Mesenchymal Stem Cells Combined With IFNγ Induce Apoptosis of Breast Cancer Cells Partially Through TRAIL.

BACKGROUND: Mesenchymal stem cells (MSCs) have gained remarkable attention because of their ability to dualistically regulate tumor growth. The main objective of this study was to evaluate the apoptotic effects of human bone marrow-derived (hBM) MSCs in combination with interferon gamma (IFN-γ) on MCF-7 breast cancer cells, and to determine the cytokines involved in the apoptotic process. MATERIALS AND METHODS: hBM-MSCs were co-cultured with MCF-7 cells either directly and indirectly for 72 h in-vitro. Levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), apoptosis and cytokines were analyzed. RESULTS: hBM-MSCs increased the apoptosis of MCF-7 cells partially through TRAIL in vitro. IFN-γ enhanced the apoptotic effect of hBM-MSCs (p<0.001). CONCLUSION: hBM-MSCs in combination with IFN-γ might be a suitable therapy for 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.

Distribution and Effects of CDKN2 p16 540 C>G and 580 C>T, and MDM2 SNP309 T>G Polymorphisms in Patients with Primary Brain Tumors.

BACKGROUND/AIM: Primary brain tumors are unique tumors due to their different pathobiological behavior, while they rarely metastasize outside the central nervous system. Regarding the oncogenesis of primary brain tumors, it was shown that changes in functions of p16 and mouse double minute 2 homolog (MDM2) are related to tumor pathogenesis by enhancing cell proliferation and malign development. The present study aims to evaluate the possible associations between cyclin-dependent kinase 2 (CDKN2) p16 540 C>G and 580 C>T, MDM2 single nucleotide polymorphism 309 (SNP309) T>G polymorphisms and primary brain tumor. MATERIALS AND METHODS: Using polymerase chain reaction-restriction fragment length polymorphism technique, we determined SNPs in 67 patients with primary brain tumors and 71 healthy volunteers without malignancy. RESULTS: The frequency of CC genotype for CDKN2 p16 540 C>G was significantly two-fold higher (p<0.001) and possessing a C allele conferred a ~7-fold increased risk (p=0.005) of primary brain tumor. We also found that the CC genotype produced a higher ~4-fold risk of glioma (p=0.001) and the G allele had a possibly protective role against meningioma (~4.8-fold reduced risk, p=0.001). We found no significant associations for CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants between cases and controls. CGT haplotype was significantly less frequent in patients with primary brain tumors and glioma cases (p=0.009 and p=0.028, respectively) than controls. CGG haplotype was significantly less frequent in patients with meningioma versus the control group (p=0.023). CONCLUSION: These findings show that CDKN2 p16 540 C>G, CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants and their haplotypes may be risk factors for the development of primary brain tumors, especially of glioma.

Individual and Combined Effects of CTLA4-CD28 Variants and Oxidant-Antioxidant Status on the Development of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most frequent cancer worldwide. Research has revealed the contributions of the immune system and anti-inflammatory pathways in the development of cancer. The balance between cluster of differentiation 28 (CD28) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) signaling is important for the regulation of immune responses. The oxidant-antioxidant balance by sustaining redox control via several defense mechanisms is also an important factor for the progression of cancer. The aim of the present study was to determine the distribution of CTLA4/CD28 variants and oxidant-antioxidant status in patients with CRC. MATERIALS AND METHODS: This study enrolled 80 patients with CRC and 115 healthy controls. We used a spectrophotometric assay to detect the levels of lipid peroxidation products malon dialdehyde (MDA) and lipid hydroperoxide (LHP), and measured the concentration of protein damage products, advanced oxidation protein products (AOPP) and protein carbonyl (PCO). Additionally, antioxidant levels were detected by measuring copper, zinc, superoxide dismutase (Zn-Cu SOD) and total thiol (T-SH) levels, and advanced glycation end-products (AGEs). The CTLA4 -318C>T, CTLA4 49A>G and CD28C>T genotypes were determined by using restriction enzymes. RESULTS: AOPP and PCO levels were increased in patients with CRC as well as those of LHP, MDA and AGE, while the levels of antioxidants such as Cu-Zn SOD and T-SH were lower. Lower serum levels of CTLA4 and higher serum levels of CD28 were detected in patients and, an association of the CTLA4 -318C/T polymorphism was found in patients with CRC. CONCLUSION: Our oxidative stress was increased in patients with CRC, suggesting the contribution of this disturbed oxidative status to serum CTLA4 and CD28 levels, and to the pathogenesis of CRC.