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1.
Int. braz. j. urol ; 47(2): 295-305, Mar.-Apr. 2021. tab, graf
Article in English | LILACS | ID: biblio-1154442

ABSTRACT

ABSTRACT The standard treatment for locally advanced cervical cancer (CC) is chemoradiotherapy. Once the bladder receives part of the radiation, a typical inflammatory condition that configures radiation-induced cystitis may develop. Chronic radiation-induced cystitis is commonly characterized by the bladder new submucosal vascularization, which is typically fragile and favors hematuria. The current study aims to investigate if Hypoxia-Induced Factor (HIF-1α) and its transcriptional target Vascular Endothelial Growth Factor A (VEGF-A) could be a primary pathway leading to increased submucosal vascularization. HIF-1α and VEGF-A mRNA levels in bladder core biopsies from CC patients treated with radiotherapy versus untreated (non-irradiated) patients were analyzed using a droplet digital polymerase chain reaction technology. Gene expression results showed that HIF-1α and VEGF-A had no significant differences between bladder samples from patients previously irradiated and untreated patient samples. However, a direct relationship between the degree of late morbidity and the expression of HIF-1α and VEGF-A has been demonstrated. Despite the lack of statistical significance precludes a definitive conclusion, the data presented herein suggests that further studies investigating the role of HIF-1α in bladder neovascularization in radiation-induced cystitis are highly recommended.


Subject(s)
Humans , Female , Uterine Cervical Neoplasms , Cystitis/etiology , Case-Control Studies , Vascular Endothelial Growth Factor A , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Neovascularization, Pathologic
2.
Braz. j. med. biol. res ; 54(10): e10653, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285657

ABSTRACT

Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. In this study, we examined CAV-1 expression levels and VM in human glioma cell lines and in 94 human gliomas with different grades of malignancy, and present Cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, western blotting, CCK-8 assays, and tubule formation assays. Cav-1 expression and VM formation were positively correlated with each other and both were closely associated with glioma development and progression as evidenced by the presence of cystic tumor, shortened survival time, and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Collectively, our study identified Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.


Subject(s)
Humans , Caveolin 1/genetics , Glioma , Cell Line, Tumor , Cell Proliferation , Neovascularization, Pathologic
3.
MedUNAB ; 24(1): 72-79, 23-04-2021.
Article in Spanish | LILACS | ID: biblio-1222634

ABSTRACT

Introducción. Las malformaciones arteriovenosas son lesiones relativamente raras e infrecuentes. Se caracterizan por presentar un aumento anormal en el número de vasos sanguíneos como consecuencia de un defecto en el desarrollo vascular. Constituyen un desafío diagnóstico y terapéutico para el médico tratante. Su incidencia es de alrededor el 1.5% de la población general. Dentro de las opciones terapéuticas se incluye la embolización selectiva, la resección quirúrgica o ambas. El objetivo del presente artículo es reportar un caso de una patología poco frecuente y hacer una revisión literaria del tema para arrojar luz sobre su diagnóstico. Reporte de caso. Se presenta el caso de un paciente adulto joven que consulta por presentar una masa en glúteo derecho de 6 años de evolución. Esta es diagnosticada erróneamente como lipoma, por lo que se lleva al paciente a cirugía sin la realización de imágenes diagnósticas previas. En la cirugía, el paciente presenta choque hipovolémico. Posteriormente, se documenta la masa como malformación arteriovenosa profunda. Discusión. Es poco usual la ubicación de dichas malformaciones en los miembros inferiores, como en el paciente del actual caso. El diagnóstico de estas lesiones puede ser clínico, pero requiere del conocimiento o sospecha de esta entidad, ya que pueden ser lesiones clínicamente no visibles, lo que lleva a que pasen inadvertidas o se diagnostiquen de forma errónea. Conclusión. Aunque se trata de una patología poco frecuente, esta puede generar repercusiones clínicas, físicas, psicológicas y estéticas importantes, por lo que es indispensable realizar adecuados métodos por imágenes que permitan establecer su correcto diagnóstico y manejo. Cómo citar. Rodriguez-Londoño NH. Malformación arteriovenosa de alto flujo en un adulto joven. MedUNAB. 2021;24(1): 72-79. doi: https://doi.org/10.29375/01237047.3785


Introduction. Arteriovenous malformations are relative rare and infrequent injuries. Their main characteristic is an abnormal increase in the number of blood vessels as a result of defective vascular development. They represent a diagnostic and therapeutic challenge for the treating physician. Their incidence in the general population is around 1.5%. Some therapeutic options include selective embolization, surgical resection, or both. The purpose of this article is to report a case of an infrequent pathology and to perform a literature review on the topic to shed light on its diagnosis. Case report. The case involves a young adult patient who inquired about the presence of a mass in the right buttock with six years of evolution. It was erroneously diagnosed as a lipoma, as a result of which the patient was taken to surgery without performing preliminary diagnostic images. During surgery, the patient went into hypovolemic shock. Afterwards, the mass was documented as a profound arteriovenous malformation. Discussion. Such malformations are rarely found in the lower limbs, as in this case. These injuries may be clinically diagnosed, but knowledge or suspicion on the existence of this entity is required, because such injuries might not be clinically visible, which implies that they may go unnoticed or be erroneously diagnosed. Conclusion. Even though it is an infrequent pathology, it may have substantial clinical, physical, psychological and aesthetic implications, which implies that it is indispensable to perform adequate imaging-based procedures to enable its adequate diagnosis and management. Cómo citar. Rodriguez-Londoño NH. Malformación arteriovenosa de alto flujo en un adulto joven. MedUNAB. 2021;24(1): 72-79. doi: https://doi.org/10.29375/01237047.3785


Introdução. As malformações arteriovenosas são lesões relativamente raras e infrequentes. São caracterizadas por apresentarem um aumento anormal do número de vasos sanguíneos como consequência de um defeito no desenvolvimento vascular. Constituem um desafio diagnóstico e terapêutico para o médico que trata. Sua incidência gira em torno de 1.5% da população geral. As opções de tratamento incluem embolização seletiva, ressecção cirúrgica ou ambas. O objetivo deste artigo é relatar um caso de patologia pouco frequente e fazer uma revisão bibliográfica sobre o assunto para lançar luz sobre seu diagnóstico. Relato de caso. Apresentamos o caso de um paciente adulto jovem que consultou por apresentar uma massa na nádega direita, de 6 anos de evolução. Isso é diagnosticado erroneamente como um lipoma, então o paciente é levado para cirurgia sem imagens diagnósticas prévias. Na cirurgia, o paciente apresenta um choque hipovolêmico. Posteriormente, a massa é documentada como uma malformação arteriovenosa profunda. Discussão. A localização dessas malformações nos membros inferiores é incomum, como no caso deste paciente. O diagnóstico dessas lesões pode ser clínico, mas requer conhecimento ou suspeita dessa entidade, pois podem ser lesões clinicamente invisíveis, o que as leva a passar despercebidas ou mal diagnosticadas. Conclusão. Embora seja uma patologia pouco frequente, pode gerar importantes repercussões clínicas, físicas, psicológicas e estéticas, pelo que é imprescindível a realização de métodos de imagem adequados para estabelecer seu correto diagnóstico e tratamento. Cómo citar. Rodriguez-Londoño NH. Malformación arteriovenosa de alto flujo en un adulto joven. MedUNAB. 2021;24(1): 72-79. doi: https://doi.org/10.29375/01237047.3785


Subject(s)
Vascular Malformations , Shock , Angiography , Embolization, Therapeutic , Neovascularization, Pathologic
4.
Odontoestomatol ; 22(35): 52-61, jul. 2020. ilus.
Article in Spanish | LILACS, BNUY, BNUY-Odon | ID: biblio-1103063

ABSTRACT

Con el fin de tener una mayor comprensión sobre el comportamiento biológico del mixoma odontogénico (MO), se realizó inmunohistoquímica en 31 muestras, utilizando marcadores relacionados con mecanismos de progresión tumoral (adhesión, angiogénesis, apoptosis, inflamación y proliferación celular). El epitelio odontogénico fue detectado en cuatro muestras mediante CK19 y CD138, este último, mostró expresión baja en matriz extracelular (MEC) y alta en las células tumorales. La microdensidad vascular (MDV) media fue de 7.51 y 5.35 vasos marcados con CD34 y VEGF-A respectivamente. Una alta expresión de Orosomucoide-1 y Mast Cell Tryptase se observó células tumorales y en MEC. El MO mostró negatividad para Calretinina. Este perfil inmunohistoquímico, la baja expresión para Ki-67, Bcl-2 y p53, y la relativamente baja MDV, sugieren que la actividad proliferativa, anti-apoptótica o angiogénica no representan los principales mecanismos de crecimiento del MO, los cuales podrían estar asociados a eventos como inmunomodulación y degradación de la MEC.


Immunohistochemistry tests were performed in 31 samples to elucidate the biological behavior of the odontogenic myxoma (OM), using markers related to mechanisms of tumor progression (adhesion, angiogenesis, apoptosis, inflammation and cell proliferation). Odontogenic epithelium was detected in four samples with CK19 and CD138; the latter had a low expression in the extracellular matrix (ECM) and a high expression in tumor cells. The mean microvascular density (MVD), assessed with CD34 and VEGF-A, was 7.51 and 5.35 blood vessels. A high expression of orosomucoid-1 and mast cell tryptase was observed in tumor cells and ECM, while calretinin was negative. The immunohistochemical profile mentioned above, as well as the low expression of Ki67, Bcl-2 and p53 and the relatively low MVD, suggest that the proliferative, antiapoptotic and angiogenic activities do not represent the main growing mechanisms of OM, which could be associated to other events, such as immunomodulation and ECM degradation.


Para melhor compreensão do comportamento biológico do mixoma odontogênico (MO), imuno-histoquímica foi realizada em 31 amostras, utilizando marcadores relacionados aos mecanismos de progressão tumoral (adesão, angiogênese, apoptose, inflamação e proliferação celular). Epitélio odontogênico foi detectado em quatro amostras por CK19 e CD138, o último mostrou baixa expressão na matriz extracelular (MEC) e alta em células tumorais. A microdensidade vascular (MDV) média foi de 7.51 e 5.35 vasos marcados com CD34 e VEGF-A, respectivamente. Uma alta expressão de Orosomucoide-1 e Mast Cell Tryptase foi observada nas células tumorais e na MEC. O MO mostrou negatividade para Calretinina. O perfil imuno-histoquímico mencionado acima, a baixa expressão de Ki-67, Bcl-2 e p53 e a relativamente baixa MDV, sugerem que a atividade proliferativa, anti-apoptótica ou angiogênica não representam os principais mecanismos de crescimento do MO, os quais poderiam estar associados com eventos como imunomodulação e degradação da MEC.


Subject(s)
Immunohistochemistry , Biomarkers, Tumor , Myxoma , Neovascularization, Pathologic
5.
Arq. neuropsiquiatr ; 78(1): 34-38, Jan. 2020. graf
Article in English | LILACS | ID: biblio-1088980

ABSTRACT

Abstract Brain tumors are one of the most common causes of cancer-related deaths around the world. Angiogenesis is critical in high-grade malignant gliomas, such as glioblastoma multiforme. Objective: The aim of this study is to comparatively analyze the angiogenesis-related genes, namely VEGFA, VEGFB, KDR, CXCL8, CXCR1 and CXCR2 in LGG vs. GBM to identify molecular distinctions using datasets available on The Cancer Genome Atlas (TCGA). Methods: DNA sequencing and mRNA expression data for 514 brain lower grade glioma (LGG) and 592 glioblastoma multiforme (GBM) patients were acquired from The Cancer Genome Atlas (TCGA), and the genetic alterations and expression levels of the selected genes were analyzed. Results: We identified six distinct KDR mutations in the LGG patients and 18 distinct KDR mutations in the GBM patients, including missense and nonsense mutations, frame shift deletion and altered splice region. Furthermore, VEGFA and CXCL8 were significantly overexpressed within GBM patients. Conclusions: VEGFA and CXCL8 are important factors for angiogenesis, which are suggested to have significant roles during tumorigenesis. Our results provide further evidence that VEGFA and CXCL8 could induce angiogenesis and promote LGG to progress into GBM. These findings could be useful in developing novel targeted therapeutics approaches in the future.


Resumo Os tumores cerebrais são uma das causas mais comuns de mortes relacionadas ao câncer em todo o mundo. A angiogênese tem caráter crítico em gliomas malignos de alto grau, como o glioblastoma multiforme. Objetivo: O objetivo deste estudo foi analisar comparativamente os genes relacionados à angiogênese, VEGFA, VEGFB, KDR, CXCL8, CXCR1 e CXCR2 em GBG vs. GBM para identificar distinções moleculares usando conjuntos de dados disponíveis no The Cancer Genome Atlas (TCGA). Métodos: Os dados de sequenciamento de DNA e expressão de mRNA para 514 pacientes com glioma cerebral de baixo grau (GBG) e 592 pacientes com glioblastoma multiforme (GBM) foram adquiridos do TCGA e as alterações genéticas e os níveis de expressão dos genes selecionados foram analisados. Resultados: Identificamos seis mutações KDR distintas nos pacientes GBG e 18 mutações KDR distintas nos pacientes GBM, incluindo mutações missense e nonsense, exclusão de mudança de quadro e região de emenda alterada. Além disso, VEGFA e CXCL8 foram significativamente super-expressos nos pacientes com GBM. Conclusões: VEGFA e CXCL8 são fatores importantes para a angiogênese, os quais parecem ter um papel significativo durante a tumorigênese. Nossos resultados fornecem evidências adicionais de que o VEGFA e o CXCL8 podem induzir a angiogênese e promover o GBG a progredir no GBM. Esses achados podem ser úteis no desenvolvimento de novas abordagens terapêuticas direcionadas no futuro.


Subject(s)
Humans , Brain Neoplasms/genetics , Glioblastoma/genetics , Carcinogenesis/genetics , Glioma/genetics , Neovascularization, Pathologic/genetics , Reference Values , Gene Expression , Interleukin-8/analysis , Point Mutation/genetics , Glioblastoma/pathology , Receptors, Interleukin-8A/analysis , Receptors, Interleukin-8B/analysis , Vascular Endothelial Growth Factor Receptor-2/analysis , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor B/analysis , Glioma/pathology
6.
Biol. Res ; 53: 41, 2020. graf
Article in English | LILACS | ID: biblio-1131885

ABSTRACT

BACKGROUND: Tumor angiogenesis is an essential event for tumor growth and metastasis. It has been showed that REC8, a component of the meiotic cohesion complex, played a vital role in Epithelial-Mesenchymal Transition (EMT) in gastric cancer. However, the role of REC8 in gastric cancer angiogenesis remains to be identified. RESULTS: Inhibition of REC8 expression in gastric cancer cells contributed to tumor angiogenesis in the gastric cancer microenvironment. The clinical analysis demonstrated that the loss of REC8 in gastric cancer with enrichment of MVD. Depletion of REC8 expression in gastric cancer cells significantly increased tube formation of human umbilical vein endothelial cells (HUVECs), which is attributed to enhancement of vascular endothelial growth factor (VEGF) secretion caused by REC8 slicing. While addition of neutralizing antibody targeted VEGF into supernatant drastically reversed the effect of REC8 loss in gastric cancer cells on tube formation. Mechanistic analyses indicated that ablation of REC8 promotes nuclear factor-κB (NF-κB) p65 activity and its downstream gene VEGF expression, leading to tube formation. CONCLUSIONS: These results demonstrated a novel REC8 function that suppressed tumor angiogenesis and progression by attenuation of VEGF in gastric cancer microenvironment.


Subject(s)
Humans , Stomach Neoplasms/pathology , NF-kappa B/genetics , Cell Cycle Proteins/genetics , Vascular Endothelial Growth Factor A/genetics , Neovascularization, Pathologic/genetics , Stomach Neoplasms/blood supply , Cell Line, Tumor , Tumor Microenvironment , Human Umbilical Vein Endothelial Cells
7.
Journal of Experimental Hematology ; (6): 2084-2088, 2020.
Article in Chinese | WPRIM | ID: wpr-880019

ABSTRACT

Exosomes are microvesicles that can be secreting in many kinds of cells, under the condition of normal and pathology. Exosomes contain abundant proteins, miRNAs and RNA fragments, which play an important role in communicating between cells, especially non-contact cells. The interaction between blood tumor cells and immune microenvironment is inseparable from the involvement of exosomes. Exosomes are involved in the interaction among tumor cells, NK cells, T cells, stromal cells and endothelial cells, such as promoting the proliferation of blood tumor cells, helping blood tumor cells to achieve immune evasion, promoting angiogenesis and migration of tumor cells. Therefore, exosomes are closely related to the diagnosis, treatment and prognosis of hematological tumors. In this review, the basic characteristics of exosomes, the important role of exosomes in the immune microenvironment of hematological tumors, and the research progress of exosomes in clinical applications was sammrized briefly.


Subject(s)
Endothelial Cells , Exosomes , Hematologic Neoplasms , Humans , Neovascularization, Pathologic , Research , Tumor Microenvironment
8.
Journal of Experimental Hematology ; (6): 1962-1971, 2020.
Article in Chinese | WPRIM | ID: wpr-880000

ABSTRACT

OBJECTIVE@#To investigate the expressions of stromal cell-derived factor (CXCL12), stromal cell-derived factor receptor (CXCR4), vascular endothelial growth factor (VEGF) and microvessel density (MVD) in bone marrow microsputum of patients with multiple myeloma (MM) and their correlation with the prognosis.@*METHODS@#The expressions of CXCL12, CXCR4, VEGF and MVD in bone marrow microtubules of 57 newly diagnosed MM patients and 26 normal bone marrow samples were detected by immunohistochemistry. The rank sum test was used to compare the differences between the two groups. The clinical data of the patients were collected to analyze the correlation between the indicators of the MM group and the prognosis.@*RESULTS@#The expressions of CXCL12, CXCR4, VEGF and MVD in the bone marrow biopsy of the patients in MM group were significantly higher than those in the normal control group (P<0.05). The expressions levels of CXCL12, CXCR4, VEGF and MVD were in the bone marrow of the patients in MM group were correlated with the ISS stage, risk stratification and the proportion of plasma cells in the bone marrow (P<0.05). Univariate analysis showed that age, ISS stage, risk stratification, plasma cell ratio, expressions of CXCL12, CXCR4, VEGF, and MVD associated with the prognosis of patients with MM (P<0.05). Multivariate analysis found that expressions of CXCR4, VEGF, MVD, age, and plasma cell ratio were independent prognostic factors.@*CONCLUSION@#The expressions of CXCL12, CXCR4, VEGF and MVD are increase in the bone marrow of patients with multiple myeloma, and their expressions levels are associate with the occurrence and development of multiple myeloma, and their high expression may indicate a poor prognosis.


Subject(s)
Chemokine CXCL12 , Humans , Multiple Myeloma , Neovascularization, Pathologic , Patients , Prognosis , Receptors, CXCR4 , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
9.
Chinese Medical Journal ; (24): 508-517, 2020.
Article in English | WPRIM | ID: wpr-877908

ABSTRACT

Neuropilins (NRP1 and NRP2) are multifunctional receptor proteins that are involved in nerve, blood vessel, and tumor development. NRP1 was first found to be expressed in neurons, but subsequent studies have demonstrated its surface expression in cells from the endothelium and lymph nodes. NRP1 has been demonstrated to be involved in the occurrence and development of a variety of cancers. NRP1 interacts with various cytokines, such as vascular endothelial growth factor family and its receptor and transforming growth factor β1 and its receptor, to affect tumor angiogenesis, tumor proliferation, and migration. In addition, NRP1+ regulatory T cells (Tregs) play an inhibitory role in tumor immunity. High numbers of NRP1+ Tregs were associated with cancer prognosis. Targeting NRP1 has shown promise, and antagonists against NRP1 have had therapeutic efficacy in preliminary clinical studies. NRP1 treatment modalities using nanomaterials, targeted drugs, oncolytic viruses, and radio-chemotherapy have gradually been developed. Hence, we reviewed the use of NRP1 in the context of tumorigenesis, progression, and treatment.


Subject(s)
Humans , Neoplasms/drug therapy , Neovascularization, Pathologic , Neuropilin-1 , Vascular Endothelial Growth Factor A
10.
Acta Physiologica Sinica ; (6): 441-448, 2020.
Article in Chinese | WPRIM | ID: wpr-827043

ABSTRACT

The aim of the present study was to investigate the role of chemokine CCL2 in angiogenesis of primary adult rat cardiac microvascular endothelial cells (CMEC). The rat CMECs were isolated and identified through morphology examination and immunostaining with CD31 and factor VIII antibodies. The angiogenesis of CMEC on Matrigel was evaluated at different time points. The expression and secretion of CCL2 during the process of angiogenesis was detected by real-time RT-PCR and ELISA, respectively. The results showed that, the primary rat CMEC was isolated successfully, and the angiogenesis of CMEC was significantly induced after Matrigel treatment for 4 h. The expression of CCL2 and CCR2 were increased during angiogenesis, and the secretion of CCL2 was detected after 2 h of angiogenesis and reached the peak concentration of 1 588.1 pg/mL after 4 h. Either CCL2 blocking antibody or CCR2 antagonist significantly reduced the angiogenesis of CMEC. These results suggest that CCL2 is secreted during the process of angiogenesis of CMEC, and CCL2/CCR2 signaling pathway may play an important role in promoting angiogenesis.


Subject(s)
Animals , Chemokine CCL2 , Endothelial Cells , Endothelium, Vascular , Heart , Neovascularization, Pathologic , Rats , Signal Transduction
11.
Int. j. morphol ; 37(4): 1572-1577, Dec. 2019. tab
Article in English | LILACS | ID: biblio-1040171

ABSTRACT

Hypoxia hypobaric (HH) can cause alterations at testicular level, with temperature increase, intrascrotal alteration and deterioration of spermatogenesis. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ketoprofen have anti-angiogenic properties, and can decrease testicular abnormalities. The objective of the study was to evaluate the effect of ketoprofen on spermatogenesis of mice exposed to continuous hypobaric hypoxia. 78 Mus musculus CF-1 male mice 3 to 4 months old were used and subjected to HH in chamber at 4200 m. They were divided into 13 groups (G) of 6 animals: 10 with HH cycles (1, 2, 3, 4 and 8, lasting 8.3 days each cycle, two groups each) and 3 in normoxia (Nx). Intraperitoneal ketoprofen 25 mg/kg was administered every 4 days. Euthanasia of these animals was performed at the end of each cycle and in the case the Nx groups at the end of cycles 1, 4 and 8. Percentage of microhematocrit and reticulocytes were measured in blood smears and a morphometric and histopathological analysis of the height of the epithelium, the tubular diameter and the diameter of the tubular lumen was made. It was shown that hematocrit increases continuously up to 8 cycles, while reticulocytes increase up to 3 cycles. Continuous HH decreases the tubular diameter in a sustained manner and proportional to HH cycles, and the height increased only in the groups subjected to 8 cycles. The groups treated with ketoprofen saw a decrease in angiogenesis, presenting some degree of protection at the testicular level.


La hipoxia hipobárica (HH) puede provocar alteraciones a nivel testicular, con aumento de la temperatura, alteración intraescrotal y deterioro de la espermatogénesis. Los antiinflamatorios no esteroidales (AINEs) como el ketoprofeno tienen propiedades antiangiogénicas, pudiendo disminuir las alteraciones testiculares. El objetivo de estudio fue evaluar el efecto del ketoprofeno en la espermatogénesis de ratones expuestos a hipoxia hipobárica continua. Se utilizaron 78 ratones macho Mus musculus CF-1 de 3 a 4 meses de edad y se sometieron a HH en cámara a 4200 m. Se dividieron en 13 grupos (G) de 6 animales: 10 con ciclos de HH (1, 2, 3, 4 y 8, con duración de 8,3 días cada ciclo, dos grupos cada uno) y 3 en normoxia (Nx). Se administró ketoprofeno intraperitoneal 25 mg/kg cada 4 días. La eutanasia de estos animales se realizó al final de cada ciclo y en el caso los grupos Nx al final de los ciclos 1, 4 y 8. Se midió porcentaje de microhematocrito y reticulocitos en frotis de sangre y se hizo un análisis morfométrico e histopatológico de la altura del epitelio, el diámetro tubular y el diámetro de la luz tubular. Se evidenció que el hematocrito aumenta de manera continua hasta los 8 ciclos, en cambio los reticulocitos aumentan hasta los 3 ciclos. La HH continua disminuye el diámetro tubular de forma sostenida y proporcional a los ciclos de HH, y la altura aumentó sólo en los grupos sometidos a 8 ciclos. Los grupos tratados con ketoprofeno se vio una disminución de la angiogénesis, presentando algún grado de protección a nivel testicular.


Subject(s)
Animals , Male , Mice , Spermatogenesis/drug effects , Testis/drug effects , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Ketoprofen/pharmacology , Hypoxia/physiopathology , Reticulocytes/drug effects , Seminiferous Tubules/drug effects , Testis/injuries , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Ketoprofen/administration & dosage , Hematocrit , Neovascularization, Pathologic
12.
Rev. Soc. Cardiol. Estado de Säo Paulo ; 29(4,Supl): 387-392, out.-dez. 2019.
Article in Portuguese | LILACS | ID: biblio-1047320

ABSTRACT

A finalidade do sistema cardiovascular é manter uma perfusão adequada e, para tanto, conta com uma bomba eficiente (coração) e um sistema de condução apropriado, representado pelos vasos arteriais e venosos. Este artigo visa abordar os diferentes ajustes funcionais e estruturais decorrentes do treinamento físico no sistema vascular, que contribuem principalmente para melhorar a capacidade física dos indivíduos. Para tanto, o sistema conta com vários mecanismos, dentre eles neurais, hormonais e locais, que podem ser avaliados por meio de diferentes técnicas, tanto in vivo quanto in vitro. Após um período de treinamento físico, tem-se evidenciado uma melhor inter-relação entre sistema neural e local, promovendo menor atividade nervosa simpática acompanhada por simpatólise mais pronunciada. Além disso, o treinamento físico melhora a reatividade vascular de artérias, por melhorar a biodisponibilidade de óxido nítrico. Na parede vascular, o treinamento melhora o equilíbrio entre os componentes da matriz extracelular, favorecendo a redução da rigidez arterial em grandes artérias e a redução da razão parede-luz em arteríolas da musculatura locomotora e não locomotora, o que contribui para melhor distensibilidade dos vasos e redução da resistência periférica total, principalmente em casos patológicos. Por fim, o treinamento físico favorece a angiogênese na microcirculação, que contribui significativamente para nutrição tecidual


The purpose of the cardiovascular system is to maintain complete perfusion and, to this end, it has an efficient pump (the heart) and an appropriate conduction system, represented by arterial and venous vessels. This article addresses the different functional and structural adjustments resulting from physical training in the vascular system, which contribute mainly to improve the physical capacity of individuals. Therefore, the system has several mechanisms, including neural, hormonal and local mechanisms, which may be evaluated by different techniques, both in vivo and in vitro. After a period of physical training, a better interrelationship between neural and local systems has been evidenced, promoting less sympathetic nervous activity accompanied by more pronounced sympatholysis. In addition, physical training improves vascular reactivity of arteries by improving nitric oxide bioavailability. In the vascular wall, training improves balance between extracellular matrix components, favoring reduced of stiffness of the large arteries and reduced wall-to-lumen ratio in locomotor and non-locomotor muscle arterioles, which contributes to improving vessel distensibility and total peripheral resistance, especially in pathological cases. Finally, physical training favors microcirculatory angiogenesis, which contributes significantly to tissue nutrition


Subject(s)
Exercise , Vascular Stiffness , Arteries , Cardiovascular Diseases , Cardiovascular System , Endothelium , Microcirculation , Neovascularization, Pathologic
13.
Arch. endocrinol. metab. (Online) ; 63(6): 568-575, Nov.-Dec. 2019. graf
Article in English | LILACS | ID: biblio-1055025

ABSTRACT

ABSTRACT Tumor development is a multistep process whereby local mechanisms enable somatic mutations during preneoplastic stages. Once a tumor develops, it becomes a complex organ composed of multiple cell types. Interactions between malignant and non-transformed cells and tissues create a tumor microenvironment (TME) comprising epithelial cancer cells, cancer stem cells, non-tumorous cells, stromal cells, immune-inflammatory cells, blood and lymphatic vascular network, and extracellular matrix. We review reports and present a hypothesis that postulates the involvement of growth hormone (GH) in field cancerization. We discuss GH contribution to TME, promoting epithelial-to-mesenchymal transition, accumulation of unrepaired DNA damage, tumor vascularity, and resistance to therapy. Arch Endocrinol Metab. 2019;63(6):568-75


Subject(s)
Humans , DNA Damage/physiology , Drug Resistance, Neoplasm/physiology , Human Growth Hormone/physiology , Epithelial-Mesenchymal Transition/physiology , Tumor Microenvironment/physiology , Neovascularization, Pathologic/physiopathology
14.
CorSalud ; 11(3): 203-210, jul.-set. 2019. tab
Article in Spanish | LILACS | ID: biblio-1089738

ABSTRACT

RESUMEN Introducción: La terapia con ondas de choque extracorpórea de baja intensidad ha demostrado ser útil en el tratamiento de los pacientes con angina de pecho refractaria. Objetivo: Valorar los resultados de este tipo de terapia en pacientes con angina refractaria al tratamiento farmacológico. Método: Se realizó un estudio cuasiexperimental en 30 pacientes con angina de pecho refractaria a tratamiento, seleccionados de forma no probabilística a partir de los criterios de inclusión. A todos los pacientes se les aplicó terapia con ondas de choque extracorpórea de baja intensidad en el Cardiocentro Ernesto Guevara de Santa Clara, en el período comprendido de enero a diciembre de 2017. Se analizaron variables epidemiológicas, clínicas y ecocardiográficas al inicio del tratamiento y 6 meses después de concluido este. Resultados: Los resultados obtenidos demostraron una mejoría de la clase funcional (CF) de la Canadian Cardiovascular Society (CCS). Previo al tratamiento el 76,7% de los pacientes tenían una CF III y un 23,3% una CF IV, y a los 6 meses de concluida la terapia el 73,3% mejoró a la CF II y solo un 26,7% quedó en CF III. También se evidenció mejoría con respecto a parámetros ecocardiográficos como la motilidad regional y la fracción de eyección del ventrículo izquierdo, la cual, en los hombres, de una media al inicio de la terapia de un 37,81% alcanzó 44,14% a los 6 meses de concluida; y en las mujeres, de una media de 37,11% inicial llegó a 47,22% a los 6 meses después. Conclusiones: El tratamiento con ondas de choque constituye una alterativa terapéutica para los pacientes con angina refractaria.


ABSTRACT Introduction: Low intensity extracorporeal shock wave therapy has proven useful in the treatment of patients with refractory angina pectoris. Objective: To assess the results of this type of therapy in patients with refractory angina to drug treatment. Method: A quasi-experimental study was carried out in 30 patients with refractory angina pectoris to treatment, selected in a non-probabilistic way, taking into account the following inclusion criteria. All patients were applied low intensity extracorporeal shock wave therapy in the Cardiocentro Ernesto Guevara of Santa Clara, in the period from January to December 2017. Epidemiological, clinical and echocardiographic variables were analyzed at the beginning of the treatment and six months after it was completed. Results: The results obtained demonstrated an improvement of the functional class (FC) of the Canadian Cardiovascular Society (CCS). Previous to treatment, 76.7% of patients had a FC III and 23.3% a FC IV, and after six months of completed therapy, 73.3% improved to FC II and only 26.7 % remained in FC III. There was also an improvement with respect to echocardiographic parameters such as regional motility and left ventricular ejection fraction, which, in men, of an average at the start of therapy of 37.81% it reached 44.14% at six months of completed; and in women, of an average of 37.11% initially, it reached 47.22 % six months later. Conclusions: The treatment with shock waves represents a therapeutic alternative for patients with refractory angina.


Subject(s)
Angina Pectoris , Extracorporeal Shockwave Therapy , Neovascularization, Pathologic
15.
Arq. bras. oftalmol ; 82(4): 339-344, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019406

ABSTRACT

ABSTRACT Wide-field angiography enables assessing peripheral areas with better quality and gives greater deep focus, which improves the image periphery. Some studies have proposed the usefulness of these angiographic systems in inflammatory diseases of the retina. However, few studies have evaluated this technique in Eales disease. We present a case series in which 5 eyes of 3 patients with Eales disease were evaluated by using retinal fluorescein angiography with 30º, 50º, and 150º lenses in a laser-scanning ophthalmoscope. These cases highlight the usefulness of wide-field fluorescein angiography in the diagnosis and follow-up of peripheral ischemic retinal areas in Eales disease, which enables better follow-up than possible with conventional fluorescein angiography images.


RESUMO A angiografia de campo amplo permite avaliar áreas periféricas com melhor qualidade e proporciona maior foco profundo, melhorando a imagem da periferia. Alguns estudos têm proposto a utilidade desses sistemas angiográficos nas doenças inflamatórias da retina. No entanto, poucos estudos avaliaram esta técnica na doença de Eales. Apresentamos uma série de casos em que 5 olhos de 3 pacientes com doença de Eales foram avaliados usando angiografia de fluoresceína da retina com lentes de 30º, 50º e 150º em um oftalmoscópio de varredura a laser. Esses casos destacam a utilidade da angiografia com fluoresceína de campo amplo no diagnóstico e no acompanhamento das áreas isquêmicas periféricas da retina na doença de Eales, permitindo um melhor acompanhamento do o possível com imagens por angiofluoresceinografia convencional.


Subject(s)
Humans , Male , Female , Adult , Young Adult , Fluorescein Angiography/methods , Retinal Vasculitis/diagnostic imaging , Neovascularization, Pathologic/diagnostic imaging , Retina/diagnostic imaging , Time Factors , Visual Acuity , Reproducibility of Results , Follow-Up Studies , Retinal Vasculitis/pathology , Retinal Vasculitis/therapy , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/therapy
16.
Int. j. morphol ; 37(2): 606-611, June 2019. tab, graf
Article in English | LILACS | ID: biblio-1002265

ABSTRACT

The purpose of this study was to examine the expression levels of the dental pulp to elucidate the role of Vascular Endothelial Growth Factor (VEGF) and CD68 on vascular angiogenesis, inflammation and odontoblast differentiation in the pulp tissue of diabetic rats depending on the effect of possible damage induced by diabetes. Wistar rats were used in the study, divided into two groups. Control group was fed with standard rat chow and drinking water ad libitum for 8 weeks. Single dose of streptozotocin (STZ) (55 mg/kg), was disolved in sodium citrate buffer and administered by intraperitoneal injection. Blood glucose concentration of rats exceeding 250 mg/dl were accepted as diabetic. Rats were sacrificed under anesthesia. Tissues were immediately dissected, fixed and embedded in paraffin and cut with a microtome then examined under light microscope. In the cross-sections of pulp tissue of diabetic group; the dilation of blood vessels besides hemorrhage and a significant increase in inflammatory cells were seen. The expression of VEGF in the blood vessel endothelial cells of the pulp was increased. VEGF showed positive reaction for degenerative odontoblast cells in the pulp. In this study, increase in VEGF and CD68 expressions in pulp tissue due to the effect of diabetes was thought to delay pulp treatment by inducing soft tissue damage and hypoxia.


El propósito de este estudio fue examinar los niveles de expresión en la pulpa dental para dilucidar el papel del Factor de Crecimiento Endotelial Vascular (VEGF) y el CD68 en la angiogénesis, la inflamación y la diferenciación de odontoblastos en el tejido pulpar de ratas diabéticas, dependiendo del efecto de daño inducido por la diabetes. Se utilizaron ratas Wistar divididas en dos grupos. El grupocontrol se alimentó con comida estándar para ratas y agua potable ad libitum durante 8 semanas. Se administró mediante inyección intraperitoneal dosis única de estreptozotocina (STZ) (55 mg / kg), se disolvió en tampón de citrato de sodio. La concentración de glucosa en sangre de ratas que excedían los 250 mg / dl se aceptó como diabética. Las ratas fueron sacrificadas bajo anestesia. Los tejidos se disecaron de inmediato, se fijaron en parafina y se cortaron para luego ser examinados con un microscopio óptico. En las secciones transversales del tejido pulpar del grupo diabético se observó la dilatación de los vasos sanguíneos además de hemorragia y un aumento significativo de células inflamatorias. La expresión de VEGF se incrementó en las células endoteliales de los vasos sanguíneos de la pulpa. VEGF mostró una reacción positiva para las células odontoblásticas degenerativas en la pulpa. El aumento en la expresión de VEGF y CD68 en el tejido de la pulpa debido al efecto de la diabetes puede retrasar el tratamiento de la pulpa al inducir hipoxia y daños en los tejidos blandos.


Subject(s)
Animals , Male , Rats , Dental Pulp/metabolism , Dental Pulp/pathology , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Immunohistochemistry , Antigens, CD/metabolism , Blotting, Western , Rats, Wistar , Vascular Endothelial Growth Factor A/metabolism , Inflammation , Neovascularization, Pathologic
17.
Int. arch. otorhinolaryngol. (Impr.) ; 23(1): 60-64, Jan.-Mar. 2019. tab, graf
Article in English | LILACS | ID: biblio-1002175

ABSTRACT

Abstract Introduction The human larynx is a very important organ for communication. Many conditions lead to scarring of the vocal folds, decreasing voice quality. Objective We aimed to determine whether fibroblast growth factors (FGFs) may influence tissue integration of grafted fascia into the vocal folds of an animal model. Methods This is an experimental animal study with 12 adult rabbits that were submitted to a grafting fragment obtained from superficial cervical fascia into the vocal fold lamina propria, bilaterally. The right vocal fold was injected with FGFs. The animals were sacrificed after 1 month or 12 months, depending on the group they were assigned to, and a histological analysis of their vocal folds was performed.We analyzed the histological changes (such as the presence of fibrosis and neovascularization) induced by the acute or chronic inflammatory reactions. Results The FGFs induced acute inflammatory changes in all animals after 1 month of the initial experiment. The presence of FGFs triggered more fibrosis than the expected due to the surgical procedure itself when compared with the control side of all animals after 12 months of the initial experiment. Conclusions Fibroblast growth factors alone do not represent a good therapeutic option in phonosurgery, since we observed higher levels of fibrosis in the vocal fold lamina propria. Further studies combining more substances may be necessary to elucidate the best option to be used in this kind of surgery. (AU)


Subject(s)
Animals , Vocal Cords/pathology , Fascia Lata/transplantation , Fibroblast Growth Factors/pharmacology , Rabbits , Fibrosis/etiology , Laryngeal Diseases/congenital , Inflammation/chemically induced , Neovascularization, Pathologic/etiology
18.
Article in English | WPRIM | ID: wpr-776888

ABSTRACT

Integrin is a large family of cell adhesion molecules (CAMs) which involves in the interaction of cells/cells and cells/ extracellular matrix (ECM) to mediate cell proliferation, differentiation, adhesion, migration, etc. In recent years, aberrant expression of integrin has been clearly found in many tumor studies, indicating that integrin is closely related to tumor formation and development. Meanwhile, it has effects on tumor cell differentiation, cell migration, proliferation and tumor neovascularization. The study of drugs targeting integrins is of great significance for the clinical treatment of tumors. Because of its important role in tumorigenesis and development, integrin has become a promising target for the treatment of cancer. This review summarizes the role of integrin in tumor development and the current state of integrin inhibitors to provide a valuable reference for subsequent research.


Subject(s)
Antineoplastic Agents , Pharmacology , Therapeutic Uses , Biological Products , Pharmacology , Therapeutic Uses , Cell Movement , Cell Proliferation , Extracellular Matrix , Metabolism , Humans , Integrins , Classification , Genetics , Metabolism , Neoplasms , Drug Therapy , Pathology , Neovascularization, Pathologic , Drug Therapy , Pathology , Signal Transduction
19.
Article in Chinese | WPRIM | ID: wpr-773499

ABSTRACT

OBJECTIVE@#To isolate tumor stem-like cells from human epithelial ovarian cancer SKOV3 cells and explore their role in the formation of vascularization mimicry (VM).@*METHODS@#SKOV3 cells were passaged to the 7th generation by suspension culture in serum-free medium, and the percentages of CD133- and CD117-positive cells in the 1st, 3rd, 5th and 7th generations were analyzed using flow cytometry. The proliferative activity of the cells sorted from the 7th generation SKOV3 cells was assessed with colony formation assay. A three-dimensional cell culture model was established to compare the ability of VM formation between the sorted cells and the parental SKOV3 cells. The expression levels of matrix metalloproteinases-2 (MMP-2) and MMP-9 in the two groups were detected using real-time PCR and Western blotting.@*RESULTS@#Some SKOV3 cells formed typical cell spheres with suspension growth in serum-free medium and were passaged to the 7th generation. Flow cytometry revealed that the percentage of CD133-positive cells increased with cell passaging. The cloning efficiency of the sorted cells was significantly higher than that of the parental SKOV3 cells (50.33% 5.33%, < 0.001). The VM formation ability of the sorted cells was stronger than that of the parental SKOV3 cells in the three-dimensional cell culture system. RT-PCR and Western blotting showed that the expression levels of MMP-2 and MMP-9 were significantly higher in the 7th passage cells than in the parental cells ( < 0.05).@*CONCLUSIONS@#The sorted cells from SKOV3 cells cultured in serum-free medium exhibit biological properties of tumor stem cells with strong VM formation ability, suggesting their role in VM formation.


Subject(s)
Carcinoma, Ovarian Epithelial , Pathology , Cell Line, Tumor , Cell Movement , Female , Humans , Matrix Metalloproteinase 2 , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Neoplastic Stem Cells , Cell Biology , Neovascularization, Pathologic , Pathology , Ovarian Neoplasms , Pathology
20.
Article in Chinese | WPRIM | ID: wpr-776040

ABSTRACT

Retinopathy of prematurity(ROP)is a pathological neovascularization with fibrotic changes in the fundus of premature infants.It is a major cause of preventable blindness in children in both developing and developed countries.Treatment of ROP has long been a hot research topic in ophthalmology and pediatrics.With a clearer knowledge of the pathogenesis of ROP,more basic and clinical studies have been carried out.The anti-vascular endothelial growth factor therapy and surgical treatment have become mature strategies,and a variety of therapeutic drugs including insulin-like growth factor-1,transforming growth factor-β,polyunsaturated fatty acids,and β-adrenergic receptor blockers have been developed.This article reviews the recent advances in ROP.


Subject(s)
Child , Humans , Infant, Newborn , Infant, Premature , Neovascularization, Pathologic , Therapeutics , Retinopathy of Prematurity , Drug Therapy , General Surgery , Vascular Endothelial Growth Factor A
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