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1.
Cells ; 13(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38891095

RESUMO

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30). CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS. Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Linfócitos do Interstício Tumoral , Neoplasias Cutâneas , Células Th1 , Células Th17 , Humanos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Células Th17/imunologia , Linfócitos do Interstício Tumoral/imunologia , Células Th1/imunologia , Carcinoma Basocelular/imunologia , Carcinoma Basocelular/patologia , Feminino , Masculino , Idoso , Estudos Transversais , Pessoa de Meia-Idade , Linfócitos T CD8-Positivos/imunologia , Idoso de 80 Anos ou mais , Adulto
3.
Photochem Photobiol ; 87(6): 1427-32, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21824151

RESUMO

As previously described, Psoralen plus UVA (PUVA) therapy induces chromosome damage in psoriatic patients. This study evaluates whether these effects are transitory or persistent. In addition, we studied these effects after narrowband UVB (nUVB) and anti-tumor necrosis factor (TNF)-α treatments. Among 40 responder patients, 10 received PUVA, 10 nUVB, 10 Infliximab and 10 Etanercept. Disease activity was determined with Psoriasis Area and Severity Index. Chromosomal breakage was evaluated by the clastogenic factor (CF) test. Potential clastogenic agents, malondialdehyde (MDA) and TNF-α were measured. Before treatment, the plasma-adjusted clastogenic scores (ACS) of patients were increased. During treatment, a further increase in ACS was observed in both phototherapy groups. Chromosome damage persisted for PUVA patients at week 32, while it diminished after nUVB to ACS values lower than before treatment. MDA and TNF-α values were also increased at baseline. MDA decreased during treatment in all groups, but without reaching normal levels. Plasma TNF-α remained unchanged in PUVA and nUVB but decreased in both anti-TNF-α treatment groups. Psoriasis is accompanied by CF-induced chromosomal breakage that increases during PUVA and nUVB treatments. Plasma clastogenic activity persisted in the follow-up after PUVA, while after nUVB ACS returned to values even lower than baseline. Clastogenic activity during the induction phase with anti-TNF-α remained unchanged.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunoglobulina G/uso terapêutico , Fototerapia , Psoríase/terapia , Receptores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Etanercepte , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico
4.
Mov Disord ; 22(10): 1471-1475, 2007 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-17516496

RESUMO

Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies.


Assuntos
Doença de Parkinson/fisiopatologia , Lesões Pré-Cancerosas/fisiopatologia , Neoplasias Cutâneas/fisiopatologia , Idoso , Estudos de Casos e Controles , Intervalos de Confiança , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Inquéritos e Questionários
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