RESUMO
OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.
Assuntos
Entesopatia , Espondilartrite , Ultrassonografia Doppler , Humanos , Feminino , Masculino , Entesopatia/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Ultrassonografia Doppler/métodos , Espondilartrite/diagnóstico por imagem , Espondilartrite/complicações , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/complicações , Índice de Gravidade de Doença , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/patologia , Estudos de Casos e ControlesRESUMO
OBJECTIVES: We aimed to 1) evaluate by power Doppler (PD) ultrasound (US) the response to therapy of the most inflamed joint and enthesis (target sites) in psoriatic arthritis (PsA) patients starting a biologic disease-modifying anti-rheumatic drug (bDMARD); and 2) to investigate the correlation between the US response and clinical data. METHODS: Consecutive PsA patients with US synovitis and US 'active' enthesitis, starting a bDMARD, were included. The joint with the highest OMERACT-EULAR-US composite score and the enthesis with the highest PD grade (targets) were identified at baseline. The US examination and clinical assessment were performed at 0, 3 and 6 months. The response of OMERACT-EULAR-US synovitis composite score was defined as reaching a grade = 0 at follow-up examination; synovial and entheseal PD responses were defined as a PD=0 and/or a reduction of ≥2 PD grades at follow-up examination. RESULTS: Thirty patients were included. Synovitis composite score, synovial PD and entheseal PD showed significant responses at 3 and 6 months compared to baseline (p<0.01). Synovial PD responses were higher than entheseal PD responses at 3 months (71.4% vs 40.0%, p=0.01) and 6 months (77.8% vs. 46.7%, p=0.02). US synovitis responses were correlated with DAPSA (p<0.01) and MDA responses (p=0.01 for composite score, p=0.02 for PD). CONCLUSIONS: US was found sensitive for monitoring treatment response in PsA patients starting a biologic drug. Entheseal PD was less responsive than synovial PD, suggesting that enthesitis may represent a 'difficult-to-treat' domain in PsA.
Assuntos
Antirreumáticos , Artrite Psoriásica , Entesopatia , Sinovite , Humanos , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/tratamento farmacológico , Ultrassonografia , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico , Antirreumáticos/uso terapêutico , Entesopatia/diagnóstico por imagem , Entesopatia/tratamento farmacológico , Entesopatia/etiologia , Terapia Biológica , Ultrassonografia DopplerRESUMO
The objective of this study is to estimate the prevalence of US findings indicative of calcium pyrophosphate deposition (CPPD) in patients with knee pain. Consecutive patients with knee pain, equally distributed among males and females in seven different age-decades (21-90 years), were enrolled in a cross-sectional study. The presence of US OMERACT-defined CPPD (medial and lateral menisci and femoral hyaline cartilage) and osteophytes (medial and lateral compartments of the tibiofemoral joint) was scored as presence/absence in both knees. Four hundred twenty participants were enrolled (210 men/210 women). Fibrocartilage and hyaline cartilage CPPDs were detected by US in 94/420 (22.4%) and 41/420 (9.8%) participants, respectively. No significant sex differences were noted. The prevalence and the extent of CPPD increased with age. Fibrocartilage and hyaline cartilage CPPDs were identified in 0/60 participants in the third decade, and in 28/60 (46.7%) and 14/60 (23.3%) participants in the ninth decade, respectively (p for trend < 0.01). While fibrocartilage and hyaline cartilage CPPD is virtually absent in subjects younger than 40 and 50 years old, their prevalence steeply increases above from these age groups. Age (aIRR, 1.03; 95% CI, 1.02-1.05), osteophyte score (aIRR, 1.40; 95% CI, 1.22-1.60), and hyaline cartilage CPPD score (aIRR, 2.68; 95% CI, 2.06-3.49) were associated with fibrocartilage CPPD score, whereas age (aIRR, 1.02; 95% CI, 1.01-1.05) and fibrocartilage CPPD score (aIRR, 2.92; 95% CI, 2.29-3.72) were associated with hyaline cartilage CPPD score in multivariable negative binomial regression analyses. In conclusion, we report the US prevalence of CPPD in patients with knee pain. Fibrocartilage CPPD occurs at a younger age and is more prevalent than hyaline cartilage CPPD. Key points ⢠Fibrocartilage CPPD occurs at a younger age and is more prevalent than hyaline cartilage CPPD. ⢠Fibrocartilage and hyaline cartilage CPPDs are virtually absent in subjects younger than 40 and 50 years old. ⢠In subjects older than 80 years, fibrocartilage and hyaline cartilage CPPD prevalence rises up to 46.7% and 23.3%, respectively.
Assuntos
Calcinose , Condrocalcinose , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pirofosfato de Cálcio , Condrocalcinose/epidemiologia , Prevalência , Estudos Transversais , Articulação do Joelho/diagnóstico por imagem , Dor/epidemiologiaRESUMO
The aim of this paper is to identify factors associated with interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) and build an algorithm to better define this association for a personalised application in clinical practice. METHODS: A total of 78 SSc patients underwent HRCT to assess ILD. Demographic, clinical and laboratory variables were collected, focusing on those associated either directly or indirectly with lung involvement. The discriminant value of each variable was determined using the operating characteristic curves (ROC) and included in a model to estimate the strength of ILD association in SSc. RESULTS: Thirty-three (42.31%) patients showed ILD on HRCT. DLco, M-Borg, GERD-Q and capillary density were significantly associated with the presence of ILD-SSc. A model including these variables had a coefficient of determination (R2) of 0.697. DLco had an AUC of 0.861 (p < 0.001) with a cut-off of ≤72.3% (sensitivity 78.8%, specificity 91.1%, +LR 8.86). The m-Borg Scale showed an AUC of 0.883 (p < 0.001) with a cut-off >2 (sensitivity 84.8%, specificity 82.2%, +LR 4.77), GERD-Q had an AUC of 0.815 (p < 0.001) with a cut-off >7 (sensitivity 72.7%, specificity 86.7%, +LR 5.45). The capillary density showed an AUC of 0.815 (p < 0.001) with a cut-off of ≤4.78 (sensitivity 87.9%, specificity 68.9%, +LR 2.82). Based on the pre-test probability values, these four variables were applied to Fagan's nomogram to calculate the post-test probability of this association. CONCLUSIONS: Our study identified four associated clinical factors of ILD in SSc patients. Moreover, their inclusion in an algorithm for the post-test probability, tailored to the specific patients' characteristics, significantly increases the ability to find out the presence of SSc-ILD.
RESUMO
OBJECTIVES: i) To explore the agreement between the OMERACT ultrasound lesions of enthesitis and physical examination in assessing enthesitis in spondyloarthritis (SpA) patients; ii) To investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centres participated in this cross-sectional study. SpA patients, including axial SpA (axSpA) and psoriatic arthritis (PsA) patients, underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for 'active enthesitis' by our group. Subclinical enthesitis was defined as the presence of 'active enthesitis' in ≥1 enthesis in SpA patients without clinical enthesitis (i.e., number of positive entheses on physical examination and Leeds Enthesitis Index score =0). RESULTS: 4130 entheses in 413 SpA patients (224 axSpA/189 PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (i.e., enthesophytes) to almost perfect (i.e., power Doppler and 'active enthesitis'). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158/413 (38.3%) SpA patients with clinical enthesitis, 108 (68.4%) exhibited no 'active enthesitis' on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of SpA patients with and without subclinical enthesitis. CONCLUSIONS: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in SpA patients.
RESUMO
OBJECTIVE: To explore the association of the Outcome Measures in Rheumatology ultrasound (US) entheseal abnormalities with the presence of US joint bone erosions in psoriatic arthritis (PsA). METHODS: Consecutive patients with PsA were included in this cross-sectional study. Demographic and clinical variables were collected. A bilateral US assessment was carried out at the following entheses: plantar fascia, and the quadriceps, patellar (proximal and distal), and Achilles tendons. The following US entheseal abnormalities were registered: hypoechogenicity, thickening, Doppler signal < 2 mm from the bony cortex, calcification/enthesophyte, and bone erosion. The presence of US joint bone erosions was investigated at the second and fifth metacarpophalangeal joints, ulnar head, and fifth metatarsophalangeal (MTP) joint, bilaterally, as well as at the level of the most inflamed joint on physical examination. Multiple linear regression analysis was performed to identify clinical and/or US variables associated with US-detected joint bone erosions. RESULTS: A total of 104 patients with PsA were enrolled. At least 1 joint bone erosion was found in 47 of 104 patients (45.2%). Bone erosions were most frequently detected at the fifth MTP joint level (42/208 joints [20.2 %] in 32/104 patients [30.8%]). In the multivariate model, only a power Doppler (PD) signal at the enthesis (P < 0.001, standardized ß = 0.51), bone erosions at the enthesis (P = 0.02, standardized ß = 0.20), PsA disease duration (P = 0.04, standardized ß = 0.17), and greyscale joint synovitis (P = 0.03, standardized ß = 0.42) were associated with US-detected joint bone erosions. CONCLUSION: PD signal and bone erosions at the enthesis represent sonographic biomarkers of a more severe subset of PsA in terms of US-detected joint erosive damage.
Assuntos
Artrite Psoriásica , Sinovite , Humanos , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/complicações , Estudos Transversais , Ultrassonografia Doppler , Ultrassonografia , Sinovite/complicaçõesRESUMO
OBJECTIVES: To better define the spectrum of new-onset post-COVID-19 and post-COVID-19 vaccine inflammatory rheumatic diseases (IRD) from a large multicentric observational study. METHODS: Consecutive cases of IRD encountered during a 12-month period and satisfying one of the following inclusion criteria: (a) onset of the rheumatic manifestations within 4 weeks from SARS-CoV-2 infection or (b) onset of the rheumatic manifestations within 4 weeks from the administration of one of the COVID-19 vaccines ws recruited. RESULTS: The final analysis cohort comprised 267 patients, of which 122 (45.2%) in the post-COVID-19 and 145 (54.8%) in the postvaccine cohort. Distribution of IRD categories differed between the two cohorts: the post-COVID-19 cohort had a higher percentage of patients classified as having inflammatory joint diseases (IJD, 52.5% vs 37.2%, p=0.013) while the post-vaccine cohort had a higher prevalence of patients classified as polymyalgia rheumatica (PMR, 33.1% vs 21.3%, p=0.032). No differences were detected in the percentage of patients diagnosed with connective tissue diseases (CTD 19.7% vs 20.7%, p=0.837) or vasculitis (6.6% vs 9.0%, p=0.467). Despite the short follow-up period, IJD and PMR patients' response to first-line therapy was favourable, with both groups achieving a drop in baseline disease activity scores of ~30% and ~70% respectively. CONCLUSION: Our article reports the largest cohort published to date of new-onset IRD following SARS-CoV-2 infection or COVID-19 vaccines. Although causality cannot be ascertained, the spectrum of possible clinical manifestations is broad and includes IJD, PMR, CTD and vasculitis.
Assuntos
Transtorno do Espectro Autista , COVID-19 , Arterite de Células Gigantes , Polimialgia Reumática , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , VacinaçãoRESUMO
Objectives: To investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases. Methods: Forty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0-3) and a continuous quantitative measurement ("VAS echogenicity," 0-100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall's Tau and Pearson's Rho coefficients. Results: The semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57-0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68-0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. "VAS echogenicity" showed a high reliability both in the inter-observer [ICC = 0.80 (0.75-0.85)] and intra-observer [ICC = 0.88 (0.88-0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and "VAS echogenicity" [ICC = 0.52 (0.50-0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively). Conclusion: The results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases.
RESUMO
One of the most common problems encountered while deciphering results from expression profiling experiments is in relating differential expression of genes to molecular functions and cellular processes. A second important problem is that of comparing experiments performed by different labs using different microarray platforms, or even unrelated techniques. Gene Ontology (GO) is now used to describe biological features, since GO terms are associated with genes, to overcome the apparent distance between expression profiles and biological comprehension. Here we describe the development, implementation and use of GOAL (Gene Ontology Automated Lexicon), a web-based application for the identification of functions and processes regulated in microarray and SAGE (serial analysis of gene expression) experiments. We applied GOAL to a range of experimental datasets related to different biological problems, including cancer and the cell cycle. By using GOAL, reported and novel relevant processes were identified in a number of experiments by our collaborators and by us. Different datasets could also be compared with each other to define conserved functional modules. GOAL allows a seamless and high-level analysis of expression profiles and is implemented as a free WWW resource (http://microarrays.unife.it).
Assuntos
Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Software , Interpretação Estatística de Dados , Internet , Biossíntese de Proteínas , Proteínas/genética , Proteínas/fisiologia , Transcrição Gênica , Interface Usuário-ComputadorRESUMO
Differentially expressed genes among different benign and malignant salivary gland tumors were identified by use of cDNA microarrays containing 19,000 human expressed sequence tags. Tumors were classified by using a subset of 486 genes. Benign Warthin's tumor and pleomorphic adenoma showed very distinctive gene expression patterns. One hundred and thirty-three genes differentiated the single malignant clear cell carcinoma from non-tumor salivary glands (P < 0.01), whereas only 16 genes separated it from the highly related benign pleomorphic adenoma (P < 0.01). Fifty-seven cDNAs were associated with mucoepidermoid carcinoma (P < 0.01). The identified genes might help to disclose the molecular mechanisms and processes underlying malignant salivary gland tumors.
Assuntos
Regulação Neoplásica da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , DNA Complementar/metabolismo , Etiquetas de Sequências Expressas , Humanos , RNA/metabolismoRESUMO
Zirconium oxide ceramics have outstanding mechanical properties, a high biocompatibility and a high resistance to scratching. Expression profiling by DNA microarray is a molecular technology that allows the analysis of gene expression in a cell system. By using DNA microarrays containing 19,200 genes, we identified in osteoblast-like cells line (MG-63) cultured on zirconium oxide discs (Cercon, Degussa Dental, Hanau, Germany) several genes whose expression was significantly up or down-regulated. The differentially expressed genes cover a broad range of functional activities: (a) immunity, (b) vesicular transport and (c) cell cycle regulation. It was also possible to detect some genes whose function is unknown. The data reported are, to our knowledge, the first genetic portrait of a zirconium oxide surface. They can be relevant to better understand the molecular mechanism of biocompatibility and as a model for comparing other materials.
Assuntos
Materiais Dentários/farmacologia , Expressão Gênica/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Zircônio/farmacologia , Animais , Regulação para Baixo , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Regulação para CimaRESUMO
Cisplatin [cis-diamminedichloroplatinum(II)] (CDDP) is an organic compound that is widely used for the treatment of a large number of tumors. Its clinical use is limited by the presence of some undesired side effects, like as oto- and nephro toxicity, whose mechanisms of action are not understood. One of the possible CDDP toxicity mechanism seems to involve the generation of reactive oxygen species (ROS), that can impair morphology and function of hair cells (HC) in the organ of Corti. To test this hypothesis we evaluated the effect of CDDP treatment on RNA steady-state levels of 15,000 genes by microarray analysis, using, as a experimental model, the OC-k3 cell line, obtained from the organ of Corti of transgenic mice and constitutively expressing the large SV40 T antigen. We have found overexpression of several genes related to arachidonate mobilization including phospholipase A2, group IV and V, phospholipase A2 activating protein and lysophospholipase I and III, as well as lipoxygenation like arachidonate 12-lipoxygenase and arachidonate 5-lipoxygenase activating protein. In addition, we found significant transcription of genes regulating cell respiration, including cyt c oxidase, as well as genes involved in xenobiotic detoxification and lipid peroxidation such as cyt P450, and other oxidases including spermine oxidase and monoamine oxidase. As a whole, overexpression of the group of different genes seems to indicate that an oxidative burst could take place during cisplatin administration. We therefore searched for evidences of superoxide anion and hydrogen peroxide by means of electron paramagnetic resonance (EPR) spectroscopy and flow cytometry, but failed to detect them. On the other hand, we found an increase of malondialdehyde (MDA) synthesis and protein carbonylation products, indicating the occurence of lipid peroxidative degradation. When we tested the effectiveness of butylated hydroxytoluene (BHT), dithiothreitol (DTT) and N-acetylcysteine (N-Ac) as cytoprotectants, all of them reduced protein carbonylation to control levels and significantly protected OC-k3 from CDDP-induced cell death, with an higher protection when using the lipophylic antioxidant BHT. The same antioxidants prevented also the onset of protein carbonylation, which extent was decreased to basal levels. These data indicate that CDDP is able to stimulate gene expression up to 12 h after the beginning of the treatment. This increase in gene transcription involves a large number of genes potentially able to increase the level of cell ROS. Consistently, cells survival is improved by cotreatment with antioxidants, in particular lipophilics.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Órgão Espiral/efeitos dos fármacos , Órgão Espiral/metabolismo , RNA/metabolismo , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Hidroxitolueno Butilado/farmacologia , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Citoproteção , Ditiotreitol/farmacologia , Expressão Gênica/efeitos dos fármacos , Malondialdeído/metabolismo , Camundongos , Camundongos Transgênicos , Análise de Sequência com Séries de Oligonucleotídeos , Órgão Espiral/citologia , Órgão Espiral/fisiologia , Fatores de TempoRESUMO
Several features of the implant surface, such as composition, topography, roughness, and energy, play a relevant role in implant integration with bone. Little is known about the structural and chemical surface properties that may influence biological responses. Expression profiling by DNA microarray is a molecular technology that allows the analysis of gene expression in a cell system. By using DNA microarrays containing 19200 genes, we identified several genes whose expression was significantly down-regulated in osteoblast-like cell line MG63 on a new implant surface (titanium pull spray superficial [TPSS] surface, Oralplant, Cordenons, PN, Italy). The differentially expressed genes cover a broad range of functional activities: (1) signaling transduction, (2) translation, (3) cell cycle regulation, (4) structural and metabolic functions, and (5) apoptosis. It was also possible to detect some genes whose functions are unknown. The data reported can be relevant to better understand the role of the type of surface on the molecular mechanism of implant osseointegration and as a model for comparing other materials.
Assuntos
Implantes Dentários , Materiais Dentários/química , Osteoblastos/fisiologia , Titânio/química , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular , Materiais Revestidos Biocompatíveis/química , Citoesqueleto/genética , Regulação para Baixo/genética , Regulação da Expressão Gênica/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Osseointegração/genética , Osteoblastos/metabolismo , Transdução de Sinais/genética , Propriedades de SuperfícieRESUMO
Classification and prognosis of larynx squamous cell carcinoma (LSCC) depends on clinical and histopathological examination. Currently, expression profiling harbors the potential to investigate, classify, and better manage cancer. Gene expression profiles of 22 primary LSCCs were analyzed by microarrays containing 19,200 cDNAs. GOAL functionally classified differentially expressed genes, and a novel "in silico" procedure identified physical gene clusters differentially transcribed. A signature of 158 genes differentiated tumors with nodal metastasis. A novel statistical method allowed categorization of metastatic tumors into 2 distinct subgroups of differential gene expression patterns. Among genes correlated to nodal metastatic progression, we verified in vitro that NM23-H3 reduced cell motility and TRIM8 were a growth suppressor. Six chromosomal regions were specifically downregulated in metastatic tumors. This large-scale gene expression analysis in LSCC provides information on changes in genomic activity associated with lymphonodal metastasis and identifies molecules that might prove useful as novel therapeutic targets.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundário , Proteínas de Transporte/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Laríngeas/genética , Nucleosídeo NM23 Difosfato Quinases/genética , Proteínas do Tecido Nervoso/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Análise por Conglomerados , DNA Complementar/genética , Progressão da Doença , Regulação para Baixo/genética , Perfilação da Expressão Gênica , Genes Neoplásicos , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Prognóstico , RNA Neoplásico/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Supressoras de Tumor/genética , Regulação para Cima/genéticaRESUMO
OBJECTIVE: To retrospectively investigate whether the genetic profile from chorionic villous sampling (CVS) found in euploid fetuses with increased NT differs from matched controls. STUDY DESIGN: We employed cDNA microarray technology to characterize and compare the gene expression profile of chorionic villous tissues (which encompass the trophoblast and inner mesenchymal core) belonging to four singleton male fetuses with increased NT at 10-11 weeks' gestation. A pool of four normal chorionic villous tissues belonging to four respective fetuses, matched for gestational age and gender, was used as controls. RESULTS: In euploid fetuses, we found several underexpressed genes, possibly involved in mechanisms associated with the abnormal NT thickness. All these genes are likely to belong to the mesenchymal core of the villus that originates from the extraembryonic mesoderm, and thus might be closely representative of the embryonic genetic profile. They include: (1) genes of embryonic development and differentiation such as Endothelin 3 (EDN3) and secreted frizzled-related protein 4 (SFRP4); (2) genes of the extracellular matrix (ECM) metabolism such as tissue inhibitor of metalloproteinase1 (TIMP1), and disintegrin-like and matrix metalloproteinase (MMP) (reprolysin type) with thrombospondin type 1 Motif or ADAMTS2, exostoses (multiple)-like 1 (EXTL1), heparan sulfate (HS) 6-O-sulfotransferase 1 or HS6ST1, fibronectin 1 (FN1) and Integrin Alpha 10 (ITGA10) involved in HS and proteoglycan bio-synthesis, ECM synthesis and cell-matrix adhesion; (3) genes involved in vessel formation and differentiation such as angiogenic factor (VG5Q), and in blood pressure control and muscle contraction, like Endothelin 3 or EDN3 and sarcolemma associated protein (SLMAP). Such lower expressions of the villous tissues might be related to an immature genetic profile of the embryo development as well as abnormal regulation of ECM bio-synthesis and/or improper vessel growth and blood pressure control. Also, the results partially support the theories proposed for NT enlargement such as altered composition of ECM and abnormal/delayed development of the circulatory system. CONCLUSIONS: Abnormal extraembryonic genetic expression is found at 10-11 weeks' gestation in euploid fetuses with increased NT. If both extra- and intraembryonic mesoderms express the same genetic alterations, then microarray analyses on CVS could be used to screen several mesoderm-derivate anomalies.
Assuntos
Amostra da Vilosidade Coriônica/métodos , Transtornos Cromossômicos/diagnóstico , Doenças Fetais/diagnóstico , Regulação da Expressão Gênica no Desenvolvimento/genética , Medição da Translucência Nucal/métodos , Estudos de Casos e Controles , Transtornos Cromossômicos/genética , Feminino , Doenças Fetais/genética , Perfilação da Expressão Gênica , Idade Gestacional , Humanos , Cariotipagem , Idade Materna , Análise de Sequência com Séries de Oligonucleotídeos , Gravidez , Primeiro Trimestre da Gravidez , Estudos RetrospectivosRESUMO
Surface implant modifications have been shown to have a relevant importance in modifying cell response. Expression profiling by DNA microarray is a new molecular technology that allows the analysis of gene expression in a cell system. By using DNA microarrays containing 19,200 genes, we identified in osteoblast-like cells line (MG-63) on new implant surface (nanoPORE, Out-Link, Sweden and Martina, Due Carrare, Padova, Italy), several genes whose expressions were significantly down-regulated. The differentially expressed genes cover a broad range of functional activities: (a) immunity, (b) vesicular transport (c) apoptosis and cell cycle regulation. It was also possible to detect some genes whose function is unknown. The data reported are, to our knowledge, the first genetic portrait of an implant surface. They can be relevant to better understand the molecular mechanism of implant osseointegration and as a model for comparing other materials.
Assuntos
Implantes Dentários , Osseointegração/genética , Osteoblastos/fisiologia , Titânio , Apoptose/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular , Regulação para Baixo , Perfilação da Expressão Gênica , Humanos , Imunidade/genética , Análise de Sequência com Séries de Oligonucleotídeos , Porosidade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Propriedades de Superfície , Vesículas Transportadoras/genéticaRESUMO
In the head and neck region, clear cell tumors are usually derived from salivary glands, odontogenic tissues, and metastasis. The World Health Organization has classified clear cell odontogenic tumor among benign tumors, but it is now recognized as a more sinister lesion, and current opinion is that it should be designated as a carcinoma. It is characterized by aggressive growth, recurrences, and metastasis. By using complementary DNA microarrays, several genes in clear cell odontogenic tumor were identified that are differentially regulated when compared with non-tumor tissue. In conclusion, the first genetic profiling of clear odontogenic carcinoma is reported. DNA microarrays can potentially help in identifying some genes whose products could be disease-specific targets for cancer therapy as well as a tool for better classifying odontogenic tumor.