The interactions of paclitaxel with tumour microenvironment.

Today, it is well-known that the interactions and secretion within the tumour are crucial to consider for cancer therapy. Some novel cancer therapy modalities such as immunotherapy or tumour vaccination therapy work based on the control of interactions within the tumour microenvironment (TME). It has been revealed that anti-cancer drugs or radiotherapy can modulate some interactions in favour of cancer therapy. However, they may induce some mechanisms to increase the resistance of cancer cells to therapy. Paclitaxel is known as the first approved herbal derived chemotherapy drug. Although the main known anti-cancer effect of paclitaxel is the inhibition of the cell cycle, today, it has been well known that paclitaxel may suppress the tumour via modulating several interactions in TME. Furthermore, paclitaxel may increase the expression of some tumour resistance drivers. This review aims to discuss the interactions within TME following treatment with paclitaxel. The effects of paclitaxel on the anti-tumour immunity, immunosuppressive cells, hypoxia, and also angiogenesis will be discussed. The targeting of these interactions may be interesting to increase therapy efficiency using the combination modalities.

Targeted Inhibition of HK-II Reversed the Warburg Effect to Improve the Radiosensitivity of Laryngeal Carcinoma.

PURPOSE: Hexokinase-II (HK-II) is the key enzyme in the first rate-limiting step of glycolysis that catalyzes the conversion of glucose to glucose-6-phosphate. Here, we examined the association between HK-II expression and radioresistance in laryngeal carcinoma and whether the inhibition of HK-II expression can enhance the radiosensitivity of these tumors. METHODS: The effects of HK-II small interfering RNA (siRNA) on the radiosensitivity of Tu212 cells were examined in vitro and in vivo in a mouse model. Cells were irradiated using a 6-MV linear accelerator. The cell viability, cell survival, proliferation, apoptosis, and cell cycle of Tu212 cells were evaluated using trypan blue staining, colony formation assays, CCK-8 assays, and flow cytometry, respectively. Oxygen consumption, lactic acid production, glucose consumption, and the ATP level of Tu212 cells were also examined. The expression of glycolytic and regulatory enzymes involved in the tricarboxylic acid cycle was assessed using Western blotting. RESULTS: The HK-II siRNA and X-ray combination treatment led to a significantly greater reduction of cell viability, inhibition of cell survival and proliferation, increased apoptosis, and increased G2 phase arrest compared to either treatment alone (all, P<0.01). HK-II siRNA increased the oxygen consumption rate of cells, significantly inhibited lactic acid production and glucose consumption, and significantly suppressed the upregulation of HK-II, pyruvate kinase M2 (PKM2), pyruvate dehydrogenase (PDH), phosphofructokinase platelet (PFKP), lactate dehydrogenase (LD), and citrate synthase (CS) (all, P<0.01). CONCLUSION: The inhibition of HK-II by siRNA enhances the radiosensitivity of laryngeal carcinoma Tu212 cells by inhibiting glycolysis and partially inhibiting oxidative phosphorylation.

Fault tolerant control of multivariable processes using auto-tuning PID controller.

Fault tolerant control of dynamic processes is investigated in this paper using an auto-tuning PID controller. A fault tolerant control scheme is proposed composing an auto-tuning PID controller based on an adaptive neural network model. The model is trained online using the extended Kalman filter (EKF) algorithm to learn system post-fault dynamics. Based on this model, the PID controller adjusts its parameters to compensate the effects of the faults, so that the control performance is recovered from degradation. The auto-tuning algorithm for the PID controller is derived with the Lyapunov method and therefore, the model predicted tracking error is guaranteed to converge asymptotically. The method is applied to a simulated two-input two-output continuous stirred tank reactor (CSTR) with various faults, which demonstrate the applicability of the developed scheme to industrial processes.