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  1. Article: The CD28-B7 Family of Co-signaling Molecules.

    Nagai, Shigenori / Azuma, Miyuki

    Advances in experimental medicine and biology

    2019  Volume 1189, Page(s) 25–51

    Abstract: Immune responses are controlled by the optimal balance between protective immunity and immune tolerance. T-cell receptor (TCR) signals are modulated by co-signaling molecules, which are divided into co-stimulatory and co-inhibitory molecules. By ... ...

    Abstract Immune responses are controlled by the optimal balance between protective immunity and immune tolerance. T-cell receptor (TCR) signals are modulated by co-signaling molecules, which are divided into co-stimulatory and co-inhibitory molecules. By expression at the appropriate time and location, co-signaling molecules positively and negatively control T-cell differentiation and function. For example, ligation of the CD28 on T cells provides a critical secondary signal along with TCR ligation for naive T-cell activation. In contrast, co-inhibitory signaling by the CD28-B7 family is important to regulate immune homeostasis and host defense, as these signals limit the strength and duration of immune responses to prevent autoimmunity. At the same time, microorganisms or tumor cells can use these pathways to establish an immunosuppressive environment to inhibit the immune responses against themselves. Understanding these co-inhibitory pathways will support the development of new immunotherapy for the treatment of tumors and autoimmune and infectious diseases. Here, we introduce diverse molecules belonging to the members of the CD28-B7 family.
    MeSH term(s) B7-1 Antigen/metabolism ; CD28 Antigens/metabolism ; Humans ; Immune Tolerance ; Immunotherapy ; Lymphocyte Activation ; Signal Transduction ; T-Lymphocytes/cytology
    Chemical Substances B7-1 Antigen ; CD28 Antigens
    Language English
    Publishing date 2019-11-22
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-981-32-9717-3_2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Fabrications of boron-containing apatite ceramics via ultrasonic spray-pyrolysis route and their responses to immunocytes.

    Nakagawa, Daiki / Nakamura, Mariko / Nagai, Shigenori / Aizawa, Mamoru

    Journal of materials science. Materials in medicine

    2020  Volume 31, Issue 2, Page(s) 20

    Abstract: Immunotherapy without side effects has been expected as a novel medical treatment for cancer. However, drugs such as cytokines typically used for immunotherapy are very expensive. Therefore, we propose the concept of immunoceramics that affect the immune ...

    Abstract Immunotherapy without side effects has been expected as a novel medical treatment for cancer. However, drugs such as cytokines typically used for immunotherapy are very expensive. Therefore, we propose the concept of immunoceramics that affect the immune system. Previous studies have shown that polymers including the phenylboronic acid group activate lymphocytes. This activation may be due to interaction between the sugar chains in cells and the OH group in B(OH)
    MeSH term(s) Animals ; Apatites ; Boron/chemistry ; Cell Adhesion ; Ceramics ; Female ; Lymphocytes/physiology ; Materials Testing ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron, Scanning ; Spleen/cytology ; Surface Properties
    Chemical Substances Apatites ; Boron (N9E3X5056Q)
    Language English
    Publishing date 2020-01-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1031752-1
    ISSN 1573-4838 ; 0957-4530
    ISSN (online) 1573-4838
    ISSN 0957-4530
    DOI 10.1007/s10856-020-6358-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Polymorphonuclear Myeloid-Derived Cells That Contribute to the Immune Paralysis Are Generated in the Early Phase of Sepsis via PD-1/PD-L1 Pathway.

    Ao, Xiang / Yang, Yue / Okiji, Takashi / Azuma, Miyuki / Nagai, Shigenori

    Infection and immunity

    2021  Volume 89, Issue 6

    Abstract: Immune paralysis is a protracted state of immune suppression following the early/acute inflammatory phase of sepsis. ... ...

    Abstract Immune paralysis is a protracted state of immune suppression following the early/acute inflammatory phase of sepsis. CD11b
    MeSH term(s) Animals ; B7-H1 Antigen/metabolism ; Biomarkers ; Cytokines/metabolism ; Disease Models, Animal ; Immunomodulation ; Immunophenotyping ; Mice ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Neutrophils/immunology ; Neutrophils/metabolism ; Programmed Cell Death 1 Receptor/metabolism ; Sepsis/etiology ; Sepsis/metabolism ; Signal Transduction ; Spleen/cytology ; Spleen/immunology ; Spleen/metabolism
    Chemical Substances B7-H1 Antigen ; Biomarkers ; CD274 protein, human ; Cytokines ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2021-05-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/IAI.00771-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: [Prognostic significance of the number of axillary lymph nodes examined in breast cancer].

    Nagai, Shigenori E

    Nihon rinsho. Japanese journal of clinical medicine

    2012  Volume 70 Suppl 7, Page(s) 154–157

    MeSH term(s) Axilla ; Breast Neoplasms/pathology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Prognosis
    Language Japanese
    Publishing date 2012-09
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 390903-7
    ISSN 0047-1852
    ISSN 0047-1852
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Overexpression of PD-L1 in gingival basal keratinocytes reduces periodontal inflammation in a ligature-induced periodontitis model.

    Wongtim, Keeratika / Ikeda, Eri / Ohno, Tatsukuni / Nagai, Shigenori / Okuhara, Shigeru / Kure, Keitetsu / Azuma, Miyuki

    Journal of periodontology

    2021  Volume 93, Issue 1, Page(s) 146–155

    Abstract: Background: The immune checkpoint programmed cell death 1 (PD-1): PD-1 ligand 1 (PD-L1) pathway plays a crucial role in maintaining immune tolerance and preventing tissue damages by excessive immune responses. PD-L1 is physiologically expressed and ... ...

    Abstract Background: The immune checkpoint programmed cell death 1 (PD-1): PD-1 ligand 1 (PD-L1) pathway plays a crucial role in maintaining immune tolerance and preventing tissue damages by excessive immune responses. PD-L1 is physiologically expressed and upregulated in keratinocytes (KCs) in the oral cavity. We here investigated the contribution of PD-L1 that was overexpressed in gingival basal KCs in a ligature-induced periodontitis model.
    Methods: Wild-type (WT) BALB/c and K14/PD-L1 transgenic (tg) mice, in which PD-L1 was overexpressed in basal KCs under control of the keratin 14 promoter, were used. To induce periodontitis, a 9-0 silk ligature was placed around the upper right second molar, and lipopolysaccharide from Porphyromonas gingivalis was applied on the suture. Gingival tissues were collected on day 7, after which histological analyses were performed, including by hematoxylin and eosin and tartrate-resistant acid phosphate staining (TRAP) and quantitative PCR for proinflammatory cytokines and bone metabolism-related genes. Alveolar bone loss at 7 weeks after ligature placement was assessed by micro-computed tomography analysis.
    Results: PD-L1 was overexpressed in the basal KCs of all gingival epithelia in K14/PD-L1tg mice. Early ligature-induced periodontal inflammation, as assessed based on histological changes, elevation of proinflammatory cytokine (IL-1β, IL-6, TNF-α) expression, periodontal ligament degeneration, and osteoclastogenesis as assessed by Rankl and Opg expression and TRAP+ cells, was markedly impaired in K14/PD-L1tg mice. Alveolar bone resorption at a late time point was also clearly minimized in K14/PD-L1tg mice.
    Conclusion: Overexpression of PD-L1 in gingival basal keratinocytes in K14/PD-L1tg mice reduces periodontal inflammation and alveolar bone resorption in a ligature-induced periodontitis model.
    MeSH term(s) Alveolar Bone Loss/genetics ; Animals ; B7-H1 Antigen ; Cytokines/metabolism ; Disease Models, Animal ; Inflammation ; Keratinocytes/metabolism ; Keratinocytes/pathology ; Mice ; Periodontitis/metabolism ; Programmed Cell Death 1 Receptor ; X-Ray Microtomography
    Chemical Substances B7-H1 Antigen ; Cytokines ; Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2021-06-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390921-9
    ISSN 1943-3670 ; 0022-3492 ; 1049-8885 ; 0095-960X
    ISSN (online) 1943-3670
    ISSN 0022-3492 ; 1049-8885 ; 0095-960X
    DOI 10.1002/JPER.21-0017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Orthotopic tongue squamous cell carcinoma (SCC) model exhibiting a different tumor-infiltrating T-cell status with margin-restricted CD8+ T cells and regulatory T cell-dominance, compared to skin SCC

    Kashima, Yoshihisa / Nishii, Naoto / Tachinami, Hidetake / Furusawa, Emi / Nagai, Shigenori / Harada, Hiroyuki / Azuma, Miyuki

    Biochemical and biophysical research communications. 2020 May 21, v. 526, no. 1

    2020  

    Abstract: The immunological, and especially T cell, status of the tumor microenvironment affects tumor development and the efficacy of cancer treatment. To devise suitable combination therapies based on the results of murine tumor models, a more realistic ... ...

    Abstract The immunological, and especially T cell, status of the tumor microenvironment affects tumor development and the efficacy of cancer treatment. To devise suitable combination therapies based on the results of murine tumor models, a more realistic orthotopic model is required. In this study, we generated a murine model of tongue squamous cell carcinoma (SCC), in which the tumor–immune cell interactions were recapitulated, and examined tumor- and T-cell status compared to a skin-transplanted SCC model by multiplex immunofluorescence staining for epidermal growth factor receptor, CD31, CD8, CD4, and Foxp3. Administration of SCCVII cells did not induce undesirable tissue damage or inflammation. In tongue SCC, abundant T-cell infiltration was observed at the tumor margin, but not in the core. Tongue SCC predominantly showed CD8⁺ T or Foxp3⁺ regulatory T cell (Treg)-infiltration. In contrast, skin-transplanted SCC showed abundant infiltration of T cells in the whole tumor area, which was dominated by Tregs. An orthotopic tongue SCC model showed differences in tumor and T-cell status compared to the skin-transplanted SCC model. Our tongue SCC model may enhance understanding of tumor-host interactions and enable evaluation of therapeutic efficacy.
    Keywords animal models ; cancer therapy ; epidermal growth factor receptors ; fluorescent antibody technique ; inflammation ; mice ; research ; squamous cell carcinoma ; tongue
    Language English
    Dates of publication 2020-0521
    Size p. 218-224.
    Publishing place Elsevier Inc.
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2020.03.022
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: The Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, 2022 Edition: changes from the 2018 edition and general statements on breast cancer treatment.

    Yamamoto, Yutaka / Yamauchi, Chikako / Toyama, Tatsuya / Nagai, Shigenori / Sakai, Takehiko / Kutomi, Goro / Yoshimura, Michio / Kawai, Masaaki / Ohtani, Shoichiro / Kubota, Kazunori / Nakashima, Kazutaka / Honma, Naoko / Yoshida, Masayuki / Tokunaga, Eriko / Taira, Naruto / Iwata, Hiroji / Saji, Shigehira

    Breast cancer (Tokyo, Japan)

    2024  Volume 31, Issue 3, Page(s) 340–346

    Abstract: The Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, 2022 Edition was published in June 2022. The guidelines were prepared while conforming as much as possible to the "Minds Manual for Guideline Development 2020 ver. 3.0." ... ...

    Abstract The Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, 2022 Edition was published in June 2022. The guidelines were prepared while conforming as much as possible to the "Minds Manual for Guideline Development 2020 ver. 3.0." edited by the Minds Manual Development Committee of the Japan Council for Quality Health Care in 2021. In addition, a survey of Japanese Breast Cancer Society members on the 2018 edition of the guidelines was conducted from February 19 to March 4, 2021. Based on the responses from over 600 members, original innovations were made to make the guidelines more user-friendly. The 2018 edition of the guidelines was developed to provide support tools for physicians and patients to utilize shared decision-making. The 2022 guidelines consist of two volumes: (1) an "Epidemiology and Diagnosis" section covering "Screening and Diagnosis", "Radiological diagnosis", and "Pathological diagnosis", and (2) a "Treatment" section covering "Surgical therapy", "Radiation therapy", and "Systemic therapy". We believe that this concise summary of the guidelines will be useful to physicians and researchers in Japan and overseas.
    MeSH term(s) Humans ; Breast Neoplasms/therapy ; Breast Neoplasms/diagnosis ; Breast Neoplasms/pathology ; Female ; Japan ; Societies, Medical ; Practice Guidelines as Topic ; Medical Oncology/standards ; East Asian People
    Language English
    Publishing date 2024-04-03
    Publishing country Japan
    Document type Journal Article ; Practice Guideline
    ZDB-ID 2052429-8
    ISSN 1880-4233 ; 1340-6868
    ISSN (online) 1880-4233
    ISSN 1340-6868
    DOI 10.1007/s12282-024-01566-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Correction: The Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, 2022 Edition: changes from the 2018 edition and general statements on breast cancer treatment.

    Yamamoto, Yutaka / Yamauchi, Chikako / Toyama, Tatsuya / Nagai, Shigenori / Sakai, Takehiko / Kutomi, Goro / Yoshimura, Michio / Kawai, Masaaki / Ohtani, Shoichiro / Kubota, Kazunori / Nakashima, Kazutaka / Honma, Naoko / Yoshida, Masayuki / Tokunaga, Eriko / Taira, Naruto / Iwata, Hiroji / Saji, Shigehira

    Breast cancer (Tokyo, Japan)

    2024  

    Language English
    Publishing date 2024-05-12
    Publishing country Japan
    Document type Published Erratum
    ZDB-ID 2052429-8
    ISSN 1880-4233 ; 1340-6868
    ISSN (online) 1880-4233
    ISSN 1340-6868
    DOI 10.1007/s12282-024-01589-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Real-world progression-free survival and overall survival of palbociclib plus endocrine therapy (ET) in Japanese patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer in the first-line or second-line setting: an observational study.

    Yoshinami, Tetsuhiro / Nagai, Shigenori E / Hattori, Masaya / Okamura, Takuho / Watanabe, Kenichi / Nakayama, Takahiro / Masuda, Hiroko / Tsuneizumi, Michiko / Takabatake, Daisuke / Harao, Michiko / Yoshino, Hiroshi / Mori, Natsuko / Yasojima, Hiroyuki / Oshiro, Chiya / Iwase, Madoka / Yamaguchi, Miki / Sangai, Takafumi / Kosaka, Nobuyoshi / Tajima, Kentaro /
    Masuda, Norikazu

    Breast cancer (Tokyo, Japan)

    2024  

    Abstract: Background: A recent large real-world study conducted in the United States reported the effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- advanced breast cancer (ABC). However, local clinical practice and available medical treatment can ...

    Abstract Background: A recent large real-world study conducted in the United States reported the effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- advanced breast cancer (ABC). However, local clinical practice and available medical treatment can vary between Japan and Western countries. Thus, it is important to investigate Japanese real-world data. This observational, multicenter study (NCT05399329) reports the interim analysis of effectiveness of palbociclib plus ET as first-line or second-line treatment for HR+/HER2- ABC by estimating real-world progression-free survival (rwPFS) and overall survival (OS) in Japanese routine clinical practice.
    Methods: Real-world clinical outcomes and treatment patterns of palbociclib plus ET were captured using a medical record review of patients diagnosed with HR+/HER2- ABC who had received palbociclib plus ET in the first-line or second-line treatment across 20 sites in Japan. The primary endpoint was rwPFS; secondary endpoints were OS, real-world overall response rate, real-world clinical benefit rate, and chemotherapy-free survival.
    Results: Of the 677 eligible patients, 420 and 257 patients, respectively, had received palbociclib with ET as first-line and second-line treatments. Median rwPFS (95% confidence interval) was 24.5 months (19.9-29.4) for first-line and 14.5 months (10.2-19.0) for second-line treatment groups. Median OS was not reached in the first-line group and was 46.7 months (38.8-not estimated) for the second-line group. The 36-month OS rates for de novo metastasis, treatment-free interval (TFI) ≥ 12 months, and TFI < 12 months were 80.2% (69.1-87.7), 82.0% (70.7-89.3), and 66.0% (57.9-72.9), respectively.
    Conclusion: The addition of palbociclib to ET was effective for treating HR+/HER2- ABC in Japanese routine clinical practice.
    Language English
    Publishing date 2024-04-20
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2052429-8
    ISSN 1880-4233 ; 1340-6868
    ISSN (online) 1880-4233
    ISSN 1340-6868
    DOI 10.1007/s12282-024-01575-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Dose-dense adjuvant chemotherapy: a systematic review and meta-analysis of the Japanese Breast Cancer Society Clinical Practice Guideline, 2018 edition.

    Yoshinami, Tetsuhiro / Koizumi, Kei / Nagai, Shigenori E / Toyama, Tatsuya / Iwata, Hiroji

    Breast cancer (Tokyo, Japan)

    2020  Volume 27, Issue 3, Page(s) 334–339

    Abstract: Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles may enhance efficacy. Dose-dense chemotherapy, which is adopted as adjuvant chemotherapy of high-risk breast cancer, is addressed in the Japanese Breast Cancer ... ...

    Abstract Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles may enhance efficacy. Dose-dense chemotherapy, which is adopted as adjuvant chemotherapy of high-risk breast cancer, is addressed in the Japanese Breast Cancer Society Clinical Practice Guideline for breast cancer, 2018 edition (in Japanese). To evaluate the benefits and safety of dose-dense adjuvant chemotherapy described in the guideline, we performed a systematic review and meta-analysis of data of randomized trials using the same drugs, doses, and numbers of cycles. The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant publications reporting randomized trials published until November 2016. Overall survival (OS), disease-free survival (DFS), and toxicity were assessed. Three trials comprising 5190 patients were included. Compared with conventional chemotherapy, dose-dense chemotherapy lengthened OS (RR = 0.76; 95% CI = 0.64-0.90) and DFS (RR = 0.83; 95% CI = 0.75-0.92) and increased the risk of anemia (RR = 4.56; 95% CI = 2.01-10.34). We conclude that dose-dense chemotherapy can be highly recommended as adjuvant chemotherapy for patients with breast cancer with a high risk of recurrence risk and sufficient bone marrow function.
    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Female ; Humans ; Medical Oncology ; Practice Guidelines as Topic/standards ; Prognosis
    Language English
    Publishing date 2020-01-08
    Publishing country Japan
    Document type Journal Article ; Meta-Analysis ; Systematic Review
    ZDB-ID 2052429-8
    ISSN 1880-4233 ; 1340-6868
    ISSN (online) 1880-4233
    ISSN 1340-6868
    DOI 10.1007/s12282-019-01039-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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