Objective To study the effect of Coxsackie virus B3 (CVB3) infection on islet cells in vitro, and to explore the mechanism of islet cells caused by CVB3. Methods Bone marrow mesenchymal stem cells( BMSCs) were separated from the bone marrow and cultured. Then they were induced to differentiate into islet-like cells using nicotinamide and mercaptoethanol. Differentiated cells were detected by morphology , special staining and RT-PCR. Observe CVB3 infection on islet cells under inverse microscope and detect the specific gene fragment by RT-PCR. Results BMSCs showed half suspended shape and gathered to form a cluster after induction. Cells became red brown by dithizone specific staining. RT-PCR also proved the existence of mRNA expressing insulin. Infected islet cells appeared typical pathological changes like shrinks, refraction decreases. RT-PCR detected the desired specific gene fragment of 299 bp in infected islet cells. Conclusion CVB3 can directly injury islet cells, and damage the function of islet cells of secreting insulin.

Background and purpose:Integrinαvβ3 receptor plays an important role in promoting, sustaining and regulating the angiogenesis. It is overexpressed on neovascular endothelial cells and tumor cells. RGD peptide specifically binds to integrinαvβ3, which could evaluate growth status and invasiveness of tumor. This study aimed to investigate the biodistribution in healthy KM mice and micro PET/CT imaging in U87MG tumor-bearing mice of 18F-E[c(RGDfK)2]. Methods: 18F-E[c(RGDfK)2] was produced using an automated synthesis module via a simple one-step 18F-labeling strategy of the precursor 4-NO2-3-TFMBz-E[c(RGDfK)2]. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated at 0.5, 1, 2, 4 h post injection of the probe. Micro PET/CT images of U87MG tumor-bearing nude mice with or without 18F-E[c(RGDfK)2] blocking were acquired at each time point. Results: The labeling efficiency and radiochemical purity of 18F-E[c(RGDfK)2] were 10% and 98%, respectively. 18F-E[c(RGDfK)2] was excreted via renal route, with a high blood clearance. The other organs had background-level activity accumulation. At 1 h, the%ID/g of kidney, liver, intestine, muscle and blood was (1.02±0.16)%ID/g,(0.24±0.06)%ID/g, (0.35±0.03)%ID/g, (0.13±0.03)%ID/g and (0.11±0.03)%ID/g 18F-E[c(RGDfK)2] had initial high tumor uptake [(5.2±0.56)%ID/g] and good tumor-to-background contrast (5.36) at 1 h post injection. Tumor uptake for blocking group was lower than those without blocking, and T/M reduced to 1.57. Conclusion: 18F-E[c(RGDfK)2] appears a promising PET molecular imaging probe targeting integrin αvβ3, with high tumor uptake. It could be suitable for prognosis evaluation of integrin-positive tumor, selection of vascular targeting therapy and therapy effect monitoring.

Objective:To investigate clinical features of distant metastases ( DM ) and analyze clinico-pathologic risk factors associated with DM from salivary gland carcinomas after being treated by surgery combined with 125 I internal brachytherapy. Methods: Between October 2001 and March 2010, 197 pa-tients with salivary gland carcinoma were treated by surgery combined with 125 I internal brachytherapy and had follow-up for 2 years or more. Univariate and multivariate analyses were performed to evaluate clini-copathologic risk factors that might influence the risk of distant metastases. Results:DM occurred in 28 of 197 patients (14. 2%). The commonest site of distant metastases overall was the lung 89. 3% (25/28), followed by bones 17. 9% (5/28) and liver (4/28). DM developed after an average interval of (44. 2 ± 45. 8) months from the time of initial diagnosis, and the mean interval was 64 months. The average time to death after the diagnosis of DM was only (9. 7 ± 13. 4) months, and the mean time was 12 months. The 3-year locoregional control rate and survival rate were 90. 8%, and 87. 8% respectively,and the 5-year ones 84. 0% and 81. 0%, respectively. Univariate analyses revealed that the risk of distant metasta-ses was significantly influenced by locoregional tumor failure (F=26. 997,P<0. 01) and histologic dif-ferentiation (F=1. 592,P<0. 01). Multivariate analysis of freedom from distant metastases revealed that locoregional control (F=29. 332,P<0. 01) significantly influenced this end point. Conclusion: Sali-vary gland carcinoma could achieve high local control rate after being treated by surgery combined with 125 I internal brachytherapy, and the average interval from diagnosis to DM was prolonged, DM was signifi-cantly influenced bylocoregional control.

Objective: To investigate clinical features of distant metastases from malignant salivary gland carcinomas after treated by 125I internal brachy therapy alone.Methods: Between 2002 and 2010, 43 patients with locally advanced unresectable or recurrent malignant salivary gland carcinomas were treated by 125I internal brachy therapy alone at Peking University School and Hospital of Stomatology.All of them had been follow-up at least 2 years.The primary sites of malignant salivary gland carcinomas were the parotid for 12 patients, infratemporal fossa for 9 patients, tongue for 7 patients, maxilla for 6 patients, parapharyngeal for 4 patients, floor of months for 3 patients, submandibular gland for 1 patient, and lip for 1 patient.The overall survival rate, local control rate, and distant metastases were retrospectively reviewed.Results: Distant metastases occurred in 23 of the 43 patients (53.5%).Distant metastases developed from 5 to 96 months, with an average interval of (27.0±23.7) months from the time of initial diagnosis, the mean interval was 21 months.The commonest site of distant metastases overall was the lung 69.6%(16/23).The most common pathological types of distant metastases were adenoid cystic carcinoma (14/23, 60.9%) and nonspecific adenocarcinoma (7/23, 30.4%).At the time of the last follow-up, 26 patients died, and 18 of them due to distant metastases (69.2%, 18/26).In the study, 27 patients got complete remission(CR), 12 got partial remission(PR) more than 50%, 2 less than 50%, and 2 patients were invalid.The effective rate (CR+ PR) was 90.7%.The 3 year loco-regional control rate and survival rate were 60.1%, 82.6%, respectively, and the 5 year's 53.4% and 56.0%.Conclusion: The 125I brachy therapy is a feasible and effective modality for the treatment of locally advanced unresectable or recurrent malignant salivary gland carcinomas.However, further studies are needed with larger numbers of patients and for a longer follow-up assessment.Distant metastasis was the main cause of treatment failure, and the lung was the most common site of distant metastases.

Objective To evaluate the treatment of malignant submandibular gland tumors with surgery combined with 125I radioactive implantation.Methods Thirty-two patients with malignant submandibular gland tumors were treated with surgery combined with 125I seed implantation from December 2005 to December 2012.All of the 32 patients with primary disease were treated by excision of the submandibular gland and neoplasm.None of the patients received wide excision or neck dissection without the evidence of the neck metastases.The planning targets was based on computerized tomography (CT)images,tumors site,extent and pathologic type.The matched peripheral dose (mPD) was 90-110 Gy.Recurrence-free survival (RFS),overall survival (OS) rates and side effects were retrospectively reviewed.Results Totally 32 patients received 1394 radioactive seeds implantation,radioactive seeds and dose distributed were well in all patients.All patients were followed for 15-126 months (mean of 64 months),with 5 recurrence,5 distant metastases,and 4 patients who died of disease.The 3-and 5-year RFS were 93.1％ and 87.9％,and OS rates were 93.3％ and 84.5％,respectively.No severe complications were observed during follow-up.Conclusions The excision of the neoplasm and the submandibular gland,combined with 125I seed implantation brachytherapy was an effective modality for the treatment of malignant submandibular gland tumors.

Objective To observe the fixity of 125I seed after implantation in parotid region. Methods Ten patients treated with 125I seed interstitial brachytherapy in parotid were randomly selected. Within one week after the treatment, two plane radiographs were taken by radiotherapy simulator and 125I seed was counted. All plane dosimetry analysis were performed by treatment planning system. The areas surrounded by 50%, 100% and 150% of prescription dose curve and dose equality index were calculated. Two months after the treatment, the same examination were repeated and were compared with t test. Results The number of seeds was equal in two examination. There were no signifieant differences in two examinations either for the areas surrounded by 50%, 100% and 150% of prescription dose curve or for the dose equality index. Conclusions The position of 125I seed after implantation in parotid region is quite fixable, which can ensure the curative effect.

Objective To evaluate the feasibility of individual template assisting permanent interstitial brachytherapy for skull base region.Methods From August 2010 to June 2012,20 patients with recurrent malignancies of skull base region received 125I seed permanent implantation.Before implanting,all patients underwent CT scan,the data were stored in Dicom format and imported into brachytherapy treatment planning system (BTPS).The preplan were finished by BTPS.Then,the digital model based on virtual needle and skin CT slices was reconstructed by Mimics and Geomagic.According to the digital model,the individual template was made from medical light-cured resin using rapid forming machine.During implanting,needles were inserted under the individual template assistance and 125I seeds were implanted according to preplan.After implanting,implantation quality was evaluated by 2D and 3D CT images and BTPS.The needles and seed distribution were observed.The actual dose distribution of target volumes D90,V100 and V150 was calculated.The complications were recorded within 72 hours.Results Interstitial implantation of 20 patients were performed successfully and efficiently under the individual template assistance without serious complications.Because of containing the virtual needle positioning and face surface feature information at the same time,the individual template significantly improved precision of needle location and orientation.The actuarial median number of 125I seeds implanted was 70 (range,20-172),and actuarial median D90,V100 and V150 was 181.6 Gy (127.4-279.6 Gy),98.2％ (94.6％-100％),43.2％ (24.3％-52.2％),respectively.The seed distribution and dosimetric quality were well controlled.Conclusions The method of individual template assisting permanent interstitial brachytherapy for skull base region is feasible,which can improve the accuracy of needle position placement.

Objective To explore the method of target volume determination of postoperative 125I seeds interstitial brachytherapy in parotid gland carcinoma.Methods A total of 31 cases( 14 males and 17 famales) with primary parotid carcinoma who were treated in Peking University Hospital of Stomatology from Oct 2002 to Nov 2006.The patients' average age was 38.2 years.All patients underwent tumor resection and postoperative 125I seeds interstitial brachytherapy with 60 Gy matched peripheral dose.The spiral CT was performed for treatment plan and quality verification before and after the brachytherapy.The bone and muscle landmarks surrounding parotid were selected as reference for target volume determination.D90 of target volume and dose of organs at risk were calculated,while the target volume and D90 of target volume of verification were compared with that of treatment plan through quality verification.Results The target volume or D90 of target volume before and after treatment was not statistically different.D90 of target volume was more than 60 Gy.During 3 -7 years of follow-up,all patients had no recurrence.ConclusionsAccording to the follow-up results,the method used for target volume determination in this paper might be satisfied.

Background and purpose: One of the main mechanism of chemotherapy is inducing tuomr apoptosis. Molecular imaging can allow noninvasively and dynamically monitor tumor apoptosis in vivo, and help to drug screening and therapeutic evaluation. The purpose of this study was to evaluate the feasibility of 18F-SFB-Annexin B1 in detecting apoptosis at an early phase after chemotheraphy. Methods:Annexin B1 was labeled with 18F using SFB as a chelating agent. Tissue distribution of 18F-SFB-Annexin B1 was studied in healthy mice by the dissection method. W256 tumor-bearing rats were injected with 18F-SFB-Annexin B1 intravenously at 24 h after the treatment of cyclophosphamide (CTX 200 mg/kg) or saline. Then imaging was acquired at 1, 2, 3, and 4 h postinjection on a PET/CT, and the tumor-to-muscle ratio of SUVmax (T/M) and the AI from TUNEL testing were compared. Results: 18F-SFB-Annexin B1 had a radiochemical pruity (RCP)>95%. Biodistribution of this probe showed a predominant uptake in the kidney, then was liver, spleen, and myocardium, rapid clearance from blood and urinary was observed. The radios of T/M were 4.38±0.56, 6.75±1.16, 6.44±1.12, 4.81±0.17, respectively at 1, 2, 3, 4 h post injection of the chemotherapy group, much higher than that of the saline group (2.35±0.14, 2.99±0.55, 3.04±0.41, 2.33±0.47, respectively). The differences between the two groups were significant (F=23.790, 16.913, 14.046, 77.517, respectively, all P<0.05). TUNEL staining revealed that chemotherapy treatment significantly increased the percentage of apoptosis cells with an AI of (21.00±0.04)%in the chemotherapy group, higher than that in the saline group (8.58±0.01)%, the difference was significant (F=21.539, P<0.05). The radios of T/M were significantly correlated with the values of AI (r=0.91, P<0.05). Conclusion: 18F-SFB-Annexin B1 can be used to apoptosis imaging and early therapeutic evaluation in vivo because it can reflect apoptosis at an early stage after chemotheraphy.

Objective To evaluate the efficacy of 125Ⅰ brachytherapy alone for the treatment of recurrent parotid gland carcinoma.Methods Recurrent parotid gland carcinoma patients (n =24) treated by 125Ⅰ brachytherapy alone between 2006 and 2013 at Peking University Hospital of Stomatology were enrolled in this retrospective study.All patients underwent surgery or radiotherapy.The local control rate,survival rate,and side effects were evaluated.Results The median follow-up time was 21 months (range,4-59 months).Among the 24 patients,6 had local failure and 10 died during the follow-up period.The 1-and 3-year overall survival rates,progression-free survival rates,local control rates were 74.8％ and 39.3％,74.8％ and 31.5％,82.0％ and 69.4％,respectively.No grade 3 or over radiation injury was found.Conclusions 125Ⅰ seed brachytherapy alone could provide an ahernative treatment method for inoperable recurrent parotid gland carcinoma patients.