Analysis of cytosine-adenine repeats in P1 promoter region of IGF-1 gene in peripheral blood cells and cervical tissue samples of females with cervical intraepithelial lesions and squamous cervical cancer.

High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervical cancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine­adenine (CA) repeat polymorphism in the P1 promoter region of the insulin­like growth factor­1 (IGF­1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF­1, and cervical cancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low­grade squamous intraepithelial lesions (L­SILs), high­grade squamous intraepithelial lesions (H­SILs) and invasive cervical cancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF­1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme­linked immunosorbent assay. The identification of the IGF­1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF­1 in the blood serum were observed between H­SILs and controls, only (p=0.047). However, the concentration of IGF­1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H­SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF concentration in blood serum and tissues and the development of cervical cancer.

Evaluation of IL-10 and TGF-ß levels and myeloid and lymphoid dendritic cells in ovarian cancer patients.

AIM: The aim of the study was to evaluate IL-10 and TGF-beta levels in the peritoneal fluid (PF) and plasma of patients with ovarian cancer (n=104), serous cyst (n=32) or normal controls (n=20). IL-10 and TGF-beta levels were correlated to myeloid (M) and lymphoid (L) dendritic cells (DC). MATERIAL AND METHODS: IL- 10 and TGF-beta concentrations were evaluated using the enzyme linked immunosorbent assay (ELISA). The percentage of DC in mononuclear cells was quantified by using flow cytometry. RESULTS: The PF and plasma IL-10 concentrations were significantly higher in epithelial ovarian cancer (EOC) patients when compared to the women with serous cyst (the reference group). Plasma levels of IL-10 were elevated in EOC patients in comparison with the reference and control groups. There were significant differences in the PF and plasma IL-10 levels with respect to tumor stage, grade and histology Significant negative correlations were found between the plasma IL-10 levels, MDC and LDC in the peripheral blood. TGF-beta levels were detected in PF of all EOC patients and were significantly lower when compared with plasma. Plasma levels of TGF-beta were elevated in EOC patients compared with the control group. No significant differences in the PF and plasma TGF-beta levels were noted between EOC patients and the reference group. The authors did not find a correlation between the plasma and PF TGF-beta levels and the percentage of MDC and LDC. CONCLUSIONS: IL-10 production in EOC patients depends on the tumor stage, grade and histological type of the tumor cells. IL-10 may have impact on the percentage of dendritic cells in EOC patients.

SDF-1alpha/CXCL12 and dendritic cells in ovarian cancer microenvironment.

AIM: To evaluate the a-chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 levels in the peritoneal fluid (PF) and plasma of patients with epithelial ovarian cancer (EOC, n=101), serous cyst (n=34) or normal controls (n=20). SDF-1alpha concentrations were correlated to myeloid (M) and lymphoid (L) dendritic cells (DC). MATERIAL AND METHODS: SDF-1alpha levels were analysed using a sensitive enzyme-linked immunosorbent assay (ELISA). DC were evaluated by flow cytometry. RESULTS: The SDF-1alpha concentrations in peritoneal fluid were elevated in the EOC patients in comparison to the patients with serous cyst (the reference group). The PF SDF-1alpha levels were significantly higher in FIGO III and IV patients than in FIGO stage I. There were no significant differences in the PF SDF-1alpha levels with respect to tumor grade or histology Additionally there were no significant differences in the plasma SDF-1alpha levels in EOC patients in comparison with the reference and control groups. The SDF-1alpha levels in the plasma of FIGO stage III patients were significantly higher than that of stage I. Patients with undifferentiated carcinoma had significantly higher plasma SDF-1alpha levels than patients with serous cystadenocarcinoma. No significant differences were noted in the plasma SDF-1alpha levels within different tumor grades. There was no significant correlation between PF and plasma SDF-1alpha levels and the percentage of myeloid and lymphoid DC in the PB and PF of EOC patients. CONCLUSION: SDF-1alpha production in EOC patients may depend on the clinical stage of the tumor. Increased levels of SDF-1alpha and lymphoid DC in the PF of EOC patients may play an important role in the pathogenesis of this disease.