Research progress on radiobiological effects of ferroptosis in cancer / 中华放射肿瘤学杂志

Ferroptosis is a new form of regulated cell death discovered in recent years, which is iron-dependent cell death characterized by peroxidation of polyunsaturated fatty acid phospholipids. Recent studies have shown that radiotherapy can induce ferroptosis in cancer cells via ionizing radiation. Targeting ferroptosis plays a synergistic role in tumor suppression with radiation, which not only further deepens the connotation of radiobiology, but also provides a new perspective for tumor radiosensitization. This review systematically summarizes the occurrence and defense of ferroptosis, focusing on the key role of ferroptosis in the radiobiological effects of tumor cells and the potential application of ferroptosis in radiosensitization.

Study on the inhibitory effect of UBE2T on radiosensitivity of lung adenocarcinoma / 中华放射肿瘤学杂志

Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.

Research progress of oxidative stress in the sensitivity of chemoradiotherapy for gliomas / 国际肿瘤学杂志

Following oxidative stress, reactive oxygen species are produced and accumulate in glioma cells in large quantities, and to avoid the occurrence of cellular dysfunction, glioma cells can respond adaptively in the biological processes of DNA damage repair, lipid peroxidation and protein modification to produce radiotherapy resistance. The expression of nuclear factor erythroid 2-related factor 2, solute carrier family 7 member 11, glutathione and microRNA, as key regulatory molecules, can regulate reactive oxygen species levels, alter glioma oxidative stress status, and affect radiochemotherapy sensitivity. Further study on the relationship between oxidative stress and sensitivity to radiotherapy and chemotherapy of glioma can provide theoretical basis for precise treatment of glioma.

Experimental study on the radiosensitization effect of etanidazole and paclitaxel on hepatocellular carcinoma H22 cells in mice / 肿瘤研究与临床

Objective To investigate the synergistic effect of etanidazole and paclitaxel on hepatocellular carcinoma H22 cells in mice. Methods To establish the murine xenografts, H22 cells was inoculated subcutaneously into the back of BALB/c mice. Among them, 40 tumor-bearing mice were divided into 4 groups by random number table method, 10 mice in each group, and each group injected with phosphate buffered saline (PBS), etanidazole (200 mg/kg), paclitaxel (1 mg/kg) and two drugs combination. Two hours after the administration, the mice were sacrificed by dislocation, and the drugs content in blood and tumor tissues of mice was measured by high-performance liquid chromatography. Sixty-five tumor-bearing mice were selected and divided into PBS non-irradiation group, PBS irradiation group, etanidazole irradiation group, paclitaxel irradiation group and two drugs combination irradiation group by random number table method, 13 mice/group. According to the grouping, the irradiated mice received 60Co source irradiation 2 hours after administration; the survival of 10 mice was observed at different time points, and the tumor volume was measured and calculated. The survival mice were killed by cervical dislocation 180 days after radiation. The other 3 mice in each group were killed after 2 days of irradiation, the tumor tissues were taken, and the expression of hypoxia inducible factor 1 (HIF-1) in these tumor tissues was detected by using immunohistochemistry. Statistical analysis of measurement data between groups was performed by using the one-way ANOVA and t test, and the survival analysis was made by Kaplan-Meier method. Results There was no significant difference of etanidazole and paclitaxel content in blood and tumor tissues between alone and combination administration groups at 2 hours after administration [etanidazole in blood: (55.5 ±4.7) μg/ml vs. (50.7±5.2) μg/ml; etanidazole in tumor: (31.2±3.5) μg/g vs. (33.6±5.4) μg/g; paclitaxel in blood: (316.9± 9.6)μg/ml vs. (289.5±10.3)μg/ml;paclitaxel in tumor: (161.7±7.2) μg/g vs. (181.3±11.6) μg/g; all P>0.05]. Within 40 days from the 10th day after the irradiation, the body weight of the irradiated group at each time point was significantly lower than that of the unirradiated group (all P< 0.05), but there was no significant difference in the body weight among the administration groups (all P>0.05). On the 40th day after irradiation, the tumor inhibition rates of the PBS irradiation group, etanidazole irradiation group, paclitaxel irradiation group, and two drugs combination irradiation group were 19.2％, 33.9％, 48.7％, and 61.6％, respectively. On the 180th day after irradiation, the survival rates of the PBS non-irradiation group, PBS irradiation group, etanidazole irradiation group, paclitaxel irradiation group, and two drugs combination irradiation group were 0, 0, 0, 12.5％, and 25.0％, respectively, and the median survival interval was 30.2, 54.7, 55.6, 83.4, and 102.8 d. After 2 days of irradiation, the positive expression rate of HIF-1 in the tumors tissues of PBS irradiation group, etanidazole irradiation group, paclitaxel irradiation group and two drugs combination irradiation group was lower than that in the PBS non-irradiation group, the differences were statistically significant [(45.7 ±4.8)％, (40.6 ±5.9)％, (24.5±5.6)％, (17.2±3.7％)％vs. (63.1±7.2)％, all P<0.05]. The positive expression rate of HIF-1 in the paclitaxel irradiation group and two drugs combination irradiation group was lower than that in the PBS irradiation group and etanidazole irradiation group (all P<0.05). Conclusion The combination of etanidazole and paclitaxel has synergistic radiation sensitization effect on hepatocellular carcinoma H22 cells in mice, and the expression level of HIF-1 is decreased, reflecting the decrease of hypoxic cells.

Effect of insulin-like growth factor-I receptor on radiosensitivity of HepG2 cells / 中华肝胆外科杂志

Objective@#To explore the effect of insulin-like growth factor-Ⅰ (IGF-Ⅰ) receptor on radiosensitivity of HepG2 cells and the underlying mechanism.@*Methods@#HepG2 cells were divided into the following groups: negative control group, siRNA group, irradiation group and combined group. HepG2 cells were transfected with IGF-Ⅰ receptor siRNA combined with irradiation therapy to investigate the effect on cell proliferation by methyl thiazolyl tetrazolium and cell cycle using flow cytometry. Expression of IGF-Ⅰ receptor, proliferating cell nuclear antigen (PCNA), cyclin-dependent kinases 1(CDK1) and Survivin were detected using Western blotting and Q-PCR.@*Results@#The expression of IGF-Ⅰ receptor in HepG2 cells was decreased significantly after siRNA transfection compared with the control group. After the combinational therapy, cell viability was decreased significantly according with control group [(1.02±0.08) vs. (1.08± 0.10) vs. (0.60±0.07)]; In addition, cell cycle was arrested in G2/M[(20.3±0.3)% vs. (22.6±0.4)% vs. (34.7±0.5)%] and CDK1 expression was reduced significantly. The relative expression of Survivin in siRNA group was lower than negative control group, the difference was statistically significant (P<0.05).@*Conclusion@#Inhibition of IGF-Ⅰ receptor can enhance the radiosensitivity of HepG2 cells through cell cycle arrest.

Preliminary investigation into construction of sensitivity model of adjuvant radiotherapy in cervical cancer based on gene expression data in vivo / 肿瘤研究与临床

Objective To construct a radiosensitivity model based on gene expression in tumor tissues, and to explore the feasibility of using this model to select the patients benefiting from adjuvant radiotherapy in cervical cancer. Methods Patients underwent radical hysterectomy alone or radical hysterectomy plus adjuvant radiotherapy were selected from The Cancer Genome Atlas (TCGA) cervical cancer dataset. Candidate radiosensitive genes were identified through multivariate Cox regression analysis with recurrence free survival (RFS) as end-point events. The sum of regression coefficients and products of expression levels of candidate genes was calculated as radiosensitivity index. Time-dependent receiver operating characteristic (ROC) curve analysis was used to analyze the predictive accuracy of this model for RFS. Kaplan-Meier plot coupled with Log-rank test was used to evaluate difference in RFS between subgroups with different radiosensitivity. Results A total of 155 patients underwent radical hysterectomy was retrieved from the phenotype dataset among which 18 patients was completely treated with planned adjuvant radiotherapy. Expression values of 17156 genes and 480 microRNAs after probes filtration were included into analysis. Twenty-three genes were identified consistent with statistical criterion. Hierarchical cluster analysis revealed 7 subgroups existed across these 23 genes. The MAT2A, PIGY, SUSD1, ZNF341, TMEM85, HIF1AN and CLEC18A genes were finally selected to calculate radiosensitivity index. The median value and range of RI was 0.7258 (-5.501 - 9.046). In subset consist of patients underwent radical hysterectomy alone, adjusted for intravascular tumor thrombus, radiosensitivity index was independent prognostic factor (HR = 1.456, 95％CI 1.192-1.780, P<0.01). Whereas, radiosensitivity index was remained significantly associated with RFS after adjustment for the number of positive nodes in subset comprised of patients underwent radical hysterectomy plus adjuvant radiotherapy (HR = 0.572, 95％ CI 0.328-0.998, P = 0.049). Moreover, radiosensitivity index exhibited more accuracy in prediction for 3 or 5 years RFS compared with clinical prognostic factors N stage and intravascular tumor thrombus. Conclusion The radiosensitivity model based on gene expression data in tumor tissues has potential value to select the cervical cancer patients benefiting from adjuvant radiotherapy.

Effect of ubiquitin-specific protease on radiosensitivity of tumor / 国际肿瘤学杂志

Ubiquitin-specific protease is a member of the deubiquitinating enzyme family,which can reverse the ubiquitination of proteins and stabilize proteins. It affects radiosensitivity of tumor by regulating DNA damage,cell cycle,nuclear factor-κB signaling pathway,Nrf2-Keap1 signaling pathway and oncogene c-myc. It is expected to become a new target for tumor radiotherapy sensitization.

Screening of radiosensitivity associated genes in esophageal squamous cell carcinoma based on the copy number variance in whole genome / 肿瘤研究与临床

Objective To analyze copy number variance (CNV) in whole genome by using gene chip technology, and to screen the radiosensitivity associated genes on esophageal squamous cell carcinoma (ESCC). Methods The patients with ESCC who received radiotherapy alone in Anyang Tumor Hospital from December 2013 to August 2016 were selected, and biopsy paraffin samples were preserved in the center of pathology. The patients were divided into radiosensitivity group (group S) and radio-resistance group (group R). DNA was extracted from these paraffin samples in both groups. Whole human genome CNV was detected by using genechip from OncoScan Array platform designed by Affymetrix company, and the differences of gene segments were screened in the two groups. Results Nineteen samples of ESCC patients were collected to extract DNA in this study. To balance pair analysis in the two groups, 10 samples were selected from the qualified patients, including 5 cases in group S and 5 cases in group R respectively. There were no statistical differences in gender, age, lesion site, lesion length, radiation dose of the two groups (all P> 0.05). Loss of heterozygosity (LOH) was the main type of CNV. The analysis results showed that LOH in q24.32-q24.33 of chromosome 10 and LOH in q21.2-q21.31 of chromosome 18 had high frequencies (100 ％) in group R, however, none were detected in group S. LOH in q27-q28.1 of chromosome 4 had a high frequency (80％) in group S , however, none were detected in group R. Conclusion LOH in 10q/18q is related to radio-resistance in ESCC, and LOH in 4p is associated with radiosensitivity in ESCC.

Expression of programmed death-1 ligand-1 in esophageal squamous cell carcinoma and its effect on radiosensitivity and prognosis / 肿瘤研究与临床

Objective To investigate the relationship of programmed death ligand-1 (PD-L1) with clinicopathological characteristics,radiosensitivity and prognosis of the patients with esophageal squamous cell carcinoma(ESCC). Methods Ninety ESCC patients who received radical radiotherapy diagnosed by ESCC in Affiliated Hospital of North Sichuan Medical College were enrolled. Twenty cases of normal esophageal mucosa were used as the controls. The expression of PD-L1 was detected by using immunohistochemical SP method. Results The expression of PD-L1 protein was not correlated with age, gender, the maximum diameter of tumor, the length of lesion, the local aggressive of tumor, clinical stage and primary tumor volume (all P> 0.05). However, it was statistically correlated with the lymphatic metastasis (χ2= 4.404, P= 0.036). Meanwhile, PD-L1 positive expression was sensitive to radiation(χ2=4.888, P< 0.05). Single factor analysis showed that the maximum diameter of tumor and radiosensitivity were correlated with progression-free survival (PFS) (χ2=6.239,P =0.013;χ2=6.852,P =0.008; χ2= 6.312, P= 0.012) and overall survival (OS) (χ2=8.170, P = 0.004; χ 2= 4.261, P = 0.039; χ2= 5.003, P= 0.025) of ESCC patients. Multifactor analysis showed that the radiosensitivity and the maximum diameter of tumor affected PFS (OR= 0.512, 95 % CI 0.275-0.954, P= 0.035) and OS (OR= 0.507, 95 % CI 0.266-0.968, P= 0.039) in ESCC patients, respectively.Conclusions The level of PD-L1 expression is increased significantly in ESCC tissues compared with the normal esophageal mucosa tissues. PD-L1 may be a novel biomarker for predicting metastatic potential and radiosensitivity in ESCC patients, rather than the prognosis predictors of ESCC patients treated by radiotherapy.

Curcumin induce the radiosensitivity of human lung carcinoma NCI-H460 cells through the NF-κB pathway / 重庆医学

Objective To study the combination effectof curcumin and γray on the activity of human lung carcinoma NCI-H460 cells and explore the sensitization of curcumin to γray.Methods The NCI-H460 cells proliferation were detected by MTT,the cell cycle and apoptosis by flow cytometry.The expression of Bcl-2 and Bax were detected by Western Blot and the NF-κB gene expression by RT-PCR.In addition,the mice model of lung cancer was randomly divided into 4 groups:control group,curcumin group,γ ray group and combination group.After 28 days,the tumor volume was measured.Results The proliferation and cell cycle of NCI-H460 cells were inhibited and the apoptosis was increased in combination group.In addition,compared with curcumin group or γray group,the expression of Bcl-2 was inhibited,but the expression of Bax was increased and the mRNA expression of NF-KB was inhibited in combination group(all P＜0.05).Also in combination group the tumor volume was significantly inhibited compared with curcumin group or γ ray group(all P＜0.05).Conclusion Curcumin might induce the radiosensitivity of Human Lung Carcinoma NCI-H460 cells through the pathway.

A phase Ⅱ prospective study on raltitrexed combined with concurrent radiotherapy for elderly esophageal carcinoma / 国际肿瘤学杂志

Objective To evaluate the clinical effects and adverse reaction of raltitrexed combined with radiation for esophageal carcinoma in elderly patients.Methods Sixty patients were randomly divided into two groups by the envelope method, 30 patients in experimental group received raltitrexed combined with radiotherapy and 30 patients in control group received radiotherapy only.Patients in both groups received conventional radiotherapy with a total dose of 56-60 Gy/28-30 F.In experimental group, raltitrexed 2.6 mg/m2 was administered concurrently with the radiotherapy on d1 and d22.Two cycles of concurrent chemotherapy were administered during radiotherapy.The short-term effects, survival times and adverse reactions of the two groups were compared.Results The total effective rates of experimental group and control group were 93.3% and 73.3%, respectively, and there was statistically significant difference between the two groups (χ2=4.320, P=0.038).The median survival times of experimental group and control group was 24.0 months and 12.0 months, respectively, and there was statistically significant difference by Log-rank test (χ2=6.048, P=0.014).The major adverse reactions of grade 3-4 in experimental group and control group were radiation-induced esophagitis (10.0% vs.3.3%;χ2=0.268, P=0.605), leukopenia (13.3% vs.10.0%;χ2=0.000, P=1.000), thrombocytopenia (3.3% vs.0;P=1.000), nausea and vomiting (6.7% vs.0;χ2=0.517, P=0.472), and the differences were not statistically significant.Conclusion Raltitrexed combined with radiotherapy can enhance the short-term effect and prolong the survival time for the elderly esophageal carcinoma patients, and the adverse reactions are mild.It is worthy of further clinical study.

Expression of UHRF1 protein in breast cancer tissue and its correlation with local recurrence / 肿瘤研究与临床

Objective To investigate the expression of UHRF1 protein in breast cancer and adjacent normal tissues, and its relationship with local recurrence. Methods Immunohistochemistry (IHC) was applied to detect the expression of UHRF1 protein in 69 specimens of breast cancer and 33 specimens of corresponding adjacent normal tissues; Chi-square test was used to analyze the relationship between UHRF1 protein expression and clinical factors. Results The positive rate expression of UHRF1 protein in breast cancer was 55.1 % (38/69), and UHRF1 protein expression was not found in adjacent normal tissues. The positive expression rate of UHRF1 protein in stage III was higher than that in stageⅠ-Ⅱ[68.4%(26/38) vs. 38.7 % (12/31), P< 0.05]. The positive expression rate of cancer tissue in breast cancer patients with chest wall recurrence after radiotherapy within 1 year was higher than that in patients without recurrence [83.3 %(10/12) vs. 49.1 % (28/57), P< 0.05], and UHRF1 protein expression of patients in different age and Herb-2 had no statistical significance (P> 0.05). Conclusions The positive expression rate of UHRF1 protein is obviously higher than that in adjacent normal tissue. Besides, UHRF1 protein is related to the stage and chest wall of local recurrence after radiotherapy.

Expression of UHRF1 protein in breast cancer tissue and its correlation with local recurrence / 肿瘤研究与临床

Objective To investigate the expression of UHRF1 protein in breast cancer and adjacent normal tissues, and its relationship with local recurrence. Methods Immunohistochemistry (IHC) was applied to detect the expression of UHRF1 protein in 69 specimens of breast cancer and 33 specimens of corresponding adjacent normal tissues; Chi-square test was used to analyze the relationship between UHRF1 protein expression and clinical factors. Results The positive rate expression of UHRF1 protein in breast cancer was 55.1 % (38/69), and UHRF1 protein expression was not found in adjacent normal tissues. The positive expression rate of UHRF1 protein in stage III was higher than that in stageⅠ-Ⅱ[68.4%(26/38) vs. 38.7 % (12/31), P< 0.05]. The positive expression rate of cancer tissue in breast cancer patients with chest wall recurrence after radiotherapy within 1 year was higher than that in patients without recurrence [83.3 %(10/12) vs. 49.1 % (28/57), P< 0.05], and UHRF1 protein expression of patients in different age and Herb-2 had no statistical significance (P> 0.05). Conclusions The positive expression rate of UHRF1 protein is obviously higher than that in adjacent normal tissue. Besides, UHRF1 protein is related to the stage and chest wall of local recurrence after radiotherapy.

Research advances in DNA methylation and radiosensitivity of cancer cells / 中华放射肿瘤学杂志

A methylation is one of the important approaches for regulation of gene expression. It plays a role in tumor development and progression and is closely associated with the radiosensitivity of cancer cells. The aberrant DNA methylation in cancer cells can provide biomarkers for early diagnosis of cancer. Moreover, it can contribute to the evaluation of the efficacy of radiotherapy, radiosensitivity enhancement, prognostic assessment, and disease monitoring. In order to provide a theoretical basis for further investigation of the epigenetic mechanisms for radioresistance of cancer cells, this paper reviews the relationship between DNA methylation and radiosensitivity and the potential value of DNA methylation in radiotherapy.

Gene expression profiling of a radioresistant esophageal squamous cancer cell line / 中华放射肿瘤学杂志

Objective To establish a radioresistant esophageal squamous cancer cell line,and to identify the radioresistant genes and mechanisms.Methods The radioresistant KYSE410-res cell line was established by repeated exposure of cell line KYSE410 to radiation.The proliferation and apoptosis of esophageal squamous cancer cells were evaluated before and after radiation.The changes in gene expression of the esophageal squamous cancer cells after radiation were determined by gene microarray and analyzed by group t test.The genes with significant difference in expression after radiation were validated.Results The KYSE410-res cells had significantly enhanced proliferation and anti-apoptosis than the KYSE410 cells (all P＜0.05).The result of gene microarray showed that compared with the KYSE410 cells,the KYSE410-res cells had the expression of 463 and 251 genes upregulated and downregulated by no less than 4 folds,respectively.Those genes with different expression levels after radiation were mainly responsible for cell proliferation,adhesion,signal transduction,angiogenesis,reactive oxygen metabolism,cell damage repair,and the MAPK/ERK signaling pathway.OAS2 and UBD were key proteins in the network.In the KYSE410-res cells,the expression of HLA-DQBI,MMP1,NCAM1,ZNF521,GPC6,SELENBP1,LCN15,and TFPI-2 genes measured by real-time PCR was consistent with that measured by gene microarray.Conclusions Abnormal activation of the MAPK/ERK signaling pathway,upregulated expression of OAS2 and UBD,downregulated expression of TFPI-2,and upregulated expression of MMPs may play a role in radioresistance of esophageal cancer cells.

Polymorphic Variants in Oxidative Stress Genes and Acute Toxicity in Breast Cancer Patients Receiving Radiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Reactive oxygen species (ROS) are generated as an indirect product of radiation therapy (RT). Genetic variation in genes related to ROS metabolism may influence the level of RT-induced adverse effects. We evaluated the potential association of single nucleotide polymorphism (SNP)-related response to radiotherapy injury in breast cancer patients undergoing RT. MATERIALS AND METHODS: Eighty patients receiving conventional RT were included. Acute effects were evaluated according to the Radiation Therapy Oncology Group (RTOG) scores. DNA was extracted from blood and buccal swab samples. SNPs were genotyped for GSTP1, GSTA1, SOD2, and NOS3 genes by polymerase chain reaction-based restriction fragment length polymorphism. Univariate analysis (odds ratios [ORs] and 95% confidence interval [CI]) and principal component analysis were used for correlation of SNPs and factors related to risk of developing ≥ grade 2 acute effects. RESULTS: Sixty-five patients (81.2%) showed side effects, 32 (40%) presented moderate to severe acute skin toxicity, and 33 (41.2%) manifested minimal acute skin reactions by the end of treatment. In both univariate and multivariate analyses, nominally significant associations were found among body mass index (OR, 3.14; 95% CI, 8.5338 to 1.1274; p=0.022), breast size (OR, 5.11; 95% CI, 17.04 to 1.54; p=0.004), and grade ≥ 2 acute radiation skin toxicity. A significant association was also observed between NOS3 G894T polymorphism (OR, 9.8; 95% CI, 211.6 to 0.45; p=0.041) and grade ≥ 2 acute radiation skin toxicity in patients with neo-adjuvant chemotherapy treatment. CONCLUSION: The analysis of the factors involved in individual radiosensitivity contributed to the understanding of the mechanisms underlying this trait.

Study of the impact of CLPTM1L on radiosensitivity of lung cancer / 国际生物医学工程杂志

Objective To study the correlation of cleft lip and palate transmembrane 1 like(CLPTM1L)expression and radiosensitivity of lung cancer cells.Methods Thiazolyl blue tetrazolium bromide(MTT) and cell colony formation assays were used to determine cell growth and survival.Western Blot assay was employed to measure protein expression.Results The results demonstrated a negative correlation between the CLPTM1L expression level and radiosensitivity of lung cancer cells.A lower radiosensitivity in lung cancer cells containing high level of CLPTM1L expression,and vice versa.Enforced expression of CLPTM1L resulted in a significant reduction of radiosensitivity in lung cancer cells irradiated with γ-rays.On the contrary,a marked elevation of radiosensitivity was observed in lung cancer cells transfected with CLPTM1L siRNA.Conclusions CLPTM1L may be a novel target gene in mediating radiosensitivity of lung cancer cells.

Establishment of a logistic regression model for the predicting of radio-sensitivity of preoperative radiotherapy in rectal cancer / 肿瘤研究与临床

Objective To investigate the correlation between the biomarkers related to radio-sensitivity and preoperative radiotherapy in rectal cancer patients, and to establish a logistic regression model to predict the effect of the preoperative radiotherapy through detecting the expression levels of the molecular markers. Methods 33 patients with rectal cancer who received preoperative radiotherapy from January 2010 to January 2015 were retrospectively analyzed. Patients' information was also collected including the serum level of carcino-embryonic antigen (CEA), the immune-histochemical expression levels of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), thymidylate synthase (TS) and Ki-67, and image data (CT or magnetic resonance imaging) before radiotherapy, preoperative clinical staging and the postoperative pathologic staging. According to the postoperative pathological remission, the treatment effects of preoperative radiotherapy included effective (CR+PR) and ineffective (PD+SD) were evaluated. The relationship between these molecular markers and the curative effect of preoperative radiotherapy was analyzed by logistic regression analysis using SPSS v17.0 software, and a logistic curative effect prediction model was established. Results As a result of single factor and multiple factors logistic binary regression analysis, CEA, VEGF and Ki-67 were recognized as the interested factors for the radio-sensitivity predicting in patients with rectal cancer who received preoperative radiotherapy. A molecular markers predictive model for radio-sensitivity in preoperative radiotherapy in rectal cancer is as follow: log P=1.700-0.276×CEA-0.238×VEGF-0.135 ×EGFR+1.377 ×TS+0.080 ×Ki-67. Serum CEA level and the expression of VEGF might associate with radio-resistant, and the expression of Ki-67 might associate with better reaction to preoperative radiotherapy. Conclusion The levels of serum CEA, VEGF and Ki-67 may be the predictors of radio-sensitivity in rectal cancer patients who received preoperative radiotherapy.

Astaxanthin enhanced radiotherapy sensitivity of human lung cancer A549 cells transplanted in nude mice / 天津医药

Objective To observe the effect of astaxanthin on radiotherapy sensitivity of lung cancer A549 cells transplanted in nude mice. Methods Twenty BALB/c nude mice were divided into four groups:control group (mice were gavaged with pure water containing with 10% DMSO), astaxanthin group (mice were gavaged with astaxanthin suspension containing with 10%DMSO, astaxanthin was given to mice with the dose of 50 mg/kg on the first day, and every other day in the following days with a total of 7 times), radiotherapy group (mice were gavaged with pure water containing with 10%DMSO, the tumor site was given local radiotherapy with a dose of 5 Gy per time and the total dose was 15 Gy) and combination group (mice were given 50 mg/kg astaxanthin and radiotherapy with 15 Gy total irradiated dose). When the minor axis of the tumor reached 5 mm we began experiment. Tumor growth curve was measured by detecting the line of apsides every other day. Mice were killed on the second day after the last time of astaxanthin administration. Weights of tumor were measured by a balance and then tumor mass was processed into paraffin sections. Expressions of proliferating tumor cell antigen Ki-67, phosphorylated-signal transducers and activators of transcription (p-STAT3), and cell apoptosis (measured by terminal deoxynucleotidyl transferase mediated dUTP nick- end labeling, Tunnel) were detected by immunohistochemistry. Results Compared with control group, the transplanted tumor growth rate slowed down in other three groups (P<0.05), and tumor growth was the most slowly in the combination group. Tumor weight, Ki-67 and p-STAT3 expressions were decreased gradually in turn in control group, astaxanthin group, radiotherapy group and combination group. The anti-tumor rate and percentage of cell apoptosis were increased gradually in turn. There was significant difference between groups by multiple comparison statistics(P<0.05). Conclusion Astaxanthin enhances radiotherapy sensitivity of human lung cancer A549 cells in nude mice by down-regulating the expression of p-STAT3.

Radiosensitizing effect of genistein on laryngeal carcinoma Hep-2 cells / 中国耳鼻咽喉头颈外科

OBJECTIVETo investigate whether the genistein can increase the radiosensitizing effect on laryngeal squamous carcinoma Hep-2 cells.METHODS Hep-2 cells were treated with genistein, radiation, and genistein plus radiation respectively. DMSO was used as the control group. EdU assay was performed to assess the short-term effect of genistein and (or) radiation on the proliferation of Hep-2 cells. Clonegenic assay was used to detect the survival rate of Hep-2 cells after treatment with radiation doses of 0, 2, 4, 6, 8 Gy and radiation combined with genistein. The data was fitted into the classic single-hit multi-target mathematical model to analyze the long-term effect on cell proliferation death of Hep-2 cells.RESULTSIt was observed that radiation combined with genistein could significantly inhibit the proliferation of Hep-2 cells. And the SER of 10μmol/L genistein was 1.412.CONCLUTIONGenistein can inhibit the proliferation of Hep-2 cells by DNA synthesis inhibition, and can be an adjunct agent of radiotherapy.