ABSTRACT
The prognosis of advanced gastric cancer and gastroesophageal junction (GEJ) adenocarcinoma is poor. Although che-motherapy prolongs patient survival and improves quality of life to a greater extent best supportive care compared to, the median over-survival of patients with advanced gastric cancer is limited to approximately 7-10 months. With remarkable progress in the understand-ing of molecular mechanisms, molecular-targeted agents have been developed and evaluated in international randomized phaseⅢclini-cal trials. These agents may change the treatment mode of this disease. A ToGA study initially demonstrated that the trastuzumab, the monoclonal antibody of HER-2, as a molecular-targeted agent, in combination with chemotherapy, can prolong the overall survival of patients to 13.8 months. Several agents targeting angiogenesis, c-Met, PARP, and immunotherapy are currently subjected to clinical tri-als. This review summarizes the current status of molecular-targeted therapies for gastric cancer and GEJ adenocarcinoma.
ABSTRACT
Objective: This study aims to analyze the therapeutic effect and prognostic factors of carcinoma of parotid gland (CPG). Methods: Data on 103 CPG patients were retrospectively analyzed. The patients were divided into the simple surgery group (Group One) and post-operative radio-chemotherapy group (Group Two). Kaplan-Meier survival analysis, Log-rank test, and Cox re-gression analysis were employed to analyze the five-year overall survival. Chi-square test was applied to compare the local control rate and recurrence-free survival. Logistic regression analysis was used to determine the correlation between all factors and the local control rate. Results:For all patients, the five-year local control rate, five-year recurrence-free survival rate, and five-year overall survival rate were 71.49%, 69.61%, and 76.10%respectively. The five-year local control ratio (81.96%vs. 61.90%), five-year recurrence-free surviv-al (78.69%vs. 59.52%), and five-year overall survival (88.12%vs. 68.50%) were significantly improved in Group Two compared with Group One. The logistic regression analysis showed that the therapeutic method, T staging, as well as pN(+) neck and tumor differentia-tion were significantly correlated to the five-year local control rate and five-year recurrence-free survival (P<0.01). Cox regression anal-ysis showed that therapeutic method, T stage, as well as pN(+) neck and tumor differentiation were significantly correlated to the five-year overall survival (P<0.01). Conclusion:Post-operative radio-chemotherapy can improve the local control and overall survival rates. This therapeutic method is applicable to patients with T3-4 tumors, as well as pN(+) neck and middle-low differentiation.
ABSTRACT
Objective To explore the effects of silencing Livin gene by RNA interference mediated by lentiviral vector on colorectal cancer HT-29 cell xenograft growth and sensitivity to radiotherapy in nude mice.Methods BALB/c nude mice models were established by subcutaneously inoculating differently treated HT-29 cells into nude mice and the tumor growth situation of tumors was observed by measuring the volume of tumors and the weight of the nude mice at different time points after cell seeding.Livin expression was detected by RT-PCR and immunohistochemistry,respetively.Apoptosis rate was detected by TUNEL.Normal saline,lentivirus carring unrelated sequences,lentivirus caning Livin shRNA were injected intratumorally.All the nude mice were given 10 Gy of 6 MV X-ray irradiation.The changes of mice weight and the tumor volume were measured at different time points and the weight and tumor growth curves were drawn.Results The inhibition rate of tumor volume was(50.04 ± 0.07)％ and the tumor weight of the RNA interfering group was significantly less than that in experimental group compared to the blank and negative groups(F=4.85,P＜0.05),and the inhibition rate of tumor weight was(50.27 ±0.17)％.Relative Livin mRNA expression level in the RNA interfering experimental group was(17.75 ±0.08)％,and was significantly lower than that of the blank group(67.60 ± 0.05)％ and the negative group(68.54 ± 0.03)％(F=89.97,P＜0.01).Livin protein expression level in the RNA inferring group was also significantly lower[(36.00 ± 3.40)％ versus(85.00 ± 3.15)％,(80.33 ± 3.08)％,F=107.32,P＜0.01].The apoptosis rate in the RNA interfering experimental group was significantly higher than that in the blank and the negative groups[(23.67 ± 2.25)％ versus(5.00 ± 1.50)％,(8.33 ± 1.82)％,F=56.94,P＜0.01].Combined with radiotherapy,the tumor volume at different groups had significant difference(F=10.70,P＜0.01),and RNA interfering group was significantly less than negative group and blank group(F=7.01-9.32,P＜0.01).Conclusions Silencing of Livin gene expression by lentiviral vector-mediated RNA interference could inhibit the growth of colorectal HT-29 cell xenograft and increase the sensitivity of the transplanted tumors to radiotherapy.
ABSTRACT
The effects of over-expression of ANXA10 gene on proliferation and apoptosis of hepato-cellular carcinoma cell line HepG2 were elucidated. The human ANXA10 gene was subcloned into the lentiviral vector, PGC-FU, to generate the lentiviral expression vector, PGC-FU-ANXA10. The corrected ANXA10 was confirmed by endoenzyme digestion, and sequencing. Recombinant lentiviruses were produced by 293T cells following the co-transfection of PGC-FU-ANXA10 with the packaging plasmids pHelper1.0 and pHelper2.0. The resulting recombinant lentiviruses carrying ANXA10 were then used to infect human embryonic kidney epithelial cells, and lentiviral particles were produced. The ANXA10 expression in 293T cells was detected by using fluorescent microscope and Western blotting. HepG2 cells were infected, and divided into PGC-Fu-ANXA10 group, PGC-Fu group and HepG2 cell group. The changes of ANXA10 mRNA and protein expression were detected by using RT-PCR and Western blotting respectively. Flow cytometry and MTT assay were performed to examine the changes in cell apoptosis and proliferation respectively. The recombinant PGC-FU-ANXA10 vector was successfully constructed, the ANXA10 protein was detected by using Western blotting, and virus titer was 2×10(8) TU/mL. The recombinant lentiviruses were effectively infected into HepG2 cells in vitro and the infection efficiency was 70%. At 72 h after infection, the ANXA10 mRNA and protein expression levels in PGC-Fu-ANXA10 group were significantly higher than in PGC-Fu group and HepG2 cell group (P<0.05); the in vitro growth inhibition rate of HepG2 cells in PGC-Fu-ANXA10 group was 24.65%, significantly higher than that in PGC-Fu group and HepG2 cell group (P<0.05), but there was no significant difference between PGC-Fu group and HepG2 cell group; the apoptosis rate in PGC-Fu-ANXA10 group, PGC-Fu group and HepG2 cell group was (51.92±1.41)%, (19.00±1.12)% and (3.59±0.89)% respectively. The apoptosis rate in PGC-Fu-ANXA10 group was significantly higher than in PGC-Fu group and HepG2 cell group (P<0.05). The recombinant lentiviruses PGC-FU-ANXA10 were constructed successfully and infected into HepG2 cells. The overexpression of ANXA10 gene can significantly inhibit proliferation and promote apoptosis of HepG2 cells in vitro.
ABSTRACT
The effects of over-expression of ANXA10 gene on proliferation and apoptosis of hepato-cellular carcinoma cell line HepG2 were elucidated. The human ANXA10 gene was subcloned into the lentiviral vector, PGC-FU, to generate the lentiviral expression vector, PGC-FU-ANXA10. The corrected ANXA10 was confirmed by endoenzyme digestion, and sequencing. Recombinant lentiviruses were produced by 293T cells following the co-transfection of PGC-FU-ANXA10 with the packaging plasmids pHelper1.0 and pHelper2.0. The resulting recombinant lentiviruses carrying ANXA10 were then used to infect human embryonic kidney epithelial cells, and lentiviral particles were produced. The ANXA10 expression in 293T cells was detected by using fluorescent microscope and Western blotting. HepG2 cells were infected, and divided into PGC-Fu-ANXA10 group, PGC-Fu group and HepG2 cell group. The changes of ANXA10 mRNA and protein expression were detected by using RT-PCR and Western blotting respectively. Flow cytometry and MTT assay were performed to examine the changes in cell apoptosis and proliferation respectively. The recombinant PGC-FU-ANXA10 vector was successfully constructed, the ANXA10 protein was detected by using Western blotting, and virus titer was 2×10(8) TU/mL. The recombinant lentiviruses were effectively infected into HepG2 cells in vitro and the infection efficiency was 70%. At 72 h after infection, the ANXA10 mRNA and protein expression levels in PGC-Fu-ANXA10 group were significantly higher than in PGC-Fu group and HepG2 cell group (P<0.05); the in vitro growth inhibition rate of HepG2 cells in PGC-Fu-ANXA10 group was 24.65%, significantly higher than that in PGC-Fu group and HepG2 cell group (P<0.05), but there was no significant difference between PGC-Fu group and HepG2 cell group; the apoptosis rate in PGC-Fu-ANXA10 group, PGC-Fu group and HepG2 cell group was (51.92±1.41)%, (19.00±1.12)% and (3.59±0.89)% respectively. The apoptosis rate in PGC-Fu-ANXA10 group was significantly higher than in PGC-Fu group and HepG2 cell group (P<0.05). The recombinant lentiviruses PGC-FU-ANXA10 were constructed successfully and infected into HepG2 cells. The overexpression of ANXA10 gene can significantly inhibit proliferation and promote apoptosis of HepG2 cells in vitro.