ABSTRACT
SUMMARY: Angiogenesis, a process by which new blood vessels are generated from pre-existing ones, is significantly compromised in tumor development, given that due to the nutritional need of tumor cells, pro-angiogenic signals will be generated to promote this process and thus receive the oxygen and nutrients necessary for its development, in addition to being a key escape route for tumor spread. Although there is currently an increase in the number of studies of various anti-angiogenic therapies that help reduce tumor progression, it is necessary to conduct a review of existing studies of therapeutic alternatives to demonstrate their importance.
La angiogénesis, proceso por el cual se generan nuevos vasos sanguíneos a partir de otros preexistentes, se encuentra comprometida de forma importante en el desarrollo tumoral, dado que por necesidad nutritiva de las células tumorales se generarán señales pro angiogénicas para promover este proceso y así recibir el oxígeno y los nutrientes necesarios para su desarrollo, además de ser una ruta de escape clave para la diseminación tumoral. Si bien, actualmente existe un aumento en la cantidad de estudios de diversas terapias anti angiogénicas que ayudan a reducir el avance tumoral, es necesario realizar una revisión de los estudios existentes de alternativas terapéuticas para demostrar su importancia.
Subject(s)
Humans , Angiogenesis Inhibitors/therapeutic use , Celecoxib/therapeutic use , Neoplasms/drug therapy , Neovascularization, Pathologic/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Cyclooxygenase 2 Inhibitors , Neoplasms/pathology , Antineoplastic Agents/therapeutic useABSTRACT
Objetivo: Este trabalho tem como propósito fornecer uma análise abrangente das características clínicas, etiológicas, radiográficas e histopatológicas da osteonecrose dos maxilares relacionada ao uso de medicamentos, além de abordar os métodos de diagnóstico, prevenção e estratégias terapêuticas. Materiais e métodos: foi realizada uma busca por artigos científicos publicados no período de 2015 a 2023, utilizando as bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) e ScienceDirect. Conclusão: Embora infrequente, há um considerável potencial de ocorrência de osteonecrose dos maxilares em pacientes submetidos a terapia prolongada com medicamentos antirreabsortivos e antiangiogênicos, especialmente quando não são adotadas medidas preventivas adequadas. A implementação de práticas preventivas, a vigilância das condições bucais e a colaboração de uma equipe multidisciplinar são fundamentais para reduzir os riscos associados a essa condição patológica.(AU)
Objective: This work aims to provide a comprehensive analysis of the clinical, etiological, radiographic and histopathological characteristics of Medication-Related Jaw Osteonecrosis, in addition to addressing diagnostic methods, prevention and therapeutic strategies. Materials and methods: A search was carried out for scientific articles published between 2015 and 2023, using the Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) and ScienceDirect databases. Conclusion: Although infrequent, there is a considerable potential for osteonecrosis of the jaw to occur in patients undergoing prolonged therapy with antiresorptive and antiangiogenic medications, especially when adequate preventive measures are not adopted. The implementation of preventive practices, surveillance of oral conditions and the collaboration of a multidisciplinary team are essential to reduce the risks associated with this pathological condition.(AU)
Subject(s)
Humans , Osteonecrosis/chemically induced , Osteonecrosis/therapy , Jaw Diseases/chemically induced , Jaw Diseases/therapy , Risk Factors , Angiogenesis Inhibitors/adverse effects , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy , Denosumab/adverse effectsABSTRACT
Abstract Dill (Anethum graveolens L.) essential oil is wide spread in the food, beverage and pharmaceutical sectors. Dill is a member of the Apiaceae (Umbelliferae) family. It has the following biological activities: antioxidant, antifungal, antibacterial, antimicrobial, antihyperlipidemic, antihypercholesterolemic, antispasmodic, antiproliferative and anti-inflammatory. Aqueous extract of dill seed has reported effects on sex hormones and infertility potential. Moreover, boiled dill seed has an impact on reducing labor duration in giving birth. Implantation and placentation are necessary for a healthy pregnancy in the early stages. Angiogenesis is responsible for these essential processes. This study aimed to investigate dill seed oil's cytotoxic and antiangiogenic effects on rat adipose tissue endothelial cells (RATECs). Dill seed oil showed dose-dependent cytotoxicity on RATECs. It disrupted endothelial tube formation and depolymerized F-actin stress fibers. According to this study, depolymerization of F-actin stress fiber by dill seed oil could inhibit angiogenesis by suppressing endothelial cell proliferation, tube formation and motility. In other words, dill seed oil can be a new anti-angiogenic agent and a novel contraceptive.
Subject(s)
Seeds/anatomy & histology , Oils, Volatile/analysis , Angiogenesis Inhibitors/adverse effects , Anethum graveolens/adverse effects , Endothelial Cells/metabolism , Contraceptive Agents/classification , Infertility/pathologyABSTRACT
La osteonecrosis de los maxilares (ONM) secundaria al consumo de medicamentos antirresortivos y antiangiogénicos es una patología oral que afecta el funcionamiento del organismo de los seres humanos no sólo a nivel bucal, sino que disminuye su calidad de vida y aumenta su morbilidad. La ONM se define como la presencia de hueso necrótico expuesto que puede ser explorado mediante una fístula en el territorio maxilofacial, que se mantiene durante un periodo mínimo de ocho se- manas. Los fármacos antirresortivos y antiangiogénicos son indicados a pacientes que presentan patologías osteometabólicas, cáncer, entre otras, de ahí la importancia de mantener una estrecha relación entre médico tratante-odontólogo-paciente. El propósito de este artículo es establecer un protocolo de cuidado oral básico y definir las funciones del médico tratante, cirujano dentista y cirujano maxilofacial mediante una revisión bibliográfica con el fin de crear una propuesta preventiva para el tratamiento de estos pacientes (AU)
Medication-related osteonecrosis of the jaw (MRONJ), secondary to the consumption of antiresorptive and antiangiogenic drugs is an oral pathology that affects the functioning of the human body, not only at the oral level, but also decreasing their quality of life and increasing their morbidity. MRONJ is defined as the presence of exposed necrotic bone that can be explored through a fistula in the maxillofacial territory, which is maintained for a minimum period of eight weeks. Antiresorptive and antiangiogenic drugs are indicated for patients with osteometabolic pathologies, cancer, among others. For the same reasons, the importance of maintaining a close relationship between the treating physician, dentist and patient. The purpose of this article is to establish a clinical guide for basic oral care and define the functions of the treating physician, dental surgeon and maxillofacial surgeon through a bibliographic review; in order to create a preventive proposal for the treatment of these patients (AU)
Subject(s)
Humans , Male , Female , Angiogenesis Inhibitors/adverse effects , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/complications , Patient Care Team , Jaw Diseases/etiology , Clinical Protocols , Dental Care for Chronically Ill/methods , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & controlABSTRACT
Introducción: El uso del medicamento ranibizumab intravítreo favorece la reducción del edema macular generador de las oclusiones vasculares retinianas causantes de la pérdida visual. Objetivo: Evaluar la eficacia y seguridad de la administración intravítreo de ranibizumab en el cambio de espesor macular central en las oclusiones vasculares retinianas analizado mediante tomografía de coherencia óptica. Material y métodos: Se desarrolló un estudio de tipo retrospectivo, analítico, correlacional y observacional de campo con diseño no experimental en 125 pacientes mayores de 30 años con oclusión vascular retiniana diagnosticados en la consulta de oftalmología del Hospital "Teodoro Maldonado Carbó" durante enero de 2017 a junio de 2018. La técnica ANOVA compara las medias para determinar mediante el proceso de contraste de hipótesis si existen diferencias estadísticamente significativas entre estas. Resultados: El análisis de la agudeza visual con escala logMAR demostró diferencias estadísticamente significativas entre los promedios obtenidos 3 meses antes y después de la aplicación del tratamiento (p=0,0001). Se encontró 28,8 por ciento de efectos adversos. Con frecuencia en aumento de presión intraocular (4 por ciento), sequedad ocular (16 por ciento) y hemorragia conjuntival (11,2 por ciento). Conclusiones: El ranibizumab en oclusiones vasculares retinianas proporciona una mejor agudeza visual corregida en relación con el grosor macular, favorece el desarrollo de nuevos vasos sanguíneos a partir de vasos preexistentes desde migración de células endoteliales(AU)
Introduction: The use of the intravitreal ranibizumab favors the reduction of the macular edema that generates retinal vascular occlusions that cause visual loss. Objective: To evaluate the efficacy and safety of the intravitreal administration of ranibizumab in the change in central macular thickness in retinal vascular occlusions analyzed by optical coherence tomography. Material and methods: A retrospective, analytical, correlational and observational field study with a non-experimental design was carried out on 125 patients over 30 years of age diagnosed with retinal vascular occlusion in the Ophthalmology Service of "Teodoro Maldonado Carbó" Hospital during the period between January 2017 and June 2018. The ANOVA technique was used to compare means in order to determine, through the hypothesis contrast process, if there are statistically significant differences between them. Results: Visual acuity analysis using the logMAR scale showed statistically significant differences between the averages obtained 3 months before and after the application of the treatment (p =0.0001). In addition, 28,8 percent of adverse effects were found. The most frequent ones included increased intraocular pressure (4 percent), dry eyes (16 percent), and conjunctival hemorrhage (11,2 percent). Conclusions: In retinal vascular occlusions, Ranibizumab provides a better corrected visual acuity in relation to macular thickness, favors the development of new blood vessels from pre-existing vessels from endothelial cell migration(AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Vitreous Body , Retinal Vein Occlusion/therapy , Angiogenesis Inhibitors/therapeutic use , Tomography, Optical Coherence , Ranibizumab/therapeutic use , Visual Acuity , Macular Edema/therapy , Retrospective Studies , Treatment OutcomeABSTRACT
RESUMEN: La angiogénesis es el proceso de formación de vasos sanguíneos a partir de otros formados previamente. Existen varios factores que están involucrados en el proceso, así como agentes capaces de modular distintas etapas de esta. Si bien, se ha observado que Celecoxib es capaz de inhibir la angiogénesis en distintos modelos, aún no se ha observado la potencial capacidad antiangiogénica de este agente cuando es microencapsulado en PLGA. Se incubaron huevos fertilizados y a las 48 horas se dividieron en 4 grupos para ser instilados con PBS (control), PLGA, Celecoxib 1000 ppm o Celecoxib 1000 ppm + PLGA. Se realizó un conteo de los vasos sanguíneos a las 48, 72 y 96 horas post aplicación de la solución a estudiar. Los resultados muestran que tanto Celecoxib como Celecoxib+PLGA reducen los vasos sanguíneos, manteniendo el mismo efecto a las 48, 72 y 96 horas y no existen diferencias significativas entre los dos tratamientos. Esto podría ser explicado por la concentración de Celecoxib usada o el margen de tiempo analizado, pudiendo encontrarse diferencias posteriores a este rango de tiempo o con concentraciones distintas.
SUMMARY: Angiogenesis is the process of blood vessel formation from previously formed ones. There are several factors involved in the process, as well as agents capable of modulating different stages of it. Although, it has been observed that Celecoxib is capable of inhibiting angiogenesis in different models, the potential antiangiogenic capacity of this agent has not yet been observed when it is microencapsulated in PLGA. Fertilized eggs were incubated and at 48 hours they were divided into 4 groups to be instilled with PBS (control), PLGA, Celecoxib 1000ppm or Celecoxib 1000 ppm + PLGA. A blood vessel count was performed at 48, 72 and 96 hours after application of the solution to be studied. The results show that both Celecoxib and Celecoxib + PLGA reduce blood vessels, maintaining the same effect at 48, 72 and 96 hours and there are no significant differences between the two treatments. This could be explained by the concentration of Celecoxib used or the time frame analyzed, being able to find differences after this time range or with different concentrations.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Celecoxib/pharmacology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , CapsulesABSTRACT
RESUMO O hemangioma de coroide é um tumor vascular benigno, de coloração vermelho-alaranjada, bem delimitado, caracterizado por uma placa elevada. É um tumor raro, com prevalência de um caso a cada 40 tumores de coroide. O diagnóstico pode ser feito por meio da clínica associada à avaliação biomicroscópica e a exames complementares para diferenciação de outros tumores. O tratamento pode ser expectante nos casos assintomáticos. Para os casos sintomáticos ou com presença de fluido sub-retiniano, existem diversas terapias. O objetivo deste estudo foi relatar um caso de hemangioma circunscrito de coroide submetido a tratamento combinado de terapia fotodinâmica com verteporfina e injeção intravítrea de antiangiogênico (bevacizumabe). A decisão de tratar um hemangioma de coroide deve ser individualizada com base nos sintomas, na perda visual e em qualquer potencial de sua recuperação. O exame oftalmológico completo é necessário, mesmo em casos assintomáticos, para rastreamento precoce de doenças oculares.
ABSTRACT Choroid hemangioma is a benign, well-delimited orange-red, vascular tumor characterized by an elevated plaque. It is a rare tumor with a prevalence of one case in every 40 choroidal tumors. It can be diagnosed by the clinic associated with biomicroscopic evaluation and complementary tests to differentiate from other tumors. Treatment can be expectant in asymptomatic cases. For symptomatic cases or those with the presence of subretinal fluid, there are several therapies. The objective of this study was to report a case of circumscribed choroidal hemangioma submitted to combined treatment of photodynamic therapy with verteporfin and intravitreal injection of an antiangiogenic agent (bevacizumab). The decision to treat choroidal hemangioma must be individualized based on symptoms, visual loss, and any potential for recovery. A complete eye examination is necessary, even in asymptomatic cases, for early screening for eye diseases.
Subject(s)
Humans , Male , Middle Aged , Photochemotherapy/methods , Choroid Neoplasms/diagnosis , Choroid Neoplasms/therapy , Tomography, Optical Coherence , Bevacizumab/therapeutic use , Verteporfin/therapeutic use , Hemangioma/diagnosis , Hemangioma/therapy , Fluorescein Angiography , Choroid Neoplasms/pathology , Ultrasonography , Angiogenesis Inhibitors/therapeutic use , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Drug Therapy, Combination , Hemangioma/pathologyABSTRACT
ABSTRACT Reticular pigmentary retinal dystrophy, also known as Sjögren's reticular dystrophy, is a rare condition characterized by macular lesions with a reticular pattern, which are best seen on fluorescein angiogram. Choroidal neovascularization secondary to this type of dystrophy is even less common. This report describes a case of reticular pigmentary retinal dystrophy with vision loss due to neovascular membrane, which responded well to treatment with anti-vascular endothelial growth factor.
RESUMO A distrofia reticular pigmentar da retina, também conhecida como distrofia reticular de Sjögren, é uma doença rara, caracterizada por lesões maculares com um padrão reticular, que são mais bem visualizadas na angiografia com fluoresceína. A neovascularização de coroide secundária a este tipo de distrofia é ainda menos comum. Este relato descreve um caso de distrofia reticular pigmentar da retina, com perda de visão devido à membrana neovascular, que respondeu bem ao tratamento com fator de crescimento endotelial antivascular.
Subject(s)
Humans , Male , Aged , Retinitis Pigmentosa/complications , Choroidal Neovascularization/etiology , Choroidal Neovascularization/drug therapy , Retinal Dystrophies/complications , Ranibizumab/administration & dosage , Sjogren's Syndrome/complications , Follow-Up Studies , Choroidal Neovascularization/diagnosis , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Intravitreal Injections , Ranibizumab/therapeutic useABSTRACT
Breast cancer is the most common cancer in the world, and 5-year survival rate of metastatic breast cancer is about 20%. The treatment of metastatic breast cancer is mainly chemotherapy, endocrine therapy and targeted therapy. However, after multiline treatment, patients with MBC especially the triple negative breast cancer face the problem of drug resistance. Tumor angiogenesis theory suggests that blocking angiogenesis can inhibit tumor growth and migration. Based on this, angiogenesis treatment strategy is proposed. Antiangiogenic drugs mainly include biological macromolecular drugs targeting vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) and small molecule VEGFR inhibitors. Angiogenesis is known to play a key role in the growth and metastasis of breast cancer. Therefore, anti-angiogenetic therapy has potential in metastatic breast cancer patients. Since the approval of tumor drug indications by NPMA in China is often later than the release of the latest research data, the National Health Commission issued "the guiding principles for the clinical application of new antitumor drugs" in 2020. The principle pointed out that under special circumstances such as the absence of better treatment, medical institutions should manage the usage of drugs that are not clearly defined in the instructions but have evidence-based data. Based on the latest research progress in breast cancer, the consensus writing expert group collated published reports, international academic conferences, conducted analysis, discussion and summary, collected data on the use of small molecule anti-vascular targeting drugs for advanced breast cancer, and formulated "expert consensus on the application of small molecule anti-angiogenic drugs in the treatment of advanced breast cancer" . For clinicians' reference only.
Subject(s)
Female , Humans , Angiogenesis Inhibitors/therapeutic use , Breast Neoplasms/pathology , Consensus , Neovascularization, Pathologic/pathology , Off-Label Use , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented. .
Subject(s)
Humans , Angiogenesis Inhibitors/pharmacology , Bevacizumab/therapeutic use , Brain/metabolism , Consensus , Lung Neoplasms/drug therapy , Necrosis/etiology , Radiation Injuries/etiology , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Lung cancer is a highly vascular tumors, over the past ten years, anti-angiogenes is has been proved to be an effective and highly promising combinational treatment. The data of the combination of anti-angiogenesis with chemotherapy, targeted therapy, immunotherapy has been constantly updating. Advanced lung cancer patients, no matter different groups or different stages of the disease, are benefited from anti-angiogenes. In this paper, based on the clinical status and unsolved problems, combined with the latest clinical and translational research data, we reviewed the current anti-angiogenesis treatment of lung cancer. .
Subject(s)
Humans , Angiogenesis Inhibitors/therapeutic use , Immunotherapy , Lung Neoplasms/pathology , Molecular Targeted Therapy , Neovascularization, Pathologic/drug therapyABSTRACT
The present study investigated the mechanism of components in stasis-resolving and collateral-dredging Chinese herbal medicines, including scutellarin(Scu), paeonol(Pae), and hydroxy safflower yellow A(HSYA), in the treatment of psoriasis by regulating angiogenesis and inflammation. The human umbilical vein endothelial cells(HUVECs) cultured in vitro were divided into a normal group, a model group, a VEGFR tyrosine kinase inhibitor Ⅱ(VRI) group, and Scu, Pae, and HSYA groups with low, me-dium, and high doses. Cell viability was detected by the CCK-8 assay. Cell migration was detected by wound healing assay. Tube formation assay was used to measure the tube formation ability. Western blot was used to detect the protein expression of the VEGFR2/Akt/ERK1/2 signaling pathway. The secretion levels of inflammatory cytokines IFN-γ, IL-1β, IL-6, and TNF-α were detected by ELISA. The results showed that compared with the model group, all the Scu, Pae, and HSYA groups could reduce cell viability, inhibit cell migration and tube formation(P<0.05, P<0.01), and down-regulated the protein expression of VEGFR2, p-VEGFR2, Akt, p-Akt, ERK1/2, and p-ERK1/2. Scu and Pae could down-regulate VEGFR2 expression(P<0.05, P<0.01), while other groups only showed a downward trend. Scu and Pae significantly reduced IFN-γ and IL-6 levels(P<0.01), and HSYA significantly reduced the levels of IFN-γ, IL-1β, and IL-6(P<0.01). Scu, Pae, and HSYA had no significant effect on TNF-α. The results suggested that Scu, Pae, and HSYA may exert a therapeutic role in psoriasis-related angiogenesis and inflammation by inhibiting VEGFR2/Akt/ERK1/2 signaling pathway and inhibiting the secretion of IFN-γ, IL-1β, and IL-6.
Subject(s)
Humans , Angiogenesis Inhibitors/pharmacology , China , Human Umbilical Vein Endothelial Cells , Neovascularization, Pathologic/drug therapy , Vascular Endothelial Growth Factor A/metabolismABSTRACT
ABSTRACT Purpose: This study was conducted to evaluate visual function and changes in the central macular thickness of patients with unresponsive neovascular age-related macular degeneration who were switched from ranibizumab (Lucentis®) to aflibercept (Eylea®) treatment at 30 months. Methods: This retrospective study examined patients with neovascular age-related macular degeneration who were switched to aflibercept after ≥6 previous intravitreal ranibizumab injections at 4- to 8-week intervals. All patients were switched to intravitreal aflibercept (2.0 mg) and analyzed after 3 consecutive injections followed by a prore nata dosing regimen and after 30 months of treatment. Best corrected visual acuity, biomicroscopic examination, intraocular pressure, fundus examination, and central macular thickness were recorded at the start of treatment, before the transition to intravitreal aflibercept treatment, and at 6, 12, 18, 24, and 30 months of intravitreal aflibercept treatment. Results: A total of 33 eyes met the inclusion criteria. The median age of the patients was 73.57 ± 7.98 years, and 21 (61.8%) patients were males and 12 (35.3%) were females. Before the transition, the patients received a mean of 16.8 ± 8.8 ranibizumab injections (range 6-38).After the transition to intravitreal aflibercept treatment, the mean number of aflibercept injections was 9.09 ± 3.94. No significant differences were observed in best corrected visual acuity after the aflibercept switch in any of the months. The central macular thickness was significantly decreased at 6, 12, 18, and 30 months (p=0.01, p=0.03, p=0.05, p=0.05, p<0.001, respectively). Conclusion: Patients with neovascular age-related macular degeneration who were switched to intravitreal aflibercept treatment due to unresponsiveness to intravitreal ranibizumab exhibited a significant anatomic improvement in the retina, and although this state persisted, there was no significant functional gain.(AU)
RESUMO Objetivo: Avaliar, depois de 30 meses, a função visual e as alterações na espessura macular central de pacientes com degeneração macular relacionada à idade sem resposta terapêutica ao ranibizumabe (Lucentis®) que mudaram seu tratamento para o aflibercepte (Eylea®). Métodos: Realizou-se um estudo retrospectivo de pacientes com degeneração macular neovascular relacionada à idade que mudaram o tratamento para o aflibercepte após 6 ou mais injeções intravítreas de ranibizumabe a intervalos de 4-8 semanas. Todos os pacientes mudaram para o aflibercepte intravítreo (2,0 mg) e depois de 3 injeções consecutivas, seguidas de um regime de dosagem pro re nata, foram avaliados após 30 meses de tratamento. A melhor acuidade visual corrigida, o exame biomicroscópico, a pressão intraocular, a fundoscopia e a espessura macular central foram registrados no início do tratamento, antes da transição para o tratamento com aflibercepte intravítreo e aos 6, 12, 18, 24 e 30 meses de tratamento com o aflibercepte intravítreo. Resultados: Satisfizeram aos critérios de inclusão 33 olhos. A mediana da idade dos pacientes foi de 73,57 ± 7,98 anos. Dos pacientes, 21 (61,8%) eram homens e 12 (35,3%) eram mulheres. Antes da transição para o tratamento com o aflibercepte intravítreo, os pacientes receberam em média 16,8 ± 8,8 injeções de ranibizumabe (faixa 6-38).Depois da transição, o número médio de injeções de aflibercepte foi de 9,09 ± 3,94. Não houve diferenças significativas na melhor acuidade visual corrigida depois da mudança para o aflibercepte em qualquer das avaliações. Houve diminuição significativa da espessura macular central aos 6, 12, 18 e 30 meses (respectivamente, p=0,01, p=0,03, p=0,05, p=0,05 e p<0,001). Conclusão: Pacientes com degeneração macular neovascular relacionada à idade que mudaram seu tratamento para o aflibercepte intravítreo devido à falta de resposta ao ranibizumabe intravítreo, tiveram melhora anatômica significativa da retina; mas embora esse estado tenha persistido, não foi observado nenhum ganho funcional significativo.(AU)
Subject(s)
Humans , Retina/pathology , Visual Acuity , Angiogenesis Inhibitors/therapeutic use , Ranibizumab/therapeutic use , Macular Degeneration/physiopathology , Retrospective StudiesABSTRACT
Snake venoms are composed of pharmacologically active proteins that are evolutionarily diverse, stable and specific to targets. Hence, venoms have been explored as a source of bioactive molecules in treating numerous diseases. Recent evidences suggest that snake venom proteins may affect the formation of new blood vessels. Excessive angiogenesis has been implicated in several pathologies including tumours, diabetic retinopathy, arthritis, inter alia. In the present study, we have examined the effects of P-I metalloproteinases isolated from Bothrops moojeni (BmMP-1) and Bothrops atrox (BaMP-1) and L-amino acid oxidases (LAAO) isolated from B. moojeni (BmLAAO) and B. atrox (BaLAAO) on biochemical and functional aspects of angiogenesis. Methods: P-I metalloproteinases and LAAO were purified from venom by molecular size exclusion and ion-exchange chromatography and subsequently confirmed using mass spectrometry. The P-I metalloproteinases were characterized by azocaseinolytic, fibrinogenolytic and gelatinase activity and LAAO activity was assessed by enzyme activity on L-amino acids. Influence of these proteins on apoptosis and cell cycle in endothelial cells was analysed by flow cytometry. The angiogenic activity was determined by in vitro 3D spheroid assay, Matrigel tube forming assay, and in vivo agarose plug transformation in mice. Results: P-I metalloproteinases exhibited azocaseinolytic activity, cleaved α and partially β chain of fibrinogen, and displayed catalytic activity on gelatin. LAAO showed differential activity on L-amino acids. Flow cytometry analysis indicated that both P-I metalloproteinases and LAAO arrested the cells in G0/G1 phase and further induced both necrosis and apoptosis in endothelial cells. In vitro, P-I metalloproteinases and LAAO exhibited significant anti-angiogenic properties in 3D spheroid and Matrigel models by reducing sprout outgrowth and tube formation. Using agarose plug transplants in mice harbouring P-I metalloproteinases and LAAO we demonstrated a marked disruption of vasculature at the periphery. Conclusion: Our research suggests that P-I metalloproteinases and LAAO exhibit anti-angiogenic properties in vitro and in vivo.(AU)
Subject(s)
Animals , Oxidoreductases , Bothrops/physiology , Angiogenesis Inhibitors , Crotalid Venoms , MetalloproteasesABSTRACT
RESUMO Este trabalho visou evidenciar a importância da detecção precoce da coroidite interna punctata e destacar sua fisiopatologia inflamatória e possíveis diagnósticos diferenciais dentro das white dot syndromes. O destaque foi dado principalmente à coroidite multifocal e à panuveíte, ao se demonstrar sua epidemiologia peculiar em mulheres jovens, caracterizar sua apresentação clínica típica na fundoscopia e explorar as vantagens e as desvantagens de realizar os exames complementares que fazem parte da análise multimodal útil para o diagnóstico (especialmente a angiografia fluoresceínica, a tomografia de coerência óptica e a indocianina verde). Descreve-se o caso de uma mulher de 28 anos diagnosticada com coroidite interna punctata com membrana neovascular coroidal em olho direito. O tratamento foi realizado com injeção intravítrea de aflibercepte e corticoterapia sistêmica 1mg/kg ao dia. Este relato é importante por permitir debater o manejo da coroidite interna punctata durante a gestação e a decisão de realizar o tratamento mediante uma diversidade de opções terapêuticas.
ABSTRACT This work aimed to demonstrate the importance of early detection of punctate inner choroidopathy, highlighting the pathophysiology of inflammation and the differential diagnoses among white dot syndromes. Special attention was given to multifocal choroiditis and panuveitis, by demonstrating the peculiar epidemiology in young women, characterizing the typical clinical presentation in ophthalmoscopy, and exploring the advantages and disadvantages of performing the complementary examinations, which are part of the multimodal analysis useful for diagnosis (particularly fluorescein angiography, optical coherence tomography, and indocyanine green). We report the case of a 28-year-old female, diagnosed as punctate inner choroidopathy with choroidal [N.T. no título aparece subretinal = subrretiniana] neovascular membrane in the right eye. She was treated with intravitreal injection of aflibercept and systemic corticosteroid 1 mg/kg/day. This case report is important for addressing the management of punctate inner choroidopathy during pregnancy, and the decision to carry out treatment considering diverse therapeutic options.
Subject(s)
Humans , Female , Adult , Choroiditis/complications , Choroiditis/diagnosis , Choroiditis/physiopathology , Choroidal Neovascularization/etiology , Angiogenesis Inhibitors/therapeutic use , Intravitreal Injections/methods , Fluorescein Angiography/methods , Tomography, Optical Coherence/methodsABSTRACT
- Introdução: As demandas tumorais são supridas pela angiogênese (surgimento de vasos sanguíneos). Em hipóxia, são secretadas moléculas pró-angiogênicas, como o fator de crescimento vascular endotelial (VEGF), ativando vias de progressão, invasão e metástase tumoral; portanto, tais substâncias tornaram-se alvo nas terapias anti-tumorais. Objetivo: Analisar produções científicas sobre câncer e angiogênese, focando em VEGF, seu mecanismo de ação e vias terapêuticas. Método: Revisão integrativa de literatura utilizando base de dados PubMed e Scielo, com os descritores angiogenesis, cancer, VEGF, anti-angiogenic e treatment. Resultados: O VEGF, especialmente VEGF-A, liga-se ao receptor tirosina-quinase VEGFR-2 para induzir a migração de células endoteliais e ativar vias intracelulares, promovendo a liberação de proteases destrutoras da matriz extracelular que permitem o brotamento de vasos sanguíneos. Drogas anti-angiogênicas inibem o mecanismo de VEGF/VEGFR-2. Conclusão: Inibidores de VEGF desaceleram o crescimento neoplásico e melhoram a distribuição sistêmica de fármacos associados, sendo ampla a recomendação da administração conjunta de fármacos anti-angiogênicos e quimioterápicos tradicionais
Introduction: Tumor demands are supplied by angiogenesis (arise of blood vessels). In hypoxia, pro-angiogenic molecules are secreted, as vascular endothelial growth factor (VEGF), which activate pathways of tumor progression, invasion and metastasis. Therefore, such substances have become a target in anti-tumor therapies. Objective: Analyse scientific productions on cancer and angiogenesis, focusing on VEGF, its mechanism and therapeutics pathways. Method: Integrative literature review using the online databases PubMed and Scielo and the terms angiogenesis, cancer, VEGF, anti-angiogenic and treatment. Results: VEGF, especially VEGF-2, binds at VEGFR-2 tyrosine kinase receptor to induce endothelial cells migration and activate intracellular pathways to promote the release of destructive proteases from the extracellular matrix,, which allow blood vessels to sprout. Anti-angiogenic drugs inhibit the mechanism of VEGF/ VEGFR-2. Conclusion: VEGF inhibitors slow neoplastic growth and improve systemic distribution of associated drugs, which are widely recommended in joint administration of traditional anti-angiogenic and chemotherapeutic drugs
Subject(s)
Humans , Vascular Endothelial Growth Factors , Neoplasms , Neoplasms/therapy , Angiogenesis InhibitorsABSTRACT
The vascular network expansion and functioning are important factors affecting normal intra-uterine fetal development. This study addressed the previously reported antiangiogenic potential of beta-2-glycoprotein I (β2GPI) in vivo in the chick embryo model of angiogenesis. The effects of two naturally occurring β2GPI forms on the development of the chorioallantoic membrane (CAM) vessels and the chicken embryo were investigated. β2GPI monomers and dimers were obtained by fractioned purification and characterized using SDS-PAGE, immunoblot, and ELISA. The egg exposure was performed by injection of small volumes of 2.5 µg/mL solutions of the β2GPI subfractions. Angiogenesis was evaluated through quantitative measurements of vascular architecture parameters in the captured CAM images, using computational analysis of texture contrasts and computer vision techniques. Quantitative information was assigned to the CAM vasculature modifications. In vivo, the β2GPI dimer completely halted the formation of CAM vessels and led to embryo death after 48 h of exposure. The β2GPI monomer allowed the embryo to develop up to the 10th day, despite early changes of CAM vessels. The impaired normal vessel growth proceeded as a self-limited effect. The β2GPI monomer-exposed eggs showed reduced vascularization on the 6th day of incubation, but embryos were viable on the 10th day of incubation, with ingurgitated CAM vessels implying sequelae of the angiogenesis inhibition. Both subfractions impaired CAM vasculature development. The β2GPI dimer proved to be largely more harmful than the β2GPI monomer. β2GPI modification by cleavage or dimerization may play a role in angiogenesis control in vivo.
Subject(s)
Chickens , Chorioallantoic Membrane , Chick Embryo , Neovascularization, Physiologic , Angiogenesis Inhibitors/pharmacology , beta 2-Glycoprotein IABSTRACT
Immunotherapy has dramatically altered the treatment of non-small cell lung cancer. Currently, the emergence of combination strategies in immunotherapy has brightened the prospects of improved clinical outcomes and manageable safety profiles in the first/second-line settings. However, sub-optimal response rates are still observed in several clinical trials. Hence, alternative combination models and candidate selection strategies need to be explored. Herein, we have critically reviewed and commented on the published data from several clinical trials, including combined immunotherapy and chemotherapy, anti-angiogenic agents, epidermal growth factor receptor/anaplastic lymphoma kinase tyrosine kinase inhibitors, radiotherapy, and other immune checkpoint inhibitors.
Subject(s)
Humans , Angiogenesis Inhibitors/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Immunotherapy , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic useABSTRACT
Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.
Subject(s)
Humans , Angiogenesis Inhibitors/therapeutic use , Diabetes Mellitus , Diabetic Retinopathy/drug therapy , Intravitreal Injections , Macular Edema/drug therapy , Pharmaceutical Preparations , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors/therapeutic useABSTRACT
ABSTRACT Age-related macular degeneration is the leading cause of vision loss in elderly individuals, as well as a medical and socio-economic challenge. The treatment of dry age-related macular degeneration is based on vitamin supplementation. New treatment studies are focused on preventing the progression of degeneration and repopulating the atrophic macula. Recently, research on the treatment of neovascular age-related macular degeneration experienced a breakthrough with the advent of anti-vascular endothelial growth factor inhibitors. Nevertheless, despite the fact that ranibizumab, aflibercept, and bevacizumab are effective in reducing severe visual impairment, patients usually lose some vision over time. Therefore, the search for new therapies and diagnostic methods is fundamentally important. Current studies are focused on new anti-vascular endothelial growth factor drugs, nucleoside reverse transcriptase inhibitors, antibody against sphingosine-1-phosphate, anti-platelet-derived growth factor, gene therapy, and RNA interference. The results of ongoing clinical studies may improve the therapy of age-related macular degeneration.
RESUMO Degeneração macular relacionada à idade (DMRI) é a principal causa de perda de visão em pessoas idosas. É também um desafio médico e socioeconômico. O tratamento da degeneração macular relacionada à idade seca baseia-se na suplementação vitamínica. Novos tratamentos estão focados na prevenção da progressão da degeneração e tentativas de repovoar a mácula atrófica. A degeneração macular relacionada à idade neovascular experimentou um grande avanço com o advento dos inibidores do fator de crescimento endotelial anti-vascular (anti-VEGF); no entanto, apesar do ranibizumab, aflibercept e bevacizumab serem eficazes na redução do comprometimento visual grave, os pacientes geralmente perdem visão ao longo do tempo. Portanto, a busca por novas terapias, tratamentos e diagnósticos é de fundamental importância. Os estudos estão focados em novos fármacos sobre fator de crescimento endotelial anti-vascular, inibidores nucleosideos da transcriptase reversa, anticorpos contra esfingosina-1-fosfato, fator de crescimento derivado de plaquetas, terapia genética e RNA de interferência. A terapia para degeneração macular relacionada à idade está prestes a melhorar como resultado desses estudos clínicos em andamento.