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Objective:To investigate the effect of heat shock protein 90 (Hsp90) inhibitor PU-H71 combined with X-ray on radioresistant human cervical cancer cells.Methods:The expression levels of Hsp90 gene between cervical cancer tissues and adjacent tissues were analyzed by bioinformatics. Radioresistant cervical cancer cell lines HeLa RR and SiHa RR were obtained by fractional irradiations (2 Gy per fraction, 30 fractions). The cell lines were divided into the control group (treated with dimethyl sulfoxide), irradiation alone group, PU-H71 group (treated with 0.5 μmol/L PU-H71), and PU-H71+irradiation group (irradiation at 24 h after treatment with 0.5 μmol/L PU-H71). Cell survival was detected by clonal formation assay. Immunofluorescence assay was used to detect γH2AX foci at 1, 6, and 24 h after cell treatment. The expression level of Rad51 protein at 1, 2, 6, 12, and 24 h after cell treatment was detected using Western blot. The expression level of phosphorylated DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) was measured at 2 h after cell treatment. Cell apoptosis at 48 h after cell treatment was assessed by flow cytometry. Results:PU-H71 enhanced the sensitivity of radioresistant cervical cancer cells to X-ray. Compared with the irradiation alone group, the radiation sensitization ratios (SER) of HeLa RR and SiHa RR cells at 10% survival were 1.36 and 1.27, and the apoptosis rates were increased by approximately 72.1% and 63.1% in the PU-H71+irradiation group, respectively. PU-H71 delayed the duration of γH2AX foci induced by X-ray, inhibited the phosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), thus preventing non-homologous end joining (NHEJ) repair and delaying homologous recombination repair.Conclusion:PU-H71 increases the radiosensitivity of radioresistant cervical cancer cells by inhibiting the repair pathway of DNA double-strand break, which is expected to be a radiosensitizer to enhance the efficacy of radiotherapy for cervical cancer.
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Objective:To compare and analyze the efficacy and safety of intraoperative radiotherapy (IORT) combined with conventional therapy (surgery combined with radiochemotherapy) and conventional therapy alone for pancreatic cancer.Methods:Literature review was conducted from PubMed, Cochrane Library, Web of Science, Embase, Chongqing VIP, CNKI, Wanfang Data and China Biomedical Literature Service System (SinoMed). The literatures that met the inclusion criteria were screened and the data were extracted. Meta-analysis was carried out by RevMan 5.4 software.Results:A total of 11 studies consisting of 813 patients were included. According to the combined results, compared with conventional therapy, IORT combined with conventional therapy could improve the overall survival rate of pancreatic cancer ( HR=0.66, 95% CI=0.54-0.81, Z=4.03, P<0.001), and did not increase the treatment-related side effects ( OR=1.00, 95% CI=0.69-1.46, Z=0.01, P=0.99), but failed to bring benefit to the local control rate ( HR=0.56, 95% CI=0.31-1.01, Z=1.93, P=0.05). Conclusions:The overall survival rate in the IORT combined with conventional therapy group is significantly better than that in the conventional therapy group. No significant difference is found in the treatment-related adverse reactions between two groups. IORT combined with conventional therapy is worthy of clinical application.
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Objective@#To evaluate the efficacy of ginsenoside Rg3(GRg3) in the treatment of acute radiation proctitis in rat models.@*Methods@#On the 7th day after 21.5 Gy irradiation, 100 rats were divided into the control group (normal saline, n=20), GRg3 group (gavage of 20 mg/kg, 40 mg/kg and 80 mg/kg GRg3, n=20 for each dose) and Smecta mixture enema group (n=20). After 2 weeks, all rats were anesthetized with chloral hydrate (3 ml/kg) and approximately 5 ml of blood sample was collected from the abdominal aorta prior to sacrifice. The rectal tissues were taken and prepared for detection of Bax and NF-κB contents and HE staining to observe the pathological changes of the rectal tissues. After the blood samples were centrifuged, the supernatants were collected for ELISA to detect the serum levels of IL-2, IL-6, TNF-α and MPO in each group.@*Results@#In the GRg3 group, the serum inflammatory cytokines, serum MPO concentration and the concentration of Bax and NF-κB in the intestinal tissues of rats were decreased along with the increasing dose of GRg3. These parameters in the high-dose GRg3 group were significantly lower than those in the saline group (all P<0.05), whereas did not significantly differ from those in the Smecta mixture enema group (all P>0.05), suggesting that GRg3 exerted good therapeutic effect on acute radiation proctitis in rat models.@*Conclusions@#GRg3 can significantly reduce the concentration of inflammatory cytokines, Bax and NF-κB in the intestinal tissues of rat models with acute radiation proctitis, which is more efficacious than the normal saline. GRg3 can be used to treat acute radiation proctitis in rat models.
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Objective To systematically review the efficacy and safety of postoperative radiotherapy and postoperative chemotherapy for patients with endometrial cancer,which may give support for clinical proper selection.Methods The randomized controlled trials (RCTs)comparing postoperative radiotherapy with post-operative chemotherapy for patients with endometrial cancer were searched in EMBase,PubMed,Cochrane Library,Chinese Biomedical Literature Data,China National Knowledge Infrastructure,and VIP database from the inception to August 201 5.Two reviewers independently assessed the quality of included studies and extrac-ted data.We analyzed the statistic data using RevMan 5.1 software.Results Three RCTs concluding 1 1 21 patients were included.Meta analysis showed that there were no significant differences between the two groups in five-year survival rate (RR =0.94,95%CI:0.80-1 .1 0,Z =0.77,P =0.440),five-year progression-free survival rate (RR =0.98,95%CI:0.90-1 .07,Z =0.52,P =0.61 0)and recurrence rate (RR =1 .06, 95%CI:0.91 -1 .24,Z =0.75,P =0.450),but there were significant differences between the two groups in grade 3-4 thrombocytopenia (RR =0.1 3,95%CI:0.07-0.27,Z =5.62,P <0.000 01 )and grade 3-4 neu-tropenia (RR =0.01 ,95%CI:0.00-0.03,Z =8.27,P <0.000 01 ).Subgroup analysis showed that there were significant differences between the two groups in five-year survival rate (RR =0.79,95%CI:0.68-0.91 , Z =3.1 5,P =0.002)and five-year progression-free survival rate (RR =0.82,95%CI:0.69-0.97,Z =2.31 ,P =0.020)for patients with Ⅲ-Ⅳ stage endometrial cancer.Conclusion Current evidence indicates that compared with postoperative radiotherapy,postoperative chemotherapy may improve the survival rate for pa-tients with advanced stage endometrial cancer.The long-term curative effects still need to be confirmed by RCTs with high quality and large sample.
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Objective To evaluate the toxicity and efficacy of carbon ion radiotherapy for cutaneous malignant melanoma. Methods Form December 2006 to May 2009, 13 patients with superficial malignant melanoma were treated with carbon ion radiotherapy in the Institute of Modern Physics, Chinese Academy of Sciences. The total dose was 60 -66 GyE in 6 -12 fractions within 6 -12 days. The disease was Stage Ⅱ_a in 2, Ⅱ_b in 3, Ⅱ_c in 5, and Ⅲ_c in 3 patients. The toxicities were assessed according to the Radiation Therapy Oncology Group (RTOG) criteria, and the efficacy was evaluated with WHO criteria. Results The median follow-up time was 13.5 months (range, 1 -25 months) and the follow-up rate was 100%. Of the 13 patients, 10(77%) achieved complete remission (CR), and 3(23%) partial remission (PR). The overall response rate (RR) was 100%, and the median survival time was 21.3 months (95% CI, 18. 1 -24.5 months). The grade 0, 1,2 and 3 skin reaction occurred in 3, 6, 2 and 2 patients, respectively. The hematologic toxicities were mild. Conclusions Carbon ion radiotherapy is a safe and effective treatment for cutaneous malignant melanoma.