Antiangiogenic Medications Research Articles

Design and synthesis of new nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers.

Background: Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery.Aim: Development of novel nicotinamides as VEGFR-2 inhibitors.Methods: different in vitro and in silico assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity.Results: Compound 16c displayed strongest anti-VEGFR-2 potentiality and good anti-proliferative effects. Compound 16c enhanced apoptosis and caused cell cycle arrest in the Pre-G1 and S phases. Compound 16c boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound 16c against VEGFR-2.Conclusion: Compound 16c is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.

Reporting MRONJ as an adverse drug reaction: an oral surgery survey.

Introduction Medication-related osteonecrosis of the jaw (MRONJ) is a significant adverse drug reaction associated with anti-angiogenic and anti-resorptive medications. The aim of this survey was to highlight the importance of reporting adverse drug reactions, including MRONJ.Methodology An electronic survey was disseminated to dentists working in the oral surgery department Birmingham Community Healthcare Trust in November 2021. The survey consisted of 14 open and closed questions relating to the identification and reporting of MRONJ as an adverse drug reaction.Results Although 97% of participants had seen a patient with MRONJ, only 19% had reported an adverse drug reaction to any medication. Interestingly, 27% of respondents felt that MRONJ should be classified as a 'post-operative complication' rather than an 'adverse drug reaction'. In total, 22% of participants were unaware of how to report an adverse drug reaction.Conclusion This survey acts as an important reminder to encourage both patients and dental professionals to report adverse drug reactions, including suspected MRONJ, to the Medicines and Healthcare products Regulatory Agency. Reporting aids accurate national data collection, highlights risk and supports ongoing research in this area.

Autologous platelet concentrates as adjuvant in the surgical management of medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is an infectious side effect associated with bisphosphonates and monoclonal antibodies (denosumab, immune modulators, and antiangiogenic medications). Adjunctive therapies for the surgical management of MRONJ include autologous platelet concentrates (APCs). These APCs serve as a source of various cells and growth factors that aid tissue healing and regeneration. This review evaluated the use of platelet-rich plasma (PRP), plasma-rich in growth factors (PRGF), and leukocyte- and platelet-rich fibrin (L-PRF) as adjuvant therapies for the surgical management of MRONJ by conducting analyses on the results of 58 articles. Compared to surgical treatment alone, the application of PRP and L-PRF after surgery appears to increase healing in the management of patients with MRONJ. No studies have reported unhealed lesions as a result of surgical treatment of MRONJ with PRGF application or compared it with surgical treatment alone. The overall results of this review have shown favorable healing rates of MRONJ lesions managed with the application of APCs after surgical treatment; however, significant methodological limitations may limit the scientific evidence supporting their use. Further randomized controlled trials with strict criteria are needed to establish the extent to which APCs can improve wound healing and quality of life in patients with MRONJ requiring surgical treatment.

Predicting prognosis for epithelial ovarian cancer patients receiving bevacizumab treatment with CT-based deep learning

Epithelial ovarian cancer (EOC) presents considerable difficulties in prognostication and treatment strategy development. Bevacizumab, an anti-angiogenic medication, has demonstrated potential in enhancing progression-free survival (PFS) in EOC patients. Nevertheless, the identification of individuals at elevated risk of disease progression following treatment remains a challenging task. This study was to develop and validate a deep learning (DL) model using retrospectively collected computed tomography (CT) plain scans of inoperable and recurrent EOC patients receiving bevacizumab treatment diagnosed between January 2013 and January 2024. A total of 525 patients from three different institutions were retrospectively included in the study and divided into training set (N = 400), internal test set (N = 97) and external test set (N = 28). The model’s performance was evaluated using Harrell’s C-index. Patients were categorized into high-risk and low-risk group based on a predetermined cutoff in the training set. Additionally, a multimodal model was evaluated, incorporating the risk score generated by the DL model and the pretreatment level of carbohydrate antigen 125 as input variables. The Net Reclassification Improvement (NRI) metric quantified the reclassification performance of our optimal model in comparison to the International Federation of Gynecology and Obstetrics (FIGO) staging model. The results indicated that DL model achieved a PFS predictive C-index of 0.73 in the internal test set and a C-index of 0.61 in the external test set, along with hazard ratios of 34.24 in the training set (95% CI: 21.7, 54.1; P < 0.001) and 8.16 in the internal test set (95% CI: 2.5, 26.8; P < 0.001). The multimodal model demonstrated a C-index of 0.76 in the internal test set and a C-index of 0.64 in the external test set. Comparative analysis against FIGO staging revealed an NRI of 0.06 (P < 0.001) for the multimodal model. The model presents opportunities for prognostic assessment, treatment strategizing, and ongoing patient monitoring.

The adjunctive use of Leukocyte-Platelet Rich Fibrin (L-PRF) in the management of Medication Related Osteonecrosis of the Jaw (MRONJ): a retrospective observational study.

Medication related osteonecrosis of the jaw (MRONJ) is a risk for patients taking anti-resorptive or anti-angiogenic medications. The American Association of Oral and Maxillofacial Surgeons (AAMOS) has classified MRONJ in stages to reflect the severity of the disease and allows implementation of suitable treatment pathways. MRONJ risk is < 5% in cancer patients and < 0.05% in osteoporosis patients. Management is subdivided into operative and non-operative, with advances in the literature investigating adjuvants. Leukocyte-Platelet Rich Fibrin (L-PRF) is an autologous biomaterial consisting of leukocytes and platelets embedded within a fibrin matrix with the ability to release growth factors enabling angiogenesis, bone regeneration and soft tissue healing. This paper's aim is to investigate the effects of L-PRF in conjuction with surgical debridement for management of MRONJ. Twenty-two cases with established MRONJ were treated with either surgical intervention (Group A) or with surgical intervention and L-PRF (Group B), from 2016 to 2023 at Edinburgh Dental Institute (EDI). Treatments were deemed successful when the patients were asymptomatic, displayed complete soft tissue healing with the absence of infection/inflammation, fistula, or exposed bone. All cases in Group B had healed in contrast to 54.5% not healed in Group A; p value < 0.05 indicating statistical significance. The use of L-PRF as an adjuvant to surgical management of MRONJ is promising with its favourable functional capacity, simple application, and success of treatment outcomes.

The Role of Cone Beam Computed Tomography (CBCT) in the Diagnosis and Clinical Management of Medication-Related Osteonecrosis of the Jaw (MRONJ).

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating condition associated with antiresorptive and antiangiogenic medications that are frequently used in treating osteoporosis and cancers. With the ability to produce high-resolution images with a lower radiation dose, cone beam computed tomography (CBCT) is an emerging technology in maxillofacial imaging that offers several advantages in evaluating MRONJ. This review aims to summarise the radiological features of MRONJ as observed via CBCT and highlight its advantages over two-dimensional plain films in assessing MRONJ. CBCT has the capability to detect early MRONJ lesions, characterise the extent and nature of lesions, distinguish MRONJ from other osseous pathologies, and assist in treatment planning. By leveraging the advantages of CBCT, clinicians can enhance their understanding of MRONJ, improve decision making, and ultimately optimize patient care.

Intravitreal Antiangiogenic Treatment for Diabetic Retinopathy: A Mexican Real-Life Scenario Experience.

The objective of this study was to analyze the effectiveness of two intravitreal antiangiogenic drugs, ranibizumab and aflibercept, in a Mexican population over a period of 5 years, evaluating the improvement in visual acuity (VA) and central retinal thickness (CRT) in a real-world scenario. This is a retrospective study with subjects diagnosed with diabetic retinopathy (DR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME) receiving intravitreal injections of ranibizumab and/or aflibercept. In this study, we analyzed 588 eyes of 294 patients who received intravitreal antiangiogenic injections. The results showed an improvement regardless of antiangiogenic treatment or diagnosis in both VA and CRT. We found that both aflibercept and ranibizumab improved VA, while subjects with DME responded less to antiangiogenic treatment (p < 0.05), and that this difference did not correspond to the CRT measured by OCT. These results support evidence that intravitreal antiangiogenic medications are effective for ophthalmic complications of diabetes in our population; however, damage to visual structures is not reversed in most patients. And that the perception by the patient (VA) and that of the ophthalmologist (CRT) do not completely correlate in our study.

Medication-Related Osteonecrosis of the Jaw: Bibliometric Analysis from 2003 to 2023.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious condition associated with the use of antiresorptive and antiangiogenic medications. Despite extensive research, the pathophysiology of MRONJ remains poorly understood. Bibliometric analysis provides insights into the academic impact of research, helping identify influential works and emerging trends in this field. This study employed a bibliometric analysis of MRONJ publications indexed in Web of Science from 2003 to 2023. The analysis included English-language articles and utilized the VOSviewer, R Studio Bibliometrix package, and Graphpad to evaluate citation counts, publication trends, and collaboration patterns. This study unveils the current situation of the MRONJ research, addressing well-recognized safety issues of antiresorptive and antiangiogenic agents. Our findings may suggest that the overall trend of the MRONJ research continues to evolve and is not likely to reach its peak or plateau yet. We believe that our work will help to identify gaps in the literature and future research directions, contributing to a better understanding of MRONJ management.

The discovery of new potent VEGFR2 inhibitors for potential anti-angiogenesis agent through a combination of structure-based virtual screening, molecular dynamics simulation and ADME-Tox prediction

The discovery of the importance of angiogenesis in the mechanisms of tumor growth has empowered the improvement of new particles that are utilized in the therapy of various cancers. The goal of this research was to identify novel compounds functioning as potent VEGFR2 inhibitors in silico. It is an interesting therapeutic target for developing new anti-angiogenic drugs. In this work, molecular simulation studies of enzyme inhibition was carried out by structure-based virtual screening with FlexX program of VEGFR2. This approach makes it possible to model the interactions between a protein and thousands of small chemical compounds. A collection of 6,000 compounds originating from the ZINC chemical library, were tested against the active site of VEGFR2. The ADME-Tox characteristics and molecular dynamics simulation of the potential compounds were also examined. At the end of this screening, the compounds ZINC01534124 and ZINC00588595 appear as new inhibitors theoretically more active towards VEGFR2. Again, these inhibitors have shown significant binding energy by interacting with important residues in the active site. Furthermore, the in silico prediction of a similar drug positively informs us about the ADME-Tox properties of these new compounds. Finally, the stable binding of VEGFR2 with ZINC01534124 and ZINC00588595 is shown using 100 ns molecular dynamics simulations. These findings point to the chemicals ZINC01534124 and ZINC00588595 as potential candidates for VEGFR2 inhibitor research. They might also act as a starting point for further chemical modifications in order to produce therapeutically relevant anti-angiogenic medications.

Advances in Anti-Cancer Drug Development: Metformin as Anti-Angiogenic Supplemental Treatment for Glioblastoma.

According to the WHO 2016 classification, glioblastoma is the most prevalent primary tumor in the adult central nervous system (CNS) and is categorized as grade IV. With an average lifespan of about 15 months from diagnosis, glioblastoma has a poor prognosis and presents a significant treatment challenge. Aberrant angiogenesis, which promotes tumor neovascularization and is a prospective target for molecular target treatment, is one of its unique and aggressive characteristics. Recently, the existence of glioma stem cells (GSCs) within the tumor, which are tolerant to chemotherapy and radiation, has been linked to the highly aggressive form of glioblastoma. Anti-angiogenic medications have not significantly improved overall survival (OS), despite various preclinical investigations and clinical trials demonstrating encouraging results. This suggests the need to discover new treatment options. Glioblastoma is one of the numerous cancers for which metformin, an anti-hyperglycemic medication belonging to the Biguanides family, is used as first-line therapy for type 2 diabetes mellitus (T2DM), and it has shown both in vitro and in vivo anti-tumoral activity. Based on these findings, the medication has been repurposed, which has shown the inhibition of many oncopromoter mechanisms and, as a result, identified the molecular pathways involved. Metformin inhibits cancer cell growth by blocking the LKB1/AMPK/mTOR/S6K1 pathway, leading to selective cell death in GSCs and inhibiting the proliferation of CD133+ cells. It has minimal impact on differentiated glioblastoma cells and normal human stem cells. The systematic retrieval of information was performed on PubMed. A total of 106 articles were found in a search on metformin for glioblastoma. Out of these six articles were Meta-analyses, Randomized Controlled Trials, clinical trials, and Systematic Reviews. The rest were Literature review articles. These articles were from the years 2011 to 2024. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on metformin use in the treatment of glioblastoma were searched on clinicaltrials.gov. In this article, we examine and evaluate metformin's possible anti-tumoral effects on glioblastoma, determining whether or not it may appropriately function as an anti-angiogenic substance and be safely added to the treatment and management of glioblastoma patients.

Medication-Related Osteonecrosis of the Jaw – 2024 Update

As the global number of patients with osteoporosis and malignant diseases such as breast cancer, multiple myeloma, and prostate cancer increases every year, there is an associated rise in the use of antiangiogenic medications and antiresorptive medications. With increasing frequencies in the use of antiangiogenic and antiresorptive medications, there is an associated increase in the number of medication-related osteonecrosis of the jaw (MRONJ) cases reported from patients. MRONJ has emerged as a significant comorbidity in cancer patients treated with antiangiogenics or high doses of potent antiresorptive agents, such as bisphosphonates (BPs) or denosumab. MRONJ first emerged from BP-treated cancer patients who presented with a spectrum of dental problems, including delayed wound healing following a dental extraction or oral surgery, exposed bone, soft tissue infection and inflammation, anesthesia, paresthesia, odontalgia, sinus pain, and aching bone pain in the mandible, which continues to be a significant source of problems for dentists, physicians, and patients today. A significant number of MRONJ cases secondary to osteoporosis have also been reported in osteoporotic patients receiving antiresorptive medications. The American Association of Oral and Maxillofacial Surgeons (AAOMS) has established diagnostic standards for MRONJ based on pharmacological history, clinical signs, and radiographic findings. However, as the expertise and knowledge base for MRONJ continues to evolve, revisions and refinements for MRONJ pathogenesis and treatment strategies are necessary to reflect the current research status of the disease correctly. This review highlights current scientific information associated with MRONJ to identify and summarize preventative measures, and treatment interventions for reading the impact of this debiliating disorders.

Awareness of Medication-Related Osteonecrosis of the Jaws Amongst Patients on Antiresorptive and Antiangiogenic Medications.

Background Medication-related osteonecrosis of the jaws (MRONJ) is a rare but severe condition that has garnered increasing attention in recent years. It primarily affects individuals undergoing treatment with antiresorptive and antiangiogenic medications, such as bisphosphonates and denosumab, commonly prescribed for osteoporosis and cancer-related bone metastases. Therefore, the present study aimed to assess awareness and understanding of MRONJ among patients receiving antiresorptive and antiangiogenic medications. Methods A cross-sectional survey was conducted among 110 patients receiving antiresorptive and antiangiogenic medications in a clinical setting. Participants were given a structured questionnaire to assess their awareness of MRONJ. The questionnaire covered aspects such as MRONJ, bisphosphonate usage, and awareness of the condition's potential complications. Demographic information was also collected. Chi-square and Fisher's tests were performed using SPSS statistical software. Results In terms of gender distribution, 63.6% of the participants were female. Concerning age distribution, the majority (43.6%) fell within the 21 to 40 age group, whereas only 5.5% were aged over 60. Regarding educational attainment, a substantial majority (58.2%) of the participants held a bachelor's degree. The study findings reveal that a considerable proportion (35.5%) of participants possess awareness regarding jaw osteonecrosis, and this association is statistically significant (p=0.002). A substantial number of participants administered the medication orally (30.9%), while others utilized various administration routes, including injection (IV and others) (40%), and this difference was also statistically significant (p=0.001). Most participants took bisphosphonates for osteoporosis (41.8%) or cancer (13.6%), both statistically significant (p<0.01). Gender had no significant impact (p>0.01), but age showed potential associations (p=0.07 for awareness, p=0.003 for medication use). Educational backgrounds had no significant link, except for bisphosphonate usage (p<0.01) and side effects reporting (p<0.01). Conclusion Notably, a small percentage of participants demonstrated awareness of this condition, indicating a need for continued education and awareness campaigns. Further research and interventions may be warranted to address the specific needs of different age groups and educational backgrounds in promoting safe and effective medication management.

Knowledge of Dental Students and Practitioners About Medication-Related Osteonecrosis of the Jaw in the Central Region of Saudi Arabia.

Bisphosphonates (BPs) are often used in treating benign and malignant disorders. Medication-related osteonecrosis of the jaw (MRONJ) is a significant problem that arises from the long-term use of BPs. In this study, we assessed the knowledge of students and dentists about MRONJ in the central region of Saudi Arabia. A cross-sectional study was conducted to collect information from dental students and practitioners from the central region of Saudi Arabia. A valid, reliable, and structured questionnaire was used to gather data using a non-probability convenient sampling technique. IBM SPSS Statistics for Windows, Version 22.0 (Released 2013; IBM Corp., Armonk, New York, United States) was used to analyse the data. The descriptive data were expressed as frequencies and percentages to evaluate the association between dentists and students concerning overall knowledge related to osteonecrosis of the jaw, and a chi-squared test was applied. In total, 250 individuals completed the questionnaire. The general knowledge of antiresorptive/antiangiogenic medications showed that most dentists (87.5%) and students (68.4%) knew about BP medications. A general lack of understanding about the therapeutic uses of antiangiogenic and antiresorptive medications was demonstrated by the participants. A significant proportion of dentists (58.8%) and students (50.9%) were not convinced that invasive dental procedures can be safely performed on patients receiving intravenous BP therapy. A significant proportion of the participants in the sample were unclear of the principal diseases that antiresorptive and antiangiogenic medications target. A mere 22% of respondents were aware of the accurate definition of medications-related MRONJ. There is insufficient knowledge about MRONJ among students and practitioners. Therefore, these findings suggest increased emphasis should be placed on educating dentists and students about this condition to ensure patients receive the best possible care.

The role of leukocyte and platelet-rich fibrin in the prevention of medication-related osteonecrosis of the jaw, in patients requiring dental extractions: an observational study.

Medication-related osteonecrosis of the jaw (MRONJ) is a significant complication which can present following a dental extraction in patients receiving anti-resorptive and anti-angiogenic medications. The purpose of this study was to investigate the possible beneficial effect of L-PRF in the prevention of MRONJ in patients receiving these medications and requiring dental extractions. Thirty-nine patients were included and divided into two groups, depending on whether L-PRF was used after the required dental extraction or not. Subsequently, the patients were categorised into low and high-risk for developing MRONJ, as recommended by the SDCEP guidance. None of the patients in the L-PRF group returned with established MRONJ. Five high-risk patients in the control group presented with established MRONJ in the follow-up appointment. A significant statistical difference (p = 0.04) was observed following a comparison of the high-risk patients of the two groups. These encouraging results suggest that L-PRF may be useful in the prevention of MRONJ following a dental extraction especially in patients of the higher risk category. A protocol for the management of this type of patients is also introduced.

Knowledge and attitudes of undergraduate dental students at the University of Barcelona regarding antiresorptive and antiangiogenic medications: A cross-sectional study.

This study was carried out to determine the knowledge and attitudes of dental students at the University of Barcelona (Spain) concerning antiresorptive and antiangiogenic medications and their implications in dental treatment. A cross-sectional study was conducted among dentistry students at the University of Barcelona using a 27-item questionnaire. This anonymous survey gathered demographic variables and assessed student interest in attending an educational session on oral pathology. Descriptive and bivariate analyses were performed following data collection. A total of 105 students were surveyed. They all demonstrated awareness of antiresorptive medications, their pharmacokinetics and indications. Less than half, however, could identify drugs linked to osteonecrosis of the jaws (ONJ) or associated risk factors for oral complications. The students had a better understanding of antiresorptive drugs in comparison with antiangiogenic medications. Moreover, comparative analysis revealed that 5th year dental students had a higher level of knowledge of the dental implications of these drugs. This study shows that dental student knowledge of antiresorptive and antiangiogenic medications needs to be improved. The development of educational strategies to address the implications of these drugs in dental treatment is clearly indicated. Key words:Medication-Related Osteonecrosis, Antiresorptive Drugs, Antiangiogenic Therapy.

Medication-related osteonecrosis of the jaw (MRONJ): a review of pathogenesis hypothesis and therapy strategies.

Medication-related osteonecrosis of the jaw (MRONJ), a severe side effect caused by antiresorptive antiangiogenic medication, particularly bisphosphonates (BPs), has become a challenging disease with serious and profound effects on the physical and mental health of patients. Although it occurs with high frequency and is harmful, the exact mechanism of MRONJ remains unknown, and systematic and targeted approaches are still lacking. Maxillofacial surgeons focus on the etiology of osteonecrosis in the mandible and maxilla as well as the appropriate oral interventions for high-risk patients. Adequate nursing care and pharmacotherapy management are also crucial. This review provides a current overview of the clinicopathologic feature and research of MRONJ caused by BPs, with an emphasis on the potential mechanisms and current therapy and prevention strategies of the disease. We are of the opinion that an in-depth comprehension of the mechanisms underlying MRONJ will facilitate the development of more precise and efficacious therapeutic approaches, resulting in enhanced clinical outcomes for patients.

Influence of antiresorptive/antiangiogenic therapy on changes in periodontal and oral tissue structures: a histomorphometrical analysis in rats

ObjectiveThe objective of this study was to investigate the influence of various antiresorptive and antiangiogenic medications on morphological changes in periodontal and oral tissue structures.Materials and methodsFifty-five Wistar rats randomly received dual application (i.e., at baseline and after 12-weeks) one of the following medications: (1) amino-bisphosphonate [zoledronate (Zo)], (2) RANKL inhibitor [denosumab (De)], (3) antiangiogenic [bevacizumab (Be)], (4) Zo + Be, (5) De + Be or (6) no medication [Control (Co)]. Periodontal and oral tissue biopsies were obtained at 17 (n = 21 animals, Phase 1, (De = 3, De + Be = 3, Zo = 5, Be = 3, Zo + Be = 2, Co = 5) and 29 (n = 34 animals, (De = 8, De + Be = 6, Zo = 2, Be = 7, Zo + Be = 4, Co = 7, Phase 2) weeks after the second drug application. The following outcomes were histomorphometrically assessed: periodontal space width in the coronal (PLS-C, mm) and apical sections (PLS- A), number of empty alveolar bone lacunae in the coronal, apical sections and at the apex at respective tooth sites (EL – C, EL- A, EL- Ap), mucosal thickness at edentulous alveolar ridge areas (MT, mm), and, when present, associated areas of inflammatory cell infiltrates (ICI, mm2).ResultsComparable mean PLS-C, PLS-A, ET-A, ET-C, ET-Ap, and MT values were observed in all experimental groups after Phases 1 and 2. The presence of ICI was identified in 3 animals in the Co group (Phase 1: 1, Phase 2: 2), and 17 animals in the test groups (Phase 1: 4; Phase 2: 14). The estimated ICI surface area was significantly higher in the Zo + Be group, followed by the Zo and Be groups compared to that measured in the Co group. The time (i.e., Phases 1 and 2) was not found to be a predictor for the extent of the ICI area. In all groups, the EL-C, EL-A, and EL-Ap values were significantly higher after Phase 2 compared to those assessed after Phase 1. The MT values were significantly reduced in all groups after Phase 2 compared to those measured after Phase 1.ConclusionsThe present evaluation was not able to find any morphological effects of different antiresorptive and antiangiogenic medications on periodontal and oral tissue structures. The presence of inflammatory cell infiltrates was more frequently observed in the animals administered with antiresorptive and antiangiogenic medications as well as combinations thereof.Clinical relevanceAdministration of antiresorptive and antiangiogenic medications may be capable of inducing inflammatory reactions in periodontal tissues.

Mammary Tumors in Dogs, Recent Perspectives and Antiangiogenesis as a Therapeutic Strategy: Literature Study

A particular type of tumor that is frequently detected in female dogs who are sexually active is a mammary tumor. Neoplasia results from DNA-based alterations in cell cycle regulating genes. The mammary gland is prone to the formation of tumors due to its dynamic structure. The development of this tumor is supported by numerous variables. It has been recently discovered that there is substantial evidence linking the BRCA2 gene to the process of cancer. Standard examination techniques, such as fine needle aspiration, histopathology, and immunohistochemistry, are used along with ancillary tests to determine the tumor type and degree of malignancy. The primary treatment option for malignant tumors is surgical resection followed by adjuvant chemotherapy; benign tumors necessitate surgical resection as well. Adjuvant therapy options include hormone therapy and non-steroidal anti-inflammatory medications. Tumor tissue undergoes angiogenesis as it grows and develops to accommodate the abundant supply of nutrients. Therefore, angiogenesis-inhibiting therapies can be utilized to halt the growth of tumor cells. A number of antiangiogenic medications are now being studied in clinical settings on humans, and several more are undergoing trials on animals. In addition to pharmaceuticals, viruses may be used as a therapeutic to block tumor angiogenesis.

Influence of antiresorptive/antiangiogenic therapy on the surgical treatment outcomes of experimentally induced peri-implantitis lesions

ObjectiveTo investigate the influence of various antiresorptive and antiangiogenic medications on the resolution of experimentally induced peri-implantitis lesions after different surgical treatment approaches.Materials and methodsForty-eight albino rats randomly received a dual application of the following medications: (1) amino-bisphosphonate (zoledronate (Zo)) (n = 8), (2) RANKL inhibitor (denosumab (De)) (n = 8), (3) antiangiogenic (bevacizumab (Be)) (n = 8), (4) Zo + Be (n = 8), (5) De + Be (n = 8), or (6) no medication (control (Co)) (n = 8). Ligature-induced peri-implantitis lesions were established at 2 maxillary implants over 16 weeks. Afterward, animals were randomly treated either with open flap debridement (OFD) or reconstructive therapy (RT). Treatment procedures were followed by a 12-week healing period. The histological outcomes included residual defect length (DL); defect width (DW) at the bone crest (BC-DW); 25%, 50%, and 75% of the DL; and areas of inflammatory cell infiltrate (ICT). When present, areas of bone sequester (BS) were assessed considering the animal as a statistical unit.ResultsA total of 21 animals were analyzed (Zo: RT = 3, OFD = 1; De: RT = 3, OFD = 2; Be: OFD = 1; Zo + Be: RT = 2, OFD = 2; Co: RT = 3, OFD = 2). Implant loss rates were comparable among the experimental groups. Except for the 25% and 75% DW values that were significantly higher in the Zo + Be group compared to the Co group (p = 0.04 and p = 0.03, respectively), no significant differences were found among the experimental groups for the DL (lowest—Be: 0.56 mm; highest—Co: 1.05 mm), BC-DW (lowest—De: 0.86 mm, highest—Co: 1.07 mm), 50% DW (lowest—De: 0.86 mm; highest—Be + Zo: 1.29 mm), and ICT (lowest—Be: 0.56 mm2; highest—Be + Zo: 1.65 mm2). All groups, except for the Zo and Be following RT, showed presence of BS.ConclusionsThe present findings did not reveal a marked effect of various antiresorptive/antiangiogenic medications on the resolution of experimentally induced peri-implantitis lesions, regardless of the surgical approach employed (OFD and RT).Clinical relevanceResolution of peri-implantitis lesions may not be affected by the investigated antiresorptive/antiangiogenic medications.

Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis

BackgroundPathological neovascularization plays a pivotal role in the onset and progression of tumors and neovascular eye diseases. Despite notable advancements in the development of anti-angiogenic medications that target vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), the occurrence of adverse reactions and drug resistance has somewhat impeded the widespread application of these drugs. Therefore, additional investigations are warranted to explore alternative therapeutic targets. In recent years, owing to the swift advancement of high-throughput sequencing technology, pan-cancer analysis and single-cell sequencing analysis have emerged as pivotal methodologies and focal areas within the domain of omics research, which is of great significance for us to find potential targets related to the regulation of pathological neovascularization.MethodsPan-cancer analysis and scRNA-seq data analysis were employed to forecast the association between Actin filament-associated protein 1 like 1 (AFAP1L1) and the development of tumors and endothelial cells. Tumor xenograft model and ocular pathological neovascularization model were constructed as well as Isolectin B4 (IsoB4) staining and immunofluorescence staining were used to assess the effects of AFAP1L1 on the progression of neoplasms and neovascular eye diseases in vivo. Transwell assay, wound scratch assay, tube forming assay, three-dimensional germination assay, and rhodamine-phalloidin staining were used to evaluate the impact of AFAP1L1 on human umbilical vein endothelial cells (HUVECs) function in vitro; Dual luciferase reporting, qRT-PCR and western blot were used to investigate the upstream and downstream mechanisms of pathological neovascularization mediated by AFAP1L1.ResultsOur investigation revealed that AFAP1L1 plays a crucial role in promoting the development of various tumors and demonstrates a strong correlation with endothelial cells. Targeted suppression of AFAP1L1 specifically in endothelial cells in vivo proves effective in inhibiting tumor formation and ocular pathological neovascularization. Mechanistically, AFAP1L1 functions as a hypoxia-related regulatory protein that can be activated by HIF-1α. In vitro experiments demonstrated that reducing AFAP1L1 levels can reverse hypoxia-induced excessive angiogenic capacity in HUVECs. The principal mechanism of angiogenesis inhibition entails the regulation of tip cell behavior through the YAP-DLL4-NOTCH axis.ConclusionIn conclusion, AFAP1L1, a newly identified hypoxia-related regulatory protein, can be activated by HIF-1α. Inhibiting AFAP1L1 results in the inhibition of angiogenesis by suppressing the germination of endothelial tip cells through the YAP-DLL4-NOTCH axis. This presents a promising therapeutic target to halt the progression of tumors and neovascular eye disease.