RESUMO
PURPOSE: To histologically quantify the different tissues that make up the porcine ureter, (epithelial, connective, and muscular tissue) in the three segments labelled: cranial, middle and caudal, in order to identify the segment most compatible for use as a vascular graft. METHODS: Fifteen porcine ureters were collected, divided into the three segments, and the samples were stained with hematoxylin and eosin, picrosirius red and Weigert's resorcin-fuchsin. The immunohistochemistry technique was applied for alpha-smooth muscle actin. Collagen fibers, muscle, epithelium, and elastic fibers tissue were quantified, in the entire ureter, and divided into hemispheres, comparing the different segments. RESULTS: When comparing hemisphere segments, significant differences were observed (p < 0.01) for collagen and muscle tissue, with the cranial segment presenting the greatest amount of these components when compared to the middle and caudal. No significant difference was observed between the segments when comparing the entire ureters. CONCLUSIONS: After comparing the segments by hemisphere, the cranial segment presented a slight advantage for use as a vascular graft due to presenting greater collagen fiber content.
Assuntos
Colágeno , Ureter , Animais , Ureter/anatomia & histologia , Ureter/cirurgia , Suínos , Colágeno/análise , Imuno-Histoquímica , Prótese Vascular , Xenoenxertos , Tecido Elástico/anatomia & histologiaRESUMO
SUMMARY: Tissue engineering aims to fabricate a scaffold that exhibits a suitable surface topography for a desired cellular response. Therefore, a study analyzing the characteristics of bone grafts is important for future research directions. This work aims to analyze the physical-chemical characteristics of commercially available bone grafts of human and bovine origin for dental use, using morphological analysis of the surface and chemical composition by variable pressure scanning electron microscope (VP-SEM) and energy-dispersive x-ray (EDX) spectrometry. In addition, pore diameter and surface area were analyzed by degassing method using a porosimeter, and particle size by laser diffraction. The analyzed allograft and xenograft particles differ in morphological characteristics and chemical composition. The allograft particles present a cuboidal and prismatic geometric morphology with angled edges and the absence of macropores. On the contrary, the xenograft particles present an irregular morphology with macropores in their structure. There is a statistically significant difference in C, P, and Ca between the xenograft and allografts (p < 0,05). The analyzed composition of allografts showed mainly the presence of C and O. In contrast, the composition of the xenograft was mainly Ca. These differences could influence the osteogenic properties of allografts and xenografts. This analysis provides basic information to understand the physicochemical properties of allografts and xenografts that facilitate cell-graft interaction.
La ingeniería de tejidos tiene como objetivo fabricar un andamio que muestre una topografía de superficie adecuada para una respuesta celular deseada. Por tanto, un estudio que analice las características de los injertos óseos es importante para futuros enfoques de investigación. Este trabajo tiene como objetivo analizar las características físico-químicas de injertos óseos de origen humano y bovino disponibles comercialmente para uso odontológico, mediante análisis morfológico de la superficie y composición química mediante microscopio electrónico de barrido de presión variable (VP-SEM) y x-dispersivo de energía. espectrometría de rayos (EDX). Además, el diámetro de los poros y el área superficial se analizaron mediante el método de desgasificación utilizando un porosímetro y el tamaño de las partículas mediante difracción láser. Las partículas de aloinjerto y xenoinjerto analizadas difieren en características morfológicas y composición química. Las partículas del aloinjerto presentan una morfología geométrica cúbica y prismática con bordes angulados y ausencia de macroporos. Por el contrario, las partículas de xenoinjerto presentan una morfología irregular con macroporos en su estructura. Existe una diferencia estadísticamente significativa en C, P y Ca entre el xenoinjerto y los aloinjertos (p < 0,05). La composición analizada de los aloinjertos mostró principalmente la presencia de C y O. Por el contrario, la composición del xenoinjerto fue principalmente Ca. Estas diferencias podrían influir en las propiedades osteogénicas de los aloinjertos y xenoinjertos. Este análisis proporciona información básica para comprender las propiedades fisicoquímicas de aloinjertos y xenoinjertos que facilitan la interacción célula-injerto.
Assuntos
Humanos , Animais , Bovinos , Aloenxertos/anatomia & histologia , Aloenxertos/química , Espectrometria por Raios X , Regeneração Óssea , Microscopia Eletrônica de Varredura , Porosidade , Transplante Ósseo , Xenoenxertos/anatomia & histologia , Xenoenxertos/químicaRESUMO
BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood. RESULTS: miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models. CONCLUSIONS: These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.
Assuntos
Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , MicroRNAs , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Glioma/genética , Glioma/metabolismo , Animais , Camundongos , Xenoenxertos , Transplante de Neoplasias , Neoplasias Encefálicas/genética , MicroRNAs/metabolismoRESUMO
PURPOSE: To evaluate the survival rates of dental implants with a hybrid macrostructure and the surface biomimetically coated with nanohydroxyapatite, placed in horizontally atrophic maxillae previously submitted to the guided bone regeneration (GBR) procedure, associated with the use of a deproteinized bovine bone graft (DBB). METHODS: Twenty-five patients who received 196 implants were involved in this study. First, these patients were submitted to GBR procedures and maxillary sinus lift, where DBB was used as the grafting material. The dental implants were placed after a minimum period of 6 months of the grafting procedures. The patients were followed up every six months and clinical/radiographic examinations were performed to assess the implants, using the following indicators as a reference: (1) Absence of mobility; (2) Absence of pain. Data about the age, surgery time, smoking status, implant size, and time between the grafting procedure and implant placement were correlated with implant failures. RESULTS: Twelve implants failed, generating a survival rate of 94.23%. None of the variables analysed correlated with the implant failures. CONCLUSION: Implants with a hybrid macrostructure and surface biomimetically coated with nanohydroxyapatite present good survival rates in horizontally atrophic maxillae grafted with DBB.
Assuntos
Implantes Dentários , Maxila , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Maxila/cirurgia , Idoso , Animais , Falha de Restauração Dentária , Adulto , Transplante Ósseo/métodos , Durapatita , Bovinos , Levantamento do Assoalho do Seio Maxilar/métodos , Substitutos Ósseos , Perda do Osso Alveolar/cirurgia , Perda do Osso Alveolar/diagnóstico por imagem , Xenoenxertos/transplante , Implantação Dentária Endóssea/métodos , Análise de SobrevidaRESUMO
AIM: The present systematic review aimed to identify and summarize the clinical, radiographic, and histological outcomes of alveolar ridge preservation using bone xenografts and absorbable sealing materials compared with spontaneous healing in the esthetic zone. MATERIALS AND METHODS: Randomized clinical trials (RCTs) fulfilling specific eligibility criteria were included. Two review authors independently searched for eligible studies, extracted data from the published reports and performed the risk of bias assessment (RoB 2 tool). Study results were summarized using random effects meta-analyses. RESULTS: Thirteen articles concerning 10 RCTs were included, involving a total of 357 participants. Most of studies were considered as "low" risk of bias. Meta-analyses indicated less horizontal (difference in means-MD = 1.88 mm; p < 0.001), vertical mid-buccal (MD = 1.84 mm; p < 0.001) and vertical mid-lingual (MD = 2.27 mm; p < 0.001) bone resorption in alveolar ridge preservation compared to spontaneous healing as assessed clinically. Bone changes assessed radiographically showed consistent results in terms of horizontal (at 1 mm: MD = 1.84 mm, p < 0.001), vertical mid-buccal (MD = 0.95 mm; p < 0.001) and mid-lingual (MD = 0.62 mm; p = 0.05) resorption. Part of the bone resorption in the spontaneous healing group was compensated by soft-tissues, since the observed differences between groups in linear ridge reduction evaluated through cast models superimposition were smaller (MD = 0.52 mm; p < 0.001). CONCLUSIONS: Alveolar ridge preservation with xenogeneic bone substitutes and non-autogenous resorbable socket sealing materials is efficacious in reducing post-extraction bone and ridge changes in the esthetic region.
Assuntos
Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Humanos , Processo Alveolar/cirurgia , Alvéolo Dental/cirurgia , Aumento do Rebordo Alveolar/métodos , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/cirurgia , Xenoenxertos , Remissão Espontânea , Extração Dentária/métodos , Estética DentáriaRESUMO
Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical GBM xenograft studies without a standardized methodology. This systematic review aims to summarize the advances in zebrafish GBM xenografting, compare research protocols to pinpoint advantages and underlying limitations, and designate the predominant xenografting parameters. Based on the PRISMA checklist, we systematically searched PubMed, Scopus, and ZFIN using the keywords "glioblastoma," "xenotransplantation," and "zebrafish" for papers published from 2005 to 2022, available in English. 46 articles meeting the review criteria were examined for the zebrafish strain, cancer cell line, cell labeling technique, injected cell number, time and site of injection, and maintenance temperature. Our review designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding of these predominate among the zebrafish strains. Orthotopic transplantation is more commonly employed. A number of 50-100 cells injected at 48 h post-fertilization in high density and low infusion volume is considered as an effective xenografting approach. U87 cells are used for GBM angiogenesis studies, U251 for GBM proliferation studies, and patient-derived xenograft (PDX) to achieve clinical relevance. Gradual acclimatization to 32-33 °C can partly address the temperature differential between the zebrafish and the GBM cells. Zebrafish xenograft models constitute valuable tools for preclinical studies with clinical relevance regarding PDX. The GBM xenografting research requires modification based on the objective of each research team. Automation and further optimization of the protocol parameters could scale up the anticancer drug trials.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Humanos , Glioblastoma/patologia , Transplante Heterólogo , Peixe-Zebra , Xenoenxertos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Modelos Animais de DoençasRESUMO
The TGF signaling pathway is a key regulator of cancer progression. In this work, we report for the first time the antitumor activity of TßRII-SE/Fc, a novel peptibody whose targeting domain is comprised of the soluble endogenous isoform of the human TGF-ß type II receptor (TßRII-SE). Overexpression of TßRIISE/Fc reduces in vitro cell proliferation and migration while inducing cell cycle arrest and apoptosis in human colorectal cancer-derived cell lines. Moreover, TßRII-SE/Fc overexpression reduces tumorigenicity in BALB/c nude athymic mice. Our results revealed that TRII-SE/Fc-expressing tumors were significantly reduced in size or were even incapable of developing. We also demonstrated that the novel peptibody has the ability to inhibit the canonical TGF-ß and BMP signaling pathways while identifying SMAD-dependent and independent proteins involved in tumor progression that are modulated by TßRII-SE/Fc. These findings provide insights into the underlying mechanism responsible for the antitumor activity of TßRII-SE/Fc. Although more studies are required to demonstrate the effectiveness and safety of the novel peptibody as a new therapeutic for the treatment of cancer, our initial in vitro and in vivo results in human colorectal tumor-derived cell lines are highly encouraging. Our results may serve as the foundation for further research and development of a novel biopharmaceutical for oncology.
Assuntos
Neoplasias , Receptores de Fatores de Crescimento Transformadores beta , Camundongos , Animais , Humanos , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Xenoenxertos , Lentivirus/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Linhagem CelularRESUMO
Purpose: To histologically quantify the different tissues that make up the porcine ureter, (epithelial, connective, and muscular tissue) in the three segments labelled: cranial, middle and caudal, in order to identify the segment most compatible for use as a vascular graft. Methods: Fifteen porcine ureters were collected, divided into the three segments, and the samples were stained with hematoxylin and eosin, picrosirius red and Weigert's resorcin-fuchsin. The immunohistochemistry technique was applied for alpha-smooth muscle actin. Collagen fibers, muscle, epithelium, and elastic fibers tissue were quantified, in the entire ureter, and divided into hemispheres, comparing the different segments. Results: When comparing hemisphere segments, significant differences were observed (p < 0.01) for collagen and muscle tissue, with the cranial segment presenting the greatest amount of these components when compared to the middle and caudal. No significant difference was observed between the segments when comparing the entire ureters. Conclusions: After comparing the segments by hemisphere, the cranial segment presented a slight advantage for use as a vascular graft due to presenting greater collagen fiber content.
Assuntos
Suínos , Ureter , Imuno-Histoquímica , XenoenxertosRESUMO
The aim of this work is to estimate the effect of Imatinib, exosomes, and Imatinib-exosomes mixture in chronic myeloid leukemia (CML). For this purpose, mathematical models based on Gompertzian and logistic growth differential equations were proposed. The models contained parameters representing the effects of the three components on CML proliferation. Parameters estimation was performed under the Bayesian statistical approach. Experimental data reported in the literature were used, corresponding to four trials of a human leukemia xenograft in BALB/c female rats over a period of forty days. The models were fitted to the following growth dynamics: normal tumor growth, growth with exosomes, growth with Imatinib, and growth with exosomes-Imatinib mixture. For the proposed logistic growth model, it was determined that when using Imatinib treatment the growth rate is 0.93 (95% CrI: 84.33-99.64) slower and reduces the tumor volume to approximately 10% (95% CrI : 8.67-10.81). In the presence of exosome treatment, the growth rate is 0.83 (95% CrI: 1.52-16.59) faster and the tumor volume is expanded by 40% (95% CrI: 25.36-57.28). Finally, in the presence of Imatinib-exosomes mixture treatment, the growth rate is 0.82 (95% CrI: 76.87-88.51) slower and the tumor volume is reduced by 95% (95% CrI: 86.76-99.85). It is concluded that the presence of exosomes partially inactivates the effect of the Imatinib drug on tumor growth in a mouse xenograft model.
Assuntos
Antineoplásicos , Exossomos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Feminino , Camundongos , Ratos , Animais , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Teorema de Bayes , Xenoenxertos , Exossomos/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
BACKGROUND: Tumour hypoxia is associated with increased metastasis, invasion, poor therapy response and prognosis. Most PET radiotracers developed and used for clinical hypoxia imaging belong to the 2-nitroimidazole family. Recently we have developed novel 2-nitroimidazole-derived PET radiotracer [18F]FBNA (N-(4-[18F]fluoro-benzyl)-2-(2-nitro-1H-imidazol-1-yl)-acet-amide), an 18F-labeled analogue of antiparasitic drug benznidazole. The present study aimed to analyze its radio-pharmacological properties and systematically compare its PET imaging profiles with [18F]FMISO and [18F]FAZA in preclinical triple-negative (MDA-MB231) and estrogen receptor-positive (MCF-7) breast cancer models. METHODS: In vitro cellular uptake experiments were carried out in MDA-MB321 and MCF-7 cells under normoxic and hypoxic conditions. Metabolic stability in vivo was determined in BALB/c mice using radio-TLC analysis. Dynamic PET experiments over 3 h post-injection were performed in MDA-MB231 and MCF-7 tumour-bearing mice. Those PET data were used for kinetic modelling analysis utilizing the reversible two-tissue-compartment model. Autoradiography was carried out in tumour tissue slices and compared to HIF-1α immunohistochemistry. Detailed ex vivo biodistribution was accomplished in BALB/c mice, and this biodistribution data were used for dosimetry calculation. RESULTS: Under hypoxic conditions in vitro cellular uptake was elevated in both cell lines, MCF-7 and MDA-MB231, for all three radiotracers. After intravenous injection, [18F]FBNA formed two radiometabolites, resulting in a final fraction of 65 ± 9 % intact [18F]FBNA after 60 min p.i. After 3 h p.i., [18F]FBNA tumour uptake reached SUV values of 0.78 ± 0.01 in MCF-7 and 0.61 ± 0.04 in MDA-MB231 tumours (both n = 3), representing tumour-to-muscle ratios of 2.19 ± 0.04 and 1.98 ± 0.15, respectively. [18F]FMISO resulted in higher tumour uptakes (SUV 1.36 ± 0.04 in MCF-7 and 1.23 ± 0.08 in MDA-MB231 (both n = 4; p < 0.05) than [18F]FAZA (0.66 ± 0.11 in MCF-7 and 0.63 ± 0.14 in MDA-MB231 (both n = 4; n.s.)), representing tumour-to-muscle ratios of 3.24 ± 0.30 and 3.32 ± 0.50 for [18F]FMISO, and 2.92 ± 0.74 and 3.00 ± 0.42 for [18F]FAZA, respectively. While the fraction per time of radiotracer entering the second compartment (k3) was similar within uncertainties for all three radiotracers in MDA-MB231 tumours, it was different in MCF-7 tumours. The ratios k3/(k3 + k2) and K1*k3/(k3 + k2) in MCF-7 tumours were also significantly different, indicating dissimilar fractions of radiotracer bound and trapped intracellularly: K1*k3/(k2 + k3) [18F]FMISO (0.0088 ± 0.001)/min, n = 4; p < 0.001) > [18F]FAZA (0.0052 ± 0.002)/min, n = 4; p < 0.01) > [18F]FBNA (0.003 ± 0.001)/min, n = 3). In contrast, in MDA-MB231 tumours, only K1 was significantly elevated for [18F]FMISO. However, this did not result in significant differences for K1*k3/(k2 + k3) for all three 2-nitroimidazoles in MDA-MB231 tumours. CONCLUSION: Novel 2-nitroimidazole PET radiotracer [18F]FBNA showed uptake into hypoxic breast cancer cells and tumour tissue presumably associated with elevated HIF1-α expression. Systematic comparison of PET imaging performance with [18F]FMISO and [18F]FAZA in different types of preclinical breast cancer models revealed a similar tumour uptake profile for [18F]FBNA with [18F]FAZA and, despite its higher lipophilicity, still a slightly higher muscle tissue clearance compared to [18F]FMISO.
Assuntos
Neoplasias da Mama , Nitroimidazóis , Humanos , Camundongos , Animais , Feminino , Neoplasias da Mama/diagnóstico por imagem , Xenoenxertos , Distribuição Tecidual , Nitroimidazóis/química , Hipóxia , Tomografia por Emissão de Pósitrons/métodos , Hipóxia Celular , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: The significant challenge in treating triple-negative breast cancer (TNBC) lies in its high rate of distant metastasis. To address this, inhibiting metastasis formation in TNBC is vital. Rac is a key player in cancer metastasis. Previously, we developed Ehop-016, a Rac inhibitor that successfully reduced tumor growth and metastasis in mice. In this study, we assessed the effectiveness of HV-107, a derivative of Ehop-016, in inhibiting TNBC metastasis at lower doses. METHODS: Rho GTPases activity assays were performed with the use of GST-PAK beads and Rac, Rho, and Cdc42 GLISA. Cell viability was assessed through trypan blue exclusion and MTT assays. Cell cycle analysis was conducted using flow cytometry. To evaluate invading capabilities, transwell assays and invadopodia formation assays were performed. Metastasis formation studies were conducted using a breast cancer xenograft mouse model. RESULTS: HV-107 inhibited Rac activity by 50% in MDA-MB-231 and MDA-MB-468 cells at concentrations of 250-2000 nM, leading to a 90% decrease in invasion and invadopodia activity. Concentrations of 500 nM and above caused dose-dependent reductions in cell viability, resulting in up to 20% cell death after 72 h. Concentrations exceeding 1000 nM upregulated PAK1, PAK2, FAK, Pyk2, Cdc42, and Rho signallings, while Pyk2 was downregulated at 100-500 nM. Through in vitro experiments, optimal concentrations of HV-107 ranging from 250 to 500 nM were identified, effectively inhibiting Rac activity and invasion while minimizing off-target effects. In a breast cancer xenograft model, administration of 5 mg/kg HV-107 (administered intraperitoneally, 5 days a week) reduced Rac activity by 20% in tumors and decreased metastasis by 50% in the lungs and liver. No observed toxicity was noted at the tested doses. CONCLUSION: The findings indicate that HV-107 exhibits promising potential as a therapeutic medication utilizing Rac inhibition mechanisms to address metastasis formation in TNBC.
Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Quinase 2 de Adesão Focal , Sobrevivência Celular , Citometria de Fluxo , XenoenxertosRESUMO
La pérdida ósea en el sector anterior, ya sea por un defecto horizontal, vertical o combinado, actualmente es un desafío, no sólo por la integración del implante, sino por la estética involucrada. Entre las técnicas de regeneración ósea que permiten solucionar estos defectos, cabe destacar la técnica de expansión de crestas. Se presenta el caso de una paciente de 58 años con reborde atrófico, que se sometió a la expansión de crestas con colocación simultánea de implantes en sector anterior, con xenoinjerto previo a técnica de expansión de crestas con piezoeléctrico, colocación simultánea de implantes Narrow Connection SLActive Straumann. Se logró ganancia ósea y estabilidad primaria de los implantes, sin complicaciones. En escenarios seleccionados, la técnica de expansión de crestas de manera predecible permite ganancia de hueso horizontal adecuada, el éxito de los implantes con tasa de supervivencia y mínimas complicaciones intra y postoperatorias (AU)
Bone loss in the anterior sector, both a horizontal, vertical or combined defect is a challenge today; not only for the integration of the implant but also the aesthetic involved. There are techniques of bone regeneration that help us to solve this type of defects, among them we should highlight the crest expansion technique. We present the case of a 58-year-old patient with atrophic flange, who underwent the expansion of crests with simultaneous placement of implants in the anterior sector, with xenograft prior to the piezoelectric crest expansion technique, Simultaneous placement of Narrow Connection SLActive Straumann implants, bone gain and primary stability of the implants were obtained, without complications. In selected scenarios, the crest expansion technique could be considered a predictable approach that demonstrates a high implant survival rate, adequate horizontal bone gain, and minimal intra- and postoperative complications (AU)
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Implantação Dentária Endóssea/métodos , Aumento do Rebordo Alveolar/métodos , Osteotomia/métodos , Piezocirurgia/métodos , XenoenxertosRESUMO
BACKGROUND: Xenotransplantation is a worth investing branch of science, since it aims to fulfil the demand on human cells, tissues and organs. Despite decades of consistent work in preclinical assessments, clinical trials on xenotransplantation are far from reaching the targeted goal. Our study aims to track the characteristics, assess the content and summarize the plan of each trial on skin, beta-island, bone marrow, aortic valve and kidney xenografts, leading to a clear sorting of efforts made in this field. METHODS: In December 2022, we searched clinicaltrial.gov for interventional clinical trials related to xenograft of skin, pancreas, bone marrow, aortic valve and kidney. A total of 14 clinical trials are included in this study. Characteristics on each trial were gathered. Linked publications were searched using Medline/PubMed and Embase/Scopus. Content of trials was reviewed and summarized. RESULTS: Only 14 clinical trials met our study's criteria. The majority were completed, and most of the trials' enrolment was between 11 and 50 participants. Nine trials used a xenograft of porcine origin. Six trials targeted skin xenotransplantation, four targeted ß-cells, two targeted bone marrow and one trial targeted each of the kidney and aortic valve. The average length of trials was 3.38 years. Four trials were conducted in the United States and two trials in each of Brazil, Argentina and Sweden. Of all the included trials, none had any results provided and only three had published work. Phases I, III, and IV had only one trial each. A total of 501 participants were enrolled in these trials. CONCLUSION: This study sheds the light on the current state of clinical trials on xenograft. Characteristically, trials on this field are of low number, low enrolment, short duration, few related publications and no published results. Porcine organs are the most used in these trials, and skin is the most studied organ. An extension of the literature is highly needed due to the variety of conflicts mentioned. Overall, this study sheds the light on the necessity of managing research efforts, leading to the initiation of more trials targeting the field of xenotransplantation.
Assuntos
Xenoenxertos , Animais , Humanos , Argentina , Suínos , Transplante Heterólogo , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND AND PURPOSE: Arsenic trioxide (ATO) exerts anticancer effects on lung cancer. However, the clinical use of ATO is limited due to its systemic toxicity and resistance of lung cancer cells. The present study aimed to investigate the effects of ATO, alone and in combination with 125I seed implantation on tumor growth and proliferation in lung cancer xenograft mice, and investigate the possible molecular mechanisms. METHODS: The transmission electron microscope observed the tumor ultrastructure of lung cancer xenograft mice. The proliferation index of Ki-67 and the number and morphology of tumor microvessels were detected with immunohistochemical staining. The protein and mRNA expression were examined by western blot and real-time PCR assay. RESULTS: The in vivo results demonstrated that ATO combined with 125I seed significantly inhibited tumor growth and proliferation, as well as promoted apoptosis, and decreased the Ki-67 index and microvessel density in lung cancer xenograft mice. Moreover, ATO combined with 125I seed decreased the protein and mRNA expression levels of HIF-1α, VEGF, and BCL-2, and increased those of BAX and P53. CONCLUSIONS: ATO combined with 125I seed significantly inhibited tumor growth and proliferation in lung cancer, which may be accomplished by inhibiting tumor angiogenesis and inducing apoptosis.
Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Trióxido de Arsênio/uso terapêutico , Xenoenxertos , Antígeno Ki-67 , Ensaios Antitumorais Modelo de Xenoenxerto , Apoptose , Neoplasias Pulmonares/patologia , RNA Mensageiro , Linhagem Celular Tumoral , Proliferação de Células , Antineoplásicos/uso terapêuticoRESUMO
BACKGROUND: Photobiomodulation therapy (PBMT) is an effective method for the prevention of oral mucositis. However, the effects of PBMT on oral squamous cell carcinoma (OSCC) have not yet been fully elucidated. This study aimed to evaluate the impact of PBMT in an OSCC-patient-derived xenograft (OSCC-PDX) model. METHODS: BALB/c nude mice with OSCC-PDX models were divided into Control, without PBMT (n = 8); Immediate irradiation, PBMT since one week after tumor implantation (n = 6); and Late irradiation, PBMT after tumors reached 200 mm3 (n = 6). OSCC-PDX were daily irradiated (660 nm; 100 mW; 6 J/cm2 ; 0,2 J/point) for 12 weeks. The tumors were collected and submitted to volumetric, histological, immunohistochemistry, and cell cycle analysis. RESULTS: No significant differences in the volumetric measurements (p = 0.89) and in the histopathological grade (p > 0.05) were detected between the groups. The immunohistochemical analysis of Ki-67 (p = 0.9661); H3K9ac (p = 0.3794); and BMI1 (p = 0.5182), and the evaluation of the cell cycle phases (p > 0.05) by flow cytometry also did not demonstrate significant differences between the irradiated and non-irradiated groups. CONCLUSION: In this study, PBMT did not impact the behavior of OSCC-PDX models. This is an important preclinical outcome regarding safety concerns of the use of PBMT in cancer patients.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Terapia com Luz de Baixa Intensidade , Neoplasias Bucais , Animais , Camundongos , Humanos , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/radioterapia , Xenoenxertos , Camundongos Nus , Modelos Animais de Doenças , Terapia com Luz de Baixa Intensidade/métodosRESUMO
As recessões gengivais acometem grande parte da população e frequentemente tratam-se de lesões combinadas onde há recessão acompanhada de lesão cervical não-cariosa. Diferentes estudos avaliaram opções de tratamentos cirúrgicorestauradores para melhor reestabelecimento estético e funcional desse tipo de condição. No entanto, estudos avaliando a longo prazo o desempenho de biomateriais para o tratamento de defeitos combinados restaurados ainda são escassos na literatura. Desta forma, o objetivo do presente estudo é avaliar longitudinalmente o desempenho da matriz colágena suína associada ao retalho posicionado coronariamente e a restauração parcial para o tratamento de defeitos combinados. Para tal, foi realizado um acompanhamento pós-operatório de 5 anos de um estudo previamente realizado. Quarenta pacientes (n=40) apresentaram-se na revocação e foram previamente tratados com: restauração parcial da lesão cervical e cirurgia para recobrimento radicular associado à matriz colágena xenógena de origem suína (CAF+MC; grupo teste; n=22) ou recobrimento radicular por meio do retalho posicionado coronariamente (CAF; grupo controle; n=18) foram avaliados. Foram realizados parâmetros clínicos, fotográficos e centrados no paciente, analisados e comparados em baseline e 1 ano após o procedimento cirúrgico-restaurador. Aos 5 anos, CAF e CAF+MC apresentaram resultados satisfatórios e sem diferença estatisticamente relevante entre si de Redução da Recessão (RedRec; 1,82 ± 0,89; 2,08 ± 1,08), Porcentagem de Recobrimento do Defeito Combinado (%CDC; 56,80 ± 23,90%; 57,25 ± 27,48%) e Recessão Gengival Relativa (RGR; 9,04 ± 0,99; 9,47 ± 1,51), sugerindo eficácia do tratamento em longo prazo. Os parâmetros ATQ e ETQ mostraram-se estáveis longitudinalmente no grupo CAF, embora os resultados de 1 ano do grupo teste tenham sido superiores, aos 5 anos não apresentaram diferença estatisticamente relevante ao grupo controle. Todos os grupos apresentaram redução significativa da hipersensibilidade dentinária (p<0,001) e melhora nas condições estéticas (p<0,001). Pode-se concluir que, em comparação a dados anteriores, o grupo que foi tratado com associação do biomaterial não mostrou benefícios adicionais quanto ao recobrimento radicular em 5 anos. (AU)
The gingival recessions affect the population majority and - very often these are combined defects, associating recessions, and non-carious cervical lesions. Different studies evaluated options of surgical-restorative treatments for a better aesthetic and functional reestablishment for that type of condition. However, studies evaluating a long-term of soft tissue substitutes performance to the treatment of combined defects restored are scarce in the literature. Thus, the objective of the present study is to evaluate longitudinally the performance of a xenogeneic collagen matrix associated to coronally positioned flap and partial restoration for the treatment of combined defects. To this end, a 5-year postoperative follow-up of a previously conducted study was carried out. Forty patients (n=40) presented for recall and were previously treated with: partially restoration of the non-carious cervical lesion and root coverage procedure by coronally advanced flap associated with collagen matrix (CAF+MC; test group; n=22) or partial restoration of the cervical lesion and root coverage through the coronally advanced flap alone (CAF; control group; n=18) were evaluated. Clinical, photographic, and patient-centered parameters were analyzed and compared at baseline and 1 year after the surgical-restorative procedure. At 5 years, CAF, and CAF+MC showed satisfactory results, with no statistically significant difference between them in Gingival Recession Reduction (RedRec; 1.82 ± 0.89; 2.08 ± 1.08), CD Coverage (%CDC; 56.80 ± 23.90; 57.25 ± 27.48) and Relative Gingival Recession (RGR; 9.04 ± 0.99; 9.47 ± 1.51), suggesting long-term treatment efficiency. The ATQ and ETQ parameters were shown to be longitudinally stable in the CAF group, although the 1-year results of the test group were superior, at 5 years there was no statistically significant difference in relation to the control group. All groups showed a significant reduction in dentin hypersensitivity (p<0.001) and improvement in esthetic conditions (p<0.001). It can be concluded that, compared to previous data, the group that was treated with the biomaterial association did not show additional benefits in terms of root coverage in 5 years. (AU)
Assuntos
Humanos , Sensibilidade da Dentina , Xenoenxertos , Retração GengivalRESUMO
Evaluation of ridge alteration after 1 year follow up after immediate loading implant placement. Methods: Ten patients were included in the study, in whom the ridge volume, height, and thickness were evaluated from region of interest (ROI) of tomographic images of the operated areas (test group) and compared to the opposite tooth (control group). Results: After one year, there was no implant loss and all patients were satisfied with the treatment. In the test group there was a statistically significant increase in ridge height (2.89±1.05 mm) when compared to the control group. No significant difference in relation to ridge volume and thickness was observed. In the intragroup evaluation, a significant gain in ridge height (2.65±3.08 mm) was observed when compared to baseline. Conclusion: The placement of an immediate implant, temporary crown, and tissue regeneration in sockets with buccal defects promotes the regeneration of the buccal wall while preventing the reduction of bone volume and thickness
Assuntos
Humanos , Masculino , Feminino , Regeneração , Implantes Dentários , Processo Alveolar , XenoenxertosRESUMO
Substitutos de enxerto de tecido conjuntivo têm sido amplamente utilizados para superar as limitações dos enxertos autógenos no tratamento de defeitos dos tecidos moles periodontais e peri-implantares. No entanto, o desempenho clínico desses biomateriais ainda é inferior. A biofuncionalização de matrizes colágenas usando fibrina rica em plaquetas injetável (i-PRF) foi proposta como uma estratégia para aprimorar a bioatividade e, portanto, a eficácia clínica desses substitutos mucosos. Desta forma, o objetivo deste estudo foi avaliar a eficácia do uso da matriz colágena estável em volume (FG) biofuncionalizada com i-PRF no tratamento de recessões gengivais unitárias (RGs) do ponto de vista clínico, estético e de parâmetros centrados no paciente. Para tal, foram selecionados 66 pacientes portadores de RGs unitárias RT1, os quais foram alocados aleatoriamente em um dos seguintes grupos: grupo CAF (n=22), retalho posicionado coronariamente (CAF); grupo CAF+FG (n=22), CAF associado à FG; e grupo CAF+FG+i-PRF (n=22), CAF associado à FG biofuncionalizada com i-PRF. Após 6 meses, os três grupos apresentaram taxas de recobrimento radicular significativas [CAF: 69,1% (2,02 ± 1,06 mm); CAF+FG: 67,44% (1,7 ± 0,81 mm) e CAF+FG+i-PRF: 64,92% (1,64 ± 0,80 mm), sem diferença entre os grupos (p=0,33). Os grupos que receberam os biomateriais forneceram um maior ganho em espessura de tecido queratinizado (ETQ) (CAF: 0,12 ± 0,2 mm; CAF+FG: 0,43 ± 0,24 mm; CAF+FG+i-PRF: 0,48 ± 0,25 mm; p=0,000). Não foram observadas diferenças significativas em termos de altura de tecido queratinizado em nenhum dos grupos e tempos avaliados (p>0,05). Todos os grupos apresentaram redução significativa da hipersensibilidade dentinária e melhorias nas condições estéticas (p>0,05). Também não foram observadas diferenças em termos de dor e morbidade pósoperatórias (p>0,05). Dentro das limitações do presente estudo, conclui-se que as três abordagens forneceram resultados semelhantes e satisfatórios após 6 meses de acompanhamento. A adição da FG, biofuncionalizada ou não com i-PRF, proporcionou benefícios adicionais em termos de ganho de ETQ. (AU)
Soft tissue graft substitutes have been widely used to overcome the limitations of autogenous grafts in the treatment of periodontal and peri-implant soft tissue defects. However, the clinical performance of these biomaterials is still inferior. The biofunctionalization of collagen matrices using injectable platelet-rich fibrin (i-PRF) has been proposed as a strategy to enhance the bioactivity and, therefore, the clinical efficacy of these biomaterials. Thus, the aim of this study was to evaluate the effectiveness of using biofunctionalized volume-stable collagen matrix (VCMX) with i-PRF in the treatment of single gingival recessions (GRs) from clinical, esthetic, and patient-centered parameters. For this purpose, 66 patients with single RT GRs were selected and randomly allocated to one of the following groups: CAF group (n=22), coronally advanced flap (CAF); CAF+VCMX group (n=22), CAF combined with VCMX; and CAF+ VCMX +iPRF group (n=22), CAF combined with biofunctionalized VCMX with i-PRF. After 6 months, all three groups exhibited significant root coverage rates [CAF: 69.1% (2.02 ± 1.06 mm); CAF+FG: 67.44% (1.7 ± 0.81 mm); and CAF+FG+iPRF: 64.92% (1.64 ± 0.80 mm), with no difference between the groups (p=0.33). The groups that received the biomaterials showed a greater gain in keratinized tissue thickness (KTT) (CAF: 0.12 ± 0.2 mm; CAF+FG: 0.43 ± 0.24 mm; CAF+FG+i-PRF: 0.48 ± 0.25 mm; p=0.000). No significant differences were observed in terms of keratinized tissue height in any of the groups and assessed time points (p>0.05). All groups showed a significant reduction in dentin hypersensitivity and improvements in esthetic conditions (p>0.05). No differences were also observed in terms of post-operative pain and morbidity (p>0.05). Within the limitations of this study, it is concluded that all three approaches provided similar and satisfactory results after 6 months of follow-up. The addition of VCMX, whether biofunctionalized or not with i-PRF, provided additional benefits in terms of keratinized tissue thickness gain. (AU)
Assuntos
Humanos , Materiais Biocompatíveis , Autoenxertos , Xenoenxertos , Fibrina Rica em Plaquetas , Retração GengivalRESUMO
Objective: inflammation may play a role in bone loss by altering the boné remodelling process, favouring bone resorption by osteoclasts over bone synthesis by osteoblasts. Matrix metalloproteinase 13 (MMP-13) has the ability to activate osteoclasts, leading to bone resorption. Regenerative treatments have been widely used in periodontology. When combined with Platelet-rich fibrin (PRF), xenografts will give better results in bone regeneration. The aim of this study was to evaluate the effect of xenograft combined with PRF on MMP-13 expression in a bone defect using an experimentally created bone defect. Material and Methods: eighteen New Zealand rabbits were assigned to three groups. Each group consisted of six New Zealand rabbits. A critical bone defect with a diameter size of 5 mm was created in the right tibia of each rabbit in group 1 (application: xenograft), group 2 (application: PRF), and group 3 (application: xenograft and PRF). The PRF was produced from 5 ml of blood taken from each rabbit's ears. After 30 days, the rabbits were euthanized. The tissue samples were evaluated by immunohistochemical staining. Results: group 3 showed the lowest mean expression of MMP-13 (4.50) compared to group 1 (20.50) and group 2 (11.70). Group 3 showed a significant difference in the MMP-13 expression compared to group 1 and group 2 (P = 0.000) (P < 0.05). Conclusion: this research showed that the combination of xenograft and PRF had the lowest expression of MMP-13. The application of a xenograft and PRF has better osteogenesis ability in bone regeneration.(AU)
Objetivo: inflamação pode interferir na perda óssea através de alterações no processo de remodelação, favorecendo a reabsorção óssea pelos osteoclastos ao invés da síntese pelos osteoblastos. A metaloproteinases de matriz 13 (MMP-13) ativa osteoclastos causando reabsorção óssea. Tratamentos regenerativos têm sido amplamente usados na periodontia. Quando combinamos Plasma rico em plaquetas (PRP) e xenoenxerto levam a melhores resultados de regeneração óssea. O objetivo deste estudo foi avaliar os efeitos de xenoenxerto combinado com PRP na expressão de MMP-13 em defeitos ósseos experimentais. Material e Métodos: dezoitos coelhos Nova Zelândia foram distribuídos em 3 grupos de 6 coelhos cada. Um defeito ósseo de 5 mm de diâmetro foi feito na tíbia direita dos animais do grupo 1 (xenoenxerto), grupo 2 (PRP) e grupo 3 (Xenoenxerto+PRP). O PRP foi obtido pela coleta de 5mL de sangue das orelhas dos coelhos. Após 30 dias, os coelhos foram eutanasiados. As amostras foram submetidas a coloração imuno-histoquímica. Resultados: o grupo 3 apresentou a menor expressão de MMP-13 (4.50) quando comparado ao grupo 1 (20.50) e ao grupo 2 (11.70). O grupo 3 mostrou diferença estatística significante em relação a expressão de MMP-13 quando comparado aos grupos 1 e 2 (p=0.000) (p< 0.05). Conclusão: esta pesquisa mostra que a combinação de xenoenxerto e PRP teve a menor expressão de MMP-13. A combinação de xenoenxerto e PRP têm maior habilidade de osteogênese na regeneração óssea (AU)
Assuntos
Animais , Coelhos , Regeneração Óssea , Plasma Rico em Plaquetas , Metaloproteinase 13 da Matriz , Xenoenxertos , InflamaçãoRESUMO
Introduction: Due to the extensive number of studies developed on periodontal pathologies and the clinical need generated to correct bonvze defects, we have carried out an Overview of systematic reviews using the FRISBEE methodology. Material and Methods: Through this study we expect to bridge the knowledge gap generated regarding the clinical question on the effectiveness of autologous bone substitutes and xenografts in maxillary and mandibular bone defects. Results: For this study, we carried out a systematic search in Epistemonikos and PubMed, we included 3 systematic reviews and 5 primary studies included in these reviews to extract their data. We analyzed data using RevMan 5.4. and GRADEpro. Assessed outcomes included: bone gain [MD 0.06 mm lower (0.26 lower to 0.14 higher)] and bone resorption [MD 0.03 mm higher (0.12 lower to 0.18 higher)], where no significant differences were found between the study groups. The certainty of the evidence was moderate for both outcomes. Bone length and bone density outcomes were not measured or reported in the included studies. Conclusion: We concluded that there are no significant clinical differences between the application of autologous bone grafts and xenografts for bone defects correction for the assessed outcomes, therefore, these biomaterials should be applied at the discretion of the clinician and according to the needs and preferences of patients.
Introducción: Debido al extenso número de estudios desarrollados sobre patologías periodontales y a la necesidad clínica generada para corregir defectos óseos, hemos realizado un Overview de revisiones sistemáticas tipo FRISBEE para acortar la brecha de conocimiento generada respecto a la pregunta clínica sobre la efectividad de sustitutos óseos tipo autólogo y xenoinjertos en defectos óseos a nivel maxilar y mandibular. Material y Métodos: Para este estudio realizamos una búsqueda sistemática en Epistemonikos y PubMed, de los cuales incluimos 3 revisiones sistemáticas y 5 estudios primarios incluidos en estas revisiones para extraer sus datos. Los datos fueron analizados a través de RevMan 5.4. Y GRADEpro. Resultados: Los estudios analizaron los desenlaces propuestos: ganancia ósea posterior a la aplicación del injerto óseo [MD 0.06 mm menos (0.26 menos a 0.14 más)] y reabsorción ósea posterior a la aplicación del injerto óseo [MD 0.03 mm más (0.12 menos a 0.18 más)], donde no se encontraron diferencias significativas entre los grupos de estudio. La certeza de la evidencia fue moderada para ambos desenlaces. Los desenlaces longitud ósea y densidad ósea no fueron medidos o reportados en los estudios incluidos. Conclusión: Se concluyó que no hay diferencias que sean clínicamente significativas entre la aplicación de injertos óseos autólogos y xenoinjertos para la corrección de defectos óseos para los desenlaces analizados, por lo que, la aplicación de estos biomateriales queda a criterio del clínico, y de acuerdo a las necesidades y preferencias de los pacientes.