Publications by authors named "Takeshi Ota"

23 Publications

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Subsequent systemic therapy for non-small cell lung cancer patients with immune checkpoint inhibitor-related interstitial lung disease.

Transl Lung Cancer Res 2021 Jul;10(7):3132-3143

Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: Although immune checkpoint inhibitors (ICIs) are effective for advanced non-small cell lung cancer (NSCLC), ICIs may cause interstitial lung disease (ILD), which results in treatment discontinuation and is sometimes fatal. Despite the high incidence of ICI-related ILD, there are few cancer treatment options for patients. This study aimed to evaluate the safety and efficacy of subsequent systemic cancer therapy in NSCLC patients with ICI-related ILD.

Methods: We retrospectively assessed NSCLC patients who received programmed cell death-1 (PD-1) inhibitors as first- to third-line therapy at participating institutions of the Niigata Lung Cancer Treatment Group from January 2016 to October 2017.

Results: This analysis included 231 patients, 32 (14%) of whom developed ICI-related ILD. Of these patients, 16 (7%) received subsequent systemic cancer treatments. The median overall survival (OS) tended to be longer in the systemic cancer therapy group than in the no systemic cancer therapy group [22.2 months (95% CI: 1-NE) 4.5 months (95% CI: 1-NE); P=0.067]. ICI-related ILD recurred in half of the patients who received systemic cancer therapy, and the median OS tended to be shorter in patients with recurrent ICI-related ILD [22.0 months (95% CI: 1-NE) 7.0 months (95% CI: 1-NE); P=0.3154].

Conclusions: According to the current study, systemic cancer treatment is effective in patients with ICI-related ILD; however, its safety is uncertain because of the high risk of ICI-related ILD recurrence and poor survival outcome following ILD recurrence.
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http://dx.doi.org/10.21037/tlcr-21-198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350095PMC
July 2021

Case report: pulmonary nocardiosis caused by Nocardia exalbida in an immunocompetent patient.

BMC Infect Dis 2021 Aug 9;21(1):776. Epub 2021 Aug 9.

Department of Respiratory Medicine, Niigata prefecturasl Shibata hospital, 1-2-8 Shibata, Niigata, 957-8588, Japan.

Background: Nocardiosis is known as an opportunistic infection in immunocompromised hosts, but it occasionally has been reported in immunocompetent patient. The Nocardia exalbida is first-reported in 2006 from Japan, and a few cases of have been reported in only immunocompromised host, and the characteristic is still unclear. We herein describe the first case of pulmonary nocardiosis caused by N. exalbida in an immunocompetent patient.

Case Presentation: A77 -year-old Japanese man was admitted to our hospital on November 2, 2018. He was a lifelong non-smoker with no childhood history of respiratory disease. He had a medical history of dyslipidemia. One month before this admission fevers, sputum, mild cough were developed and he was evaluated in a clinic near our hospital. His diagnosis was community acquired pneumonia within his right middle lobe. He was treated with ceftriaxone 1 g/day intravenously for a week, however his symptoms relapsed a few days later. So, the physician retried ceftriaxone for another 3 days, but his symptoms did not improve. He was referred to our hospital. He was treated with sitafloxacin as an outpatient for a week, however his symptoms got worse. The chest CT showed consolidation and atelectasis in his right middle lobe. Low density area was scattered in consolidation, and right pleural effusion was observed. The patient was diagnosed with pulmonary abscess and he was admitted. Administration of piperacillin/tazobactam improved his condition. We switched antibiotics to amoxicillin/clavulanate, and he was discharged. After 2 weeks, he relapsed and was admitted again. After administration of piperacillin/tazobactam for 3 weeks, we perform bronchoscopy and Nocardia species were cultured from samples of the bronchial wash. The isolates were identified as N. exalbida using 16S rRNA gene sequencing. We prescribed Trimethoprim / Sulfamethoxazole (TMP/SMX) for 4 months. Then we switched to minocycline for renal dysfunction caused from TMP-SMX for 1 more month. After 5 months therapy, Consolidation on CT disappeared, and Nocardiosis was cured.

Conclusion: we reported the first case of pulmonary nocardiosis caused by N. exalbida in an immunocompetent patient. N. exalbida infection might be associated with a good response to treatment.
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http://dx.doi.org/10.1186/s12879-021-06416-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351411PMC
August 2021

Application of Finnish phlogopite to reduce radiocesium uptake by paddy rice.

J Environ Radioact 2021 Oct 26;237:106687. Epub 2021 Jun 26.

Tohoku Agricultural Research Center, National Agriculture and Food Research Organization, Fukushima, Fukushima, 960-2156, Japan.

Field and pot experiments were conducted to evaluate the effectiveness of coarse Finnish phlogopite application to reduce radiocesium uptake by paddy rice (Oryza sativa L.). The application of phlogopite was expected to reduce radiocesium uptake by crops through K supply and radiocesium retention. Three fields were set in Fukushima Prefecture, and coarse (mean particle size of 450 μm) phlogopite from Siilinjärvi (Finland) was applied at a rate of 5 t ha. Paddy rice was cultivated for 2-4 successive years. In all fields, the average Cs transfer factor (TF) of brown rice harvested from plots with added phlogopite was significantly lower than that of brown rice from plots without added phlogopite over the 2-4-year experiments. TF was decreased by up to 80% following phlogopite application, without an adverse effect on yield. Exchangeable K and soil solution K were higher in the soils with added phlogopite, suggesting K released from phlogopite reduced Cs uptake by paddy rice. Moreover, in a pot cultivation experiment, even when 55% of the total K was removed from phlogopite prior to application, the TF in pots with phlogopite application was less than half of that in pots without added phlogopite. The results from the field study and the pot cultivation experiment suggested that the application of Finnish phlogopite is effective to reduce the TF of brown rice. Exchangeable K and tetraphenylborate-extractable-K (TPB-K) at rooting stage, and soil solution K at tillering and heading stages showed significant negative correlation with TF. TPB-K was significantly positively correlated with soil solution K at tillering stage and heading stage, whereas exchangeable K at rooting stage did not exhibit significant correlation with soil solution K at heading stage. The results suggest that TPB-K is more reliable than exchangeable K, which could facilitate as a basis of K fertilizer recommendation for radiocesium-contaminated fields.
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http://dx.doi.org/10.1016/j.jenvrad.2021.106687DOI Listing
October 2021

Comparative dynamics of potassium and radiocesium in soybean with different potassium application levels.

J Environ Radioact 2021 Jul 12;233:106609. Epub 2021 Apr 12.

Agricultural Radiation Research Center, Tohoku Agricultural Research Center, NARO, 50 Harajuku-minami, Arai, Fukushima, Fukushima, 960-2156, Japan; Research Faculty of Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-8589, Japan. Electronic address:

We conducted a field experiment in soybean with different levels of K application to elucidate the comparative dynamics of Cs and K. The inventory of K in the shoots increased substantially from the fifth trifoliate stage to the full seed stage, and as the absorption of K increased, so too did the absorption of Cs. Overall, the effect of K application was much greater in terms of Cs dynamics than K dynamics or biomass production. K application reduced not only the accumulation of Cs in the shoots, but also the distribution of Cs to the grains. However, the decrease of Cs distribution to the grain had a much smaller effect on Cs accumulation in the grains than Cs absorption. A positive correlation was also observed between the exchangeable Cs/K ratio in the soil and the Cs/K ratio in the shoots for each growth stage, and the Cs/K ratios in the shoots at the full seed and full maturity stage were much higher than those at the fifth trifoliate and full bloom stage under the same exchangeable Cs/K ratio in the soil. These findings suggest a decrease in the discrimination of Cs from K during absorption after the full bloom stage. As a result of this and the increase in soil-exchangeable Cs/K with growth, radiocesium was more transferable to the shoots after the full bloom stage. Overall, these results suggest that lowering the soil-exchangeable radiocesium/potassium ratio after the full bloom stage by increasing K availability could efficiently reduce the transfer of radiocesium to the grains.
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http://dx.doi.org/10.1016/j.jenvrad.2021.106609DOI Listing
July 2021

Alfacalcidol improves the growth velocity in children with vitamin D deficiency/insufficiency: A single center retrospective cohort study.

PLoS One 2021 8;16(3):e0247886. Epub 2021 Mar 8.

Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.

Objectives: To investigate the growth velocity-improving effects of vitamin D replacement therapy in pediatric patients diagnosed with vitamin D deficiency and insufficiency.

Study Design: A retrospective cohort study was conducted in 34 pediatric patients diagnosed with vitamin D deficiency/insufficiency. Based on the clinical findings, the subjects were divided into two groups: a bowed leg (BL) group and a non-bowed leg (non-BL) group. After the initiation of alfacalcidol, the standard deviation score (SDS) of their heights, weights and growth velocities in each group were monitored.

Results: The median age at the first visit was significantly lesser in the BL group (1.58 years old [interquartile range (IQR): 1.33, 2.17]) than that in the non-BL group (3.00 years old [IQR: 2.33, 3.67]). On the contrary, the SDS for height was significantly lower in the non-BL group (-2.27 [IQR: -2.63, -1.94]) than that in the BL group (-1.37 [IQR: -1.91, -1.07]). One-year treatment with alfacalcidol showed significant improvements in both height SDSs and growth velocity SDSs not only in the BL group but also in the non-BL group.

Conclusions: The current study revealed that vitamin D replacement therapy improved the growth rate in children with vitamin D deficiency/insufficiency, regardless of the presence of BL. This study emphasizes the importance of assessing the vitamin D status in children with poor growth rates and suggests that alfacalcidol could be a valid option for the treatment of short stature.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247886PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939371PMC
March 2021

Rpd3/CoRest-mediated activity-dependent transcription regulates the flexibility in memory updating in Drosophila.

Nat Commun 2021 01 27;12(1):628. Epub 2021 Jan 27.

Hakubi Center, Kyoto University Graduate School of Medicine, Konoecho, Yoshida, Sakyo-ku, Kyoto, Kyoto, 606-8315, Japan.

Consolidated memory can be preserved or updated depending on the environmental change. Although such conflicting regulation may happen during memory updating, the flexibility of memory updating may have already been determined in the initial memory consolidation process. Here, we explored the gating mechanism for activity-dependent transcription in memory consolidation, which is unexpectedly linked to the later memory updating in Drosophila. Through proteomic analysis, we discovered that the compositional change in the transcriptional repressor, which contains the histone deacetylase Rpd3 and CoRest, acts as the gating mechanism that opens and closes the time window for activity-dependent transcription. Opening the gate through the compositional change in Rpd3/CoRest is required for memory consolidation, but closing the gate through Rpd3/CoRest is significant to limit future memory updating. Our data indicate that the flexibility of memory updating is determined through the initial activity-dependent transcription, providing a mechanism involved in defining memory state.
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http://dx.doi.org/10.1038/s41467-021-20898-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840730PMC
January 2021

45,X/46,X,psu idic(Y)(q11.2) in a phenotypically normal male with short stature: a case report.

Clin Pediatr Endocrinol 2020 3;29(4):189-193. Epub 2020 Oct 3.

Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.

We report a case of 15-yr-old phenotypically normal male with short stature associated with the chromosomal abnormalities of 46,X,psu idic(Y)(q11.2)/45,X. At 3 yr of age, he underwent urethroplasty for scrotal hypospadias. At 15 yr of age, he was referred to our hospital due to short stature (-3.71 SD). The results of blood examination were mostly normal. A radiological examination revealed his bone age was 15.7 yr (based on the TW2-RUS method). Chromosome analysis of peripheral lymphocytes revealed 46,X,psu idic(Y)(q11.2)[16]/45,X[14], and array comparative genomic hybridization (aCGH) showed a large deletion of Yq which was located distal to the Y chromosome growth-control gene () region. It is likely that these structural abnormalities in the Y chromosome were responsible for the short stature. This case might provide new insights regarding and emphasizes the importance of chromosome analysis in not only females but also males with short stature, especially when associated with genital anomalies.
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http://dx.doi.org/10.1297/cpe.29.189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534520PMC
October 2020

Salvage stereotactic body radiotherapy for post-operative oligo-recurrence of non-small cell lung cancer: A single-institution analysis of 59 patients.

Oncol Lett 2020 Apr 17;19(4):2695-2704. Epub 2020 Feb 17.

Department of Radiology, University of Tokyo Hospital, Tokyo 113-8655, Japan.

A standard treatment for patients with early-stage non-small cell lung cancer (NSCLC) who undergo surgery, and subsequently develop local failure or intrathoracic oligo-recurrence, has not yet been established. The present study aimed to assess the feasibility of stereotactic body radiotherapy (SBRT) for this subgroup of patients. Consequently, a retrospective analysis was conducted of patients with NSCLC recurrence who were treated with SBRT, and previously underwent curative surgical resection between October 2011 and October 2016. Post-SBRT survival [overall survival (OS); progression-free survival (PFS); and local control (LC)] and toxicity were analyzed. Prognostic factors for OS were identified using univariate and multivariate analysis. A total of 52 patients and 59 tumors were analyzed. The median follow-up time was 25 months (35 months for surviving patients), and median OS following salvage SBRT was 32 months. The 1- and 3-year OS rates were 84.4 and 67.8%, respectively. 1- and 3-year PFS rates were 80.8 and 58.7%, respectively. Only 4 patients (7.7%) developed local failure. Median LC was 71 months and 1- and 3-year LC rate were 97.9 and 94.9%, respectively. A total of 4 patients experienced grade 3 or higher adverse events (AEs) and two experienced grade 5 AEs (pneumonitis and hemoptysis). Central tumor location and the possibility of re-operation were independent prognostic factors for OS. The present study indicated that post-operative salvage SBRT is a promising therapeutic option for patients with NSCLC with locoregional or intrathoracic oligo-recurrence. We regard toxicity was also acceptable. However, further research is required on the appropriate selection of subjects, and stratification of the analysis by certain risk factors would increase the accuracy of the conclusions.
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http://dx.doi.org/10.3892/ol.2020.11407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068670PMC
April 2020

Prognostic significance of the radiologic features of pneumonitis induced by anti-PD-1 therapy.

Cancer Med 2020 05 9;9(9):3070-3077. Epub 2020 Mar 9.

Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: Interstitial lung disease (ILD) induced by anti-programmed-cell death-1 (PD-1) and anti-PD-ligand 1 (PD-L1) is potentially life-threatening and is a common reason of the discontinuation of therapy. In contrast, an enhancement in antitumor effects was reported in patients who developed immune-related adverse events, including ILD. Although recent evidence suggests that radiologic patterns of ILD may reflect the severity of ILD and the antitumor immune responses to anti-PD-1/PD-L1 therapies, the association between radiologic features and clinical outcomes remains unclear.

Methods: Patients with advanced non-small-cell lung cancer who were treated with 1st to 3rd line anti-PD-1 therapy from January 2016 through October 2017 were identified at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. ILD was diagnosed by the treating physicians, and chest computed tomography scans were independently reviewed to assess the radiologic features of ILD.

Results: A total of 231 patients who received anti-PD-1 therapy were enrolled. Thirty-one patients (14%) developed ILD. Sixteen patients were classified as having ground glass opacities (GGO), 16 were classified as having cryptogenic organizing pneumonia (COP), and one was classified as having pneumonitis not otherwise specified. Patients with GGO had significantly worse overall survival time compared to patients with COP (7.8 months (95% CI: 2.2-NE) versus not reached (95% CI: 13.2-NE); P = 0.0175). Multivariate analysis of all 231 patients also revealed that PS = 1 and ≥2 and GGO were significant predictors of a worse overall survival.

Conclusions: This study demonstrated that patients who developed GGO exhibited worse outcomes among non-small-cell lung cancer patients receiving anti-PD-1 therapies.
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http://dx.doi.org/10.1002/cam4.2974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196069PMC
May 2020

Variations in radioactive cesium accumulation in wheat germplasm from fields affected by the 2011 Fukushima nuclear power plant accident.

Sci Rep 2020 02 28;10(1):3744. Epub 2020 Feb 28.

Agricultural Radiation Research Center, Tohoku Agricultural Research Center, National Agriculture and Food Research Organization (NARO), 50 Harajukuminami, Arai, Fukushima, 960-2156, Japan.

Decreasing the transfer of radioactive cesium (RCs) from soil to crops has been important since the deposition of RCs in agricultural soil owing to the Fukushima nuclear power plant accident of 2011. We investigated the genotypic variation in RCs accumulation in 234 and 198 hexaploid wheat (Triticum spp.) varieties in an affected field in 2012 and 2013, respectively. The effects of soil exchangeable potassium (ExK) content to RCs accumulation in wheat varieties were also evaluated. A test field showed fourfold differences in soil ExK contents based on location, and the wheat varieties grown in areas with lower soil ExK contents tended to have higher grain RCs concentrations. RCs concentrations of shoots, when corrected by the soil ExK content, were positively significantly correlated between years, and RCs concentrations of shoots were significantly correlated with the grain RCs concentration corrected by the soil ExK content. These results indicated that there were genotypic variations in RCs accumulation. The grain to shoot ratio of RCs also showed significant genotypic variation. Wheat varieties with low RCs accumulations were identified. They could contribute to the research and breeding of low RCs accumulating wheat and to agricultural production in the area affected by RCs deposition.
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http://dx.doi.org/10.1038/s41598-020-60716-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048790PMC
February 2020

Concurrent Bacteremia Due to Non-vaccine Serotype 24F Pneumococcus in Twins: A Rapid Increase in Serotype 24F-invasive Pneumococcal Disease and its High Invasive Potential.

Pediatr Infect Dis J 2020 01;39(1):85-87

Department of Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Although concurrent bacteremia in siblings is rare, serotype 24F Streptococcus pneumoniae was isolated from the blood of twin 1-year-old girls within a 3-day interval, supporting the high invasive potential of this serotype. As the prevalence of childhood serotype 24F-invasive pneumococcal diseases increases in Europe and the Western Pacific Region, investigation and surveillance of this serotype are necessary.
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http://dx.doi.org/10.1097/INF.0000000000002508DOI Listing
January 2020

ACE2 exerts anti-obesity effect via stimulating brown adipose tissue and induction of browning in white adipose tissue.

Am J Physiol Endocrinol Metab 2019 12 22;317(6):E1140-E1149. Epub 2019 Oct 22.

Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

The angiotensin II (ANG II)-ANG II type 1 receptor (ATR) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts the ANG II/ATR axis via converting ANG II to angiotensin 1-7 (Ang 1-7), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1-7 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2, 2.0 mg·kg·day) for 28 days to high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, brown adipose tissue (BAT) mass increased, accompanied with ameliorated insulin signaling and increased protein levels of uncoupling protein-1 (UCP-1) and PRD1-BF1-RIZ1 homologous domain containing 16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is the result of increased H3K27 acetylation via the downregulation of histone deacetylase 3 and increased H3K9 acetylation via upregulation of GCN5 and P300/CBP-associated factor. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1-7 axis represent a potential therapeutic approach to prevent the development of obesity.
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http://dx.doi.org/10.1152/ajpendo.00311.2019DOI Listing
December 2019

Successful treatment with 2-chlorodeoxyadenosine of refractory pediatric Langerhans cell histiocytosis with initial involvement of the gastrointestinal tract.

Int J Hematol 2019 Dec 26;110(6):756-762. Epub 2019 Jul 26.

Department of Pediatrics, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Gastrointestinal (GI) tract involvement in Langerhans cell histiocytosis (LCH) is extremely rare. Langerhans cell histiocytosis with GI tract involvement (GI-LCH) is frequently associated with multi-system disease, and usually presents with severe systemic symptoms, such as protein-losing enteropathy (PLE). Although the GI tract is not included among the organs at risk, the prognosis of GI-LCH is poor, and no effective chemotherapeutic regimen has been identified. Here, we report an infant case of primary refractory GI-LCH with PLE that showed marked improvement in response to 2-chlorodeoxyadenosine (2-CdA) therapy with no severe adverse events, even under conditions of deteriorating general health. The present findings indicate that 2-CdA may be effective for refractory GI-LCH with PLE. Further studies are warranted to determine the optimal therapeutic strategies for GI-LCH with PLE.
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http://dx.doi.org/10.1007/s12185-019-02711-0DOI Listing
December 2019

Erythropoietin and long-acting erythropoiesis stimulating agent ameliorate non-alcoholic fatty liver disease by increasing lipolysis and decreasing lipogenesis via EPOR/STAT pathway.

Biochem Biophys Res Commun 2019 01 21;509(1):306-313. Epub 2018 Dec 21.

Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.

Erythropoietin (EPO) has been reported to exert a beneficial effect on glucose metabolism in obesity. However, the effect of EPO on lipid metabolism and non-alcoholic fatty liver disease (NAFLD) was unclear. Furthermore, the effect of long acting erythropoiesis stimulating agents (ESA) on metabolism has not been poorly understood. The objective of this study was to investigate the effect of EPO and long acting ESA on NAFLD and lipid metabolism. We administered EPO and darbepoetin alpha (DEPO), a long acting ESA, by intraperitoneally injection for 4 weeks to mice with high-fat-diet (HFD)-induced obesity. EPO and DEPO treatment reduced body weight, ameliorated glucose tolerance and insulin resistance, and prevented lipid accumulation in liver and white adipose tissue (WAT). Administration of EPO and DEPO suppressed lipid synthesis-related protein in liver, including sterol regulatory element-binding protein 1 (SREBP-1), acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS). EPO and DEPO also increased lipolysis protein in visceral WAT, including hormone-sensitive lipase (HSL), atni-adipose triglyceride lipase (ATGL). EPO and DEPO increased phosphorylation signal transducer and activator of transcription 3 (STAT3) and STAT5, transcriptional factors with crucial roles of lipid metabolism. These data suggest that EPO and DEPO ameliorated NAFLD by improving lipid metabolism via EPO/EPOR-induced STAT3 and STAT5 activation. EPO and DEPO may be a therapeutic option for NAFLD.
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http://dx.doi.org/10.1016/j.bbrc.2018.12.131DOI Listing
January 2019

Stereotactic body radiotherapy for centrally-located lung tumors with 56 Gy in seven fractions: A retrospective study.

Oncol Lett 2018 Oct 23;16(4):4498-4506. Epub 2018 Jul 23.

Department of Radiology, University of Tokyo Hospital, Tokyo 113-8655, Japan.

Stereotactic body radiotherapy (SBRT) for centrally-located lung tumors remains a challenge because of the increased risk of treatment-related adverse events (AEs), and uncertainty around prescribing the optimal dose. The present study reported the results of central tumor SBRT with 56 Gy in 7 fractions (fr) at the University of Tokyo Hospital. A total of 35 cases that underwent SBRT with or without volumetric-modulated arc therapy consisting of 56 Gy/7 fr for central lung lesions between 2010 and 2016 at the University of Tokyo Hospital were reveiwed. A central lesion was defined as a tumor within 2 cm of the proximal bronchial tree (RTOG 0236 definition) or within 2 cm in all directions of any critical mediastinal structure. Local control (LC), overall survival (OS), and AEs were investigated. The Kaplan-Meier method was used to estimate LC and OS. AEs were scored per the Common Terminology Criteria for Adverse Events Version 4.0. Thirty-five patients with 36 central lung lesions were included. Fifteen lesions were primary non-small cell lung cancer (NSCLC), 13 were recurrences of NSCLC, and 8 had oligo-recurrences from other primaries. Median tumor diameter was 29 mm. Eighteen patients had had prior surgery. At a median follow-up of 13.1 months for all patients and 18.3 months in surviving patients, 22 patients had died, ten due to primary disease (4 NSCLC), while three were treatment-related. The 1- and 2-year OS were 57.3 and 40.4%, respectively, and median OS was 15.7 months. Local recurrence occurred in only two lesions. 1- and 2-year LC rates were both 96%. Nine patients experienced grade ≥3 toxicity, representing 26% of the cohort. Two of these were grade 5, one pneumonitis and one hemoptysis. Considering the background of the subject, tumor control of our central SBRT is promising, especially in primary NSCLC. However, the safety of SBRT to central lung cancer remains controversial.
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http://dx.doi.org/10.3892/ol.2018.9188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126178PMC
October 2018

A statistical model for estimating the radiocesium transfer factor from soil to brown rice using the soil exchangeable potassium content.

J Environ Radioact 2018 Dec 23;195:114-125. Epub 2018 Aug 23.

Tohoku Agricultural Research Center, NARO, 50 Harajukuminami, Arai, Fukushima-shi, Fukushima 960-2156, Japan.

To reduce radiocesium uptake by rice, large amounts of potassium fertilizer have been applied to paddy fields contaminated by radiocesium released from the Fukushima Dai-ichi Nuclear Power Plant owned by the Tokyo Electric Power Company. The Fukushima Prefectural Government recommended maintenance of the soil exchangeable K content up to 200 mg K kg before conventional fertilization in rice production. We constructed an equation to predict the transfer factor from soil to brown rice using the soil exchangeable K content. This equation was then used to calculate the appropriate soil exchangeable K content, which ensures a low risk (5%) of brown rice exceeding the standard limit (100 Bq kg for grains) established in 2012. The equations were constructed using field data obtained by an investigation (measurement of the Cs concentrations in soil and brown rice and measurement of the soil exchangeable K content at harvest) that was performed from 2012 to 2015 in 321 paddy fields distributed all over Fukushima Prefecture. We found that the stochastic fluctuation of the transfer factor approximately follows a lognormal distribution under the given environmental conditions. Four factors are considered in predicting the logarithmic quantity of the transfer factor: (1) the linear influence of the logarithm of the exchangeable K content in soil, (2) the non-linear influence of the logarithm of the exchangeable K content in soil, (3) three districts in the Fukushima Prefecture and (4) the year. The linear model of the logarithm of exchangeable K content in soil was adopted by the R criterion, which indicates the absolute goodness of models for prediction. The predictive ability of the model increased by 29% after including the logarithm of the exchangeable K content in soil (factor 1), while the predictive ability further increased by 10% after including spatial and temporal information (factors 3 and 4). The validity of the exchangeable K content recommended by the Fukushima Prefectural Government was re-examined using the proposed equations, which indicated that the conventional recommendation was appropriate at 2012 but is not fully appropriate under the current situation in which the radiocesium concentration in soil has decreased.
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http://dx.doi.org/10.1016/j.jenvrad.2018.04.026DOI Listing
December 2018

Landau-Zener-Stückelberg interference in coherent charge oscillations of a one-electron double quantum dot.

Sci Rep 2018 Apr 3;8(1):5491. Epub 2018 Apr 3.

NTT Basic Research Laboratories, NTT Corporation, 3-1 Morinosato-Wakamiya, Atsugi, 243-0198, Japan.

Landau-Zener (LZ) transition has received renewed interest as an alternative approach to control single-qubit states. An LZ transition occurs when a system passes through an avoided crossing that arises from quantum mechanical coupling of two levels, taking the system to a coherent superposition of the two states. Then, multiple LZ transitions induce interference known as Landau-Zener-Stückelberg (LZS) interference whose amplitude strongly depends on the velocity or adiabaticity of the passage. Here, we study the roles of LZ transitions and LZS interference in coherent charge oscillations of a one-electron semiconductor double quantum dot by time-domain experiments using standard rectangular voltage pulses. By employing density matrix simulations, we show that, in the standard setup using rectangular pulses, even a small distortion of the pulse can give rise to LZ transitions and hence LZS interference, which significantly enhances the measured oscillation amplitude. We further show experimentally that the nature of the coherent charge oscillations changes from Rabi-type to LZS oscillations with increasing pulse distortion. Our results thus demonstrate that it is essential to take into account LZS interference for both precise control of charge qubits and correct interpretation of measurement results.
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http://dx.doi.org/10.1038/s41598-018-23468-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882656PMC
April 2018

Soluble HLA-associated peptide from PSF1 has a cancer vaccine potency.

Sci Rep 2017 09 11;7(1):11137. Epub 2017 Sep 11.

Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Osaka, 561-0825, Japan.

Partner of sld five 1 (PSF1) is an evolutionary conserved DNA replication factor involved in DNA replication in lower species, which is strongly expressed in normal stem cell populations and progenitor cell populations. Recently, we have investigated PSF1 functions in cancer cells and found that PSF1 plays a significant role in tumour growth. These findings provide initial evidence for the potential of PSF1 as a therapeutic target. Here, we reveal that PSF1 contains an immunogenic epitope suitable for an antitumour vaccine. We analysed PSF1 peptides eluted from affinity-purified human leukocyte antigen (HLA) by mass spectrometry and identified PSF1 peptide (YLYDRLLRI) that has the highest prediction score using an in silico algorithm. PSF1 peptide induced PSF1-specific cytotoxic T lymphocyte responses such as the production of interferon-γ and cytotoxicity. Because PSF1 is expressed in cancer cell populations and highly expressed in cancer stem cell populations, these data suggest that vaccination with PSF1 peptide may be a novel therapeutic strategy for cancer treatment.
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http://dx.doi.org/10.1038/s41598-017-11605-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593935PMC
September 2017

The inhibitory effects of potassium chloride versus potassium silicate application on (137)Cs uptake by rice.

J Environ Radioact 2016 Mar 13;153:188-194. Epub 2016 Jan 13.

Fukushima Agricultural Technology Centre, 116 Shimonakamichi, Takakura-Aza, Hiwada-machi, Koriyama, Fukushima 963-0531, Japan. Electronic address:

After the accident at the Fukushima Dai-ichi Nuclear Power Plant owned by the Tokyo Electric Power Company on 11 March 2011, potassium fertilizer was applied to agricultural fields in the southern Tohoku and northern Kanto regions of Japan to reduce the uptake of radiocesium by crops. In this study, we examined the effects of two types of potassium fertilizers, potassium chloride (a readily available potassium fertilizer) and potassium silicate (a slow-release potassium fertilizer), as well as a split application of potassium, on the accumulation of (137)Cs by rice plants in two pot experiments. The (137)Cs concentrations in the brown rice and in the above-ground plants were significantly lower after potassium chloride application than after potassium silicate application. The potassium ion (K(+)) concentrations in soil solutions sampled 9 and 21 d after transplanting were significantly higher for the potassium chloride application than for the potassium silicate application. The K(+) concentrations in soil solutions observed in the application of potassium silicate were similar to those in the treatment when no potassium was applied. This finding indicates that the application of potassium silicate did not sufficiently increase the available K(+) for rice plants in the soil, which led to a greater uptake of (137)Cs after the potassium silicate application than after the application of potassium chloride. The (137)Cs concentration in brown rice was higher in the split application of potassium fertilizer with the second application at the full heading stage than that without split application and the split application with the second application before heading.
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http://dx.doi.org/10.1016/j.jenvrad.2016.01.001DOI Listing
March 2016

Optimization of enrichment conditions on TiO2 chromatography using glycerol as an additive reagent for effective phosphoproteomic analysis.

J Proteome Res 2013 Dec 21;12(12):5587-97. Epub 2013 Nov 21.

Shionogi Pharmaceutical Research Center, Shionogi & Co. Ltd. , 3-1-1 Futaba-cho, Toyonaka-shi, Osaka 561-0825, Japan.

Metal oxide affinity chromatography (MOAC) represented by titanium dioxide (TiO2) chromatography has been used for phosphopeptide enrichment from cell lysate digests prior to mass spectrometry. For in-depth phosphoproteomic analysis, it is important for MOAC to achieve high phosphopeptide enrichment efficiency by optimizing purification conditions. However, there are some differences in phosphopeptide selectivity and specificity enriched by various TiO2 materials and procedures. Here, we report that binding/wash buffers containing polyhydric alcohols, such as glycerol, markedly improve phosphopeptide selectivity from complex peptide mixtures. In addition, the elution conditions combined with secondary amines, such as bis-Tris propane, made it possible to recover phosphopeptides with highly hydrophobic properties and/or longer peptide lengths. To assess the practical applicability of our improved method, we confirmed using PC3 prostate cancer cells. By combining the hydrophilic interaction chromatography (HILIC) with the optimized TiO2 enrichment method prior to LC-MS/MS analysis, over 8300 phosphorylation sites and 2600 phosphoproteins were identified. Additionally, some dephosphorylations of those were identified by treatment with dasatinib for a kinase inhibitor. These results indicate that our method is applicable to understanding the profiling of kinase inhibitors such as anticancer compounds, which will be useful for drug discovery and development.
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http://dx.doi.org/10.1021/pr400546uDOI Listing
December 2013

Low-frequency spin fluctuations in Skyrmions confined by wires: measurements of local nuclear spin relaxation.

Phys Rev Lett 2011 Sep 16;107(12):126807. Epub 2011 Sep 16.

NTT Basic Research Laboratories, NTT Corporation, Atsugi-shi, Kanagawa 243-0198, Japan.

We investigate low-frequency electron spin dynamics in a quantum Hall system with wire confinement by nuclear spin relaxation measurements. We developed a technique to measure the local nuclear spin relaxation rate T(1)(-1). T(1)(-1) is enhanced on both sides of the local filling factor ν(wire)=1, reflecting low-frequency fluctuations of electron spins associated with Skyrmions inside the wire. As the wire width is decreased, the fast nuclear spin relaxation is suppressed in a certain range of Skyrmion density. This suggests that the multi-Skyrmion state is modified and the low-frequency spin fluctuations are suppressed by the wire confinement.
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http://dx.doi.org/10.1103/PhysRevLett.107.126807DOI Listing
September 2011

Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis.

BMC Cancer 2011 Jan 1;11. Epub 2011 Jan 1.

Department of Medicine, Niigata University Medical and Dental Hospital, Niigata City, Japan.

Background: Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2(nd) EGFR-TKI administration.

Methods: We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment.

Results: Three patients (27%) were treated with gefitinib as the 2(nd) EGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2(nd) EGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2(nd) EGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2(nd) EGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy.

Conclusions: Our results indicate that a 2(nd) EGFR-TKI treatment can be an effective treatment option for gefitinib responders.
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http://dx.doi.org/10.1186/1471-2407-11-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022883PMC
January 2011

Correlated coherent oscillations in coupled semiconductor charge qubits.

Phys Rev Lett 2009 Jul 28;103(5):056802. Epub 2009 Jul 28.

NTT Basic Research Laboratories, NTT Corporation, 3-1 Morinosato-Wakamiya, Atsugi, 243-0198, Japan.

We study coherent dynamics of two spatially separated electrons in a coupled semiconductor double quantum dot (DQD). Coherent oscillations in one DQD are strongly influenced by electronic states of the other DQD, or the two electrons simultaneously tunnel in a correlated manner. The observed coherent oscillations are interpreted as various two-qubit operations. The results encourage searching quantum entanglement in electronic devices.
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http://dx.doi.org/10.1103/PhysRevLett.103.056802DOI Listing
July 2009
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