نتائج البحث - "Naozumi Harada"

الوصف: Abstract Background Cancer testis (CT) antigens are promising targets for cancer immunotherapies such as cancer vaccines and genetically modified adoptive T cell therapy. In this study, we evaluated the expression of three CT antigens, melanoma-associated antigen A4 (MAGE-A4), New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) and sarcoma antigen gene (SAGE). Methods MAGE-A4, NY-ESO-1 and/or SAGE antigen expression in tumour samples was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Informed consent was obtained from individuals prior to study enrolment. Results In total, 585 samples in 21 tumour types were evaluated between June 2009 and March 2018. The positive expression rates of these CT antigens were as follows: MAGE-A4, 34.6% (range, 30.7–38.7); NY-ESO-1, 21.0% (range, 17.2–25.1); and SAGE, 21.8% (range, 18.5–25.4). The MAGE-A4 antigen was expressed in 54.9% of oesophageal cancers, 37.5% of head and neck cancers, 35.0% of gastric cancers and 34.2% of ovarian cancers; the NY-ESO-1 antigen was expressed in 28.6% of lung cancers, 25.3% of oesophageal cancers and 22.6% of ovarian cancers; and the SAGE antigen was expressed in 35.3% of prostate cancers, 32.9% of oesophageal cancers and 26.3% of ovarian cancers. The most common tumour type in this study was oesophageal cancer. MAGE-A4, NY-ESO-1 and SAGE antigen expression were assessed in 214 oesophageal cancer samples, among which 24 (11.2%) were triple-positive, 58 (27.1%) were positive for any two, 59 (27.6%) were positive for any one, and 73 (34.1%) were triple negative. Conclusions Oesophageal cancer exhibited a relatively high rate of CT antigen mRNA expression positivity.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12885-020-07098-4Test; https://doaj.org/toc/1471-2407Test

الوصول الحر: https://doaj.org/article/20436dffba2045e08c3308ed02b352e7Test

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النص الكامل

4

دورية أكاديمية

Activated CD8+ T cell extracellular vesicles prevent tumour progression by targeting of lesional mesenchymal cells

المؤلفون: Naohiro Seo, Yoshitaka Shirakura, Yoshiro Tahara, Fumiyasu Momose, Naozumi Harada, Hiroaki Ikeda, Kazunari Akiyoshi, Hiroshi Shiku

المصدر: Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018)

مصطلحات موضوعية: Science

الوصف: Immune cells have an important role in tumour progression. Here, the authors show that extracellular vesicles from activated CD8+ T cells attenuate tumour progression by depletion of mesenchymal tumour stromal cells.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/6a2cc30b31e1417ba6551dd38e924e4aTest

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النص الكامل

5

دورية أكاديمية

Nanogel antigen DDS toward overcoming immune resistance of cancer / ナノゲル抗原DDSによる免疫療法抵抗性がんの克服に向けて

المؤلفون: Daisuke Muraoka, Hiroshi Shiku, Kazunari Akiyoshi, Naozumi Harada, 原田直純, 村岡大輔, 珠玖洋, 秋吉一成

المصدر: Drug Delivery System. 2020, 35(1):64

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6

دورية أكاديمية

Identification of an immunogenic neo-epitope encoded by mouse sarcoma using CXCR3 ligand mRNAs as sensors

المؤلفون: Keisuke Fujii, Yoshihiro Miyahara, Naozumi Harada, Daisuke Muraoka, Mitsuhiro Komura, Rui Yamaguchi, Hideo Yagita, Junko Nakamura, Sahoko Sugino, Satoshi Okumura, Seiya Imoto, Satoru Miyano, Hiroshi Shiku

المصدر: OncoImmunology, Vol 6, Iss 5 (2017)

مصطلحات موضوعية: checkpoint blockade, cxcr3 ligands, immune response, mutated antigen, neo-epitope, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: The CXCR3 ligands CXCL9, 10, and 11 play critical roles in the amplification of immune responses by recruiting CXCR3+ immune effector cells to the tumor site. Taking advantage of this property of CXCR3 ligands, we aimed to establish a novel approach to identify immunogenic mutated-antigens. We examined the feasibility of using CXCR3 ligand mRNAs as sensors for detection of specific immune responses in human and murine systems. We further investigated whether this approach is applicable for the identification of immunogenic mutated-antigens by using murine sarcoma lines. Rapid synthesis of CXCR3 ligand mRNAs occurred shortly after specific immune responses in both human and murine immune systems. Particularly, in CMS5 tumor-bearing mice, we detected specific immune responses to mutated mitogen-activated protein kinase 2 (ERK2), which has previously been identified as an immunogenic mutated-antigen. Furthermore, by combining this approach with whole-exome and transcriptome sequencing analyses, we identified an immunogenic neo-epitope derived from mutated staphylococcal nuclease domain-containing protein 1 (Snd1) in CMS7 tumor-bearing mice. Most importantly, we successfully detected the specific immune response to this neo-epitope even without co-administration of anti-cytotoxic T-lymphocyte protein-4 (CTLA-4), anti-programmed cell death-1 (PD-1) and anti-glucocorticoid-induced TNFR-related protein (GITR) antibodies, which vigorously augmented the immune response and consequently enabled us to detect the specific immune response to this neo-epitope by conventional IFNγ intracellular staining method. Our data indicate the potential usefulness of this strategy for the identification of immunogenic mutated-antigens. We propose that this approach would be of great help for the development of personalized cancer vaccine therapies in future.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2162-402XTest

الوصول الحر: https://doaj.org/article/26648c4bec8742d4aebf80ea73663b44Test

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النص الكامل

7

دورية أكاديمية

Epirubicin, Identified Using a Novel Luciferase Reporter Assay for Foxp3 Inhibitors, Inhibits Regulatory T Cell Activity.

المؤلفون: Hajime Kashima, Fumiyasu Momose, Hiroshi Umehara, Nao Miyoshi, Naohisa Ogo, Daisuke Muraoka, Hiroshi Shiku, Naozumi Harada, Akira Asai

المصدر: PLoS ONE, Vol 11, Iss 6, p e0156643 (2016)

مصطلحات موضوعية: Medicine, Science

الوصف: Forkhead box protein p3 (Foxp3) is crucial to the development and suppressor function of regulatory T cells (Tregs) that have a significant role in tumor-associated immune suppression. Development of small molecule inhibitors of Foxp3 function is therefore considered a promising strategy to enhance anti-tumor immunity. In this study, we developed a novel cell-based assay system in which the NF-κB luciferase reporter signal is suppressed by the co-expressed Foxp3 protein. Using this system, we screened our chemical library consisting of approximately 2,100 compounds and discovered that a cancer chemotherapeutic drug epirubicin restored the Foxp3-inhibited NF-κB activity in a concentration-dependent manner without influencing cell viability. Using immunoprecipitation assay in a Treg-like cell line Karpas-299, we found that epirubicin inhibited the interaction between Foxp3 and p65. In addition, epirubicin inhibited the suppressor function of murine Tregs and thereby improved effector T cell stimulation in vitro. Administration of low dose epirubicin into tumor-bearing mice modulated the function of immune cells at the tumor site and promoted their IFN-γ production without direct cytotoxicity. In summary, we identified the novel action of epirubicin as a Foxp3 inhibitor using a newly established luciferase-based cellular screen. Our work also demonstrated our screen system is useful in accelerating discovery of Foxp3 inhibitors.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4902191?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/af4abd82df1e4e5bbae3febfaf2d1e8bTest

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النص الكامل

8

دورية أكاديمية

Guanine-Rich Sequences Are a Dominant Feature of Exosomal microRNAs across the Mammalian Species and Cell Types.

المؤلفون: Fumiyasu Momose, Naohiro Seo, Yasushi Akahori, Shin-Ichi Sawada, Naozumi Harada, Toru Ogura, Kazunari Akiyoshi, Hiroshi Shiku

المصدر: PLoS ONE, Vol 11, Iss 4, p e0154134 (2016)

مصطلحات موضوعية: Medicine, Science

الوصف: Exosome is an extracellular vesicle released from multivesicular endosomes and contains micro (mi) RNAs and functional proteins derived from the donor cells. Exosomal miRNAs act as an effector during communication with appropriate recipient cells, this can aid in the utilization of the exosomes in a drug delivery system for various disorders including malignancies. Differences in the miRNA distribution pattern between exosomes and donor cells indicate the active translocation of miRNAs into the exosome cargos in a miRNA sequence-dependent manner, although the molecular mechanism is little known. In this study, we statistically analyzed the miRNA microarray data and revealed that the guanine (G)-rich sequence is a dominant feature of exosome-dominant miRNAs, across the mammalian species-specificity and the cell types. Our results provide important information regarding the potential use of exosome cargos to develop miRNA-based drugs for the treatment of human diseases.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4839687?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/912bde45f92241a39e45ce0e8ea076deTest

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النص الكامل