Chemoresistance is a major obstacle to the curative cancer chemotherapy and presents one of the most formidable challenges in both research and management of cancer. From the detailed studies of a multi-chemosensitive (5637) versus a chemoresistant (H-bc) bladder cancer cell lines, we showed that miR-193a-3p [GenBank: NR_029710.1] promotes the multi-chemoresistance of bladder cancer cells. We further demonstrated that lysyl oxidase-like 4 (LOXL4) gene [GenBank: NM_032211.6] is a direct target of miR-193a-3p and executes the former’s impact on bladder cancer chemoresistance. The Oxidative Stress pathway activity is drastically affected by a forced reversal of miR-193a-3p or LOXL4 levels in cell and may act at the downstream of LOXL4 gene to relay the miR-193a-3p’s impact on the multi-chemoresistance in both cultured cells and the tumor xenografts in nude mice. In addition to a new mechanistic insight, our results provide a set of the essential genes in this newly identified miR-193a-3p/LOXL4/Oxidative Stress axis as the diagnostic targets for a guided anti-bladder cancer chemotherapy.

The efficacy of chemotherapeutic agents for colon cancer treatment is limited by multidrug resistance (MDR) and insufficient intracellular release of the administered nanomedicine. To overcome these limitations, we constructed a pH/ROS cascade-responsive and self-accelerating drug release nanoparticle system (PLP-NPs) for the treatment of multidrug-resistant colon cancer. The PLP-NPs comprised a reactive oxygen species (ROS)-sensitive polymeric paclitaxel (PTX) prodrug (DEX-TK-PTX), a pH-sensitive poly(l-histidine) (PHis), and beta-lapachone (Lapa), a ROS-generating agent. We found that PLP-NPs could accumulate in tumor tissue through enhancement of the permeability and retention (EPR) effect, and were subsequently internalized by cancer cells via the endocytic pathway. Within the acidic endo-lysosomal environment, PHis protonation facilitated the escape of the PLP-NPs from the lysosome and release of Lapa. The released Lapa generated a large amount of ROS, consumed ATP, and downregulated P-glycoprotein (P-gp) production through the activity of NQO1, an enzyme that is specifically overexpressed in tumor cells. In addition, the generated ROS promoted the release of PTX from DEX-TK-PTX to kill cancer cells, while ATP depletion inhibited P-gp-mediated MDR. In vitro and in vivo experiments subsequently confirmed that PLP-NPs induced tumor-specific cytotoxicity and overcame the MDR of colon cancer. Our findings indicate that the use of the PLP-NPs system represents a promising strategy to counter MDR in the treatment of colon cancer.

To investigate risk factors for acute oral mucosal reaction during head and neck squamous cell carcinoma radiotherapy. A retrospective study of patients with head and neck squamous cell carcinoma who underwent radiotherapy from November 2013 to May 2016 in Anhui Provincial Cancer Hospital was conducted. Data on the occurrence and severity of acute oral mucositis were extracted from clinical records. Based on the Radiation Therapy Oncology Group (RTOG) grading of acute radiation mucosal injury, the patients were assigned into acute reaction (grades 2–4) and minimum reaction (grades 0–1) groups. Preradiotherapy characteristics and treatment factors were compared between the 2 groups. Multivariate logistic regression analysis was used to detect the independent factors associated with acute oral mucosal reactions. Eighty patients completed radiotherapy during the study period. Oral mucosal reactions were recorded as 25, 31, and 24 cases of grades 1, 2, and 3 injuries, respectively. Significant differences between acute reaction and minimum reaction groups were detected in cancer lymph node (N) staging, smoking and diabetes history, pretreatment platelet count and T-Helper/T-Suppressor lymphocyte (Th/Ts) ratio, concurrent chemotherapy, and total and single irradiation doses. Multivariate analysis showed that N stage, smoking history, single dose parapharyngeal irradiation, and pretreatment platelet count were independent risk factors for acute radiation induced oral mucosal reaction. Smoking history, higher grading of N stage, higher single dose irradiation, and lower preirradiation platelet count may increase the risk and severity of acute radiation oral mucosal reaction in radiotherapy of head and neck cancer patients.