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1.
Cell Prolif ; 53(3): e12784, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32080957

RESUMO

OBJECTIVES: CD31hi EMCNhi vessels (CD31, also known as PECAM1 [platelet and endothelial cell adhesion molecule 1]; EMCN, endomucin), which are strongly positive for CD31 and endomucin, couple angiogenesis and osteogenesis. However, the role of CD31hi EMCNhi vessels in bone regeneration remains unknown. In the present study, we investigated the role of CD31hi EMCNhi vessels in the process of bone regeneration. MATERIALS AND METHODS: We used endothelial-specific Krüppel like factor 3 (Klf3) knockout mice and ophiopogonin D treatment to interfere with CD31hi EMCNhi vessel formation. We constructed a bone regeneration model by surgical ablation of the trabecular bone. Immunofluorescence and micro-computed tomography (CT) were used to detect CD31hi EMCNhi vessels and bone formation. RESULTS: CD31hi EMCNhi vessels participate in the process of bone regeneration, such that endothelial-specific Klf3 knockout mice showed increased CD31hi EMCNhi vessels and osteoprogenitors in the bone regeneration area, and further accelerated bone formation. We also demonstrated that the natural compound, ophiopogonin D, acts as a KLF3 inhibitor to promote vessels formation both in vitro and in vivo. Administration of ophiopogonin D increased the abundance of CD31hi Emcnhi vessels and accelerated bone healing. CONCLUSIONS: Our findings confirmed the important role of CD31hi Emcnhi vessels in bone regeneration and provided a new target to treat bone fracture or promote bone regeneration.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Saponinas/farmacologia , Sialoglicoproteínas/metabolismo , Espirostanos/farmacologia , Animais , Células Cultivadas , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteogênese/efeitos dos fármacos
2.
PLoS One ; 15(1): e0228030, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31971966

RESUMO

BACKGROUND: Wavelet transformed reconstructions of dynamic susceptibility contrast (DSC) MR perfusion (wavelet-MRP) are a new and elegant way of visualizing vascularization. Wavelet-MRP maps yield a clear depiction of hypervascular tumor regions, as recently shown. OBJECTIVE: The aim of this study was to elucidate a possible connection of the wavelet-MRP power spectrum in glioblastoma (GBM) with local vascularity and cell proliferation. METHODS: For this IRB-approved study 12 patients (63.0+/-14.9y; 7m) with histologically confirmed IDH-wildtype GBM were included. Target regions for biopsies were prospectively marked on tumor regions as seen on preoperative 3T MRI. During subsequent neurosurgical tumor resection 43 targeted biopsies were taken from these target regions, of which all 27 matching samples were analyzed. All specimens were immunohistochemically analyzed for endothelial cell marker CD31 and proliferation marker Ki67 and correlated to the wavelet-MRP power spectrum as derived from DSC perfusion weighted imaging. RESULTS: There was a strong correlation between wavelet-MRP power spectrum (median = 4.41) and conventional relative cerebral blood volume (median = 5.97 ml/100g) in Spearman's rank-order correlation (κ = .83, p < .05). In a logistic regression model, the wavelet-MRP power spectrum showed a significant correlation to CD31 dichotomized to no or present staining (p = .04), while rCBV did not show a significant correlation to CD31 (p = .30). No significant association between Ki67 and rCBV or wavelet-MRP was found (p = .62 and p = .70, respectively). CONCLUSION: The wavelet-MRP power spectrum derived from existing DSC-MRI data might be a promising new surrogate for tumor vascularity in GBM.


Assuntos
Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Glioblastoma/irrigação sanguínea , Glioblastoma/patologia , Imagem por Ressonância Magnética , Neovascularização Patológica/diagnóstico por imagem , Perfusão , Análise de Ondaletas , Biópsia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Proliferação de Células , Volume Sanguíneo Cerebral , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Curva ROC
3.
Nat Commun ; 11(1): 460, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974363

RESUMO

Recent interest in the control of bone metabolism has focused on a specialized subset of CD31hiendomucinhi vessels, which are reported to couple angiogenesis with osteogenesis. However, the underlying mechanisms that link these processes together remain largely undefined. Here we show that the zinc-finger transcription factor ZEB1 is predominantly expressed in CD31hiendomucinhi endothelium in human and mouse bone. Endothelial cell-specific deletion of ZEB1 in mice impairs CD31hiendomucinhi vessel formation in the bone, resulting in reduced osteogenesis. Mechanistically, ZEB1 deletion reduces histone acetylation on Dll4 and Notch1 promoters, thereby epigenetically suppressing Notch signaling, a critical pathway that controls bone angiogenesis and osteogenesis. ZEB1 expression in skeletal endothelium declines in osteoporotic mice and humans. Administration of Zeb1-packaged liposomes in osteoporotic mice restores impaired Notch activity in skeletal endothelium, thereby promoting angiogenesis-dependent osteogenesis and ameliorating bone loss. Pharmacological reversal of the low ZEB1/Notch signaling may exert therapeutic benefit in osteoporotic patients by promoting angiogenesis-dependent bone formation.


Assuntos
Neovascularização Fisiológica/fisiologia , Osteogênese/fisiologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/farmacologia , Idoso , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/farmacologia , Células Endoteliais/metabolismo , Epigênese Genética , Feminino , Humanos , Camundongos Knockout , Camundongos Transgênicos , Pessoa de Meia-Idade , Neovascularização Fisiológica/genética , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteoporose/terapia , Ovariectomia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
4.
Acta Biochim Biophys Sin (Shanghai) ; 52(1): 18-25, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31828297

RESUMO

As a highly malignant tumor, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. In most HCC patients, the development of HCC begins with hepatitis, which is followed by fibrosis and cirrhosis before progressing to HCC. Cancer-associated fibroblasts (CAFs), which are generally believed to be derived from activated hepatic stellate cells (HSCs), are highly involved in the development of HCC through the secretion of cytokines and angiogenic factors. The results of our study showed that a considerable number of CAFs highly expressed CD90 and were enriched in HCC tissues. Bioinformatics analysis of the transcriptome of HCC tissues revealed that placental growth factor (PlGF) is significantly correlated with CD90 expression. The isolated primary CAFs and activated HSCs overexpressed PlGF and CD90. In addition, the results of gene expression profiling interactive analysis based on The Cancer Genome Atlas showed that high levels of both PlGF and CD90 are correlated with tumor angiogenesis markers (CD31, CD34, and CD105) and predict poor HCC patient prognosis. In summary, our results suggest that CAFs can generate PlGF and may provide an effective target for CAFs-regulated neoangiogenesis in HCC.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Fibroblastos/metabolismo , Neoplasias Hepáticas/irrigação sanguínea , Neovascularização Patológica/metabolismo , Fator de Crescimento Placentário/metabolismo , Actinas/metabolismo , Antígenos CD34/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Endoglina/metabolismo , Regulação Neoplásica da Expressão Gênica , Células Estreladas do Fígado/metabolismo , Humanos , Neoplasias Hepáticas/genética , Fator de Crescimento Placentário/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Prognóstico , Antígenos Thy-1/genética , Antígenos Thy-1/metabolismo , Transcriptoma/genética
5.
PLoS One ; 14(12): e0226475, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851698

RESUMO

It is now well established that for tumour growth and survival, tumour vasculature is an important element. Studies have demonstrated that ultrasound-stimulated microbubble (USMB) treatment causes extensive endothelial cell death leading to tumour vascular disruption. The subsequent rapid vascular collapse translates to overall increases in tumour response to various therapies. In this study, we explored USMB involvement in the enhancement of hyperthermia (HT) treatment effects. Human prostate tumour (PC3) xenografts were grown in mice and were treated with USMB, HT, or with a combination of the two treatments. Treatment parameters consisted of ultrasound pressures of 0 to 740 kPa, the use of perfluorocarbon-filled microbubbles administered intravenously, and an HT temperature of 43°C delivered for various times (0-50 minutes). Single and multiple repeated treatments were evaluated. Tumour response was monitored 24 hours after treatments and tumour growth was monitored for up to over 30 days for a single treatment and 4 weeks for multiple treatments. Tumours exposed to USMB combined with HT exhibited enhanced cell death (p<0.05) and decreased vasculature (p<0.05) compared to untreated tumours or those treated with either USMB alone or HT alone within 24 hours. Deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and cluster of differentiation 31 (CD31) staining were used to assess cell death and vascular content, respectively. Further, tumours receiving a single combined USMB and HT treatment exhibited decreased tumour volumes (p<0.05) compared to those receiving either treatment alone when monitored over the duration of 30 days. Additionally, tumour response monitored weekly up to 4 weeks demonstrated a reduced vascular index and tumour volume, increased fibrosis and lesser number of proliferating cells with combined treatment of USMB and HT. Thus in this study, we characterize a novel therapeutic approach that combines USMB with HT to enhance treatment responses in a prostate cancer xenograft model in vivo.


Assuntos
Hipertermia Induzida , Microbolhas/uso terapêutico , Neoplasias da Próstata/terapia , Terapia por Ultrassom , Animais , Terapia Combinada , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos SCID , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Bull Cancer ; 106(11): 946-958, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31711572

RESUMO

AIM: A HER2-specific second-generation chimeric antigen receptor (5.137.z) was introduced into NK-92 cells, designated as NK-92/5.137.z cells. To evaluate the function and effectiveness of NK-92/5.137.z cells against gastric cancer cells and further determined whether combination with apatinib can synergize with this NK cell-based practice to better suppress gastric cancer. METHODS: The expression of HER2 was examined in gastric cancer. The in vitro and in vivo cytotoxic activities of NK-92/5.137.z cells with or without apatinib were evaluated against gastric cancer cell lines. RESULTS: HER2 proteins were over-expressed in a considerable proportion of gastric cancer cells. NK-92/5.137.z cells specifically lysed gastric cancer cells expressing HER2 and had higher levels of cytokine production. In vivo, NK-92/5.137.z cells were particularly efficient at eliminating small tumor xenografts, whereas larger solid tumors were not effectively controlled with NK-92/5.137.z cells. Treatment with apatinib increased NK cell infiltration into large tumor xenografts and improved the therapeutic efficacy of NK-92/5.137.z cells. CONCLUSION: NK-92/5.137.z cells could represent a novel treatment option for patients with gastric cancer, either used alone or combined with apatinib.


Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia Adotiva/métodos , Células Matadoras Naturais/imunologia , Piridinas/uso terapêutico , Receptor ErbB-2/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Neoplasias Gástricas/terapia , Animais , Antígeno CD56/metabolismo , Degranulação Celular , Linhagem Celular Tumoral , Terapia Combinada/métodos , Xenoenxertos , Humanos , Células Matadoras Naturais/fisiologia , Células Matadoras Naturais/transplante , Lentivirus , Camundongos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Carga Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Parasit Vectors ; 12(1): 517, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685001

RESUMO

BACKGROUND: Bovine besnoitiosis, caused by the cyst-forming apicomplexan parasite Besnoitia besnoiti, is a chronic and debilitating cattle disease that continues to spread in Europe in the absence of control tools. In this scenario, in vitro culture systems are valuable tools to carry out drug screenings and to unravel host-parasite interactions. However, studies performed in bovine target cells are scarce. METHODS: The objective of the present study was to obtain primary bovine aortic endothelial cells (BAECs) and fibroblast cell cultures, target cells during the acute and the chronic stage of the disease, respectively, from healthy bovine donors. Afterwards, expression of surface (CD31, CD34 and CD44) and intracellular markers (vimentin and cytokeratin) was studied to characterize cell populations by flow cytometry. Next, the lytic cycle of B. besnoiti tachyzoites was studied in both target cells. Invasion rates (IRs) were determined by immunofluorescence at several time points post-infection, and proliferation kinetics were studied by quantitative PCR (qPCR). Finally, the influence of bovine viral diarrhea virus (BVDV) co-infection on the host cell machinery, and consequently on B. besnoiti invasion and proliferation, was investigated in BAECs. RESULTS: Morphology and cytometry results confirmed the endothelial and fibroblast origins. CD31 was the surface marker that best discriminated between BAECs and fibroblasts, since fibroblasts lacked CD31 labelling. Expression of CD34 was weak in low-passage BAECs and absent in high-passage BAECs and fibroblasts. Positive labelling for CD44, vimentin and cytokeratin was observed in both BAECs and fibroblasts. Regarding the lytic cycle of the parasite, although low invasion rates (approximately 3-4%) were found in both cell culture systems, more invasion was observed in BAECs at 24 and 72 hpi. The proliferation kinetics did not differ between BAECs and fibroblasts. BVDV infection favoured early Besnoitia invasion but there was no difference in tachyzoite yields observed in BVDV-BAECs compared to BAECs. CONCLUSIONS: We have generated and characterized two novel standardized in vitro models for Besnoitia besnoiti infection based on bovine primary target BAECs and fibroblasts, and have shown the relevance of BVDV coinfections, which should be considered in further studies with other cattle pathogens.


Assuntos
Doenças dos Bovinos/parasitologia , Coccidiose/veterinária , Células Endoteliais/parasitologia , Fibroblastos/parasitologia , Sarcocystidae/crescimento & desenvolvimento , Animais , Antígenos CD34/metabolismo , Bovinos , Coccidiose/parasitologia , Receptores de Hialuronatos/metabolismo , Estágios do Ciclo de Vida , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Fatores de Tempo
8.
Int J Nanomedicine ; 14: 7515-7531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571861

RESUMO

Background: Glioblastoma mutliforme is the most common and has the poorest prognosis of any malignant tumor of the central nervous system. Luteolin, the most abundant xanthone extracted from vegetables and medicinal plants, has been shown to have treatment effects in various cancer cell types. Luteolin is however, hydrophobic and has poor biocompatibility, which leads to low bioavailability. Patients and methods: In this study, folic acid modifiedpoly(ethylene glycol)-poly(e-caprolactone) (Fa-PEG-PCL) nano-micelles was used to encapsulate the luteolin, creating luteolin loaded PEG-PCL (Lut/Fa-PEG-PCL) micelles to treat glioma both in vitro and in vivo. Results: When compared with the free luteolin and Lut/MPEG-PCL, Lut/Fa-PEG-PCL induced a significant cell growth inhibition and more apoptosis of GL261 cells both in vitro and in vivo. The safety assessment also showed no obvious side effects were observed in mice which were administrated with free luteolin or Lut/MPEG-PCL and Lut/Fa-PEG-PCL. Conclusion: These results suggested Lut/Fa-PEG-PCL may be used as an excellent intravenously injectable formulation for the treatment and chemoprevention.


Assuntos
Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Glioma/tratamento farmacológico , Luteolina/uso terapêutico , Nanopartículas/química , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Glioma/irrigação sanguínea , Humanos , Luteolina/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Micelas , Modelos Moleculares , Nanopartículas/ultraestrutura , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Poliésteres/química , Polietilenoglicóis/química , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Sprague-Dawley
9.
Expert Rev Med Devices ; 16(11): 989-997, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31648570

RESUMO

Background: Saline is not biocompatible with saphenous vein grafts and does not protect against ischemia reperfusion injury. We compared normal heparinized saline with DuraGraft, a new graft-storage solution, in in-vitro and ex-vivo assays to evaluate the effects on cells and vascular graft tissue.Methods: Human saphenous vein (HSV) segments and isolated pig mammary veins (PMVs) were flushed and submerged in heparinized DuraGraft or heparinized saline for prespecified times. Following exposure, HSV segments were evaluated for viability and tissue morphology, and PMVs underwent histological assessments, to evaluate vein morphology and effects on the vascular endothelium. The performance of saline versus DuraGraft was compared in an ISO-compliant biocompatibility assay for cytotoxicity.Results: Loss of HSV graft-cell viability was observed as early as 15 minutes post-exposure to saline whereas viability was maintained up to 5 hours' exposure to DuraGraft. Histological analyses performed with PMVs demonstrated endothelial damage in PMVs stored in saline. Cytotoxicity assays demonstrated that saline-induced microscopically visible cell damage occurred within 60 minutes. DuraGraft-treated cells did not show evidence of damage or reactivity.Conclusions: Normal saline caused damage to vascular endothelium, loss of graft cell viability, and mediated cell damage; no evidence of damage or reactivity was observed in DuraGraft-exposed cells.


Assuntos
Prótese Vascular , Ponte de Artéria Coronária , Cuidados Intraoperatórios , Veia Safena/transplante , Idoso , Animais , Morte Celular , Linhagem Celular , Feminino , Humanos , Masculino , Glândulas Mamárias Animais/irrigação sanguínea , Camundongos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Suínos , Fator de von Willebrand/metabolismo
10.
World Neurosurg ; 131: 346-355, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31658577

RESUMO

BACKGROUND: Erythropoietin (EPO) is a cytokine primarily involved in the regulation of erythropoiesis. In response to hypoxia-ischemia, hypoxia-inducible factor 1 induces EPO production, which, in turn, inhibits apoptosis of erythroid progenitor cells. By the same mechanism and acting through other signaling pathways, EPO exerts neuroprotective effects. Increased resistance to hypoxia and decreased apoptosis are thought to be important mechanisms for tumor progression, including malignant glioma. Because recent studies have demonstrated that EPO and its receptor (EPOR) are expressed in several tumors and can promote tumor growth, in the present study, we investigated EPO and EPOR expression in human glioma and the effect of EPO administration in a rat model of glioma implantation. METHODS: Using Western blotting and immunohistochemical analysis, we examined the expression of EPO, EPOR, platelet endothelial cell adhesion molecule, and Ki-67 in human glioma specimens and experimentally induced glioma in rats. In the experimental setting, a daily dose of recombinant human EPO (rHuEPO) or saline solution were administered for 21 days in Fischer rats subjected to 9L cell line implantation. RESULTS: In both human and animal specimens, we found an increase in EPOR expression as long as the lesion presented with an increasing malignant pattern. A significant direct correlation was found between the expression of EPOR and Ki-67 and EPOR and platelet endothelial cell adhesion molecule in low- and high-grade gliomas. The rats treated with rHuEPO presented with significantly larger tumor spread compared with the saline-treated rats. CONCLUSIONS: The results of our study have shown that the EPO/EPOR complex might play a significant role in the aggressive behavior of high-grade gliomas. The larger tumor spread in rHuEPO-treated rats suggests a feasible role for EPO in the aggressiveness and progression of malignant glioma.


Assuntos
Neoplasias Encefálicas/metabolismo , Eritropoetina/metabolismo , Glioma/metabolismo , Receptores da Eritropoetina/metabolismo , Adulto , Idoso , Animais , Western Blotting , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Eritropoetina/farmacologia , Eritropoetina/fisiologia , Feminino , Glioma/etiologia , Glioma/patologia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Transplante de Neoplasias , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos Endogâmicos F344 , Receptores da Eritropoetina/fisiologia , Proteínas Recombinantes/farmacologia , Carga Tumoral/efeitos dos fármacos
11.
Pan Afr Med J ; 33: 134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31558933

RESUMO

Primary angiosarcoma of the breast is an extremely rare tumour with a difficult diagnosis and poor prognosis. We report a case of primary breast angiosarcoma diagnosed in the pathology department of the University Hospital of Oujda. An analysis of the epidemiological, diagnostic and therapeutic aspects of this type of tumour is made in this manuscript. Mastectomy is the standard treatment; the place of radiotherapy and chemotherapy is not well established. We report a case of a 18- year-old woman having an infectious symptomatology of the right breast for which she received an anti-infectious therapy inducing regression of inflammatory symptoms presented with a quick growing mass. Initial core needle biopsy showed a malignant vascular proliferation. The patient underwent a mastectomy. The tumor histology showed papillary formations and vascular structures lined by atypical cells with hyperchromatic nucleus and eosinophilic cytoplasm. The tumor cells expressed CD34 and CD31 but were negative for cytokeratin. The diagnosis of angiosarcoma grade I was made. The patient is now receiving chemotherapy. She is still alive.


Assuntos
Neoplasias da Mama/diagnóstico , Hemangiossarcoma/diagnóstico , Mastectomia/métodos , Adolescente , Antígenos CD34/metabolismo , Antineoplásicos/administração & dosagem , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Humanos , Gradação de Tumores , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo
12.
Cancer Sci ; 110(11): 3424-3433, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31495050

RESUMO

Tongue squamous cell carcinoma (TSCC) has a poor prognosis due to its early metastasis through blood and lymphatic vessels. We undertook a systematic review to investigate the prognostic significance of blood microvessel density (MVD) and lymphatic vessel density (LVD) in TSCC patients. We carried out a systematic search in Ovid Medline, Scopus, and Cochrane libraries. All studies that evaluated the prognostic significance of MVD/LVD markers in TSCC were systematically retrieved. Our results showed that MVD/LVD markers, CD31, CD34, CD105, factor VIII, lymphatic vessel endothelial hyaluronan receptor-1, and D2-40 were evaluated in TSCC patients until 28 June 2018. Six out of 13 studies reported markers that were associated with poor prognosis in TSCC. Two out of three studies suggested that a high number of D2-40+ vessels predicated low overall survival (OS); the third study reported that the ratio of D2-40+ over factor VIII+ vessels is associated with low OS. Most of the other markers had controversial results for prognostication. We found higher expression of MVD/LVD markers were commonly, but not always, associated with shorter survival in TSCC patients. It is therefore not currently possible to recommend implementation of these markers as reliable prognosticators in clinical practice. More studies (especially for D2-40) with larger patient cohorts are needed.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Vasos Linfáticos/metabolismo , Microvasos/metabolismo , Neoplasias da Língua/metabolismo , Anticorpos Monoclonais Murinos/metabolismo , Antígenos CD34/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Endoglina/metabolismo , Fator VIII/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Linfangiogênese , Neovascularização Patológica , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Prognóstico , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Proteínas de Transporte Vesicular/metabolismo
13.
Folia Histochem Cytobiol ; 57(3): 127-138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489604

RESUMO

INTRODUCTION: Diabetes mellitus (DM) is a serious, chronic metabolic disorder commonly complicated by diabetic foot ulcers with delayed healing. Metformin was found to have a wound healing effect through several mechanisms. The current study investigated the effect of both bone marrow-derived mesenchymal stem cells (BM-MSCs) and metformin, considered alone or combined, on the healing of an experimentally induced cutaneous wound injury in streptozotocin-induced diabetic rats. MATERIAL AND METHODS: Forty adult male albino rats were used. Diabetes was induced by single intravenous (IV) injection of streptozotocin (STZ). Next, two circular full thickness skin wounds were created on the back of the animals, then randomly assigned into 4 groups, ten rats each. BM-MSCs were isolated from albino rats, 8 weeks of age and labeled by PKH26 before intradermal injection into rats of Group III and IV. Groups I (diabetic positive control), II (metformin-treated, 250 mg/kg/d), III (treated with 2×106 BM-MSCs), and IV (wounded rats treated both with metformin and BM-MSCs cells). Healing was assessed 3, 7, 14, and 21 days post wound induction through frequent measuring of wound diameters. Skin biopsies were obtained at the end of the experiment. RESULTS: Gross evaluation of the physical healing of the wounds was done. Skin biopsies from the wound areas were processed for hematoxylin and eosin (H&E), Masson's trichrome staining and immunohistochemical staining for CD31. The results showed better wound healing in the combined therapy group (IV) as compared to monotherapy groups. CONCLUSIONS: Although both metformin and BM-MSCs were effective in the healing of experimentally induced skin wounds in diabetic rats, the combination of both agents appears to be a better synergistic option for the treatment of diabetic wound injuries.


Assuntos
Transplante de Células-Tronco Mesenquimais , Metformina/uso terapêutico , Cicatrização/efeitos dos fármacos , Ferimentos Penetrantes/tratamento farmacológico , Ferimentos Penetrantes/terapia , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Masculino , Células-Tronco Mesenquimais/citologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos , Pele/lesões , Pele/patologia , Lesões dos Tecidos Moles/tratamento farmacológico , Lesões dos Tecidos Moles/terapia , Estreptozocina
14.
Adv Gerontol ; 32(3): 357-363, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31512421

RESUMO

The aim of this work was to examine the content of Piezo1 in fibroblasts and blood vessels of human dermis from the development until deep aging (from 20 weeks of pregnancy until 85 years old), and defining of a role of Piezo1 in age-dependent changes in the number of fibroblasts and blood vessels in the dermis. Piezo1, proliferating cells nuclear antigen (PCNA), endothelial cells marker CD31 were detected with indirect immunohistochemical technique. Results showed that a portion of fibroblasts with positive staining for Piezo1 in the dermis is decreased from 20 weeks of pregnancy to 40 years old. Percent of Piezo1 positive fibroblasts in dermis is increased sufficiently since 41 years old until 60-85 years old group. The content of Piezo1 in blood vessels in the human dermis is decreased sufficiently from 20 weeks of pregnancy until 40 years old. Age-related changes in the content of Piezo1 in fibroblasts and blood vessels is not associated with an age-related decrease in total number and percent of PCNA positive fibroblasts, the number of blood vessels in the dermis.


Assuntos
Vasos Sanguíneos , Derme , Fibroblastos , Canais Iônicos , Envelhecimento da Pele , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasos Sanguíneos/fisiologia , Criança , Pré-Escolar , Derme/irrigação sanguínea , Derme/citologia , Derme/embriologia , Derme/crescimento & desenvolvimento , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Lactente , Canais Iônicos/metabolismo , Masculino , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Gravidez , Antígeno Nuclear de Célula em Proliferação/metabolismo , Envelhecimento da Pele/fisiologia
15.
ACS Appl Mater Interfaces ; 11(40): 37147-37155, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31513742

RESUMO

Drug-loading hydrogels are promising candidates in the bioengineering research field; nevertheless, hydrophobic drug loading into a hydrophilic carrier system remains unsolved and is full of challenges. In this work, following the potential dual interactions between peptides and aromatic drugs, we developed a potent hybrid hydrogel formation method, namely, "peptide-/drug-directed self-assembly". The hybrid hydrogels were synthesized using polyethylene glycol (PEG)-based Fmoc-FF peptide hybrid polyurethane, in which curcumin could be encapsulated through self-assembly with Fmoc-FF peptide via π-π stacking. On the basis of this, curcumin loading capacity could be improved to as high as 3.3 wt % with sustained release. In addition, the curcumin loading enhanced the hydrogel mechanical properties from 4 kPa to over 10 kPa, similar to that of natural soft tissues. Furthermore, the hydrogels were injectable with self-healing properties since the Fmoc-FF peptide/curcumin coassembly was noncovalent and reversible. Spectroscopy results confirmed the existence of the coassembly of Fmoc-FF peptide/curcumin. Further in vivo experiments effectively demonstrated that the hydrogels could improve the cutaneous wound healing in a full-thickness skin defected model. This peptide-/drug-directed self-assembly of hybrid polyurethane hydrogel could be used as a promising platform for tissue-engineering scaffold and biomedical application.


Assuntos
Hidrogéis/farmacologia , Peptídeos/farmacologia , Poliuretanos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Curcumina/farmacologia , Dipeptídeos/farmacologia , Liberação Controlada de Fármacos , Fluorenos/farmacologia , Tecido de Granulação/patologia , Hidrogéis/química , Peso Molecular , Peptídeos/química , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Poliuretanos/química , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia
16.
Biomed Pharmacother ; 118: 109369, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545229

RESUMO

The main characteristic of glioma is recurrence, even after intensive multidisciplinary treatment. Studies show that enhanced invasive ability will increase the ability of tumor cells to escape from the primary tumor mass, which is a key factor contributing to tumor relapse and recurrence. In this study, we assessed the expression of MMP-2, MMP-9, two important matrix metallopeptidases that increase the invasive ability of glioma, and their suppressors, TIMP-1, TIMP-2 in glioma tissues from primary and recurrent glioma patients by immunohistochemistry. Glioma cells and nude mice were used for in vitro and in vivo studies. Results showed that the expression of MMP-2 and MMP-9 in recurrent gliomas were significantly higher than those in primary gliomas (P = 3.075 × 10-11, P = 1.510 × 10-5, respectively). We also found that radiotherapy increased the expression of MMP-9, but had no effect on MMP-2 and TIMP-1/2. With glioma cell line U251, we found that irradiation increased the expression of MMP-9 in vitro. Tumor tissues from an orthotopic xenograft model showed that after irradiation treatment, the expression of MMP-9 increased significantly in vivo. We also found that knocking down MMP-9 decreased irradiation-induced invasion obviously. Above all, we concluded that higher expressions of MMP-2/-9 indicate poor prognosis in glioma recurrence. The increased expression of MMP-9 after radiotherapy suggests that MMP-9 might be an important target in the radiosensitization of glioma.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/enzimologia , Glioma/diagnóstico , Glioma/enzimologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Criança , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/enzimologia , Recidiva Local de Neoplasia/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Prognóstico , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Adulto Jovem
17.
BMJ Case Rep ; 12(9)2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31501171

RESUMO

The authors described a case of sclerosing angiomatoid nodular transformation of the spleen (SANT) in a 50-year-old woman presented with persistent neutrophilia and unintentional weight loss. An incidental splenic mass was initially found on abdominal ultrasound. It was found to be progressive in size and with high likelihood of central necrosis on further CT of abdomen and pelvis. The patient subsequently underwent an uneventful laparoscopic splenectomy. The splenic specimens were sent for laboratory analysis and the histopathological findings were highly suggestive of SANT. The patient then had routine surgical follow-ups and was eventually discharged with no further clinical concern.


Assuntos
Esplenopatias/patologia , Antígenos CD34/metabolismo , Antígenos CD8/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Laparoscopia , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Esplenectomia , Esplenopatias/diagnóstico por imagem , Esplenopatias/metabolismo , Esplenopatias/cirurgia , Tomografia Computadorizada por Raios X , Ultrassonografia
18.
BMC Dev Biol ; 19(1): 15, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277570

RESUMO

BACKGROUND: Prostate androgen-regulated mucin-like protein 1 (PARM1) is a pro-proliferative and anti-apoptotic glycoprotein involved in the endoplasmic reticulum (ER) stress response. A single nucleotide polymorphism in the coding region of PARM1 has been associated with competence of bovine embryos to develop to the blastocyst stage. Here we tested the importance of PARM1 for development by evaluating consequences of reducing PARM1 mRNA abundance on embryonic development and differentiation, gene expression and resistance to ER stress. RESULTS: Knockdown of PARM1 using an anti-PARM1 GapmeR did not affect competence of embryos to develop into blastocysts but decreased the number of trophectoderm (TE) cells in the blastocyst and tended to increase the number of cells in the blastocyst inner cell mass (ICM). Treatment of embryos with anti-PARM1 GapmeR affected expression of 4 and 3 of 90 genes evaluated at the compact-morula and blastocyst stage of development at days 5.5 and 7.5 after fertilization, respectively. In morulae, treatment increased expression of DAB2, INADL, and STAT3 and decreased expression of CCR2. At the blastocyst stage, knockdown of PARM1 increased expression of PECAM and TEAD4 and decreased expression of CCR7. The potential role of PARM1 in ER stress response was determined by evaluating effects of knockdown of PARM1 on development of embryos after exposure to heat shock or tunicamycin and on expression of ATF6, DDIT3 and EIF2AK3 at the compact morula and blastocyst stages. Both heat shock and tunicamycin reduced the percent of embryos becoming a blastocyst but response was unaffected by PARM1 knockdown. Similarly, there was no effect of knockdown on steady-state amounts of ATF6, DDIT3 or EIF2AK3. CONCLUSION: PARM1 participates in formation of TE and ICM cells in early embryonic development but there is no evidence for the role of PARM1 in the ER stress response.


Assuntos
Proteína de Ligação a Androgênios/genética , Blastocisto/citologia , Desenvolvimento Embrionário/genética , Estresse do Retículo Endoplasmático/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Animais , Bovinos , Diferenciação Celular/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/genética , Receptores CCR2/metabolismo , Receptores CCR7/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas de Junções Íntimas/metabolismo , Tunicamicina/farmacologia , Proteínas Ativadoras de ras GTPase/metabolismo
19.
Eur J Pharmacol ; 858: 172466, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31220437

RESUMO

Icariin is a flavonoid from plant belonging to the genus Epimedium, commonly known as Horny goat weed or Yin Yang Huo. The compound possesses multiple biological activities which are associated with the modulation of many signalling pathways, like NF-κB, Erk-p38-JNK, and release of various cytokines and growth factors. The present study determined wound healing potential of icariin in male Wistar rats. Icariin ointment (0%, 0.004%, 0.02%, 0.1% and 0.5%), was applied daily (b.i.d.) for 14 days on ≈ 400 mm2 cutaneous wound in different groups of rats. On day 14 post-wounding, 0.1% and 0.5% icariin treatment significantly (P < 0.01 and P < 0.001, respectively) increased wound contraction, as compared to control. Western blots revealed upregulation of IL-10 and downregulation of NF-κB and TNF-α. Increased expression of CD-31 showed abundance of microvessels in healing tissues after treatment with icariin. The MMP-2 and MMP-9 activities were reduced in icariin treated groups. Masson's trichrome staining revealed relatively better completion of re-epithelisation as well as increased deposition of well organised collagen fibres in the healing tissues compared to control. It is concluded that icariin has potential to accelerate cutaneous wound healing in rats.


Assuntos
Flavonoides/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-10/metabolismo , Masculino , NF-kappa B/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Pele/citologia , Fator de Necrose Tumoral alfa/metabolismo
20.
Colloids Surf B Biointerfaces ; 181: 612-622, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31202132

RESUMO

Nanoemulsion-based synthesis has been introduced to enhance the bioavailability of natural compounds at target sites for their various biomedical applications. In this study, we synthesized carvacrol nanoemulsion (CN) an oil-in-water (O/W) as a nano-emulsion vehicle system by using ultrasonication emulsification for anti-angiogenesis therapy formulated by combining MCT, lecithin, and polysorbate 80 at the O/W interface called carvacrol encapsulated nanoemulsion (CEN). The diameter of CEN determined by TEM analysis was 105.32 nm. The hydrodynamic droplet size was 101.0 nm with a -39.38-mV zeta potential. The stability of the synthesized CEN was approved till 100 days without any change in diameter size distribution and encapsulation efficiency. We evaluated the role of CEN on angiogenesis in lung adenocarcinoma A549 cells both in vitro and in vivo and observed that it reduced the growth and MMP levels of A549 cells in a dose-dependent manner. Exposure to CEN decreased the activation of MAPK p38 as well as ERK. Moreover, we found that CEN reduced the expression of VEGF and CD31 in A549 cells both in vitro and in vivo. Our in-silico study also indicated the binding of carvacrol to COX-2 and VEGF at the active and allosteric sites of CD31 with low binding energy. Overall, CEN induced anti-angiogenic effects in A549 cells in vitro, in silico, and in vivo, thereby establishing its potential as targeted drug delivery vehicle against angiogenesis.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Neovascularização Patológica/tratamento farmacológico , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Emulsões/química , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Tamanho da Partícula , Molécula-1 de Adesão Celular Endotelial a Plaquetas/antagonistas & inibidores , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Propriedades de Superfície , Células Tumorais Cultivadas , Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fatores de Crescimento do Endotélio Vascular/metabolismo
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