Cancer is a common disease threatening human health, chemotherapy is widely used in clinical treatment of cancer, but chemotherapy-induced peripheral neuropathy (CIPN) has a relevant impact on life quality of cancer patients. Administration of gastrodin can relieve chronic pain to cancer patients with CIPN and attenuated the inflammatory response by reducing the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). However, its exact molecular mechanisms remain unclear. In this study, we established an animal model of CIPN using Walker-256 breast cancer cell and vincristine. We found that the mechanical and thermal pain threshold of rats was decreased with treatment of vincristine. Using gastrodin could restore the mechanical and thermal threshold without interfering anti-tumor effect of vincristine. Gastrodin relieved CIPN by inhibiting activation of spinal microglia through Fractalkine (CX3CL1) and its receptor CX3CR1, then inhibited P38/mitogen-activated protein kinase (MAPK) signaling pathway and reduced the expression of inflammatory factor TNF-α and interleukin-1β (IL-1β). Taking together, our study demonstrated that gastrodin is a potential drug for the treatment of CIPN and likely to improve cancer patient’s life quality.

VX680 is an Aurora A inhibitor. It has been reported to inhibit the growth of the HepG2 cell line in several studies. However, whether it enhances chemosensitivity to cisplatin remains unclear. In this study, the synergistic effect of VX680 and cisplatin on the proliferation of HepG2 cells was determined by MTT assay. The changes in cell apoptosis were detected by flow cytometry. Aurora A, Bcl-2 and p53 protein levels were analyzed by western blotting. This study demonstrated that VX680, cisplatin and a combination of the two inhibit the growth of HepG2 cells in a dose- and time-dependent manner. A synergistic effect was observed with the combined therapy. Moreover, the inhibitory effect of VX680 was positively correlated with the expression of Aurora A. The rate of apoptosis in the combined group was significantly higher compared with that of the VX680 and cisplatin groups. In addition, VX680 and cisplatin increased the expression of the p53 protein. Cisplatin reduced the expression of Bcl-2 protein, while VX680 did not. In the combined group, the expression of Bcl-2 and p53 changed significantly compared with the single drug group and control group. This study suggests that Aurora A may represent a valid target in hepatocellular carcinoma. We also demonstrated that the Aurora A inhibitor VX680 has a synergistic effect with cisplatin.

Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer

Objective The aim of this study was to establish a clinical scoring formula of liver injury (SFLI) using the matter element analysis method, in order to provide the necessary information for the preoperative assessment and treatment of liver cirrhosis in clinical practice. Materials and methods We collected preoperative information for 12 serum biochemical markers (ALB, PA, TBil, SCr, INR, ALT, AST, γ-GT, ALP, PT, APTT, and TT) from patients with liver cirrhosis, statistically analyzed the relationship between the serum biochemical markers and the extent of liver injury, and obtained the liver injury scoring formula using the matter element analysis method. Results In our formula, the serum biochemical markers of patients with different degrees of liver cirrhosis damage led to different R-values, which represented the severity of the disease and the liver functional reserve. R=1 indicates that the liver tissue is normal; 0.770≤R<1 indicates that the liver is in the early stage of cirrhosis (SFLI I stage); 0.712≤R<0.770 indicates that the liver is in the intermediate state of compensated cirrhosis and decompensated cirrhosis (SFLI I+ stage); 0.629≤R<0.712 indicates that the liver is in the decompensated cirrhosis stage with ascites (SFLI II stage); 0.401≤R<0.629 indicates that the liver is in the stage of severely decompensated cirrhosis with ascites, and patients present with varying degrees of hepatic encephalopathy, hepatic coma, and other complications. Conclusion The SFLI that we constructed can sensitively and accurately reflect the conditions of liver cirrhosis damage and liver functional reserve.

We examined the effect of E-cadherin expression on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) molecular targeted therapy sensitivity/resistance. We treated MCF-7, MDA-MB-231, T24, SiHa, H460, SK-HEP-1, MHCC97-H, and THP-1 cells with the EGFR-TKIs PD153035 and gefitinib, and then tested the drug-resistance and sensitivity using the MTT method, calculated IC50 values for each cell line, and compared the results to E-cadherin content. The MTT assay was used to determine the survival rates of MCF-7, MDA-MB-231, T24, SiHa, H460, SK-HEP-1, MHCC97-H, and THP-1 cells upon the action of EGFR-TKI (PD153035, gefitinib). For PD153035, the IC50 in MCF-7, MDA-MB-231, T24, and SiHa cells differed from that of H460, SK-HEP-1, MHCC97-H, and THP-1 (P < 0.05). Following gefitinib treatment, the IC50 values of MCF-7, MDA-MB-231, T24, and SiHa cells differed from those of H460, SK-HEP-1, MHCC97-H, and THP-1 cells (P < 0.01). The survival rate of MCF-7, MDA-MB-231, T24, and SiHa cells clearly decreased with increasing drug concentration, indicating the cells were sensitive to the drugs and that E-cadherin expression was positive; however, H460, SK-HEP-1, MHCC97-H, and THP-1 cells showed no significant decreased with increasing drug concentration, indicating that they were resistant to the drugs and that E-cadherin expression was negative. The survival rate of epithelial tumor cells through the action of EGFR-TKI is related to E-cadherin expression. E-cadherin may play a significant role in the sensitivity regulation of EGFR molecular targeting treatment. E-cadherin may provide important clues for selecting proper EGFR-TKI molecular targeting treatment.