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  • Induction Chemotherapy in Hypopharyngeal Cancer: Influence of DNA Repair Gene Polymorphisms. Anticancer research Hirakawa, H., Ikegami, T., Azechi, S., Agena, S., Uezato, J., Kinjyo, H., Yamashita, Y., Kiyuna, A., Tanaka, K., Kondo, S., Maeda, H., Suzuki, M., Ganaha, A. 2020; 40 (6): 3277-3285

    Abstract

    The aim was to clarify whether DNA repair gene polymorphisms can be used to predict response to cisplatin, 5-fluorouracil, and docetaxel (TPF) as induction chemotherapy (ICT) in Japanese patients with hypopharyngeal cancer (HPC).DNA repair gene polymorphisms (rs3212986, rs1799793, rs13181, and rs25487) were analyzed in 117 HPC patients and 125 control subjects by PCR-restriction fragment length polymorphism. Forty-one HPC patients who received TPF-based ICT, followed by surgery or chemoradiotherapy/radiotherapy were analyzed for ICT response, laryngeal preservation, and survival outcome.ICT responders (29 cases) had significantly better overall survival than ICT non-responders (12 cases; 86.0% vs. 37.0%, respectively, p<0.01 by log-rank test) and better laryngeal preservation rates. The DNA repair gene polymorphisms were not related to ICT response.ICT is beneficial for chemoselection of HPC patients, but a role for DNA repair gene polymorphisms in ICT response was not confirmed.

    View details for DOI 10.21873/anticanres.14310

    View details for PubMedID 32487623

  • ERCC1 C8092A polymorphism predicts fair survival outcome in Japanese patients with pharyngo-laryngeal squamous cell carcinoma. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery Hirakawa, H., Ikegami, T., Azechi, S., Agena, S., Uezato, J., Kinjyo, H., Yamashita, Y., Tanaka, K., Kondo, S., Maeda, H., Suzuki, M., Gahana, A. 2020; 277 (2): 601-610

    Abstract

    To evaluate the prognostic significance of DNA excision repair gene polymorphisms, excision repair cross-complementation group 1 (ERCC1) and X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) polymorphisms were investigated in Japanese patients with head and neck squamous cell carcinoma (HNSCC).A total of 225 consecutive patients with HNSCC who underwent surgery or chemoradiotherapy/radiotherapy (CRT/RT) with curative intent as primary treatment from 2006 to 2017 were recruited. ERCC1 C8092A and XRCC1 Arg399Gln polymorphisms in DNA extracted from individual blood samples were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Cumulative survival was estimated by Kaplan-Meier analysis with a log-rank test and Cox proportional hazards model stratified by treatment arm, adjusting for clinical prognostic factors.Multivariate analysis showed that carriers with the ERCC1 8092 (C/A+A/A) genotype (hazard ratio, 3.56; 95% confidence interval, 1.22-7.39; pā€‰=ā€‰0.02) had significantly worse survival than those with ERCC1 8092 C/C who received CRT/RT. Conversely, the XRCC1 Arg399Gln polymorphism did not influence survival in patients who received CRT/RT as well as surgery.The ERCC1 C8092A polymorphism might be an independent predictor of response to CRT and survival outcome in patients with HNSCC. This is the first report to investigate the role of DNA excision repair gene polymorphisms in patients with head and neck cancer in a Japanese population.

    View details for DOI 10.1007/s00405-019-05731-y

    View details for PubMedID 31749055

    View details for PubMedCentralID 3097775

  • CCR8 regulates contact hypersensitivity by restricting cutaneous dendritic cell migration to the draining lymph nodes. International immunology Yabe, R., Shimizu, K., Shimizu, S., Azechi, S., Choi, B. I., Sudo, K., Kubo, S., Nakae, S., Ishigame, H., Kakuta, S., Iwakura, Y. 2015; 27 (4): 169-81

    Abstract

    Allergic contact dermatitis (ACD) is a typical occupational disease in industrialized countries. Although various cytokines and chemokines are suggested to be involved in the pathogenesis of ACD, the roles of these molecules remain to be elucidated. CC chemokine receptor 8 (CCR8) is one such molecule, of which expression is up-regulated in inflammatory sites of ACD patients. In this study, we found that Ccr8(-/-) mice developed severer contact hypersensitivity (CHS) responses to 2,4-dinitrofluorobenzene, a murine model of ACD, compared with wild-type mice. T cells from Ccr8(-/-) mice showed enhanced proliferative recall responses and Th1 and Th17 cell populations were expanded in these mice. However, CHS responses were similar between SCID mice adoptively transferred with Ccr8(-/-) and wild-type T cells, suggesting that CCR8 in T cells is not responsible for the exacerbation of CHS. Notably, skin-resident dendritic cells (DCs), such as Langerhans cells and dermal DCs, and inflammatory DCs were highly accumulated in lymph nodes (LNs) of Ccr8(-/-) mice after sensitization. Consistent with this, Ccr8(-/-) antigen-presenting cells readily migrated from the skin to the draining LNs after sensitization. These observations suggest that CCR8 negatively regulates migration of cutaneous DCs from the skin to the draining LNs in CHS by keeping these cells in the skin.

    View details for DOI 10.1093/intimm/dxu098

    View details for PubMedID 25344933