Levels of chemokine receptors expressed on peripheral blood T lymphocytes of Egyptian patients with hepatocellular carcinoma.

CC chemokine receptors (CCR) have an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 and CCR5 are highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we estimated the surface expression of chemokine receptors CCR1 and CCR5 on the lymphocytes of peripheral blood from patients with HCC in an attempt to identify their roles in tumorigenesis. The study was conducted on 52 patients of which, 24 of them with confirmed HCC and 28 with chronic hepatitis C virus infection. In addition, 20 apparently healthy controls with matched age and sex were also included in the study. All patient and control groups were subjected to the following: thorough history taking, clinical examination, abdominal ultrasonography and fine needle liver biopsy for patient's group when needed, complete blood count, liver function tests, viral markers for hepatitis B and C, serum alpha fetoprotein and flowcytometric detection of chemokine receptors CCR1 and CCR5 on peripheral blood T lymphocytes. The expression of chemokine receptors CCR1 and CCR5 on CD4+ and CD8+ T lymphocytes was significantly less in HCC and hepatitis C patient groups as compared to control group. Moreover, a significant decrease in the levels of CCR1 and CCR5 on CD8+ T lymphocytes was detected in HCC patients compared to patients with chronic HCV; however, it was not statistically significant for CD4+ cells. Furthermore in HCC patients, levels of CCR1 and CCR5 were significantly less in patients with large tumor size than small sized tumor. Data obtained showing reduced surface expression of CCR1 and CCR5 on CD4 and CD8 T lymphocytes reflect their possible role in altering the host's immune defense and disease pathogenesis, thus may be helpful for therapy design to ameliorate disease progression.

Gene deletion of glutathione S-transferase M1 and T1 and risk factors of hepatocellular carcinoma in Egyptian patients.

Genetic polymorphic forms of glutathione-S-transferase (GST) were found to be associated with risk for various malignancies. The present study was undertaken to evaluate the risks-associated with GSTT1 and GSTM1 gene polymorphisms and hepatitis virus-related hepatocellular carcinoma (HCC) in an Egyptian population. Sixty patients diagnosed with HCC were subdivided into 3 groups: group I, 31 patients with HCC and HCV-related cirrhosis; group II, 19 patients with HCC and HBV- related cirrhosis and group III, 10 patients with HCC and cirrhosis of non-viral aetiology. Fifty cirrhotic patients without HCC were also included as a control group. Patients and controls were subjected to thorough history taking and clinical examination, liver function tests, hepatitis viral markers, anti-Bilharzial antibodies and serum alpha fetoprotein levels. Rectal snip for the diagnosis of active Bilharziasis, abdominal ultra-sonography and CT abdomen were performed for patients as well as liver biopsy when indicated. GSTM1 and GSTT1 were tested in peripheral blood mononuclear cells by PCR. GSTM1 gene deletion (null genotype) was observed in 56.7% of HCC patients and in 38% of the control group (P < 0.05). The GSTT1 null genotype was detected in 41.7% of the HCC patients compared to 22% of control patients (P < 0.05). The double genes null of GSTM1 and GSTT1 was detected in 10% of all HCC patients and in 2% of the control cases (P < 0.05). Comparison between the subgroups of HCC revealed that the GSTM1 null genotype was detected in 67.7% of group I, 47.4% of group II and 40% of group III cases, with a significant increase in group I compared to other HCC subgroups (P < 0.001). In addition, the GSTT1 null gene was observed in 35.5% of group I, 57.9% of group II, and 30% of group III, with a significant increase in group II (P < 0.01). In conclusion, our findings suggest that GSTM1 and GSTT1 polymorphisms appear to be associated with a modest increase in the risk of HCC in Egyptian patients. Studies with a larger sample size are still required to confirm the results and to explore the association with risk factors other than HCV and HBV in this population.