Improvement of Survival Rate for Patients with Hepatocellular Carcinoma Using Transarterial Chemoembolization in Combination with Three-Dimensional Conformal Radiation Therapy: A Meta-Analysis.

BACKGROUND Transarterial chemoembolization (TACE) has been used alone or in combination with three-dimensional conformal radiation therapy (3DCRT) for treating hepatocellular carcinoma (HCC). The overall survival rate of HCC patients undergoing both treatments, however, has not been systematically studied. The aim of this meta-analysis-based study was to evaluate the overall efficacy of the combined therapy or monotherapy, thereby providing information for clinical treatment. MATERIAL AND METHODS We searched Google Scholar, PubMed, and Chinese National Knowledge Infrastructure (CNKI) for eligible studies, and a total of 17 case-control studies (including HCC patients treated by TACE plus 3DCRT or TACE alone) were included to perform the meta-analysis. Based on the available data, we assessed the improvements of 1-year, 2-year, and 3-year survival rate for the combination therapy of TACE and 3DCRT or TACE alone. Furthermore, the analysis was also stratified by the tumor response: complete response (CR), partial response (PR), no response (NR) and progressive disease (PD). Statistical analysis was performed using STATA 12 (Stata Statistical Software: Release 12). RESULTS The results show that HCC patients receiving combination therapy have significantly increased overall survival rate when compared to those receiving TACE alone (1-year survival rate: OR=1.95, 95% CI 1.54-2.47, p=7.3×10^-8; 2-year survival rate: OR=1.87, 95% CI 1.49-2.34, p=1.6×10^-7; 3-year survival rate: OR=2.00, 95% CI 1.52-2.64, p=1.8×10^-6). CONCLUSIONS Assessment of tumor response demonstrates that the combination therapy can efficiently increase the tumor response rate (CR+PR: OR=2.29, 95% CI 1.70-3.08, p=1.1×10^-7), with a lower rate of subsequent tumor development (PD: OR=0.25, 95% CI 0.15-0.40, p=5.5×10^-8).

Advances in the application of Let-7 microRNAs in the diagnosis, treatment and prognosis of leukemia.

The lethal-7 (Let-7) family of microRNAs (miRNAs) controls the process of development and differentiation, but is also related to the occurrence of tumors and a poor prognosis of patients with tumors. Thus, a more comprehensive exploration of its functions will provide further insights into these processes, and may promote the diagnosis and treatment of tumors. Leukemia is a type of progressive malignant disease, and its pathogenesis involves a variety of epigenetic factors. Amongst the several related epigenetic factors, the Let-7 miRNAs are an important family of molecules that play a crucial role in maintaining a variety of critical biological processes, including development, differentiation and proliferation. In the present study, the role of Let-7 as a tumor suppressor gene and oncogene is reviewed, and the complex regulatory functions of several Let-7 family members in different subtypes of leukemia are described. The current body of knowledge thus far indicates that Let-7 is not only a potential diagnostic and prognostic marker of leukemia, but also a potential therapeutic target for the treatment of affected patients, with particular potential when targeted by adjuvant treatments alongside traditional treatment to improve their survival rate.

Down-regulation of TRRAP-dependent hTERT and TRRAP-independent CAD activation by Myc/Max contributes to the differentiation of HL60 cells after exposure to DMSO.

Myc/Max/Mad often play pivotal roles in the proliferation, apoptosis, differentiation and cell cycle progress of leukemia cells. Myc and Mad are known to be unstable proteins and their expression is tightly regulated throughout cell cycle progression and differentiation. Usually, c-Myc expression is implicated in cell growth and proliferation, and the deregulated expression of c-Myc in both myeloid leukemia cells and normal myeloid cells not only blocks terminal differentiation but also its associated growth arrest. HL60 cells could be induced to differentiate into mature granulocytes by DMSO in vitro, but the mechanism of this effect has not been elucidated clearly. We proposed the hypothesis that down-regulation of c-Myc expression by DMSO contributed to the differentiation of HL60 cells by way of activating target genes hTert and CAD. The results showed that c-Myc expression was down-regulated in differentiated HL60 cells but not in exponentially-growing HL60 cells, without or with the target gene activation of hTert and CAD, respectively. Further study indicated that hTert activation is TRRAP-dependent while CAD activation is TRRAP-independent. On the other hand, up-regulation of P(21) and P(27) and down-regulation of cyclinA and cyclinE also play important roles in induction of the terminal differentiation of HL60 cells. Our results support the hypothesis that c-Myc expression and activation of target genes for hTert and CAD play critical roles in the proliferation of HL60 cells, while down-regulation of c-Myc expression and activation of target genes for hTert and CAD contributed to the terminal differentiation of HL60 cells after exposure to DMSO in vitro.