B cell dysfunction due to obesity can be associated with alterations in the levels of micro-RNAs (miRNAs). However, the role of miRNAs in these processes remains elusive. Here, we show that miR-802 is increased in the pancreatic islets of obese mouse models and demonstrate that inducible transgenic overexpression of miR-802 in mice causes impaired insulin transcription and secretion. We identify Foxo1 as a transcription factor of miR-802 promoting its transcription, and NeuroD1 and Fzd5 as targets of miR-802-dependent silencing. Repression of NeuroD1 in β cell and primary islets impairs insulin transcription and reduction of Fzd5 in β cell, which, in turn, impairs Ca 2+ signaling, thereby repressing calcium influx and decreasing insulin secretion. We functionally create a novel network between obesity and β cell dysfunction via miR-802 regulation. Elucidation of the impact of obesity on microRNA expression can broaden our understanding of pathophysiological development of diabetes.

Two patients with multiple lung metastases (≥ 5) were treated using frameless stereotactic body radiation therapy (SBRT) on an Elekta Axesse linear accelerator equipped with an interdigitation‐capable multileaf collimator and four‐dimensional cone‐beam CT (4D CBCT). The technique and the early clinical outcomes were evaluated. Patient A with five lung metastases and Patient B with seven lung metastases underwent SBRT (48 Gy/8 fractions for Patient A, 42 Gy/7 fractions for Patient B). The treatments were administered using a 6 MV photon beam. The nominal dose rate was 660 MUs/min. Patients were positioned and immobilized using thermoplastic masks and image guidance was done using 4D CBCT. The targets were delineated on the images of the 4D CT, and the positron emission tomography‐computed tomography (PET‐CT) images were taken as references. A two‐step, volumetric‐modulated arc therapy (VMAT) plan was designed for each patient. Step 1: the lesions in one lung were irradiated by a 210° arc field; Step 2: the rest of the lesions in the other lung were irradiated by a 120° arc field. Plans were evaluated using conformity index (CI) and homogeneity index (HI). Patients were followed up and adverse events were graded according to the Common Terminology Criteria for Adverse Events v4.0 (CTCAE v4.0). The beam‐on time of each treatment was less than 10 min. The CI and HI for the two plans were 0.562, 0.0709 and 0.513, 0.0794, respectively. Pulmonary function deteriorated slightly in both patients, and the patient with seven lung lesions was confirmed to have Grade 1 radiation pneumonitis. The technique was fast, accurate, and well tolerated by patients, and the two‐step plan is a helpful design in reducing the dose to the lungs.PACS numbers: 87.55‐x, 87.56.J‐, 87.56.‐v, 87.56.nk, 87.57.qp

BackgroundThe performance of single arc VMAT (VMAT1) for nasopharyngeal carcinoma (NPC) on the Axesse linac has not been well described in previous studies. The purpose of this study is to assess the feasibility of VMAT1 for NPC by comparing the dosimetry, delivery efficiency, and accuracy with dual arc VMAT (VMAT2), dynamic MLC intensity-modulated radiotherapy (dIMRT), and step-and-shoot intensity-modulated radiotherapy (ssIMRT).MethodsTwenty consecutive patients with non-metastatic NPC were selected to be planned with VMAT1, VMAT2, dIMRT and ssIMRT using Monaco 3.2 TPS on the Axesse™ linear accelerator. Three planning target volumes (PTVs), contoured as high risk, moderate risk and low risk regions, were set to receive median absorbed-dose (D50%) of 72.6 Gy, 63.6 Gy and 54 Gy, respectively. The Homogeneity Index (HI), Conformity Index (CI), Dose Volume Histograms (DVHs), delivery efficiency and accuracy were all evaluated.ResultsMean HI of PTV72.6 is better with VMAT1(0.07) and VMAT2(0.07) than dIMRT(0.09) and ssIMRT(0.09). Mean HI of PTV63.6 is better with VMAT1(0.21) and VMAT2(0.21) than dIMRT and ssIMRT. Mean CI of PTV72.6 is also better with VMAT1(0.57) and VMAT2(0.57) than dIMRT(0.49) and ssIMRT(0.5). Mean CI of PTV63.6 is better with VMAT1(0.76) and VMAT2(0.76) than dIMRT(0.73) and ssIMRT(0.73). VMAT had significantly improved homogeneity and conformity compared with IMRT. There was no significant difference between VMAT1 and VMAT2 in PTV coverage. Dose to normal tissues was acceptable for all four plan groups. VMAT1 and VMAT2 showed no significant difference in normal tissue sparring, whereas the mean dose of the parotid gland of dIMRT was significantly reduced compared to VMAT1 and VMAT2. The mean delivery time for VMAT1, VMAT2, dIMRT and ssIMRT was 2.7 min, 3.9 min, 5.7 min and 14.1 min, respectively. VMAT1 reduced the average delivery time by 29.8%, 51.1% and 80.8% compared with VMAT2, dIMRT and ssIMRT, respectively. VMAT and IMRT could all be delivered accurately based on our quality assurance standards.ConclusionsIn the treatment of NPC using the Axesse™ linear accelerator, single arc VMAT has shown superiority to double arc VMAT, dIMRT and ssIMRT in delivery efficiency, without compromise to the PTV coverage. However, there is still room for improvement in terms of OAR sparing.

This study evaluated radiotherapy techniques with 15 cases for simultaneous integrated boost to treat whole left breast and tumor bed following breast conserving surgery. Treatment plans were generated using three techniques: volumetric modulated arc therapy (VMAT) with a partial arc of 190° (1ARC), VMAT with two tangential mini-arcs of 50° each (2TARC) and intensity modulated radiation therapy with four fixed angle fields (4IMRT). Dosimetric parameters for the whole breast (Target), the boost tumor bed (Boost), and surrounding normal organs were compared. Chair Index (CHI) was introduced to evaluate the dose homogeneity in Target given the two levels of prescription dose. The dose coverage in Target was better in 1ARC and 2TARC than that in 4IMRT. The mean CHI in 1ARC (2.47) and 2TARC (2.62) were higher than that in 4IMRT (1.71, p < 0.05), and this indicated the dose homogeneity of Target was better in 1ARC and 2TARC than that in 4IMRT. The mean doses to right lung, and contralateral breast in 4IMRT were lower than those in 2TARC but the differences between them were small. 2TARC was better than 4IMRT with respect to the dose to ipsilateral lung and heart. Overall, 2TARC was optimal among three techniques.