ABSTRACT
Objective@#To evaluate the oncolytic effect of herpes simplex virus type 1 which carried recombined human granulocyte-macrophage colony-stimulating factor (HSV1-hGM-CSF) on the mouse breast cancer cell line 4T1 and compare the anticancer effects of HSV1-hGM-CSF, doxorubicin alone or combination on the breast cancer in mice.@*Methods@#We investigated the cytotoxic effect on 4T1 cells in vitro, the cell growth, cell apoptosis and cell cycle of 4T1 cells treated with oncolytic HSV1-hGM-CSF at different MOIs (0, 0.5, 1 and 2) and doxorubicin at different concentrations (0, 2, 4 and 8 μg/ml). The effects of oncolytic HSV1-hGM-CSF and doxorubicin on the tumor growth, survival time and their side effects on the mouse breast cancer model were observed.@*Results@#Both oncolytic HSV1-hGM-CSF and doxorubicin significantly inhibited the proliferation of 4T1 cells in vitro. Doxorubicin induced the G2/M phase arrest of 4T1 cells, while the cytotoxicity of oncolytic HSV1-hGM-CSF was no cell cycle-dependent.At day 16 after treatment with doxorubicin and HSV1-hGM-CSF, the tumor volume of 4T1 tumor bearing mice were (144.40±27.68)mm3, (216.80±57.18)mm3, (246.10±21.90)mm3, (327.50±44.24)mm3, (213.30±32.31)mm3 and (495.80±75.87)mm3 in the groups of doxorubicin combined with high dose HSV1-hGM-CSF, doxorubicin combined with low dose HSV1-hGM-CSF, doxorubicin alone, high dose HSV1-hGM-CSF alone, low dose HSV1-hGM-CSF alone and control, respectively.Compared with the control group, both doxorubicin and HSV1-hGM-CSF treatment exhibited significant reduction of primary tumor volume in vivo (P<0.001). The median survival times were 48, 50, 40, 42, 43 and 37 days in the six groups mentioned above, respectively. The median survival period of doxorubicin alone, high dose HSV1-hGM-CSF alone and low dose HSV1-hGM-CSF alone were significantly longer than that of control (P<0.05).@*Conclusion@#Synergistic effect of sequential treatment with doxorubicin and oncolytic HSV1-hGM-CSF is observed in 4T1 mouse breast cancer.
ABSTRACT
Objective To investigate the associations between expression of Tensin1 protein and clinicpathological characteristics and prognoses of gastric cancer (GC) patients.Methods The retrospective casecontrol study was conducted.The clinicopathological data of 163 GC patients who were admitted to the Affiliated Hospital of Jiangsu University between July 31,2011 and December 31,2013 were collected.The GC tissues and adjacent normal tissues were taken to paraffin imbedding,and then were detected by immunohistochemistry.Observation indicator:(1) expressions of Tensinl protein in GC tissues and adjacent normal tissues;(2) association between expression of Tensinl protein in GC tissues and clinicopathological characteristics;(3) followup and survival situations;(4) prognostic factors analysis.Follow-up using telephone interview was performed to detect survival up to January 1,2017.Measurement data with skewed distribution were described as M (range).Count data were analyzed using the chi-square test or pairing chi-square test.The survival curve and rate were respectively drawn and calculated using the Kaplan-Meier method,and Log-rank test was used for survival analysis.The univariate analysis and multivariate analysis were done using the COX roportional hazard model.Results (1) Expressions of Tensinl protein in GC tissues and adjacent normal tissues:immunohistochemistry showed that Tensinl protein in GC tissues and adjacent normal tissues mainly expressed in cytoplasm.Of 163 patients,154 (66 with high expression and 88 with low expression) and 9 had respectively positive and negative expressions of Tensinl protein in GC tissues;79 (37 with high expression and 42 with low expression) and 84 had respectively positive and negative expressions of Tensinl protein in adjacent normal tissues,with statistically significant differences in positive expression ratio and expression levels (x2=64.65,12.93,P＜0.05).(2) Association between expression of Tensinl protein in GC tissues and clinicopathological characteristics:high expression rate of Tensinl protein in GC tissues were respectively 31.34％ (21/67) in GC patients with tumor metastases and 46.88％ (45/96) in GC patients without tumor metastasis,with a statistically significant difference (x2 =3.95,P＜0.05).(3) Follow-up and survival situations:all the 163 patients were followed up for 3.3-64.7 months,with a median time of 28.7 months.The 3-year cumulative disease-free survival rate and cumulative overall survival rate in GC tissues were 63.12％,74.22％ in 66 patients with high expression of Tensinl protein and 47.30％,55.74％ in 97 patients with low and negative expressions of Tensin1 protein,showing statistically significant differences in above indicators (x2 =4.58,4.11,P＜0.05).Survival analysis of subgroups showed that 3-year cumulative disease-free survival rate in GC tissues of patients with maximum tumor dimension ≥ 5 cm,nerve and / or vascular invasions and stage Ⅲ of TNM staging were 45.98％,62.79％,52.75％ in patients with high expression of Tensin1 protein and 18.11％,31.10％,32.80％ in patients with low and negative expressions of Tensin1 protein,with a statistically significant difference (x2 =5.85,7.89,4.96,P＜0.05).The 3-year cumulative overall survival rate was respectively 66.00％,75.75％,67.93％ in patients with high expression of Tensin1 protein and 30.74％,40.15％,44.67％ in patients with low and negative expressions of Tensinl protein,with statistically significant differences (x2 =7.59,9.62,4.32,P ＜ 0.05).(4) Prognostic factors analysis:results of univariate analysis showed that maximum tumor dimension,histological grade,nerve and / or vascular invasions,postoperative TNM staging,postoperative adjuvant chemotherapy and expression of Tensin1 protein were related factors affecting prognoses of GC patients [hazard ratio (HR) =3.66,2.45,2.17,3.36,0.41,0.54,95％ confidence interval (CI):2.09-6.41,1.43-4.19,1.17-4.04,1.52-7.41,0.23-0.72,0.31-0.96,P＜0.05].Results of multivariate analysis showed that maximum tumor dimension ≥ 5 cm and grade Ⅲ of histological grade were independent risk factors affecting prognoses of GC patients (HR=3.21,2.17,95％CI:1.63-6.32,1.18-3.99,P＜0.05),and postoperative adjuvant chemotherapy and high expression of Tensin1 protein were independent protective factors affecting prognoses of GC patients (HR=0.50,0.44,95％CI:0.28-0.90,0.24-0.82,P＜0.05).Conclusion High expression of Tensin1 protein may inhibit GC metastasis,and it is also an independent protective factor affecting prognoses of GC patients.