ABSTRACT
Sorafenib (Sor) is a multi-kinase inhibitor. It is recommended for the treatment of advanced hepatocellular carcinoma (HCC). However, Sor has severe and marked side effects. On the other hand, taurine (Tau) has been shown to enhance the therapeutic effects of cancer chemotherapy and also to enhance the function of leukocytes. Here, we aimed to investigate the enhancing efficacy of Sor as well as minimizing its marked side effects by using Tau in combination in an immunological aspect. We evaluated the influence of Sor and Tau combination on the expression pattern of FOXP3 gene in HepG2 cells compared to peripheral blood mononuclear leukocytes (PBMCs) as control normal cells. Also, the levels of TGF-ß and IL-10 released in culture media of both cells were determined. Our results revealed that, Tau reduced cytotoxicity of Sor on PBMC indicated by lactic dehyrogenase (LDH) release assay. In addition, Sor-Tau combination led to FOXP3 down-regulation in hepatic cancer cells (HepG2). The results showed also that, TGF-ß levels decreased significantly in their culture media. In contrary, the cytokine increased in PBMCs culture media. Moreover, IL-10 was significantly elevated in the culture media of both cells. This study could open new avenues for the improvement of therapeutic efficacy of Sorafenib treated HCC patients by using Tau in combination.
Subject(s)
Carcinoma, Hepatocellular/drug therapy , Cell Proliferation/drug effects , Cytokines/metabolism , Leukocytes, Mononuclear/drug effects , Protein Kinase Inhibitors/pharmacology , Sorafenib/pharmacology , Taurine/pharmacology , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cytokines/immunology , Drug Therapy, Combination , Forkhead Transcription Factors/metabolism , Hep G2 Cells , Humans , L-Lactate Dehydrogenase/metabolism , Leukocytes, Mononuclear/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Transforming Growth Factor beta/metabolismABSTRACT
BACKGROUND: A number of hepatocellular carcinoma (HCC) patients have developed resistance against transcatheter arterial chemoembolization (TACE) treatment. In this study, we aimed to develop a panel of microRNAs (miRs) biomarkers to predict clinical outcomes in HCC patients after TACE treatment. METHODS: The expression level of twenty miRs was evaluated in FFPE tissues collected from 33 HCC patients. We selected four differentially expressed miRs in TACE-responders versus non-responders and re-assessed their expression in 51 serum samples. The expressions of miRs associated with overall survival (OS), progression-free survival (PFS), and treatment outcomes were investigated. The diagnostic accuracy of these miRs in predicting patients' response to TACE was also evaluated. RESULTS: The baseline of miR-106b, miR-107 and miR-133b was significantly elevated (pâ¯<â¯.001) in sera of TACE-responders while miR-26a was elevated (pâ¯<â¯.001) in non-responders. miR-26a and miR-133b recorded the highest diagnostic performance as individual classifiers in response to TACE (AUCâ¯=â¯1.0 and 100% sensitivity and specificity). Intriguingly, miR-133b distinguished complete responders from partial responders and non-responders (AUCâ¯≥â¯0.90). The PFS was improved (pâ¯<â¯.05) in the high expression group of miR-31, miR-200b, miR-133b and miR-181a over their low expression group. CONCLUSION: Circulating miR-133b, miR-26a, miR-107 and miR-106 in serum are potential candidates to be utilized as prognostic biomarkers for predication of TACE treatment outcomes in HCC patients.
Subject(s)
Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Liver Neoplasms/blood , Liver Neoplasms/therapy , MicroRNAs/blood , Biomarkers, Tumor/blood , Humans , Real-Time Polymerase Chain Reaction , Treatment OutcomeABSTRACT
BACKGROUND: Hepatocelluar carcinoma (HCC) is a major health problem in Egypt as well as in many countries. Transarterial chemoemoblization (TACE) is a treatment modality applicable to locally advanced HCC beyond surgery or ablative therapies and is associated with survival improvements. The aim of this study was to assess the outcomes of TACE in our center over the past four years. METHODS: This is a retrospective cohort study that included 221 patients with locally advanced HCC treated with TACE in a single center between the years 2007 and 2010. The median age was 57 years with male predominance. Liver cirrhosis, viral hepatitis and Bilharziasis were encountered in 64%, 31% and 8% of patients, respectively. Abdominal pain was the most common presenting symptom (67%). Most cases were diagnosed based on radiology (57%) with a TNM stage I or II (73%) and a median AFP value of 150 ng/mL. RESULTS: 221 patients received 440 cycles of TACE with a median of 2 cycles per patient. Cisplatin and doxorubicin (50mg per cycle, each) were the most commonly used drugs. Impaired liver function was the most common toxicity. Liver cell failure occurred in 17% of patients. An objective tumor response was achieved in 44% of cases. The median overall survival (OS) was 16 months (95% CI, 13-19 months) and the median progression free survival (PFS) was 6 months (95% CI, 4.3-7.8 months). Responding patients, Child-Pugh class A and patients receiving standard doses of chemotherapy had a significantly better OS than their counterparts. Only Child-Pugh class A was associated with significantly longer PFS (p < 0.001). CONCLUSION: TACE produces reasonable responses and fair survival rates in locally advanced HCC but with noticeable toxicities. Proper patients' selection and prompt liver support are mandates for improving TACE outcomes.
