Reactive oxygen species mediate oxaliplatin-induced epithelial-mesenchymal transition and invasive potential in colon cancer.

Therapeutic benefits offered by common chemotherapy drugs, such as oxaliplatin, are limited due to the development of resistance, which contributes to treatment failure and metastasis. The epithelial-mesenchymal transition (EMT) is a key event contributing to the development of resistance to chemotherapeutics. Although the relationship between oxaliplatin and chemotherapy resistance has been described for decades, the molecular mechanisms have remained elusive. The aim of the present study was to investigate the underlying mechanisms of oxaliplatin-mediated metastasis. Here, we identify reactive oxygen species (ROS) as mediators that promote the oxaliplatin-induced EMT. Following oxaliplatin treatment, the messenger RNA (mRNA) levels of most peroxiredoxin family genes, except for peroxiredoxin 1 (prdx1) gene, were constant or even decreased, resulting in ROS abundance. And the antioxidant guardian Nrf2 was unconspicuously raised both transcriptionally and translationally with oxaliplatin treatment as compared to those induced by topotecan treatment, which has been proved with no induced metastasis. In addition, the study evaluated high levels of ROS leading to EMT via activation of the known oncogenes Akt and Snail. Using the Akt inhibitor LY294002 or knocking down Snail expression via RNA interference (RNAi) reversed the effects of oxaliplatin on the EMT and metastasis. Our studies establish a role for the ROS-Akt-Snail axis as a mechanism by which chemotherapeutics induce EMT and cancer metastasis.

Efficacy and safety of nab-paclitaxel combined with carboplatin in Chinese patients with melanoma.

This study aimed to evaluate the efficacy and safety of nab-paclitaxel combined with carboplatin in Chinese patients with melanoma. The treatment regimen consisted of nab-paclitaxel (100 mg/m(2)) and carboplatin (area under the curve = 2) administered on days 1 and 8 every 21 days. All of the patients were evaluated on the basis of efficacy and safety in a two-cycle interval. Of the 45 patients, 18 were chemotherapy naive and 27 were chemotherapy treated. Of these cases, 18 manifested acral melanoma and 27 showed non-acral melanomas. Although chemotherapy-naive patients exhibited a higher response to the treatment, similar progression-free survival (PFS) and overall survival (OS) were detected in chemotherapy-naive and chemotherapy-treated patients. A higher response was observed in non-acral melanomas; however, similar PFS and OS occurred between acral and non-acral melanomas. The most common side effects were alopecia, myelosuppression, and gastrointestinal reaction. Nab-paclitaxel combined with carboplatin is a well-tolerated and effective regimen to treat Chinese patients with melanoma, including acral and non-acral melanomas. This treatment may be an alternative approach for Chinese patients with melanoma, especially those without the opportunity to undergo therapy with immune checkpoint inhibitors.

[The significance of IGF-1, VEGF, IL-6 in multiple myeloma progression].

OBJECTIVE: To study the alteration and significance of IL-6, vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1) in MM progression and the interaction between the three cytokines. METHODS: Bone marrow samples from 28 patients with multiple myeloma (MM) (evolution group and steady group), 10 iron deficiency anemia (as normal control) and 2 monoclonal gammopathy of undetermined significance (MGUS) were studied. Bone marrow stromal cells (BMSCs) were established from the bone marrow MNCs. ELISA was performed to detect the concentration of IL-6, VEGF, IGF-1 in culture supernates. RESULTS: (1) The levels of IL-6 and VEGF secreted by BMSCs were increased in an order from normal control to steady group to evolution group (P < 0.05). However, the concentration of IGF-1 did not increase in MM patients (P > 0.05). (2) The levels of IL-6, VEGF and IGF-1 in the coculture supernates of U266 and BMSCs were increased significantly (P < 0.05), being in an ascending order from normal control to steady group to evolution group (P < 0.05). (3) BMSCs stimulated by exogenous IL-6, VEGF or IGF-1, secreted more VEGF, IGF-1/IL-6, IGF-1/VEGF, IL-6 than unstimulated (P < 0.05). (4) The levels of IL-6, VEGF, IGF-1 secreted by BMSCs from MGUS were similar to that from control group. CONCLUSIONS: IL-6, VEGF, IGF-1 levels associate with evolution of MM; IL-6, VEGF and IGF-1 induce an increase in cytokines secretion of BMSCs.