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1.
Stem Cell Res Ther ; 9(1): 259, 2018 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-30292232

RESUMO

The original article [1] contained a minor error regarding the mean diameter of the alginate microcapsules described in relation to Fig. 4 in the Results section. The microcapsules had an actual mean diameter of 3000 µm instead of 1000 µm as mistakenly mentioned in the original article.

2.
Monoclon Antib Immunodiagn Immunother ; 37(2): 100-104, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29708868

RESUMO

We report an immunization technique that can update the production of monoclonal antibodies (mAbs): the multiple tolerization subtractive immunization (MTSI). A total of 10 BALB/C mice were used. Animals in group 1 received one inoculation of RWPE-1 cells (nontumoral), followed by cyclophosphamide, and then received serial inoculations of nonirradiated PC3 cells (tumoral). Animals in group 2 received our MTSI protocol, as follows: one inoculation of RWPE-1 cells, followed by cyclophosphamide (Cy). This whole tolerization step was repeated three other times, with 14-day intervals between the last Cy exposure and the next RWPE-1 cell inoculation. Finally, the animals received the same nonirradiated PC3 cell exposure as group 1. Blood was taken from each animal, and their polyclonal sera individually tested against the nontumoral RWPE-1 cells in flow cytometry. We found out that, after the MTSI was employed, the serum of the immunized animals, in group 2, contained considerably less antibodies that reacted against the tolerogenic cells, compared with the serum of the animals that underwent regular subtractive immunization. We showed that, by repeating the tolerization cycles, the polyclonal antibodies produced by mice have a reduced specificity toward common/immunodominant epitopes present at nontumoral cells, and thus this technique can be readily used by others in studies involving murine mAb protocols.


Assuntos
Anticorpos Monoclonais/biossíntese , Células Epiteliais/transplante , Tolerância Imunológica/efeitos dos fármacos , Imunização/métodos , Vacinação/métodos , Animais , Anticorpos Monoclonais/isolamento & purificação , Linhagem Celular Transformada , Linhagem Celular Tumoral , Ciclofosfamida/administração & dosagem , Humanos , Hibridomas/química , Hibridomas/imunologia , Imunossupressores/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Próstata/imunologia , Próstata/patologia
4.
MAbs ; 10(1): 46-54, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28581886

RESUMO

Despite fast advances in genomics and proteomics, monoclonal antibodies (mAbs) are still a valuable tool for areas such as the evolution of basic research in stem cells and cancer, for immunophenotyping cell populations, diagnosing and prognosis of diseases, and for immunotherapy. To summarize different subtractive immunization approaches successfully used for the production of highly specific antibodies, we identified scientific articles in NCBI PubMed using the following search terms: subtractive immunization, monoclonal antibody, tolerization, neonatal, high-zone tolerance, masking immunization. Patent records were also consulted. From the list of results, we included all available reports, from 1985 to present, that used any enhanced immunization technique to produce either polyclonal or monoclonal antibodies. Our examination yielded direct evidence that these enhanced immunization techniques are efficient in obtaining specific antibodies to rare epitopes, with different applications, such as to identify food contaminants or tumor cells.


Assuntos
Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Antígenos/administração & dosagem , Antígenos/imunologia , Imunização/métodos , Epitopos Imunodominantes/imunologia , Animais , Animais Recém-Nascidos , Humanos , Tolerância Imunológica , Esquemas de Imunização
5.
Acta Cir Bras ; 32(9): 706-711, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29019588

RESUMO

PURPOSE: To investigate the ultrastructural characteristics and analysis of residual DNA in scaffold models, produced with decellularized vena cava in an experimental model with rabbits. METHODS: Three groups were created for ultrastructural and residual DNA analysis: group 1 - control, consisting of samples of vena cava in natura; group 2 - SD, consisting of vein fragments submitted to 2% sodium deoxycholate decellularization by shaking (160rpm - Shaker News Brunswick Scientific®) for 1 hour at controlled temperature shaker at 37°C; group 3 - SDS, consisting of vein fragments submitted to 1% sodium dodecyl sulfate decellularization under the same previous condition, for 2 hours. RESULTS: The ultrastructural matrix of the blood vessel maintained its vintegrity after either decellularization models. The results of the two quantification methods demonstrated a significant decrease in the DNA content of the decellularized vena cava samples as compared to the control samples and, differed statistically from each other, p <0.05. CONCLUSION: The 2% DS protocol for vein decellularization, in this experimental model, was considered the best protocol because it presented less amount of residual DNA without causing substantial destruction of the extracellular matrix.


Assuntos
DNA/ultraestrutura , Engenharia Tecidual , Tecidos Suporte , Veias Cavas/ultraestrutura , Animais , Feminino , Microscopia Eletrônica de Transmissão , Coelhos
6.
Acta cir. bras ; 32(9): 706-711, Sept. 2017. graf
Artigo em Inglês | LILACS-Express | ID: biblio-886236

RESUMO

Abstract Purpose: To investigate the ultrastructural characteristics and analysis of residual DNA in scaffold models, produced with decellularized vena cava in an experimental model with rabbits. Methods: Three groups were created for ultrastructural and residual DNA analysis: group 1 - control, consisting of samples of vena cava in natura; group 2 - SD, consisting of vein fragments submitted to 2% sodium deoxycholate decellularization by shaking (160rpm - Shaker News Brunswick Scientific®) for 1 hour at controlled temperature shaker at 37°C; group 3 - SDS, consisting of vein fragments submitted to 1% sodium dodecyl sulfate decellularization under the same previous condition, for 2 hours. Results: The ultrastructural matrix of the blood vessel maintained its vintegrity after either decellularization models. The results of the two quantification methods demonstrated a significant decrease in the DNA content of the decellularized vena cava samples as compared to the control samples and, differed statistically from each other, p <0.05. Conclusion: The 2% DS protocol for vein decellularization, in this experimental model, was considered the best protocol because it presented less amount of residual DNA without causing substantial destruction of the extracellular matrix.

7.
Biochem Biophys Res Commun ; 457(4): 538-41, 2015 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-25600809

RESUMO

Matrix metalloproteinases (MMPs) are zinc (Zn(2+)) and calcium (Ca(2+)) dependant endopeptidases, capable of degradation of numerous components of the extracellular matrix. Cadmium (Cd(2+)) is a well known environmental contaminant which could impair the activity of MMPs. In this sense, this study was conducted to evaluate if Cd(2+) intake inhibits these endopeptidases activities at the rat prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9 at gelatinolytic assays when present in the incubation buffer. To investigate this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n = 9), or 15 ppm CdCl2 diluted in drinking water, during 10 weeks (n = 9) and 20 weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal prostate, and testicles were removed. These tissue samples were processed for protein extraction and subjected to gelatin zymography evaluation. Additionally, we performed an experiment of gelatin zymography in which 5 µM or 2 mM cadmium chloride (CdCl2) was directly dissolved at the incubation buffer, using the prostatic tissue samples from untreated animals that exhibited the highest MMP2 and MMP9 activities in the previous experiment. We have found that CdCl2 intake in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p < 0.05) at the ventral prostate and testis, respectively, in Cd(2+) treated animals when compared to controls. Moreover, the activities of the referred enzymes were 80% and 100% inhibited by 5 µM and 2 mM of CdCl2, respectively, even in the presence of 10 mM of CaCl2 within the incubation buffer solution. These important findings demonstrate that environmental cadmium contamination may deregulate the natural balance in the extracellular matrix turnover, through MMPs downregulation, which could contribute to the toxic effects observed in prostatic and testicular tissue after its exposure.


Assuntos
Cádmio/toxicidade , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/toxicidade , Próstata/enzimologia , Testículo/enzimologia , Poluentes Químicos da Água/toxicidade , Animais , Masculino , Próstata/efeitos dos fármacos , Ratos Wistar , Testículo/efeitos dos fármacos
8.
Trials ; 15: 497, 2014 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-25527165

RESUMO

BACKGROUND: The prevalence of chronic venous disease is high and occurs more frequently in females. According to the clinical, etiological, anatomical, and pathological classification (CEAP) definition, the reticular veins are included in the C1 class and are mainly associated with aesthetic complaints. Several invasive techniques are used for treatment, including mini phlebectomy, laser ablation, and radiofrequency ablation. However, a wide range of sclerosing agents may serve as minimally invasive alternatives, promoting chemical sclerosis of the vein wall. Although this technique is routinely performed around the world, there is no consensus on the most efficacious and safe chemical agent to be used. METHODS/DESIGN: Inclusion criteria are women between 18 and 69 years old with at least 10 cm long reticular veins in the lower limbs, on the outer side of the leg/thigh. Patients with CEAP 2 to 6, or with allergies, pregnancy, performing breastfeeding, or with any dermatologic or clinical problems will be excluded. Patients with venous ultrasound mapping showing involvement of saphenous trunks and/or a deep venous system will also be excluded. Patients will be randomized into two groups, one receiving 75% pure glucose and the other group receiving 0.2% polidocanol diluted in 70% glucose. Just one limb and one session per patient will be performed. The sclerosing agent volume will not exceed 5 mL. Clinical follow-up will include visits on days 7 and 60, always with photographic documentation. DISCUSSION: This project aims to enroll 96 patients and subject them to a double-blind treatment after the randomization process. The design is intended to evaluate efficacy through a primary end point and safety through a secondary end point. Forty-eight patients have currently been enrolled. Preliminary results for these patients showed that 25 received treatment, 2 were excluded, and 22 returned after 7 days and showed no greater adverse events. To date, establishing efficacy criteria has not been possible, and no patients have reached the 60-day return point. These data may help doctors choose the best chemical agent for the treatment of reticular veins. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02054325, 3/02/2014.


Assuntos
Solução Hipertônica de Glucose/administração & dosagem , Extremidade Inferior/irrigação sanguínea , Polietilenoglicóis/administração & dosagem , Projetos de Pesquisa , Soluções Esclerosantes/administração & dosagem , Escleroterapia/métodos , Telangiectasia/terapia , Varizes/terapia , Adolescente , Adulto , Idoso , Brasil , Doença Crônica , Protocolos Clínicos , Método Duplo-Cego , Feminino , Solução Hipertônica de Glucose/efeitos adversos , Humanos , Pessoa de Meia-Idade , Polidocanol , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos , Soluções Esclerosantes/efeitos adversos , Escleroterapia/efeitos adversos , Telangiectasia/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Varizes/diagnóstico , Adulto Jovem
9.
Acta Cir Bras ; 29(8): 485-92, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25140589

RESUMO

PURPOSE: To obtain a decellularized tracheal scaffold associating traditional approaches with the novel light-emitting diode (LED) proposal. METHODS: This study was performed with New Zealand adult rabbits weighing 3.0 - 4.0 kg. Different protocols (22) were used combining physical (agitation and LED irradiation), chemical (SDS and Triton X-100 detergents), and enzymatic methods (DNase and RNase). RESULTS: Generally, the cells surrounding soft tissues were successfully removed, but none protocol removed cells from the tracheal cartilage. However, longer protocols were more effective. The cost-benefits relation of the enzymatic processes was not favorable. It was possible to find out that the cartilaginous tissue submitted to the irradiation with LED 630nm and 475 nm showed an increased number of gaps without cells, but several cells were observed to be still present. CONCLUSION: The light-emitting diode is a promising tool for decellularization of soft tissues.


Assuntos
Luz , Engenharia Tecidual/métodos , Tecidos Suporte , Traqueia/ultraestrutura , Animais , Desoxirribonucleases/metabolismo , Detergentes/farmacologia , Matriz Extracelular/ultraestrutura , Coelhos , Ribonucleases/metabolismo , Traqueia/efeitos dos fármacos , Traqueia/enzimologia
10.
Acta cir. bras ; 29(8): 485-492, 08/2014. graf
Artigo em Inglês | LILACS | ID: lil-719186

RESUMO

PURPOSE: To obtain a decellularized tracheal scaffold associating traditional approaches with the novel light-emitting diode (LED) proposal. METHODS: This study was performed with New Zealand adult rabbits weighing 3.0 - 4.0 kg. Different protocols (22) were used combining physical (agitation and LED irradiation), chemical (SDS and Triton X-100 detergents), and enzymatic methods (DNase and RNase). RESULTS: Generally, the cells surrounding soft tissues were successfully removed, but none protocol removed cells from the tracheal cartilage. However, longer protocols were more effective. The cost-benefits relation of the enzymatic processes was not favorable. It was possible to find out that the cartilaginous tissue submitted to the irradiation with LED 630nm and 475 nm showed an increased number of gaps without cells, but several cells were observed to be still present. CONCLUSION: The light-emitting diode is a promising tool for decellularization of soft tissues. .


Assuntos
Animais , Coelhos , Luz , Tecidos Suporte , Engenharia Tecidual/métodos , Traqueia/ultraestrutura , Desoxirribonucleases/metabolismo , Detergentes/farmacologia , Matriz Extracelular/ultraestrutura , Ribonucleases/metabolismo , Traqueia/efeitos dos fármacos , Traqueia/enzimologia
11.
Exp Cell Res ; 326(1): 103-11, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24929113

RESUMO

Clinical experience for peripheral arterial disease treatment shows poor results when synthetic grafts are used to approach infrapopliteal arterial segments. However, tissue engineering may be an option to yield surrogate biocompatible neovessels. Thus, biological decellularized scaffolds could provide natural tissue architecture to use in tissue engineering, when the absence of ideal autologous veins reduces surgical options. The goal of this study was to evaluate different chemical induced decellularization protocols of the inferior vena cava of rabbits. They were decellularized with Triton X100 (TX100), sodium dodecyl sulfate (SDS) or sodium deoxycholate (DS). Afterwards, we assessed the remaining extracellular matrix (ECM) integrity, residual toxicity and the biomechanical resistance of the scaffolds. Our results showed that TX100 was not effective to remove the cells, while protocols using SDS 1% for 2h and DS 2% for 1h, efficiently removed the cells and were better characterized. These scaffolds preserved the original organization of ECM. In addition, the residual toxicity assessment did not reveal statistically significant changes while decellularized scaffolds retained the equivalent biomechanical properties when compared with the control. Our results concluded that protocols using SDS and DS were effective at obtaining decellularized scaffolds, which may be useful for blood vessel tissue engineering.


Assuntos
Tensoativos/farmacologia , Engenharia Tecidual , Tecidos Suporte , Transplante de Tecidos , Veia Cava Inferior/citologia , Veia Cava Inferior/fisiologia , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Fenômenos Biomecânicos , Diferenciação Celular , Células Cultivadas , Matriz Extracelular/química , Feminino , Técnicas Imunoenzimáticas , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Coelhos , Veia Cava Inferior/efeitos dos fármacos
12.
J Vasc Surg ; 59(6): 1677-85, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23830317

RESUMO

BACKGROUND: Cardiovascular diseases remain leaders as the major causes of mortality in Western society. Restoration of the circulation through construction of bypass surgical treatment is regarded as the gold standard treatment of peripheral vascular diseases, and grafts are necessary for this purpose. The great saphenous vein is often not available and synthetic grafts have their limitations. Therefore, new techniques to produce alternative grafts have been developed and, in this sense, tissue engineering is a promising alternative to provide biocompatible grafts. This study objective was to reconstruct the endothelium layer of decellularized vein scaffolds, using mesenchymal stem cells (MSCs) and growth factors obtained from platelets. METHODS: Fifteen nonpregnant female adult rabbits were used for all experiments. Adipose tissue and vena cava were obtained and subjected to MSCs isolation and tissue decellularization, respectively. MSCs were subjected to differentiation using endothelial inductor growth factor (EIGF) obtained from human platelet lysates. Immunofluorescence, histological and immunohistochemical analyses were employed for the final characterization of the obtained blood vessel substitute. RESULTS: The scaffolds were successfully decellularized with sodium dodecyl sulfate. MSCs actively adhered at the scaffolds, and through stimulation with EIGF were differentiated into functional endothelial cells, secreting significantly higher quantities of von Willebrand factor (0.85 µg/mL; P < .05) than cells cultivated under the same conditions, without EIGF (0.085 µg/mL). Cells with evident morphologic characteristics of endothelium were seen at the lumen of the scaffolds. These cells also stained positive for fascin protein, which is highly expressed by differentiated endothelial cells. CONCLUSIONS: Taken together, the use of decellularized bioscaffold and subcutaneous MSCs seems to be a potential approach to obtain bioengineered blood vessels, in the presence of EIGF supplementation.


Assuntos
Prótese Vascular , Células Endoteliais/citologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Procedimentos Cirúrgicos Reconstrutivos/métodos , Engenharia Tecidual/métodos , Animais , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Coelhos , Tecidos Suporte
14.
Cytotherapy ; 15(11): 1436-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23993645

RESUMO

BACKGROUND: Platelet-rich plasma has been largely used as a therapeutic option for the treatment of chronic wounds of different etiologies. The enhanced regeneration observed after the use of platelet-rich plasma has been systematically attributed to the growth factors that are present inside platelets' granules. AIM: We hypothesize that the remaining plasma and platelet-bound fibronectin may act as a further bioactive protein in platelet-rich plasma preparations. METHODS: Recent reports were analyzed and presented as direct evidences of this hypotheses. RESULTS: Fibronectin may directly influence the extracellular matrix remodeling during wound repair. This effect is probably through matrix metalloproteinase expression, thus exerting an extra effect on chronic wound regeneration. CONCLUSIONS: Physicians should be well aware of the possible fibronectin-induced effects in their future endeavors with PRP in chronic wound treatment.


Assuntos
Plaquetas/metabolismo , Fibronectinas/metabolismo , Plasma Rico em Plaquetas/metabolismo , Cicatrização/fisiologia , Ferimentos e Lesões/terapia , Matriz Extracelular/metabolismo , Humanos , Metaloproteinases da Matriz/metabolismo , Regeneração
16.
Platelets ; 24(3): 219-25, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22646294

RESUMO

Articular lesions are still a major challenge in orthopedics because of cartilage's poor healing properties. A major improvement in therapeutics was the development of autologous chondrocytes implantation (ACI), a biotechnology-derived technique that delivers healthy autologous chondrocytes after in vitro expansion. To obtain cartilage-like tissue, 3D scaffolds are essential to maintain chondrocyte differentiated status. Currently, bioactive 3D scaffolds are promising as they can deliver growth factors, cytokines, and hormones to the cells, giving them a boost to attach, proliferate, induce protein synthesis, and differentiate. Using mesenchymal stem cells (MSCs) differentiated into chondrocytes, one can avoid cartilage harvesting. Thus, we investigated the potential use of a platelet-lysate-based 3D bioactive scaffold to support chondrogenic differentiation and maintenance of MSCs. The MSCs from adult rabbit bone marrow (n = 5) were cultivated and characterized using three antibodies by flow cytometry. MSCs (1 × 10(5)) were than encapsulated inside 60 µl of a rabbit platelet-lysate clot scaffold and maintained in Dulbecco's Modified Eagle Medium Nutrient Mixture F-12 supplemented with chondrogenic inductors. After 21 days, the MSCs-seeded scaffolds were processed for histological analysis and stained with toluidine blue. This scaffold was able to maintain round-shaped cells, typical chondrocyte metachromatic extracellular matrix deposition, and isogenous group formation. Cells accumulated inside lacunae and cytoplasm lipid droplets were other observed typical chondrocyte features. In conclusion, the usage of a platelet-lysate bioactive scaffold, associated with a suitable chondrogenic culture medium, supports MSCs chondrogenesis. As such, it offers an alternative tool for cartilage engineering research and ACI.


Assuntos
Plaquetas , Cartilagem , Condrogênese/fisiologia , Células-Tronco Mesenquimais/metabolismo , Engenharia Tecidual , Tecidos Suporte , Animais , Técnicas de Cultura de Células , Células-Tronco Mesenquimais/citologia , Coelhos
17.
Biochem Biophys Res Commun ; 430(4): 1319-21, 2013 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-23261429

RESUMO

High-grade prostate cancers express high levels of matrix metalloproteinases (MMPs), major enzymes involved in tumor invasion and metastasis. However, the tumor cell lines commonly employed for prostate cancer research express only small amounts of MMPs when cultivated as monolayer cultures, in common culture media. The present study was conducted to ascertain whether culture conditions that include fibronectin can alter MMP2 and MMP9 expression by the human prostatic epithelial cell lines RWPE-1, LNCaP and PC-3. These cells were individually seeded at 2×10(4) cells/cm(2), cultivated until they reached 80% confluence, and then exposed for 4h to fibronectin, after which the conditioned medium was analyzed by gelatin zymography. Untreated cells were given common medium. Only RWPE-1 cells express detectable amounts of MMP9 when cultivated in common medium, whereas the addition of fibronectin induced high expression levels of pro and active forms of MMP2 in all tested cell lines. Our findings demonstrate that normal and tumor prostate cell lines express MMP2 activity when in contact with extracellular matrix components or blood plasma proteins such as fibronectin. Future studies of transcriptomes and proteomes in prostate cancer research using these cell lines should not neglect these important conclusions.


Assuntos
Fibronectinas/metabolismo , Metaloproteinase 2 da Matriz/biossíntese , Neoplasias da Próstata/enzimologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Fibronectinas/sangue , Fibronectinas/farmacologia , Humanos , Masculino , Metaloproteinase 9 da Matriz/biossíntese , Neoplasias da Próstata/sangue
18.
PLoS One ; 8(12): e84757, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24386413

RESUMO

INTRODUCTION: The use of the 5-alpha reductase inhibitors (5-ARIs) finasteride and dutasteride for prostate cancer prevention is still under debate. The FDA recently concluded that the increased prevalence of high-grade tumors among 5-ARI-treated patients must not be neglected, and they decided to disallow the use of 5-ARIs for prostate cancer prevention. This study was conducted to verify the effects of finasteride on prostate cell migration and invasion and the related enzymes/proteins in normal human and tumoral prostatic cell lines. MATERIALS AND METHODS: RWPE-1, LNCaP, PC3 and DU145 cells were cultivated to 60% confluence and exposed for different periods to either 10 µM or 50 µM finasteride that was diluted in culture medium. The conditioned media were collected and concentrated, and MMP2 and MMP9 activities and TIMP-1 and TIMP-2 protein expression were determined. Cell viability, migration and invasion were analyzed, and the remaining cell extracts were submitted to androgen receptor (AR) detection by western blotting techniques. Experiments were carried out in triplicate. RESULTS: Cell viability was not significantly affected by finasteride exposure. Finasteride significantly downregulated MMP2 and MMP9 activities in RWPE-1 and PC3 cells and MMP2 in DU145 cells. TIMP-2 expression in RWPE-1 cells was upregulated after exposure. The cell invasion of all four tested cell lines was inhibited by exposure to 50 µM of finasteride, and migration inhibition only occurred for RWPE-1 and LNCaP cells. AR was expressed by LNCaP, RWPE-1 and PC3 cells. CONCLUSIONS: Although the debate on the higher incidence of high-grade prostate cancer among 5-ARI-treated patients remains, our findings indicate that finasteride may attenuate tumor aggressiveness and invasion, which could vary depending on the androgen responsiveness of a patient's prostate cells.


Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Finasterida/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Proteínas de Neoplasias/biossíntese , Neoplasias da Próstata/enzimologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Enzimológica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptores Virais/biossíntese , Receptores Virais/genética , Inibidor Tecidual de Metaloproteinase-2/biossíntese , Inibidor Tecidual de Metaloproteinase-2/genética
19.
Reprod Toxicol ; 35: 137-43, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23099337

RESUMO

The aim of this study was to investigate the effects of caffeine (20 mg/L) intake on cadmium (15 mg/L) accumulation in the rat blood, testes, epididymis and prostate as well as cadmium-induced changes to the antioxidant defense system of the epididymis. Caffeine reduced the cadmium concentration in all tissues analyzed. Meanwhile, cadmium reduced catalase activity and increased superoxide dismutase (SOD) activity in the epididymis. Caffeine increased SOD activity, catalase and glutathione tissue expression and sustains the cadmium's effect on catalase and GSP-Px activity. No differences in the expression of metallothionein and lipid peroxidation were observed among the different treatments in the epididymis. In conclusion, low doses of cadmium alter the antioxidant enzymatic profile of the epididymis, but not induced oxidative lipid damage. Caffeine intake reduces overall cadmium accumulation in the organism and enhances the levels of antioxidant protein expression in the epididymis, thus exerting a protective effect against this metal.


Assuntos
Cádmio/toxicidade , Cafeína/farmacologia , Poluentes Ambientais/toxicidade , Epididimo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Catalase/metabolismo , Epididimo/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peróxidos Lipídicos/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Distribuição Tecidual
20.
Int J Exp Pathol ; 93(6): 429-37, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23136995

RESUMO

Coffee intake has been associated with a low risk of developing cancer, including prostate cancer, which is one of the most commonly diagnosed cancer in men. However, few studies have evaluated the chronic effects of caffeine, which is the most abundant methylxanthine in coffee, on prostate morphology and physiology. In the present study, we investigated the effects of chronic, low-dose caffeine intake on rat prostate morphology from puberty to adulthood. Five-week-old male Wistar rats were randomized into two experimental groups: caffeine-treated (20 ppm in drinking water, n = 12) and control (n = 12). The ventral and dorsolateral prostates were dissected, weighted and submitted to morphological, morphometrical and immunohistochemical analysis of cellular proliferation, apoptosis and androgen receptor (AR) tissue expression. The testosterone (T) and dihydrotestosterone (DHT) concentrations were measured in the plasma. Our results show that caffeine intake increased the concentrations of T and DHT, organ weight, epithelial cell proliferation and AR tissue expression in the ventral prostatic lobe. All the ventral prostates from the caffeine-treated animals presented various degrees of epithelial and stromal hyperplasia. Our results suggest that chronic caffeine intake from puberty increases androgenic signalling and cell proliferation in the rat prostate gland and can be related to the development of benign prostatic hyperplasia.


Assuntos
Cafeína/toxicidade , Estimulantes do Sistema Nervoso Central/toxicidade , Próstata/efeitos dos fármacos , Hiperplasia Prostática/induzido quimicamente , Administração Oral , Androgênios/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células , Doença Crônica , Di-Hidrotestosterona/sangue , Relação Dose-Resposta a Droga , Masculino , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/patologia , Ratos , Ratos Wistar , Receptores Androgênicos/metabolismo , Transdução de Sinais , Testosterona/sangue , Abastecimento de Água
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