Migration and invasion of drug-resistant lung adenocarcinoma cells are dependent on mitochondrial activity

A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated. Cells with a higher MMP exhibited greater migration and invasion than those with a lower MMP. Cells that survived treatment with cisplatin, a standard chemotherapeutic drug for lung adenocarcinoma, exhibited increased MMP and enhanced migration and invasion compared with parental cells. Consistent with these findings, inhibition of mitochondrial activity significantly impeded the migration and invasion of cisplatin-resistant cells. RNA-sequencing analysis indicated that the expression of mitochondrial complex genes was upregulated in cisplatin-resistant cells. These results suggested that drug-resistant cells have a greater MMP and that inhibition of mitochondrial activity could be used to prevent metastasis of drug-resistant lung adenocarcinoma cells.

Waldenstrom's Macroglobulinemia: Clinical Course and Outcome of 14 Cases / 대한혈액학회지

BACKGROUND: Waldenstrom's Macroglobulinemia (WM) is a low grade lymphoproliferative disorder that produces monoclonal immunoglobulin M (IgM). Information on the clinical feature and outcome of Korean patients with WM is scanty. METHODS: Patients with WM newly diagnosed at 5 university hospitals in Daegu and Gyeongju from 1990 to 2002 were enrolled. Data on 14 patients were retrospectively analyzed. RESULTS: The median age at diagnosis was 66 years (range: 48~77) and the male/female ratio was 6:1. All patients except one were symptomatic at presentation. Anemia was observed in all patients and beta2 microglobulin was elevated in 90% of patients. Overall response rate was 45% in the patients treated with alkylating agent and steroid. The median survival of our patients was 39 months (95% confidence interval:13.7~64.3 months) and the only factor associated with poor survival was albumin level by univariate analysis. CONCLUSION: Incidence of WM was lower and the median survival of our patients was shorter than that of Western reports. Further studies are needed to confirm prognostic factors and risk adapted treatment guideline of Korean WM patients.