1.Interleukin-34 cancels anti-tumor immunity by PARP inhibitor
Takayoshi NAKAMURA ; Nabeel KAJIHARA ; Naoki HAMA ; Takuto KOBAYASHI ; Ryo OTSUKA ; Nanumi HAN ; Haruka WADA ; Yoshinori HASEGAWA ; Nao SUZUKI ; Ken-ichiro SEINO
Journal of Gynecologic Oncology 2023;34(3):e25-
Objective:
Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME).
Methods:
In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34.
Results:
We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34.
Conclusion
These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.
2.Future Possibilities for Endotracheal Suctioning Ontologies Based on the Ocular Movement of Skilled Nurses
Noriyo COLLEY ; Hiromi SHIMIZU ; Nozomi TAKAHASHI ; Shunsuke KOMIZUNAI ; Atsushi KONNO ; Satoshi KANAI ; Shinji NINOMIYA ; Ken OTSUKA ; Tadayoshi ASAKA
Medical Education 2018;49(2):117-125
Introduction: Due to the advancement of the home-based healthcare, increasing the number of professionals who are able to administer homebased treatments, such as endotracheal suctioning, is an urgent issue.Methods: By measuring the ocular movement of nurses, nursing students and previous researches, an endotracheal suctioning ontology was visualized. It included a multiplex task structure, recognition, and judgment, as well as identifying procedures used during endotracheal suctioning that could contribute to a discussion on educational feasibility.Results: From the hierarchical structure of the constructed endotracheal suctioning ontology, not only the procedural knowledge but also knowledge about medical devices, knowing what options exist when endotracheal suctioning is ineffective, and a wide range of other expertise is needed to perform endotracheal suctioning safely.Discussion: An endotracheal suctioning ontology was created from the ocular movement of nurses. Ontologies are a potential tool for defining minimum requirements and the scope of ability that must be evaluated before clinical practicum.