119 had colorectal cancer (42 women, 77 men) and 117 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific oligonucleotide (ASO) PCR methods were used. In addition, the serum galectin-3 level was studied with the enzyme-linked immunosorbent assay (ELISA) method. For the rs4644 variant of the LGALS3 gene, the CC genotype a mucinous component was significantly more common than those without a mucinous component (p=0.026). C allele frequency of the rs214250 variant of the AXIN1 gene was significantly correlated to tumor size in the advanced tumor stage (p=0.022). The CCAACT haplotype was more common in colorectal cancer patients (p=0.022). Serum galectin-3 level was higher in the patient group compared to the control group (5.9± 0.69 ng/ml vs. 0.79±0.01 ng/ml; p<0.001). In conclusion, variants of LGALS3 and AXIN1 genes affect tumor sizes and the mucinous component via Wnt/ ß-catenin pathway in the pathogenesis of colorectal cancer.

Possible relationship between the resistin gene C-420G polymorphism and colorectal cancer in a Turkish population.

BACKGROUND/AIMS: In recent years, with improvements in genotyping, a possible relationship between obesity-related gene polymorphisms and colorectal cancer (CRC) has been studied. The promoter region C-420G of the resistin gene is believed to have an important role in the development of malignancy. We prospectively evaluated the possible effect of the resistin C-420G polymorphism on the risk and prognosis of CRC. MATERIALS AND METHODS: One hundred twenty-three patients with CRC and 79 healthy individuals were included in the study. Blood samples were genotyped, and the relationship between the resistin C-420G polymorphism and demographic characteristics and tumor features was evaluated. RESULTS: No statistically significant difference was found in genotype distribution between the patient and control groups and among patients in the means of gender, biochemical findings, and tumor characteristics (p>0.05). CONCLUSION: The relationship between the C-420G polymorphism and various diseases has been evaluated in many studies to date. With the increased importance of obesity in etiopathogenesis, studies have focused on CRC. According to our results, the GG genotype may be associated with a decreased CRC risk. Our study is important because to our knowledge, it is the first one to be conducted in a Turkish population to date, but we believe that more patients and controls are needed to obtain statistically significant results.

Analyses of EGF A61G Gene Variation and Serum EGF Level on Gastric Cancer Susceptibility and Clinicopathological Parameters.

BACKGROUND: Epidermal growth factor (EGF) induces various biological signaling pathways, including proliferation and differentiation and it is the natural ligand of the epidermal growth factor receptor (EGFR) which is a member of tyrosine kinase transmembrane receptor family. EGF and EGFR control important processes in carcinogenesis and several differences in this signaling pathway are very common in certain types of cancers. In present study, we examined EGF A61G gene polymorphism as a marker of risk and progression in gastric cancer. MATERIALS AND METHODS: A total of 84 patients with gastric cancer and 146 control individuals were enrolled in the current study. EGF A61G gene variation was genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The distribution of EGF A61G genotypes were different between patients with gastric cancer and controls (p=0.039). Serum EGF levels in gastric cancer cases were significantly lower than those in controls (p=0.012). There were no correlations between the serum EGF levels according to EGF A61G genotype and allelic distributions in patients with gastric cancer. CONCLUSION: Our findings suggested that EGF A61G gene variations and EGF serum levels might be associated with the risk of gastric cancer.