Automatic synthesis of 18F-FB-RGD and evaluation of its biodistribution / 中华核医学杂志

Objective To evaluate the automatic synthesis of 18F-labeled cyclic RGD peptide c(RGDyK)and its biological distribution in the tumor-bearing mice. Methods N-succinimidyl-4-18 F-fluorobenzoate (18F-SFB) was automatically synthesized and then re-dissolved in acetonitrile (MeCN). The cyclic RGD peptide c(RGDyK) was mixed with an hydrous DMSO and N, N-diisopropyl ethylamine (DIPEA). 18F-FBRGD was obtained by the reaction of peptide solution with 18 F-SFB. The final product was purified by HPLC gradient separation system and solid-phase extraction method. The biodistribution study and competition test of N-4-18F- fluorobenzoyl-RGD (18F-FB-RGD) in the tumor-bearing mice was performed. Results The labeling yield of 18 F-FB-RGD was (33.6 ± 3.5)%. The synthesis time was 110 min. The radiochemical purity was more than 98%. The tumor uptake of 18F-FB-RGD was (3.43 ±0.15), (2.61 ±0.14), (2.11 ±0.13), and (1.79 ±0.18) %ID/g, respectively, at 30, 60, 90 and 120 min after injection. The ratio of tumor to muscle activity ranged from 4.26 ±0.69 to 5.80 ±0.78. The tumor uptake decreased dramatically after RGD blockage. The uptake was (0.46 ±0.21) %ID/g and (2.87 ±0.59) %ID/g in the blocked and unblocked mice, respectively, at 60 min after blockage. Conclusions 18 F-FB-RGD can be automatically synthesized and it may become a promising tumor imaging agent.

Utility of squamous cell carcinoma antigen, carcinoembryonic antigen, Cyfra 21-1 and neuron specific enolase in lung cancer diagnosis: a prospective study from China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Early detection and diagnosis is urgent for the sake of effective treatment strategy for lung cancer. However, a convenient, economical and relatively precise method is not available. We here report a prospective study to find the possible value of the combined use of four popular tumor markers in the early diagnosis of lung cancer among patients with suspicious nodules in the lung.</p><p><b>METHODS</b>Six hundred and sixty inpatients with suspicious nodules in the lung were divided into a lung cancer group and a benign pulmonary tumor group according to post-operative histological examinations. Serum levels of four tumor markers including squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), Cyfra 21-1 and neuron specific enolase (NSE) were assayed for each patient. Receiver operating characteristic (ROC) curves were constructed for each tumor marker. The power of lung cancer diagnosis of each tumor marker, as well as a combination of them were analyzed and compared.</p><p><b>RESULTS</b>The serum levels (median, range) of SCC, CEA, Cyfra 21-1 and NSE were 0.44 (0.01 - 35.70) ng/ml, 2.49 (0.30 - 26.78) ng/ml, 2.30 (0.82 - 73.33) ng/ml and 10.54 (0.10 - 56.41) ng/ml respectively in lung cancer group, and were 0.32 (0.01 - 0.90) ng/ml, 1.60 (0.20 - 8.93) ng/ml, 1.41 (0.72 - 4.82) ng/ml and 9.36 (6.56 - 24.24) ng/ml respectively in the benign pulmonary tumor group. The difference in each tumor marker between the two groups was significant (P < 0.05). The ROCs of SCC, CEA, Cyfra 21-1 and NSE were 0.702 (95%CI, 0.654 - 0.751), 0.611 (95%CI, 0.563 - 0.659), 0.650 (95%CI, 0.601 - 0.700) and 0.598 (95%CI, 0.542 - 0.654) respectively, indicating very low power of these four tumor markers. When a combination of SCC, CEA, Cyfra 21-1 and NSE were employed, the diagnosis power was strengthened.</p><p><b>CONCLUSION</b>SCC, CEA, Cyfra 21-1 and NSE are valuable in the early diagnosis of lung cancer among suspicious nodules in the lung, especially when they were assayed together for one patient.</p>

Expression of dopamine receptor D2 in pulmonary carcinoma cells and effects of dopamine on the cell apoptosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the expression of dopamine receptor D2 in different pulmonary carcinoma cells and investigate the effect of dopamine in inducing apoptosis of A549 cells.</p><p><b>METHODS</b>Western blotting and RT-PCR were employed to detect the expression of dopamine receptor D2 in different pulmonary carcinoma cells (95D, H460, GLC-82, A549 and H446 cells). The apoptosis of A549 cells after a 6-hour exposure to 0.02%, 0.04%, 0.08% and 0.1% dopamine was analyzed by flow cytometry. The apoptosis-inducing effect of dopamine in vivo was also tested by intratumoral injection of 1% dopamine in 2 BALB/c-nu mice bearing A549 tumor xenograft using flow cytometry.</p><p><b>RESULTS</b>The presence of dopamine receptor D2 expression was detected by Western blotting and RT-PCR in 95D, H460, GLC-82, A549 and H446 cells. Flow cytometry detected obvious apoptosis of A549 cells following dopamine exposure in vitro in positive correlation to dopamine concentration. In the tumor-bearing mice, dopamine also showed an obvious apoptosis-inducing effect on A549 cells.</p><p><b>CONCLUSION</b>Dopamine receptor D2 exists extensively in different pulmonary carcinoma cells. Dopamine may promote the apoptosis of pulmonary carcinoma cells through dopamine receptor D2.</p>

Diagnosis and surgical treatment of congenital bronchoesophageal fistula in adult / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the clinical characteristics, diagnosis and surgical treatment of adult congenital bronchoesophageal fistula.</p><p><b>METHODS</b>Eleven cases of adult congenital bronchoesophageal fistula that were diagnosed and surgically treated between May 1990 and August 2010 had been reviewed. There were 7 male and 4 female patients, ranging in age from 28 to 66 years (mean 48.7 years). The chief clinical presentation included coughing and sputum in 10 cases, recurrent bouts of coughing after drinking liquid food in 6 cases, hemoptysis in 6 cases, low fever in 4 cases, chest pain in 3 cases. The duration of symptoms before diagnosis ranged from 5 to 36 years (mean 16.8 years). The diagnosis of bronchoesophageal fistula was confirmed most by esophagography. Associated diseased lung was resected in all patients (lobectomy in 10 cases and pneumonectomy in 1 case). The operation included right thoracotomy in 7 cases and left thoracotomy in 4 cases. The fistula was completely resected in 10 cases. The tract was simply divided and the end was sutured in 1 case.</p><p><b>RESULTS</b>The postoperative course was uneventful in 10 patients who were discharged from hospital 10 to 18 d after operation. One patient suffered from esophageal fistula and received second operation. Regular follow-up was conducted on all 11 patients, proving that 3-year survival rate was 11/11 and 5-year survival rate was 9/11.</p><p><b>CONCLUSION</b>Persistence of congenital bronchoesophageal fistula into adulthood is rare. The main symptom is nonspecific coughing and bouts of coughing after drinking liquid food. The most useful diagnostic method is the esophagography. Even though it is benign disease, life-threatening complications might occur and it must be treated surgically as soon as the diagnosis is established.</p>

Comparison of the biodistribution and PET imaging with (11)C-PDT and (18)F-FDG in the mouse model of lung adenocarcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The objective of this study was to compare the biodistribution and PET imaging of (11)C-PDT and (18)F-FDG in a mouse model of lung adenocarcinoma, and to evaluate the value of (11)C-PDT as a new tracer for PET imaging of lung cancer.</p><p><b>METHODS</b>Twenty four lung adenocarcinoma-bearing mice were randomly divided into two groups, 12 each. The mice received (11)C-PDT or (18)F-FDG injection i.v. respectively. The biodistribution of (11)C-PDT or (18)F-FDG in the mice was measured with a well-gamma detector at 60 min after injection. The PET imagings of mice were performed using either of the two tracers.</p><p><b>RESULTS</b>Considerable uptake of the both radioactive tracers in the tumors was observed. The tumor uptake of (11)C-PDT [(0.65 +/- 0.20)%ID/g] was significantly lower than that of (18)F-FDG [(7.44 +/- 1.56)%ID/g, P < 0.01]. In the (11)C-PDT group, the highest uptake was observed in the liver, kidney and blood in a successively declining order, while the highest uptake of (18)F-FDG was seen in a order of heart, tumor and kidneys. The tumor/muscle ratio of (11)C-PDT uptake was relatively high (2.02 +/- 0.56), but still lower than that of (18)F-FDG (2.95 +/- 0.49, P < 0.01). All values of other tumor/organ ratios (T/NT) of (11)C-PDT uptake were < 2. High radioactive uptake was showed in the tumor and abdominal organs on PET images in the tumor-bearing mice injected with (11)C-PDT, and (18)F-FDG uptake was showed in the heart, tumor and abdominal organs. The tumor PET images with (11)C-PDT and (18)F-FDG were all clear.</p><p><b>CONCLUSION</b>The uptake of (11)C-PDT in lung cancer is higher than that in muscle tissues, and pulmonary cancers can be detected by PET imaging. (11)C-PDT may be a promising PET tracer for lung cancers.</p>

Effects and mechanisms of non-restrictive external stent for prevention of vein graft restenosis in a rabbit model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Among various treatments preventing vein graft restenosis, external stent is receiving more and more attention. This study aimed to investigate the effect of non-restrictive external stent on the prevention of vein graft restenosis and the potential mechanisms of platelet-derived growth factor (PDGF) in the process of restenosis.</p><p><b>METHODS</b>Thirty-six "New Zealand white rabbits" were randomly divided into two groups, stented group (group S) and control group (non-stented group, group NS). Each rabbit underwent a reversed autologous external jugular vein into common carotid artery bypass grafting. In group S, the vein grafts were surrounded by a non restrictive stent which was 6 mm in diameter (a kind of Dacron vascular prosthesis); and in group NS, there was no stent to support the vein grafts. The grafts were harvested at the first week (1W), second week (2W) and fourth week (4W) after surgery respectively. The dimensions (including the thickness and area of the intima and media, luminal area) were measured by computer-aided image analysis system, and the intimal hyperplasia ratio was defined as the percentage of the area enclosed by the internal elastic lamina occupied by the intima.</p><p><b>RESULTS</b>At 1W, the difference of the thickness and area of the intima between groups S and NS was not significant (P > 0.05); at 2W and 4W, the thickness and area of the intima and the intimal hyperplasia ratio in group S were less significant than those in group NS (P < 0.05); from 1W to 4W, the thickness and area of the media in group S were smaller than those in group NS (P < 0.05). Immunocytochemistry staining of PDGF-B showed that the percentage of positive cells of intima in both two groups was peaked at 2W, and a significantly smaller percentage was detected in group S compared with that in group NS at 2W and 4W (P < 0.05); the percentage of PDGF-B positive cells of media in both two groups was also peaked at 2W, and that in group S was smaller than that in group NS from 1W to 4W (P < 0.05); and the percentage of PDGF-B positive cells of adventitia in group S was peaked at 4W, whereas the percentage of adventitia in group NS peaked at 2W, and the percentage of adventitia in group S was greater than in group NS at 4W (P < 0.05).</p><p><b>CONCLUSIONS</b>Non-restrictive external stenting inhibits the hyperplasia of the intima and media of the vein grafts and reduces the thickness and area of the intima and media; Non-restrictive external stenting inhibits the synthesis of PDGF and changes its distribution, and then inhibits the hyperplasia of the intima.</p>

Prognostic analysis of partial atrium or large blood vessel resection for treatment of locally advanced lung cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the value of partial atrium or large blood vessel resection for the treatment of locally advanced lung cancer.</p><p><b>METHODS</b>Thirty-five patients with locally advanced lung cancer (T(4)N(0)-N(2)M(0)) underwent lobectomy or pneumonectomy combined with intrapericardial vascular management or partial resection of the atrium. Of the 35 patients , 15 underwent left pneumonectomy combined with partial resection of the left atrium, 3 had pneumonectomy and partial resection of pulmonary artery trunk, 11 received right pneumonectomy and partial resection of the left atrium, 3 had middle and lower lobectomies and partial resection of the left atrium, and 3 underwent right upper lobectomy, partial resection of the superior vena cava and replacement of artificial blood vessel.</p><p><b>RESULTS</b>No death occurred in the 35 patients. Postoperative arrhythmia occurred in 4 cases and respiratory failure in 2 cases. The 1, 2, 3 and 4 year survival rates of the patients were 79.2% (19/24), 53.3% (8/15), 46.2% (6/13) and 36.4% (4/11), respectively. Pathologically, 27 patients had squamous carcinoma, 3 had adenocarcinoma, 3 had adenosquamous carcinoma and 2 had large cell carcinoma. In TNM staging, 6 were in T(4)N(0)M(0), 11 in T(4)N(1)M(0) and 18 in T(4)N(2)M(0).</p><p><b>CONCLUSION</b>Pneumonectomy or lobectomy combined with intrapericardial vascular management or partial resection of the atrium can enhance the possibility of radical resection of locally advanced lung cancer and increase the long term survival rate.</p>

Expression of EYA2 in non-small cell lang cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To identify the expression of Drosophila Eyes Absent Homologue 2 (EYA2) in non-small cell lung cancer (NSCLC) and to investigate its correlation with clinical parameters.</p><p><b>METHODS</b>59 fresh specimens of lung cancer and paired normal lung tissue were obtained from 59 NSCLC cases treated in the department of thoracic surgery in our hospital from June 2006 to October 2007. Western blotting and immunohistochemistry were used to assay the specimens with goat anti-human EYA2 polyclone antibody. Clinicopathological parameters were collected and the correlation with EYA2 expression was subsequently analyzed.</p><p><b>RESULTS</b>The expression of EYA2 was detected in cytoplasm and nucleus of the cancer cells, but mostly in cytoplasm. Western blotting and immunohistochemistry showed the expression of EYA2 in NSCLC was increased and correlated with pathological type, but not with gender, age, pTNM stage, histological differentiation and lymph node metastasis. EYA2 expression was significantly up-regulated in adenocarcinoma, while not changed in lung squamous cell carcinoma.</p><p><b>CONCLUSION</b>The results of this study suggest that expression of EYA2 in lung adenocarcinoma is augmented. EYA2 is likely participating in the development of lung adenocarcinoma as a transcriptional activator.</p>

Diagnosis and surgical treatment of the primary mediastinal teratoma / 中华外科杂志

<p><b>OBJECTIVE</b>To review the experience of diagnosis and surgical treatment of the primary mediastinal teratomas.</p><p><b>METHODS</b>The clinical data of forty-nine cases with teratoma were retrospectively analysed from March 1996 to March 2006.</p><p><b>RESULTS</b>Based on history, physical examination, chest X-ray, CT scan and magnetic resonance, the diagnosis of forty-eight cases were confirmed before surgery. Surgical procedures were performed in all cases. Forty-six patients were subjected to radical excision, two patients to partial excision and one patient to exploratory operation. Among all the cases, Wedge resection of the lung was performed in eight cases, partial pericardium excision in six cases. There was no surgically related mortality or complications in any patients. The diagnosis of teratoma was confirmed by postoperative histopathological examination. No relapse occurred during follow-up.</p><p><b>CONCLUSIONS</b>History, physical examination and radiological imaging are the main diagnostic means for the primary mediastinal teratoma. Surgical resection is an effective therapy. Early diagnosis and correct selection of operation according to the characteristic of the tumor are important to therapy.</p>