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1.
Article in Chinese | WPRIM | ID: wpr-878899

ABSTRACT

To investigate the effects of Dahuang Zhechong Pills combined with hepatic arterial chemoembolization(TACE) on tumor index and immune function of patients with primary liver cancer(blood stasis and collaterals blocking type), observe its application values in treatment of such patients, and provide effective treatment means for this disease. From June 2019 to December 2019, 79 patients with confirmed primary liver cancer(blood stasis and collaterals blocking type) treated in Wenzhou Hospital of Traditional Chinese Medicine were included in this study, all of which were grouped with random number table method before inclusion in this study. 40 patients in the control group were treated with TACE, while 39 patients in the observation group were treated with Dahuang Zhechong Pills combined with TACE. The efficacy was compared between two groups after 4 weeks of treatment. The immune function indexes of serum CD4~+ cells, CD4~+/CD8~+, CD3~+ cells of the observation group were higher than those in control group after treatment(P<0.05), and tumor indexes such as serum alpha-fetoprotein(AFP), carbohydrate antigen 199(CA199) and glutamic-pyruvic transaminase(ALT), total bilirubin(TBiL) levels were lower than those in the control group, with statistically significant differences(P<0.05). Plasma vascular endothelial growth factor(VEGF), transforming growth factor-β1(TGF-β1), and matrix metalloprotei-nase-2(MMP-2) levels in the observation group were lower than those in the control group after treatment, with statistically significant differences(P<0.05). The total effective rate of the observation group was 87.18%, higher than 67.50% in the control group, and the benefit rate was 94.87% in the observation group, higher than 85.00% in the control group(P<0.05). The total incidence of adverse reactions such as bone marrow suppression, gastrointestinal reaction, fever, renal function injury and peripheral nerve injury in the observation group was 48.72%, lower than 82.50% in the control group, with statistically significant difference(P<0.05). In summary, the combination of Dahuang Zhechong Pills with TACE could improve immunity, protect liver function, and reduce the risk of metastasis and the incidence of adverse reactions from chemotherapy, so it is worth popularizing for patients with primary liver cancer(blood stasis and collaterals blocking type).


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Drugs, Chinese Herbal , Humans , Liver Neoplasms/drug therapy , Matrix Metalloproteinase 2 , Transforming Growth Factor beta1 , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
2.
Article in Chinese | WPRIM | ID: wpr-921540

ABSTRACT

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)
Angiogenesis Inhibitors/therapeutic use , Diabetes Mellitus , Diabetic Retinopathy/drug therapy , Humans , Intravitreal Injections , Macular Edema/drug therapy , Pharmaceutical Preparations , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors/therapeutic use
3.
Chinese Journal of Biotechnology ; (12): 4083-4094, 2021.
Article in Chinese | WPRIM | ID: wpr-921489

ABSTRACT

Vascular endothelial growth factor (VEGF165) is a highly specific vascular endothelial growth factor that can be used to treat many cardiovascular diseases. The development of anti-tumor drugs and disease detection reagents requires highly pure VEGF165 (at least 95% purity). To date, the methods for heterologous expression and purification of VEGF165 require multiple purification steps, but the product purity remains to be low. In this study, we optimized the codons of the human VEGF165 gene (vegf165) according to the yeast codon preference. Based on the Pichia pastoris BBPB vector, we used the Biobrick method to construct a five-copy rhVEGF165 recombinant expression vector using Pgap as the promoter. In addition, a histidine tag was added to the vector. Facilitated by the His tag and the heparin-binding domain of VEGF165, we were able to obtain highly pure rhVEGF165 (purity > 98%) protein using two-step affinity chromatography. The purified rhVEGF165 was biologically active, and reached a concentration of 0.45 mg/mL. The new design of the expression vector enables production of active and highly pure rhVEGF165 ) in a simplified purification process, the purity of the biologically active natural VEGF165 reached the highest reported to date.


Subject(s)
Codon/genetics , Humans , Pichia/genetics , Recombinant Proteins/genetics , Saccharomycetales , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factors
4.
Braz. j. med. biol. res ; 54(10): e11028, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285653

ABSTRACT

Engeletin is a natural derivative of Smilax glabra rhizomilax that exhibits anti-inflammatory activity and suppresses lipid peroxidation. In the present study, we sought to elucidate the mechanistic basis for the neuroprotective and pro-angiogenic activity of engeltin in a human umbilical vein endothelial cells (HUVECs) oxygen-glucose deprivation and reoxygenation (OGD/R) model system and a middle cerebral artery occlusion (MCAO) rat model of cerebral ischemia and reperfusion injury. These analyses revealed that engeletin (10, 20, or 40 mg/kg) was able to reduce the infarct volume, increase cerebral blood flow, improve neurological function, and bolster the expression of vascular endothelial growth factor (VEGF), vasohibin-2 (Vash-2), angiopoietin-1 (Ang-1), phosphorylated human angiopoietin receptor tyrosine kinase 2 (p-Tie2), and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in MCAO rats. Similarly, engeletin (100, 200, or 400 nM) markedly enhanced the migration, tube formation, and VEGF expression of HUVECs in an OGD/R model system, while the VEGF receptor (R) inhibitor axitinib reversed the observed changes in HUVEC tube formation activity and Vash-2, VEGF, and CD31 expression. These data suggested that engeletin exhibited significant neuroprotective effects against cerebral ischemia and reperfusion injury in rats, and improved cerebrovascular angiogenesis by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways.


Subject(s)
Animals , Rats , Reperfusion Injury/prevention & control , Brain Ischemia/prevention & control , Infarction, Middle Cerebral Artery , Endothelial Cells , Flavonols , Angiopoietin-1 , Vascular Endothelial Growth Factors , Vascular Endothelial Growth Factor A , Glycosides
5.
Rev. Méd. Paraná ; 79(1): 106-111, 2021.
Article in Portuguese | LILACS | ID: biblio-1282511

ABSTRACT

- 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 Inhibitors
6.
ABCS health sci ; 45(Supl. 3): e020108, 10 June 2020.
Article in English | LILACS | ID: biblio-1252391

ABSTRACT

Diabetic Macular Edema is a major cause of visual impairment in economically active population, being responsible for a significant impact in quality of life in the affected population, as well as high costs to the health care system. Over decades, some studies have compared treatments using Laser, Anti-VEGF and intravitreous corticosteroids, establishing protocols to reach effectives therapies. Thus, it is essential an entire understanding of available therapies to reach the goal of disease control, in an individual basis and in a collective health care system, as efficient as possible.


Subject(s)
Humans , Macular Edema/therapy , Diabetes Complications , Laser Coagulation , Vascular Endothelial Growth Factors , Tomography, Optical Coherence , Intravitreal Injections
7.
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
8.
Braz. arch. biol. technol ; 63: e20200059, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132201

ABSTRACT

Abstract Hypoxia occurs in the splanchnic region during exercise associated with sympathetic activity. In the elderly, vascular insufficiency and low vascular endothelial growth factor (VEGF) expression are observed. Compared to young people, sympathetic signals of older individuals are blunted and more resistant to splanchnic blood flow alterations during exercise. VEGF induces vasodilation responses and hence may retain blood in the splanchnic vascular bed. We hypothesized that regular mild-intensity exercise triggers weak VEGF expression in the digestive tract of the elderly. The effects of exercise on the levels of VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) in the stomach, jejunum, ileum and colon tissues were evaluated. With exercise, the VEGF levels in the stomach and colon increased. Although the SOD, GPx, and MDA levels decreased in the stomach, they increased in the colon. T-AOC increased in the stomach and there was no change in the jejunum, ileum and colon. The hypoperfusion during exercise was not equal in all regions of the gastrointestinal tract in the aged subjects. Hypoxia and other exercise-related mechanisms could have led to this VEGF induction. The stomach, jejunum, and ileum might have developed resistance to ischemia. The induction of VEGF may be beneficial in aging-associated impaired gastrointestinal homeostasis and neovascularization.


Subject(s)
Animals , Male , Rats , Superoxide Dismutase/blood , Exercise/physiology , Gastrointestinal Tract/metabolism , Vascular Endothelial Growth Factors/metabolism , Glutathione Peroxidase/blood , Malondialdehyde/blood , Vasodilation , Rats, Sprague-Dawley , Exercise Test
9.
Article in English | WPRIM | ID: wpr-762682

ABSTRACT

PURPOSE: Despite plasma biomarkers offering a number of advantages over tissue-based markers, the relationship between serum vascular endothelial growth factor (VEGF) and VEGF receptor (VEGF-R) tumor expression in colorectal cancer (CRC) is still unclear. This study was designed to establish the relationship between the concentration of serum VEGF and tumor VEGF-R expression in patients with CRC. METHODS: A prospective study of consecutive patients undergoing elective colorectal surgery during 1 year. Preoperative VEGF was determined by enzyme-linked immunosorbent assay and VEGF-R3 by immunochemistry. RESULTS: The initial sample included 134 patients with CRC diagnosis. Results showed significant association of serum values of VEGF with VEGF-R3 expression (P < 0.001), even in the presence of confounders (sex, age, body mass index, tumor location, and surgical approach). The estimated effect size was high (η² = 0.35). CONCLUSION: Serum VEGF has a significant correlation with tumoral VEGF-R3 expression in CRC.


Subject(s)
Biomarkers , Body Mass Index , Colorectal Neoplasms , Colorectal Surgery , Diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Immunochemistry , Immunohistochemistry , Plasma , Prospective Studies , Receptors, Vascular Endothelial Growth Factor , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
10.
Säo Paulo med. j ; 136(6): 543-550, Nov.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-991686

ABSTRACT

ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Colitis, Ulcerative/blood , Irritable Bowel Syndrome/blood , Endostatins/blood , Vascular Endothelial Growth Factors/metabolism , Intestinal Mucosa/blood supply , Enzyme-Linked Immunosorbent Assay , Colitis, Ulcerative/pathology , Case-Control Studies , Cross-Sectional Studies , Irritable Bowel Syndrome/pathology , Vascular Endothelial Growth Factors/blood , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology
11.
Article in English | WPRIM | ID: wpr-717365

ABSTRACT

Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities—including hyperpermeability, hypoperfusion, and neoangiogenesis—that eventually lead to anatomical and functional alterations in retinal neurons and glial cells. Recent advances in retinal imaging systems using optical coherence tomography technologies and pharmacological treatments using anti-vascular endothelial growth factor drugs and corticosteroids have revolutionized the clinical management of DR. However, the cellular and molecular mechanisms underlying the pathophysiology of DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects of subclinical and early DR. Conversely, non-diabetic mouse models that represent the hallmark vascular disorders in DR, such as pericyte deficiency and retinal ischemia, have provided clues toward an understanding of the sequential events that are responsible for vision-impairing conditions. In this review, we summarize the clinical manifestations and treatment modalities of DR, discuss current and emerging concepts with regard to the pathophysiology of DR, and introduce perspectives on the development of new drugs, emphasizing the breakdown of the blood-retina barrier and retinal neovascularization.


Subject(s)
Adrenal Cortex Hormones , Angiopoietins , Animals , Diabetic Retinopathy , Endothelial Cells , Endothelial Growth Factors , Ischemia , Macular Edema , Mice , Models, Animal , Neuroglia , Pericytes , Retinal Neovascularization , Retinal Neurons , Retinaldehyde , Tomography, Optical Coherence , Vascular Endothelial Growth Factors
12.
Article in English | WPRIM | ID: wpr-716899

ABSTRACT

OBJECTIVE: The favored method of preserving fertility in young female cancer survivors is cryopreservation and autotransplantation of ovarian tissue. Reducing hypoxia until angiogenesis takes place is essential for the survival of transplanted ovarian tissue. The aim of this study was to investigate the role of angiopoietin-1 (Angpt-1), angiopoietin-2 (Angpt-2), and vascular endothelial growth factor (VEGF) in ovarian tissue grafts that were cryopreserved using two methods. METHODS: Ovarian tissues harvested from ICR mice were divided into three groups: group I (control), no cryopreservation; group II, vitrification in EFS (ethylene-glycol, ficoll, and sucrose solution)-40; and group III, slow freezing in dimethyl sulfoxide. We extracted mRNA for VEGF, Angpt-1, and Angpt-2 from ovarian tissue 1 week following cryopreservation and again 2 weeks after autotransplantation. We used reverse transcriptase-polymerase chain reaction to quantify the levels of VEGF, Angpt-1, and Angpt-2 in the tissue. RESULTS: Angpt-1 and Angpt-2 expression decreased after cryopreservation in groups II and III. After autotransplantation, Angpt-1 and Angpt-2 expression in ovarian tissue showed different trends. Angpt-1 expression in groups II and III was lower than in group I, but Angpt-2 in groups II and III showed no significant difference from group I. The vitrified ovarian tissues had higher expression of VEGF and Angpt-2 than the slowfrozen ovarian tissues, but the difference was not statistically significant. CONCLUSION: Our results indicate that Angpt-2 may play an important role in ovarian tissue transplantation after cryopreservation although further studies are needed to understand its exact function.


Subject(s)
Angiopoietin-1 , Angiopoietin-2 , Animals , Hypoxia , Autografts , Cryopreservation , Dimethyl Sulfoxide , Female , Fertility , Fertility Preservation , Ficoll , Freezing , Humans , Methods , Mice , Mice, Inbred ICR , Ovary , Reverse Transcriptase Polymerase Chain Reaction , RNA, Messenger , Sucrose , Survivors , Tissue Transplantation , Transplantation, Autologous , Transplants , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors , Vitrification
13.
Article in English | WPRIM | ID: wpr-764785

ABSTRACT

PURPOSE: Bone marrow has long been a source of primary cells. This study was performed to evaluate the effects of age and sex on the cellular viability and expression of stem cell markers of mRNA and on the protein expression of bone marrow stem cells (BMSCs) derived from healthy donors. MATERIALS AND METHODS: Stem cells were isolated from human bone marrow and plated in culture plates. The shape of the BMSCs was observed under inverted microscope. Quantitative cellular viability was evaluated using a Cell-Counting Kit-8 assay. The expression of stem cell surface markers was tested and a series of quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot was performed to evaluate the expression in each group. RESULT: The shapes of the cells at 20s, 30s, and 50s were similar to each other. No significant changes in cellular viability were noted among different age groups or sex groups. The BMSCs expressed CD44, CD73, and CD90 surface markers but did not express CD14 and CD34. There were no noticeable differences in CD surface markers among the different age groups. The expressions of CD surface markers were similar between men and women. No significant differences in the secretion of vascular endothelial growth factors (VEGFs) were noted at Day 3 between different age groups. qRT-PCR regarding the expression showed differences between the age groups. However, Western blot analysis showed a decrease in expression but did not reach statistical significance (P>0.05). CONCLUSION: This study clearly showed no significant differences in shape, cell viability, expression of stem cell surface markers, or secretion of human VEGF among different age groups. However, western blot analysis showed a tendency of age-related decrease which did not reach statistical significance. Collectively, autologous or allogeneic BMSCs should be meticulously applied to obtain optimal results regarding age and sex.


Subject(s)
Age Factors , Blotting, Western , Bone Marrow , Cell Shape , Cell Survival , Female , Humans , Male , Real-Time Polymerase Chain Reaction , RNA, Messenger , Stem Cells , Tissue Donors , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
14.
Campinas; s.n; 2018. 162 p. ilus, tab.
Thesis in Portuguese | LILACS, Inca | ID: biblio-912068

ABSTRACT

Resumo: Introdução: endometriose é uma doença benigna, capaz de progredir extensamente e gerar clones atípicos. Considerada precursora dos carcinomas de células claras (CCOC) e endometrióide (EOC) de ovário, atualmente chamados carcinomas de ovário associados à endometriose (EAOC). Objetivos: comparar o perfil epidemiológico, a associação com endometriose e a expressão de marcadores imuno-histoquímicos para ARID1A, VEGF, PD-L1 e PARP-1 em mulheres com CCOC e EOC, e sua correlação com a sobrevida livre de progressão (SLP) e sobrevida global (SG). Métodos: estudo de coorte reconstituída, com 50 casos incluídos de CCOC e EOC tratados no CAISM-UNICAMP entre 1995 até 2016, acompanhados até 02/2017. Microarranjos de tecido com amostras de CCOC, EOC e endometriose foram corados com anticorpos monoclonais contra ARID1A, e para os biomarcadores proteicos VEGF, PD-L1, PARP-1 através de imuno-histoquímica. A expressão de ARID1A foi classificada (0 a 100) conforme a porcentagem de células não coradas. A expressão de VEGF, PD-L1 e PARP-1 foi classificada (0 a 300) conforme a multiplicação da porcentagem de células coradas por um fator da intensidade de expressão (ausente=0; fraco=1; moderado=2; forte=3). Idade ao diagnóstico; menopausa; índice de massa corpórea (IMC); CA-125; diagnóstico de endometriose; datas do diagnóstico, da progressão, do óbito e da última consulta foram recuperados dos prontuários. Comparação entre grupos foi realizada através de testes T e de ?2. A SLP (diferença de tempo entre o diagnóstico e a data de progressão) e a SG (diferença de tempo entre o diagnóstico e o óbito ou data da última data de consulta) foi avaliada através de curvas de Kaplan-Meyer e teste de Log-Rank ou regressão de COX. Resultados: 23 mulheres com CCOC (46%), e 27 com EOC (54%) foram incluídas; 80% tinham endometriose associada, 42% eram nulíparas, 42% eram pré-menopausa e CA125 foi elevado em todos estádios (FIGO I-II= média 614.7Ui/mL; FIGO III-IV= media 2361.2Ui/mL). A média de idade ao diagnóstico foi 7 anos menor em mulheres com EOC do que naquelas com CCOC. O CCOC foi mais diagnosticado em estágios iniciais quando associado à endometriose (p=0,03). O prognóstico dos EOC e CCOC em estádios iniciais foi semelhante (p=0,96). Os CCOC não associado à endometriose tiveram menor SG (p=0,04). A expressão de todos os biomarcadores esteve presente nos EAOC e na endometriose. O aumento da expressão de VEGF entre endometriose e câncer foi significativo (p=0,0002). A hiperexpressão de PARP-1 correlacionou-se negativamente com a SLP (p=0,03) e SG (p=0,01) em estádios iniciais. Conclusão: Os CCOC e EOC são comumente diagnosticados em estádios iniciais (FIGO I-II= 68%) e estão frequentemente associados à endometriose (80% dos casos). Quando associados à endometriose, os CCOC foram mais diagnosticados em estádios iniciais e tiveram SG maior. Houve elevada porcentagem de células com ARID1A mutado nos EAOC (>40%). VEGF se expressou mais intensamente nos CCOC e EOC que na endometriose, já a expressão de PD-L1 e de PARP-1 foi similar. Apenas a hiperexpressão de PARP-1 reduziu significativamente a SLP e a SG nos CCOC e EOC nos estádios iniciais(AU)


Abstract: Introduction: Endometriosis is a benign disease, able to progress widely and generate atypical clones. It is a precursor of clear cell ovarian carcinomas (CCOC) and endometrioid ovarian carcinomas (EOCs), now called endometriosis-associated ovarian carcinomas (EAOC). Objectives: To compare the epidemiological profile, association with endometriosis and the expression of immunohistochemical markers for ARID1A, VEGF, PD-L1 and PARP-1 in women with CCOC and EOC, and its correlation with progression-free survival (PFS) and overall survival (OS). Methods: A reconstituted cohort study with 50 cases of CCOC and EOC included. Cases were treated at CAISM-UNICAMP between 1995 and 2016, followed up until 02/2017. Tissue microarrays with CCOC, EOC and endometriosis samples were stained with monoclonal antibodies against ARID1A, and for VEGF, PD-L1, PARP-1 biomarkers by immunohistochemistry. The expression of ARID1A was classified (0 to 100) according to the percentage of unstained cells. The expression of VEGF, PD-L1 and PARP-1 was classified (0 to 300) multiplying the percentage of stained cells by an intensity of expression factor (absent=0, weak=1, moderate=2, strong=3). Age at diagnosis; menopause; BMI (body mass index); CA-125 levels; diagnosis of endometriosis; date of diagnosis, date of progression, date of death and date of last consultation were retrieved from the medical records. Comparison between groups was performed through T and ?2 tests. The PFS (difference in time between diagnosis and progression date) and OS (difference in time between diagnosis and death or the last date of consultation) was assessed using Kaplan-Meyer curves and Log-Rank test or COX multivariate models. Results: twenty-three women with CCOC (46%), and 27 with EOC (54%) were included; 80% had associated endometriosis, 42% were nulliparous, 42% were premenopausal, and CA125 was elevated at all stages (FIGO I-II = mean 614.7Ui / mL; FIGO III-IV = mean 2361.2Ui / mL). The mean age at diagnosis was 7 years lower in women with EOC than in those with CCOC. CCOC when associated with endometriosis were more diagnosed at early stages (p=0.03). The prognosis of EOC and CCOC at early stages was similar (p=0.96). CCOCs not associated with endometriosis had shorter OS (p=0.04). Expression of all biomarkers was present in the EAOC and endometriosis. The increase in VEGF expression between endometriosis and cancer was significant (p=0.0002). The overexpression of PARP-1 correlated negatively with PFS (p=0.03) and OS (p=0.01) at FIGO I-II stages. Conclusion: The diagnosis of women with EOC was made earlier than in those with CCOC. CCOC and EOC are commonly diagnosed in early stages (FIGO I-II - 68%) and were associated with endometriosis (80% of cases). When associated with endometriosis, clear cell carcinomas are more likely diagnosed at early stages, and the association of endometriosis with CCOC improves OS. There was a high percentage of cells with mutated ARID1A gene in EAOC (> 40%). VEGF was expressed more intensely in CCOC and EOC than in endometriosis, whereas expression of PD-L1 and PARP-1 was similar. Only the overexpression of PARP-1 significantly reduced PFS and OS in CCOC and EOC at early stages(AU)


Subject(s)
Humans , Female , Prognosis , Carcinoma, Endometrioid , Endometriosis , Survival Rate , Adenocarcinoma, Clear Cell , Vascular Endothelial Growth Factors , Endometriosis/epidemiology , Programmed Cell Death 1 Receptor , Poly (ADP-Ribose) Polymerase-1
15.
J. appl. oral sci ; 26: e20170601, 2018. graf
Article in English | LILACS, BBO | ID: biblio-954526

ABSTRACT

Abstract Despite the successful clinical application of titanium (Ti) as a biomaterial, the exact cellular and molecular mechanisms responsible for Ti osseointegration remains unclear, especially because of the limited methodological tools available in this field. Objective: In this study, we present a microscopic and molecular characterization of an oral implant osseointegration model using C57Bl/6 mice. Material and Methods: Forty-eight male wild-type mice received a Ti implant on the edentulous alveolar crest and the peri-implant sites were evaluated through microscopic (μCT, histological and birefringence) and molecular (RealTimePCRarray) analysis in different points in time after surgery (3, 7, 14 and 21 days). Results: The early stages of osseointegration were marked by an increased expression of growth factors and MSC markers. Subsequently, a provisional granulation tissue was formed, with high expression of VEGFb and earlier osteogenic markers (BMPs, ALP and Runx2). The immune/inflammatory phase was evidenced by an increased density of inflammatory cells, and high expression of cytokines (TNF, IL6, IL1) chemokines (CXCL3, CCL2, CCL5 and CXC3CL1) and chemokine receptors (CCR2 and CCR5). Also, iNOS expression remained low, while ARG1 was upregulated, indicating predominance of a M2-type response. At later points in time, the bone matrix density and volume were increased, in agreement with a high expression of Col1a1 and Col21a2. The remodelling process was marked by peaks of MMPs, RANKL and OPG expression at 14 days, and an increased density of osteoclasts. At 21 days, intimate Ti/bone contact was observed, with expression of final osteoblast differentiation markers (PHEX, SOST), as well as red spectrum collagen fibers. Conclusions: This study demonstrated a unique molecular view of oral osseointegration kinetics in C57Bl/6 mice, evidencing potential elements responsible for orchestrating cell migration, proliferation, ECM deposition and maturation, angiogenesis, bone formation and remodeling at the bone-implant interface in parallel with a novel microscopic analysis.


Subject(s)
Animals , Male , Dental Implants , Osseointegration/physiology , Models, Animal , Dental Implantation, Endosseous/methods , Bone-Implant Interface/physiology , Maxilla/surgery , Time Factors , Titanium , Wound Healing , Bone Matrix/physiology , Bone Screws , Microscopy, Electron, Scanning , Biomarkers/analysis , Gene Expression , Reproducibility of Results , Cytokines/analysis , Bone Remodeling/physiology , Vascular Endothelial Growth Factors/analysis , X-Ray Microtomography , Real-Time Polymerase Chain Reaction , Bone-Implant Interface/pathology , Maxilla/pathology , Mice, Inbred C57BL
16.
Braz. j. med. biol. res ; 51(2): e6520, 2018. tab, graf
Article in English | LILACS | ID: biblio-889032

ABSTRACT

Multiple growth factors can be administered to mimic the natural process of bone healing in bone tissue engineering. We investigated the effects of sequential release of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) from polylactide-poly (ethylene glycol)-polylactide (PELA) microcapsule-based scaffolds on bone regeneration. To improve the double emulsion/solvent evaporation technique, VEGF was encapsulated in PELA microcapsules, to which BMP-2 was attached. The scaffold (BMP-2/PELA/VEGF) was then fused to these microcapsules using the dichloromethane vapor method. The bioactivity of the released BMP-2 and VEGF was then quantified in rat mesenchymal stem cells (rMSCs). Immunoblotting analysis showed that BMP-2/PELA/VEG promoted the differentiation of rMSCs into osteoblasts via the MAPK and Wnt pathways. Osteoblast differentiation was assessed through alkaline phosphatase expression. When compared with simple BMP-2 plus VEGF group and pure PELA group, osteoblast differentiation in BMP-2/PELA/VEGF group significantly increased. An MTT assay indicated that BMP-2-loaded PELA scaffolds had no adverse effects on cell activity. BMP-2/PELA/VEG promoted the differentiation of rMSCs into osteoblast via the ERK1/2 and Wnt pathways. Our findings indicate that the sequential release of BMP-2 and VEGF from PELA microcapsule-based scaffolds is a promising approach for the treatment of bone defects.


Subject(s)
Animals , Rabbits , Rats , Polyesters/pharmacology , Polyethylene Glycols/pharmacology , Mitogen-Activated Protein Kinases/metabolism , Vascular Endothelial Growth Factors/metabolism , Tissue Scaffolds , Bone Morphogenetic Protein 2/metabolism , Mesenchymal Stem Cells/cytology , Time Factors , Bone Regeneration , Signal Transduction/physiology , Cells, Cultured , Models, Animal , Cell Proliferation , beta Catenin/physiology , Nanoparticles , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Wnt Signaling Pathway/physiology
17.
Acta cir. bras ; 32(12): 1045-1055, Dec. 2017. graf
Article in English | LILACS | ID: biblio-886197

ABSTRACT

Abstract Purpose: To evaluate the effect of transforming growth factor β1 (TGF-β1) on tendon-to-bone reconstruction of rotator cuff tears. Methods: Seventy-two rat supraspinatus tendons were transected and reconstructed in situ. At 8 and 16 weeks, specimens of three groups; that is control, L-dose (low dose), and H-dose (high dose) were harvested and underwent a biomechanical test to evaluate the maximum load and stiffness values. Histology sections of the tendon-to-bone interface were identified by hematoxylin-eosin or Masson trichrome stain. Collagen type III was observed by picric acid sirius red staining under polarized light. The level of insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) was measured by the enzyme-linked immunosorbent assay (ELISA) method. Results: Collagen type III of the H-dose group had a significant difference in histology structure compared with the L-dose group (P<0.05). The maximum load and stiffness decreased significantly in the control group compared with the values of the L-dose and H-dose groups. The stiffness among the three groups differed significantly at the same postoperative time (P<0.05). Interestingly, progressive reestablishment of collagen type III affected tendon-to-bone healing significantly in the later stages. Conclusion: The H-dose was associated with an increased collagen type III morphology stimulated by TGF-β1.


Subject(s)
Animals , Male , Rats , Tendon Injuries/drug therapy , Wound Healing/physiology , Rotator Cuff/surgery , Vascular Endothelial Growth Factors/metabolism , Transforming Growth Factor beta1/metabolism , Rotator Cuff Injuries/surgery , Tendon Injuries/metabolism , Tensile Strength/physiology , Wound Healing/drug effects , Biomechanical Phenomena , Enzyme-Linked Immunosorbent Assay , Rotator Cuff/metabolism , Rats, Sprague-Dawley , Collagen Type III/metabolism , Disease Models, Animal , Elasticity/physiology , Transforming Growth Factor beta1/pharmacology , Muscle Strength/physiology , Fibroblasts/drug effects , Fibroblasts/physiology , Rotator Cuff Injuries/metabolism
18.
Einstein (Säo Paulo) ; 15(4): 403-408, Oct.-Dec. 2017. tab
Article in English | LILACS | ID: biblio-891431

ABSTRACT

ABSTRACT Objective: To evaluate the frequency of polymorphisms in the vascular endothelial growth factor (VEGF) gene, as well as to identify a potential risk haplotype among the polymorphic regions in this gene in patients with disc degeneration and in the Control Group. Methods: This study analyzed a total of 217 individuals distributed into the Disc Degeneration and Control Groups. Peripheral blood was collected from all patients to detect VEGF gene polymorphisms identified by qPCR (rs699947, rs1570360, rs2010963, rs833061 and rs3025039). All patients presenting disc degeneration had the confirmation by nuclear magnetic resonance test and were rated according to disc degeneration level. Results: All polymorphisms were in Hardy- Weinberg equilibrium (p>0.05) in the studied population. The genotypic frequency for Disc Degeneration and Control Group were rs699947 p = 0.475, rs1570360 p = 0.862, rs2010963 p = 0.823, rs833061 p=0.596 and rs3025039 p=0.230. In haplotype analysis, the compositions CAGGC (p=0.094) and CCGGC (p=0.054) stood out. Conclusion: The correlation between VEGF gene polymorphism as a risk predictor for disc degeneration was negative in the studied population. However, the VEGF gene has a large polymorphic region, and it is activated by various catabolic and metabolic factors in the disc degeneration process, which has not been fully elucidated.


RESUMO Objetivo: Avaliar a frequência dos polimorfismos no gene fator de crescimento endotelial vascular (VEGF), bem como identificar potencial haplótipo de risco entre as regiões polimórficas deste gene em pacientes com degeneração discal e em Grupo Controle. Métodos: Este estudo analisou 217 pacientes distribuídos nos Grupos Degeneração Discal e Grupo Controle. Foi coletado sangue periférico de todos os pacientes para a detecção dos polimorfismos do gene VEGF identificados por qPCR (rs699947, rs1570360, rs2010963, rs833061 e rs3025039). Todos os pacientes que apresentaram degeneração discal tiveram a confirmação por meio de ressonância magnética nuclear e avaliação do nível de degeneração do disco. Resultados: Todos os polimorfismos foram encontrados no equilíbrio de Hardy-Weinberg (p>0,05) na população estudada. A frequência genotípica para o Grupo Degeneração de Disco e do Grupo Controle foi rs699947 p=0,475, rs1570360 p=0,862, rs2010963 p=0,823, rs833061 p=0,596 e rs3025039 p=0,230. Para a análise do haplótipo, destacaram-se as composições CAGGC (p=0,094) e CCGGC (p=0,054). Conclusão: A correlação entre os polimorfismos do gene VEGF como preditor de risco para degeneração discal foi negativa na população estudada. No entanto, o VEGF possui grande região polimórfica, ativada por vários fatores catabólicos e metabólicos no processo de degeneração discal, que não está completamente elucidado.


Subject(s)
Humans , Male , Female , Adult , Young Adult , Polymorphism, Genetic , Haplotypes , Vascular Endothelial Growth Factors/genetics , Intervertebral Disc Degeneration/genetics , Genetic Variation , Magnetic Resonance Imaging , Case-Control Studies , Risk Assessment , Vascular Endothelial Growth Factors/physiology , Alleles , Real-Time Polymerase Chain Reaction/methods , Gene Frequency , Genotype , Middle Aged
19.
Arq. bras. oftalmol ; 80(4): 252-256, July-Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-888121

ABSTRACT

ABSTRACT Purpose: To evaluate and compare the effects of topical application and subconjunctival injection of bevacizumab on corneal neovascularization (CNV) in rabbits' eyes after chemical burning of the cornea. Methods: The animals were randomly distributed into four groups of five animals. In one group, the drug was instilled, while in another, it was administered by subconjunctival injection. The two procedures using bevacizumab were compared with instillation and subconjunctival injection of saline solution (S). Neovascularization was evaluated according to the size of the invasion area of new blood vessels and through computerized analysis of this area. The data were analyzed using the Kruskal-Wallis test followed by Dunn's test for two-by-two comparison of the groups, to assess the external examination of CNV. Analysis of variance was used to assess the area of CNV. P<0.05 was considered statistically significant. Results: Assessing both the external examination and the invasion area of neovessels on the 5th and 10th days, there was a clear difference between the groups. The group to which saline solution had been applied showed higher scores for CNV, as well as increases in the invasion area of neovessels. Two-by-two comparison of groups revealed no significant differences. However, an analysis of the factors involved (injection vs. instillation and bevacizumab vs. saline solution) showed that injection did not differ from instillation, but that bevacizumab differed from saline solution. Conclusion: Bevacizumab showed an inhibitory effect on CNV in rabbits' eyes after chemical burning of the cornea. There was no difference between the topical or subconjunctival administration of bevacizumab in the inhibition of CNV.


RESUMO Objetivos: Avaliar e comparar o efeito do uso tópico e da injeção subconjuntival do bevacizumabe na neovascularização corneana de olhos de coelhos após queimadura química. Métodos: Os animais foram distribuídos de forma aleatória em quatro grupos de cinco animais. Em um grupo de coelhos a droga foi instilada, enquanto em outro foi aplicada injeção subconjuntival, sendo os dois procedimentos comparados com a instilação e injeção subconjuntival de soro fisiológico 0,9% (SF) e entre si. A neovascularização foi avaliada conforme o tamanho da área de invasão dos neovasos e com análise computadorizada da mesma. Na análise de dados aplicou-se o teste de Kruskal-Wallis seguido do teste de Dunn com p<0,05 para comparação dos grupos dois a dois na análise do exame externo da neovascularização corneana. Na análise da área de neovascularização corneana, aplicou-se o teste F de análise de variância. A significância estatística foi definida como valor de p<0.05. Resultados: A avaliação do exame externo e da área de invasão de neovasos, no 5º e 10º dia, mostrou nítida diferença entre os grupos. Com o uso de soro fisiológico houve maior graduação na escala de neovascularização corneana e também na área de invasão dos nevasos, o que demonstrou o efeito inibitório do bevacizumabe. Nas comparações dos grupos dois a dois não foram detectadas diferenças significativas, porém, ao analisar os fatores envolvidos (procedimentos: injeção ou instilação, e as drogas: bevacizumabe ou soro fisiológico), verificou-se que a injeção não diferiu da instilação, mas o bevacizumabe diferiu do soro fisiológico. Conclusão: O bevacizumabe apresentou efeito inibitório na neovascularização corneana de olhos de coelhos após queimadura química, tanto por via tópica como por via subconjuntival e não houve diferença entre a via tópica e a via subconjuntival de administração do bevacizumabe na inibição da neovascularização corneana.


Subject(s)
Animals , Male , Rats , Corneal Neovascularization/drug therapy , Cornea/drug effects , Angiogenesis Inhibitors/administration & dosage , Bevacizumab/administration & dosage , Ophthalmic Solutions , Burns, Chemical , Random Allocation , Eye Burns , Administration, Topical , Corneal Neovascularization/pathology , Cornea/innervation , Vascular Endothelial Growth Factors/antagonists & inhibitors , Disease Models, Animal , Injections, Intraocular , Corneal Injuries/chemically induced
20.
Article in English | WPRIM | ID: wpr-220607

ABSTRACT

Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.


Subject(s)
Angiogenesis Inhibitors , Bevacizumab , Disease-Free Survival , Esophagogastric Junction , Humans , Medical Oncology , Neoplasm Metastasis , Prognosis , Prospective Studies , Protein-Tyrosine Kinases , Stomach Neoplasms , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
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