Huanrong Ma

Theranostic, pH-Responsive, Doxorubicin-Loaded Nanoparticles Inducing Active Targeting and Apoptosis for Advanced Gastric Cancer

This study developed a kind of magnetic-polymer nanocarrier with folate receptor-targeting and pH-sensitive multifunctionalities to carry doxorubicin (DOX) for treatment of advanced gastric cancer (AGC). Folate-conjugated, pH-sensitive, amphiphilic poly(β-aminoester) self-assembled with hydrophobic oleic acid-modified iron oxide nanoparticles, and the resulting hydrophobic interaction area is a reservoir for lipophilic DOX (F-P-DOX). Confocal microscopy illustrated that F-P-DOX treatment could keep higher DOX accumulation in cells than P-DOX (without folate conjugation), and therefore get a higher efficiency of DOX internalization at pH 6.5 than at pH 7.4. Electron microscope characterization and real-time polymerase chain reaction revealed cell apoptosis promoted by F-P-DOX. The better efficacy of F-P-DOX on GC than free DOX and P-DOX was determined by MTT assay and xenograft model. Moreover, the accumulation of F-P-DOX in the tumor site was detected by magnetic resonance imaging (MRI). All those observations suggest F-P-DOX could be a promising theranostic candidate for AGC treatment.

Impact of liver tumor percutaneous radiofrequency ablation on circulating tumor cells

Radiofrequency ablation has become an increasingly common therapeutic technique for patients with hepatocellular carcinoma or metastatic liver tumors. However, reports on the effect of percutaneous radiofrequency ablation (PRFA) on circulating tumor cells (CTCs) are limited. The present study aimed to further investigate the impacts of PRFA on the numbers and phenotypes of CTCs in patients with hepatocellular carcinoma or metastatic liver tumors. A total of 43 patients with hepatocellular carcinoma or 7 types of metastatic liver tumors were treated with PRFA. A total of 5 ml blood per sample were collected from the peripheral circulation 30 min before and 3 days after PRFA. The total number of CTCs significantly increased 3 days after PRFA, and the mesenchymal phenotype CTCs, which also increased significantly, significantly contributed to the overall increase in CTCs. Furthermore, the lymphocyte levels were significantly decreased following PRFA, and the CTC level was significantly higher in patients with decreased lymphocyte levels compared with those with increased lymphocyte levels. Liver tumor PRFA may increase the level of mesenchymal phenotype CTCs, which is significantly associated with the lymphocyte count. Factors pertaining to the performance of PRFA were also investigated in the present research, but no significant results were identified.

Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab: SLC1A5 inhibition enhances the efficacy of cetuximab

Cetuximab resistance is a key barrier in treating metastatic colorectal cancer (mCRC). Targeting of metabolic resources import could resensitize drug‐resistant cancer cells to anticancer treatments. Here we showed that the expression of the glutamine transporter solute carrier 1 family member 5 (SLC1A5) in clinical CRC samples of patients resisted to cetuximab was significantly higher than in those of patients responded to cetuximab. Inhibition of SLC1A5 by shRNA‐mediated gene silencing or pharmacological inhibitor significantly suppressed the growth of CRC. Moreover, inhibition of SLC1A5 significantly enhanced the inhibitory efficacy of cetuximab on CRC proliferation both in vitro and in vivo. Mechanistically, SLC1A5 inhibition facilitated EGFR degradation through the ubiquitin‐proteasome pathway, and decreased the expression of nuclear EGFR, both of which might have contribution to the improved response to cetuximab. This study provides the metabolic molecule SLC1A5 as a potential therapeutic target to increase the efficacy of cetuximab on CRC.