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.Case Report of a COVID-19 Sub-acute Patient with Rehabilitation Therapy
Kazumi KASHIWABARA ; Toru TAKEKAWA ; Midori HAMA ; Naoki YAMADA ; Shu WATANABE ; Gentaro HASHIMOTO ; Masahiro ABO ; Kyota SHINFUKU
The Japanese Journal of Rehabilitation Medicine 2022;():20064-
COVID-19 spread from Wuhan City, People's Republic of China, in December 2019, followed by an explosion of infections worldwide. The number of infected people has also risen dramatically in Japan and has become a major social problem. Patients with severe disease require a long period to return to society due to significant physical weakness even after recovery. We report a patient in his 40s with a history of nephrectomy who was infected with COVID-19 and became critically ill.After being diagnosed with COVID-19 by PCR test, the patient was admitted to our hospital. His respiratory status rapidly worsened and he was temporarily managed by ECMO in the intensive care unit. At the time of his first contact with us (day 31 post-hospitalization), he was unable to hold himself in a standing position for a long time and required a walker. Initially, from the perspective of preventing the spread of infection, we instructed him in self-directed training rather than individual therapy. From day 49, he began to receive physical therapy. He was discharged on day 53 with independence in outdoor walking. He was instructed to consume protein after exercising and he was managed on an outpatient basis. He returned to work. His skeletal muscle mass increased by BIA and his respiratory and motor functions were restored.He received instructions on recovering from severe illness after COVID-19 infection, which focused on nutrition, voluntary training, and monitored individual therapy in accordance with rehabilitation therapy. He was able to return to society with no sequelae.
3.Case Report of a COVID-19 Sub-acute Patient with Rehabilitation Therapy
Kazumi KASHIWABARA ; Toru TAKEKAWA ; Midori HAMA ; Naoki YAMADA ; Shu WATANABE ; Gentaro HASHIMOTO ; Masahiro ABO ; Kyota SHINFUKU
The Japanese Journal of Rehabilitation Medicine 2022;59(3):329-336
COVID-19 spread from Wuhan City, People's Republic of China, in December 2019, followed by an explosion of infections worldwide. The number of infected people has also risen dramatically in Japan and has become a major social problem. Patients with severe disease require a long period to return to society due to significant physical weakness even after recovery. We report a patient in his 40s with a history of nephrectomy who was infected with COVID-19 and became critically ill.After being diagnosed with COVID-19 by PCR test, the patient was admitted to our hospital. His respiratory status rapidly worsened and he was temporarily managed by ECMO in the intensive care unit. At the time of his first contact with us (day 31 post-hospitalization), he was unable to hold himself in a standing position for a long time and required a walker. Initially, from the perspective of preventing the spread of infection, we instructed him in self-directed training rather than individual therapy. From day 49, he began to receive physical therapy. He was discharged on day 53 with independence in outdoor walking. He was instructed to consume protein after exercising and he was managed on an outpatient basis. He returned to work. His skeletal muscle mass increased by BIA and his respiratory and motor functions were restored.He received instructions on recovering from severe illness after COVID-19 infection, which focused on nutrition, voluntary training, and monitored individual therapy in accordance with rehabilitation therapy. He was able to return to society with no sequelae.