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  • Pathological angiogenesis occurs when an imbalance of endoge

    2024-02-23

    Pathological angiogenesis occurs when an imbalance of endogenous proangiogenic and antiangiogenic factors occurs. Although the focus of angiogenesis-related drug development has been geared to the discovery of antiangiogenic compounds for use in pathologies where excessive angiogenesis occurs (cancer, rheumatoid arthritis, retinopathy to name a few), an increase interest has been directed towards the development of proangiogenic drugs for use in pathologies were insufficient angiogenesis occurs (coronary heart disease, stroke, chronic wounds to name a few) [173]. Given that a number of natural compounds have exhibited proangiogenic activity, the approach of explore these compounds in such applications configures a promising field of research [115].
    Concluding remarks All cells need a steady supply of oxygen, nutrients and a way to remove waste materials, and this is accomplished by an efficient network by blood vessels. Angiogenesis is a biological process through which new blood vessels are formed and is essential for various biological processes. Pathological angiogenesis is related with the development of various and serious diseases, particularly cancer. In this case, the angiogenesis is very important for development, survival and metastases formation. Angiogenesis is very complex and involves different and numerous angiogenic factors and signaling pathways, including growth factors, MMP, cytokines, arachidonic mlkl derivatives, transcription factors and cell cycle related proteins among others. VEGF and his membrane receptor is the most studied growth factor. Several antiangiogenic drugs have been developed, and bevacizumab was the mlkl first one to be used in therapies applied in vivo to tumor angiogenesis. Still, due to toxicity and cost constraints of these drugs, the development of new treatments is becoming highly important. In this context, natural bioactive compounds, present in various natural products, have shown high antiangiogenic capacity together with well-being effects. Compared with currently available antiangiogenic drugs, plant-derived products may not only have similar therapeutic potential, presenting also clear advantages due to their lower toxicity and ease way of administration. Also, they can be regarded as inexpensive solutions, when compared with synthetic counterparts. The approach of applying natural compounds in the treatment to angiogenesis-related pathologies is, therefore, a promising field of research. However, novel and effective strategies are necessary to improve their bioavailability for clinical use.
    Conflicts of interest
    Introduction Bisphosphonate-related osteonecrosis of the jaw (BRONJ) was first reported by Marx in 2003 [1]. Since then, reports concerning BRONJ have increased. The diagnosis of BRONJ was also addressed by a position paper of the American Association of Oral and Maxillofacial Surgeons (AAOMS) in 2007 [2]. An updated position paper was published by the AAOMS in 2014 [3], which recommended changing the nomenclature of BRONJ. The committee favors the term medication-related osteonecrosis of the jaw (MRONJ). This change sought to accommodate the growing number of osteonecrosis cases involving the maxilla and mandible associated with other antiresorptive (denosumab) and antiangiogenic therapies [3]. Patients may be considered to have MRONJ if all of the following characteristics are present: 1) Current or previous treatment with antiresorptive or antiangiogenic agents, 2) Exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region that has persisted for more than eight weeks, 3) No history of radiation therapy to the jaws or obvious metastatic disease of the jaws [3]. The present case was diagnosed with MRONJ related to antiangiogenic agents.
    Presentation of case A 62-year-old woman visited the Department of Oral and Maxillofacial Surgery complaining of gingival bleeding and pus discharge. According to past medical history she had been diagnosed with renal cell carcinoma. She was treated via radical nephrectomy and chemotherapy with pazopanib (Votrient®, GlaxoSmithKline Inc., London, UK) and everolimus (Afinitor®, Novartis Inc., Basel, Switzerland) as antiangiogenic agents for renal cell carcinoma. Votrient administration started on October 10, 2013. It was administered for approximately six months by the urologist. After that, afinitor was administered for about seven weeks. And then the patient complained that her gums were sore, and afinitor was stopped.