Ovarian cancer (OC) remains the most fatal disease of gynecologic malignant tumors. Angiogenesis refers to the development of new vessels from pre-existing ones, which is responsible for supplying nutrients and removing metabolic waste. Although not yet completely understood, tumor vascularization is orchestrated by multiple secreted factors and signaling pathways. The most central proangiogenic signal, vascular endothelial growth factor (VEGF)/VEGFR signaling, is also the primary target of initial clinical anti-angiogenic effort. However, the efficiency of therapy has so far been modest due to the low response rate and rapidly emerging acquiring resistance. This review focused on the current understanding of the in-depth mechanisms of tumor angiogenesis, together with the newest reports of clinical trial outcomes and resistance mechanism of anti-angiogenic agents in OC. We also emphatically summarized and analyzed previously reported biomarkers and predictive models to describe the prospect of precision therapy of anti-angiogenic drugs in OC.

Transarterial chemoembolization (TACE) has been widely used for hepatocellular carcinoma. Reducing hypoxia in the tumor microenvironment after TACE remains a challenge as tumor progression is common in post‐TACE patients due to the hypoxic tumor microenvironment. In this study, melatonin loaded on p(N‐isopropyl‐acrylamide‐co‐butyl methylacrylate) (PIB‐M) was used for tumor embolism. Two types of human hepatoma cell lines were used to explore the mechanism by which melatonin prevents the growth and metastasis of cancer cells in vitro. A VX2 rabbit tumor model was used to evaluate the efficacy, mechanism, and safety of PIB‐M in vivo. We found that under hypoxic condition, melatonin could inhibit tumor cell proliferation and migration by targeting hypoxia inducible factor‐1α (HIF‐1α) and vascular endothelial growth factor A (VEGF‐A) in vitro. In vivo, PIB‐M inhibited tumor growth and metastasis in rabbit VX2 tumors by promoting apoptosis of tumor cells and targeting related angiogenic proteins and vascular permeability proteins. A high concentration of melatonin in the PIB‐M group could be maintained in tumor tissue for 72 h after embolization. The liver and kidney functions were most damaged on the first day but recovered to normal on the seventh day after embolization in the PIB‐M group. This novel method may open avenues for reduction of tumor growth and metastasis after TACE and is efficacy and safety, which may be used for treatment for other solid tumors and clinical translation.

A sensitive and specific high‐performance liquid chromatography–tandem mass spectrometry method has been developed to determine the pharmacokinetic interactions of the antiplatelet agents aspirin and clopidogrel combined with dl‐3‐n‐butylphthalide. For the determination of aspirin metabolite salicylic acid, clopidogrel inactive metabolite SR26334 and NBP prototype drug in rat plasma, plasma samples were prepared by precipitation of proteins using methanol containing 0.1% formic acid, followed by centrifugation. Chromatography was performed on a C18 column, eluting with a gradient of acetonitrile (with 0.1% formic acid)–water (with 0.1% formic acid). The detection adopted electrospray ion source and positive ion multiple reaction monitoring modes. The linear detection response range of salicylic acid is 80–80,000 ng/ml, and the linear detection response range of SR26334 and dl‐3‐n‐butylphthalide is 10–10,000 ng/ml. Our study revealed that dl‐3‐n‐butylphthalide affected the pharmacokinetics of aspirin and clopidogrel when administered to rats.