Background ^11C-4-N-（3-bromoanilino）-6,7-dimethoxyquinazoline （1^11C-PD153035） has been reported as a tracer for imaging human tumors that overexpress epidermal growth factor receptor （EGFR）. However it is still...Background ^11C-4-N-（3-bromoanilino）-6,7-dimethoxyquinazoline （1^11C-PD153035） has been reported as a tracer for imaging human tumors that overexpress epidermal growth factor receptor （EGFR）. However it is still unclear whether ^11C-PD153035 uptake correlates with EGFR expression levels. The objective of this study was to investigate the relationship between ^11C-PD153035 accumulation and EGFR expression levels. Methods Synthesis of ^11C-PD153035 was performed in the Tracerlab FXc system. Accumulation of ^11C-PD153035 by MDA-MB-468, A549 and MDA-MB-231 cells was measured in vitro. There were six tumor-bearing mice in each group. ^11C-PD153035 uptake in tumors was determined by positron emission tomography/computed tomography （PET/CT）. Tumor/normal muscle tissue （TINT） analysis in PET images was applied to quantify the PET data. Sixty minutes after PET/CT scanning, the nude mice were sacrificed and the tumors were excised. The ^11C-PD153035 accumulation in different tumors was determined by a gamma counter. Results Close correlation existed between the uptake and the level of EGFR expression both in vitro and ex vivo （r^2=0.72, P〈0.001; r^2=0.63, P=0.003）. When the static TINT analysis method was applied to analyze the PET data, the observed correlation was again excellent （^2=0.70, P=-0.001）. Conclusions The uptake of PET tracer ^11C-PD153035 closely correlates with the EGFR expression levels in tumor cells. ^11C-PD153035 has the potential to yield useful information for both cancer diagnosis and therapy.展开更多
Background Hepatitis B virus （HBV） x protein （HBx） in HepG2 cells causes a moderate decrease in proteolysis activity of the proteasome. A highly conserved Kunitz-type serine protease inhibitor domain within 154 am...Background Hepatitis B virus （HBV） x protein （HBx） in HepG2 cells causes a moderate decrease in proteolysis activity of the proteasome. A highly conserved Kunitz-type serine protease inhibitor domain within 154 amino acid residues of HBx has been identified. In this study, a peptide chain derived from the Kunitz domain （PKD） was used to study its effect on the cell cycle and apoptosis of HepG2 cells, and investigated the function of PKD on the activities of proteasomes and AAA-ATPase p97, which involves in the ubiquitin-proteasome protein degradation pathway. Methods The PKD peptide （Phe-Val-Leu-Gly-Gly-Cys-Arg-His-Lys） was chemically synthesized. MTT assays were used to determine the effects of PKD on HepG2 cell growth. Mouse anti-p97 antibody was developed for Western blotting to detect the expression of p97. ATPase activity of proteasomes was measured using a colorimetric assay. Peptidase activities of proteasomes were analyzed with various peptidase-specific fluorogenic peptide substrates. Flow cytometry was used to determinate cell cycle phase and apoptosis. Results Viability of HepG2 cells decreased in a PKD-dose-dependent manner. Cells exhibited significant cytotoxicity in the presence of 15 mmol/L of PKD. Western blotting analysis showed that expression of p97 was suppressed in HepG2 cells treated with PKD compared to untreated cells. The ATPase activity of proteasomes from immunoprecipitates of HepG2 cells pretreated with PKD was apparently decreased. Chymotryptic activity of proteasomes in HepG2 cells was significantly inhibited by 10mmol/L PKD; tryptic activity and peptidylglutamyl peptide hydroiase activity of proteasomes were less inhibited by PKD than chymotryptic activity. The cell cycle phase of HepG2 cells treated with PKD for 36 hours was blocked largely at the G0-G1 phase, while untreated control cells were mainly in S phase. PKD also significantly induced apoptosis. Conclusions The peptide derived from Kunitz domain of HBx protein induces HepG2 cell growth arrest and apoptosis, which may result from down-regulation of p97 expression, and decrease of both the ATPase and chymotryptic activities of proteasomes.展开更多
Background The lung functional status could be displayed on lung perfusion images. With the images, the radiotherapy plans of lung cancer could be guided to more optimized. This study aimed to assess quantitatively th...Background The lung functional status could be displayed on lung perfusion images. With the images, the radiotherapy plans of lung cancer could be guided to more optimized. This study aimed to assess quantitatively the impact of incorporating functional lung imaging into 3-dimensional conformal radiotherapy （3DCRT） and intensity-modulated radiation therapy （IMRT） planning for non-small cell lung cancer （NSCLC）. Methods Ten patients with NSCLC who had undergone radiotherapy were included in this study. Before radiotherapy, each patient underwent CT simulation and lung perfusion imaging with single photon emission computed tomography （SPECT）. The SPECT images were registered with simulation planning CT and used to contour functional lung （lung-F） and non-functional lung （lung-NF）. Two 3DCRT plans and two IMRT plans were designed and compared in each patient： two anatomic plans using simulation CT alone and two functional plans using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the four types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Total radiation dose was set at 66 Gy （2 Gyx33 fractions）. Results In incorporating perfusion information in 3DCRT and IMRT planning, the reductions on average in the mean doses to the functional lung in the functional plan were 168 cGy and 89 cGy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with 〉5 Gy, 〉10 Gy, 〉20 Gy, 〉30 Gy and 〉40 Gy for functional lung in the functional plans were 6.50%, 10.21%, 14.02%, 22.30% and 23.46% in 3DCRT planning, respectively, and 3.05%, 15.52%, 14.16%, 4.87%, and 3.33% in IMRT planning, respectively. No greater degree of sparing of the functional lung was achieved in functional IMRT than in 3DCRT. Conclusion Function-guided 3DCRT and IMRT plannings both appear to be effective in preserving functional lung in NSCLC patients.展开更多
Tumoural hypoxia can influence response to radiotherapy and other treatments, and oxygenation status has proved to be a prognostic indicator of the outcome of radiotherapy.1 Therefore, it is important to assess tumour...Tumoural hypoxia can influence response to radiotherapy and other treatments, and oxygenation status has proved to be a prognostic indicator of the outcome of radiotherapy.1 Therefore, it is important to assess tumoural hypoxia and reoxygenation before selection of treatment protocols. During the last two decades, much attention has been paid to noninvasive imaging techniques using radiolabelled markers for the detection of hypoxic cells in solid tumours.2 Technetium （^99mTc） is a very convenient isotope for use with such imaging because it is readily available and suited to routine clinical use.展开更多
Objective To review the current status and progress on nuclear medical molecular imaging of angiogenesis. Data sources A literature search was performed in Medline and PubMed published in English up to May 31, 2012. T...Objective To review the current status and progress on nuclear medical molecular imaging of angiogenesis. Data sources A literature search was performed in Medline and PubMed published in English up to May 31, 2012. The search terms were molecular imaging, nuclear medicine and angiogenesis. Study selection Articles studying molecular imaging of angiogenesis using radionuclide were selected and reviewed. Results Molecular imaging has been used for studying angiogenesis by targeting integrin aVI33, VEGF/VEGFR, and matrix metalloproteinases （MMPs） with radionuclide-labeled tracers. The technology has been shown to be able to assess the angiogenesis status and/or predict the efficacy of anti-angiogenic therapy. Future directions of the research on the molecular imaging of angiogenesis include development of new tracers with better tumor targeting efficacy, desirable pharmacokinetics, and easy translation to clinical applications. Conclusion Advances in molecular imaging of angiogenesis using radioculcide will make the technology a valuable tool for personalized anti-angiogenesis treatment.展开更多
Background An elevated serum lipid is one of the major risk factors for coronary heart disease （CHD）. Physicians＇ awareness contributes to successful adoption of practice guidelines. Community medical centers are t...Background An elevated serum lipid is one of the major risk factors for coronary heart disease （CHD）. Physicians＇ awareness contributes to successful adoption of practice guidelines. Community medical centers are the primary defense against chronic disease. This study aimed to investigate community physicians＇ awareness of cholesterol guidelines and their utilization.Methods Six hundred and one community physicians were randomly selected from four different regions, and completed a confidential and semi-structured questionnaire. Four hundred and ninety-one completed the questionnaire, and 486 valid questionnaires were available.Results The physicians＇ fundamental knowledge of lipids was astonishingly poor, while the awareness of cholesterol guidelines was low. Only 24% and 14% of the physicians reported the right optimal low-density lipoprotein cholesterol （LDL-C） level for CHD and diabetes patients respectively. More than half of the physicians （55.8%） mistakenly considered elevated transaminases to be the lethal side effect of statins. More than half of the physicians （51.9%） would give up statin treatment in the case of transaminase elevation.Conclusion Educational interventions to improve cholesterol knowledge and to publicize standard treatment are needed among Chinese community physicians.展开更多
Background Prevention is presently the only available method to limit radiation-induced lung morbidity. A good predictor is the key point of prevention. This study aimed to investigate if [^18F]2-fluoro-2-deoxyglucose...Background Prevention is presently the only available method to limit radiation-induced lung morbidity. A good predictor is the key point of prevention. This study aimed to investigate if [^18F]2-fluoro-2-deoxyglucose （FDG） uptake changes in the lung after radiotherapy could be used as a new predictor for acute radiation pneumonitis （RP）. Methods Forty-one patients with lung cancer underwent FDG positron emission tomography/computed tomography （FDG-PET/CT） imaging before and after radiotherapy. The mean standardized uptake value （SUV） was measured for the isodose regions of 0-9 Gy, 10-19 Gy, 20-29 Gy, 30-39 Gy, 40-49 Gy. The mean SUV of these regions after radiotherapy was compared with baseline. The mean SUV in patients who developed RP was also compared with that in those who did not. The statistical difference was determined by matched pair t test. The Radiation Therapy Oncology Group （RTOG） criteria were used for diagnosis and grading of RP. Results With a median follow-up of 12 months, 11 （26.8%） of the 41 patients developed grade 2 and above acute RP. The mean SUV of regions （10-19 Gy, 20-29 Gy, 30-39 Gy, 40-49 Gy） increased after radiation therapy in all 41 patients. The mean SUVs after radiation therapy were 0.54, 0.68, 1.31, 1.74 and 2.27 for 0-9 Gy, 10-19 Gy, 20-29 Gy, 30-39 Gy and 40-49 Gy, respectively. Before the radiation therapy, the mean SUV in each region was 0.53, 0.52, 0.52, 0.53 and 0.54, respectively. These patients had significantly higher FDG activities in regions receiving 10 Gy or more （P 〈0.001）. Compared with their counterparts, the elevation of SUV was significantly greater in those patients who developed acute RP subsequently. Conclusion The mean SUV of the lung tissue may be a useful predictor for the acute RP. FDG-PET/CT may play a new role in the study of the radiation damage of the lung.展开更多
文摘Background ^11C-4-N-（3-bromoanilino）-6,7-dimethoxyquinazoline （1^11C-PD153035） has been reported as a tracer for imaging human tumors that overexpress epidermal growth factor receptor （EGFR）. However it is still unclear whether ^11C-PD153035 uptake correlates with EGFR expression levels. The objective of this study was to investigate the relationship between ^11C-PD153035 accumulation and EGFR expression levels. Methods Synthesis of ^11C-PD153035 was performed in the Tracerlab FXc system. Accumulation of ^11C-PD153035 by MDA-MB-468, A549 and MDA-MB-231 cells was measured in vitro. There were six tumor-bearing mice in each group. ^11C-PD153035 uptake in tumors was determined by positron emission tomography/computed tomography （PET/CT）. Tumor/normal muscle tissue （TINT） analysis in PET images was applied to quantify the PET data. Sixty minutes after PET/CT scanning, the nude mice were sacrificed and the tumors were excised. The ^11C-PD153035 accumulation in different tumors was determined by a gamma counter. Results Close correlation existed between the uptake and the level of EGFR expression both in vitro and ex vivo （r^2=0.72, P〈0.001; r^2=0.63, P=0.003）. When the static TINT analysis method was applied to analyze the PET data, the observed correlation was again excellent （^2=0.70, P=-0.001）. Conclusions The uptake of PET tracer ^11C-PD153035 closely correlates with the EGFR expression levels in tumor cells. ^11C-PD153035 has the potential to yield useful information for both cancer diagnosis and therapy.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30672433）.
文摘Background Hepatitis B virus （HBV） x protein （HBx） in HepG2 cells causes a moderate decrease in proteolysis activity of the proteasome. A highly conserved Kunitz-type serine protease inhibitor domain within 154 amino acid residues of HBx has been identified. In this study, a peptide chain derived from the Kunitz domain （PKD） was used to study its effect on the cell cycle and apoptosis of HepG2 cells, and investigated the function of PKD on the activities of proteasomes and AAA-ATPase p97, which involves in the ubiquitin-proteasome protein degradation pathway. Methods The PKD peptide （Phe-Val-Leu-Gly-Gly-Cys-Arg-His-Lys） was chemically synthesized. MTT assays were used to determine the effects of PKD on HepG2 cell growth. Mouse anti-p97 antibody was developed for Western blotting to detect the expression of p97. ATPase activity of proteasomes was measured using a colorimetric assay. Peptidase activities of proteasomes were analyzed with various peptidase-specific fluorogenic peptide substrates. Flow cytometry was used to determinate cell cycle phase and apoptosis. Results Viability of HepG2 cells decreased in a PKD-dose-dependent manner. Cells exhibited significant cytotoxicity in the presence of 15 mmol/L of PKD. Western blotting analysis showed that expression of p97 was suppressed in HepG2 cells treated with PKD compared to untreated cells. The ATPase activity of proteasomes from immunoprecipitates of HepG2 cells pretreated with PKD was apparently decreased. Chymotryptic activity of proteasomes in HepG2 cells was significantly inhibited by 10mmol/L PKD; tryptic activity and peptidylglutamyl peptide hydroiase activity of proteasomes were less inhibited by PKD than chymotryptic activity. The cell cycle phase of HepG2 cells treated with PKD for 36 hours was blocked largely at the G0-G1 phase, while untreated control cells were mainly in S phase. PKD also significantly induced apoptosis. Conclusions The peptide derived from Kunitz domain of HBx protein induces HepG2 cell growth arrest and apoptosis, which may result from down-regulation of p97 expression, and decrease of both the ATPase and chymotryptic activities of proteasomes.
文摘Background The lung functional status could be displayed on lung perfusion images. With the images, the radiotherapy plans of lung cancer could be guided to more optimized. This study aimed to assess quantitatively the impact of incorporating functional lung imaging into 3-dimensional conformal radiotherapy （3DCRT） and intensity-modulated radiation therapy （IMRT） planning for non-small cell lung cancer （NSCLC）. Methods Ten patients with NSCLC who had undergone radiotherapy were included in this study. Before radiotherapy, each patient underwent CT simulation and lung perfusion imaging with single photon emission computed tomography （SPECT）. The SPECT images were registered with simulation planning CT and used to contour functional lung （lung-F） and non-functional lung （lung-NF）. Two 3DCRT plans and two IMRT plans were designed and compared in each patient： two anatomic plans using simulation CT alone and two functional plans using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the four types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Total radiation dose was set at 66 Gy （2 Gyx33 fractions）. Results In incorporating perfusion information in 3DCRT and IMRT planning, the reductions on average in the mean doses to the functional lung in the functional plan were 168 cGy and 89 cGy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with 〉5 Gy, 〉10 Gy, 〉20 Gy, 〉30 Gy and 〉40 Gy for functional lung in the functional plans were 6.50%, 10.21%, 14.02%, 22.30% and 23.46% in 3DCRT planning, respectively, and 3.05%, 15.52%, 14.16%, 4.87%, and 3.33% in IMRT planning, respectively. No greater degree of sparing of the functional lung was achieved in functional IMRT than in 3DCRT. Conclusion Function-guided 3DCRT and IMRT plannings both appear to be effective in preserving functional lung in NSCLC patients.
基金This study was sponsored by grants from the National Natural Science Foundation of China(No.30371381)Key Projects Foundation of Department of Science and Technology of Shandong province(No.031050102).
文摘Tumoural hypoxia can influence response to radiotherapy and other treatments, and oxygenation status has proved to be a prognostic indicator of the outcome of radiotherapy.1 Therefore, it is important to assess tumoural hypoxia and reoxygenation before selection of treatment protocols. During the last two decades, much attention has been paid to noninvasive imaging techniques using radiolabelled markers for the detection of hypoxic cells in solid tumours.2 Technetium （^99mTc） is a very convenient isotope for use with such imaging because it is readily available and suited to routine clinical use.
文摘Objective To review the current status and progress on nuclear medical molecular imaging of angiogenesis. Data sources A literature search was performed in Medline and PubMed published in English up to May 31, 2012. The search terms were molecular imaging, nuclear medicine and angiogenesis. Study selection Articles studying molecular imaging of angiogenesis using radionuclide were selected and reviewed. Results Molecular imaging has been used for studying angiogenesis by targeting integrin aVI33, VEGF/VEGFR, and matrix metalloproteinases （MMPs） with radionuclide-labeled tracers. The technology has been shown to be able to assess the angiogenesis status and/or predict the efficacy of anti-angiogenic therapy. Future directions of the research on the molecular imaging of angiogenesis include development of new tracers with better tumor targeting efficacy, desirable pharmacokinetics, and easy translation to clinical applications. Conclusion Advances in molecular imaging of angiogenesis using radioculcide will make the technology a valuable tool for personalized anti-angiogenesis treatment.
文摘Background An elevated serum lipid is one of the major risk factors for coronary heart disease （CHD）. Physicians＇ awareness contributes to successful adoption of practice guidelines. Community medical centers are the primary defense against chronic disease. This study aimed to investigate community physicians＇ awareness of cholesterol guidelines and their utilization.Methods Six hundred and one community physicians were randomly selected from four different regions, and completed a confidential and semi-structured questionnaire. Four hundred and ninety-one completed the questionnaire, and 486 valid questionnaires were available.Results The physicians＇ fundamental knowledge of lipids was astonishingly poor, while the awareness of cholesterol guidelines was low. Only 24% and 14% of the physicians reported the right optimal low-density lipoprotein cholesterol （LDL-C） level for CHD and diabetes patients respectively. More than half of the physicians （55.8%） mistakenly considered elevated transaminases to be the lethal side effect of statins. More than half of the physicians （51.9%） would give up statin treatment in the case of transaminase elevation.Conclusion Educational interventions to improve cholesterol knowledge and to publicize standard treatment are needed among Chinese community physicians.
文摘Background Prevention is presently the only available method to limit radiation-induced lung morbidity. A good predictor is the key point of prevention. This study aimed to investigate if [^18F]2-fluoro-2-deoxyglucose （FDG） uptake changes in the lung after radiotherapy could be used as a new predictor for acute radiation pneumonitis （RP）. Methods Forty-one patients with lung cancer underwent FDG positron emission tomography/computed tomography （FDG-PET/CT） imaging before and after radiotherapy. The mean standardized uptake value （SUV） was measured for the isodose regions of 0-9 Gy, 10-19 Gy, 20-29 Gy, 30-39 Gy, 40-49 Gy. The mean SUV of these regions after radiotherapy was compared with baseline. The mean SUV in patients who developed RP was also compared with that in those who did not. The statistical difference was determined by matched pair t test. The Radiation Therapy Oncology Group （RTOG） criteria were used for diagnosis and grading of RP. Results With a median follow-up of 12 months, 11 （26.8%） of the 41 patients developed grade 2 and above acute RP. The mean SUV of regions （10-19 Gy, 20-29 Gy, 30-39 Gy, 40-49 Gy） increased after radiation therapy in all 41 patients. The mean SUVs after radiation therapy were 0.54, 0.68, 1.31, 1.74 and 2.27 for 0-9 Gy, 10-19 Gy, 20-29 Gy, 30-39 Gy and 40-49 Gy, respectively. Before the radiation therapy, the mean SUV in each region was 0.53, 0.52, 0.52, 0.53 and 0.54, respectively. These patients had significantly higher FDG activities in regions receiving 10 Gy or more （P 〈0.001）. Compared with their counterparts, the elevation of SUV was significantly greater in those patients who developed acute RP subsequently. Conclusion The mean SUV of the lung tissue may be a useful predictor for the acute RP. FDG-PET/CT may play a new role in the study of the radiation damage of the lung.
