Hepatocellular carcinoma (HCC) has a high recurrence rate, and patients exhibit poor survival mainly because intrahepatic metastasis is common. We previously reported that let-7c down-regulation is significantly associated with poor differentiation level in HCC. In the present study, we demonstrate that miR-199a-5p and let-7c are frequently down-regulated in HCC cells and tissues, and low expression of miR-199a-5p is correlated with tumor size, liver envelope invasion. Furthermore, miR-199a-5p and let-7c cooperatively inhibit HCC cell migration and invasion in vitro. MAP4K3 is identified as the direct target of miR-199a-5p and let-7c and this regulation is further confirmed by luciferase reporter assays and Western blotting. In addition, MAP4K3 functions as a metastasis promoter since the results demonstrate that MAP4K3 could promote HCC cell migration and invasion. We also find that miR-199a-5p and let-7c increase the sensitivity of HCC cells to sorafenib.ConclusionsWe report that miR-199a-5p and let-7c cooperatively and efficiently inhibit HCC cell migration and invasion by targeting the metastasis promoter MAP4K3 and MAP4K3-mediated drug sensitization, suggesting that the use of miRNAs and sorafenib in combination therapy may be a powerful approach to the treatment of HCC.
BackgroundHER2 mutations are identified in approximately 2% of non-small-cell lung cancer (NSCLC) cases and are predominantly observed in non-smokers, females, and adenocarcinoma patients. Although afatinib is recommended for treating NSCLC patients with HER2 mutation, the therapy is most efficacious in patients harboring HER2 exon 20 insertions, especially the in-frame insertion YVMA. Research on the treatment of the extracellular domain mutation is relatively rare.Case presentationWe discuss a 76-year-old Chinese man with a heavy-smoking history who was diagnosed with stage IV squamous cell lung carcinoma. First-line treatment with the angiogenesis inhibitor endostar and systemic chemotherapy with docetaxel plus cisplatin were administered, but the patient ceased treatment because of chemotherapy-induced adverse events. Based on the test result from an amplification refractory mutation system PCR, EGFR-inhibitor icotinib was prescribed, but there was still no evidence of a response. Then, next-generation sequencing identified an HER2 S310Y mutation, and afatinib therapy resulted in a gradual, but substantial reduction in tumor size.ConclusionThis is the first published case report of the successful management of HER2 S310Y mutation squamous cell lung carcinoma with afatinib. Considering the fact that this rare HER2 mutation clinically benefited from afatinib treatment, attention should be paid to the incidence of HER2 in NSCLC patients with inconsistent histological characteristics compared with those previous published. With the guidance of a precise diagnosis, we should realize the significance of other HER2 gene mutations and next-generation sequencing as a diagnostic method.
The clinical significance of palliative interventional therapy in the management of patients with advanced hilar cholangiocarcinoma (HCCA; stages III–IV) has yet to be studied. The present work was aimed to compare the clinical outcomes of the patients treated with surgery or interventional therapy.A total of 90 patients with advanced HCCA, who admitted Fuyang First People's Hospital from May 2015 to February 2016, were enrolled. Forty-five of them were assigned to the experimental group receiving biliary drainage as the interventional therapy, and the remaining 45 patients were designated as the conventional group receiving radical/palliative surgery. Before and after the treatment total bilirubin from blood was measured. The length of treatment and medical cost were also examined. All patients were followed up for at least 1 year after the treatment.For both the experimental and conventional groups, the serum bilirubin levels after treatment were significantly lower than those before treatment (P < .05); however, no significant differences between groups were seen. There were no significant differences between experimental and conventional groups in the incidence of postoperative complications and survival outcomes. Of note, the length of treatment of the experimental group was substantially shorter than that of the conventional group (P < .05). The medical expense of the experimental group was only about one-third of that of the conventional group (P < .05).Although the interventional therapy does not improve patients’ survivals and reduce the incidence of complications, it significantly shortens the treatment length, reducing substantially the medical expense. This finding provides new insights into the treatment strategy for patients with advanced HCCA.
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