20.500.12556/DiRROS-19549 Poor perfusion of the microvasculature in peritoneal metastases of ovarian cancer Most women with epithelial ovarian cancer (EOC) suffer from peritoneal carcinomatosis upon first clinical presentation. Extensive peritoneal carcinomatosis has a poor prognosis and its pathophysiology is not well understood. Although treatment with systemic intravenous chemotherapy is often initially successful, peritoneal recurrences occur regularly. We hypothesized that insufficient or poorly-perfused microvasculature may impair the therapeutic efficacy of systemic intravenous chemotherapy but may also limit expansive and invasive growth characteristic of peritoneal EOC metastases. In 23 patients with advanced EOC or suspicion thereof, we determined the angioarchitecture and perfusion of the microvasculature in peritoneum and in peritoneal metastases using incident dark field (IDF) imaging. Additionally, we performed immunohistochemical analysis and 3-dimensional (3D) whole tumor imaging using light sheet fluorescence microscopy of IDF-imaged tissue sites. In all metastases, microvasculature was present but the angioarchitecture was chaotic and the vessel density and perfusion of vessels was significantly lower than in unaffected peritoneum. Immunohistochemical analysis showed expression of vascular endothelial growth factor and hypoxia inducible factor 1α, and 3D imaging demonstrated vascular continuity between metastases and the vascular network of the peritoneum beneath the elastic lamina of the peritoneum. We conclude that perfusion of the microvasculature within metastases is limited, which may cause hypoxia, affect the behavior of EOC metastases on the peritoneum and limit the response of EOC metastases to systemic treatment. microvasculature microcirculation EOC peritoneal carcinomatosa incident dark feld imaging mikrovaskulatura mikrocirkulacija EOC karcinomatoza peritone true false true Angleški jezik Slovenski jezik Neznano 2024-07-19 03:45:01 2024-07-23 12:42:04 2024-07-24 03:47:57 0000-00-00 00:00:00 2020 0 0 str. 293-304 37 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2020-02-01 577 0262-0898 10.1007/s10585-020-10024-4 40667909 RAZ_Kastelein_Arnoud_W._2020.pdf RAZ_Kastelein_Arnoud_W._2020.pdf 1 E498C1F660C211C21B12C520662E4CED ee63707053b1345c4cf3e546cec93658fc1deb210fd21c46e57738bfb3ed070a 885589c3-48cf-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27179 https://doi.org/10.1007/s10585-020-10024-4 0 ada8a9ce-48cf-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27180 Nacionalni inštitut za biologijo 0 0 0