Angiogenesis is known as one of the hallmarks in cancer which could play a key role in providing oxygen and nutrients for tumor cells. It has been shown that tumor cannot grow without sufficient development of new blood vessels. Accordingly, targeting angiogenesis, especially endothelial cells, could be considered as a common therapeutic target in tumors and more investigation on already existing biomarkers and potentially new biomarkers of endothelial cells seems to be necessary in cancer therapy. Moreover, the use of effective targeting approaches such as proteins and peptides, aptamers, and small molecules is an important step for targeting biomarkers associated with endothelial cells and angiogenesis in cancer therapy. These agents are FDA approved, or are currently under investigation in pre-clinical and clinical studies. Among various biomarkers for angiogenesis microRNAs are suitable candidates for target therapy. These molecules play key roles in tumor angiogenesis which exert their effect via targeting a variety of cellular and molecular pathways involved in tumor angiogenesis. Here, we summarize a variety of biomarkers which their expressions or their functions could change the function of endothelial cells in tumor microenvironments. Moreover, we highlighted various therapeutic agents which could target these biomarkers.

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Context: It has been proved that fresh frog skin is efficient in the wound healing process. Objective: The purpose of study is to introduce a formulation of frog skin powder for evaluation of wound repair where fresh frog skin is not available. Materials and methods: Rana ridibunda (Ranidae) skins were lyophilized, and a powder was prepared. The powder (0.0005 g) was then mixed with ointment (0.0065 g) for treating each wound. Formulation was used on full-thickness wounds on mice (FO group) and compared to positive and negative controls. In order to study the wound healing process, wound contraction, inflammation, number of fibroblast cells, neovascularization and collagen density were evaluated on days 2, 4 and 6 following the injury. Moreover, CFU measurement was performed for the evaluation of wound contamination. Results: Acceleration in wound contraction in the FO group compared to control groups was significant (p50.001) on days 4 and 6. Results showed that FO treatment considerably decreased inflammatory cells during the study. On day 4, FO treatment was significantly effective in increasing the number of fibroblast cells and collagen density (p50.01 and p50.05, respectively). On day 6 the number of fibroblast cells (p50.001), collagen density (p50.05) and neovascularization (p50.05), were higher in the FO group than the control groups. Results of CFU measurement demonstrated significant reduction of wound contamination in FO treated wounds on days 2 (p50.05) and 4 (p50.01). Discussion and conclusion: Our findings indicated that the pharmaceutical form of frog skin used in this study has considerable healing and antibacterial effects on wounds.