Fusun Ozmen

Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer.

AIM To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their levels and clinicopathological parameters in gastric cancer. METHODS Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry. RESULTS LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic features such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the distribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining. CONCLUSION LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.

Lymph nodes in gastric cancer.

Surgery is the only curative therapy for gastric cancer and controversy still exist on the extend of surgery. As the lymphatic distribution of stomach is very complex, the determination of the actual lymph node involvement is important for making the decision in order to avoid complications. Sentinel node navigation surgery has recently been introduced in gastrointestinal tract cancer. Present article reviews the detection techniques of lymph nodes and significance of lymphadenectomies in gastric cancer. J. Surg. Oncol.

STEAP4 and HIF-1α gene expressions in visceral and subcutaneous adipose tissue of the morbidly obese patients

AIM AND BACKGROUND Obesity is a multifactorial disease in which environmental and genetic factors play an integrated role. Determining such target genes will help to elucidate the mechanisms underlying complex diseases such as obesity and diabetes which are usually seen together. Present study investigates the expression levels of STEAP4 and HIF-1α in visceral and subcutaneous adipose tissue. PATIENTS AND METHODS 30(6M) morbidly obese patients undergoing bariatric surgery were included in the study. The patients were grouped according to the BMI as Group I (BMI <50kg/m(2)) and Group II (BMI ≥50kg/m(2)). Samples from visceral (omentum) and subcutaneous adipose tissues were obtained from each patient and real-time PCR (qPCR) was carried out for STEAP4 and HIF-1α gene expressions. Correlations between expression levels and clinical parameters were analyzed. RESULTS Mean age of the patients recruited to the study was 37.4 (18-64) years. Mean BMI was 46 (36-60) kg/m(2). STEAP4 expression in visceral adipose tissue was significantly higher than subcutaneous tissue. Visceral STEAP4 expression was also found to be reduced with increased BMI. It was also lower in patients with HbA1C over 6. Furthermore, expression of subcutaneous and visceral HIF-1α was significantly higher in Group II. There was a significant correlation between BMI, glycosylated hemoglobin, STEAP4 and HIF-1α gene expression. CONCLUSIONS Obesity and related disease are linked with the fact that there is a low grade inflammation in the adipose tissue of the obese individuals. Counter-regulatory processes such as STEAP4 protein family are overwhelmed by the proinflammatory stimuli. HIF-1α expression is increased due to tissue hypoxia and pro-inflammatory stimuli in the obese individuals, which results in increased visceral STEAP4 expressions.

The roles of epigenetic modifications of proapoptotic BID and BIM genes in imatinib-resistant chronic myeloid leukemia cells.

Abstract In chronic myeloid leukemia (CML), epigenetic modifications such as promoter hypermethylation and inactive histone modification are known mechanisms of drug resistance. In our study, we investigated the roles of promoter hypermethylation of BIM and BID genes and H3K27me3 histone modification on imatinib resistance. We detected higher expression levels of BIM and BID genes and lower expression levels of EZH2, EED2, SIRT1, and SUZ12 genes in imatinib-resistant K562/IMA-3 cells compared to imatinib-non-resistant K562 cells. While we determined the EZH2 and DNMT enzymes as bounded to the promoter of the BIM gene, we did not detect hypermethylation of this promoter. We also found the H3K27me3 histone modification promoter of BIM and BID genes in both cell lines. In conclusion, our results support the notion that DNA promoter methylation may be formed independently from EZH2-H3K27me3 and pro-apoptotic BIM and BID genes are not methyllated in the imatinib resistance of CML cells.

Netrin-1 is associated with macrophage infiltration and polarization in human epicardial adipose tissue in coronary artery disease

BACKGROUND Inflammatory activity originating from the epicardial adipose tissue (EAT) may have a role in coronary artery disease (CAD) pathogenesis. The relationship between macrophage infiltration, polarization in the EAT, and netrin-1 gene expression was investigated. METHODS Macrophage infiltration and polarization were examined by immunohistochemical methods and expression levels of netrin-1, Unc5b, and cytokines related with M1-macrophage subtype (IL-12 and IL-18) were determined by quantitative polymerase chain reaction in subcutaneous and epicardial adipose tissue obtained from patients undergoing coronary artery bypass grafting and non-coronary cardiac surgery. RESULTS CAD patients had higher CD68+ (p=0.005) and CD11c+ (p<0.001) macrophage count in EAT when compared to the controls. CD11c+/CD206+ macrophage ratio, which reflects dominancy of M1-macrophage phenotype, was significantly increased in EAT of CAD patients when compared to that of the controls (p=0.008). CAD patients had significantly higher netrin-1, Unc5b, and IL-18 gene expression in the EAT when compared to the control group (p<0.001, p<0.001, and p=0.006 respectively). Increased macrophage infiltration and polarization were associated with higher netrin-1, Unc5b, and IL-12 gene expression in EAT (p<0.05). CONCLUSIONS Findings suggest a link between enhanced netrin-1 expression in EAT and macrophage infiltration and polarization in patients with CAD.

Current Adjuvant Therapeutic Approaches for Pancreatic Cancer

Pancreatic cancer continues to be the fourth leading cause of death despite advancements in surgical and adjuvant therapeutic approaches. In the present review, the current cytotoxic therapeutic approaches and advanced targeted therapies are objectively discussed with consideration to the current literature.