2016 Vol. 40, No. 2

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Original Article
HPV16 E6/E7 Negatively Affect Radiosensitivity of Lung Cancer Cells
Lu Lu, Qinghui Meng, Ming Cui, Xiaofei Chu, Shuyi Zhao, Huiwen Xiao, Jiali Dong, Eliot Marty Rosen, Saijun Fan
2016, 40(2): 85-90. doi: 10.3760/cma.j.issn.1673-4114.2016.02.001
Abstract:
Objective Lung cancer cells associated with radioresistance are likely to give rise to local recurrence and distant metastatic relapse, but little is known about its underlying mechanisms. In the present paper, the effects of the HPV16 E6 and HPV16 E7 oncoprotein on the radiosensitivity of lung cancer cell lines were investigated. Methods The HPV16 E6 or HPV16 E7 oncoprotein was expressed by a transient transfection with pcDNA3-HPV16 E6 or pcDNA3-HPV16 E7 expression vector. Human lung cancer H2179 cells and mouse lung cancer Lewis cells were exposed to a γ-ray radiation source, cellular survival was evaluated by using a colony formation assay. The expression of HPV16 oncoproteins E6/E7, extracellular signal-regulated kinases 1/2(ERK1/2) and AKT signaling was determined by Western blot assay. VEGF secretion was determined by ELISA. Results Both HPV16 oncoproteins E6 and E7 significantly decreased radiosensitivity of H2179 cells, associated with a promotion of the ERK1/2 and AKT phosphorylation. A decrease of reactive oxygen species(ROS) and an increase of VEGF levels were observed in the cells expressing the HPV16 oncoproteins E6 and E7. Furthermore, a similar reduction of radiosensitivity mediated by the HPV16 oncoproteins E6 and E7 was also observed in a mouse lung cancer Lewis cells. Conclusion The findings indicate that the HPV16 oncoproteins E6 and E7 negatively affects susceptibility of lung cancer cells to radiotherapy via regulation of the ERK1/2 and Akt signaling pathway and VEGF expression.
Ionizing Radiation Induces HMGB1 Cyto-plasmic Translocation and Extracellular Release
Lili Wang, Li He, Guoqiang Bao, Xin He, Saijun Fan, Haichao Wang
2016, 40(2): 91-99. doi: 10.3760/cma.j.issn.1673-4114.2016.02.002
Abstract:
Objective A nucleosomal protein, HMGB1, can be secreted by activated immune cells or passively released by dying cells, thereby amplifying rigorous inflammatory responses. In this study we aimed to test the possibility that radiation similarly induces cytoplasmic HMGB1 translocation and release. Methods Human skin fibroblast (GM0639) and bronchial epithelial (16HBE) cells and rats were exposed to X-ray radiation, and HMGB1 translocation and release were then assessed by immunocytochemistry and immunoassay, respectively. Results At a wide dose range(4.0-12.0 Gy), X-ray radiation induced a dramatic cytoplasmic HMGB1 translocation, and triggered a time- and dose-dependent HMGB1 release both in vitro and in vivo. The radiation-mediated HMGB1 release was also associated with noticeable chromosomal DNA damage and loss of cell viability. Conclusions Radiation induces HMGB1 cytoplasmic translocation and extracellular release through active secretion and passive leakage processes.
Risk factor analysis for predicting radiation pneumonitis in extensive stage small cell lung cancer patients receiving IMRT thoracic radiotherapy
Jingtao Li, Lei Deng, Wenjue Zhang, Zefen Xiao, Qinfu Feng, Dongfu Chen, Jun Liang, Jima Lyu, Zongmei Zhou
2016, 40(2): 100-105. doi: 10.3760/cma.j.issn.1673-4114.2016.02.003
Abstract:
Objective To evaluate the clinical factors and dose-volume histogram-based factors as predictors of radiation pneumonitis(RP)in extensive-stage small cell lung cancer(ES-SCLC) patients treated with thoracic IMRT after chemotherapy. Methods Medical records of 130 ES-SCLC patients irradiated in our institution between 2007 and 2012 were retrospectively reviewed. Most patients received an initial chemotherapy regimen of combined carboplatin and etoposide or with cisplatin combined with etoposide. The median thoracic radiation dose was 55.3 Gy(32-67 Gy) with 1.8-2.3 Gy per fraction. RP was graded according to Common Terminology Criteria for Adverse Events version 4.0, and RP at a grade of ≥Ⅱ is considered as a complication. Univariate and multivariate analyses were conducted to identify the predictive factors. Results Median follow-up period was 37 months (range:4-66 months). A total of 37 patients(28.5%) showed an RP grade of ≥Ⅱ. The univariate analysis revealed that in the entire population, age and many dosimetric parameters(V5, V10, V20, V30, mean lung dose, and total lung volume)were significantly associated with RP. By contrast, multivariate analysis showed that only V5 was significantly associated with RP. Conclusions In this study, a number of clinical and dosimetric factors are associated with a high risk of RP. However, V5 was the only significant factor associated with this condition. Multiple clinical and dosimetric factors should be considered in IMRT planning for ES-SCLC patients receiving thoracic radiotherapy after chemotherapy. It is proposed that V5 should be kept low to reduce the development of RP in ES-SCLC patients after chemotherapy.
Synthesis of 11C-methionine on home-made module by the improved LOOP method
Haifeng Li, Xiaojun Zhang, Yungang Li, Zhihui Shen, Jinming Zhang
2016, 40(2): 106-110. doi: 10.3760/cma.j.issn.1673-4114.2016.02.004
Abstract:
Objective The synthesis of radiopharmaceutical 11C-methionine(11C-MET) by LOOP and C-18 on-column method on home-made 11C-multifunction synthesis module was compared. Method The synthesis conditions of 11C-MET with home-made synthesis module by LOOP method was studied, which included the alkali equivalent, solvents and the amount of precursor. Results The optimum condition was 2-3 mg of precursor in NaOH solution(2 mol/L), alkali equivalent(5.6-11.5 eq) and ethanol(100 μL), and at room temperature for synthesis of 11C-MET. It could be got with radiochemical yield of (65.31±4.32)%(n=24, end of synthesis of 11C-CH3I). The radiochemical purity of 11C-MET was higher than 95% and the production radioactivity was (6.61±1.38) GBq(n=24). Conclusions By the method of LOOP, it showed that the production efficiency was increased, the output was increased and production cost of synthetic was reduced. The synthetic process was reliable and full automatic, and the product synthesized by this process was suitable for clinical use.
Diagnostic value of technetium 99Tcm sestamibi and X-ray mammography in breast cancer: a comparison study
Lei Yang, Weihong Yuan, Jiaping Wang, Jiale Gao, Qing Yang, Lili Zhao, Yi Zhang, Zhi Zeng, Lijuan Wang, Jianghong Yue
2016, 40(2): 111-114. doi: 10.3760/cma.j.issn.1673-4114.2016.02.005
Abstract:
Objective To compare the diagnostic value of 99Tcm-MIBI SPECT/CT chest imaging combined with X-ray mammography and to investigate their complementarity. Methods This study included 83 female patients, including those suspected to have breast nodules and those diagnosed with breast cancer. All patients were examined initially via 99Tcm-MIBI chest SPECT/CT imaging and delayed imaging followed by X-ray mammography, and all data were compared with final pathological results. Results Among the 99Tcm-MIBI imaging results of the 83 female patients, 52 lesions were revealed by delay images(T/NT ratio >3.33). The final criterion for diagnosis was based on positive delay imaging. The T/NT ratio between benign and malignant breast lesions was statistically significant(P < 0.05). The sensitivity, specificity, positive predictive value and negative predictive value of diagnosis via 99Tcm-MIBI SPECT/CT chest imaging were 93.33%, 73.68%, 80.77%, and 90.32%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of X-ray were 64.44%, 73.68%, 74.36%, 63.63%, respectively. 99Tcm-MIBI imaging superior value to diagnosis X-ray mammogragh for breast cancer(χ2=4.11, P < 0.05), but two methods of consistency spreads(Kappa=0.217, P < 0.05). Conclusions The sensitivity and specificity of 99Tcm-MIBI were higher than those of X-ray mammography in diagnosis of early-stage breast cancer. 99Tcm-MIBI imaging offers advantages in detecting virus infection aslar-pacific nodules. It is speculated that detecting regular breast nodules and occult lesions can be improved if these two methods are combined because they are complementary techniques.
Construction and identification of pprM-complemented Deinococcus radiodurans strain
Liang Fu, Shuya He, Baoping Pan, Yang Zeng, Fangzhu Xiao, Shuai Tian, Xianzhou Lu, Bo Huang, Yun Ma
2016, 40(2): 115-119. doi: 10.3760/cma.j.issn.1673-4114.2016.02.006
Abstract:
Objective To investigate the function of PprM protein by constructing a pprM-complemented strain of Deinococcus radiodurans. Methods HA-pprM gene was amplified by PCR from the plasmid DNA of pGEX-6p-1-pprM(approximately 438 bp) and then inserted into the shuttle expression vector pRADK to construct pRADK-HA-pprM. The correctness of the inserted sequences was confirmed through agarose gel electrophoresis, restriction enzyme digestion, and gene sequencing. The recombinant plasmid was transformed into the pprM mutant strain of Deinococcus radiodurans, and the recombinant protein was analyzed by Western blot. Results The recombinant plasmid pRADK-HA-pprM and a complemented strain were obtained. The recombinant protein can be highly expressed in the complemented strain. Conclusion This study provided a foundation for further studies on the interaction between the PprM protein and its target DNA.
Value of 18F-FDG PET/CT on diagnosis of Hodgkin lymphoma recurrence using Deauville criterion
Wenjie Shi, Zhaowei Meng, Jian Tan
2016, 40(2): 120-124. doi: 10.3760/cma.j.issn.1673-4114.2016.02.007
Abstract:
Objective To investigate the diagnostic value of 18F-FDG PET/CT on Hodgkin lymphoma(HL) recurrence according to Deauville criterion. Methods Retrospective analysis was performed on 24 HL cases for a period of 5-27 months after treatment. These patients were clinically suspected of recurrence. Results of 18F-FDG PET/CT imaging according to Deauville criterion, lymph node biopsies, and(or) bone marrow biopsy pathology were analyzed and compared. Results Seventeen cases of recurrence were confirmed by pathologic findings. Three cases of lymph node reactive hyperplasia, 1 case of lung cancer with mediastinal lymph node metastasis, and 3 cases without recurrence were recorded. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100%, 50%, 85%, 100%, and 87% for 18F-FDG PET/CT on HL recurrence diagnosis. Conclusion 18F-FDG PET/CT is of important clinical value on the diagnosis of HL recurrence according to the standard of Deauville criterion.
Immune-induced aplastic anemia IRM-2 mice model research
Lijuan Zhang, Rui Ma, Yueying Wang, Deguan Li
2016, 40(2): 125-127,138. doi: 10.3760/cma.j.issn.1673-4114.2016.02.008
Abstract:
Objective To perform traditional blood and immunologic examinations for the pathogenesis of immune-induced aplastic anemia(AA) IRM-2 mice model. Methods IRM-2 mice were divided into three groups, namely, the control, radiation, and AA model groups. IRM-2 inbred mice in the AA model group were used to set up the AA model by whole body 137Cs γ irradiation and eye venous plexus injection with DBA/2 mice thymus cells. After 15 days of radiation, blood and bone marrow cells were counted, and immunologic detection was performed. Results The peripheral WBC, RBC, bone marrow cells, and reticulocyte[(2.38±0.53)×109/L, (8.22±0.21)×1012/L, (7.14±1.19)×106/femur, and(50.2±8.9)‰] in the AA model group were lower than those of the control group [(8.23±0.41)×109/L, (10.24±0.91)×1012/L, (16.5±1.61)×106/femur, and(76.2±9.7)‰]. CD4+ cells [(8.91±2.55)%] of the AA model group were lower than those of the control group[(16.14±3.09)%], whereas CD8+ cells [(13.55±2.12)%] were higher than those of the control group [(6.83±1.14)%]. Peripheral blood and immunological indexes of the AA model group were statistically different from those of the control group. Conclusion IRM-2 mice AA model was successfully established as a good model for the study of AA.
Review
Learning From Biomarkers in Victims Acci-dentally Exposed to Ionizing Radiation
Yan Wang, Liqing Du, Chang Xu, Qin Wang, Zhiyi Song, Jianxiang Liu, Xu Su, Qiang Liu
2016, 40(2): 128-132. doi: 10.3760/cma.j.issn.1673-4114.2016.02.009
Abstract:
Biomarkers, such as chromosome aberration and micronuclei assays, prove to be reliable for facilitating clinical diagnosis in radiation accidents. In a radiation accident in India, chromosomal aberration, γ-H2AX, as well as other blood markers, were detected in accidentally exposed victims. This multi-parametric approach aided in confirming that individuals had been exposed by ionizing radiation. However, doses were impossible to estimate because of a 30-day delay in accident awareness. Exposure dose for victims was estimated using a dose-response curve previously established. Dose estimation, blood cell depletion kinetics, and no appearance of prodromal symptoms suggested that doses of exposure were low. Hematologic investigation, sampling time, and chromosome aberration scoring were all proposed according to data from the victims exposed to 60Co. Finally, knowledge regarding chromosome aberration analysis and the importance of international co-operation and assistance should be shared from this accident.
Long Non-coding RNAs in Response to Genotoxic Stress
Xiaoman Li, Dong Pan, Baoquan Zhao, Burong Hu
2016, 40(2): 133-138. doi: 10.3760/cma.j.issn.1673-4114.2016.02.010
Abstract:
Long non-coding RNAs(lncRNAs) are increasingly involved in diverse biological processes. Upon DNA damage, the DNA damage response(DDR) elicits a complex signaling cascade, which includes the induction of lncRNAs. LncRNA-mediated DDR is involved in non-canonical and canonical manners. DNA-damage induced lncRNAs contribute to the regulation of cell cycle, apoptosis, and DNA repair, thereby playing a key role in maintaining genome stability. This review summarizes the emerging role of lncRNAs in DNA damage and repair.
Advances in radionuclide-labeled HER2 affibody molecular probes for precise diagnosis and treatment
Yu Xing, Xinming Zhao
2016, 40(2): 139-144. doi: 10.3760/cma.j.issn.1673-4114.2016.02.011
Abstract:
Human epidermal growth factor receptor type 2(HER2) affibody molecules hold the advantage of high specificity and affinity, small size, simple synthesis, and excellent biological dynamics. It has been widely used in molecular imaging and treatment of tumor, with an eye towards clinical translation. The molecular probes of radionuclide-labeled HER2 affibody can not only be used in receptor imaging and response evaluation of tumor, but also in targeted therapy. This article reviewed the latest researches on radionuclide-labeled HER2 affibody.
Evolution of radionuclide imaging of sentinel node lymphscintigraphy in breast cancer
Le Ma, Wanchun Zhang, Xiaomin Li
2016, 40(2): 145-148, 158. doi: 10.3760/cma.j.issn.1673-4114.2016.02.012
Abstract:
Breast cancer is the most common cancer that affects women worldwide. Axillary sentinel lymph node biopsy was introduced in the 1900s and has become a routine in breast-conserving surgery to ensure survival of patients and reduce complications related to the disease. The importance of the internal mammary sentinel lymph node, in addition to the axillary sentinel lymph node, cannot be ignored. A controversial issue is whether to accept the internal mammary sentinel lymph node as object of sentinel node biopsy. Nuclear medicine researchers have extensively investigated the response of sentinel node lymphoscintigraphy to clinical requirements, thereby improving the detection rate of both axillary and internal mammary sentinel lymph nodes. This review presents the evolution of sentinel node lymphoscintigraphy in terms of nuclide tracer, injection technology, and imaging devices over an almost 10-year period locally and internationally.
Progress in molecular probes of radionuclide tumor apoptosis imaging
Shunjun Chen, Bing Cheng
2016, 40(2): 149-153. doi: 10.3760/cma.j.issn.1673-4114.2016.02.013
Abstract:
Apoptosis is one of the important indices about the early assessment of the efficacy of tumor treatment. Among molecular imaging techniques of tumor apoptosis, radionuclide imaging is the most extensively studied and the most sensitive imaging modality, which can noninvasively and dynamically detect cell apoptosis induced by treatment in vivo, especially for efficacy of cancer therapies and prognosis of malignancies. Recently, as one of the key techniques, specific molecular probes are being developed. The representative molecular probes of the radionuclide imaging for tumor apoptosis are reviewed.
Damages of ionizing radiation on mitochondria
Yurui Zhang, Wenqing Xu
2016, 40(2): 154-158. doi: 10.3760/cma.j.issn.1673-4114.2016.02.014
Abstract:
The radiobiology hypothesis is widely accepted by people that damage to the nuclear DNA is the main cause for the effects of radiation. However, some studies shown that the extranulear radiation effects are also very important, especially for mitochondria which contains the coding DNA and important proteins. Mitochondria plays a very important role in oxidative stress and cell death after irradiation. Some experiments present the effects of ionizing radiation on the mitochondria. Here, we discussed the ionizing radiation how to influence the mitochondria. And authors summary some available research data that specific protection of mitochondria could reduce damage to healthy cells exposed to ionizing radiation.
Progress of microRNAs in regulating tumor radiation sensitivity
Jia Liu, Gang Gao, Chunnan Piao, Jianxiang Liu
2016, 40(2): 159-164. doi: 10.3760/cma.j.issn.1673-4114.2016.02.015
Abstract:
MiRNA is a small non-protein coding RNA that play an important role in gene regulation by targeting the 3'untranslated region of specific target gene mRNA, leading to the degradation of target RNA or inhibition of protein synthesis in post-transcriptional level. Radiation therapy is a main method for cancer treatment. Tumor radiation biological effect is critical in radiotherapy and a core determining factor of tumor radioresistance or radiosensitivity. Recent studies have demonstrated that miRNA can regulate tumor radiosensitivity by affecting DNA damage repair, cell cycle checkpoint, apoptosis, signal transduction pathways and tumor microenvironment etc. miRNA offer potential new approach to complement the radiotherapy for tumor treatment.