Parkinson’s disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. A characteristic pathological feature of PD is cytoplasmic accumulation of α-synuclein (SNCA) protein. Multiplication of the SNCA gene in familial PD and pathological accumulation of SNCA protein during progression of sporadic PD suggest that increased SNCA protein levels increase the risk of PD. Thus, reducing SNCA expression levels could delay PD onset or modify the disease course. For efficient knock down, we designed and synthesized an amido-bridged nucleic acids (AmNA)-modified antisense oligonucleotide (ASO) that targeted SNCA with improved stability and cellular uptake in vivo . AmNA-ASO efficiently downregulated SNCA at both the mRNA and protein level in vitro and in vivo . Notably, AmNA-ASO was efficiently delivered into the mouse brain by intracerebroventricular injection without the aid of additional chemicals. Furthermore, administration of AmNA-ASO ameliorated neurological defects in PD model mice expressing human wild type SNCA. Taken together, these findings suggest that AmNA-ASO is a promising therapeutic strategy for SNCA-associated pathology in PD.

A combined system comprising the TrueBeam linear accelerator and a new real‐time, tumor‐tracking radiotherapy system, SyncTraX, was installed in our institution. The goals of this study were to assess the capability of SyncTraX in measuring the position of a fiducial marker using color fluoroscopic images, and to evaluate the dosimetric and geometric accuracy of respiratory‐gated radiotherapy using this combined system for the simple geometry. For the fundamental evaluation of respiratory‐gated radiotherapy using SyncTraX, the following were performed: 1) determination of dosimetric and positional characteristics of sinusoidal patterns using a motor‐driven base for several gating windows; 2) measurement of time delay using an oscilloscope; 3) positional verification of sinusoidal patterns and the pattern in the case of a lung cancer patient; 4) measurement of the half‐value layer (HVL in mm AL), effective kVp, and air kerma, using a solid‐state detector for each fluoroscopic condition, to determine the patient dose. The dose profile in a moving phantom with gated radiotherapy having a gating window ≤4 mm was in good agreement with that under static conditions for each photon beam. The total time delay between TrueBeam and SyncTraX was <227 ms for each photon beam. The mean of the positional tracking error was <0.4 mm for sinusoidal patterns and for the pattern in the case of a lung cancer patient. The air‐kerma rates from one fluoroscopy direction were 1.93±0.01, 2.86±0.01, 3.92±0.04, 5.28±0.03, and 6.60±0.05 mGy/min for 70, 80, 90, 100, and 110 kV X‐ray beams at 80 mA, respectively. The combined system comprising TrueBeam and SyncTraX could track the motion of the fiducial marker and control radiation delivery with reasonable accuracy; therefore, this system provides significant dosimetric improvement. However, patient exposure dose from fluoroscopy was not clinically negligible.PACS number(s): 87.53.Bn, 87.55.km, 87.55.Qr

This study aimed to identify factors that predict prognosis after radiotherapy for brain metastases (BMs) from small-cell lung cancer (SCLC). This study retrospectively evaluated 48 consecutive patients who underwent whole-brain radiotherapy (WBRT) for BMs from SCLC between February 2008 and December 2017. WBRT was delivered at a median dose of 30 Gy (range: 30–40 Gy) in 10 fractions (range: 10–16 fractions). Clinical factors were tested for associations with overall survival after WBRT. The median survival and 1-year overall survival rate after WBRT treatment were 232 days and 34.4%, respectively. Univariate analyses revealed that longer survival was associated with Eastern Cooperative Oncology Group performance status of 0–1, asymptomatic BMs, lactate dehydrogenase (LDH) in the normal range, Radiation Therapy Oncology Group–recursive partitioning analysis class 2, and a graded prognostic assessment score of ≥1.5 (P < 0.01, P < 0.01, P < 0.01, P < 0.01 and P < 0.05, respectively). In the multivariate analyses, longer survival was independently associated with asymptomatic BMs [hazard ratio for death (HR), 0.32; 95% confidence interval (CI), 0.12–0.79; P < 0.05] and LDH in the normal range (HR, 0.42; 95% CI, 0.21–0.83; P < 0.05). The presence of symptoms due to BMs and LDH values independently predicted prognosis after WBRT for BMs from SCLC. Elevated LDH may provide valuable information for identifying patients with BMs who could have poor survival outcomes.

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