ABSTRACT
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.
ABSTRACT
<p><b>OBJECTIVE</b>To examine adaptive changes in the shape of the upper airway during titrated mandibular advancement. Furthermore, to understand the mechanism of mandible-adjustable therapy to improve the ventilation.</p><p><b>METHODS</b>Fourteen non-apnea participated in the study. A custom-made oral device was used to keep the mandible in titrated advancement at 0% (F0), 50% (F50), 75% (F75), 100% (F100) of the maximum advancement. Magnetic resonance imaging was used to investigate the difference in the shape of upper-airway in these 4 positions. Changes in the anteroposterior direction (AP), lateral direction (Lat) and its ratio (AP/Lat) were calculated, which were transformed into the percentage of the original ones.</p><p><b>RESULTS</b>The dose-dependent decrease of AP/Lat was found when the mandible was advanced (P = 0.0001). Lateral change rate in percentage increased by degrees (P = 0.0023), while the increase of anteroposterior change rate in percentage showed no statistical significance.</p><p><b>CONCLUSION</b>The shape of upper airway tended to be less round. The enlargement of upper airway during titrated mandibular advancement was mainly the result of enlargement in lateral direction.</p>