2016 Vol. 40, No. 5
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2016, 40(5): 323-328.
doi: 10.3760/cma.j.issn.1673-4114.2016.05.001
Abstract:
Objective To identify a novel retinoblastoma protein(RB)-associated protein(RBAP 96) and to explore the impact of RBAP96 on radiosensitivity of human breast cancer cells. Methods An in vivo and in vitro association of RBAP96 with RB was determined by immunoprecipitation-Western blotting and GST pull-down assay. Protein expression was measured by Western blot assay. Cellular survival was evaluated by using a colony formation assay. Results In both in vitro and in vivo assays, we found that the RBAP96 and RB interaction required a 513LXCXE517 motif on the RBAP96 protein and an intact A/B binding pocket of RB. RBAP96 enhances RB-mediated transcriptional repression. Finally, enforced expression of RBAP96 caused an elevated radiosensitivity of human breast cancer cells bearing wtRB, but did not affect radiosensitivity of breast cancer cells bearing mutant RB. Expression of a full-length RBAP96 with an 513LXCXE517 inactivating mutation(LXCXE?RXRXH) failed to result in any radiosensitivity alteration. Conclusion This study for the first time characterizes a novel RB-interacting protein RBAP96 and demonstrates that enforced expression of RBAP96 causes an increase of RBAP96-mediated transcription activation and radiosensitivity via a RB-interacting dependent manner.
Objective To identify a novel retinoblastoma protein(RB)-associated protein(RBAP 96) and to explore the impact of RBAP96 on radiosensitivity of human breast cancer cells. Methods An in vivo and in vitro association of RBAP96 with RB was determined by immunoprecipitation-Western blotting and GST pull-down assay. Protein expression was measured by Western blot assay. Cellular survival was evaluated by using a colony formation assay. Results In both in vitro and in vivo assays, we found that the RBAP96 and RB interaction required a 513LXCXE517 motif on the RBAP96 protein and an intact A/B binding pocket of RB. RBAP96 enhances RB-mediated transcriptional repression. Finally, enforced expression of RBAP96 caused an elevated radiosensitivity of human breast cancer cells bearing wtRB, but did not affect radiosensitivity of breast cancer cells bearing mutant RB. Expression of a full-length RBAP96 with an 513LXCXE517 inactivating mutation(LXCXE?RXRXH) failed to result in any radiosensitivity alteration. Conclusion This study for the first time characterizes a novel RB-interacting protein RBAP96 and demonstrates that enforced expression of RBAP96 causes an increase of RBAP96-mediated transcription activation and radiosensitivity via a RB-interacting dependent manner.
2016, 40(5): 329-337.
doi: 10.3760/cma.j.issn.1673-4114.2016.05.002
[PDF 674KB]
Abstract:
Objective Triple negative breast cancer(TNBC) represents a group of refractory breast cancers with aggressive clinical manifestations as well as poor prognoses. Human epidermal growth factor receptor(EGFR) expression is strongly associated with TNBC progression and it may serve as a therapeutic target for TNBC. We aimed to evaluate EGFR affibody-based PET imaging to profile EGFR expression in small animal models. Methods 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA) conjugated Ac-Cys-ZEGFR:1907 was chemically synthesized using solid phase peptide synthesizer and then radiolabeled with 64Cu. The in vitro cell uptake study was performed using SUM159 and MCF7 cells. The biodistribution and small animal PET imaging using 64Cu-DOTA-ZEGFR:1907 were further carried out with nude mice bearing subcutaneous MDA-MB-231 and SUM159 tumors. Results DOTA-Ac-Cys-ZEGFR:1907 was successfully synthesized and radiolabeled with 64Cu. Biodistribution study showed that tumor uptake value of 64Cu-DOTA-Ac-Cys-ZEGFR:1907 remained at(4.07?.93)%ID/g at 24 h in nude mice(n=4) bearing SUM159 xenografts. Furthermore, small animal PET imaging study clearly showed that 64Cu-DOTA-Ac-Cys-ZEGFR:1907 specifically delineated the EGFR positive TNBC tumors at 4 h or later. Conclusion The study demonstrates that 64Cu-DOTA-Ac-Cys-ZEGFR:1907 is a promising molecular probe for PET imaging of EGFR positive TNBC. EGFR based small protein scaffold holds great promise as a novel platform that can be used for EGFR profiling of TNBC.
Objective Triple negative breast cancer(TNBC) represents a group of refractory breast cancers with aggressive clinical manifestations as well as poor prognoses. Human epidermal growth factor receptor(EGFR) expression is strongly associated with TNBC progression and it may serve as a therapeutic target for TNBC. We aimed to evaluate EGFR affibody-based PET imaging to profile EGFR expression in small animal models. Methods 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA) conjugated Ac-Cys-ZEGFR:1907 was chemically synthesized using solid phase peptide synthesizer and then radiolabeled with 64Cu. The in vitro cell uptake study was performed using SUM159 and MCF7 cells. The biodistribution and small animal PET imaging using 64Cu-DOTA-ZEGFR:1907 were further carried out with nude mice bearing subcutaneous MDA-MB-231 and SUM159 tumors. Results DOTA-Ac-Cys-ZEGFR:1907 was successfully synthesized and radiolabeled with 64Cu. Biodistribution study showed that tumor uptake value of 64Cu-DOTA-Ac-Cys-ZEGFR:1907 remained at(4.07?.93)%ID/g at 24 h in nude mice(n=4) bearing SUM159 xenografts. Furthermore, small animal PET imaging study clearly showed that 64Cu-DOTA-Ac-Cys-ZEGFR:1907 specifically delineated the EGFR positive TNBC tumors at 4 h or later. Conclusion The study demonstrates that 64Cu-DOTA-Ac-Cys-ZEGFR:1907 is a promising molecular probe for PET imaging of EGFR positive TNBC. EGFR based small protein scaffold holds great promise as a novel platform that can be used for EGFR profiling of TNBC.
2016, 40(5): 338-344.
doi: 10.3760/cma.j.issn.1673-4114.2016.05.003
Abstract:
Objective To explore 18F-FDG brain metabolism and 11C-2βcarbomethoxy-3β(4-fluorophenyl) tropane (11C-CFT) brain dopamine transporter(DAT) PET dual imaging in the diagnosis and evaluation of the severity of Parkinson's disease(PD). Methods Fifty-five patients with different severity of PD and 30 cases of healthy controls were subjected to 18F-FDG cerebral metabolic imaging and 11C-CFT DAT PET imaging examination, in which ROI were outlined to compare the differences in glucose metabolism and DAT distribution in the basal ganglia of PD with different severity among the patients and those of healthy controls based on the PET images. 18F-FDG PET and 11C-CFT PET imaging were used to assess severity of PD. Results By comparison with the healthy controls, 18F-FDG PET imaging indicates that the changes in brain metabolism caused by PD mainly show improvement in symmetry of bilateral basal ganglia putamen. Moreover, some PD cases are accompanied with reduction in the metabolism of cerebral cortex to varying degrees. 11C-CFT PET imaging in PD patients indicates that DAT distribution in their bilateral caudate nucleus, bilateral anterior putamen, medio-putamen, and posterior putamen decreased in different degrees. Based on the symptoms of unilateral or bilateral PD, DAT distribution on the contralateral basal ganglia putamen decreased, whereas posterior putamen DAT distribution decreased more prominently. Conclusion 18F-FDG PET and 11C-CFT PET imaging dual joint inspection has a significant value in diagnosing and assessing the severity of PD.
2016, 40(5): 345-349.
doi: 10.3760/cma.j.issn.1673-4114.2016.05.004
Abstract:
Objective To analyze the feasibility of labeling MAG3-isoDGR-2C with 99Tcm and investigate the biodistribution of the tracer in normal mice. Methods Glucoheptonate was initially labeled with 99Tcm as the intermediate, followed by MAG3-isoDGR-2C. High-performance liquid chromatography was employed to determine the radiochemical purity. The biodistribution of 99Tcm-MAG3-isoDGR-2C was studied at 15, 30, 60, 120, 240 and 360 min after caudal vein injection in normal mice. Results MAG3-isoDGR-2C was successfully labeled with 99Tcm, and the radiochemical purity was 94.2%. The biodistribution revealed that the tracer was rapidly cleared out from the blood with mild activity in the heart, lung, spleen, stomach, and bone. Conclusions MAG3-isoDGR-2C was labeled with 99Tcm with high radiochemical purity, and the tracer could be cleared out quickly. Therefore, MAG3-isoDGR-2C is a potential molecular tracer in the study of early cancer diagnosis.
2016, 40(5): 350-356.
doi: 10.3760/cma.j.issn.1673-4114.2016.05.005
Abstract:
Objective Subclinical hypothyroidism is a common disease. However, whether L-thyroxine replacement treatment can affect serum lipids in cases of subclinical hypothyroidism remains controversial. The objective of this meta-analysis was to assess the effect of L-thyroxine therapy on serum lipid levels of patients with subclinical hypothyroidism. Methods Literature dated until July 2015 was retrieved from the Cochrane Library, PubMed, Medline, Google Scholar, and Embase searching for the keywords "hyroxine", "levothyroxin" and "levothyroxine". All randomized controlled trials(RCTs) to determine the effects of L-thyroxine replacement on serum lipid levels were included in this study. After screening, the eligible RCTs were included in this meta-analysis. Statistical analyses were performed by the Review Manager 5.2 software. All the assessed outcomes were continuous data. Results A total of 7 RCTs involving 319 patients were included. The overall methodological quality of the RCTs was good. Results showed that the serum low density lipoprotein-cholesterol(LDL-C) level significantly decreased after L-thyroxine treatment [mean difference(MD):-0.23; 95% CI: [-0.44, -0.03]; P=0.02]. Meanwhile, changes in the total cholesterol(MD: -0.18; 95% CI: [-0.40, 0.03]; P=0.09), triglyceride(MD: -0.02; 95% CI: [-0.17, 0.13]; P=0.78), and high density lipoprotein-cholesterol(MD: -0.06; 95% CI: [-0.14, 0.02]; P=0.14) levels were not significant. Conclusions All available RCT evidence on the effect of L-thyroxine on serum lipid levels in subclinical hypothyroidism revealed a significant improvement in the serum LDL-C levels. However, the serum TC, TG, and HDL-C levels did not significantly change.
2016, 40(5): 357-362.
doi: 10.3760/cma.j.issn.1673-4114.2016.05.006
Abstract:
Objective To investigate the radiation sensitization effect of endostatin on transplanted tumors in nude mice with 125I radioactive seed. Methods Mice were randomly assigned to four groups(n=20):control group(group A), 125I radioactive seed group(group B), endostatin group(group C), and 125I radioactive seed combined with endostatin group(group D). When the diameter of the transplanted tumor was greater than 2 cm, 125I radioactive particles were implanted. The prescription dose was 20 Gy. Treatment planning system was used to calculate the target area and size of tumors. Endostatin was injected intraperitoneally at 20 mg/kg once every day for 14 days, and the changes in tumor growth and size were observed. The animals were sacrificed at 15 and 30 days. The expression levels of vascular endothelial growth factor(VEGF) and microvessel density(MVD) in tumor tissues were detected by immunohistochemistry, whereas αvβ3 mRNA levels were determined by RT-PCR. Results Compared with groups B and C, the tumor size, tumor weight, and tumor growth inhibitory rate of group D significantly increased at 15 and 30 days. The tumor size, tumor weight, and tumor growth inhibitory rate of groups B and D significantly increased at 30 days compared with those at 15 days. Immunohistochemical staining revealed that the expression levels of VEGF and MVD in group D were significantly different at 15 and 30 days compared with those in groups A, B, and C. The expression of VEGF and MVD in group C was significantly different at 15 and 30 days compared with that in groups A and B. VEGF and MVD in group C were significantly up-regulated at 30 days compared with those at 15 days. RT-PCR analysis demonstrated that the expression of αvβ3 mRNA in group B obviously increased with time compared with that in group A. Compared with group A, αvβ3 mRNA in group B was up-regulated, whereas αvβ3 mRNA in groups C and D was significantly down-regulated. Compared with groups C and B, group D exhibited a statistically significant difference. Conclusion Endostatin is helpful to brachytherapy of lung tumor with radiosensitizing enhancement effects. Changes in VEGF, MVD, and αvβ3 mRNA may be the rational treatment mechanism.
2016, 40(5): 363-373.
doi: 10.3760/cma.j.issn.1673-4114.2016.05.007
Abstract:
Human epidermal growth factor receptor-2(HER2) is a kind of transmembrane receptor with tyrosine kinase activity, and also is a biomarker highly expressed in various cancer cells, often indicating poor clinical prognosis. HER2 expression molecular imaging mainly utilizes the labeled-ligands'ability of specific binding with HER2, such as radionuclide, magnetic materials and fluorescent substances, by which the high-HER2 expressed lesions are shown. This technique provides a strong support for diagnosing HER2-expressed diseases, selecting patients who are respondent to HER2-targeted therapy and evaluating the therapeutic effect, and has become one of the hot spots in the research of precise treatment of tumors in recent years.
Human epidermal growth factor receptor-2(HER2) is a kind of transmembrane receptor with tyrosine kinase activity, and also is a biomarker highly expressed in various cancer cells, often indicating poor clinical prognosis. HER2 expression molecular imaging mainly utilizes the labeled-ligands'ability of specific binding with HER2, such as radionuclide, magnetic materials and fluorescent substances, by which the high-HER2 expressed lesions are shown. This technique provides a strong support for diagnosing HER2-expressed diseases, selecting patients who are respondent to HER2-targeted therapy and evaluating the therapeutic effect, and has become one of the hot spots in the research of precise treatment of tumors in recent years.
Clinical research progress in diagnosis, prevention and treatment of radiation-induced heart disease
2016, 40(5): 374-378.
doi: 10.3760/cma.j.issn.1673-4114.2016.05.008
Abstract:
Radiation therapy is one of the necessary and effective treatment methods for the patients with thoracic tumors. However, the heart will be inevitably affected by irradiation simultaneously, leading to radiation-induced heart disease(RIHD). As the radiotherapy technology improving, the survival period is significantly prolonged in patients with tumor, the RIHD incidence increase as well, especially the delayed heart damage, reaching 50% or even higher. Unfortunately, there′s no effective means about the prevention and treatment for RIHD currently. Therefore, early detection and treatment about RIHD is very essential for improving curative effect and quality of life of the patients. This review discussed the diagnosis, prevention and treatment methods for RIHD.
Radiation therapy is one of the necessary and effective treatment methods for the patients with thoracic tumors. However, the heart will be inevitably affected by irradiation simultaneously, leading to radiation-induced heart disease(RIHD). As the radiotherapy technology improving, the survival period is significantly prolonged in patients with tumor, the RIHD incidence increase as well, especially the delayed heart damage, reaching 50% or even higher. Unfortunately, there′s no effective means about the prevention and treatment for RIHD currently. Therefore, early detection and treatment about RIHD is very essential for improving curative effect and quality of life of the patients. This review discussed the diagnosis, prevention and treatment methods for RIHD.
2016, 40(5): 379-383.
doi: 10.3760/cma.j.issn.1673-4114.2016.05.009
Abstract:
With the widely application of the X-ray, the radiation carcinogenesis to the medical workers attracts more and more people′s attention. Accurate radiation carcinogenesis dose-response assessment is based on complete personal dose information. But early in the application of X-ray, there are no personal dose information of medical X-ray workers, so it needs dose reconstruction to estimate the early personal dose information. The dose estimation status and progress of early medical diagnostic X-ray workers at home and abroad paper were reviewed in this paper.
With the widely application of the X-ray, the radiation carcinogenesis to the medical workers attracts more and more people′s attention. Accurate radiation carcinogenesis dose-response assessment is based on complete personal dose information. But early in the application of X-ray, there are no personal dose information of medical X-ray workers, so it needs dose reconstruction to estimate the early personal dose information. The dose estimation status and progress of early medical diagnostic X-ray workers at home and abroad paper were reviewed in this paper.
2016, 40(5): 384-393.
doi: 10.3760/cma.j.issn.1673-4114.2016.05.010
Abstract:
For malignant tumor, the traditional treatments mainly include surgery, chemotherapy, conventional radiotherapy, etc. Although these treatments play an important role in tumor therapy, however, there are still significant deficiencies:some clinical treatment ineffective, and some serious complications. In order to solve these problems which caused by the above treatment in tumor therapy, domestic and foreign researchers have successfully developed a new treatment—proton heavy ion radiotherapy. The author makes a detailed introduction to the basic principles and clinical application of this treatment method, and provide more information and support for cancer patients and oncologist.
For malignant tumor, the traditional treatments mainly include surgery, chemotherapy, conventional radiotherapy, etc. Although these treatments play an important role in tumor therapy, however, there are still significant deficiencies:some clinical treatment ineffective, and some serious complications. In order to solve these problems which caused by the above treatment in tumor therapy, domestic and foreign researchers have successfully developed a new treatment—proton heavy ion radiotherapy. The author makes a detailed introduction to the basic principles and clinical application of this treatment method, and provide more information and support for cancer patients and oncologist.
2016, 40(5): 389-393.
Abstract:
Given the unique advantages of dual-source computed tomography(DSCT), such as high temporary and spatial resolutions and fast scanning speed, its application in angiography has made possible for high-quality images to be obtained. In high-pitch scanning mode, DSCT can obtain high-quality angiography images with low effective radiation dose at a short scan time. This paper reviewed the progress and clinical applications of high-pitch mode DSCT in computed tomography angiography.
Given the unique advantages of dual-source computed tomography(DSCT), such as high temporary and spatial resolutions and fast scanning speed, its application in angiography has made possible for high-quality images to be obtained. In high-pitch scanning mode, DSCT can obtain high-quality angiography images with low effective radiation dose at a short scan time. This paper reviewed the progress and clinical applications of high-pitch mode DSCT in computed tomography angiography.
2016, 40(5): 394-402.
Abstract:
Radioprotectors are designed to disrupt the progress of damage caused by radiation in normal tissues and to promote the recovery of the damaged tissues. This article review the function of the following agents as radioprotectors and their mechanism of action: sulfhydryl compounds, natural antioxidants, nitroxides, and angiotensin-converting enzyme inhibitors. Prospective functions of these agents were also discussed. This article hope to provide researchers with insights into radioprotector research.
Radioprotectors are designed to disrupt the progress of damage caused by radiation in normal tissues and to promote the recovery of the damaged tissues. This article review the function of the following agents as radioprotectors and their mechanism of action: sulfhydryl compounds, natural antioxidants, nitroxides, and angiotensin-converting enzyme inhibitors. Prospective functions of these agents were also discussed. This article hope to provide researchers with insights into radioprotector research.
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