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Tatsuki Ueda Ayako Kumagai Shoichi Iriguchi Yutaka Yasui Tadayo Miyasaka Kengo Nakagoshi Kazuki Nakane Keigo Saito Mari Takahashi Aki Sasaki Shinsuke Yoshida Naoko Takasu Hiroshi Seno Yasushi Uemura Koji Tamada Tetsuya Nakatsura Shin Kaneko 《Cancer science》2020,111(5):1478-1490
The use of allogeneic, pluripotent stem‐cell‐derived immune cells for cancer immunotherapy has been the subject of recent clinical trials. In Japan, investigator‐initiated clinical trials will soon begin for ovarian cancer treatment using human leukocyte antigen (HLA)‐homozygous‐induced pluripotent stem cell (iPSC)‐derived anti–glypican‐3 (GPC3) chimeric antigen receptor (CAR)‐expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent stem cells as the source for allogeneic immune cells facilitates stringent quality control of the final product, in terms of efficacy, safety and producibility. In this paper, we describe our methods for the stable, feeder‐free production of CAR‐expressing NK/ILC cells from CAR‐transduced iPSC with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8‐3.6 × 106 iPSC within 7 weeks was 1.8‐4.0 × 109. These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity and interferon gamma (IFN‐γ) production against GPC3‐expressing tumor cells. When the CAR‐NK/ILC cells were injected into a GPC3‐positive, ovarian‐tumor‐bearing, immunodeficient mouse model, we observed a significant therapeutic effect that prolonged the survival of the animals. When the cells were injected into immunodeficient mice during non–clinical safety tests, no acute systemic toxicity or tumorigenicity of the final product or residual iPSC was observed. In addition, our test results for the CAR‐NK/ILC cells generated with clinical manufacturing standards are encouraging, and these methods should accelerate the development of allogeneic pluripotent stem cell‐based immune cell cancer therapies. 相似文献
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Matti O. Ruuskanen Pande P. Erawijantari Aki S. Havulinna Yang Liu Guillaume Mric Jaakko Tuomilehto Michael Inouye Pekka Jousilahti Veikko Salomaa Mohit Jain Rob Knight Leo Lahti Teemu J. Niiranen 《Diabetes care》2022,45(4):811
OBJECTIVETo examine the previously unknown long-term association between gut microbiome composition and incident type 2 diabetes in a representative population cohort.RESEARCH DESIGN AND METHODSWe collected fecal samples from 5,572 Finns (mean age 48.7 years; 54.1% women) in 2002 who were followed up for incident type 2 diabetes until 31 December 2017. The samples were sequenced using shotgun metagenomics. We examined associations between gut microbiome composition and incident diabetes using multivariable-adjusted Cox regression models. We first used the eastern Finland subpopulation to obtain initial findings and validated these in the western Finland subpopulation.RESULTSAltogether, 432 cases of incident diabetes occurred over the median follow-up of 15.8 years. We detected four species and two clusters consistently associated with incident diabetes in the validation models. These four species were Clostridium citroniae (hazard ratio [HR] 1.21; 95% CI 1.04–1.42), C. bolteae (HR 1.20; 95% CI 1.04–1.39), Tyzzerella nexilis (HR 1.17; 95% CI 1.01–1.36), and Ruminococcus gnavus (HR 1.17; 95% CI 1.01–1.36). The positively associated clusters, cluster 1 (HR 1.18; 95% CI 1.02–1.38) and cluster 5 (HR 1.18; 95% CI 1.02–1.36), mostly consisted of these same species.CONCLUSIONSWe observed robust species-level taxonomic features predictive of incident type 2 diabetes over long-term follow-up. These findings build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome. The gut microbiome can potentially be used to improve disease prediction and uncover novel therapeutic targets for diabetes. 相似文献
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Aki Semih Özden Ali Veysel Alptekin Hasan Kerem Öncü Alptekin Jülide 《Manuelle Medizin》2020,58(4-5):237-245
Manuelle Medizin - The current study was designed to compare the short-term effects of chiropractic applications (diversified technique) and dry needling on chronic mechanical neck pain.... 相似文献
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Pneumocystis jiroveci pneumonia as a complication of glucocorticoid therapy for interstitial pneumonia] 总被引:1,自引:0,他引:1
Tatsuji Enomoto Arata Azuma Aki Matsumoto Takahito Nei Kumiko Hiramatsu Shinji Abe Jiro Usuki Shoji Kudoh 《Nihon Kokyūki Gakkai zasshi》2005,43(12):725-730
We evaluated the clinical features of pneumocystis jiroveci pneumonia (PCP) as a complication of glucocorticoid therapy for interstitial pneumonia We analyzed 74 interstitial pneumonia patients receiving glucocorticoid therapy, of whom 7 patients developed PCP. At the time of PCP diagnosis, the average duration of the glucocorticoid therapy was 71 days and the average daily dose of predonisolone was 37 mg. Circulating CD4+ lymphocyte counts were 370/microl on the average and more than 200/microl in three cases. PCP cases showed less circulating lymphocyte counts four weeks after the initiation of the therapy. Any cases receiving sulfamethoxazole-trimethoprim (TMP-SMX) did not develop PCP. In conclusion, interstitial pneumonia patients, who are treated with glucocorticoid, are benefit from TMP-SMX as PCP prophylaxis, but CD4 + lymphocyte counts greater than 200/microl is no reason to denying PCP. 相似文献
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Aki Takahashi Kazuya Tomihara Toshihiko Shiroishi Tsuyoshi Koide 《Behavior genetics》2010,40(3):366-376
Genetic studies are indispensable for understanding the mechanisms by which individuals develop differences in social behavior.
We report genetic mapping of social interaction behavior using inter-subspecific consomic strains established from MSM/Ms
(MSM) and C57BL/6J (B6) mice. Two animals of the same strain and sex, aged 10 weeks, were introduced into a novel open-field
for 10 min. Social contact was detected by an automated system when the distance between the centers of the two animals became
less than ~12 cm. In addition, detailed behavioral observations were made of the males. The wild-derived mouse strain MSM
showed significantly longer social contact as compared to B6. Analysis of the consomic panel identified two chromosomes (Chr
6 and Chr 17) with quantitative trait loci (QTL) responsible for lengthened social contact in MSM mice and two chromosomes
(Chr 9 and Chr X) with QTL that inhibited social contact. Detailed behavioral analysis of males identified four additional
chromosomes associated with social interaction behavior. B6 mice that contained Chr 13 from MSM showed more genital grooming
and following than the parental B6 strain, whereas the presence of Chr 8 and Chr 12 from MSM resulted in a reduction of those
behaviors. Longer social sniffing was observed in Chr 4 consomic strain than in B6 mice. Although the frequency was low, aggressive
behavior was observed in a few pairs from consomic strains for Chrs 4, 13, 15 and 17, as well as from MSM. The social interaction
test has been used as a model to measure anxiety, but genetic correlation analysis suggested that social interaction involves
different aspects of anxiety than are measured by open-field test. 相似文献