الفهرس 
HEPATOCELLULAR CARCINOMA (HCC)Only 14 pages are availabe for public view
 |  | from | 210 |  |  |
| | | from | 210 | | |
Abstract
Hepatocellular carcinoma is the third most common cause of cancer death in the world. It results in 598,000 deaths per year worldwide. Because of its poor prognosis, this number of deaths is almost the same as the number of cases being diagnosed each year (626,000)( McGlynn and London , 2005 ).
The natural history of hepatocellular carcinoma depends on the severity of underlying chronic liver disease, tumor characteristics and the efficacy of treatment interventions. Beside these features a number of biological markers including cytokines and growth factors have been demonstrated to be increased in the sera of patients with hepatocellular carcinoma and may be associated with a poor prognosis ( Talwalkar and Gores , 2004 ).
The pro-inflammatory environment created by cytokines and chemokines is thought to play a major role in the promotion of tumor development and progression. There are multiple mechamisms by which inflammation and cytokines might result in tumor development including promotion of cell survival and proliferation, tumor cell differentiation and cell migration (Balkwill and Mantovani , 2001).
The level of serum IL-8 was markedly elevated in most patients with HCC compared with healthy subjects. A high serum IL-8 level was observed more frequently in patients with tumor > 5cmm in diameter and advanced tumor stage (p TNM stages ІІІ or ІV ). Serum IL-8 levels were also found to be significantly correlated with tumor progression, venous invasion and survival. These data suggested that serum IL-8 might be useful in clinical setting to predict venous invasion and advanced tumor stage ( Ren et al . , 2003 ).
Serum IL-8 levels increased significantly in patients with poor prognosis and whose survival periods were less than 1 year, as compared with patients with better prognosis. When we performed multivariate regression analysis of possible prognostic factors, IL-8 as well as platelet counts and albumin levels were found to be a significant factors. These findings suggest that serum IL-8 can be a marker predicting the prognosis of patients with HCC ( Tachibana et al . , 2007 ).
Increased levels of interleukin-10 have been described as a negative prognostic indicator for survival in patients with various types of cancer. IL-10 exerts tolerogenic and immunosuppressive effects on dendritic cells (DCs) which are crucial for the induction of an antitumor immune response ( Beckebaum et al . , 2004 ).
Plasma IL-10 levels are frequently elevated in HCC patients but not in patients with benign liver disease or non-HCC tumors. IL-10 may be especially helpful in identifying a subset of HCC patients with low AFP level, may serve as complementary tumor marker that contribute to the differential diagnosis ( Hsia et al . , 2007 ).
The immune mechanisms of IL-12-mediated tumor killing might be mainly attributed to the activation of DCs from which IL-12 might function by : (1) stimulating γ-interferon (IFN-γ) production from NK and T cells and (2) promoting the cellular immune responses by facilitating the proliferation and activation of Th1 cells. ( Banchereau et al . , 2001 ).
The non-immune mechanisms of IL-12-mediated tumor killing have been identified and the most prominent is its ability to inhibit tumor angiogenesis in vivo. In addition to enhancing tumor killing, the activation of Th1 responses has been shown to play an important role in the successful treatment of viral hepatitis B and C as well as in viral clearance of acute hepatitis C ( Tsai et al . , 2003 ).
Recent results show that in situ tumor therapy with co-administration of granulocyte macrophage -colony stimulating factor (GM-CSF) and IL-12 synergistically reduces tumor volumes, compared to single cytokine gene therapy and that NK cells are the main effector cells responsible for tumor regression in the IL-12 mediated gene therapy, whereas, CD8+ T cells, NK cells and possibly macrophages as well are the major effectors involved in the ( IL-12 +GM-CSF ) combination therapy, which leads to significantly high levels of IFN-γ secretion, the NK cells were believed to be one of the major sources of IFN-γ production ( Chang et al . , 2007 ).
IL-18 is also up-regulated in patients with hepatitis C virus infection, which is the most common underlying disease in HCC. The IL-18 receptor was expressed in both hepatocellular carcinoma tissues and two cell lines. The expression of IL-18 receptor in tumor tissues was a significant predictor of a poor outcome suggesting that IL-18 favorably affects tumor viability ( Asakawa et al . , 2006 ).
Frequently augmented IL-18 levels are directly associated with cancer diseases progression and aggressiveness and correlate with tumor stage, clinical outcome and survival, moreover, in some types the increase of IL-18 may indicate metastatic recurrence risk ( Vidal-Vanaclocha et al . , 2006 ).
Recent data demonstrated that serum IL-18 levels in patients with HCC correlated with advanced tumor stage classified by Okud’s criteria and the presence of venous invasion. Serum IL-18 level also exhibited an independent predictor of prognosis in patients with HCC ( Tangkijvanich et al . , 2007 ).