We aimed to compare the survival benefit of transarterial chemoembolization (TACE) with conservative treatment for patients with advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT), furthermore, to reveal which PVTT types benefit from TACE treatment. From August 2007 to January 2010, a prospective controlled study was performed on consecutive patients with advanced HCC and PVTT. Of a total of 150 patients, 115 were treated with TACE (lipiodol and anticancer agents ± gelatin sponge embolization), and 35 who refused to accept the procedure were treated with conservative treatment. We performed survival analysis of the two treatment groups and then stratified by a new classification of PVTT that was divided into four types. Overall survival was significantly better in the TACE group than in the conservative group (8.67 months vs. 1.4 months, P<0.001). The overall median survival for types I-IV PVTT were 12.0, 8.3, 5.0, and 2.43 months (P<0.01). On subgroup analysis of PVTT, the median survival in the TACE group compared with conservative group for type I, II, III, and IV PVTT was 19.0 months versus 4.0 months, 11.0 months versus 1.43 months, 7.1 months versus 1.3 months, and 4.0 months versus 1.0 months, respectively (P<0.01). The TACE group had significantly better survival than the conservative group for different extent of PVTT. TACE is an effective treatment mode compared with conservative treatment for HCC and PVTT and may provide a significantly better survival benefit for different extent of PVTT.
The aim of the present study was to determine the effect of the long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) in chemoresistance of non-small cell lung cancer (NSCLC) cells. Expression of lncRNA BLACAT1, microRNA (miR)-17, autophagy-related protein 7 (ATG7), multidrug-resistance protein 1 (MRP1), and the autophagy-associated proteins light chain 3 (LC3)-II/LC3-I and Beclin 1 were detected using the reverse transcription-quantitative polymerase chain reaction and western blot analysis. Cell viability was determined using an MTT assay. The interaction between BLACAT1 and miR-17 was determined using RNA immunoprecipitation and RNA pull-down assays. A cisplatin (DDP)-resistant NSCLC cell A549/DDP xenograft model in nude mice was established to investigate the effect of BLACAT1 on the chemoresistance of NSCLC cells. Compared with in DDP-sensitive NSCLC cells, expression of BLACAT1, ATG7, MRP1, LC3-II/LC3-I and Beclin 1 was significantly upregulated in DDP-resistant NSCLC cells, whereas miR-17 was downregulated in DDP-resistant NSCLC cells. Short interfering RNA against BLACAT1 decreased the viability of DDP-resistant NSCLC cells. In addition, BLACAT1 interacted with miR-17, and negatively regulated miR-17. BLACAT1 promoted ATG7 expression through miR-17, and facilitated autophagy and promoted chemoresistance of NSCLC cells through miR-17/ATG7. Finally, in vivo experiments indicated that inhibition of BLACAT1 ameliorated the chemoresistance of NSCLC. BLACAT1 was upregulated in DDP-resistant NSCLC cells, and promoted autophagy and chemoresistance of NSCLC cells through the miR-17/ATG7 signaling pathway.
Raltitrexed has shown efficacy and safety in many tumor types; however, the clinical data on the treatment of hepatocellular carcinoma is rare. In this report, we aim to assess the efficacy and safety of raltitrexed plus oxaliplatin (OXA)-based transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (uHCC). Patients with uHCC were recruited from multi-centers in China and assigned randomly to raltitrexed+OXA-based (n=76), fluorouracil+OXA-based (n=76), and doxorubicin+OXA-based (n=75) TACE treatment. The primary end point was overall survival (OS). Tumor response was assessed using response evaluation criteria in solid tumors (RECIST), modified response evaluation criteria in solid tumors (mRECIST), and European Association for the Study of the Liver criteria (EASL). Safety and toxicity were evaluated using the National Cancer Institute Common Toxicity Criteria. The raltitrexed group showed a better disease control rate evaluated using RECIST (raltitrexed vs. fluorouracil vs. doxorubicin: 96.1 vs. 84.2 vs. 86.7%, P=0.05) and a better overall response rate on the basis of mRECIST (67.1 vs. 47.4 vs. 50.7%, P=0.03) and EASL (67.1 vs. 47.4 vs. 49.3%, P=0.02). The median OS and median progression-free survival (PFS) were higher in the raltitrexed group (median OS: 13.4 vs. 9.6 vs. 8.5 months; median PFS: 6.7 vs 4.9 vs 4.6 months). The most common toxicities included elevated aspartate aminotransferase (78.9 vs. 86.8 vs. 81.3%) and abdominal nonspecific pain (68.4 vs. 81.6 vs. 78.7%). No significant differences were found in the overall number of patients who experienced any toxicity. Raltitrexed plus OXA-based TACE suggested a safe and efficacious regimen in uHCC patients. The results warrant further clinical investigation.
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