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2.
Eur Arch Otorhinolaryngol ; 271(6): 1641-51, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24402377

RESUMO

To examine the prognostic significance of the immunohistochemical expression of p63 and Ki-67 oncoproteins in patients with laryngeal squamous cell carcinoma, a retrospective evaluation was carried out on a cohort of 108 patients with primary laryngeal squamous cell carcinoma (LSCC) treated by primary surgery. For the immunohistochemical evaluation, tissue section obtained by formalin-fixed and paraffin-embedded tissue blocks from resection of each patient was used. Clinicopathologic data were associated with the immunostaining results. The association among the considered variables was assessed by Fisher's exact test, Mann-Whitney test, non-parametric χ(2) test, and Spearman's rho rank test was used to assess the relations among them. Differences in p63 and Ki-67 immunoreactivity among the different groups were compared via Kruskal-Wallis test and post hoc tests were performed using Mann-Whitney test with Bonferroni correction. The overall survival rate was estimated via Kaplan-Meier method, and the cumulative incidence functions for different groups were compared using log-rank statistics. Cox proportional hazard model was employed in a multivariate analysis to assess the effect of prognostic factors in the overall survival rate. Furthermore, taking into account death due to other causes, we estimated LSCC-related survival and disease-free survival rates using competing risk analysis. The results of immunohistochemical examination showed a statistically significant relationship between the up-regulation of P63 and Ki-67, an increase in histological grading, and primary tumours associated with lymph node metastases. p63 and Ki-67 up-regulation was related to a shorter disease-free survival and a significant association was found between p63 and Ki-67 percentage of positive cells and patient survival. Finally, we noticed a significant relation between p63 and Ki-67 (ρ = 0.87). On the other hand, no statistically significant associations were found between p63 and Ki-67 down-regulation and clinicopathologic data. Our findings suggest that abnormal p63 and Ki-67 immunoreactivity may be involved in the early phases of laryngeal tumorigenesis and may become a significant prognostic predictor for both overall and disease-free survivals. These biomarkers could thus help in the selection of high-risk patients with LSCC who may benefit from more aggressive therapy or chemoprevention.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Laríngeas/metabolismo , Proteínas de Membrana/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Laringectomia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Regulação para Cima
3.
J Biol Regul Homeost Agents ; 27(1): 121-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23489692

RESUMO

To analyse the relationship of the immunohistochemical p63 expression with tumoral extent, histologic grade, lymph node involvement and clinical stage in laryngeal squamous cell carcinoma (LSCC), a series of 81 patients with primary LSCC treated by primary surgery was retrospectively evaluated. Immunohistochemistry was performed on formalin-fixed and paraffin-embedded tissue blocks from surgical samples. Clinicopathologic data were correlated with the p63 staining results. Differences in p63 immunoreactivity between the different groups were compared using both parametric analysis of variance (ANOVA) and non-parametric Kruskal-Wallis test. Statistical significance was set at p less than 0.05. All statistical analyses were performed using the R statistical package. We found a statistically significant association between p63 protein expression and increase of tumor extension (T1 vs T3), of histological grading, of level of lymph node involvement (N0 vs N1 and N2), and clinical stage (I vs IV). Our findings suggest that abnormal expression of p63 may be involved in the early phases of laryngeal tumorigenesis and this oncoprotein might become a useful predictor of clinical outcome.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Linfonodos/patologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias
4.
Oral Dis ; 19(1): 92-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22805780

RESUMO

OBJECTIVE: Radicular cysts occur as a result of the immunological response to continuous antigenic stimulation from root canals. We correlated the immunophenotypical composition of the lymphoid infiltrate to the microvessel density expressed by the count of CD34 reactive endothelial cells in radicular cysts. SUBJECTS AND METHODS: Thirty-four cases of radicular cysts were evaluated by immunohistochemistry, using antibodies against B- and T-cell antigens (CD20, CD3, CD4, CD8) and against the endothelial cell marker CD34. Statistical analysis was performed. RESULTS: In the epithelium, we observed a low amount of lymphoid infiltrate in all 34 radicular cysts, and a strong significant negative correlation between T and B lymphocytes and between T-helper and T-cytotoxic/suppressor lymphocytes. In the cyst capsule, we observed a significant positive correlation between B and T lymphocytes, B and T-cytotoxic/suppressor lymphocytes, T and T-helper lymphocytes and between the number of CD34+ blood vessels and T and T-helper lymphocytes, respectively. We observed a statistically significant correlation between percentage of CD34+ vessels and inflammatory infiltrate grade. CONCLUSIONS: Both humoral and cellular immune reactions and neovascularization are likely to occur in the complex events of tissue destruction. The inflammatory infiltrate has an important role in neoangiogenesis and consequently in radicular cysts development and growth.


Assuntos
Linfócitos/patologia , Microvasos/patologia , Cisto Radicular/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/análise , Antígenos CD34/análise , Complexo CD3/análise , Antígenos CD4/análise , Linfócitos T CD4-Positivos/patologia , Antígenos CD8/análise , Linfócitos T CD8-Positivos/patologia , Tecido Conjuntivo/patologia , Células Endoteliais/patologia , Endotélio Vascular/patologia , Epitélio/patologia , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Linfócitos T Citotóxicos/patologia , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Reguladores/patologia , Adulto Jovem
5.
Oral Dis ; 19(6): 620-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23279259

RESUMO

OBJECTIVE: To understand the role of angiogenesis and hypoxia in cancer progression of primary oral melanoma (POM). MATERIALS AND METHODS: Sixteen malignant primary melanomas were immunostained with markers CD34, VEGF and HIF-1α. Stained cells were counted in the invasive front and inside the tumour, and the differences were compared and correlated with histological parameters and disease-specific survival of the patients. RESULTS: Tumour invasive front showed increased MVD and increased vessel VEGF and HIF-1α expression compared with the intratumoural compartment. No such differences were seen in tumoural melanocytes of the two compartments. Positive correlations were observed between CD34 and VEGF, CD34 and HIF-1α and VEGF and HIF-1α expression in invasive front vessels. CD34 expression was statistically correlated with the level of infiltration. A significant trend to worse disease-free survival was also determined with increased invasive front vessel expression of CD34, VEGF and HIF-1α. CONCLUSIONS: Our data highlight the importance of the invasive margin in POM biology. The high angiogenic activity and endothelial VEGF and HIF-1α expression in invasive front vessels have a significant impact on patient survival and future agents targeted against VEGF pathway may represent a novel and effective therapeutic opportunity. Larger studies are needed to further address our findings.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Melanoma/irrigação sanguínea , Microvasos/patologia , Neoplasias Bucais/irrigação sanguínea , Fator A de Crescimento do Endotélio Vascular/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/análise , Progressão da Doença , Intervalo Livre de Doença , Endotélio Vascular/patologia , Feminino , Humanos , Hipóxia/patologia , Imuno-Histoquímica , Masculino , Melanócitos/patologia , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Invasividade Neoplásica , Neovascularização Patológica/patologia , Neoplasias Palatinas/irrigação sanguínea , Neoplasias Palatinas/patologia , Prognóstico , Fatores Sexuais , Taxa de Sobrevida
6.
Br J Dermatol ; 166(5): 948-52, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22233400

RESUMO

BACKGROUND: Neoplastic T-cell recruitment into the skin is a critical step in the pathogenesis of mycosis fungoides (MF), and the cutaneous T-cell attracting chemokine, CTACK/CCL27, might be involved. OBJECTIVES: To investigate the clinical and prognostic significance of CTACK/CCL27 levels in patients with early-stage MF. METHODS: Serum samples and skin biopsy specimens were collected from 15 patients at the time of diagnosis and after the end of treatment with psoralen plus ultraviolet A/interferon alfa-2b combination therapy. Serum samples were also collected from 20 healthy donors as controls. CTACK/CCL27 serum levels were analysed by enzyme-linked immunosorbent assays. CTACK/CCL27 tissue expression was determined by immunohistochemistry on skin biopsy specimens taken at diagnosis and after therapy. Event-free survival was taken as the primary clinical outcome. RESULTS: In patients with MF at diagnosis, CTACK/CCL27 serum levels were not significantly different from healthy controls, whereas CTACK/CCL27 expression in the skin was increased in 87% of cases compared with normal controls. After therapy, all patients obtained a clinical complete remission, serum levels did not change significantly and tissue expression remained abnormal in 80% of patients, even if complete histological remission was recorded. Serum levels were not significantly different in cases with different intensity of cutaneous immunostaining. Eight patients experienced a relapse: the combination of high CTACK/CCL27 levels both in sera and skin increased the probability of experiencing an event at 51 months from 36% to 83%. CONCLUSIONS: Our data seem to indicate that CTACK/CCL27 levels in skin and sera after therapy might be correlated with risk of recurrence.


Assuntos
Antineoplásicos/uso terapêutico , Quimiocina CCL27/metabolismo , Interferon-alfa/uso terapêutico , Micose Fungoide/tratamento farmacológico , Terapia PUVA/métodos , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Micose Fungoide/sangue , Recidiva Local de Neoplasia/etiologia , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
7.
Eur J Clin Microbiol Infect Dis ; 31(11): 3047-55, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22729599

RESUMO

The aim of this study was to evaluate the efficacy of distinctin in the management of cutaneous methicillin-resistant Staphylococcus aureus (MRSA) wound infections in an experimental mouse model. Wounds, made in the panniculus carnosus of BALB/c mice, were inoculated with 5 × 10(7) colony-forming units (CFU) of MRSA. Mice were treated with topical distinctin (1 mg/kg of body weight), topical teicoplanin (7 mg/kg of body weight), intraperitoneal teicoplanin (7 mg/kg of body weight); topical teicoplanin and daily intraperitoneal teicoplanin; topical distinctin and daily intraperitoneal teicoplanin. Bacterial cultures of excised tissues and histological examination of microvessel density and of vascular endothelial growth factor (VEGF) expression were studied. It was found that topical distinctin combined with parenteral teicoplanin inhibited bacterial growth to levels comparable with those observed in uninfected animals. Wounded areas of animals treated with distinctin were characterized by a more mature granulation tissue, with a more organized and denser type of connective tissue, compared to mice treated only with teicoplanin. Treatment with topical distinctin had a significant impact on VEGF expression and microvessel density. The combined use of distinctin with teicoplanin may be useful in the management of infected wounds by significantly inhibiting bacterial growth and accelerating the repair process.


Assuntos
Proteínas de Anfíbios/administração & dosagem , Antibacterianos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Administração Tópica , Animais , Carga Bacteriana , Modelos Animais de Doenças , Histocitoquímica , Masculino , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Camundongos Endogâmicos BALB C , Pele/microbiologia , Pele/patologia , Infecções Cutâneas Estafilocócicas/microbiologia , Teicoplanina/administração & dosagem , Resultado do Tratamento , Infecção dos Ferimentos/microbiologia
8.
Dermatol Ther ; 25(2): 207-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22741939

RESUMO

Acne agminata is a rare asymptomatic, inflammatory dermatosis, which affects adolescence and young adults, whose etiopathogenesis is already controversial. Clinically, acne agminata is characterized by red-yellow-brown papular-pustular eruption involving the central face, in particular cheeks, chin, forehead, and eyelids. The authors report a case of a 25-year-old Caucasian man affected by acne agminata treated with doxycycline and isoniazid.


Assuntos
Erupções Acneiformes/tratamento farmacológico , Doxiciclina/uso terapêutico , Isoniazida/uso terapêutico , Erupções Acneiformes/patologia , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Doxiciclina/administração & dosagem , Quimioterapia Combinada , Face , Humanos , Isoniazida/administração & dosagem , Masculino , Resultado do Tratamento
9.
G Ital Dermatol Venereol ; 147(6): 573-80, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23149703

RESUMO

Primary cutaneous T-cell lymphomas are a heterogeneous group of extranodal NH lymphomas primarily presenting in the skin without extracutaneos involvement at diagnosis. Treatment choices closely depend on clinic-pathologic entity and disease stage. Among available choices, oral bexarotene has shown efficacy and safety both in monotherapy and in association with other treatments, by virtue of its versatility and high synergism with alpha-interferon, photochemotherapy (PUVA), and chemotherapy. Moreover, when associated with a wise management of its side effects, bexarotene is well tolerated if used in long-term administration, and it is therefore a good candidate to maintenance treatment after different induction therapies. Recently, the Gruppo Italiano Linfomi Cutanei (GILC) has started some pilot studies, with the aim to investigate bexarotene potential in association with PUVA and single agent chemotherapy (as pegylated liposomal doxorubicin and gemcitabine), and as consolidation/maintenance treatment. The preliminary results of GILC pilot studies confirm the good tolerability and safety of low-intermediate dose bexarotene, and its potential synergism with PUVA and chemotherapy. In addition, its use in consolidation/maintenance has proven efficacy in improving overall response rate.


Assuntos
Anticarcinógenos/uso terapêutico , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Tetra-Hidronaftalenos/uso terapêutico , Bexaroteno , Ensaios Clínicos como Assunto , Humanos , Itália , Linfoma Cutâneo de Células T/mortalidade , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida
10.
G Ital Dermatol Venereol ; 147(6): 523-31, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23149698

RESUMO

Mycosis fungoides (MF), which represents the most common subtype of primary cutaneous T-cell lymphoma (CTCL), is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known. In this review, a summary of published data on MF large patients cohorts will be presented, together with the results obtained by a retrospective analysis of clinical features and follow-up data of 1,422 MF patients diagnosed and followed-up from 1975 to 2010 in 27 Italian Centres (Italian Study Group for Cutaneous Lymphoma). From a clinical perspective, the amount of data support the relevance of a stage-tailored, differentiated follow-up strategy, in as much as the TNMB staging appears not only to be associated with different progression rates, but also shows as a new finding a relationship with different patterns of disease progression. From a biological point of view, there is the need to understand the molecular basis of the different clinical pathways of disease progression, to be able to potentially identify at an earlier phase of disease evolution, the patients who are more likely to develop erythroderma or tumour-stage progression. In conclusion, if MF is indeed a true "lion queen", as dermatologists we need to be expert and wise tamers to keep it under control.


Assuntos
Micose Fungoide , Neoplasias Cutâneas , Progressão da Doença , Humanos , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia
11.
Br J Dermatol ; 164(1): 33-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21070199

RESUMO

BACKGROUND: To date, the diagnosis of psoriasis is based on both clinical history and physical examination, and its severity is assessed by the Psoriasis Area and Severity Index (PASI). Continuous technological advances in the field of sonography have led to the development of equipment with high power Doppler frequency, which allows for very detailed morphological information regarding the dermal blood flow. OBJECTIVES: To compare power Doppler sonography (PDS) with clinical and histological findings before and after etanercept treatment in patients with psoriasis. METHODS: Twelve patients with a clinical diagnosis of psoriasis were enrolled in this study. The PASI, PDS and histological examinations were assessed in all patients on the same day at baseline, and after 12 weeks of biological treatment. PDS examination was performed by an experienced sonographer, using a sonographic system equipped with transducer ranging from 6 to 18 MHz and Doppler frequency ranging from 7 to 14 MHz. RESULTS: At follow up there was a significant decrease in PASI. A significant change was also detected for the PDS findings (P = 0·005). At baseline the median value for factor VIII staining was 1·5, and the median value for vascular endothelial growth factor (VEGF) staining was also 1·5. At follow up there was a significant decrease in both factor VIII and VEGF staining scores. Moreover, a positive correlation between reduction in PDS score and improvement in clinical and histological scores was found: Spearman's ρ = 0·639, P = 0·0022; Spearman's ρ = 0·619, P = 0·0013; Spearman's ρ = 0·765, P = 0·0002, respectively. CONCLUSIONS: Our results show a significant correlation between PDS findings and both PASI and histological degree of vascularization before and after etanercept treatment. These data provide evidence in favour of the validity of PDS in the assessment of dermal perfusional changes in patients with psoriatic plaques.


Assuntos
Imunoglobulina G/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Psoríase , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Biópsia , Etanercepte , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico por imagem , Psoríase/tratamento farmacológico , Psoríase/patologia , Índice de Gravidade de Doença , Pele/irrigação sanguínea , Pele/diagnóstico por imagem , Ultrassonografia Doppler/normas
12.
Int J Immunopathol Pharmacol ; 24(3): 557-66, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21978688

RESUMO

Mast cells (MCs) are motile granule-containing cells that originate from bone marrow pluripotential haematopoietic cells, circulate in blood and extravasate in tissues where they play an important role in inflammation, host defense and tissue repair. We herein review the English literature over the past twenty years concerning the biology and function of MCs with particular focus on their role in the inflammatory process in dental implant failure due to osseointegration absence or to peri-implantitis. Due to immunological or non-immunological stimulation, in a few minutes MCs release prestored granule-associated mediators into the extracellular environment promoting pro-/anti-inflammatory events/response. MCs can either protect the host by activating defense mechanisms and initiating tissue repair and osseointegration if their function is transient, or lead to considerable tissue damage if it is inappropriate and continuous leading to osseointegration absence or peri-implantitis. We hypothesize that administration of histamine receptor antagonists, serine protease inhibitors and MC preformed mediator release inhibitors before and after implantation could represent novel therapeutic strategies to improve the osseointegration, the functionality and longevity of implants or prevent and treat peri-implant inflammatory conditions.


Assuntos
Implantes Dentários/efeitos adversos , Inflamação/etiologia , Inflamação/patologia , Mastócitos/fisiologia , Próteses e Implantes/efeitos adversos , Animais , Quimiocinas/fisiologia , Citocinas/fisiologia , Implantação Dentária Endóssea , Histamina/fisiologia , Humanos , Metaloproteinases da Matriz/fisiologia , Serina Proteases/fisiologia
13.
Leuk Res Rep ; 15: 100243, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34040959

RESUMO

Major disease complications for patients with essential thrombocythemia (ET) include thrombosis and fibrotic or leukemic transformation. Calreticulin (CALR) mutation type 1 frequencies in ET are estimated between 7% and 11% and ET patients carrying CALR type 1 mutation are associated with lower risk of thrombosis but higher risk of myelofibrosis transformation compared to ET patients with JAK2 mutation. Leukemic transformation rates at 20 years are estimated at less than 5% for ET and risk factors for leukemic transformation are advanced age, thrombosis history, leukocytosis, and anemia. Amongst the subtypes of blast phase myeloproliferative neoplasms, acute promyelocytic leukemia is extremely rare. Herein, we present a case of a promyelocytic blast crisis of post-ET myelofibrosis with associated life-threatening splanchnic vein thrombosis. This case suggests that inflammation plays a key role in thrombotic events and fibrotic/leukemic transformation in ET patients, regardless the molecular landscape.

14.
Int J Immunopathol Pharmacol ; 22(2): 371-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19505391

RESUMO

Several studies suggest that microangiopathy plays a crucial role in the pathogenesis of psoriasis. TNFalpha up-regulates the genetic transcription of VEGF, a pro-angiogenetic cytokine over-expressed in psoriatic skin, which promotes micrangiopathic modifications in psoriatic plaque. Etanercept is a chimeric protein used in the treatment of psoriasis and other immunomediated disorders, which blocks inflammatory response by interfering in the binding of TNF-alpha to its receptors. Starting from this data, we retain that etanercept can improve microangiopathy in psoriatic skin by reducing the synthesis of pro-angiogenetic chemokine VEGF. The aims of the study are: to verify the effect of etanercept on cutaneous en plaque capillaries in vivo using intra-vital videocapillaroscopy analysis, to evaluate the relation between the en plaque videocapillaroscopic pattern and the immunohistochemical cutaneous expression of VEGF in psoriasis, and finally to correlate all these in data with clinical disease activity. Eighteen patients (10 male and 8 female, mean age 51, range 21-60) suffering from stable, en plaque type psoriasis, involving at least 10 percent of body surface area (BSA), and not responsive to conventional therapy were included in the study. All the enrolled patients received etanercept 50mg/twice/week, subcutaneously, for 12 weeks, and were carefully followed up for clinical response with PASI score and DLQI index both before (T0) and after 12 weeks (T12) of treatment with etanercept. A well demarcated psoriatic plaque of the extensor surface of upper extremities was chosen to perform an intra-vital videocapillaroscopy analysis (IVCP), and a skin biopsy for immunohistochemical study both at T0 and T12 in all the included patients, in order to evaluate the presence of microangiopathy and its modification after therapy. All the patients experienced a clinical improvement of cutaneous disease with a significant decrease of PASI score (p<0.0001) and DLQI level (p<0.0001), throughout the twelve weeks of treatment. On IVCP analysis, microangiopathy dramatically decreased (p<0.0001), this modification being significantly related with PASI and DLQI decrease at T12. Immunohistochemical expression of VEGF decreased significantly from T0 to T12 (p<0.0001), and was related with a reduction of psoriatic microangiopathy at T12. The results of our videocapillaroscopic and immunohistochemical investigation confirm that the therapeutic potentiality of etanercept is based also on its capability to promote the regression of psoriatic microangiopathy. Moreover, according to these considerations, videocapillaroscopic evaluation of psoriatic plaque, both before and after treatment with etancercept, may be a useful tool to objectively demonstrate its effect on microcirculation.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Imunoglobulina G/administração & dosagem , Imuno-Histoquímica , Imunossupressores/administração & dosagem , Microscopia de Vídeo , Neovascularização Patológica/prevenção & controle , Psoríase/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/administração & dosagem , Pele/efeitos dos fármacos , Adulto , Capilares/efeitos dos fármacos , Capilares/patologia , Etanercepte , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Psoríase/metabolismo , Psoríase/patologia , Índice de Gravidade de Doença , Pele/irrigação sanguínea , Pele/patologia , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
15.
J Dent Res ; 86(4): 357-62, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17384032

RESUMO

It has been stated that cyclosporin and nifedipine produce gingival overgrowth. However, the specific pathogenic mechanism remains uncertain. We used an experimental rat model to test the hypothesis that changes in collagen metabolism and numbers of gingival blood vessels are not mediated by intracellular calcium concentration (ratiometric Fura-2 AM measurement) in gingival fibroblasts. In the cyclosporin group, both width (364.2 +/- 67.5 mum) and microvessel density (number of vessels/mm(2), stained with anti-CD34 antibody) (41.6 +/- 5.1) of gingiva were statistically different when compared with those in the control group (width = 184.3 +/- 35.2 mum, microvessel density = 19.6 +/- 2.4). The nifedipine group showed the highest content of collagen (proportion of total stroma occupied by collagen, stained with Picro-Mallory) (nifedipine group = 66.3 +/- 9.4, cyclosporin group = 55.2 +/- 7.9, control group = 30.1 +/- 10.2). Freshly cultured fibroblasts from the cyclosporin group exhibited higher ratiometric values of fluorescence than did both the control and nifedipine groups (p = 0.03). Our results support the hypothesis that changes in gingival collagen metabolism are not mediated by calcium intracellular oscillations.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/metabolismo , Colágeno/metabolismo , Ciclosporina/farmacologia , Gengiva/efeitos dos fármacos , Crescimento Excessivo da Gengiva/metabolismo , Imunossupressores/farmacologia , Nifedipino/farmacologia , Animais , Cálcio/análise , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Gengiva/irrigação sanguínea , Gengiva/citologia , Gengiva/metabolismo , Crescimento Excessivo da Gengiva/induzido quimicamente , Masculino , Microcirculação/efeitos dos fármacos , Distribuição Aleatória , Ratos
16.
Int J Immunopathol Pharmacol ; 20(2): 325-33, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17624244

RESUMO

Cells with a dendritic morphology and/or expression of dendritic cell (DC) markers have been repeatedly described in several human tumors, but the distribution and density of melanoma-associated DCs have not yet been reported. The aim of the present study is to analyze the density and topographical distribution of melanoma-associated DCs and their relation with CD3(+), CD4(+) and CD8(+) T lymphocytes in forty cases of cutaneous human melanoma. In melanocytic tumours different pools of DCs were recognised in the epidermis and in the dermis, particularly in intimate relation with lymphocyte clusters inside the melanocytic proliferation, and more often at the edges of tumours. The number of Langerin-positive DCs showed an inverse correlation with tumour depth (correlation coefficient r= -0.59, P=0.0001) and was significantly lower in thick melanomas compared to thin and intermediate ones (P<0.0005). The density of CD83(+) DCs was significantly lower in thick melanomas compared to thin and intermediate ones (P<0.009). A significant correlation was found between the density of the two DCs subsets (r=0.57, p<0.0001). The number of CD3(+) lymphocytes was inversely correlated to the depth of infiltration (r=-0.596, P<0.0001): melanoma cases with II-III Clark level showed a higher T lymphocyte mean density compared to cases with IV-V Clark level (P<0.0001). T lymphocyte density was significantly lower in thick melanomas compared to thin and intermediate melanomas (P<0.0005). In conclusion, our study indicates a progressive loss of DCs and T lymphocytes in the neoplastic progression of melanomas; further identification of the molecular pathways involved in the functional impairment of these immunitary cells may lead to new immunotherapeutic approaches for melanoma patients that would improve the clinical outcome of the patients.


Assuntos
Células Dendríticas/patologia , Melanoma/patologia , Antígenos CD/biossíntese , Antígenos CD/genética , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Humanos , Imunoglobulinas/biossíntese , Imunoglobulinas/genética , Imuno-Histoquímica , Lectinas Tipo C/biossíntese , Lectinas Tipo C/genética , Masculino , Lectinas de Ligação a Manose/biossíntese , Lectinas de Ligação a Manose/genética , Melanoma/imunologia , Melanoma/metabolismo , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Antígeno CD83
18.
Int J Immunopathol Pharmacol ; 19(4): 751-60, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17166397

RESUMO

Psoriasis is a chronic skin disease, characterized by epidermal hyperplasia, inflammation, angiogenesis and vascular remodelling. An immunohistochemical study on fifteen cryosections of psoriatic skin was performed using antibodies against VEGF, HIF1-alpha, CD34, Factor VIII, MMP-2, MMP-9, TIMP-1 and TIMP-2. Psoriatic skin showed a diffuse VEGF positive staining (13.15+/-6.6), while no expression was observed in normal epidermis. No or faint HIF-1alpha immunostaining was detected in healthy skin, while in psoriatic skin HIF-1alpha was diffusely expressed. A positive correlation between HIF-1alpha and VEGF was reported in psoriatic skin (r= 0.644; p=0.010). In psoriatic sections CD34 expression was significantly higher in respect to control skin (19.15+/-12.61 vs 3.0+/-0.23; p= 0.04), factor VIII immunostaining also demonstrated a significant increased development of the microvasculature in comparison with healthy skin (18.39+/-8.16 vs 7.4+/-0.20; p= 0.033). Total MMP-2 expression of healthy skin (30+/-2.26) was significantly lower in respect to the MMP-2 psoriatic skin (71.5+/-4.13; p= 0.0001) and a positive correlation was observed between VEGF and MMP-2 in psoriatic patients (r= 0.688; p= 0.046). In psoriatic skin MMP-9 expression was significantly increased in comparison to control skin (31+/-3.3 vs 8+/-6.1; p=0.007). All cases of psoriatic skin tissue showed that TIMP-2 and TIMP-1 expression statistically decreased in psoriatic skin (respectively 11+/-1.2 and 12+/-1.5) in comparison with healthy skin (respectively 15+/-3.2 and 53+/-3.8; p=0.0001). In conclusion, we observed that VEGF overexpression correlated with HIF-1alpha and MMP-2 expression, underlining the role of VEGF in psoriasis as a key factor in the link between inflammation and angiogenesis.


Assuntos
Inflamação/fisiopatologia , Neovascularização Patológica , Psoríase/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Adulto , Antígenos CD34/fisiologia , Fator VIII/fisiologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Imuno-Histoquímica , Metaloproteinases da Matriz/fisiologia
19.
Int J Immunopathol Pharmacol ; 19(2): 421-31, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16831308

RESUMO

This study correlates bone marrow changes after Rituximab (RTX) treatment with the clinical characteristics and outcome of 26 patients with small B-cell lymphomas. The percentage, phenotypic profile and clonality pattern of bone marrow lymphoid infiltrate were analysed before and after RTX treatment. Clinical, histological and molecular responses to RTX were correlated to the clinical outcome of the patients. Sixteen out of twenty-six patients obtained a complete clinical remission (CR). A favourable histology--follicular lymphoma (FL), hairy cell leukaemia (HCL) and marginal zone lymphoma (MZL)--was associated with a higher frequency of clinical CR and histological remission (HR), in comparison with mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL) and lymphoplasmacytic lymphoma (LPL). Two patterns of bone marrow HR were observed: 1) complete lymphoid cell disappearance (9 patients); or 2) nodular/interstitial T-cell infiltration (10 patients). Three histological persistence (HP) patterns were observed: 1) persistence of CD20+ small lymphoid cells in 1 patient with MCL; 2) loss of CD20 antigen expression in 4 patients with CLL; or 3) persistence only of clusters of monotypic plasma cells in 2 patients with LPL. CR and HR were strongly correlated. The percentage of lymphomatous infiltrate after RTX was higher in patients who subsequently died of the disease. Molecular response showed no correlations with the further clinical course in 12 patients achieving a complete clinical remission. In conclusion, bone marrow morphological and immunohistochemical analysis with a restricted panel of antibodies is useful to avoid 42% false positive and 85% false negative interpretations. Persistence of monoclonality after RTX might have a role in evaluating the molecular pattern of CD20-negative clones that can emerge after RTX as a tumoral escape to therapy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Medula Óssea/metabolismo , Medula Óssea/patologia , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Adulto , Idoso , Anticorpos Monoclonais Murinos , Clonagem Molecular , Feminino , Seguimentos , Humanos , Linfócitos/imunologia , Linfoma de Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rituximab , Resultado do Tratamento
20.
Int J Immunopathol Pharmacol ; 18(3 Suppl): 33-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16848985

RESUMO

The molecular mechanisms involved in the development of oral squamous cell carcinomas (OSCC) are not yet well understood. Evidence of recent studies suggests that aberrant beta-catenin signalling may participate in the neoplastic transformation and that it is implicated in the development of several tumours. Beta-catenin is a component of the catenin family and plays a crucial role in cadherin mediated cell adhesion. However, it has recently been shown that beta-catenin is also involved in other functions such as intracellular signalling and the regulation of gene transcription. The aim of this study is to evaluate the presence of mutation in exon 3 of the beta-catenin gene in 20 OSCC cell lines. DNA was extracted using Qiagen Qiamp DNA minikit and a region encompassing the exon 3 of beta-catenin gene was amplified using a single PCR assay. The PCR products were analysed by SSCP and direct sequencing to detect any mutation of the gene. Most of the cell lines examined showed, by immunofluorescence, a beta-catenin delocalization. SSCP and sequence analysis of the PCR products did not show any mutation of the beta-catenin gene in any of the cell lines. In conclusion, although aberrant expressions or abnormal localization of beta-catenin have been detected in several OSCC cells, it appears that this finding has no relationship with beta-catenin gene mutations.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Mutação , beta Catenina/genética , Linhagem Celular Tumoral , Éxons , Humanos
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