Developing novel approaches to reverse the drug resistance of tumor-repopulating cells (TRCs) or stem cell-like cancer cells is an urgent clinical need to improve outcomes of cancer patients. Here we show an innovative approach that reverses drug resistance of TRCs using tumor cell-derived microparticles (T-MPs) containing anti-tumor drugs. TRCs, by virtue of being more deformable than differentiated cancer cells, preferentially take up T-MPs that release anti-tumor drugs after entering cells, which in turn lead to death of TRCs. The underlying mechanisms include interfering with drug efflux and promoting nuclear entry of the drugs. Our findings demonstrate the importance of tumor cell softness in uptake of T-MPs and effectiveness of a novel approach in reversing drug resistance of TRCs with promising clinical applications.

Percutaneous microwave ablation and radiofrequency ablation are both effective methods in treating hepatocellular carcinomas. The local tumor control, complications related to treatment, and long-term survivals were equivalent for the two modalities.

Percutaneous microwave coagulation therapy is an effective and safe therapeutic modality for hepatocellular carcinoma. A multiple electrode insertion technique can enhance the effectiveness of this therapy in tumors 6 cm or smaller.

Developing novel drugs that can abrogate the growth and metastasis of malignant tumors is a major challenge for cancer researchers. Here we describe a novel synthetic retinoid, namely WYC-209, which inhibits proliferation of malignant murine melanoma tumor-repopulating cells (TRCs), known to resist conventional drug treatment, with an IC50 of 0.19 μM in a dose-dependent manner. WYC-209 also inhibits proliferation of TRCs of human melanoma, lung cancer, ovarian cancer, and breast cancer in culture. Interestingly, the treated TRCs fail to resume growth even after the drug washout. Importantly, the molecule abrogates 87.5% of lung metastases of melanoma TRCs in immune-competent wild-type C57BL/6 mice at 0.22 mg kg−1 without showing apparent toxicity. Pretreating the melanoma TRCs with retinoic acid receptor (RAR) antagonists or with RAR siRNAs blocks or reduces the inhibitory effect of the molecule, suggesting that the target of the molecule is RAR. WYC-209 induces TRC apoptosis and pretreating the TRCs with caspase 3 inhibitor or depleting caspase 3 with siRNAs substantially rescues growth of TRCs from WYC-209 inhibition, suggesting that WYC-209 induces TRCs apoptosis primarily via the caspase 3 pathway. Our findings demonstrate the promise of the new retinoid WYC-209 in treating malignant melanoma tumors with high efficacy and little toxicity.

Rheumatoid arthritis (RA) is the most common autoimmune disorder. Loss of Th1/Th2 and Th17/Treg balance has been reported in several inflammatory autoimmune diseases. This study was to investigate Th1, Th2, Th17, and Treg differentiation and related cytokines in RA patients. The frequencies of Th1, Th2, Th17, and Treg cells in peripheral blood of RA patients (n = 76) and healthy controls (n = 18) were determined by flow cytometry. Eight serum cytokines were analyzed using cytometric bead array. The results demonstrated that RA patients exhibited increased peripheral Th1/Th17 cells and Th1/Th17-related cytokines. However, Th1 cells only reached significant difference at advanced stage, but Th17 at all stages, suggesting more important roles in Th17 cells. For Th2 and Treg cells, there was a different function pattern in RA progression. Although with the increase of DAS28 score, Th2 cell experienced some degree of decrease in RA patients, no significant difference was observed. IL-4 and IL-10 showed a significant increase in RA patients. These indicated that Th2 cells might exert immunosuppression effects mainly by secreting cytokines. Treg cells were found significantly decreased in RA patients, but no difference was observed in TGF-β expression, indicating a cell-cell interaction pattern in Treg cell.