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1.
J Biomol Struct Dyn ; 41(4): 1193-1205, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-34939532

RESUMO

Cocoonase is known to digest the sericin protein that encapsulates the silkworm cocoon's fibroin protein. Silk fibroin and sericin are two types of proteins that make up silk, and accounts for around 20-30% of the overall cocoon weight. The aim of the study was to see the protein-protein interaction (PPI) and molecular dynamic study of sericin, cocoonase and protein-protein docked complex of silkworm by computational approaches. Here motif analysis, phylogenetic analysis, principal component analysis, root-mean-square deviation (RMSD), root mean square fluctuation, radius of gyration, structural and functional study of cocoonase and sericin as well as molecular docking study were carried out. The 33 amino acid residues of cocoonase shows interaction with 38 aa residues of sericin involving 4 disulphide bonds, 22 hydrogen bonds and 319 non-bonded contacts. The confirmational stability and flexibility of both the proteins as well as protein-protein complex were achieved at 70 ns of MD simulation study. RMSD-based data indicated that cocoonase is more stable than sericin and complex, and complex has a greater fluctuation with more compact (higher Rg) value than cocoonase and sericin, inferring higher conformational stability and flexibility of protein-protein complex than cocoonase and sericin. This study provides a new dimension for PPI study by computational approaches.Communicated by Ramaswamy H. Sarma.


Assuntos
Bombyx , Sericinas , Animais , Bombyx/química , Sericinas/química , Sericinas/metabolismo , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Filogenia
2.
J Mol Model ; 28(5): 113, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35381900

RESUMO

There is a growing interest in designing a nanocarrier containing an EGFR targeting affibody to direct toward cancer cells. Here, cytolysin A was cloned at the N-terminus of ZEGFR:1907 affibody to guarantee its surface presentation on the OMVs while targeting the epidermal growth factor receptors (EGFRs). A separate construct including a fusogenic peptide (GALA) was also designed for the endosomal escape of the nanocarrier. Binding of the two constructs ClyA-affiEGFR and ClyA-affiEGFR-GALA to domain III of EGFR was investigated using molecular docking and molecular dynamic simulations. The higher stability of the ClyA-affiEGFR-GALA/EGFR as compared to the ClyA-affiEGFR/EGFR complex was evident. The ClyA-affiEGFR-GALA structure showed a higher RMSD during the first half of the simulation time implying a much less stable behavior. Plateau state of the radius of gyration plot of ClyA-affiEGFR-GALA confirmed a well-folded structure in the presence of the GALA sequence. Solvent accessible surface area for both proteins was in the same range. The data obtained from hydrogen bond analysis revealed a more equilibrated and stable form of the ClyA-affiEGFR-GALA structure upon interaction with EGFR. The data provided here was a requisite for our biological evaluation of the synthesized constructs as a component of a novel drug delivery system.


Assuntos
Receptores ErbB , Peptídeos , Receptores ErbB/metabolismo , Simulação de Acoplamento Molecular , Peptídeos/química
3.
J Fungi (Basel) ; 8(1)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35050024

RESUMO

In previous work, we developed a Saccharomyces cerevisiae strain (DLG-K1) lacking the main monosaccharide transporters (hxt-null) and displaying high xylose reductase, xylitol dehydrogenase and xylulokinase activities. This strain proved to be a useful chassis strain to study new glucose/xylose transporters, as SsXUT1 from Scheffersomyces stipitis. Proteins with high amino acid sequence similarity (78-80%) to SsXUT1 were identified from Spathaspora passalidarum and Spathaspora arborariae genomes. The characterization of these putative transporter genes (SpXUT1 and SaXUT1, respectively) was performed in the same chassis strain. Surprisingly, the cloned genes could not restore the ability to grow in several monosaccharides tested (including glucose and xylose), but after being grown in maltose, the uptake of 14C-glucose and 14C-xylose was detected. While SsXUT1 lacks lysine residues with high ubiquitinylation potential in its N-terminal domain and displays only one in its C-terminal domain, both SpXUT1 and SaXUT1 transporters have several such residues in their C-terminal domains. A truncated version of SpXUT1 gene, deprived of the respective 3'-end, was cloned in DLG-K1 and allowed growth and fermentation in glucose or xylose. In another approach, two arrestins known to be involved in the ubiquitinylation and endocytosis of sugar transporters (ROD1 and ROG3) were knocked out, but only the rog3 mutant allowed a significant improvement of growth and fermentation in glucose when either of the XUT permeases were expressed. Therefore, for the efficient heterologous expression of monosaccharide (e.g., glucose/xylose) transporters in S. cerevisiae, we propose either the removal of lysines involved in ubiquitinylation and endocytosis or the use of chassis strains hampered in the specific mechanism of membrane protein turnover.

4.
Data Policy ; 3: e33, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901859

RESUMO

With the outbreak of COVID-19 across Europe, anonymized telecommunications data provides a key insight into population level mobility and assessing the impact and effectiveness of containment measures. Vodafone's response across its global footprint was fast and delivered key new metrics for the pandemic that have proven to be useful for a number of external entities. Cooperation with national governments and supra-national entities to help fight the COVID-19 pandemic was a key part of Vodafone's response, and in this article the different methodologies developed are analyzed, as well as the key collaborations established in this context. In this article we also analyze the regulatory challenges found, and how these can pose a risk of the full benefits of these insights not being harnessed, despite clear and efficient Privacy and Ethics assessments to ensure individual safety and data privacy.

5.
J Mol Struct ; 1239: 130488, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-33903778

RESUMO

Corona Virus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus (SARS CoV-2) has been declared a worldwide pandemic by WHO recently. The complete understanding of the complex genomic structure of SARS CoV-2 has enabled the use of computational tools in search of SARS CoV-2 inhibitors against the multiple proteins responsible for its entry and multiplication in human cells. With this endeavor, 177 natural, anti-viral chemical entities and their derivatives, selected through the critical analysis of the literatures, were studied using pharmacophore screening followed by molecular docking against RNA dependent RNA polymerase and main protease. The identified hits have been subjected to molecular dynamic simulations to study the stability of ligand-protein complexes followed by ADMET analysis and Lipinski filters to confirm their drug likeliness. It has led to an important start point in the drug discovery and development of therapeutic agents against SARS CoV-2.

6.
Más Vita ; 2(4): 63-73, dic. 2020. ilus, tab
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1372888

RESUMO

La salud bucodental es parte inseparable de las condiciones generales de salud de todo individuo. Es por ello, que las estrategias que se implementan van dirigidas hacia la prevención de las enfermedades bucodentales La Regeneración Ósea Guiada (ROG) representa una alternativa cuando se presenta perdida de unidades dentales, para la futura rehabilitación protésica de ese espacio edentulo es aquí donde la presente investigación. Objetivos: describir de forma detallada y ordenada la efectividad del tratamiento de regeneración ósea del hueso alveolar y colocación de PRF y PRP a propósito de un caso clínico. Metodología: empleada se enmarcó en el paradigma positivista, con enfoque cuantitativo, siendo un estudio de campo-descriptivo, no experimental, en la modalidad de caso clínico único, donde se usó como método la historia clínica, consentimiento informado, radiografías periapicales, exámenes pre-operatorios y cámara radiográfica para la recolección de datos y obtención de los mismos. Resultado: un exitoso crecimiento óseo de 14mm de altura, en un tiempo menos de lo esperado, evidenciando a los dos meses el aumento del tejido, obteniendo resultados positivos, y se recomendó mantener buena higiene diaria, limpiezas periódicas cada tres meses más la general que debe ser después de cada comida, disminución del hábito de fumar y rehabilitación protésica a través de implantes dentales. Conclusión: la ROG es un tratamiento efectivo y en combinación con el PRF y el PRP como ayudares del proceso osteoblastico, estimulados por estos factores de crecimiento Autólogos se demuestra su efectividad y menor costo al paciente, para su futura rehabilitación protésica con implantes dentales(AU)


Oral health is an inseparable part of the general health conditions of every individual. That is why the strategies that are implemented are directed towards the prevention of oral diseases Guided Bone Regeneration (ROG) represents an alternative when there is loss of dental units, for the future prosthetic rehabilitation of that edentulous space is here where the present investigation. Objectives: to describe in a detailed and orderly way the effectiveness of the treatment of bone regeneration of the alveolar bone and placement of PRF and PRP in relation to a clinical case. Methodology: used was framed in the positivist paradigm, with a quantitative approach, being a descriptive field study, not experimental, in the modality of a single clinical case, where the clinical history, informed consent, periapical radiographs, pre-examinations were used as a method. -operations and radiographic camera for data collection and obtaining them. Result: a successful bone growth of 14mm in height, in less time than expected, showing tissue growth after two months, obtaining positive results, and it was recommended to maintain good daily hygiene, periodic cleanings every three months plus the general one that it should be after every meal, reduction of smoking and prosthetic rehabilitation through dental implants. Conclusion: ROG is an effective treatment and in combination with PRF and PRP as helpers of the osteoblastic process, stimulated by these Autologous growth factors, its effectiveness and lower cost to the patient is demonstrated for future prosthetic rehabilitation with dental implants(AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Doenças Periodontais , Desenvolvimento Ósseo , Regeneração Óssea , Fumantes , Terapêutica , Implantes Dentários , Saúde Bucal
7.
Biochimie ; 174: 69-73, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32325113

RESUMO

Gateway recombination-based cloning, which eliminates the use of restriction endonucleases and ligase, has been widely used for the construction of high-throughput (HTP) vectors. However, this approach is very expensive and its two-stage reaction process is laborious and time consuming. Therefore, we developed a Gateway cloning method that uses fusion-PCR to generate attL recombination site adaptors, and the PCR products, which can be directly cloned into destination vectors, giving rise to Rapid One-Step Gateway (ROG) Cloning. 100% of cloning efficiencies were obtained by this ROG method. This method has no BP reaction/entry clone step, thus halving the cost and time consumed. Overall, this work provides a highly efficient, rapid, low-cost method for directional recombination cloning.


Assuntos
Clonagem Molecular/métodos , Vetores Genéticos , Reação em Cadeia da Polimerase/métodos , Agrobacterium tumefaciens/genética , Proteínas de Plantas/biossíntese , Recombinação Genética , /genética
8.
Dev Cell ; 53(4): 444-457.e5, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32330424

RESUMO

The redox-based protein S-nitrosylation is a conserved mechanism modulating nitric oxide (NO) signaling and has been considered mainly as a non-enzymatic reaction. S-nitrosylation is regulated by the intracellular NO level that is tightly controlled by S-nitrosoglutathione reductase (GSNOR). However, the molecular mechanisms regulating S-nitrosylation selectivity remain elusive. Here, we characterize an Arabidopsis "repressor of" gsnor1 (rog1) mutation that specifically suppresses the gsnor1 mutant phenotype. ROG1, identical to the non-canonical catalase, CAT3, is a transnitrosylase that specifically modifies GSNOR1 at Cys-10. The transnitrosylase activity of ROG1 is regulated by a unique and highly conserved Cys-343 residue. A ROG1C343T mutant displays increased catalase but decreased transnitrosylase activities. Consistent with these results, the rog1 mutation compromises responses to NO under both normal and stress conditions. We propose that ROG1 functions as a transnitrosylase to regulate the NO-based redox signaling in plants.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Catalase/metabolismo , Regulação da Expressão Gênica de Plantas , Glutationa Redutase/metabolismo , Óxido Nítrico/metabolismo , Processamento de Proteína Pós-Traducional , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Catalase/química , Catalase/genética , Cisteína/química , Cisteína/genética , Cisteína/metabolismo , Glutationa Redutase/química , Glutationa Redutase/genética , Mutação , Oxirredução , Fenótipo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo
9.
Comput Struct Biotechnol J ; 17: 886-894, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333815

RESUMO

High-mobility Group Box 1 (HMGB1) is an abundant protein present in all mammalian cells and involved in several processes. During inflammation or tissue damage, HMGB1 is released in the extracellular space and, depending on its redox state, can form a heterocomplex with CXCL12. The heterocomplex acts exclusively via the chemokine receptor CXCR4 enhancing leukocyte recruitment. Here, we used multi-microsecond molecular dynamics (MD) simulations to elucidate the effect of the disulfide bond on the structure and dynamics of HMGB1. The results of the MD simulations show that the presence or lack of the disulfide bond between Cys23 and Cys45 modulates the conformational space explored by HMGB1, making the reduced protein more suitable to form a complex with CXCL12.

10.
F1000Res ; 7: 318, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29707204

RESUMO

Background: We previously identified the transcriptional regulator Zbtb32 as a factor that can promote T cell tolerance in the Non-Obese Diabetic (NOD) mouse, a model of Type 1 diabetes. Antigen targeted to DCIR2 + dendritic cells (DCs) in vivo inhibited both diabetes and effector T cell expansion in NOD mice. Furthermore, Zbtb32 was preferentially induced in autoreactive CD4 T cells stimulated by these tolerogenic DCIR2 + DCs, and overexpression of Zbtb32 in islet-specific T cells inhibited the diabetes development by limiting T cell proliferation and cytokine production. Methods: To further understand the role of Zbtb32 in T cell tolerance induction, we have now used CRISPR to target the Zbtb32 gene for deletion directly in NOD mice and characterized the mutant mice. We hypothesized that the systemic loss of Zbtb32 in NOD mice would lead to increased T cell activation and increased diabetes pathogenesis. Results: Although NOD.Zbtb32 -/- male NOD mice showed a trend towards increased diabetes incidence compared to littermate controls, the difference was not significant. Furthermore, no significant alteration in lymphocyte number or function was observed. Importantly, in vitro stimulation of lymphocytes from NOD.Zbtb32 -/- mice did not produce the expected hypersensitive phenotype observed in other genetic strains, potentially due to compensation by homologous genes. Conclusions: The loss of Zbtb32 in the NOD background does not result in the expected T cell activation phenotype.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Diabetes Mellitus Experimental/epidemiologia , Tolerância Imunológica/imunologia , Ativação Linfocitária/imunologia , Proteínas Repressoras/fisiologia , Animais , Sistemas CRISPR-Cas , Células Cultivadas , Citocinas/metabolismo , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Feminino , Incidência , Masculino , Camundongos , Camundongos Endogâmicos NOD , Proteínas Repressoras/antagonistas & inibidores
11.
Radiother Oncol ; 127(1): 27-35, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29295747

RESUMO

OBJECTIVE: To compare six HPV detection methods in pre-treatment FFPE tumour samples from patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received postoperative (N = 175) or primary (N = 90) radiochemotherapy. MATERIALS AND METHODS: HPV analyses included detection of (i) HPV16 E6/E7 RNA, (ii) HPV16 DNA (PCR-based arrays, A-PCR), (iii) HPV DNA (GP5+/GP6+ qPCR, (GP-PCR)), (iv) p16 (immunohistochemistry, p16 IHC), (v) combining p16 IHC and the A-PCR result and (vi) combining p16 IHC and the GP-PCR result. Differences between HPV positive and negative subgroups were evaluated for the primary endpoint loco-regional control (LRC) using Cox regression. RESULTS: Correlation between the HPV detection methods was high (chi-squared test, p < 0.001). While p16 IHC analysis resulted in several false positive classifications, A-PCR, GP-PCR and the combination of p16 IHC and A-PCR or GP-PCR led to results comparable to RNA analysis. In both cohorts, Cox regression analyses revealed significantly prolonged LRC for patients with HPV positive tumours irrespective of the detection method. CONCLUSIONS: The most stringent classification was obtained by detection of HPV16 RNA, or combining p16 IHC with A-PCR or GP-PCR. This approach revealed the lowest rate of recurrence in patients with tumours classified as HPV positive and therefore appears most suited for patient stratification in HPV-based clinical studies.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/virologia , Papillomavirus Humano 16/isolamento & purificação , Recidiva Local de Neoplasia/virologia , Infecções por Papillomavirus/virologia , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/metabolismo , Prognóstico , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
12.
J Biomol Struct Dyn ; 36(14): 3687-3704, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29064326

RESUMO

Kinesin spindle protein (KSP) belongs to the kinesin superfamily of microtubule-based motor proteins. KSP is responsible for the establishment of the bipolar mitotic spindle which mediates cell division. Inhibition of KSP expedites the blockade of the normal cell cycle during mitosis through the generation of monoastral MT arrays that finally cause apoptotic cell death. As KSP is highly expressed in proliferating/cancer cells, it has gained considerable attention as a potential drug target for cancer chemotherapy. Therefore, this study envisaged to design novel KSP inhibitors by employing computational techniques/tools such as pharmacophore modelling, virtual database screening, molecular docking and molecular dynamics. Initially, the pharmacophore models were generated from the data-set of highly potent KSP inhibitors and the pharmacophore models were validated against in house test set ligands. The validated pharmacophore model was then taken for database screening (Maybridge and ChemBridge) to yield hits, which were further filtered for their drug-likeliness. The potential hits retrieved from virtual database screening were docked using CDOCKER to identify the ligand binding landscape. The top-ranked hits obtained from molecular docking were progressed to molecular dynamics (AMBER) simulations to deduce the ligand binding affinity. This study identified MB-41570 and CB-10358 as potential hits and evaluated these experimentally using in vitro KSP ATPase inhibition assays.


Assuntos
Antineoplásicos/química , Cinesinas/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Antineoplásicos/farmacologia , Sítios de Ligação , Humanos , Cinesinas/antagonistas & inibidores , Ligantes , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ligação Proteica , Relação Quantitativa Estrutura-Atividade , Reprodutibilidade dos Testes
13.
J Biomol Struct Dyn ; 36(13): 3575-3585, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29048999

RESUMO

The major candidate for multiple sulfatase deficiency is a defective formylglycine-generating enzyme (FGE). Though adequately produced, mutations in FGE stall the activation of sulfatases and prevent their activity. Missense mutations, viz. E130D, S155P, A177P, W179S, C218Y, R224W, N259I, P266L, A279V, C336R, R345C, A348P, R349Q and R349W associated with multiple sulfatase deficiency are yet to be computationally studied. Aforementioned mutants were initially screened through ws-SNPs&GO3D program. Mutant R345C acquired the highest score, and hence was studied in detail. Discrete molecular dynamics explored structural distortions due to amino acid substitution. Therein, comparative analyses of wild type and mutant were carried out. Changes in structural contours were observed between wild type and mutant. Mutant had low conformational fluctuation, high atomic mobility and more compactness than wild type. Moreover, free energy landscape showed mutant to vary in terms of its conformational space as compared to wild type. Subsequently, wild type and mutant were subjected to single-model analyses. Mutant had lesser intra molecular interactions than wild type suggesting variations pertaining to its secondary structure. Furthermore, simulated thermal denaturation showed dissimilar pattern of hydrogen bond dilution. Effects of these variations were observed as changes in elements of secondary structure. Docking studies of mutant revealed less favourable binding energy towards its substrate as compared to wild type. Therefore, theoretical explanations for structural distortions of mutant R345C leading to multiple sulfatase deficiency were revealed. The protocol of the study could be useful to examine the effectiveness of pharmacological chaperones prior to experimental studies.


Assuntos
Glicina/análogos & derivados , Doença da Deficiência de Múltiplas Sulfatases/genética , Mutação de Sentido Incorreto/genética , Sulfatases/genética , Substituição de Aminoácidos/genética , Glicina/biossíntese , Humanos , Modelos Moleculares , Simulação de Dinâmica Molecular , Oxirredutases atuantes sobre Doadores de Grupo Enxofre , Estrutura Secundária de Proteína , Sulfatases/metabolismo
14.
Int J Cancer ; 138(1): 171-81, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26178914

RESUMO

We examined the prognostic value of tumour-infiltrating lymphocytes (TILs) in patients with squamous cell carcinoma of the head and neck (SCCHN) after surgery and postoperative cisplatin-based chemoradiotherapy. FFPE-tissue originating from the surgery of 161 patients treated in 8 DKTK partner sites was immunohistochemically stained for CD3 and CD8. Their expression was correlated with clinicopathological characteristics as well as overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of the HPV16-DNA/p16 status. After a median follow-up of 48 months (range: 4100 months), OS at 4 years was 46.5% for the entire cohort. In multivariate analysis, high CD8 expression was confirmed as an independent prognostic parameter for OS (p = 0.002), LPFS (p = 0.004) and DMFS (p = 0.006), while CD3 expression lacked significance. In multivariate analysis HPV16 DNA positivity was associated with improved OS (p = 0.025) and LPFS (p = 0.013) and p16-positive patients showed improved DMFS (p = 0.008). Interestingly, high CD8 expression was a prognostic parameter for the clinical outcome in both HPV16 DNA-positive and HPV16 DNA-negative patients. Similar findings were observed in the multivariate analysis for the combined HPV16 DNA/p16 status. Altogether, CD8+ TILs constitute an independent prognostic marker in SCCHN patients treated with adjuvant chemoradiotherapy. These data indicate that CD8-positive TILs have antitumour activity and could be used for treatment stratification. Further validation of the prognostic value of CD8+ TILs as a biomarker and its role in the immune response in SCCHN patients after adjuvant chemoradiotherapy is warranted and will be performed in the prospective DKTK-ROG study.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Carcinoma de Células Escamosas/etiologia , Neoplasias de Cabeça e Pescoço/etiologia , Linfócitos do Interstício Tumoral/imunologia , Papillomaviridae , Infecções por Papillomavirus/virologia , Infecções Tumorais por Vírus/virologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , DNA Viral , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Imunofenotipagem , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Fenótipo , Cuidados Pós-Operatórios , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento , Infecções Tumorais por Vírus/complicações
15.
Full dent. sci ; 7(27): 114-127, 2016. ilus
Artigo em Português | BBO - Odontologia | ID: biblio-848467

RESUMO

A regeneração óssea guiada (ROG) baseia-se na criação de um espaço segregado para a invasão de vasos sanguíneos e células osteoprogenitoras, protegendo a reparação óssea contra o crescimento de tecidos não osteogênicos que possuem velocidade de migração maior que as células osteogênicas. Diferentes técnicas e materiais, incluindo membranas reabsorvíveis e não reabsorvíveis, utilizadas sozinhas ou em conjunto com enxertos autógenos, alógenos, aloplásticos, têm sido utilizados em procedimentos de ROG com resultados encorajadores. Para que a técnica de enxertia tenha sucesso, a utilização de materiais adequados e o entendimento da biologia básica são fatores importantes. Os objetivos principais da ROG simultânea à instalação dos implantes são obter uma bem-sucedida regeneração óssea, alta previsibilidade, baixo índices de complicações, baixa morbidade e reduzido período de tratamento. Defeitos ósseos localizados podem ser tratados com alta previsibilidade e proporcionam altos índices de sucesso dos implantes a longo prazo. A colocação de implantes com simultânea regeneração óssea guiada tornaram-se procedimentos de rotina na Implantodontia e a utilização de técnicas consagradas, com materiais que apresentam evidência científica, além de uma adequada formação profissional, são as chaves para o sucesso (AU)


Guided bone regeneration (GBR) is mainly based on the segregation of the soft tissue, allowing the development of new vessels and osteogenic cells, protecting the new bone formation. Several materials and techniques, including non-resorbable and resorbable membranes, bone substitutes, autografts and combinations of these materials have been used for GBR procedures with excellent outcomes. The main objectives of the implant placement with simultaneous GBR are: successful bone regeneration; predictability; low morbidity; low risk and complications rates; reduced treatment time. Localized defects can be treated with high predictability and adequate long-term success rates. These procedures became routine in the daily practice and the use of appropriate techniques, scientific based materials and techniques, besides a proper professional education are the keys for the success (AU)


Assuntos
Materiais Biocompatíveis , Regeneração Óssea , Implantação Dentária Endóssea , Brasil , Radiografia Dentária/métodos
16.
Radiother Oncol ; 113(3): 317-23, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25480095

RESUMO

OBJECTIVE: To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy. MATERIALS AND METHODS: For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival. RESULTS: In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p=0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (p<0.01) but not with distant metastases. CONCLUSIONS: HPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/terapia , Carcinoma de Células Escamosas/virologia , Quimiorradioterapia/métodos , DNA/genética , Feminino , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Neoplasias Orofaríngeas/virologia , Papillomaviridae/genética , Período Pós-Operatório , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de Sobrevida , Resultado do Tratamento
17.
Artigo em Espanhol | LILACS | ID: lil-724861

RESUMO

Condiciones desfavorables del reborde alveolar debido a atrofia, enfermedad periodontal o traumatismos pueden generar deficiencias de volumen óseo, produciendo como consecuencia una relación corona/implante inadecuada y un aspecto estético desfavorable. La presente serie de casos propone el uso de la técnica asociada a un injerto de tejido conectivo como método de desarrollo de sitio periimplantario, con el fin de corregir deficiencias del reborde alveolar, para permitir la posterior instalación de un implante óseo integrado. Ocho pacientes con indicación de extracción de una pieza anterior, asociada a ausencia de la tabla vestibular y a una pérdida de tejidos duros y blandos, fueron sometidos a un procedimiento de regeneración ósea guiada mediante el uso de una mezcla de xenoinjerto y hueso autólogo en conjunto con una membrana reabsorbible e injerto conectivo autólogo. A los 6 meses postratamiento, fue colocado el implante, y provisionalizado inmediatamente. En todos los casos se logró una mejora y una equiparación de los contornos periimplantarios con las piezas vecinas. No existieron complicaciones posoperatorias, la regeneración de tejidos fue exitosa en todos los casos intervenidos, y todos los implantes se integraron correctamente. La regeneración ósea guiada en conjunto con un injerto de tejido conectivo fue un método efectivo para el desarrollo de sitio periimplantario previo a la colocación de implantes en el sector anterior del maxilar.


Unfavorable conditions of the alveolar ridge, due to atrophy, periodontal disease or trauma, can lead to osseous volume deficiencies, producing an inadequate crown / implant relationship and an unfavorable esthetic appearance. The present case series proposes the use of guided bone regeneration (GBR) associated with a connective tissue graft, as a method for peri-implant site development, to correct alveolar ridge deficiencies, and to allow the subsequent placement of an osseointegrated implant. Eight patients with the indication of an anterior tooth extraction, associated with a loss of the vestibular plate and a hard and soft tissue deficiency, were treated with a GBR procedure using a mixture of xenograft-autogenous bone in conjunction with a resorbable membrane and an autogenous connective tissue graft. At 6 months post-treatment, the implant was installed and immediately provisionalized. In all the cases, an improvement and matching of the tissue contours with the neighboring teeth was achieved. There were no postoperative complications. The tissue regeneration was successful in all the cases, and all the implants achieved a correct integration. GBR, in conjunction with a connective tissue graft, was an effective method to perform a peri-implant site development prior to the implant installation in the maxillary anterior region.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Doenças Periodontais/complicações , Regeneração Óssea , Regeneração Tecidual Guiada Periodontal/métodos , Tecido Conjuntivo/transplante , Transplantes , Implantação Dentária/efeitos adversos , Implantação Dentária Endóssea/métodos , Arcada Osseodentária , Membranas Artificiais , Regeneração Óssea , Implantes Absorvíveis , Estética Dentária , Enxerto de Osso Alveolar
18.
Artigo em Espanhol | LILACS | ID: lil-673086

RESUMO

Se considera como aumento óseo vertical, cualquier técnica que apunte a crear una mayor altura del reborde alveolar. A inicios de la década de los 90’s se empezó a utilizar la regeneración ósea guiada (ROG) en mandíbulas atróficas, con el fin de permitir la instalación de implantes óseointegrados. Con el fin de evaluar y exponer parte de la evidencia disponible en la actualidad, con respecto a la ROG para aumento óseo vertical, se realizó la siguiente revisión bibliográfica.


Any technique aimed to improve the alveolar ridge height is considered as a vertical bone augmentation procedure. In the early 90’s guided bone regeneration (GBR) procedures began to be used in atrophic mandibles to allow the installation of osseointegrated dental implants. The following bibliographic review was made with the purpose of evaluating and exposing part of the available evidence at present in this field.


Assuntos
Humanos , Aumento do Rebordo Alveolar/métodos , Prótese Dentária Fixada por Implante , Doenças Mandibulares/cirurgia , Regeneração Tecidual Guiada Periodontal/métodos , Dimensão Vertical
19.
Rev. bras. implantodontia ; 13(4): 22-25, out.-dez. 2007. ilus
Artigo em Português | BBO - Odontologia | ID: biblio-857134

RESUMO

O presente trabalho foi desenvolvido com a finalidade de abordar os aspectos gerais da reconstrução de rebordos alveolares com xenoenxerto associado à membrana de e-PTFE, para este fim foi realizada uma revisão da literatura. Foram encontradas várias propostas para alcançar este objetivo, desde o uso somente de membranas sem preenchimento do defeito, associação de membrana e xenoenxerto, associação de membrana e xenoenxerto com osso autógeno particulado e, associação de membrana com preenchimento com osso autógeno particulado. Os resultados, de acordo com o objetivo deste trabalho, mostraram que a associação da membrana de e-PTFE e do osso mineralizado bovino (Bio-Oss®) foi eficiente na formação óssea e que as partículas deste são substituídas por novo tecido num prazo que varia de três a sete meses


The work’s main goal is to reach of alveolar ridge augmentation techniques with xenograft associated to e-PTFE membranes. In which many proposals could be found, since the use only of the membrane without the defect filling, as well as the association of the membrane and xenograft, or the membrane together with xenograft and autogenous bone chips, or just the membrane with the autogenous bone chips. The results, according to this work’s main objective, showed that the association of the e-PTFE membrane with the inorganic bovine bone (Bio-Oss®) was efficient in the bone formation and that its particles are replaced by new tissue in a time that ranges from three to seven months


Assuntos
Humanos , Adulto , Implantes Dentários , Perda do Osso Alveolar , Transplante Heterólogo , Matriz Óssea , Politetrafluoretileno
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