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Objective@#To explore radiosensitivity-associated genes in esophageal squamous cell carcinoma by targeted sequencing panel.@*Methods@#The peripheral blood from 22 esophageal squamous cell carcinoma (ESCC) patients received radiotherapy alone were collected, respectively. The genomic DNA (gDNA) of peripheral blood was extracted and used to create a library of gDNA restriction fragments. The gDNA restriction fragments were hybridized to the HaloPlex probe capture library, which comprises 356 cancer genes selected from the Catalogue of Somatic Mutations in Cancer (Cosmic) database of 2011 updated edition. The sequencing data were aligned by the Genome Analysis Toolkit GATK (version 3.0) and Picar. The single nucleotide polymorphism and inserted-deletion (SNP/InDel) variations were annotated by online database. The pathway enrichment was analyzed by Ingenuity Pathway analysis (IPA). Moreover, according to the short-period curative effect, 22 patients were divided into two groups: the radiation- sensitivity group (CR+ PR) and the radiation-resistant group (PD+ SD). The nonsynonymous mutation sites were statistically analyzed and the genes associated with radiosensitivity of ESCC were screened.@*Results@#More than 97% sequencing reads were aligned to human genome reference sequence and more than 90% sequencing reads were the target sequences. SNP/InDel database annotation results showed that the mutations of 22 cases mainly distributed in exons, and the mutant types were mainly missense and synonymous single nucleotide variant (SNV). There were 23 genes of high-frequency mutation associated with esophageal cancer. Pathway enrichment by IPA showed that 3 pathways were associated with the development of esophageal cancer, which were roles of BRCA1 in DNA damage response pathway, DNA double-strand break repair by non-homologous end joining pathway and ATM signaling pathway. According to the curative effect, five genes including mismatch repair system component (PMS1), fibronectin 1(FN1), mutL homolog 1 (MLH1), B-Raf proto-oncogene, serine/threonine kinase (BRAF), patched 1 (PTCH1) and cytochrome P450 family 2 subfamily C member 19 (CYP2C19) were associated with radiosensitivity of ESCC patients.Moreover, the PTCH1 was mutated in all of 22 ESCC patients, while the variations of rs199476092 and rs202111971 sites of PTCH1 were only identified in the radiation-resistant group.@*Conclusions@#We find that the variations of rs199476092 and rs202111971 in the encoding region of PTCH1 gene are significantly associated with radiosensitivity of ESCC patients.
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Objective: To evaluate the effect and safety of molecular targeted therapy of apatinib mesylate combined with multiple antigen stimulatiing cellular therapy in treatment of osteosarcoma and soft tissue sarcoma. Methods:Six patients with sarcoma were collected by the failure of surgery, radiation and chemotherapy treatment or refusal surgery, radiation and chemotherapy, and at least one month from the last treatment of surgery, radiation and chemotherapy. All of the patients at least received three cycle MASCTTM . From Day 1,everyone were given Apatinib 500 mg,po,qd ,until the disease progression. To measure the patient’s quality of life depending on EORTC QLQ-C30,meanwhile,detecting the cellular immunity function and circulating tumor cells(CTCs) of patients before treatment and one month after 3 cycle MASCTTM . At last, monitoring the cellular immune responses by the Enzyme-linked immuno spot ( ELISPOT) assay. Results: All of the four patients completed the treatment of 3 cycle MASCTTM . Only one patient reduced apatinib from 500 mg to 250 mg because of palmar-plantar erythrodyses-thesia. The response rates of the four patients received MASCTTM and apatinib mesylate after treatment were 1 for complete response (CR),3 for partial response (PR). The life quality and cellular immunity function were improved in all of the patients. ELISPOT assay suggested that the majority of antigen peptides could induce specific cytotoxic T lymphocytes( CTLs) response. The Progression-Free-Survival ( PFS) of four patients received MASCTTM and apatinib mesylate was 7,6,9 and 4 months ,while the response rates of the two patients received apatinib mesylate were 1 for ( Stable disease) SD,one for ( Progression disease) PD. And PFS of the two patients were one month and two months. Conclusion:Combination of MASCTTM and apatinib mesylate is safe,effective and were good prospects for application.
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Objective To investigate the radiosensitivity of stem cells in pancreatic adenocarcinoma PANC‐1 cell line and the possible mechanism of its radiation resistance .Methods Using flow cytometry ,the cells were isolated and sorted into CD44+CD24+ ,CD44-CD24+ ,CD44+CD24- ,and CD44-CD24- .Multi‐target click model was used to fit cell survival curves and deter‐mine the sensitizer enhancement ratio .The apoptosis and cycle distribution of the four cell subsets were determined using flow cy‐tometry ,and the level of ROS was determined by DCFH‐DA probe .Results The ratio of CD44+ and CD24+ in the sorted PANC‐1 cell line was 92 .0% and 4 .7% respectively .Before radiation ,there was no statistically significant difference between four groups (P>0 .05);After treated with 6MV‐X ray ,The ratio of apoptosis was the lowest in CD44+CD24+ (P<0 .01);The percentage G0/G1 cell was the highest in CD44+CD24+ (P<0 .01) ,the sensitizer enhancement ratio of CD44+ CD24- ,CD44-CD24+ and CD44-CD24- were 1 .61 ,1 .81 ,1 .94 ,respectively .The level of ROS in CD44+CD24+ was lower (P<0 .01) .Conclusion Tumor stem cells of pancreatic adenocarcinoma have properties of a lower level of ROS and relative stationary that maybe the reasons of radio resist‐ance .
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Objective To evaluate the effect of raltitrexed plus oxaliplatin combined with concurrent radiotherapy on life quality of advanced esophageal carcinoma.Methods Oesophageal cancer specific health related quality of life questionnaire(QLQ-OES18) was used to evaluate the life quality of 54 patients with esophageal carcinoma respectively at 1 day pre-treatment(baseline level),1 day post-treatment and 1month post-treatment.Total 54 patients were treated with raltitrexed plus oxaliplatin combined with con-current radiotherapy.Comparing the differences of quality of life scores at different time points,and analyzing the correlation of the differences between the 1month post-treatment and baseline score and short term effect.Results The scores of difficulty swallo-wing,eating difficulties,saliva decreased significantly at 1 day post-treatment than that of pre-treatment(P0.05).The scores of 1 day post-treatment were significantly reduced compared to baseline levels except re-flux and speech(P<0.05).It was positive correlation between the difference of 1 month post-treatment and baseline score and short term effect,and the correlation coefficients was 0.85,0.55,0.73,0.32(P<0.05),respectively.Conclusion There is a transient im-pact of raltitrexed plus oxaliplatin combined with concurrent radiotherapy on quality of life for advanced esophageal carcinoma after treatment,but most of the life quality of the patients could be improved after 1 month obviously.
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Objective To investigate the therapeutic effects of recombinant human endostatin (RHES) combined with radiotherapy on brain metastases (BM) of non-small cell lung cancer (NSCLC) and the patients suitable for this therapy.Methods Eighty patients with BM of NSCLC were randomly divided into RHES combined with radiotherapy group (combination group) and radiotherapy alone group (each group with 40 patients).The short-term effective rate,overall survival time,cerebral edema index and adverse reactions were observed and the expressions of vascular endothelial growth factor receptor 2 (VEGFR2) protein in primary lesions were detected with immunohistochemical method in all patients.Results Compared with radiotherapy alone group,brain edema was significantly relieved (t=4.9,P=0.000) and there were no marked adverse reactions in combination group.In short-term effective rate,there was no statistical significance in total population (n=80,90％ vs.75％,x2=3.11,P=0.07),but there was statistical significance in the patients with positive VEGFR2 (93％ vs.67.7％,x2=6.31,P=0.012).In overall survival time,there was no statistical significance in total population (n=80,P=0.35,95％ CI:0.25-1.30) or in the patients with positive VEGFR2 (P=0.109,95％ CI:0.40-1.34).Conclusion Compared with radiotherapy alone,RHES combined with radiotherapy can relieve brain edema in the patients with BM of NSCLC and obtain better short-term effective rate in the patients with positive VEGFR2.
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ObjectiveTo investigate the radiosensitizing effect of 3-(5'-hydroxy-2'-furyl)-1-benzyl indazole ( YC-1 ) on hypoxic human adenocarcinoma cell line A549.MethodsMTT assay was used to test the inhibitory effect of YC-1 on proliferation of A549 cells.Clonogenic assay was performed to determine the radiosensitizing effect of YC-1 on hopxic A549 cells.Single-hit multi-target model was used to plot survival curve and calculate sensitization enhancement ratio (SER).The cell cycle and apoptosis were measured by flow cytometry.ResultsThe proliferation of A549 cells was inhibited by YC-1 in a time-dose-dependent manner.In normoxic and hypoxic cells,the IC20 was 16.7 μmol/L and 39.2 μmol/L at 24 h,respectively.In the group of hypoxia plus YC-1,SERD0 and SERDq were 1.11 and 1.26,respectively.In hypoxia,YC-1combined with 2 Gy irradiation could induce cell apoptosis and prolong G2 + M phase arrest ( ( 30.17 ±1.21 )％ ∶ ( 15.44 ±0.96) ％,P =0.000; (21.56 ±0.47 )％ ∶ (6.16 ±0.16)％,P =0.000).Concinsions YC-1 could enhance the radiosensitivity of hypoxic A549 cells.
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Objective To study the inhibitory effects of radiotherapy and 125I seed brachytherapy on the growth of transplanted human lung cancer cell line A549 in nude mice and the impact of HIF-1αexpression after therapy.Methods Forty nude mice bearing human lung cancer cell line A549 were randomly divided into control group,radiotherapy group,125I seed brachytherapy group and radiotherapy + 125I seed group when tumor volume achieved (300±50) mm3.The tumor growth was observed and the alteration of tumor size was calculated at different time.On 15th day,the expression of HIF-1α was detected by immunohistochemistry and western blot.Results When eighth day after treatment,compared with the control group,the tumor volume of the combined treatment group was significantly smaller (t = 46.4,P ＜0.05).After fifteenth day after treatment,compared with control group,the group of radiotherapy,125I seed brachytherapy and radiotherapy + 125I seed gained the tumor control rate of 45.9 %,44.4 %,69.4 % respectively.Compared with other groups,the change of expression of HIF-1α in the combined treatment group was not significant (P ＞0.05).Conclusion Radiotherapy combined with 125I seed brachytherapy can inhibit the growth of transplanted human lung cancer cell line A549 in nude mice,and the tumor regression can be observed in early stage.But in our study,the expression of HIF-1α in tumors cannot be inhibited by 125I seed.
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ObjectiveTo observe the dynamic changes of blood perfusion and hypoxic status by CT perfusion imaging and hypoxia imaging in patients with non-small cell lung cancer (NSCLC) after treatment with recombinant human endostatin (RHES). MethodsA total 15 patients with NSCLC were randomly divided into treatment group (n = 10) and control group (n = 5). The patients in treatment group continuouly received the treatment with RHES (7.5 mg/m2) by intravenous infusion for ten days, and CT perfusion imaging and hypoxia imaging were performed at day 1, 5 and 10,respectively. The time window' was observed with the blood perfusion status and hypoxic changes.ResultsIn the treatment group, capillary permeability surface (PS) and tumor to normal tissue (T/N) were firstly decreased, and then increased. Their lowest points occurred at about the fifth day. PS showed statistical significance compared with the first day (q1.5 = 12.05, P＜0.01 ) and no significance compared with the tenth day(q10.5 = 2.79, P=0.69), while T/N showed a significant difference between above time points (q1.5 = 73.81, q10.5 = 20.6, P = 0.00).Blood flow (BF) was firstly increased, and then decreased.Its highest point appeared at about the fifth day with statistical significance compared with the first and tenth day (q1.5 = 12.29, q10.5 = 10.48, P＜0.01 ). All the PS,BF and T/N between the fifth day in treatment group and the control group showed statistically significance (all P ＜ 0.01 ).Conclusions The time window of recombinant human endostatin improving blood perfusion and hypoxic status in non-small cell lung cancer is within about one week after administration.