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This report describes a case of generalized chronic periodontitis requiring periodontal regenerative therapy. The patient was a 56-year-old woman visiting the Tokyo Dental College Suidobashi Hospital with the chief complaint of swelling in the maxillary right gingiva. An initial examination revealed 34.0% of sites with a probing depth (PD) of ≥4 mm. The prevalence of sites with bleeding on probing was 32.7%. The plaque control record (PCR) score was 65.7%. Radiographic examination revealed angular bone resorption at #18 and 48. Horizontal absorption was also observed in other areas. The percent bone loss/age at #48 was 1.07. A clinical diagnosis of generalized chronic periodontitis (Stage III, Grade C) was made. Based on the clinical diagnosis of severe chronic periodontitis, initial periodontal therapy was performed. An improvement was observed in periodontal conditions at re-evaluation. The PCR score was 16.7%. Periodontal surgery was performed for teeth with a residual PD of ≥4 mm. Periodontal regenerative therapy using rhFGF-2 were performed on intrabony defects in #18 and 48. Open flap debridement was performed on #16, 26, and 27. Following evaluation, oral function was restored using all-ceramic crowns (#46). At 6 months postoperatively, the patient was transitioned to supportive periodontal therapy (SPT). During the 6-month SPT, stable periodontal conditions that facilitated a favourable level of plaque control were maintained.
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Pérdida de Hueso Alveolar , Periodontitis Crónica , Enfermedades de las Encías , Femenino , Humanos , Persona de Mediana Edad , Periodontitis Crónica/cirugía , Estudios de Seguimiento , Pérdida de Hueso Alveolar/cirugía , Tokio , Enfermedades de las Encías/cirugía , Regeneración Tisular Guiada Periodontal , Factores de Crecimiento de Fibroblastos , Pérdida de la Inserción Periodontal , Resultado del TratamientoRESUMEN
This report describes a case of periodontitis treated with periodontal surgery including guided tissue regeneration (GTR) and recombinant human fibroblast growth factor (rhFGF)-2. The patient was a 54-year-old woman who visited the Tokyo Dental College Suidobashi Hospital with the chief complaint of swelling in the maxillary right gingiva. An initial examination revealed 30.4% of sites with a probing depth (PD) of ≥4 mm. The prevalence of sites with bleeding on probing was 57.7%. The plaque control record (PCR) score was 66.1%. Radiographic examination revealed vertical bone defects in the molar region. Based on these findings, the clinical diagnosis was generalized chronic periodontitis (Stage III, Grade C). Initial periodontal therapy yielded an improvement in periodontal conditions, with the PCR score reducing to 13.8%. Periodontal surgery was performed for teeth with a residual PD ≥4 mm. Guided tissue regeneration was performed on #37 and 47. A series of periodontal regenerative treatments comprising application of rhFGF-2 was performed on angular bone defects in #14, 15, 25, and 27. Open flap debridement was performed on #16, 17, 26, 36, and 46. Following evaluation, oral function was restored by placing all-ceramic crowns on #21 and 26. The patient was then placed on supportive periodontal therapy. In the present case of generalized chronic periodontitis, periodontal regenerative therapy with GTR and rhFGF-2 yielded stable periodontal conditions.
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Pérdida de Hueso Alveolar , Periodontitis Crónica , Factores de Crecimiento de Fibroblastos , Enfermedades de las Encías , Regeneración Tisular Guiada Periodontal , Femenino , Humanos , Persona de Mediana Edad , Pérdida de Hueso Alveolar/etiología , Periodontitis Crónica/complicaciones , Periodontitis Crónica/cirugía , Estudios de Seguimiento , Enfermedades de las Encías/cirugía , Pérdida de la Inserción Periodontal , Tokio , Resultado del TratamientoRESUMEN
Recently, fibroblast growth factor-2 (FGF-2) agents for periodontal tissue regeneration have been increasingly applied to the treatment of periodontal disease. Our current challenge for resident dentists with little clinical experience is to enhance instruction in the handling of new medicine in addition to teaching conventional procedures in periodontal tissue regeneration. This report describes using case-specific, cost-effective three-dimensional (3D) models for dentists' lectures and periodontal surgical training. As an educational and training aid, preoperative and postoperative cone-beam computed tomography images were superimposed to enable three-dimensional observation of postoperative bone regeneration. A three-dimensional anatomical model was fabricated based on these images. Dental laboratory materials were used to reproduce the periosteum and gum. The fabrication time per 3D model was about 2 hours and the cost per model was about $0.5. These models were used for lectures to resident dentists and periodontal surgery training, and their feedback was obtained. The resident's response to surgical training using these 3D models was generally positive. The use of FGF-2 represents a new direction in the treatment of periodontal disease. This being new, however, means that inexperienced periodontists require training in its application and how this will affect prognosis, as this will differ from that with more conventional techniques aimed at tissue regeneration. The low-cost 3D model presented in this report can be a valuable tool to help accomplish this in teaching inexperienced dentists, such as resident dentists.
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The aim of this study was to investigate the effects of fibroblast growth factor (FGF)-2 used in combination with deproteinized bovine bone mineral (DBBM) on the healing of experimental periodontal defects. Periodontal defects created in rats were treated by FGF-2, DBBM, FGF-2 + DBBM, or left unfilled. Microcomputed tomography, histological, and immunohistochemical examinations were used to evaluate healing. In vitro cell viability/proliferation on DBBM with/without FGF-2 was assessed by WST-1. Cell behavior was analyzed using scanning electron and confocal laser scanning microscopy. Osteogenic differentiation was evaluated by staining with alkaline phosphatase and alizarin red. Bone volume fraction was significantly greater in FGF-2 and FGF-2 + DBBM groups than in other groups at 2 and 4 weeks postoperatively. In histological assessment, newly formed bone in FGF-2 and FGF-2 + DBBM groups appeared to be greater than other groups. Significantly greater levels of proliferating cell nuclear antigen-, vascular endothelial growth factor-, and osterix-positive cells were observed in FGF-2 and FGF-2 + DBBM groups compared to Unfilled group. In vitro, addition of FGF-2 to DBBM promoted cell viability/proliferation, attachment/spreading, and osteogenic differentiation. The combination therapy using FGF-2 and DBBM was similarly effective as FGF-2 alone in the healing of experimental periodontal defects. In certain bone defect configurations, the combined use of FGF-2 and DBBM may enhance healing via promotion of cell proliferation, angiogenesis, and osteogenic differentiation.
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Sustitutos de Huesos/farmacología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Osteogénesis/efectos de los fármacos , Periodoncio , Animales , Bovinos , Masculino , Periodoncio/lesiones , Periodoncio/metabolismo , Periodoncio/patología , Ratas , Ratas WistarRESUMEN
Destructive effects of hepatocellular carcinoma (HCC) is enhanced by many cellular mechanisms including activation of fibrosis, inflammation and tumor invasion. Therefore, this study was conducted to investigate the therapeutic effects of iCRT14, ß-catenin blocker, on HCC. In addition, the molecular effects of iCRT14 will be investigated on inflammation, fibrosis and tumor invasion pathways. After inducting HCC in rats, hepatic tissues were used for determination of the expression of ß-catenin, nuclear factor (NF)κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, matrix metalloproteinase (MMP)9, transforming growth factor (TGF)-ß1, fibroblast growth factor (FGF)-2 and integrin-ß6. Hepatic tissues were stained with hematoxylin/eosin and with anti-Ki67. Results revealed that iCRT14 significantly increased the survival percent of HCC rats, reduced both α-fetoprotein and average number of nodules. In parallel, hepatic sections from HCC rats stained with hematoxylin/eosin revealed vacuolated cytoplasm and necrotic nodules, which were attenuated by treatment with iCRT14. Finally, treating HCC rats with iCRT14 resulted in reduction of the expression of NFκB, TNF-α, IL-1ß, TGF-ß1, MMP9, FGF-2 and integrin-ß6. In conclusion, iCRT14 treatment exhibited antitumor effects against HCC through impairing ß-catenin signaling pathway. iCRT14 suppressed liver tissue inflammation, fibrosis and angiogenesis, possibly via reducing expression of NFκB, TNF-α, IL-1ß, TGF-ß1, MMP-9, FGF-2.
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Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Movimiento Celular/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Piridinas/farmacología , Pirroles/farmacología , Tiazolidinedionas/farmacología , beta Catenina/antagonistas & inhibidores , Animales , Citocinas/genética , Citocinas/metabolismo , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Fibrosis , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica , Neovascularización Patológica , Ratas Sprague-Dawley , Tioacetamida , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Vía de Señalización Wnt , beta Catenina/metabolismoRESUMEN
INTRODUCTION: Several studies have demonstrated that basic fibroblast growth factor (FGF-2) is one of the most effective growth factors for periodontal regeneration. The Ministry of Health, Labor and Welfare in Japan have approved 0.3% human recombinant FGF-2 for periodontal regeneration, and it has been commercially available since 2016. In this case report, a patient was treated with this periodontal regenerative medicine and demonstrated success at 15-month follow-up, as confirmed by dental X-ray and on cone-beam computed tomography (CBCT). CASE PRESENTATION: A 42-year-old woman with a one by two walled intrabony defect and Class III furcation involvement in tooth #19, and Class II furcation involvement in tooth #18 (lingual) underwent periodontal regenerative surgery with FGF-2 without any bone graft materials. Favorable clinical and radiographic outcomes were noted 15 months after the procedure. The vertical bone defect in tooth #19 showed a clinical attachment level gain of 8 mm. Moreover, CBCT analysis revealed considerable new bone formation in the Class II furcation involvement in tooth #18 and limited bone formation in the Class III furcation involvement in tooth #19. CONCLUSIONS: This case report indicates that FGF-2 showed a positive outcome in terms of periodontal regeneration in a case of one by two wall intrabony defects with Class III furcation involvement. A complete recovery of Class II furcation involvement was observed without artificial bone graft materials.
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Factor 2 de Crecimiento de Fibroblastos , Defectos de Furcación , Adulto , Femenino , Estudios de Seguimiento , Defectos de Furcación/diagnóstico por imagen , Defectos de Furcación/tratamiento farmacológico , Defectos de Furcación/cirugía , Regeneración Tisular Guiada Periodontal , Humanos , JapónRESUMEN
BACKGROUND: The combination of antiapoptotic and angiogenic actions may represent a pharmacotherapeutic strategy for the treatment of myocardial infarction. Fibroblast growth factor (FGF) is expressed in various cell types including endothelial and muscle cells and promotes their survival, migration, and proliferation. METHODS AND RESULTS: Myocardial microvascular endothelial cells were divided into four treatment groups, the sham, hypoxia, basic FGF (bFGF), and bFGF plus 2-methoxyestradiol groups, and subjected to in vitro apoptotic analysis and Matrigel assays. An in vivo model of myocardial infarction was established by ligaturing the left coronary artery of mice in the four treatment groups. Cardiac performance, myocardial injury, endothelial cell angiogenesis, and myocardial apoptosis were assessed. bFGF administration after myocardial infarction improved cardiac function and cell viability, attenuated myocardial injury and apoptosis, and enhanced angiogenesis. Western blotting of HIF-1α, p-AKT, VEGF, p53, BAX, and Bcl-2 showed that bFGF increased HIF-1α, p-AKT, VEGF, and Bcl-2 and decreased BAX protein levels. CONCLUSION: The results of the present study indicated that bFGF attenuates myocardial injury by inhibiting apoptosis and promoting angiogenesis via a novel HIF-1α-mediated mechanism and a potential utility of bFGF in protecting against myocardial infarction.
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The replacement therapy or transplantation using neural cells, which differentiated from stem cells, has emerged as a promising strategy for repairing damaged neural tissues and helping functional recovery in the treatment of neural system diseases. The challenge, however, is how to control embryonic stem cell fate so that neural differentiation can be efficiently directed to enrich a neuron cell population, and meanwhile to maintain their bioactivities. This is a key question and has a very significant impact in regenerative medicine. Here we proposed a new neural-differentiation inductive nanocomposite, containing gold nanoparticles (AuNPs), poly(2-methacrylamido glucopyranose-co-3-sulfopropyl acrylate) (PMS), and basic fibroblast growth factor (FGF2), for the high efficient directional neural-specific differentiation of mouse embryonic stem cells (mESCs). In this AuNP-PMS/FGF2 composite, PMS, playing as the high-active mimic of heparin/heparan sulfate (HS), is covalently anchored to AuNPs and bound with FGF2 on the surface of nanoparticles, forming a HS/FGF2 complex nanomimics to facilitate its binding to FGF receptor (FGFR) and promote high neural-inductive activity of mESCs. The stability, bioactivity and biocompatibility of the composite are investigated in this study. The results showed that the AuNP-PMS/FGF2 composite could maintain a long-term stability at room temperature for at least 8 days, and greatly promote the neural differentiation of mESCs. Compared with the other materials, the AuNP-PMS/FGF2 composite could significantly stimulate the expression of the specific neural differentiation markers (nestin and ß3-tubulin), while obviously down-regulate the mRNA production of pluripotency marker Oct-4 in mESCs. Moreover, the promotion effect of the composite on neuronal maturation marker ß3-tubulin expression achieved maximally at the low concentration of FGF2 (4 ng/mL), which suggested the high efficiency of AuNP-PMS/FGF2 composite in neural differentiation of mESCs. Meanwhile, both mESCs and L929 cells showed desirable growth during the incubation with AuNP-PMS/FGF2 composite. The AuNP-PMS/FGF2 system presents a new way to achieve HS/FGF2 complex nanomimics efficiently for the neural differentiation of mESCs.
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Nanopartículas del Metal , Células Madre Embrionarias de Ratones , Animales , Diferenciación Celular , Factor 2 de Crecimiento de Fibroblastos/farmacología , Oro , Heparina , RatonesRESUMEN
Increased immature neovessels contribute to plaque growth and instability. Here, we investigated a method to establish functional and stable neovessel networks to increase plaque stability. Rabbits underwent aortic balloon injury and were divided into six groups: sham, vector and lentiviral transfection with vascular endothelial growth factor-A (VEGF)-A, fibroblast growth factor (FGF)-2, platelet-derived growth factor (PDGF)-BB and FGF-2 + PDGF-BB. Lentivirus was percutaneously injected into the media-adventitia of the abdominal aorta by intravascular ultrasound guidance, and plaque-rupture rate, plaque-vulnerability index and plaque neovessel density at the injection site were evaluated. Confocal microscopy, Prussian Blue assay, Evans Blue, immunofluorescence and transmission electron microscopy were used to assess neovessel function and pericyte coverage. To evaluate the effect of FGF-2/PDGF-BB on pericyte migration, we used the mesenchymal progenitor cell line 10T1/2 as an in vitro model. VEGF-A- and FGF-2-overexpression increased the number of immature neovessels, which caused intraplaque haemorrhage and inflammatory cell infiltration, eventually resulting in the plaque vulnerability; however, FGF-2/PDGF-BB induced mature and functional neovessels, through increased neovessel pericyte coverage. Additionally, in vitro analysis of 10T1/2 cells revealed that FGF-2/PDGF-BB induced epsin-2 expression and enhanced the VEGF receptor-2 degradation, which negatively regulated pericyte function consistent with the in vivo data. These results showed that the combination of FGF-2 and PDGF-BB promoted the function and maturation of plaque neovessels, thereby representing a novel potential treatment strategy for vulnerable plaques.
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Becaplermina/administración & dosificación , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Vectores Genéticos/administración & dosificación , Lentivirus/genética , Neovascularización Patológica/prevención & control , Placa Aterosclerótica/terapia , Proteínas Adaptadoras del Transporte Vesicular , Animales , Becaplermina/genética , Becaplermina/metabolismo , Movimiento Celular , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Vectores Genéticos/genética , Masculino , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Fosforilación , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , ConejosRESUMEN
The plasmacytoma variant translocation 1 (PVT1)1 gene is a long non-coding RNA (lncRNA)2 that has been shown to be an oncogene in many cancers. Herein, the function and potential molecular mechanisms connecting PVT1 and miR-195-5p were elucidated in endometrial cancer cell lines. Quantitative real-time PCR and fluorescence in situ hybridization (FISH)3 demonstrated that PVT1 is up-regulated concomitant with miR-195-5p down-regulation in human endometrial carcinoma tissues. PVT1 knockdown inhibited cell proliferation, migration, and invasion while facilitating apoptosis of endometrial cancer cells. Moreover, restoration of miR-195-5p due to PVT1 knockdown exerted tumor-suppressive functions. We observed that PVT1 promotes malignant cell behavior by decreasing miR-195-5p expression. Binding of PVT1 and miR-195-5p was confirmed using luciferase assays. Furthermore, expression of miR-195-5p negatively correlates with PVT1 expression. At the molecular level, either PVT1 knockdown or miR-195-5p overexpression resulted in a decrease of acidic fibroblast growth factor receptor (FGFR1)4 and basic fibroblast growth factor (FGF2).5 FGFR1 and FGF2 are targets of miR-195-5p that play a critical role in endometrial carcinoma by activating PI3K/AKT and MAPK/Erk pathways. Remarkably, PVT1 knockdown combined with miR-195-5p overexpression led to tumor regression in vivo. Overall, these results depict a novel pathway mediated by PVT1 in endometrial carcinoma, which may have potential application for endometrial carcinoma therapy.
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Glioblastoma multiforme (GBM) is one of the most malignant cancers. MicroRNAs (miRs) were reported to play important roles in GBM recently. However, the role of a novel miR-186-5p in GBM tumorigenesis is still elusive. Using bioinformatics, miR-186-5p was identified as potential regulators of both fibroblast growth factor (FGF)-2 and NF-κB subunit RelA. Luciferase reporter assay was used to confirm the direct recognition FGF2 and RelA mRNAs by miR-186-5p. Invasion and migration assays were employed to study the effect of miR-186-5p on GBM cell growth in vitro. Xenograft tumor animal model was established to elucidate the in vivo function of miR-186-5p. MiR-186-5p directly targeted mRNAs of both FGF2 and RelA, and repressed their expressions. Invasive and migratory abilities of GBM cells and growth of xenograft tumors were significantly inhibited by miR-186-5p, which can be restored by re-introduction of FGF2 and RelA expressions. MiR-186-5p is a novel tumor suppressor miR that functions to inhibit tumorigenesis of GBM both in vitro and in vivo, by targeting both FGF2 and RelA. MiR-186-5p/FGF2/RelA pathway may be potentially used as molecular targets of in the clinical treatment of GBM.
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Neoplasias Encefálicas/metabolismo , Carcinogénesis/metabolismo , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Glioblastoma/metabolismo , MicroARNs/biosíntesis , Factor de Transcripción ReIA/biosíntesis , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Factor 2 de Crecimiento de Fibroblastos/antagonistas & inhibidores , Factor 2 de Crecimiento de Fibroblastos/genética , Genes Supresores de Tumor/fisiología , Glioblastoma/genética , Glioblastoma/patología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Factor de Transcripción ReIA/antagonistas & inhibidores , Factor de Transcripción ReIA/genética , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Pulmonary fibrosis is a progressive lung disorder of unknown etiology, which is characterized by alterations in alveolar epithelium function, fibroblast activation, and increased extracellular matrix deposition. Recent studies have demonstrated that PF is associated with uncontrolled production of cytokines after lung injury. In the present study, we found that transforming growth factor-ß1 (TGF-ß1) and fibroblast growth factor 2 (FGF-2) were both upregulated in bleomycin-induced fibrotic lung tissue and primary murine alveolar epithelial Type II (ATII) cells treated with bleomycin. Furthermore, we discovered that TGF-ß1 could induce the differentiation of lung resident mesenchymal stem cells (LR-MSCs) into fibroblasts, which may play an essential role in PF. LR-MSCs incubated with FGF-2 showed modest alterations in the expression of α-SMA and Vimentin. Moreover, in our study, we found that Wnt/ß-catenin signaling was activated both in vitro and in vivo as a result of bleomycin treatment. Interestingly, we also found that suppression of the Wnt/ß-catenin signaling could significantly attenuate bleomycin-induced PF accompanied with decreased expression of TGF-ß1 and FGF-2 in vitro and in vivo. These results support that controlling the aberrant expression of TGF-ß1 and FGF-2 via inhibition of Wnt/ß-catenin signaling could serve as a potential therapeutic strategy for PF.
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Factor 2 de Crecimiento de Fibroblastos/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Vía de Señalización Wnt , Animales , Bleomicina , Diferenciación Celular/efectos de los fármacos , Línea Celular , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Compuestos Heterocíclicos con 3 Anillos/farmacología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Pulmón/patología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Ratones Endogámicos C57BL , Regulación hacia Arriba/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapy, and is rarely amenable to radiotherapy. Heparanase, enzyme attacks heparan sulfate proteoglycans (HSPGs), is preferentially expressed in human tumors and its overexpression in low-metastatic tumor confers a highly invasive phenotype in experimental animals. Meanwhile, high doses of suramin dramatically increase tissue glycosaminoglycans due, in part, to inhibition of heparanase enzymes. Therefore, the following study was conducted to evaluate the chemopreventive and hepatoprotective effects of suramin in in-vivo model of HCC. Therefore, HCC was induced in SD rats by thioacetamide (200mg/kg) in presence/absence of suramin (20mg/kg). Liver impairment was assessed by measuring serum α-fetoprotein and investigating liver sections stained with Hematoxylin/Eosin. Hepatic HSPGs and heparanse were measured by ELISA. Glucosamine and glucuronic acid were measured by chemical methods. Gene expression of fibroblast growth factor (FGF)-2 and caspase-3 was measured. Apoptotic pathway was evaluated by measuring the activity of caspase-3/8/9. Suramin increased the animal survival and decreased serum α-fetoprotein. In addition, suramin ameliorated fibrosis and massive hepatic tissue breakdown. Suramin restored hepatic HSPGs and reduced the activity of hepatic heparanase leading to decreased hepatic levels of glucosamine and glucuronic acid. Moreover, suramin reduced the gene expression of FGF-2 and caspase-3. Finally, suramin blocked the elevated activity of caspase-3/8/9. In conclusion, surmain showed antitumor activity as well as hepatoprotective effects. Besides its antioxidant activity, other mechanisms are involved including restoration of HSPGs and inhibition of heparanase and FGF-2. Suramin inhibits intrinsic and extrinsic apoptotic pathway. Targeting HSPGs expression is potential therapeutic target for HCC.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Glucuronidasa/antagonistas & inhibidores , Neoplasias Hepáticas/tratamiento farmacológico , Suramina/uso terapéutico , Adulto , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/patología , Femenino , Glucuronidasa/genética , Proteoglicanos de Heparán Sulfato/genética , Proteoglicanos de Heparán Sulfato/metabolismo , Humanos , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/enzimología , Neoplasias Hepáticas Experimentales/patología , Masculino , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Suramina/administración & dosificación , Suramina/farmacología , Análisis de SupervivenciaRESUMEN
Glioblastoma multiforme (GBM) is the most malignant form of central nervous system tumor, and current therapies are largely ineffective at treating the cancer. Developing a more complete understanding of the mechanisms controlling the tumor is important in order to explore new possible treatment options. It is speculated that the presence of glioblastoma stem or stem-like cells (GSCs), a rare type of pluripotent cancer cell that possesses the ability to self-renew and generate tumors, could be an important factor contributing to the resistance to treatment and deadliness of the cancer. A comprehensive knowledge of the mechanisms controlling the expression and properties of GSCs is currently lacking, and one promising area for further exploration is in the influence of basic fibroblast growth factor (FGF-2) on GSCs. Recent studies reveal that FGF-2 plays a significant part in regulating GBM, and the growth factor is commonly included as a supplement in media used to culture GSCs in vitro. However, the particular role that FGF-2 plays in GSCs has not been as extensively explored. Therefore, understanding how FGF-2 is involved in GSCs and in GBMs could be an important step towards a more complete comprehension of the managing the disease. In this review, we look at the structure, signaling pathways, and specific role of FGF-2 in GBM and GSCs. In addition, we explore the use of FGF-2 in cell culture and using its synthetic analogs as a potential alternative to the growth factor in culture medium.