melphalan and Hepatitis-B--Chronic

The potential role of chronic inflammation in the development of cancer has been widely recognized. However, there has been little research fully and thoroughly exploring the molecular link between hepatitis B virus (HBV) and hepatocellular carcinoma (HCC).. To elucidate the molecular links between HBV and HCC through analyzing the molecular processes of HBV-HCC using a multidimensional approach.. First, maladjusted genes shared between HBV and HCC were identified by disease-related differentially expressed genes. Second, the protein-protein interaction network based on dysfunctional genes identified a series of dysfunctional modules and significant crosstalk between modules based on the hypergeometric test. In addition, key regulators were detected by pivot analysis. Finally, targeted drugs that have regulatory effects on diseases were predicted by modular methods and drug target information.. The study found that 67 genes continued to increase in the HBV-HCC process. Moreover, 366 overlapping genes in the module network participated in multiple functional blocks. It could be presumed that these genes and their interactions play an important role in the relationship between inflammation and cancer. Correspondingly, significant crosstalk constructed a module level bridge for HBV-HCC molecular processes. On the other hand, a series of non-coding RNAs and transcription factors that have potential pivot regulatory effects on HBV and HCC were identified. Among them, some of the regulators also had persistent disorders in the process of HBV-HCC including microRNA-192, microRNA-215, and microRNA-874, and early growth response 2, FOS, and Kruppel-like factor 4. Therefore, the study concluded that these pivots are the key bridge molecules outside the module. Last but not least, a variety of drugs that may have some potential pharmacological or toxic side effects on HBV-induced HCC were predicted, but their mechanisms still need to be further explored.. The results suggest that the persistent inflammatory environment of HBV can be utilized as an important risk factor to induce the occurrence of HCC, which is supported by molecular evidence.

Topics: Carcinoma, Hepatocellular; Datasets as Topic; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Hepatitis B virus; Hepatitis B, Chronic; Host-Pathogen Interactions; Humans; Immunoglobulin G; Kruppel-Like Factor 4; Liver Neoplasms; Melphalan; MicroRNAs; Protein Interaction Mapping; Protein Interaction Maps; Risk Factors; Transcription Factors

There are several reports describing acute liver decompensation in chronic carriers of HBsAg after withdrawal of chemotherapy or immunosuppressive therapy; recently the same was also reported for chronic HCV-RNA carriers. We retrospectively evaluated hepatic toxicity in eleven patients (6 carriers of HCV-RNA and 5 of HBsAg) autotransplanted at our Institution between March '92 and June '98. Male/female ratio was 7/4, median age 41 years (26-56). Nine patients (4 HBsAg) were affected by non-Hodgkin's lymphoma, 1 (HCV-RNA) by chronic myelogenous leukaemia and 1 (HBsAg) by breast cancer. In the immediate post-transplant period in only 1 patient (HBsAg carrier and affected by breast cancer) was hepatitis documented (at about 1 month from transplant) with an elevation of transaminase levels (x20-40 n.v.). Neither other complications, nor toxic deaths were observed. During the post-transplant follow-up (median 31 months, range 9-83) no hepatic abnormalities were observed. All patients are alive at 56 months (20-122) from diagnosis. Currently 10/11 patients are in complete remission, while 1 patient, affected by follicular centre lymphoma, is alive with disease 52 months from autologous stem cell transplantation. Our study shows that both conventional therapy and high-dose chemotherapy can be performed safely in chronic hepatitis B and C virus carriers.

Topics: Adult; Antineoplastic Agents, Alkylating; Busulfan; Carrier State; Feasibility Studies; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Liver; Lymphoma; Male; Melphalan; Middle Aged; Transplantation Conditioning; Transplantation, Autologous