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1. Sleep status of older adults with sleep apnoea syndrome may vary by body mass index

Author: Yuji Tanaka, Naana Baba-Mori, Takaaki Yonaga, Kazuki Mochizuki, Satoshi Igarashi, Takashi Ando, Takashi Kohda, Yasumi Ito, Kenzo Soejima, and Daiju Sakurai
Subjects: apnoea-hypopnea index, apnoea syndromes, body mass index, sleep stage, older adults, ageing, Geriatrics, RC952-954.6
Abstract: Obesity and ageing are the most important risk factors for sleep apnoea syndrome (SAS); however, the role of body mass index (BMI) on sleep status in healthy older adults is unclear. To explore sleep parameters according to BMI among active older adults, we cross-sectionally examined the relationship between sleep-related parameters and BMI in 32 Japanese adults aged from 83 to 95 years without long-term care who were unaware of having SAS. Correlation and linear regression analyses were performed. Moderate or severe SAS prevalence was high in both those with low (68.8%) and high (68.8%) BMI. A higher increase in apnoea-hypopnoea index (AHI) was negatively correlated with sleep depth in the high-BMI group. In the low-BMI group, the number of awakenings and age were positively correlated with AHI. Older adults may have SAS regardless of their BMI, and the sleep status of patients with SAS may vary by BMI.
Published: 2024
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2. Cha o 3, a cypress pollen allergen, does not activate basophils in Japanese cypress pollinosis

Author: Yoshiaki Kobayashi, MD, Keisuke Suzuki, MSc, Minoru Tateno, PhD, Yuki Nakamura, PhD, Kayoko Ishimaru, Yuka Nagasaka, Daiju Sakurai, MD, PhD, Katsuyo Ohashi-Doi, PhD, and Atsuhito Nakao, MD, PhD
Subjects: Japanese cypress pollinosis, Cha o 3, basophil activation test, Immunologic diseases. Allergy, RC581-607
Abstract: Background: In Japan, pollinosis caused by the Japanese cypress (JCy) Chamaecyparis obtusa is among the very common seasonal allergies. In JCy pollinosis, Cha o 1 is the first major allergen, and Cha o 2 is the second major allergen. Recently, Cha o 3 was identified as a new JCy pollen allergen in JCy pollinosis. However, the relative contribution of Cha o 3 to JCy pollinosis compared with that of Cha o 1 and that of Cha o 2 has not been fully elucidated. Objective: This study aimed to clarify the allergenicity of Cha o 3 compared with that of Cha o 1 and Cha o 2 in JCy pollinosis. Methods: We recruited 27 patients with JCy pollinosis and performed the basophil activation test (BAT) with native (n) Cha o 1, Cha o 2, and Cha o 3 purified from JCy pollen. In addition, we a performed JCy-specific IgE suppression test. Results: In the BAT, 26 of 27 patients (96%) and 18 of 27 patients (67%) showed positive basophil activation in response to n Cha o 1 and n Cha o 2, respectively, as judged by CD203c expression. Little CD203c expression in response to n Cha o 3 was seen. The presence of n Cha o 3 marginally reduced the titer levels of JCy-specific IgE. Conclusion: Cha o 3 showed little ability to activate basophils and suppress JCy-specific IgE titers compared with Cha o 1 or Cha o 2 in patients with JCy pollinosis. Thus, Cha o 3 may not be a major allergen in JCy pollinosis.
Published: 2024
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3. Executive summary: Japanese guidelines for allergic rhinitis 2020

Author: Mitsuhiro Okano, Shigeharu Fujieda, Minoru Gotoh, Yuichi Kurono, Atsushi Matsubara, Nobuo Ohta, Atsushi Kamijo, Takechiyo Yamada, Yuji Nakamaru, Mikiya Asako, Daiju Sakurai, Tetsuya Terada, Shuji Yonekura, Masafumi Sakashita, and Kimihiro Okubo
Subjects: Allergen immunotherapy, Mechanism, Pharmacotherapy, Pollinosis, Surgery, Immunologic diseases. Allergy, RC581-607
Abstract: The Practical Guideline for the Management of Allergic Rhinitis, the fist guideline for allergic rhinitis in Japan, was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 9th edition was published in 2020 and is widely used today.The most recent collection of evidence from the literature was supplemented to the revised guideline to incorporate evidence-based medicine. The revised guideline includes updated epidemiology of allergic rhinitis in Japan, a figure representing the mechanisms of allergic rhinitis in both the onset and sensitization phases with the introduction of regulatory T cells and type 2 innate lymphoid cells, practical assessment for diagnosis, new pharmacotherapy agents such as anti-IgE mAb and a new drug delivery system for antihistamines, sublingual immunotherapy for children, dual sublingual immunotherapy for house dust mites and Japanese cedar pollen extract, new classification for surgery for allergic rhinitis, and treatment and prescriptions for older adults. An evidence-based step-by-step strategy for treatment is also described.
Published: 2023
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4. Successful desensitization after hypersensitivity reaction to cisplatin in a patient with nasopharyngeal carcinoma

Author: Arisa Kinouchi, Hiroki Ishii, Kaname Sakamoto, and Daiju Sakurai
Subjects: carboplatin, cisplatin, desensitization, hypersensitivity reaction, nasopharyngeal carcinoma, Medicine, Medicine (General), R5-920
Abstract: Abstract Hypersensitivity reaction to cisplatin can result in discontinuation of chemoradiotherapy in patients with head and neck squamous cell carcinoma. We describe a patient with nasopharyngeal carcinoma who developed cisplatin hypersensitivity and was successfully treated with cisplatin desensitization. Furthermore, it had little impact on the therapeutic performance of cisplatin‐combined chemoradiotherapy.
Published: 2022
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5. Characteristics of Japanese cypress pollen-induced allergic rhinitis by environmental challenge chamber

Author: Minami Koriyama, Yoshitaka Okamoto, Takeshi Suzuki, Tomohisa Iinuma, Heizaburou Yamamoto, Yusuke Okuma, Sawako Hamasaki, Daiju Sakurai, Toyoyuki Hanazawa, and Syuji Yonekura
Subjects: Immunologic diseases. Allergy, RC581-607
Published: 2022
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6. Genomic and immune microenvironment profiling in a case of metastatic intrathyroid thymic carcinoma

Author: Hiroki Ishii, Takahiro Tsujikawa, Naoki Oishi, Arisa Kinouchi, Kaname Sakamoto, Junichi Mitsuda, Hiroshi Ogi, Kyoko Itoh, Tetsuo Kondo, Shigeru Hirano, and Daiju Sakurai
Subjects: immune checkpoint inhibitor, intrathyroid thymic carcinoma, mutation analysis, PD‐1/PD‐L1, tumor‐immune microenvironment, Medicine, Medicine (General), R5-920
Abstract: Abstract Metastatic intrathyroid thymic carcinoma (ITTC) is a rare cancer with no effective drugs for controlling. This case report has shown genomic and immune microenvironment profiles in metastatic ITTC and emphasized an immunosuppression via a PD‐1/PD‐L1 pathway, possibly strengthening the rationale for immune checkpoint blockade as a novel treatment.
Published: 2022
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7. Toxic epidermal necrolysis associated with nivolumab treatment for head and neck cancer

Author: Keiichi Koshizuka, Daiju Sakurai, Miki Sunagane, Yukiyoshi Mita, Sawako Hamasaki, Takeshi Suzuki, Naoko Kikkawa, Michiyo Nakano, and Toyoyuki Hanazawa
Subjects: head and neck cancer, nivolumab, Stevens‐Johnson syndrome, toxic epidermal necrolysis, Medicine, Medicine (General), R5-920
Abstract: Abstract This report is the first to document TEN caused by nivolumab treatment in head and neck cancer. We believe this article can contribute significantly in understanding the principles of nivolumab treatment in patients with head and neck cancer.
Published: 2021
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8. Risk Factors and Assessment Using an Endoscopic Scoring System for Postoperative Respiratory Complications after Anterior Cervical Decompression and Fusion Surgery

Author: Tetsuro Ohba, Hiroshi Akaike, Koji Fujita, Kotaro Oda, Nobuki Tanaka, Matsuoka Tomokazu, Daiju Sakurai, and Hirotaka Haro
Subjects: anterior cervical discectomy and fusion, postoperative respiratory complications, flexible endoscopic evaluation of swallowing, eating assessment tool, Surgery, RD1-811
Abstract: Introduction: Postoperative respiratory complications (PRC) are one of the most serious complications. Potentially life-threatening accidents can occur after an anterior cervical discectomy and fusion (ADF), such as airway obstruction and aspiration pneumonia. Despite numerous studies, preoperative predictive and preventive methodology has yet to be established. As reported in our previous study, the evaluation of preoperative dysphagia using the eating assessment tool (EAT-10) and a flexible endoscopic evaluation of swallowing (FEES) is useful for predicting the incidence and risk factors of dysphagia after ADF. Methods: This prospective study comprised 60 consecutive patients who underwent ADF. An otolaryngologist and a speech-language-hearing therapist preoperatively and 1 week postoperatively evaluated dysphagia using EAT-10 and Hyodo-Komagane (H-K) scores during FEES. Patient demographics, comorbidities, and pre- and postoperative dysphagia were compared between patients with and without PRC. Results: Seven of 60 (11.6%) patients had preoperative dysphagia diagnosed using the H-K score. A significant positive correlation existed between the pre- and postoperative H-K scores. Of all 60 cases, eight (13.3%) had PRC. Among them, two required reintubation due to airway obstruction and six had aspiration pneumonia. The PRC(+) group was significantly older and more prone to diabetes and asthma. The preoperative H-K score of the PRC(+) group was significantly higher than that of the PRC(−) group. Postoperatively, but not preoperatively, EAT-10 was significantly higher in the PRC(+) group. Conclusions: Preoperative dysphagia may potentially exacerbate postoperative dysphagia after ADF. A preoperative evaluation of dysphagia using the H-K score during FEES is a useful method for predicting and reducing the risk of PRC. Level of Evidence: 3
Published: 2021
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9. Complement Factor H Is an Early Predictive Biomarker of the Therapeutic Efficacy of Sublingual Immunotherapy for Japanese Cedar Pollinosis

Author: Riyo Yoneda, Tomohisa Iinuma, Daiju Sakurai, Junya Kurita, Tomoyuki Arai, Yuri Sonobe, Syuji Yonekura, Yoshitaka Okamoto, and Toyoyuki Hanazawa
Subjects: sublingual immunotherapy, Japanese cedar pollinosis, biomarker, Medicine
Abstract: Sublingual immunotherapy for Japanese cedar pollinosis can improve the symptoms of allergic rhinitis and modify its natural course. However, sublingual immunotherapy requires a long treatment period and some patients do not respond to treatment. In this study, we aimed to identify biomarkers that could predict the efficacy of sublingual immunotherapy at an early stage. In this study, 40 patients from phase III trials were recruited and divided into good and poor response groups. Using peripheral blood mononuclear cells from before and two months after the start of medication, microarray, discriminant analysis, and real-time polymerase chain reaction were performed to extract candidate genes that could be biomarkers. Furthermore, these genes were validated in 30 patients in general clinical practice. Complement factor H was upregulated in the good response group and downregulated in the poor response group. Complement factor H may be a useful biomarker for predicting the efficacy of sublingual immunotherapy for Japanese cedar pollinosis at early time points after treatment initiation.
Published: 2022
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10. Sublingual Immunotherapy for Japanese Cedar Pollinosis: Current Clinical and Research Status

Author: Daiju Sakurai, Hiroki Ishii, Ayumi Shimamura, Daisuke Watanabe, Takaaki Yonaga, and Tomokazu Matsuoka
Subjects: allergic rhinitis, allergen immunotherapy, Japanese cedar pollen, pollinosis, sublingual immunotherapy, Medicine
Abstract: The incidence of Japanese cedar pollinosis is increasing significantly in Japan, and a recent survey suggested that about 40% of the population will develop this disease. However, spontaneous remission is rare. The increased incident rate of Japanese cedar pollinosis is a huge issue in Japan. Allergen immunotherapy is the only fundamental treatment that modifies the natural course of allergic rhinitis and provides long-term remission that cannot be induced by general drug therapy. Sublingual immunotherapy for Japanese cedar pollinosis has been developed and has been covered by health insurance since 2014 in Japan. The indication for children was expanded in 2018. Clinical trials of sublingual immunotherapy for Japanese cedar pollinosis have demonstrated its long-term efficacy and safety. It is recommended for patients who wish to undergo fundamental treatment regardless of the severity of the practical guidelines for the management of allergic rhinitis in Japan. For sublingual immunotherapy, a long-term treatment period of 3 years or longer is recommended to obtain stable therapeutic effects. In recent years, evidence based on basic research and clinical trials has demonstrated sublingual immunotherapy-induced immunological changes and efficacy in patients; however, biomarkers that objectively predict and judge these therapeutic effects need to be established.
Published: 2022
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11. Investigating Japanese cedar pollen-induced allergic rhinitis and related terms using Google Trends

Author: Tomohisa Iinuma, Syuji Yonekura, Daiju Sakurai, Yosuke Inaba, Yohei Kawasaki, and Yoshitaka Okamoto
Subjects: Immunologic diseases. Allergy, RC581-607
Published: 2020
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12. Sublingual administration of liposomes enclosing alpha-galactosylceramide as an effective adjuvant of allergen immunotherapy in a murine model of allergic rhinitis

Author: Satoshi Suzuki, Daiju Sakurai, Toshioki Sakurai, Syuji Yonekura, Tomohisa Iinuma, Yusuke Okuma, Fumie Ihara, Tomoyuki Arai, Toyoyuki Hanazawa, Emi Fukuda-Kawaguchi, Yasuyuki Ishii, and Yoshitaka Okamoto
Subjects: Immunologic diseases. Allergy, RC581-607
Abstract: Background: Sublingual immunotherapy (SLIT) is an established efficacious approach for the treatment of allergic rhinitis (AR). However, SLIT requires a long administration period to establish stable and adequate responses. This study investigated the efficacy of the sublingual administration of an allergen with liposomes enclosing α-GalCer (α-GC-liposome) as a potential adjuvant in mice with AR. Methods: Mice with AR induced by OVA received the sublingual administration of OVA, α-GC-liposomes, or OVA plus α-GC-liposomes for 7 days. After nasal re-challenge with OVA, nasal symptoms were evaluated. The serum levels of OVA-specific Ig, the cytokine production of CD4+ T cells in the cultures of cervical lymph node (CLN) cells, and the gene expression of CLNs were analyzed. Results: Although IL-4, IL-5 and IL-13 production from CD4+ T cells in CLN cells was significantly inhibited by the sublingual administration of OVA alone in mice with AR induced by OVA, their nasal symptoms were not significantly diminished. However, the combined sublingual administration of α-GC-liposomes and OVA completely suppressed nasal symptoms, downregulated Th2 and Th17 type cytokine production in CD4+ T cells as well as Th2 and Th17 gene expressions, and upregulated Th1 type cytokine production as well as Th1 gene expressions in CLN cells. Additionally, the serum levels of specific IgG2a were promoted, and specific IgE and IgG1 were inhibited. Conclusions: Our findings suggest that the sublingual administration of an allergen with α-GC-liposomes as an adjuvant might increase the therapeutic efficacy and effectiveness of this treatment method. Keywords: Allergic, Liposome, Mice, Natural killer T-Cells, Rhinitis
Published: 2019
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13. Activated iNKT cells enhance the anti-tumor effect of antigen specific CD8 T cells on mesothelin-expressing salivary gland cancer

Author: Yuji Makita, Naoki Kunii, Daiju Sakurai, Fumie Ihara, Shinichiro Motohashi, Akane Suzuki, Toshinori Nakayama, and Yoshitaka Okamoto
Subjects: Adoptive immunotherapy, Chimeric antigen receptor, Cytotoxic T lymphocyte, Natural kiiler T-cells, Salivary gland cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Salivary gland cancers are not sensitive to conventional radiotherapy or chemotherapy regimens. Therefore, the development of a new treatment strategy is of critical importance for improving the prognosis. We examined the expression of mesothelin molecules in salivary gland cancers and the efficacy of adoptive cell therapy based on mesothelin-specific chimeric antigen receptor transduced T cells. Methods The expression of mesothelin molecule was studied in salivary gland cancer samples obtained from 16 patients as well as a salivary gland cancer cell line (A-253) and five other cell lines. The activation of mesothelin-specific chimeric antigen receptor-expressing CD8 T cells after stimulation with mesothelin and the effects of invariant natural killer T cells on this activation were evaluated. Results Mesothelin was detected in the A-253 cells and the surgical specimens except for the case of squamous cell carcinoma to various degrees. Following stimulation with mesothelin expressing cancer cells, chimeric antigen receptor T cells were dose-dependently activated; this activation was enhanced by co-culture with invariant natural killer T cells and subsequently abrogated by treatment with anti-interferon-γ antibodies. Furthermore, the cytotoxicity of chimeric antigen receptor T cells against various cancer cells was further augmented by invariant natural killer T cells. Conclusions The use of adoptive transfer with mesothelin-specific chimeric antigen receptor-expressing CD8 T cells against salivary gland cancers is an effective therapy and invariant natural killer T cells are expected to be used in adjuvant treatment for T cell-based immunotherapy.
Published: 2018
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14. Immunosuppressive property of submandibular lymph nodes in patients with head and neck tumors: differential distribution of regulatory T cells

Author: Daiju Sakurai, Ryosuke Uchida, Fumie Ihara, Naoki Kunii, Takuya Nakagawa, Hideaki Chazono, Toyoyuki Hanazawa, Shinichiro Motohashi, and Yoshitaka Okamoto
Subjects: Cervical lymph node, Dendritic cells, FcεRI, Head and neck tumor, Regulatory T cells, Submandibular lymph nodes, Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract: Abstract Objective Different sensitizations and immune responses are thought to be induced in response to antigens at different mucosal sites between the oral floor and nose. The aim of this study was to investigate differences in the distributions of lymphocyte subsets in the submandibular (SM) and upper jugular (UJ) lymph nodes (LNs), which are supposed to be regional LNs of the oral floor and nasal mucosa, respectively. SMLNs and UJLNs were collected from patients with head and neck tumors who underwent surgical resection. The populations of T cells, Natural Killer (NK) cells, Natural Killer T (NKT) cells, regulatory T cells (Tregs) and dendritic cells (DCs) in LNs without metastasis were analyzed by flow cytometry. The high-affinity IgE receptor (FcεRI) expression of LN cells were also evaluated. Results The proportions of CD4+CD25+Foxp3+ Tregs, CD4+CD45RA−Foxp3high effector Tregs and FcεRIα+CD33+CD11c+ DCs were significantly larger in SMLNs compared with UJLNs, while those of CD3+ T cells, CD3−CD56+ NK cells, CD3+Vα24+Vβ11+ NKT cells, and CD123+CD303+ DCs did not show any significant differences between SMLNs and UJLNs. The differential distributions of CD4+CD25+Foxp3+ Tregs were observed regardless of tumor region, LN metastasis and clinical staging. These data indicate that SMLNs may have immunosuppressive properties compared with UJLNs.
Published: 2018
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15. An analysis of factors related to the effect of sublingual immunotherapy on Japanese cedar pollen induced allergic rhinitis

Author: Syuji Yonekura, Yoshitaka Okamoto, Daiju Sakurai, Kimihiro Okubo, Minoru Gotoh, Shinya Kaneko, and Akiyoshi Konno
Subjects: Immunologic diseases. Allergy, RC581-607
Abstract: Background: Sublingual immunotherapy (SLIT) can improve the symptoms of allergic rhinitis and modify its natural history; however, its efficacy varies among patients. This study aimed to determine which factors modify the effect of SLIT through post hoc analysis of a previous phase 3 trial of standardized Japanese cedar (JC) pollen extract (CEDARTOLEN®). Methods: The study included 482 patients who had previously completed a phase 3 trial during two seasons. The SLIT and placebo groups each contained 241 subjects. Because pollen dispersal differed in the two seasons, we identified good and poor responders from the SLIT group in the 2nd season. We compared patient baseline characteristics, changes in serum immunoglobulin, and severity of symptoms in the 1st season between good and poor responders, as well as between SLIT and placebo groups. Results: When we compared the baseline characteristics of good and poor responders, a significant difference was observed in body mass index (BMI) such that the patients with BMI ≥25 presented with lower treatment efficacy. No significant difference was observed in correlation with any other factors or treatment-induced alterations of serum immunoglobulin levels. We found that 75.3% of the patients with moderate symptoms and 50.9% of the patients with severe or very severe symptoms in the 1st season met our criteria for good responders in the 2nd season. Conclusions: BMI might modify the effect of SLIT; however, other factors were not related clearly. The severity of symptoms in the 1st season of treatment does not predict that in the 2nd season. Keywords: Allergic rhinitis, Japanese cedar pollen, Phase 3 trial, Post hoc analysis, Sublingual immunotherapy
Published: 2018
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16. Complementary and alternative medicine for allergic rhinitis in Japan

Author: Syuji Yonekura, Yoshitaka Okamoto, Daiju Sakurai, Toshioki Sakurai, Tomohisa Iinuma, Heizaburou Yamamoto, Toyoyuki Hanazawa, Shigetoshi Horiguchi, Yuichi Kurono, Kohei Honda, Yuichi Majima, Keisuke Masuyama, Noriaki Takeda, Shigeharu Fujieda, Mitsuhiro Okano, Satoshi Ogino, and Kimihiro Okubo
Subjects: Allergic rhinitis, Complementary and alternative medicine, Conventional treatments, Questionnaire, Unconventional treatments, Immunologic diseases. Allergy, RC581-607
Abstract: Background: Complementary and alternative medicine (CAM) is extensively used in patients with allergic diseases worldwide. The purpose of this study was to investigate the actual situation of CAM practice in the treatment of allergic rhinitis. Methods: We distributed questionnaires to otolaryngologists at 114 facilities in Japan. The subjects who participated in this study included children
Published: 2017
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17. Characteristics of the Chiba Environmental Challenge Chamber

Author: Sawako Hamasaki, Yoshitaka Okamoto, Syuji Yonekura, Yusuke Okuma, Toshioki Sakurai, Tomohisa Iinuma, Heizaburo Yamamoto, Daiju Sakurai, Shigetoshi Horiguchi, and Masahiko Yokota
Subjects: environmental challenge chamber (ECC), Japanese cedar pollinosis, seasonal allergic rhinitis (SAR), validation study, α chamber, Immunologic diseases. Allergy, RC581-607
Abstract: Background: An environmental challenge chamber (ECC), which we refer to as the α-chamber, was built at Chiba University in 2008. The aim of this study was to validate the functionality of the ECC. Methods: The stability of the pollen distribution and concentration in the ECC and symptoms of patients with Japanese cedar pollinosis induced by cedar pollen exposure were examined. Carryover effects of symptoms induced by different exposure protocols and correlations between symptoms induced in the ECC and those in the natural cedar pollen season were also determined. All the studies using the α-chamber were conducted out of the cedar pollen season. Results: The severity of symptoms in the chamber reached a peak about 2 hours after the start of pollen exposure and plateaued thereafter. After subjects left the chamber, the symptoms persisted for several days. There was no significant difference between the severity of symptoms at exposure levels of 8000 and 12000 grains/m3. The symptoms were significantly increased by exposure for 3 consecutive days; however, there were no carryover effects in a study performed with a two-week interval. The total nasal symptom score (TNSS) in the natural pollen season showed a weak correlation with the mean TNSS on the day of exposure and the following 3 days. Symptoms in the ECC also had weak correlations with those in the early natural pollen season. Conclusions: The ECC under well-controlled conditions is suitable for clinical studies and might accelerate development of treatment for seasonal allergic rhinitis. A complete evaluation requires inclusion of the persistent reaction after subjects leave the ECC.
Published: 2014
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18. The Influence of Environmental Exposure to Formaldehyde in Nasal Mucosa of Medical Students during Cadaver Dissection

Author: Minako Hisamitsu, Yoshitaka Okamoto, Hideaki Chazono, Syuji Yonekura, Daiju Sakurai, Shigetoshi Horiguchi, Toyoyuki Hanazawa, Nobuhisa Terada, Akiyoshi Konno, Yoshiharu Matsuno, Emiko Todaka, and Chisato Mori
Subjects: clinical symptoms, formaldehyde, IgE, nasal hypersensitivity, olfactory disorder, Immunologic diseases. Allergy, RC581-607
Abstract: Background: Environmental exposure to formaldehyde is commonly associated with clinical symptoms such as mucosal irritation and olfactory disorders. However, the impact of such exposure on the development of mucosal inflammation and its outcome has not been carefully evaluated. Methods: The observational non-comparative study was planned. The study population consisted of group of 41 medical students who had signed up for a cadaver dissection course as part of their gross anatomy teaching at the school of medicine Chiba University in Japan. During such dissection course, the students are exposed to variable levels of environmental formaldehyde routinely employed for the preservation the cadavers. The subjects were evaluated by a detailed medical examination. We measured their serum IgE levels. In addition, an olfaction test and nasal mucosal sensitivity to histamine was serially determined, immediately before and after the course and 6 months after the completion of the course. Results: Olfactory abnormalities were observed in 13/41 (32%) subjects and increased nasal mucosal hypersensitivity to histamine was observed in 17/41 (41%) during and immediately after completion of the course. These subjects had evidence of preexisting allergic rhinitis. 6/41 (15%) other students with no prior evidence of allergic rhinitis also exhibited formaldehyde associated clinical symptoms during the dissecting course. However, the symptoms disappeared upon completion of the course in all subjects studied. Conclusions: Temporary abnormalities in the olfaction test and increased nasal mucosal hypersensitivity to histamine were observed in a few students with preexisting allergic rhinitis after environmental exposure of high concentrations of formaldehyde. These effects appeared to be transient.
Published: 2011
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19. Sublingual Immunotherapy with House Dust Extract for House Dust-Mite Allergic Rhinitis in Children

Author: Syuji Yonekura, Yoshitaka Okamoto, Daiju Sakurai, Shigetoshi Horiguchi, Toyoyuki Hanazawa, Atsuko Nakano, Fumiyo Kudou, Yuji Nakamaru, Kohei Honda, Akira Hoshioka, Naoki Shimojo, and Yoichi Kohno
Subjects: children, double blind, house dust extract, house dust-mite allergic rhinitis, placebo-controlled trial, sublingual immunotherapy, Immunologic diseases. Allergy, RC581-607
Abstract: Background: House dust extract is used in conventional immunotherapy for house dust-mite (HDM) allergic rhinitis in Japan. However, an alternative administration route is desired. The aims of the present double blind, placebo-controlled trial were to evaluate the therapeutic efficacy and safety of sublingual immunotherapy (SLIT) with house dust extract in pediatric patients with HDM allergic rhinitis. Methods: The study population comprised 31 subjects (21 males and 10 females) aged from 7 to 15 years old. Twenty patients (the active group) received house dust extract and 11 received placebo via sublingual administration. Extract or placebo (1 ml) was administered at 10-fold dilution once weekly for 40 weeks. During the study period, the subjects recorded their daily nasal symptoms and use (dose and frequency) of other medications in a nasal allergy diary. Results: The symptom scores in the active group began to decrease about 24 weeks after initiation of treatment and significant differences between the active and placebo groups were observed after 30 weeks. The average scores for the last four weeks of the study were significantly lower than those for the first four weeks in the active group but not in the placebo group. The only local adverse effect was a bitter taste reported by one patient. There were no other local or systemic adverse effects associated with SLIT. Conclusions: Our results suggest that SLIT with house dust extract for more than 30 weeks is safe and effective treatment for HDM allergic rhinitis in children.
Published: 2010
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20. Esophageal Ultrasound Video-processing Based Bolus Inflow Detection Method for Swallowing Evaluation.

Author: Yutaka Suzuki, Daiju Sakurai, Morimasa Tanimoto, Keisuke Masuyama, Osamu Sakata, and Masayuki Morisawa
Published: 2021
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21. International Session 3 Head and Nack-Basic 1

Author: Chair: Daiju, Sakurai, primary and Yorihisa, Imanishi, additional
Published: 2024
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22. Loss of intercellular bridges in the depth of invasion measurement area is a novel negative prognostic factor for oral squamous cell carcinoma: A retrospective study

Author: Kunio Yoshizawa, Yujiro Kimura, Akinori Moroi, Hiroki Ishii, Daiju Sakurai, Masao Saitoh, Naoki Oishi, Tetsuo Kondo, Masahiro Toyoura, and Koichiro Ueki
Subjects: Squamous Cell Carcinoma of Head and Neck, Prognosis, Pathology and Forensic Medicine, Head and Neck Neoplasms, Lymphatic Metastasis, Carcinoma, Squamous Cell, Humans, Mouth Neoplasms, Neoplasm Invasiveness, Radiology, Nuclear Medicine and imaging, Dentistry (miscellaneous), Surgery, Oral Surgery, Neoplasm Staging, Retrospective Studies
Abstract: This study aimed to evaluate intercellular bridges in the depth of invasion (DOI) measurement area as prognostic factors in oral squamous cell carcinoma (OSCC).The mode of invasion was determined based on the Yamamoto-Kohama classification system by observing the hematoxylin-eosin-stained whole-slide images of specimens obtained from 78 patients with OSCC, and the clinicopathologic features were characterized. The presence of intercellular bridges was analyzed in 46 patients with Yamamoto-Kohama classification grade ≥3 whose DOI was measured by dividing the measurement area into 3 parts: the surface, center, and front of the tumor.Univariate analyses identified lymph node metastasis, loss of intercellular bridges in the DOI measurement area, DOI of ≥4500 µm, and pattern of invasion 4C-4D as negative prognostic factors. Multivariate analyses revealed that lymph node metastasis and the loss of intercellular bridges in the entire area were independent factors, with hazard ratios of 9.34 (95% confidence interval, 2.09-42.03; P = .003) and 3.64 (95% confidence interval, 1.10-11.99; P = .045), respectively.Loss of intercellular bridges in the DOI measurement area is a negative prognostic factor for OSCC and may be useful in selecting treatment.
Published: 2022

23. A Case of Middle Ear Adenoma That Needed Multiple Operations

Author: Kiwako Horiuchi, Shota Tanaka, Toru Odate, Tetsuo Kondo, Akira Hayashi, Ayumi Shimamura, Shuichiro Endo, and Daiju Sakurai
Subjects: Otorhinolaryngology
Published: 2022

24. A Study on Surgical Outcomes of Pars Flaccida Cholesteatoma

Author: Akira Hayashi, Shota Tanaka, Shuichiro Endo, Mari Takahashi, Kiwako Horiuchi, Ayumi Shimamura, Hiroki Ishii, Tomokazu Matsuoka, Daiju Sakurai, and Keisuke Masuyama
Subjects: Otorhinolaryngology
Published: 2022

25. Nodular fasciitis arising from the buccal region after segmentectomy with rapid growth mimicking postirradiation myxofibrosarcoma: A case report

Author: Kunio Yoshizawa, Hiroki Ishii, Daiju Sakurai, Tomohiro Inoue, and Koichiro Ueki
Subjects: Adult, Male, Squamous Cell Carcinoma of Head and Neck, Fibrosarcoma, Sarcoma, General Medicine, Histiocytoma, Malignant Fibrous, Middle Aged, Ki-67 Antigen, Head and Neck Neoplasms, Humans, Cisplatin, Fasciitis, Pneumonectomy, Aged
Abstract: Nodular fasciitis (NF) can be misdiagnosed as a sarcoma because of its rapid growth and pathological features, such as nuclear atypia and mitoses.We present a rare case of a 72-year-old Japanese man who developed NF with suspected postirradiation myxofibrosarcoma (MFS) after segmentectomy for left-sided osteoradionecrosis (ORN) of the mandible.A mass appeared in the intraoral postoperative wound 1 year after left-sided mandibular segmentectomy and showed rapid growth, reaching a size of 50 mm within 2 months. Incisional biopsy revealed strongly Ki-67-positive spindle-shaped cells with large irregular nuclei and a diagnosis of postirradiation MFS.The patient was diagnosed with oropharyngeal cancer (T4aN2bM0) and underwent surgical resection of primary oropharyngeal squamous cell carcinoma with selective neck dissection and reconstruction with a rectus abdominis musculocutaneous flap at the age of 57 years, followed by postoperative 66 Gy of radiotherapy combined with cisplatin administration. No recurrent or metastatic lesions of oropharyngeal squamous cell carcinoma have been detected for 10 years. However, the ORN of the jaw worsened, and the patient underwent sequestrectomy 3 times on the right side of the mandible, followed by a left-sided segmentectomy at the age of 72 years. One year after segmentectomy, a 10-mm mass with soft-to-firm consistency appeared in the buccal mucosa of the wound and grew rapidly. An incisional biopsy revealed MFS. Complete resection under general anesthesia was immediately performed.The histopathological diagnosis of the excised specimen was NF without any malignant findings. Two years after surgery, there was no evidence of recurrence or metastasis.NF grows rapidly and has pathological features similar to sarcoma, making differential diagnosis difficult at the time of incisional biopsy. Further studies should be conducted to determine the clinical and pathological features of this tumor.
Published: 2022

26. Characteristics of Japanese cypress pollen-induced allergic rhinitis by environmental challenge chamber

Author: Takeshi Suzuki, Toyoyuki Hanazawa, Yoshitaka Okamoto, Tomohisa Iinuma, Daiju Sakurai, Heizaburou Yamamoto, Sawako Hamasaki, Minami Koriyama, Yusuke Okuma, and Syuji Yonekura
Subjects: Horticulture, Japanese cypress pollen, Immunology and Allergy, General Medicine, Biology, Immunologic diseases. Allergy, RC581-607
Published: 2022

27. Risk Factors and Assessment Using an Endoscopic Scoring System for Postoperative Respiratory Complications after Anterior Cervical Decompression and Fusion Surgery

Author: Nobuki Tanaka, Kotaro Oda, Tetsuro Ohba, Daiju Sakurai, Koji Fujita, Hiroshi Akaike, Matsuoka Tomokazu, and Hirotaka Haro
Subjects: medicine.medical_specialty, animal structures, lcsh:Surgery, Anterior cervical discectomy and fusion, Aspiration pneumonia, flexible endoscopic evaluation of swallowing, otorhinolaryngologic diseases, Medicine, Orthopedics and Sports Medicine, Prospective cohort study, Asthma, eating assessment tool, business.industry, postoperative respiratory complications, Incidence (epidemiology), lcsh:RD1-811, Airway obstruction, medicine.disease, Dysphagia, Surgery, Otorhinolaryngology, Original Article, Neurology (clinical), Erratum, medicine.symptom, business, anterior cervical discectomy and fusion
Abstract: Introduction Postoperative respiratory complications (PRC) are one of the most serious complications. Potentially life-threatening accidents can occur after an anterior cervical discectomy and fusion (ADF), such as airway obstruction and aspiration pneumonia. Despite numerous studies, preoperative predictive and preventive methodology has yet to be established. As reported in our previous study, the evaluation of preoperative dysphagia using the eating assessment tool (EAT-10) and a flexible endoscopic evaluation of swallowing (FEES) is useful for predicting the incidence and risk factors of dysphagia after ADF. Methods This prospective study comprised 60 consecutive patients who underwent ADF. An otolaryngologist and a speech-language-hearing therapist preoperatively and 1 week postoperatively evaluated dysphagia using EAT-10 and Hyodo-Komagane (H-K) scores during FEES. Patient demographics, comorbidities, and pre- and postoperative dysphagia were compared between patients with and without PRC. Results Seven of 60 (11.6%) patients had preoperative dysphagia diagnosed using the H-K score. A significant positive correlation existed between the pre- and postoperative H-K scores. Of all 60 cases, eight (13.3%) had PRC. Among them, two required reintubation due to airway obstruction and six had aspiration pneumonia. The PRC(+) group was significantly older and more prone to diabetes and asthma. The preoperative H-K score of the PRC(+) group was significantly higher than that of the PRC(-) group. Postoperatively, but not preoperatively, EAT-10 was significantly higher in the PRC(+) group. Conclusions Preoperative dysphagia may potentially exacerbate postoperative dysphagia after ADF. A preoperative evaluation of dysphagia using the H-K score during FEES is a useful method for predicting and reducing the risk of PRC. Level of Evidence: 3.
Published: 2021

28. A Case of Saccular Cyst with Extralaryngeal Extension Through the Cricothyroid Membrane

Author: Keisuke Masuyama, Masashi Osano, Hiroki Ishii, Shota Tanaka, Daiju Sakurai, and Tomokazu Matsuoka
Subjects: Otorhinolaryngology, business.industry, Cricothyroid membrane, Medicine, Saccular cyst, Anatomy, business
Published: 2021

29. A Case of Spontaneous Leakage of Cerebrospinal Fluid into the Middle Ear Found with Fatal Bacterial Meningitis

Author: Akira Hayashi, Hiroki Ishii, Daiju Sakurai, Ayumi Shimamura, Mari Takahashi, Shota Tanaka, Kiwako Horiuchi, and Tomokazu Matsuoka
Subjects: Pathology, medicine.medical_specialty, Cerebrospinal fluid, medicine.anatomical_structure, Otorhinolaryngology, business.industry, Middle ear, medicine, Bacterial meningitis, business, Leakage (electronics)
Published: 2021

30. A Study on Tympanoplasty in Chronic Otitis Media

Author: Daiju Sakurai, Kiwako Horiuchi, Tomokazu Matsuoka, Shota Tanaka, Hiroki Ishii, Ayumi Shimamura, Akira Hayashi, Mari Takahashi, and Shuichiro Endo
Subjects: medicine.medical_specialty, Otorhinolaryngology, business.industry, medicine.medical_treatment, Chronic otitis, Medicine, Tympanoplasty, business, Surgery
Published: 2021

31. A Questionnaire Survey Regarding Postoperative Effects on the Socio-Economic Status of Laryngectomized Patients

Author: Keisuke Masuyama, Kyoko Miyazaki, and Daiju Sakurai
Subjects: Speech and Hearing, medicine.medical_specialty, Family medicine, medicine, Questionnaire, LPN and LVN, Psychology, Socioeconomic status
Published: 2021

32. Toxic epidermal necrolysis associated with nivolumab treatment for head and neck cancer

Author: Toyoyuki Hanazawa, Michiyo Nakano, Daiju Sakurai, Naoko Kikkawa, Sawako Hamasaki, Miki Sunagane, Yukiyoshi Mita, Keiichi Koshizuka, and Takeshi Suzuki
Subjects: medicine.medical_specialty, lcsh:Medicine, Case Report, Case Reports, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, toxic epidermal necrolysis, Tongue, medicine, In patient, Basal cell, Adverse effect, nivolumab, lcsh:R5-920, business.industry, lcsh:R, Head and neck cancer, General Medicine, medicine.disease, Dermatology, Toxic epidermal necrolysis, Stevens‐Johnson syndrome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Fatal disease, head and neck cancer, Nivolumab, lcsh:Medicine (General), business
Abstract: This report is the first to document TEN caused by nivolumab treatment in head and neck cancer. We believe this article can contribute significantly in understanding the principles of nivolumab treatment in patients with head and neck cancer.
Published: 2020

33. A Case of Maxillary Sinus Small Cell Carcinoma with Cancer-associated Retinopathy

Author: Keisuke Masuyama, Daiju Sakurai, Kyousuke Hatsushika, Takaaki Yonaga, Tomokazu Matsuoka, and Ayumi Shimamura
Subjects: medicine.medical_specialty, medicine.anatomical_structure, Maxillary sinus, business.industry, medicine, Radiology, business, medicine.disease, Small-cell carcinoma, Cancer associated retinopathy
Published: 2020

34. Therapeutic Efficacy and Biomarker of Allergen Immunotherapy

Author: Daiju Sakurai
Subjects: Allergen immunotherapy, Otorhinolaryngology, business.industry, Immunology, Biomarker (medicine), Medicine, business
Published: 2020

35. A clinical study of sinonasal teratocarcinosarcoma: Report of four cases

Author: Toyoyuki Hanazawa, Rie Shimmi, Tomohisa Iinuma, Yuji Ohki, Daiju Sakurai, and Kazuki Yamasaki
Subjects: Clinical study, medicine.medical_specialty, Oncology, Otorhinolaryngology, Sinonasal teratocarcinosarcoma, medicine, Dermatology
Published: 2020

36. The examination of past cases of refractory oropharyngeal ulcer

Author: Daiju Sakurai
Subjects: medicine.medical_specialty, Refractory, business.industry, Medicine, business, Surgery
Published: 2020

37. A rare case of intracytoplasmic mucin-rich nasopharyngeal carcinoma

Author: Yohei Yamaguchi, Toru Odate, Kumiko Nakazawa, Naoki Oishi, Kunio Mochizuki, Tatsuya Shimizu, Kiwako Horiuchi, Hiroki Ishii, Daiju Sakurai, and Tetsuo Kondo
Subjects: Epstein-Barr Virus Infections, Herpesvirus 4, Human, Histology, Nasopharyngeal Carcinoma, Mucins, Humans, Nasopharyngeal Neoplasms, General Medicine, In Situ Hybridization, Fluorescence, Pathology and Forensic Medicine
Abstract: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated tumor with a high incidence in Asian countries. NPC is a type of squamous cell carcinoma originating from the nasopharyngeal mucosa. Although rare, NPCs show some uncommon histologic variants; these variations remain to be understood. We described the cytologic characteristics of a rare NPC variant with abundant intracytoplasmic mucin. A 37-year-old Japanese man presented to our hospital with bilateral ear discomfort and palpable lymph nodes. Nasopharyngeal biopsy showed tumor cells with abundant intracytoplasmic, Alcian blue-PAS-positive mucin. Immunohistochemical analysis demonstrated that the tumor cells were positive for p40 and p53. Epstein-Barr encoding region (EBER) in situ hybridization (ISH) showed EBV infection of the tumor cells. Fluorescence in situ hybridization (FISH) using MAML2 break-apart probes did not show split signals. Fine needle aspiration biopsy (FNAB) cytology of the metastatic lymph nodes was also performed. Smear samples had a necrotic and inflammatory background with both lymphocyte and neutrophil infiltration. Highly cellular tumor clusters and dispersed cells with naked nuclei were observed. The tumor cells showed a clear cytoplasm with distinct cell borders. Intracytoplasmic mucin pushing the nucleus to the periphery was observed in the scattered tumor cells in a liquid-based cytology sample. Given these findings, the final diagnosis was advanced nasopharyngeal carcinoma; cisplatin-based chemoradiation therapy was performed as the first-line treatment. The tumor recurred 8 months after completing the treatment. The recurrent nasopharyngeal tumor was a typical non-keratinizing NPC and lacked intracytoplasmic mucin.
Published: 2022

38. High expression of protein tyrosine kinase 7 in oral squamous cell carcinoma: Clinicopathological correlation and prognosis relevance

Author: Yujiro Kimura, Kunio Yoshizawa, Asami Hotta‐Osada, Akinori Moroi, Hiroki Ishii, Daiju Sakurai, Masao Saitoh, Naoki Oishi, Tetsuo Kondo, and Koichiro Ueki
Subjects: Squamous Cell Carcinoma of Head and Neck, Humans, Receptor Protein-Tyrosine Kinases, Mouth Neoplasms, Protein-Tyrosine Kinases, Prognosis, General Dentistry, Cell Adhesion Molecules
Abstract: The purpose of this study was to evaluate the association between the immunohistochemistry (IHC) of protein tyrosine kinase 7 (PTK7) expression and clinicopathological factors of oral squamous cell carcinoma (OSCC).Tissue specimens were obtained from 80 patients with primary OSCC. IHC scoring was conducted according to the rate of positive cell and staining intensity. We used the IHC score to classify the degree of PTK7 expression and evaluate clinicopathological factors and prognosis.The number of the high expression group (IHC Score 2 or 3) was 45 cases and that of the low expression group (IHC Score 0 or 1) was 35 cases. A significant difference between high expression and low expression groups was found in the N category (p = .008), degree of differentiation (p .001), and pattern of invasion (p .001). In accordance with the exacerbation of OSCC with respect to three parameters (N category, degree of differentiation, and pattern of invasion), the ratio of high expression of PTK7 increased. The overall 5-year survival rate was 59.3% in the high expression group and 87.3% in the low expression group (p .05). The pathological prognostic signs affecting overall survival were evaluated by univariate analysis and multivariate analysis with Cox proportional hazards model and showed an association with lymph node metastasis and invasion patterns.This study suggests that a high IHC score of PTK7 is a potential biomarker for predicting potential metastasis.
Published: 2021

39. Efficacy of Desloratadine and Levocetirizine in Patients with Cedar Pollen-Induced Allergic Rhinitis: A Randomized, Double-Blind Study

Author: Syuji Yonekura, Yohei Kawasaki, Daiju Sakurai, Riyo Yoneda, Toyoyuki Hanazawa, Toshioki Sakurai, Tomohisa Iinuma, Junya Kurita, and Yoshitaka Okamoto
Subjects: Adult, Male, Histamine H1 Antagonists, Non-Sedating, medicine.medical_specialty, medicine.medical_treatment, Immunology, Placebo, Gastroenterology, Levocetirizine, Placebos, Double blind study, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Internal medicine, medicine, Clinical endpoint, Humans, Immunology and Allergy, 030223 otorhinolaryngology, Cedrus, chemistry.chemical_classification, Desloratadine, Cross-Over Studies, business.industry, Rhinitis, Allergic, Seasonal, General Medicine, Loratadine, Cetirizine, Clinical trial, 030228 respiratory system, chemistry, Pollen, Female, Antihistamine, business, medicine.drug, Tricyclic
Abstract: Background: No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis. Objective: This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system. Methods: A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m3. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group. Results: The difference in TNSS from placebo was –2.42 (p < 0.0001) with levocetirizine and –1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected. Conclusion: Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown. Clinical Trial Registration number: UMIN ID: UMIN000029653.
Published: 2019

40. Measuring the Anti-moesin Antibody Titer May Diagnose Patients with Early Stage Granulomatosis with Polyangiitis Limited to the Upper Respiratory Tract

Author: Daiju Sakurai, Tomohisa Iinuma, Yuichiro Otsuka, Toyoyuki Hanazawa, Yoshitaka Okamoto, Naoki Kunii, Kazuki Yamasaki, and Kazuo Suzuki
Subjects: Pathology, medicine.medical_specialty, medicine.anatomical_structure, business.industry, Moesin, medicine, Antibody titer, Stage (cooking), business, Granulomatosis with polyangiitis, medicine.disease, Respiratory tract
Published: 2019

41. A Case of Central Mucoepidermoid Carcinoma of the Mandible in which the Primary Site was Difficult to Locate

Author: Yoshitaka Okamoto, Toshioki Sakurai, Kazuki Yamasaki, Daiju Sakurai, Keita Sasaki, Go Sasahara, Syuji Yonekura, Toyoyuki Hanazawa, and Yusuke Okuma
Subjects: Orthodontics, Otorhinolaryngology, Mucoepidermoid carcinoma, business.industry, Mandible, medicine, medicine.disease, business
Published: 2019

42. Activated iNKT cells enhance the anti-tumor effect of antigen specific CD8 T cells on mesothelin-expressing salivary gland cancer

Author: Daiju Sakurai, Shinichiro Motohashi, Yuji Makita, Yoshitaka Okamoto, Toshinori Nakayama, Akane Suzuki, Naoki Kunii, and Fumie Ihara
Subjects: 0301 basic medicine, Cancer Research, Adoptive cell transfer, endocrine system diseases, Natural kiiler T-cells, T cell, medicine.medical_treatment, CD8-Positive T-Lymphocytes, GPI-Linked Proteins, Immunotherapy, Adoptive, lcsh:RC254-282, Antibodies, Cell therapy, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, Antigen, Adoptive immunotherapy, Cell Line, Tumor, Genetics, medicine, Cytotoxic T cell, Humans, Mesothelin, Chimeric antigen receptor, Receptors, Chimeric Antigen, Cytotoxic T lymphocyte, Salivary gland cancer, biology, Chemistry, Immunotherapy, Salivary Gland Neoplasms, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Coculture Techniques, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Natural Killer T-Cells, K562 Cells, Research Article
Abstract: Background Salivary gland cancers are not sensitive to conventional radiotherapy or chemotherapy regimens. Therefore, the development of a new treatment strategy is of critical importance for improving the prognosis. We examined the expression of mesothelin molecules in salivary gland cancers and the efficacy of adoptive cell therapy based on mesothelin-specific chimeric antigen receptor transduced T cells. Methods The expression of mesothelin molecule was studied in salivary gland cancer samples obtained from 16 patients as well as a salivary gland cancer cell line (A-253) and five other cell lines. The activation of mesothelin-specific chimeric antigen receptor-expressing CD8 T cells after stimulation with mesothelin and the effects of invariant natural killer T cells on this activation were evaluated. Results Mesothelin was detected in the A-253 cells and the surgical specimens except for the case of squamous cell carcinoma to various degrees. Following stimulation with mesothelin expressing cancer cells, chimeric antigen receptor T cells were dose-dependently activated; this activation was enhanced by co-culture with invariant natural killer T cells and subsequently abrogated by treatment with anti-interferon-γ antibodies. Furthermore, the cytotoxicity of chimeric antigen receptor T cells against various cancer cells was further augmented by invariant natural killer T cells. Conclusions The use of adoptive transfer with mesothelin-specific chimeric antigen receptor-expressing CD8 T cells against salivary gland cancers is an effective therapy and invariant natural killer T cells are expected to be used in adjuvant treatment for T cell-based immunotherapy. Electronic supplementary material The online version of this article (10.1186/s12885-018-5179-7) contains supplementary material, which is available to authorized users.
Published: 2018

43. Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies

Author: Bousquet, Jean, Cristol, Jean-Paul, Czarlewski, Wienczyslawa, Anto, Josep M, Martineau, Adrian, Haahtela, Tari, Fonseca, Susana C, Iaccarino, Guido, Blain, Hubert, Fiocchi, Alessandro, Canonica, G Walter, Fonseca, Joao A, Vidal, Alain, Choi, Hak-Jong, Kim, Hyun Ju, Le Moing, Vincent, Reynes, Jacques, Sheikh, Aziz, Akdis, Cezmi A, Zuberbier, Torsten, Amir Hamzah Abdul Latiff, Baharudin, Abdullah, Werner, Aberer, Nancy, Abusada, Ian, Adcock, Alejandro, Afani, Ioana, Agache, Xenofon, Aggelidis, Jenifer, Agustin, Cezmi, A Akdis, Mübeccel, Akdis, Mona, Al-Ahmad, Abou Al-Zahab Bassam, Hussam, Alburdan, Oscar, Aldrey-Palacios, Emilio Alvarez Cuesta, Hiba Alwan Salman, Ashraf, Alzaabi, Salma, Amade, Gene, Ambrocio, Rosana, Angles, Isabella, Annesi-Maesano, Ignacio, J Ansotegui, Josep, M Anto, Paula Ara Bardajo, Stefania, Arasi, Margarete, Arrais, Hasan, Arshad, Maria-Cristina, Artesani, Estrella, Asayag, Francesca, Avolio, Khuzama, Azhari, Claus, Bachert, Diego, Bagnasco, Ilaria, Baiardini, Nissera, Bajrović, Petros, Bakakos, Sergio Bakeyala Mongono, Christine, Balotro-Torres, Sergio, Barba, Cristina, Barbara, Elsa, Barbosa, Bruno, Barreto, Joan, Bartra, Xavier, Basagana, Eric, D Bateman, Lkhagvaa, Battur, Anna, Bedbrook, Martín Bedolla Barajas, Bianca, Beghé, Antra, Bekere, Elizabeth, Bel, Ali Ben Kheder, Mikael, Benson, Elena-Camelia, Berghea, Karl-Christian, Bergmann, Roberto, Bernardini, David, Bernstein, Mike, Bewick, Slawomir, Bialek, Artur, Białoszewski, Thomas, Bieber, Nils, E Billo, Maria-Beatrice, Bilo, Carsten, Bindslev-Jensen, Leif, Bjermer, Hubert, Blain, Irina, Bobolea, Malgorzata Bochenska Marciniak, Christine, Bond, Attilio, Boner, Matteo, Bonini, Sergio, Bonini, Sinthia, Bosnic-Anticevich, Isabelle, Bosse, Sofia, Botskariova, Jacques, Bouchard, Louis-Philippe, Boulet, Rodolphe, Bourret, Philippe, Bousquet, Fulvio, Braido, Andrew, Briggs, Christopher, E Brightling, Jan, Brozek, Luisa, Brussino, Roland, Buhl, Roxana, Bumbacea, Rosalva, Buquicchio, María-Teresa Burguete Cabañas, Andrew, Bush, William, W Busse, Jeroen, Buters, Fernan, Caballero-Fonseca, Moïses, A Calderon, Mario, Calvo, Paulo, Camargos, Thierry, Camuzat, R Canevari, F, Antonio, Cano, G Walter Canonica, Arnaldo, Capriles-Hulett, Luis, Caraballo, Vicky, Cardona, Kai-Hakon, Carlsen, Jonas Carmona Pirez, Jorge, Caro, Warner, Carr, Pedro, Carreiro-Martins, Fredelita, Carreon-Asuncion, Ana-Maria, Carriazo, Carme Carrion, Y Ribas, Thomas, Casale, Mary-Ann, Castor, Elizabeth, Castro, G Caviglia, A, Lorenzo, Cecchi, Alfonso Cepeda Sarabia, Maciej, Chalubinski, Ramanathan, Chandrasekharan, Yoon-Seok, Chang, Victoria, Chato-Andeza, Lida, Chatzi, Christina, Chatzidaki, Niels, H Chavannes, Claudia Chaves Loureiro, Aurora-Alejandra Chavez Garcia, Marta, Chelninska, Yuzhi, Chen, Lei, Cheng, Sharon, Chinthrajah, Tomas, Chivato, Ekaterine, Chkhartishvili, George, Christoff, Henry, Chrystyn, Derek, K Chu, Antonio, Chua, Alexander, Chuchalin, Kian Fan Chung, Alberto, Cicerán, Cemal, Cingi, Giorgio, Ciprandi, Ieva, Cirule, Ana-Carla, Coelho, Enrico, Compalati, Jannis, Constantinidis, Jaime Correia de Sousa, Elisio Manuel Costa, David, Costa, María Del Carmen Costa Domínguez, André, Coste, Cottini, M, Linda, Cox, Carlos, Crisci, Maria Angiola Crivellaro, Alvaro, A Cruz, John, Cullen, Adnan, Custovic, Biljana, Cvetkovski, Wienczyslawa, Czarlewski, Gennaro, D'Amato, Jane da Silva, Ronald, Dahl, Sven-Erik, Dahlen, Vasilis, Daniilidis, Louei Darjazini Nahhas, Ulf, Darsow, Janet, Davies, Frédéric de Blay, Giulia De Feo, Eloisa De Guia, José-Ricardo De la Torre Navarrete, Chato De Los Santos, Esteban De Manuel Keenoy, Govert De Vries, Diana, Deleanu, Pascal, Demoly, Judah, Denburg, Philippe, Devillier, Alain, Didier, Sanja Dimic Janjic, Maria, Dimou, Anh Tuan Dinh-Xuan, Ratko, Djukanovic, Maria Do Ceu Texeira, Dejan, Dokic, Margarita Gabriela Domínguez Silva, Habib, Douagui, Nikolaos, Douladiris, Maria, Doulaptsi, Gérard, Dray, Ruta, Dubakiene, Eve, Dupas, Stephen, Durham, Marzia, Duse, Mark, Dykewicz, Didier, Ebo, Natalija, Edelbaher, Thomas, Eiwegger, Patrik, Eklund, Yehia, El-Gamal, Zeinab, A El-Sayed, Shereen, S El-Sayed, Magda, El-Seify, Regina, Emuzyte, Lourdes, Enecilla, Marina, Erhola, Heidilita, Espinoza, Jesús Guillermo Espinoza Contreras, John, Farrell, Lenora, Fernandez, Paola Fimbres Jimenez, Antje Fink Wagner, Alessandro, Fiocchi, Wytske, J Fokkens, Lenia, Folletti, Joao, A Fonseca, Jean-François, Fontaine, Francesco, Forastiere, Jose Miguel Fuentes Pèrez, Emily, Gaerlan-Resureccion, Mina, Gaga, José Luis Gálvez Romero, Amiran, Gamkrelidze, Alexis, Garcia, Cecilia Yvonne García Cobas, María de la Luz Hortensia García Cruz, Valeria Garcia Ortiz, Jacques, Gayraud, Matteo, Gelardi, Bilun, Gemicioglu, Dimitra, Gennimata, Sonya, Genova, José, Gereda, Roy Gerth van Wijk, Antonio, Giuliano, René-Maximiliano, Gomez, Miguel-Ange Gonzalez Ballester, Sandra González Diaz, Maia, Gotua, Christos, Grigoreas, Ineta, Grisle, Marta, Guidacci, Nick, Guldemond, Zdenek, Gutter, Antonieta, Guzmán, Tari, Haahtela, Ramsa, Halloum, David, Halpin, Eckard, Hamelmann, Suleiman, Hammadi, Richard, Harvey, Enrico, Heffler, Joachim, Heinrich, Adnan, Hejjaoui, Birthe, Hellquist-Dahl, Luiana Hernández Velázquez, Mark, Hew, Elham, Hossny, Peter, Howarth, Martin, Hrubiško, Yunuen Rocío Huerta Villalobos, Marc, Humbert, Salina, Husain, Michael, Hyland, Guido, Iaccarino, Moustafa, Ibrahim, Nataliya, Ilina, Maddalena, Illario, Cristoforo, Incorvaia, Antonio, Infantino, Carla, Irani, Zhanat, Ispayeva, Juan Carlos Ivancevich, Edgardo Ej Jares, Deborah, Jarvis, Ewa, Jassem, Klemen, Jenko, Rubén Darío Jiméneracruz Uscanga, Sebastian, L Johnston, Guy, Joos, Maja, Jošt, Kaja, Julge, Ki-Suck, Jung, Jocelyne, Just, Marek, Jutel, Igor, Kaidashev, Omer, Kalayci, Fuat, Kalyoncu, Jeni, Kapsali, Przemyslaw, Kardas, Jussi, Karjalainen, Carmela, A Kasala, Michael, Katotomichelakis, Loreta, Kavaliukaite, Kazi, S Bennoor, Thomas, Keil, Paul, Keith, Musa, Khaitov, Nikolai, Khaltaev, You-Young, Kim, Bruce, Kirenga, Jorg, Kleine-Tebbe, Ludger, Klimek, Fanny, W Ko, Bernard Koffi N'Goran, Evangelia, Kompoti, Peter, Kopač, Gerard, Koppelman, Anja Koren Jeverica, Seppo, Koskinen, Mitja, Košnik, Tomasz, Kostka, Kosta, V Kostov, Marek, L Kowalski, Tanya, Kralimarkova, Karmen Kramer Vrščaj, Helga, Kraxner, Samo, Kreft, Vicky, Kritikos, Dmitry, Kudlay, Mikael, Kuitunen, Inger, Kull, Piotr, Kuna, Maciej, Kupczyk, Violeta, Kvedariene, Marialena, Kyriakakou, Nika, Lalek, Massimo, Landi, Stephen, Lane, Désiree, E Larenas-Linnemann, Susanne, Lau, Daniel, Laune, Jorge, Lavrut, Lan, Le, Martina, Lenzenhuber, Gualtiero, Leo, Marcus, Lessa, Michael, Levin, Jing, Li, Philip, Lieberman, Giuseppe, Liotta, Brian, Lipworth, Xuandao, Liu, Rommel, Lobo, Karin, C Lodrup Carlsen, Carlo, Lombardi, Renaud, Louis, Stelios, Loukidis, Olga, Lourenço, Jorge, A Luna Pech, Bojan, Madjar, Enrico, Maggi, Antoine, Magnan, Bassam, Mahboub, Alpana, Mair, Anke-Hilse Maitland van der Zee, Mika, Makela, Michael, Makris, Hans-Jorgen, Malling, Mariana, Mandajieva, Patrick, Manning, Manolis, Manousakis, Pavlos, Maragoudakis, Gianluigi, Marseglia, Gailen, Marshall, Mohammad Reza Masjedi, Jorge, F Máspero, Juan José Matta Campos, Marcus, Maurer, Sandra, Mavale-Manuel, Cem, Meço, Erik, Melén, Giovanni, Melioli, Elisabete, Melo-Gomes, Eli, O Meltzer, Enrica, Menditto, Andrew, Menzies-Gow, Hans, Merk, Jean-Pierre, Michel, Yann, Micheli, Neven, Miculinic, Luís, Midão, Florin, Mihaltan, Nikolaos, Mikos, Manlio, Milanese, Branislava, Milenkovic, Dimitrios, Mitsias, Bassem, Moalla, Giuliana, Moda, María Dolores Mogica Martínez, Yousser, Mohammad, Frances-Montserrat, Moharra, Mostafa, Moin, Mathieu, Molimard, Isabelle, Momas, Monique, Mommers, Alessandro, Monaco, Stephen, Montefort, Lucia-Elvira, Montenegro, Riccardo, Monti, Dory, Mora, Mario, Morais-Almeida, Ralph, Mösges, Badr Eldin Mostafa, Joaquim, Mullol, Lars, Münter, Antonella, Muraro, Ruth, Murray, Antonio, Musarra, Tihomir, Mustakov, Robert, Naclerio, Kari, C Nadeau, Rachel, Nadif, Alla, Nakonechna, Leyla, Namazova-Baranova, Gretchen, Navarro-Locsin, Hugo, Neffen, Kristof, Nekam, Angelos, Neou, Eustachio, Nettis, Daniel, Neuberger, Laurent, Nicod, Stefania, Nicola, Verena, Niederberger-Leppin, Marek, Niedoszytko, Antonio, Nieto, Ettore, Novellino, Elizabete, Nunes, Dieudonné, Nyembue, Robyn, E O'Hehir, Cvetanka, Odjakova, Ken, Ohta, Yoshitaka, Okamoto, Kimi, Okubo, Brian, Oliver, Gabrielle, L Onorato, Maria Pia Orru, Solange, Ouédraogo, Kampadilemba, Ouoba, Francisco-Javier, Padilla, Pier Luigi Paggiaro, Aris, Pagkalos, Pajno, Giovanni Battista, Gianni, Pala, P Palaniappan, S, Isabella, Pali-Schöll, Susanna, Palkonen, Stephen, Palmer, Carmen Panaitescu Bunu, Petr, Panzner, Nikos, G Papadopoulos, Vasilis, Papanikolaou, Alberto, Papi, Bojidar, Paralchev, Giannis, Paraskevopoulos, Hae-Sim, Park, Giovanni, Passalacqua, Vincenzo, Patella, Ian, Pavord, Ruby, Pawankar, Soren, Pedersen, Susete, Peleve, Simona, Pellegino, Ana, Pereira, Mariana, Pereira, Tamara, Pérez, Andrea, Perna, Diego, Peroni, Oliver, Pfaar, Nhân, Pham-Thi, Bernard, Pigearias, Isabelle, Pin, Konstantina, Piskou, Constantinos, Pitsios, Davor, Plavec, Dagmar, Poethig, Wolfgang, Pohl, Antonija Poplas Susic, Todor, A Popov, Fabienne, Portejoie, Paul, Potter, Lars, Poulsen, Alexandra, Prados-Torres, Fotis, Prarros, David, Price, Emmanuel, Prokopakis, Francesca, Puggioni, Elisa, Puig-Domenech, Robert, Puy, Klaus, Rabe, Silvia, Rabotti, Filip, Raciborski, Josephine, Ramos, Cristina, Recalcati, Marysia, T Recto, Shereen, M Reda, Frederico, S Regateiro, Norbert, Reider, Sietze, Reitsma, Susana, Repka-Ramirez, Erminia, Ridolo, Janet, Rimmer, Daniela Rivero Yeverino, José Angelo Rizzo, Carlos, Robalo-Cordeiro, Graham, Roberts, Karen, Robles, Nicolas, Roche, Mónica Rodríguez González, Eréndira Rodríguez Zagal, Giovanni, Rolla, Christine, Rolland, Regina, Roller-Wirnsberger, Miguel Roman Rodriguez, Antonino, Romano, Jan, Romantowski, Philippe, Rombaux, Joel, Romualdez, Jose, Rosado-Pinto, Nelson, Rosario, Lanny, Rosenwasser, Oliviero, Rossi, Menachem, Rottem, Philip, W Rouadi, Nikoleta, Rovina, Irma Rozman Sinur, Mauricio, Ruiz, Lucy Tania Ruiz Segura, Dermot, Ryan, Hironori, Sagara, Daiki, Sakai, Daiju, Sakurai, Wafaa, Saleh, Johanna, Salimaki, Konstantinos, Samitas, Boleslaw, Samolinski, María Guadalupe Sánchez Coronel, Mario, Sanchez-Borges, Jaime, Sanchez-Lopez, Melissa, Sansonna, Codrut, Sarafoleanu, Faradiba Sarquis Serpa, Joaquin, Sastre, Eleonora, Savi, Agne, Savonyte, Bisher, Sawaf, Glenis, K Scadding, Sophie, Scheire, Peter, Schmid-Grendelmeier, Juan Francisco Schuhl, Holger, Schunemann, Maria, Schvalbová, Jorgen, Schwarze, Nicola, Scichilone, Gianenrico, Senna, Cecilia, Sepúlveda, Elie, Serrano, Sara, Shamai, Aziz, Sheikh, Mike, Shields, Vasil, Shishkov, Nikos, Siafakas, Alexander, Simeonov, Estelle Fer Simons, Juan Carlos Sisul, Brigita, Sitkauskiene, Ingelbjorg, Skrindo, Tanja Soklič Košak, Dirceu, Solé, Martin, Sondermann, Talant, Sooronbaev, Manuel, Soto-Martinez, Manuel, Soto-Quiros, Barnaro Sousa Pinto, Milan, Sova, Michael, Soyka, Krzysztof, Specjalski, Annette, Sperl, Otto, Spranger, Sofia, Stamataki, Lina, Stefanaki, Cristiana, Stellato, Rafael, Stelmach, Timo, Strandberg, Petra, Stute, Abirami, Subramaniam, Charlotte Suppli Ulrik, Michael, Sutherland, Silvia, Sylvestre, Aikaterini, Syrigou, Luis Taborda Barata, Nadejda, Takovska, Rachel, Tan, Frances, Tan, Vincent, Tan, Ing Ping Tang, Masami, Taniguchi, Line, Tannert, Pongsakorn, Tantilipikorn, Jessica, Tattersall, Filippo, Tesi, Uta, Thieme, Carel, Thijs, Mike, Thomas, Teresa, To, Ana Maria Todo-Bom, Alkis, Togias, Peter-Valentin, Tomazic, Vesna, Tomic-Spiric, Sanna, Toppila-Salmi, Maria-José Torres Jaen, Elina, Toskala, Massimo, Triggiani, Nadja, Triller, Katja, Triller, Ioanna, Tsiligianni, Uberti, M, Ruxandra, Ulmeanu, Jure, Urbancic, Marilyn Urrutia Pereira, Martina, Vachova, Felipe, Valdés, Rudolf, Valenta, Marylin Valentin Rostan, Antonio, Valero, Arunas, Valiulis, Mina, Vallianatou, Erkka, Valovirta, Michiel Van Eerd, Eric Van Ganse, Marianne van Hage, Olivier, Vandenplas, Tuula, Vasankari, Dafina, Vassileva, Cesar Velasco Munoz, Maria Teresa Ventura, Cécilia, Vera-Munoz, Frédéric, Viart, Dilyana, Vicheva, Pakit, Vichyanond, Petra, Vidgren, Giovanni, Viegi, Claus, Vogelmeier, Leena Von Hertzen, Theodoros, Vontetsianos, Dimitris, Vourdas, Vu Tran Thien Quan, Martin, Wagenmann, Samantha, Walker, Dana, Wallace, Yun De Wang, Susan, Waserman, Katrin, Wehner, Magnus, Wickman, Sian, Williams, Dennis, Williams, Nicola, Wilson, Gary, Wong, Kent, Woo, Lucyna, Wozniak, John, Wright, Piotr, Wroczynski, Paraskevi, Xepapadaki, Plamen, Yakovliev, Masao, Yamaguchi, Kwok, Yan, Yoke Yeow Yap, Mais, Yassin, Barbara, Yawn, Panayiotis, Yiallouros, Arzu, Yorgancioglu, Shigemi, Yoshihara, Ian, Young, Osman, B Yusuf, Asghar, Zaidi, Fares, Zaitoun, Petra, Zalud, Heather, Zar, T Zedda, M, Mario, E Zernotti, Luo, Zhang, Nanshan, Zhong, Mihaela, Zidarn, Torsten, Zuberbier, Celia, Zubrinich, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Barts & The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Central Hospital [Finland] (HUCH), Departamento de Geociencias, Ambiente e Ordenamento do Territorio (DGAOT), Universidade do Porto = University of Porto, University of Naples Federico II = Università degli studi di Napoli Federico II, Euromov (EuroMov), Université de Montpellier (UM), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Center of Research in Health Technologies and Information Systems (CINTESIS), AgroParisTech, World Institute of Kimchi [Gwangju], Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Edinburgh, Universität Zürich [Zürich] = University of Zurich (UZH), Humboldt-Universität zu Berlin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Universidade do Porto, University of Naples Federico II, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), MORNET, Dominique, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bousquet J., Cristol J.-P., Czarlewski W., Anto J.M., Martineau A., Haahtela T., Fonseca S.C., Iaccarino G., Blain H., Fiocchi A., Canonica G.W., Fonseca J.A., Vidal A., Choi H.-J., Kim H.J., Le Moing V., Reynes J., Sheikh A., Akdis C.A., Zuberbier T., Abdul Latiff A.H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis M., Al-Ahmad M., Al-Zahab Bassam A., Alburdan H., Aldrey-Palacios O., Alvarez Cuesta E., Alwan Salman H., Alzaabi A., Amade S., Ambrocio G., Angles R., Annesi-Maesano I., Ansotegui I.J., Ara Bardajo P., Arasi S., Arrais M., Arshad H., Artesani M.-C., Asayag E., Avolio F., Azhari K., Bachert C., Bagnasco D., Baiardini I., Bajrovic N., Bakakos P., Bakeyala Mongono S., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Basagana X., Bateman E.D., Battur L., Bedbrook A., Bedolla Barajas M., Beghe B., Bekere A., Bel E., Ben Kheder A., Benson M., Berghea E.-C., Bergmann K.-C., Bernardini R., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N.E., Bilo M.-B., Bindslev-Jensen C., Bjermer L., Bobolea I., Bochenska Marciniak M., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L.-P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C.E., Brozek J., Brussino L., Buhl R., Bumbacea R., Buquicchio R., Burguete Cabanas M.-T., Bush A., Busse W.W., Buters J., Caballero-Fonseca F., Calderon M.A., Calvo M., Camargos P., Camuzat T., Canevari F., Cano A., Canonican G.W., Capriles-Hulett A., Caraballo L., Cardona V., Carlsen K.-H., Carmona Pirez J., Caro J., Carr W., Carreiro-Martins P., Carreon-Asuncion F., Carriazo A.-M., CarrionyRibas C., Casale T., Castor M.-A., Castro E., Caviglia A.G., Cecchi L., Cepeda Sarabia A., Chalubinski M., Chandrasekharan R., Chang Y.-S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N.H., Chaves Loureiro C., Chavez Garcia A.-A., Chelninska M., Chen Y., Cheng L., Chinthrajah S., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D.K., Chua A., Chuchalin A., Chung K.F., Ciceran A., Cingi C., Ciprandi G., Cirule I., Coelho A.-C., Compalati E., Constantinidis J., Correia de Sousa J., Costa E.M., Costa D., del Carmen Costa Dominguez M., Coste A., Cottini M., Cox L., Crisci C., Crivellaro M.A., Cruz A.A., Cullen J., Custovic A., Cvetkovski B., D'Amato G., da Silva J., Dahl R., Dahlen S.-E., Daniilidis V., Darjazini Nahhas L., Darsow U., Davies J., de Blay F., De Feo G., De Guia E., De la Torre Navarrete J.-R., De los Santos C., De Manuel Keenoy E., De Vries G., Deleanu D., Demoly P., Denburg J., Devillier P., Didier A., Dimic Janjic S., Dimou M., Dinh-Xuan A.T., Djukanovic R., Do Ceu Texeira M., Dokic D., Dominguez Silva M.G., Douagui H., Douladiris N., Doulaptsi M., Dray G., Dubakiene R., Dupas E., Durham S., Duse M., Dykewicz M., Ebo D., Edelbaher N., Eiwegger T., Eklund P., El-Gamal Y., El-Sayed Z.A., El-Sayed S.S., El-Seify M., Emuzyte R., Enecilla L., Erhola M., Espinoza H., Espinoza Contreras J.G., Farrell J., Fernandez L., Fimbres Jimenez P., Fink Wagner A., Fokkens W.J., Folletti L., Fontaine J.-F., Forastiere F., Fuentes Perez J.M., Gaerlan-Resureccion E., Gaga M., Galvez Romero J.L., Gamkrelidze A., Garcia A., Garcia Cobas C.Y., de la Luz Hortensia Garcia Cruz M., Ortiz V.G., Gayraud J., Gelardi M., Gemicioglu B., Gennimata D., Genova S., Gereda J., Gerth van Wijk R., Giuliano A., Gomez R.-M., Gonzalez Ballester M.-A., Gonzalez Diaz S., Gotua M., Grigoreas C., Grisle I., Guidacci M., Guldemond N., Gutter Z., Guzman A., Halloum R., Halpin D., Hamelmann E., Hammadi S., Harvey R., Heffler E., Heinrich J., Hejjaoui A., Hellquist-Dahl B., Hernandez Velazquez L., Hew M., Hossny E., Howarth P., Hrubisko M., Huerta Villalobos Y.R., Humbert M., Husain S., Hyland M., Ibrahim M., Ilina N., Illario M., Incorvaia C., Infantino A., Irani C., Ispayeva Z., Ivancevich J.C., Jares E.E., Jarvis D., Jassem E., Jenko K., Jimeneracruz Uscanga R.D., Johnston S.L., Joos G., Jost M., Julge K., Jung K.-S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu F., Kapsali J., Kardas P., Karjalainen J., Kasala C.A., Katotomichelakis M., Kavaliukaite L., Bennoor K.S., Keil T., Keith P., Khaitov M., Khaltaev N., Kim Y.-Y., Kirenga B., Kleine-Tebbe J., Klimek L., Ko F.W., Koffi N'Goran B., Kompoti E., Kopac P., Koppelman G., Koren Jeverica A., Koskinen S., Kosnik M., Kostka T., Kostov K.V., Kowalski M.L., Kralimarkova T., Kramer Vrscaj K., Kraxner H., Kreft S., Kritikos V., Kudlay D., Kuitunen M., Kull I., Kuna P., Kupczyk M., Kvedariene V., Kyriakakou M., Lalek N., Landi M., Lane S., Larenas-Linnemann D.E., Lau S., Laune D., Lavrut J., Le L., Lenzenhuber M., Leo G., Lessa M., Levin M., Li J., Lieberman P., Liotta G., Lipworth B., Liu X., Lobo R., Lodrup Carlsen K.C., Lombardi C., Louis R., Loukidis S., Lourenco O., Luna Pech J.A., Madjar B., Maggi E., Magnan A., Mahboub B., Mair A., Maitland van der Zee A.-H., Makela M., Makris M., Malling H.-J., Mandajieva M., Manning P., Manousakis M., Maragoudakis P., Marseglia G., Marshall G., Masjedi M.R., Maspero J.F., Matta Campos J.J., Maurer M., Mavale-Manuel S., Meco C., Melen E., Melioli G., Melo-Gomes E., Meltzer E.O., Menditto E., Menzies-Gow A., Merk H., Michel J.-P., Micheli Y., Miculinic N., Midao L., Mihaltan F., Mikos N., Milanese M., Milenkovic B., Mitsias D., Moalla B., Moda G., Mogica Martinez M.D., Mohammad Y., Moharra F.-M., Moin M., Molimard M., Momas I., Mommers M., Monaco A., Montefort S., Montenegro L.-E., Monti R., Mora D., Morais-Almeida M., Mosges R., Mostafa B.E., Mullol J., Munter L., Muraro A., Murray R., Musarra A., Mustakov T., Naclerio R., Nadeau K.C., Nadif R., Nakonechna A., Namazova-Baranova L., Navarro-Locsin G., Neffen H., Nekam K., Neou A., Nettis E., Neuberger D., Nicod L., Nicola S., Niederberger-Leppin V., Niedoszytko M., Nieto A., Novellino E., Nunes E., Nyembue D., O'Hehir R.E., Odjakova C., Ohta K., Okamoto Y., Okubo K., Oliver B., Onorato G.L., Orru M.P., Ouedraogo S., Ouoba K., Padilla F.-J., Paggiaro P.L., Pagkalos A., Pajno G., Pala G., Palaniappan S., Pali-Scholl I., Palkonen S., Palmer S., Panaitescu Bunu C., Panzner P., Papadopoulos N.G., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H.-S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pellegino S., Pereira A., Pereira M., Perez T., Perna A., Peroni D., Pfaar O., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Plavec D., Poethig D., Pohl W., Poplas Susic A., Popov T.A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puggioni F., Puig-Domenech E., Puy R., Rabe K., Rabotti S., Raciborski F., Ramos J., Recalcati C., Recto M.T., Reda S.M., Regateiro F.S., Reider N., Reitsma S., Repka-Ramirez S., Ridolo E., Rimmer J., Rivero Yeverino D., Rizzo J.A., Robalo-Cordeiro C., Roberts G., Robles K., Roche N., Rodriguez Gonzalez M., Rodriguez Zagal E., Rolla G., Rolland C., Roller-Wirnsberger R., Roman Rodriguez M., Romano A., Romantowski J., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rossi O., Rottem M., Rouadi P.W., Rovina N., Rozman Sinur I., Ruiz M., Ruiz Segura L.T., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Samitas K., Samolinski B., Sanchez Coronel M.G., Sanchez-Borges M., Sanchez-Lopez J., Sansonna M., Sarafoleanu C., Sarquis Serpa F., Sastre J., Savi E., Savonyte A., Sawaf B., Scadding G.K., Scheire S., Schmid-Grendelmeier P., Schuhl J.F., Schunemann H., Schvalbova M., Schwarze J., Scichilone N., Senna G., Sepulveda C., Serrano E., Shamai S., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E.F., Sisul J.C., Sitkauskiene B., Skrindo I., Soklic Kosak T., Sole D., Sondermann M., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Pinto B.S., Sova M., Soyka M., Specjalski K., Sperl A., Spranger O., Stamataki S., Stefanaki L., Stellato C., Stelmach R., Strandberg T., Stute P., Subramaniam A., Suppli Ulrik C., Sutherland M., Sylvestre S., Syrigou A., Taborda Barata L., Takovska N., Tan R., Tan F., Tan V., Tang I.P., Taniguchi M., Tannert L., Tantilipikorn P., Tattersall J., Tesi F., Thieme U., Thijs C., Thomas M., To T., Todo-Bom A.M., Togias A., Tomazic P.-V., Tomic-Spiric V., Toppila-Salmi S., Torres Jaen M.-J., Toskala E., Triggiani M., Triller N., Triller K., Tsiligianni I., Uberti M., Ulmeanu R., Urbancic J., Urrutia Pereira M., Vachova M., Valdes F., Valenta R., Valentin Rostan M., Valero A., Valiulis A., Vallianatou M., Valovirta E., Van Eerd M., Van Ganse E., van Hage M., Vandenplas O., Vasankari T., Vassileva D., Velasco Munoz C., Ventura M.T., Vera-Munoz C., Viart F., Vicheva D., Vichyanond P., Vidgren P., Viegi G., Vogelmeier C., Von Hertzen L., Vontetsianos T., Vourdas D., Tran Thien Quan V., Wagenmann M., Walker S., Wallace D., De Wang Y., Waserman S., Wehner K., Wickman M., Williams S., Williams D., Wilson N., Wong G., Woo K., Wozniak L., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y.Y., Yassin M., Yawn B., Yiallouros P., Yorgancioglu A., Yoshihara S., Young I., Yusuf O.B., Zaidi A., Zaitoun F., Zalud P., Zar H., Zedda M.T., Zernotti M.E., Zhang L., Zhong N., and Zidarn M.
Subjects: MAPK/ERK pathway, ARIA group, Allergy, [SDV]Life Sciences [q-bio], NF-KAPPA-B, debelost, Review, Pharmacology, Resveratrol, PROTECTS, chemistry.chemical_compound, 0302 clinical medicine, RESPIRATORY SYNDROME CORONAVIRUS, ENDOPLASMIC-RETICULUM STRESS, Medicine and Health Sciences, Immunology and Allergy, Medicine, OXIDATIVE STRESS, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, 2. Zero hunger, 0303 health sciences, RESPIRATORY, INSULIN-RESISTANCE, Muscle cell proliferation, SULFORAPHANE, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SIGNALING PATHWAY, Signal transduction, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, NRF2 ACTIVATORS, MUSCLE-CELL PROLIFERATION, Immunology, 610 Medicine & health, Lung injury, Settore MED/10 - Malattie Dell'Apparato Respiratorio, ACUTE LUNG INJURY, 03 medical and health sciences, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, udc:616.9, odpornost proti inzulinu, SULFORAPHANE PROTECTS, Transcription factor, PI3K/AKT/mTOR pathway, 030304 developmental biology, Science & Technology, business.industry, SARS-CoV-2, food, medicine.disease, chemistry, hranila, SYNDROME CORONAVIRUS, business, hrana, GREEN TEA
Abstract: There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
Published: 2020

44. [NEXT-GENERATION ARIA CARE PATHWAYS IN ALLERGIC RHINITIS]

Author: Yoshitaka, Okamoto, Ken, Ohta, Maho, Suzukawa, Shin, Ohta, Mitsuhiro, Okano, Daiju, Sakurai, and Hiroyuki, Tashimo
Subjects: Rhinitis, Allergic, Perennial, Humans, Immunotherapy, Rhinitis, Allergic
Published: 2020

45. Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study

Author: Nobuhiro Hanai, Makoto Arai, Tomoko Yamazaki, Nobuya Monden, Naomi Kudo, Tsutomu Ueda, Shunji Takahashi, Koichi Omori, Takashi Fujii, Takayuki Yamada, Shin Kariya, Issei Doi, Kiyoaki Tsukahara, Masafumi Yoshida, Yasushi Shimizu, Kenji Hanyu, Akihiro Homma, Takahiro Asakage, Daisuke Sano, Ryuji Yasumatsu, Akihito Watanabe, Daiju Sakurai, Moriyasu Yamauchi, Tomoya Yokota, Takeharu Ono, and Hitoshi Hirakawa
Subjects: 0301 basic medicine, medicine.medical_specialty, 03 medical and health sciences, Recurrent or metastatic head and neck cancer, 0302 clinical medicine, Japan, Surgical oncology, Internal medicine, Medicine, Humans, Adverse effect, Retrospective Studies, Real-world clinical practice, business.industry, Medical record, Head and neck cancer, Correction, Retrospective cohort study, Hematology, General Medicine, medicine.disease, Confidence interval, Clinical trial, Survival Rate, 030104 developmental biology, Nivolumab, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Multicenter retrospective study, Surgery, Original Article, business
Abstract: Background To fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice. Methods This was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records. Results Overall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1–27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2–12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141. Conclusions The effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141. Trial registration number UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)
Published: 2020

46. sj-pdf-1-ajr-10.1177_1945892420983646 - Supplemental material for LPCAT2 Methylation, a Novel Biomarker for the Severity of Cedar Pollen Allergic Rhinitis in Japan

Author: Watanabe, Hiroyuki, Miyake, Kunio, Matsuoka, Tomokazu, Kojima, Reiji, Daiju Sakurai, Masuyama, Keisuke, and Zentaro Yamagata
Subjects: 110315 Otorhinolaryngology, FOS: Clinical medicine
Abstract: Supplemental material, sj-pdf-1-ajr-10.1177_1945892420983646 for LPCAT2 Methylation, a Novel Biomarker for the Severity of Cedar Pollen Allergic Rhinitis in Japan by Hiroyuki Watanabe Kunio Miyake Tomokazu Matsuoka Reiji Kojima Sakurai Daiju Keisuke Masuyama ZentaroYamagata MD, PhD in American Journal of Rhinology & Allergy
Published: 2020
Full Text: View/download PDF

47. Assessment of Laryngopharyngeal Reflux Using Hypopharyngeal Multichannel Intraluminal Impedance-pH Metry (HMII) for Chronic Cough of Unknown Etiology

Author: Tomoaki Matsumura, Kazunori Kasama, Yoshitaka Okamoto, Toshitaka Hoppo, Daiju Sakurai, Urara Funakoshi, Yoshimochi Kurokawa, Akiko Umezawa, Yosuke Seki, and Takeshi Suzuki
Subjects: medicine.medical_specialty, business.industry, medicine, Intensive care medicine, business
Published: 2018

48. An analysis of factors related to the effect of sublingual immunotherapy on Japanese cedar pollen induced allergic rhinitis

Author: Daiju Sakurai, Shinya Kaneko, Akiyoshi Konno, Kimihiro Okubo, Syuji Yonekura, Yoshitaka Okamoto, and Minoru Gotoh
Subjects: Adult, Male, 0301 basic medicine, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Adolescent, Immunoglobulin levels, Cryptomeria, Placebo, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Internal medicine, Japanese cedar pollen, Post-hoc analysis, medicine, Humans, Immunology and Allergy, Sublingual immunotherapy, Child, Sublingual Immunotherapy, Plant Extracts, business.industry, Rhinitis, Allergic, Seasonal, General Medicine, Middle Aged, Slit, Natural history, Treatment Outcome, 030104 developmental biology, 030228 respiratory system, Immunology, Female, business, lcsh:RC581-607, Body mass index
Abstract: Background: Sublingual immunotherapy (SLIT) can improve the symptoms of allergic rhinitis and modify its natural history; however, its efficacy varies among patients. This study aimed to determine which factors modify the effect of SLIT through post hoc analysis of a previous phase 3 trial of standardized Japanese cedar (JC) pollen extract (CEDARTOLEN®). Methods: The study included 482 patients who had previously completed a phase 3 trial during two seasons. The SLIT and placebo groups each contained 241 subjects. Because pollen dispersal differed in the two seasons, we identified good and poor responders from the SLIT group in the 2nd season. We compared patient baseline characteristics, changes in serum immunoglobulin, and severity of symptoms in the 1st season between good and poor responders, as well as between SLIT and placebo groups. Results: When we compared the baseline characteristics of good and poor responders, a significant difference was observed in body mass index (BMI) such that the patients with BMI ≥25 presented with lower treatment efficacy. No significant difference was observed in correlation with any other factors or treatment-induced alterations of serum immunoglobulin levels. We found that 75.3% of the patients with moderate symptoms and 50.9% of the patients with severe or very severe symptoms in the 1st season met our criteria for good responders in the 2nd season. Conclusions: BMI might modify the effect of SLIT; however, other factors were not related clearly. The severity of symptoms in the 1st season of treatment does not predict that in the 2nd season. Keywords: Allergic rhinitis, Japanese cedar pollen, Phase 3 trial, Post hoc analysis, Sublingual immunotherapy
Published: 2018

49. A case report of an intraorbital cyst excised with transnasal and trans orbital approaches

Author: Toshioki Sakurai, Yoshitaka Okamoto, Kazuki Yamasaki, Toyoyuki Hanazawa, Junya Kurita, and Daiju Sakurai
Subjects: business.industry, medicine, Cyst, Anatomy, medicine.disease, business
Published: 2018

50. Biphenotypic sinonasal sarcoma: Report of two cases

Author: Katsushige Kawase, Hideaki Chazono, Yoshitaka Okamoto, Daiju Sakurai, Shuji Yonekura, and Toyoyuki Hanazawa
Subjects: Oncology, Otorhinolaryngology, business.industry, Medicine, business
Published: 2018

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