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1.
Br J Haematol ; 181(4): 476-485, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29663325

RESUMO

Growth hormone-releasing hormone (GHRH) is secreted by the hypothalamus and acts on the pituitary gland to stimulate the release of growth hormone (GH). GHRH can also be produced by human cancers, in which it functions as an autocrine/paracrine growth factor. We have previously shown that synthetic antagonistic analogues of GHRH are able to successfully suppress the growth of 60 different human cancer cell lines representing over 20 cancers. Nevertheless, the expression of GHRH and its receptors in leukaemias has never been examined. Our study demonstrates the presence of GHRH receptor (GHRH-R) on 3 of 4 human acute myeloid leukaemia (AML) cell lines-K-562, THP-1, and KG-1a-and significant inhibition of proliferation of these three cell lines in vitro following incubation with the GHRH antagonist MIA-602. We further show that this inhibition of proliferation is associated with the upregulation of pro-apoptotic genes and inhibition of Akt signalling in leukaemic cells. Treatment with MIA-602 of mice bearing xenografts of these human AML cell lines drastically reduced tumour growth. The expression of GHRH-R was further confirmed in 9 of 9 samples from patients with AML. These findings offer a new therapeutic approach to this malignancy and suggest a possible role of GHRH-R signalling in the pathology of AML.


Assuntos
Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Receptores de Neuropeptídeos/antagonistas & inibidores , Receptores de Hormônios Reguladores de Hormônio Hipofisário/antagonistas & inibidores , Sermorelina/análogos & derivados , Transdução de Sinais/efeitos dos fármacos , Animais , Feminino , Humanos , Células K562 , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sermorelina/farmacologia , Células THP-1 , Ensaios Antitumorais Modelo de Xenoenxerto
2.
J Investig Dermatol Symp Proc ; 19(1): S25-S31, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29273101

RESUMO

Alopecia areata (AA) is an autoimmune disorder characterized by T lymphocytic infiltrates around the bulbar region of hair follicles. Statins have surfaced as potential therapeutic agents for AA, partly because of their modulation of the JAK/STAT pathway. Some data indicate that statins are a possible option for acute, but not chronic, longstanding AA. Animal studies suggest that treatment with statins increases CD4+/CD25+/Foxp3+ populations in AA-affected mice.


Assuntos
Alopecia em Áreas/tratamento farmacológico , Combinação Ezetimiba e Simvastatina/uso terapêutico , Alopecia em Áreas/imunologia , Animais , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Citocinas/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Camundongos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
3.
Lasers Surg Med ; 49(1): 27-39, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27114071

RESUMO

BACKGROUND AND OBJECTIVES: Androgenetic alopecia (AGA) affects 50% of males by age 50 and 50% of females by age 80. Recently, the use of low-level laser therapy (LLLT) has been proposed as a treatment for hair loss and to stimulate hair regrowth in AGA. This paper aims to review the existing research studies to determine whether LLLT is an effective therapy for AGA based on objective measurements and patient satisfaction. STUDY DESIGN: A systematic literature review was done to identify articles on Medline, Google Scholar, and Embase that were published between January 1960 and November 2015. All search hits were screened by two reviewers and examined for relevant abstracts and titles. Articles were divided based on study design and assessed for risk of bias. RESULTS: Eleven studies were evaluated, which investigated a total of 680 patients, consisting of 444 males and 236 females. Nine out of 11 studies assessing hair count/hair density found statistically significant improvements in both males and females following LLLT treatment. Additionally, hair thickness and tensile strength significantly improved in two out of four studies. Patient satisfaction was investigated in five studies, and was overall positive, though not as profound as the objective outcomes. CONCLUSION: The majority of studies covered in this review found an overall improvement in hair regrowth, thickness, and patient satisfaction following LLLT therapy. Although we should be cautious when interpreting these findings, LLLT therapy seems to be a promising monotherapy for AGA and may serve as an effective alternative for individuals unwilling to use medical therapy or undergo surgical options. Lasers Surg. Med. 49:27-39, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Alopecia/radioterapia , Cabelo/efeitos da radiação , Terapia com Luz de Baixa Intensidade/métodos , Satisfação do Paciente/estatística & dados numéricos , Adulto , Alopecia/diagnóstico , Estética , Feminino , Cabelo/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
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