Objective To determine the expression of Notch pathway receptors (Notch1 and Notch4) and ligands (Jagged1 and Dll4) in cutaneous malignant melanoma (CMM) tissues,and to preliminarily explore the role of the Notch signaling pathway in the pathogenesis of CMM.Methods Immunohistochemical study was performed to determine the expression pattern and intensity of Notch1,Notch4,Jagged1 and Dll4 in 40 paraffin-embedded CMM specimens and 15 paraffin-embedded pigmented nevus specimens.Statistical analysis was carried out by chi-square test and Spearman rank correlation analysis with the SPSS 21.0 software.Results Notchl was detected in 31 (77.5％) of 40 CMM specimens,as well as in 3 of 15 pigmented nevus specimens,and the positive rates significantly differed between the two groups (x2 =15.281,P ＜ 0.001).However,no significant difference in the expression intensity of Notch1 was observed between 18 in situ melanoma tissues and 22 invasive melanoma tissues (x2 =0.631,P =0.427).In addition,the positive rates of Notch4,Jagged1 and Dll4 were also significantly higher in the CMM group than those in the pigmented nevus group (all P ＜ 0.05),and the expression intensity of Notch4,Jagged1 and Dll4 significantly differed between in situ and invasive melanoma tissues (all P ＜ 0.05).In CMM tissues,the expression of Notch1 was positively correlated with that of Jagged1 (rs =0.350,P =0.027) and Dll4 (rs =0.562,P ＜ 0.001),while the expression of Jaggedl was negatively correlated with that of Dl14 (rs =-0.734,P ＜ 0.001).Conclusion Abnormality of the Notch signaling pathway may be involved in the pathogenesis of melanoma,but further researches are still needed to elucidate the detailed mechanism.

Objective:To assess the efficacy of trastuzumab combined with neoadjuvant chemotherapy in the treatment of human epidermal growth factor receptor-2 (Her-2)positive breast cancer patients,and to explore its influencing factors of prognosis of breast cancer.Methods:The clinical materials of 112 Her-2 positive breast cancer patients were collected and they were divided into combined treatment group (trastuzumab + neoadj uvant chemotherapy)and single chemotherapy group (without trastuzumab ). SPSS 1 9.0 software was employed to calculate and analyze their clinical characteristics.The survival rate and prognosis were analyzed by Kaplan-Meier method,Log-rank test, and Cox regression. Results:Among the 112 Her-2 positive breast cancer patients, 23 cases were treated with trastuzumab,89 cases were treated without trastuzumab.The disease-free survival (DFS)in combined treatment group and single chemotherapy group had significant difference (P=0.012).And there was no significant difference of overall survival (OS)between two groups (P=0.064).The HR negative group had 18 (32.7%)patients with 5-level of Miller and Payne (MP)classification which was higher than HR positive group (5/46,10.9%)(P=0.009).In univariate analysis,the tumor size,node status at diagnosis and node status after operation were the influencing factors of DFS in the Her-2 positive breast cancer patients;the tumor size,node status at diagnosis,MP classification and node status after operation were the influencing factors of OS in the Her-2 positive breast cancer patients.The result of multivariate analysis indicated that the tumor size, node status at diagnosis,and with or without radiotherapy were the independent influencing factors of DFS and OS in the Her-2 positive breast cancer patients. Conclusion:The breast lesions in the Her-2 positive breast cancer patients with negative HR are relieved after treated with trastuzumab combined with neoadjuvant chemotherapy. The combination of trastuzumab and neoadj uvant chemotherapy can significantly improve the DFS and has a positive influence in the prognosis of Her-2 positive breast cancer patients.

OBJECTIVE: To evaluate the inhibitory effect of cordycepin on oral cancer xenograft in nude mice and explore the underlying mechanisms. METHODS: Sixteen BALB/c mice bearing subcutaneous human tongue squamous cell carcinoma (TSCC) TCA-8113 cell xenografts were randomized into model group and cordycepin treatment group for daily treatment with saline and cordycepin for 4 weeks. After the treatment, the tumor xenografts were dissected and weighed to assess the tumor inhibition rate. Histological changes in the heart, spleen, liver, kidney, and lung of the mice were evaluated with HE staining, and tumor cell apoptosis was examined using TUNEL staining; The expressions of Bax, Bcl-2, GRP78, CHOP, and caspase-12 in the xenografts were detected using RT-qPCR and Western blotting. RESULTS: Cordycepin treatment resulted in a tumor inhibition rate of 56.09% in the nude mouse models, induced obvious changes in tumor cell morphology and significantly enhanced apoptotic death of the tumor cells without causing pathological changes in the vital organs. Cordycepin treatment also significantly reduced Bcl-2 expression (P < 0.05) and increased Bax, GRP78, CHOP, and caspase-12 expressions at both the RNA and protein levels in the tumor tissues. CONCLUSION Cordycepin treatment can induce apoptotic death of TCA-8113 cell xenografts in nude mice via the endogenous mitochondrial pathway and endoplasmic reticulum stress pathways.
Humans ; Animals ; Mice ; Carcinoma, Squamous Cell/drug therapy* ; Heterografts ; Mice, Nude ; Tongue Neoplasms/drug therapy* ; Cordyceps ; Caspase 12 ; Endoplasmic Reticulum Chaperone BiP ; bcl-2-Associated X Protein ; Tongue