Coronal X-ray emission from an intermediate-age brown dwarf

We report the X-ray detection of the brown dwarf (BD) companion TWA 5B in a $\simeq 12$ Myr old pre-main sequence binary system. We clearly resolve the faint companion (35 photons) separated from the X-ray luminous primary by 2 arcsec in a {\it Chandra} ACIS image. TWA 5B shows a soft X-ray spectrum with a low plasma temperature of only 0.3 keV and a constant flux during the 3 hour observation, of which the characteristics are commonly seen in the solar corona. The X-ray luminosity is 4$\times10^{27}$ erg s$^{-1}$ (0.1--10 keV band) or $\log L_X/L_{bol} = -3.4$. Comparing these properties to both younger and older BDs, we discuss the evolution of the X-ray emission in BDs. During their first few Myr, they exhibit high levels of X-ray activity as seen in higher mass pre-main sequence stars. The level in TWA 5B is still high at $t \simeq 12$ Myr in $\log L_X/L_{bol}$ while $kT$ has already substantially cooled

Novel approaches to cancer treatment based on DNA damage and tumor immunity activation induced by proton beam irradiation

科学研究費助成事業 研究成果報告書：基盤研究(B)2012-2014 課題番号：2439028

Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related Adverse Events

Nivolumab is a recently approved medication for the treatment of unresectable malignant melanoma. Many immune-related adverse events (irAEs) associated with nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how or if nivolumab should be administered to patients after they have experienced an irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1 demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2 had a diffuse alveolar damage (DAD) pattern. Oral corticosteroids improved chest shadow of CT scan in both cases. However, when nivolumab was re-administrated, case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From our cases, it is difficult to re-administrate nivolumab for the patients with pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve their symptoms

Measuring the Broad-band X-Ray Spectrum from 400 eV to 40 keV in the Southwest Part of the Supernova Remnant RX J1713.7-3946

We report on results from Suzaku broadband X-ray observations of the southwest part of the Galactic supernova remnant (SNR) RX J1713.7-3946 with an energy coverage of 0.4-40 keV. The X-ray spectrum, presumably of synchrotron origin, is known to be completely lineless, making this SNR ideally suited for a detailed study of the X-ray spectral shape formed through efficient particle acceleration at high speed shocks. With a sensitive hard X-ray measurement from the HXD PIN on board Suzaku, we determine the hard X-ray spectrum in the 12--40 keV range to be described by a power law with photon index Gamma = 3.2+/- 0.2, significantly steeper than the soft X-ray index of Gamma = 2.4+/- 0.05 measured previously with ASCA and other missions. We find that a simple power law fails to describe the full spectral range of 0.4-40 keV and instead a power-law with an exponential cutoff with hard index Gamma = 1.50+/- 0.09 and high-energy cutoff epsilon_c = 1.2+/- 0.3 keV formally provides an excellent fit over the full bandpass. If we use the so-called SRCUT model, as an alternative model, it gives the best-fit rolloff energy of epsilon_{roll} = 0.95+/- 0.04 keV. Together with the TeV gamma-ray spectrum ranging from 0.3 to 100 TeV obtained recently by HESS observations, our Suzaku observations of RX J1713.7-3946 provide stringent constraints on the highest energy particles accelerated in a supernova shock.Comment: 11 pages, 11 figures, accepted for publication in Publications of the Astronomical Society of Japan (PASJ

Dose-dependent decrease in anti-oxidant capacity of whole blood after irradiation: A novel potential marker for biodosimetry

Many reports have demonstrated that radiation stimulates reactive oxygen species (ROS) production by mitochondria for a few hours to a few days after irradiation. However, these studies were performed using cell lines, and there is a lack of information about redox homeostasis in irradiated animals and humans. Blood redox homeostasis reflects the body condition well and can be used as a diagnostic marker. However, most redox homeostasis studies have focused on plasma or serum, and the anti-oxidant capacity of whole blood has scarcely been investigated. Here, we report changes in the anti-oxidant capacity of whole blood after X-ray irradiation using C57BL/6 J mice. Whole-blood anti-oxidant capacity was measured by electron spin resonance (ESR) spin trapping using a novel spin-trapping agent, 2-diphenylphosphinoyl-2-methyl-3,4-dihydro-2H-pyrrole N-oxide (DPhPMPO). We found that whole-blood anti-oxidant capacity decreased in a dose-dependent manner (correlation factor, r > 0.9; P < 0.05) from 2 to 24 days after irradiation with 0.5–3 Gy. We further found that the red blood cell (RBC) glutathione level decreased and lipid peroxidation level increased in a dose-dependent manner from 2 to 6 days after irradiation. These findings suggest that blood redox state may be a useful biomarker for estimating exposure doses during nuclear and/or radiation accidents

Results of Proton Beam Therapy without Concurrent Chemotherapy for Patients with Unresectable Stage III Non-small Cell Lung Cancer

Introduction:This study was performed retrospectively to evaluate the outcome of patients with stage III non-small cell lung cancer (NSCLC) after proton beam therapy (PBT) alone.Methods:The subjects were 57 patients with histologically confirmed NSCLC (stage IIIA/IIIB: 24/33) who received PBT without concurrent chemotherapy. The cohort included 32 cases of squamous cell carcinoma, 18 adenocarcinoma, and 7 non-small cell carcinoma. Lymph node metastases were N0 7, N1 5, N2 30, and N3 15. Planned total doses ranged from 50 to 84.5 GyE (median, 74 GyE).Results:Planned treatment was completed in 51 patients (89%). At the time of analysis, 20 patients were alive, and the median follow-up periods were 16.2 months for all patients and 22.2 months for survivors. The median overall survival period was 21.3 months (95% confidence interval: 14.2–28.4 months), and the 1- and 2-year overall survival rates were 65.5% (52.9–78.0%) and 39.4% (25.3–53.5%), respectively. Disease progression occurred in 38 patients, and the 1- and 2-year progression-free survival rates were 36.2% (23.1–49.4%) and 24.9% (12.7–37.2%), respectively. Local recurrence was observed in 13 patients, and the 1- and 2-year local control rates were 79.1% (66.8–91.3%) and 64.1% (47.5–80.7%), respectively. Grade ≥3 lung toxicity was seen in six patients, esophageal toxicity occurred at grade ⩽2, and there was no cardiac toxicity.Conclusion:The prognosis of patients with unresectable stage III NSCLC is poor without chemotherapy. Our data suggest that high-dose PBT is beneficial and tolerable for these patients

Histone Deacetylase Inhibitor Induced Radiation Sensitization Effects on Human Cancer Cells after Photon and Hadron Radiation Exposure

Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor, which has been widely utilized throughout the cancer research field. SAHA-induced radiosensitization in normal human fibroblasts AG1522 and lung carcinoma cells A549 were evaluated with a combination of γ-rays, proton, and carbon ion exposure. Growth delay was observed in both cell lines during SAHA treatment; 2 μM SAHA treatment decreased clonogenicity and induced cell cycle block in G1 phase but 0.2 μM SAHA treatment did not show either of them. Low LET (Linear Energy Transfer) irradiated A549 cells showed radiosensitization effects on cell killing in cycling and G1 phase with 0.2 or 2 μM SAHA pretreatment. In contrast, minimal sensitization was observed in normal human cells after low and high LET radiation exposure. The potentially lethal damage repair was not affected by SAHA treatment. SAHA treatment reduced the rate of γ-H2AX foci disappearance and suppressed RAD51 and RPA (Replication Protein A) focus formation. Suppression of DNA double strand break repair by SAHA did not result in the differences of SAHA-induced radiosensitization between human cancer cells and normal cells. In conclusion, our results suggest SAHA treatment will sensitize cancer cells to low and high LET radiation with minimum effects to normal cell

Development of stepping measurement device for evaluation of and training in walking

急性膵炎の回復後その発症原因の検索において発見された小膵癌の3例を報告し，膵炎の発症原因の一つとして膵癌を常に念頭におく必要があることを強調した。またスクリーニング検査および精査において小膵癌を診断する手順について考察を加えた。症例1は初回発作の回復後に，症例2および症例3は再発発作の回復後に急性膵炎の発症原因の検索を目的に紹介された。いずれの症例においても血清腫瘍マーカーは正常植を示し，腹部USおよびCTは腫瘍から尾側の膵管の拡張を示したが腫瘍そのものは描出はできなかった。症例1ではERCP像から膵体部癌を強く疑い，症例2と症例3ではERCP像と細胞診陽性所見から膵頭部癌と確診し，手術を行った。腫瘍の最大径は症例1では0.9cm，症例2では1.5cm，症例3では2.0cmであり，いずれも転移を認めず根治切除可能であった。Although gait training equipment such as the bicycle ergometer and treadmill exists for patients whose walking ability is high, there is no appropriate gait training mehtod or training instrument for patients whose walking ability has become impaired, who often use a cane or walker, etc. in the course of daily life. In the case of gait training for persons whose walking ability involves impaired locomotion, there is always the danger of a fall. Consequently, a caregiver is required, and the effect of the training is cut by half because the patient's anxiety about falling is exacerbated. Slow stepping affords strengthening and balance training of the leg muscles for patients whose walking ability has become low, and walking ability is improved. However,whether such training appropriately carries out stepping and the degree of the effect of such training has not been evaluated. Therefore, we have developed a stepping measturement device that monitors stepping for evaluation and training of walking ability. This system consists of two mat switches for stepping, a measuring circuit for stepping detection, and a book-sized personal computer with a PC card-type AD converter. This system can detect a left or right single stance phase and a double stance phase relative to the ON, OFF condition of the mat switch. After measurement, the following items are analyzed and displayed : ・number of steps, ・average time of double stance phase, ・the average time of single stance phase, and so on. Finally, we measured the stepping of subjects whose walking ability is low, and showed the relationship between daily walking conditions and stepping conditions. The effectiveness of this system was considered in light of the results

The abscopal effect induced by in situ-irradiated peripheral tumor cells in a murine GL261 brain tumor model

Background: Localized radiotherapy is considered to act as an adjuvant for systemic anti-tumor immunity. We examined whether in situ-irradiated peripheral tumor cells can evoke an abscopal effect in the brain inhibiting malignant tumor growth.Methods: Syngeneic albino C57BL/6 mice were inoculated with mouse glioma cells (GL261) transfected with the Kusabira Orange fluorescent gene (GL261-mKO) for monitoring the tumor growth with in vivo imaging system. GL261-mKO cells were subcutaneously implanted in the thigh and irradiated by X-rays (20 Gy) for in situ vaccination. Ex vivo-irradiated GL261-mKO cells were used as a conventional whole-cell vaccine for comparison. Following these treatments, the brain was challenged with the same GL261-mKO cells, and survival analyses were performed by Kaplan-Meier analysis. In addition, IFN-γ release from splenocytes and CD8+ cells infiltration into the brain were analyzed.Results: Both in situ- and ex vivo-irradiated vaccines significantly prolonged the survival of the mice compared to the control group bearing an intracerebral tumor. Although there was no significant difference in survival between the two vaccination methods, in situ-vaccinated mice with local control by irradiation completely rejected the implanted tumor cells in the brain. In contrast, mice with local failure demonstrated a rapid growth of both subcutaneous and challenged intracerebral tumors. The cured mice demonstrated an accumulation of CD8+ cells surrounding the inoculation site, as well as increased release of IFN-γ via an ELISPOT assay.Conclusions: Our results indicate that the X-ray irradiation to peripheral tumors evoked a protective, tumor-specific immune response in the brain when the peripheral tumors were successfully cured by irradiation