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Ortega, Rose Mara 1974. "Análise dos mecanismos antiproliferativos decorrentes da inibição farmacológica da enzima ácido graxo sintase em células de melanoma murino B16-F10 : resultados in vitro e in vivo." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289497.
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Orientadores: Karina Gottardello Zecchin, Edgard GranerTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Ácido graxo sintase (FASN - fatty acid synthase, EC 2.3.1.85) é a enzima metabólica responsável pela síntese endógena do ácido graxo saturado palmitato, a partir dos precursores acetil-CoA e malonil-CoA. Diversos estudos mostram que, em contraste com a maioria das células normais, FASN é altamente expressa em vários tipos de neoplasias malignas humanas, tais como as de próstata, mama e melanoma sendo que, em alguns destes tumores, a alta expressão de FASN está associada a um pior prognóstico. A inibição da enzima FASN resulta em inibição da proliferação e induz morte celular em diversas neoplasias malignas. Recentemente demonstramos que, in vitro, a inibição específica da atividade de FASN em linhagem celular de melanoma murino, B16-F10, induz a via intrínseca da apoptose, com liberação de citocromo c e ativação de caspase-3, assim como altera a composição dos ácidos graxos livres presentes nas mitocôndrias das células B16-F10. O objetivo deste trabalho foi investigar de que maneira a inibição farmacológica de FASN reduz a proliferação de células B16-F10, in vitro e in vivo, utilizando C75 como inibidor de FASN. O tratamento de células e animais com C75 reduziu significativamente a proliferação celular e induziu apoptose. Houve significativa redução de células na fase S do ciclo celular, com acúmulo de células de G0/G1, em comparação com os controles. Western blottings feitos a partir de extratos de células em cultura e de tumores intraperitoneais mostraram aumento de p21WAF1/Cip1, p27Kip1, redução de Skp2 e cdk2, sem mudanças nos níveis de cdk4, 6 e ciclina E após tratamento com C75. A especifidade destes resultados foi confirmada pela redução da atividade enzimática de FASN após tratamento com C75 e pelo silenciamento de FASN com RNAi. Efeito anti-tumoral de C75 foi sugerido pela formação de tumores subcutâneos de menor volume quando comparados aos tumores de animais controle. Nossos achados mostram que a proliferação de células de melanoma é dependente de FASN, e que sua inibição primeiramente altera os níveis de proteínas envolvidas na transição de G1 para S, para posteriormente induzir apoptose em células de melanoma B16-F10
Abstract: Fatty acid synthase (FASN) is the metabolic enzyme responsible for the endogenous synthesis of the saturated long-chain fatty acid palmitate, from the precursors acetyl-CoA and malonyl-CoA. In contrast to most normal cells, the overexpression of FASN in several human malignancies, such as those of prostate, breast, ovary, melanoma, and soft tissue sarcomas has been associated with poor prognosis. FASN inhibition reduces cell proliferation by blocking DNA replication during S-phase, and induces apoptosis in several malignant neoplasias. We have previously shown that the specific inhibition of FASN activity significantly reduce proliferation and promote apoptosis, as demonstrated by the cytochrome c release and caspase-9 and -3 activation, as well as induces signi?cant changes in the free fatty acids composition of B16-F10 cells mitochondria. Here we investigated the events involved in cell cycle arrest subsequent to FASN inhibition with C75. C75 treatment significantly reduced melanoma cells proliferation and induced apoptosis in vitro and in mice. Cell cycle arrest after C75 treatment was evidenced by a significant increase in G0/G1 phase, as well as decline of the S phase, in comparison with untreated cells. Western blotting analysis showed significant accumulations of the tumor suppressor proteins p21WAF1/Cip1 and p27Kip1, together with decreased amounts of Skp2, essential for the proteasomal degradation of p27Kip1, and cdk2, a Ser/Thr protein kinase necessary for the G1/S transition, in C75-treated cells or mice tumors. The levels of other proteins involved in G1/S cell cycle progression, such as cyclin E, cdk4, and cdk6 were not affected by FASN inhibition. These results were confirmed by inhibition of FASN activity after C75 treatment and by RNAi for FASN. Antitumoral effect of C75 was suggested by reduced subcutaneous tumors volume when compared to controls mice. Our results suggest that melanoma murine B16-F10 cells proliferation is dependent on FASN activity, and its inhibition first modify the levels of some proteins involved in the transition G1?S of cell cycle, to finally induce apoptosis in neoplasic cells
Doutorado
Estomatologia
Doutora em Estomatopatologia
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Haridas, Parvathi. "In vitro characterisation of melanoma progression in a melanoma skin equivalent model." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/118574/1/Parvathi_Haridas_Thesis.pdf.
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Melanoma is a fatal form of skin cancer which progresses in an orchestrated pattern in human skin. Characterising these phases of melanoma in vitro can provide key insights into mechanisms of the disease progression. In this thesis, we investigate how in vitro three-dimensional (3D) model assays that recapitulate human skin can be used to identify key features underlying melanoma progression. In particular, we construct a 3D melanoma skin equivalent model using melanoma cells from the early and late phase of the disease. We further quantify melanoma cell migration, proliferation, invasion, as well as melanoma nest formation.
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SIPES, NANCY JO. "GROWTH REGULATION OF HUMAN MELANOMA: FACTORS INVOLVED IN THE EXPRESSION OF THE TRANSFORMED PHENOTYPE (SOFT AGAR, GROWTH FACTORS, PLATELETS, ENDOTHELIAL CELLS, PARACRINE)." Diss., The University of Arizona, 1986. http://hdl.handle.net/10150/183788.
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Cellular transformation is accomplished in vitro through the concerted action of growth factors and oncogenes. This association has demonstrated that malignant growth results from aberrations in pathways that normally operate to control proliferation. Activation of genes that code for growth factors, their receptors, and/or molecules essential in the transduction of signals from the cell surface to the nucleus are all potential mechanisms by which tumor cells could establish a selective growth advantage over normal cells. This dissertation addresses the question of what oncogenic mechanisms are important in the development and progression of human melanoma. These studies show that melanoma growth is regulated by endogenous substances produced by the melanoma cells themselves (autocrine stimulation), as well as by exogenous substances supplied by neighboring cells and platelets (paracrine stimulation). These factors work to drive the expression of the transformed phenotype for melanoma as evidenced by induction of serum-free soft agar growth. Human platelets were found to the the richest source of paracrine growth promoters. The factor from human platelets was characterized and partially purified. Melanoma cells respond to this 60,000 molecular weight, disulfide-bond-containing protein in colony formation assays. In addition, the protein has endothelial cell growth factor activity. Purified fractions which promoted optimal colony formation for human melanoma cells also maximally stimulated monolayer growth of bovine aortic endothelial cells, while melanocytes were nonresponsive. This implies that melanoma cells are expressing receptors for a protein which plays no known or apparent role in the normal growth of melanocytes. Melanoma cells are sensitive to growth regulatory molecules of autocrine and paracrine nature. This dissertation provides clues to the genetic lesions which have occurred in these melanoma cells to influence their proliferation. The aberrations appear to reside in those genes important in growth factor pathways at the level of endogenous production and misguided response to exogenous factors through receptor expression. We can not hope to fully inhibit the proliferation of tumor cells until we identify and understand those forces which drive their growth. These studies have increased our knowledge of those signals which stimulate melanoma cellular proliferation, and thus provide insight into important therapeutic targets.
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Petti, Carlotta. "Identification of molecular targets of oncogenic NRAs and BRAF involved in regulation of melanoma cell proliferation." Thesis, Open University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437808.
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Stacy, Andrew Jared. "Regulation of ΔNp63α by TIP60 promotes cellular proliferation." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1596151919161674.
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Thieme, Sebastian, Sabine Stopp, Martin Bornhäuser, Fernando Ugarte, Manja Wobus, Matthias Kuhn, and Sebastian Brenner. "Expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells regulates proliferation, differentiation, and maintenance of hematopoietic stem and progenitor cells." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-178636.
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The melanoma cell adhesion molecule defines mesenchymal stromal cells in the human bone marrow that regenerate bone and establish a hematopoietic microenvironment in vivo. The role of the melanoma cell adhesion molecule in primary human mesenchymal stromal cells and the maintenance of hematopoietic stem and progenitor cells during ex vivo culture has not yet been demonstrated. We applied RNA interference or ectopic overexpression of the melanoma cell adhesion molecule in human mesenchymal stromal cells to evaluate the effect of the melanoma cell adhesion molecule on their proliferation and differentiation as well as its influence on co-cultivated hematopoietic stem and progenitor cells. Knockdown and overexpression of the melanoma cell adhesion molecule affected several characteristics of human mesenchymal stromal cells related to osteogenic differentiation, proliferation, and migration. Furthermore, knockdown of the melanoma cell adhesion molecule in human mesenchymal stromal cells stimulated the proliferation of hematopoietic stem and progenitor cells, and strongly reduced the formation of long-term culture-initiating cells. In contrast, melanoma cell adhesion molecule-overexpressing human mesenchymal stromal cells provided a supportive microenvironment for hematopoietic stem and progenitor cells. Expression of the melanoma cell adhesion molecule increased the adhesion of hematopoietic stem and progenitor cells to human mesenchymal stromal cells and their migration beneath the monolayer of human mesenchymal stromal cells. Our results demonstrate that the expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells determines their fate and regulates the maintenance of hematopoietic stem and progenitor cells through direct cell-cell contact.
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Thieme, Sebastian, Sabine Stopp, Martin Bornhäuser, Fernando Ugarte, Manja Wobus, Matthias Kuhn, and Sebastian Brenner. "Expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells regulates proliferation, differentiation, and maintenance of hematopoietic stem and progenitor cells." Ferrata Storti Foundation, 2013. https://tud.qucosa.de/id/qucosa%3A28908.
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The melanoma cell adhesion molecule defines mesenchymal stromal cells in the human bone marrow that regenerate bone and establish a hematopoietic microenvironment in vivo. The role of the melanoma cell adhesion molecule in primary human mesenchymal stromal cells and the maintenance of hematopoietic stem and progenitor cells during ex vivo culture has not yet been demonstrated. We applied RNA interference or ectopic overexpression of the melanoma cell adhesion molecule in human mesenchymal stromal cells to evaluate the effect of the melanoma cell adhesion molecule on their proliferation and differentiation as well as its influence on co-cultivated hematopoietic stem and progenitor cells. Knockdown and overexpression of the melanoma cell adhesion molecule affected several characteristics of human mesenchymal stromal cells related to osteogenic differentiation, proliferation, and migration. Furthermore, knockdown of the melanoma cell adhesion molecule in human mesenchymal stromal cells stimulated the proliferation of hematopoietic stem and progenitor cells, and strongly reduced the formation of long-term culture-initiating cells. In contrast, melanoma cell adhesion molecule-overexpressing human mesenchymal stromal cells provided a supportive microenvironment for hematopoietic stem and progenitor cells. Expression of the melanoma cell adhesion molecule increased the adhesion of hematopoietic stem and progenitor cells to human mesenchymal stromal cells and their migration beneath the monolayer of human mesenchymal stromal cells. Our results demonstrate that the expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells determines their fate and regulates the maintenance of hematopoietic stem and progenitor cells through direct cell-cell contact.
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Cardim, Sílvia Guedes Braga. "Vesículas extracelulares liberadas pelas células cancerosas modulam a proliferação, morte e migração celular no melanoma humano?" Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-15122017-083004/.
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As células que compõem o tumor podem interagir entre si, através da liberação e incorporação de vesículas extracelulares, muitas vezes contribuindo para a progressão tumoral. Dessa maneira, o presente trabalho teve como objetivo observar se as vesículas extracelulares , como as microvesículas e os exossomas liberados pelas células cancerosas em condições de estresse celular, após quimioterapia e indução de hipóxia conferem alguma vantagem adaptativa às células tumorais. Nossos resultados mostram que vesículas liberadas por células de melanoma humano em hipóxia ou normóxia apresentam tamanho médio característico de exossomos e microvesículas e não modulam os processos de proliferação, morte e migração celular. As vesículas liberadas pelas células após tratamento com o quimioterápico temozolamida também apresentam tamanho característico de exossomos e microvesículas; em adição, o tratamento com a temozolamida induziu um aumento na secreção dessas vesículas pelas células de melanoma. A incubação das células tumorais com vesículas oriundas da terapêutica com a temozolamida aumentou a proliferação celular, conferindo vantagem proliferativa às células de melanoma humanoTumor cells can interact with each other by releasing and incorporating extracellular vesicles, contributing to tumor progression. Therefore, the aim of this study was to evaluate if extracellular vesicles, such as microvesicles and exossomes, released by cancer cells under cell stress conditions like chemotherapy and hypoxia, induce an adaptive advantage to tumor cells. Our results show that vesicles shed by human melanoma cells under hypoxia, or normoxia exhibit the characteristic size of exossomes and microvesicles and do not modulate cell proliferation, death or migration. The vesicles released by melanoma cells after temozolomide treatment also showed the average size of exossomes and microvesicles; moreover, temozolomide treatment induced an increase in extracellular vesicles shedding by tumor cells. Incubation of tumor cells with vesicles released under temozolamide therapeutics caused an increase in cell proliferation, providing a proliferative advantage to human melanoma cells
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Huang, Jie Min. "An amentoflavone derivative induces apoptosis and interferes with cell proliferation in melanoma by inhibition of the JAK2STAT3 signaling pathway." Thesis, University of Macau, 2017. http://umaclib3.umac.mo/record=b3690910.
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Abrantes, Julia Laura Fernandes 1984. "Expressão ectópica de miR-34a em células de melanoma metastático humano = efeitos sobre vias de sinalização relacionadas com sobrevivência, proliferação e morte celular = Ectopic expression of miR-34a in human metastatic melanoma cells: effects on signaling pathways related to survival, proliferation and cell death." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314040.
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Orientador: Carmen Veríssima Ferreira HalderTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: O melanoma é o tipo mais agressivo de câncer de pele. Seu tratamento permanece como um grande desafio, já que em estágio avançado torna-se extremamente refratário aos tratamentos convencionais. miR-34a é um microRNA supressor de tumor com expressão normalmente reduzida em células cancerosas. A fim de investigar o papel de miR-34a como supressor do melanoma, o principal objetivo deste estudo foi identificar alvos moleculares modulados pela expressão ectópica de miR-34a na linhagem celular de melanoma metastático humano SK-mel-103. miR-34a reduziu significativamente a viabilidade das células de melanoma, o que deve estar relacionado, pelo menos em parte, com o aumento na expressão da proteína pró-apoptótica Bax, ativação da caspase-3 e clivagem da PARP-1. Estes dados sugerem que miR-34a foi capaz de induzir apoptose nas células de melanoma. Além disso, houve redução na expressão de CDK4, CDK6, E2F3 e pRb, proteínas relacionadas com a progressão do ciclo celular. Aumento na expressão de p21, um inibidor de CDKs, também foi observado nessas células. Algumas moléculaschave envolvidas com os processos de proliferação celular e apoptose, como proteínas oncogênicas (Axl, AKT, ERK 1/2, ?-catenina e c-myc) e proteínas supressoras de tumor (p53 e PTEN), foram "down- e upreguladas" por miR-34a, respectivamente. Interessantemente, o fluxo autofágico foi aumentado por miR-34a, efeito que não foi correlacionado com alterações adicionais na viabilidade das células de melanoma. O aumento no fluxo autofágico ocorreu, provavelmente, como uma resposta celular ao estresse de retículo e a agregação de proteínas induzidos por miR-34a, fenômenos que também podem ter contribuído para a indução de apoptose nesse contexto. Os dados obtidos neste estudo trouxeram novos aspectos moleculares da ação de miR-34a como supressor tumoral, e permitem apontar este microRNA como um potencial alvo terapêutico contra o melanoma metastático humano
Abstract: Melanoma is the most aggressive form of skin cancer. Its treatment remains a big challenge, since in advanced stage it is extremely refractory to conventional treatments. miR-34a has emerged as an important tumor suppressor, and its expression is normally reduced in cancer cells. To provide more information about the role of miR-34a as a melanoma suppressor, the main goal of this study was to identify key molecular players modulated by ectopic expression of this microRNA in the metastatic melanoma cell line SK-mel-103. miR-34a caused a reduction of melanoma cells viability, what may be related, at least in part, with the increased expression of pro-apoptotic marker, Bax, activation of caspase 3 and PARP-1 cleavage, which indicates that miR-34a triggered apoptosis in melanoma cells. In addition, the expression of CDK4, CDK6, E2F3 and pRb, proteins related to the cell cycle progression, was reduced. An increase in p21 expression, a CDK inhibitor, was also detected in these cells. Some key molecules involved with proliferation and apoptosis processes, such as oncogenic proteins (Axl, AKT, ERK 1/2 kinases, ?- catenin and c-myc) and tumor suppressor proteins (p53 and PTEN), were down- and upregulated by miR-34a, respectively. Interestingly, the autophagic flux was stimulated by miR-34a, but this effect was not correlated with further alterations in cell viability. The increased autophagy occurred probably as a cellular response against the reticulum stress and the protein aggregation induced by miR-34a in melanoma cells, which can also be contributing to the cell death by apoptosis in this context. Our findings brought up novel molecular aspects about the role of miR-34a as melanoma suppressor. The broad action of this microRNA on key molecular players of melanoma aggressiveness was crucial for reprogramming these cells in favor of apoptosis. Altogether, this study pointed out miR-34a as a potential therapeutic agent against advanced melanoma
Doutorado
Bioquimica
Doutora em Biologia Funcional e Molecular
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Passos, Luis Augusto Abreu da Cunha. "A sinalização do co-ativador de transcrição PGC-1beta e sua relevância para a proliferação celular e desenvolvimento de melanoma." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5165/tde-31032015-162021/.
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PGC-1 beta é um co-ativador de transcrição gênica responsável pela regulação do metabolismo celular, principalmente na biogênese e função mitocondrial, disponibilidade de substrato e síntese de lipídios. Nos últimos anos, outras isoformas de PGC-1 têm sido descritos como participantes na gênese e manutenção de tumores. Portanto, nosso objetivo foi determinar se o PGC-1beta está relacionado ao aumento da proliferação celular de células de melanoma. Inicialmente, foi demonstrado que os níveis de RNAm e proteína de PGC-1beta são muito mais elevados em linhagens de células de melanoma (Tm1 e Tm5) do que na linhagem parental de melanócitos não tumorais (Melan-a) como detectado por PCR quantitativa e western blotting. A fim de descobrir uma relação causal entre a expressão de PGC-1? e crescimento celular da linhagem Tm5, células de tal linhagem foram transfectadas com um oligonucleotídeo antisense (ASO) contra PGC-1beta. As células tratados com ASO apresentaram níveis mais baixos de RNAm e proteína PGC-1beta, além de redução em sua atividade avaliada pela expressão de genes PGC-1beta dependentes. Além disso, as células transfectadas apresentaram uma taxa de proliferação inferior em comparação com células de controle Tm5. Este fenômeno também foi observado in vivo. Quando injetadas em camundongos, as células Tm5 desenvolvem-se em um tumor que atinge 1,34 ± 0,20 cm3 após nove dias. Tumores tratados com ASO após o mesmo tempo apresentaram volume tumoral de 0,75 ± 0,05 cm3. Este crescimento não estava relacionada à necrose tumoral, mas sim com a proliferação reduzida de células. Finalmente, verificamos se o mesmo fenômeno seria observado em humanos. A expressão PGC-1beta foi muito maior em amostras de melanoma do que em nevos, alterações não-malignas da pele com alto conteúdo de melanina. Por conseguinte, conclui-se que a expressão PGC-1? está aumentada no melanoma, tanto murino e humano, e que o bloqueio da sua atividade leva à diminuição da proliferação celular e crescimento tumoralPGC-1beta is a co-activator of gene transcription primarily responsible for the regulation of cellular metabolism, mainly in mitochondrial biogenesis and function and also substrate and lipid synthesis. In recent years, other isoforms of PGC-1 have been described as participating in the genesis and maintenance of tumors. Therefore, our objective was to determine whether PGC-1beta is related to increased proliferation of melanoma cells. Initially, it was demonstrated that mRNA and protein levels of PGC-1beta are much higher in melanoma cell lines (Tm1 and TM5) than in the non-tumoral parental lineage melanocytes (melan-a) as detected by quantitative PCR and Western blotting. In order to find a causal relationship between the expression of PGC-1beta and cell growth, Tm5 lineage cells were transfected with an antisense oligonucleotide (ASO) against PGC-1beta. The cells treated with ASO had lower levels of PGC-1beta mRNA and protein, as well as reduction in its activity detected by quantitation of PGC-1beta dependent genes expression. Furthermore, transfected cells showed a lower rate of proliferation compared to Tm5control cells. This phenomenon was also observed in vivo. When injected into mice, Tm5 cells develop a tumor which reaches 1.34 ± 0.20 cm3 after nine days. Tumors treated with ASO, after the same time, presented tumor volume of 0.75 ± 0.05 cm 3. This growth was not related to tumor necrosis, but with reduced cell proliferation. Finally, we checked whether the same phenomenon would be observed in humans. The PGC-1beta expression was much higher in melanoma samples than in nevi, a non-malignant skin alteration filled with melanin. Therefore, we concluded that PGC-1beta expression in melanoma is increased, both in murine and human, and that blocking its activity leads to decreased cell proliferation and tumor growth
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Azevedo, Ricardo Alexandre de. "Avaliação da atividade proliferativa, antitumoral e hematológica dos peptídeos derivados da caseína INKKI e YPVEPFTE no melanoma experimental." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-14082009-093334/.
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Os peptídeos INKKI e YPVQPFTE foram isolados a partir da hidrólise da b-caseína bovina e correspondem às seqüências 26-30 e 114-121 respectivamente. A atividade proliferativa foi avaliada em culturas primárias de linfócitos T. A atividade antitumoral in vitro foi realizada em culturas de B16F10. Foi utilizado grupo com 40 camundongos da linhagem C57BL/6J para avaliar a atividade antitumoral. Nossos resultados mostraram que o peptídeo INKKI apresentou resposta proliferativa semelhante ao mitógeno comercial PHA. O peptídeo YPVEPFTE mostrou ter ação proliferativa maior do que a apresentada pelo mitógeno comercial PHA. O peptídeo INKKI mostrou ação quimiotáxica. O tratamento in vitro mostrou que somente o pentapeptídeo INKKI induz seletiva atividade citotóxica para as células de melanoma. Os animais portadores de tumores dorsais apresentaram significativa inibição da capacidade de crescimento e a metastatização. Conclui-se que os peptídeos apresentam ação significativa tanto nos experimentos in vitro como in vivo sugerindo um possível papel fisiológico.Peptides INKKI and YPVQPFTE were isolated from the bovine b-casein after hydrolysis corresponding to the 23-30 and 114-121 sequence, respectively. Evaluation of the proliferative activity in primary cultures of lymphocytes. The activity antitumor in vitro was accomplished culture of was studied. Groups with 40 C57BL/6J lines mice had been used to evaluate the antitumoral activity. Our results showed that peptide presented similar proliferative response to the PHA commercial mitogen. The peptide YPVEPFTE showed to have proliferative action larger than presented by the commercial mitogen. The peptide INKKI showed in the chemotactic action. The treatment in vitro had shows that the peptide INKKI induces selective citotoxicity. The bearing animals of dorsal tumors had presented significant inhibition of the capacity of growth and the spread of methastasis. Thus, the peptides casein present significant action in in vitro and in vivo experiments, suggesting a possible physiologic role.
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Vo, Brenda. "Novel likelihood-free Bayesian parameter estimation methods for stochastic models of collective cell spreading." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/99588/1/Brenda_Vo_Thesis.pdf.
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Biological processes underlying skin cancer growth and wound healing are governed by various collective cell spreading mechanisms. This thesis develops new statistical methods to provide key insights into the mechanisms driving the spread of cell populations such as motility, proliferation and cell-to-cell adhesion, using experimental data. The new methods allow us to precisely estimate the parameters of such mechanisms, quantify the associated uncertainty and investigate how these mechanisms are influenced by various factors. The thesis provides a useful tool to measure the efficacy of medical treatments that aim to influence the spread of cell populations.
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Lautenschlager, Willian Wagner. "Um modelo estocástico de simulação da dinâmica dos queratinócitos, melanócitos e melanomas no desenvolvimento dos tumores." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/100/100132/tde-21082017-174520/.
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Durante as últimas décadas, pesquisas em biologia do tumor com a utilização de novas técnicas de biologia molecular produziram informações em profusão, motivando e dando condições para que fossem criados novos modelos matemáticos dedicados à análise de vários aspectos de crescimento e proliferação da população celular. Alguns desses modelos têm sido dedicados à descrição e análise do regime estacionário do processo de desenvolvimento de uma população celular sob condições químicas que se consideram favorecer a aceleração ou desaceleração do crescimento da população de células tumorais. Todavia, a dinâmica temporal do crescimento de uma população de células tumorais ainda não foi analisada nesses trabalhos. Uma das dificuldades é o estabelecimento da interação entre células de múltiplos tipos que sirvam como descrição para essa dinâmica. Nosso trabalho vem preencher essa lacuna e a presente dissertação tem como objetivo a apresentação do modelo, desenvolvido por nós, de simulação da dinâmica do crescimento e proliferação celular do melanoma (câncer de baixa incidência, mas de letalidade extremamente alta) e também dos resultados obtidos através das simulações deste modelo computacionalDuring the last decades, tumor biology research with the use of new techniques in molecular biology resulted in a profusion of information that have given conditions and motivated the development of new mathematical models dedicated to analyzing various aspects of growth and proliferation of the cell population. Some of these models have been devoted to the description and analysis of the steady state of the development process of a cell population under chemical conditions that, in theory, promote the acceleration or deceleration of the growth of tumor cell population. However, these studies have not yet analyzed the temporal dynamics of growth of a tumor cell population. One of the difficulties is the establishment of the interaction between cells of multiple types that serve as the description for this dynamic. Our work fills this gap and this dissertation aims to present the model, developed by us, to simulate the growth dynamics and cellular proliferation of melanoma (cancer of low incidence but of extremely high lethality) and the results obtained through the simulations of this computational model
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Fedele, Thiago Antonio. "Análise metabolômica de animais portadores de melanoma murino B16F10 por espectroscopia de ressonância magnética nuclear (RMN)." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-22012013-165318/.
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O metaboloma é definido como a coleção qualitativa e quantitativa de todos os metabólitos de baixa massa molecular presentes nas células, os quais participam de reações bioquímicas necessárias para a manutenção, crescimento e fisiologia celular. A avaliação metabolômica permite o delineamento do processo bioquímico de sistemas a fim de ampliar o entendimento de como as patologias se manifestam. A Espectroscopia de Ressonância Magnética Nuclear (RMN) é usada para investigar uma variedade de processos biológicos em diversos sistemas. A magnética aplicada a células e biópsias de tecido intacto de melanoma murino B16F10 contribuiu para a caracterização bioquímica de biomarcadores das diferentes fases de progressão tumoral do melanoma murino B16F10. Os resultados obtidos neste estudo permitiram a identificação de 33 metabólitos possíveis, envolvidos na carga lipídica e no metabolismo secundário da via glicolítica, que favorecem o crescimento e a progressão tumoral. A presença da taurina, prolina, serina, fenilalanina, que aumentaram quantitativamente, são possíveis marcadores da invasão, progressão e metastatização. A análise quantitativa desses metabólitos mostrou diferença significativa em 11 compostos, dos quais 9 estão diretamente envolvidos na expressão das respostas proliferativas, de morte celular e angiogênese, nos diferentes períodos de crescimento do melanoma B16F10, avaliados neste estudo. Desta forma, os achados obtidos neste estudo, quando associados no futuro a outros fatores, poderão ser úteis no diagnóstico e auxiliar na escolha terapêutica alvo com maior especificidade e menores efeitos colaterais. RMN pode ter um importante impacto na monitorização de metabólitos em células e tecidos tumorais, possibilitando a detecção mais precoce de tumores malignos, em suma, através da combinação de métodos de ressonância magnética.The metabolome is defined as the qualitative and quantitative collection of all low weight molecular metabolites in cells that participate in biochemical reactions necessary for the maintenance, growth and physiology of cell. The metabolomic evaluation allows the design of systems of biochemical process in order to broaden the understanding of how diseases manifest. The Nuclear Magnetic Resonance Spectroscopy (NMR) is used for investigating a variety of biological processes in several systems. The magnetics applied to cell and tissue biopsies intact murine melanoma B16F10 contributed to the biochemical characterization of biomarkers of different stages of tumor progression of murine melanoma B16F10. The results obtained in this study allowed the identification of 33 potential metabolites involved in lipid content in the secondary metabolism of the glycolytic pathway, which promote growth and tumor progression. The presence of taurine, proline, serine, phenylalanine, which quantitatively increased, is possibly markers of invasion and metastasis progression. Quantitative analysis of these metabolites showed a significant difference in 11 compounds, of which 9 are directly involved in the expression of proliferative responses, cell death and angiogenesis in different periods of growth of B16F10 melanoma, evaluated in this study. Thus, the findings from this study, when associated in the future with other factors, may be useful in the diagnosis and may assist in choosing therapeutic target with greater specificity and fewer side effects. NMR may have a significant impact on monitoring metabolites in tumor cells and tissues, allowing for earlier detection of malignant tumors; in short, by combining MRI methods.
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Oliveira, Maria Theresa de [UNIFESP]. "O uso de interferência por RNA para a análise da função do gene E2F1 na progressão do ciclo celular em células tumorais." Universidade Federal de São Paulo (UNIFESP), 2010. http://repositorio.unifesp.br/handle/11600/9874.
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Publico-00376f.pdf: 1677823 bytes, checksum: d93d3b40f2c273e474e7fef525f351c8 (MD5)E2F1 pertence a uma família de fatores de transcrição e possui papel central no controle da expressão de genes relacionados à regulação da proliferação celular, pois ativa genes que participam da síntese de DNA. A atividade de E2F1 é regulada por meio da proteína pRB que, quando fosforilada por quinases associadas à ciclinas (Ciclinas/CDK) libera este fator de transcrição, promovendo assim a proliferação. A disfunção da complexa via de regulação da divisão celular pode acarretar em proliferação exacerbada, sendo a superexpressão de E2F1 bastante comum em diferentes tipos de tumores. Este fenômeno pode ser o principal fator para a alta proliferação de células tumorais. Desta forma, a inibição da atividade de E2F1 através de RNA de interferência (RNAi) pode ser promissora como tratamento para a diminuição da proliferação de células de melanoma. Assim sendo, objetiva-se neste trabalho inativar por RNAi o gene E2f1 em células B16mCAR, derivadas de melanoma de C57BL/6 e que superexpressam o receptor CAR, e averiguar os efeitos de sua ausência na proliferação celular, tanto in vitro como in vivo.
E2F1 belongs to a family of transcription factors and plays a central role in controlling the expression of genes related to regulation of the cell-cycle progression, since it activates genes involved in DNA synthesis. The activity of E2F1 is regulated by pRB protein, that when phosphorylated by cyclin-dependent kinases cyclins (Cyclins/CDK) releases this transcription factor, thereby promoting proliferation. The dysfunction of the complex regulatory pathway of cell division can lead to excessive proliferation, which overexpression of E2F1 is quite common in different types of tumors. This phenomenon may be the main factor for the high proliferation of tumor cells. Thus, inhibition of E2F1 activity by RNA interference (RNAi) may be promising as a treatment for decreased proliferation of melanoma cells. Therefore, the purpose of this work is the inactivation of the E2f1 gene through RNAi in B16mCAR cells, derived from C57BL/6’s melanoma and overexpresses the CAR receptor, and also verifies the effects of its absence on cell proliferation in vitro and in vivo.
TEDE
BV UNIFESP: Teses e dissertações
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Morales, Delphine. "Modèles 3D de mélanome métastatique pour l’évaluation in vitro de l’efficacité de molécules de thérapies ciblées." Thesis, Compiègne, 2019. http://www.theses.fr/2019COMP2498.
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La sensibilité des cellules de mélanomes aux molécules de thérapies ciblées dépend du microenvironnement tumoral (interactions cellule-cellule et cellule-matrice extracellulaire). Les systèmes tridimensionnels (3D) de culture in vitro reflètent mieux l’architecture structurelle native des tissus et sont attrayants pour l’étude des interactions cellulaires. Nous avons développé et comparé plusieurs modèles de mélanome métastatique : les cellules de mélanomes (SK-MEL-28 et SK-MEL-3, mutées BRAF V600E et SK-MEL-2, BRAF sauvages) cultivées en monocouche (2D) et co-cultivées en 3D sur des équivalents de derme avec des fibroblastes, afin de mieux comprendre les facteurs modulant la sensibilité cellulaire à un inhibiteur de BRAF (BRAFi, Vémurafenib) et au Vémurafenib associé à un inhibiteur de MEK (MEKi, Cobimetinib). La sensibilité cellulaire aux traitements a été évaluée sous différents aspects : prolifération cellulaire (numération cellulaire, incorporation d'EdU, test MTS), analyse des voies de signalisation MAPK et PKB / Akt (Western-blot), apoptose (TUNEL), libération de cytokines et de facteurs de croissance (ELISA) et histologie (modèles 3D). Un effet cytostatique de BRAFi a été observé sur les cellules SK-MEL-28 et SK-MEL-3 cultivées dans les modèles 2D et 3D. La lignée cellulaire SK-MEL-2 était résistante au BRAFi lorsqu'elle a été cultivée en monocouche, mais sensible lorsqu'elle a été co-cultivée avec des fibroblastes incorporés dans une matrice de collagène de type I. Les milieux conditionnés par les fibroblastes 3D (équivalents de derme) ont sensibilisé les cellules SK-MEL-2 (2D) au BRAFi. L'analyse des surnageants de culture cellulaire a révélé que les équivalents de derme libéraient certains facteurs solubles (IL-6, IL-8, HGF, TGF-β) : ces sécrétions ont été modifiées au cours du traitement par Vémurafenib. La combinaison du traitement avec MEKi a renforcé l'action du Vémurafenib sur les cellules de mélanomes métastatiques tout en diminuant la capacité de prolifération des fibroblastes. Des populations de cellules contenant des cellules de mélanomes ou des fibroblastes associés au cancer (CAFs) ont été isolées à partir d'une biopsie de métastase cutanée provenant d'une patiente atteinte d'un mélanome métastatique. Ces cellules ont permis de réaliser des modèles de mélanome métastatique patient-spécifique afin d’étudier in vitro la sensibilité des cellules de la patiente aux traitements dans un microenvironnement tumoral (sécrétion paracrine de cellules stromales et matrice de collagène). Ces modèles prédictifs 3D patient-spécifique pourront être utilisés pour déterminer des stratégies de thérapies personnalisées, ainsi que pour comprendre les phénomènes de résistance des cellules de mélanomes aux traitementsMelanoma cell sensitivity to targeted therapy molecules is dependent on the tumor microenvironment (cell-cell and cell-extracellular matrix interactions). Three dimensional (3D) in vitro cell culture systems better reflect the native structural architecture of tissues and are attractive to investigate cellular interactions. We have developed and compared several metastatic melanoma models: melanoma cells (SK-MEL-28 and SK-MEL-3, BRAF V600E mutant and SK-MEL-2 BRAF wt) cultured as a monolayer (2D) and co-cultured on 3D dermal equivalents with fibroblasts to better unravel factors modulating cell sensitivity to a BRAF inhibitor (BRAFi, Vemurafenib) and a BRAFi combined with a MEK inhibitor (MEKi, Cobimetinib). Cell sensitivity to treatments was evaluated under various aspects: cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK and PKB/Akt signaling pathway analysis (Western-blotting), apoptosis (TUNEL), cytokine and growth factor release (ELISA) and histology (3D models). A cytostatic effect of BRAFi was observed on SK-MEL-28 and SK-MEL-3 cells in both models. SK-MEL-2 cell line was clearly resistant to BRAFi when cultured as a monolayer but not when co-cultured with 3D fibroblasts embedded in a type I collagen matrix. Conditioned media provided by 3D fibroblasts (dermal equivalents) underlined 2D SK-MEL-2 sensitivity to BRAFi. Cell culture supernatant analysis revealed that dermal equivalents released some soluble factors (IL-6, IL-8, HGF, TGF-β): these secretions were modified during vemurafenib treatment. The combination of treatment with MEKi enhances the action of Vemurafenib on metastatic melanoma cells while decreasing the proliferation capacity of fibroblasts. Cell populations containing melanoma cells or fibroblasts associated with cancer (CAFs) were isolated from a cutaneous metastasis biopsy of a patient with metastatic melanoma. These cells allowed the realization of patient-specific models of metastatic melanoma in order to study in vitro the sensitivity of the patient’s melanoma cells to treatments in a tumor microenvironment (paracrine secretion of stromal cells and collagen matrix). These 3D predictive patient-specific models could be used to determine personalized therapy strategies, as well as to understand the resistance phenomena of melanoma cells to treatments
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RODRIGUES, DANIELLE B. "Terapia antiangiogênica de tumores utilizando células produtoras de endostatina encapsuladas em sipositivos de imunoisolamento." reponame:Repositório Institucional do IPEN, 2008. http://repositorio.ipen.br:8080/xmlui/handle/123456789/11711.
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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
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Marshall, Jean-Claude. "The proliferative and invasive capabilities of five human uveal melanoma cell lines /." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82296.
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Uveal melanoma is the most common intraocular tumor in adults. Despite advances in the accuracy of diagnosis, the ten-year mortality rate for patients has remained constant at approximately fifty percent. This indicates that a further understanding of the biological mechanisms behind this malignancy is required.Our laboratory utilizes five human uveal melanoma cell lines (92.1, MKT-BR, OCM-1, SP-6.5, UW-1) that have a previously described metastatic potential from an animal model (MP). We used four methods to characterize the proliferation rate of these five cell lines. We also used a Matrigel invasion assay to assess the invasive ability of the same cell lines in response to the potential chemo-attractants: interleukin-6, Vascular Endothelial Growth Factor, and Fetal Bovine Serum.
From these results we were able to propose a novel classification system for our cell lines: high proliferation and high invasion/high MP, low proliferation and low invasion/low MP, and high proliferation and invasion/no MP.
From these results we were able to propose a novel classification system for our cell lines: high proliferation and high invasion/high MP, low proliferation and low invasion/low MP, and high proliferation and invasion/no MP.
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Andrade, Bruno Augusto Benevenuto de 1984. "Immunohistochemical analysis of the expression of FASN and proteins associated with proliferation and cell cycle control in melanocytic nevi and primary oral melanomas = Análise imunoistoquímica da expressão de FASN e de proteínas associadas à proliferação e controle do ciclo celular em nevos melanocíticos e melanomas primários de boca." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288360.
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Orientador: Oslei Paes de AlmeidaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: O melanoma bucal é um tumor potencialmente agressivo de origem melanocítica, que surge através de uma lesão melanocítica benigna ou de melanócitos da mucosa. Em melanomas é conhecido que a transformação de melanócitos em células de melanoma decorre de alterações nos mecanismos de controle do ciclo celular. Nesse caso, as alterações mais comuns são a superexpressão de ciclina D1e Skp2 e mutações ou deleções de p16, p21 e p27. A avaliação do ciclo celular usando anticorpos contra proteínas nucleares envolvidas na regulação da replicação de DNA também ganhou interesse especial na tentativa de predizer o comportamento biológico em tumores malignos e diferenciação entre lesões benignas e malignas. O objetivo desse trabalho foi avaliar a expressão imunoistoquímica de ácido graxo sintase (FASN) e de proteínas envolvidas nos mecanismos de controle e progressão do ciclo celular como p16, p21, p27, ciclina D1 e Skp2, além dos marcadores de proliferação celular Mcm-2, Ki-67 e geminina em nevos intramucosos e melanomas primários de boca. Os resultados mostraram que FASN, p21, ciclina D1, Skp2, Ki-67, Mcm-2 e geminina foram negativos ou raramente expressos nos casos de nevo, enquanto que nos casos de melanoma, observou-se alta expressão dessas proteínas. Esses marcadores podem estar envolvidos na patogênese do melanoma bucal, podendo eventualmente ser utilizados como ferramenta diagnóstica adicional para ajudar no diagnóstico diferencial entre lesões melanocíticas benignas e malignas
Abstract: Oral melanoma is a potentially aggressive tumor of melanocytic origin, which arises from a benign melanocytic lesion or mucosal melanocytes. In melanomas it is known that the transformation of melanocytes in melanoma cells is caused by alterations in the mechanisms of cell cycle control. In this case, the most common changes are the overexpression of cyclin D1 and Skp2 and mutations or deletions of p16, p21 and p27. The evaluation of the cell cycle using antibodies against nuclear proteins involved in the regulation of DNA replication has also gained particular interest in the effort to predict the biologic behavior and to differentiate between benign and malignant lesions. The aim of this study was to evaluate the immunohistochemical expression of fatty acid synthase (FASN) and proteins involved in the mechanisms of control and cell cycle progression such as p16, p21, p27, cyclin D1 and Spk2, and the cell proliferation markers Mcm-2, Ki-67 and geminin in intramucosal nevi and oral primary melanomas. The results showed that FASN, p21, cyclin D1, Skp2, Ki-67, MCM-2 and geminin were negative or rarely expressed in the cases of nevi, whereas in the cases of melanoma, it was observed a high expression of these proteins. These markers may be involved in the pathogenesis of oral melanoma and may eventually be used as additional diagnostic tool to help in the differential diagnosis between benign and malignant melanocytic lesions
Doutorado
Patologia
Doutor em Estomatopatologia
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Cheng, Shu-Wei, and 鄭舒薇. "β2-glycoprotein I inhibits melanoma cell proliferation, migration and invasion through its functional domain." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/est792.
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碩士國立陽明大學
生化暨分子生物研究所
104
Abstract β2-glycoprotein I (β2-GPI), which consists of five homologous domains, is a human plasma glycoprotein with diverse pathophysiological functions. In our previous study, β2-GPI could suppress vascular endothelial growth factor-induced human aortic endothelial cell proliferation, migration and angiogenesis. Angiogenesis is essential for tumor progression; however, the effects of β2-GPI on tumor cell proliferation, migration and invasion remain unclear. We were also interested in elucidating the correlation between the structural features of β2-GPI and their anti-tumor function. Thus, the aim of this study was to investigate the functional domain ofβ2-GPI which plays a role in anti-tumor cell proliferation, migration, invasion and its molecular mechanisms. Using cell counting assays, we found that purified β2-GPI from human plasma and recombinant peptides of different β2-GPI domains, including domain I-V (DI-V), domain I-IV (DI-IV) and domain I (DI), inhibited B16-F10 melanoma cell proliferation but not domain IV (DIV) and domain V (DV) ofβ2-GPI. Purified 2-GPI and these recombinant peptides also inhibited B16-F10 cell migration by wound healing and transwell assays. Moreover, purified β2-GPI and these recombinant peptides suppressed B16-F10 cell invasion by invasion assay. These inhibitions were also achieved by recombinant peptides of β2-GPI-DI in a dose-dependent manner. In addition, purified β2-GPI and these recombinant peptides was found to reduce Akt and p38 phosphorylation and downregulate MMP-2 protein expression in B16-F10 cells by western blot analysis. Furthermore, we found that purified β2-GPI and the functional recombinant peptides inhibited tumor volume and tumor weight in the B16-F10-implanted C57BL/6 mice. Our results suggest that β2-GPI is able to inhibit B16-F10 cell proliferation, migration and invasion in vitro as well as tumor growth in vivo, which indicates a potential for clinical therapy of melanoma.
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Swen, Shu Ping, and 孫淑萍. "The Effects of Low-Energy Helium-Neon Laser Irradiation on Migration and Proliferation in Human Melanoma cell lines." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/16418172493360860529.
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碩士高雄醫學大學
生物化學研究所
90
Abstract Helium-Neon laser can improve healing wound repair and regulation cell cycle .Those are associate with cell migration and cell proliferation .So , we are interesting in if He-Ne can influence cell migration and cell proliferation in human malignant melanoma cell lines. Cell migration is about cell cytoskeleton and cell membrane interaction and signal pathway to change cell shape and behavior on extracellular matrix to control cell survival , cell cytoskeleton reorganization, cell mobility and receptor activation Cell proliferation is a result from cell cycle , and cell cycle is a mother cell division to daughter cell pathway ,so , cell proliferation is association with increase cell proliferatic protein , DNA synthesis and cell number .Our study focus on (1)if He-Ne laser influence melanoma cell lines migration correlates with cell surface receptor signaling pathway.(2) if He-Ne laser influence melanoma cell lines cell proliferation .The results show when He-Ne laser irradiation dose is more than 0.5 J/cm2,can increase α3β1 integrin and P125FAK phosphorylation and F-actin stress fibers expression ,but no effect on cell damage and cell proliferation in A375 melanoma cell line .And when He-Ne laser irradiation dose is 1J/cm2~2 J/cm2,can increase expression Ki-67 proliferatic protein cell number and cell number after 72 hours ,but no effect on cell migration and cell damage in A2058 melanoma cell line .Our results support He-Ne laser can involve A375 melanoma cell line migration and increase A2058 melanoma cell line proliferation ,So ,we suggest He-Ne laser can effect on different bio-stimulation in different cells .
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Nemazannikova, Natalie. "Vitamin D and non-melanoma skin cancer." Thesis, 2016. https://vuir.vu.edu.au/32150/.
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Limited information is available on the direct role of vitamin D metabolites (calcidiol and calcitriol) in skin carcinogenesis. For most individuals, skin cancer can be readily managed with surgery; however, some patients may face life-threatening neoplasia. Sun exposure, specifically ultraviolet radiation, is a causative agent for development of skin cancer, though, somewhat ironically, sunlight through the endogenous production of vitamin D may have a protective effect against some skin cancers.
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Tzi-Peng and 楊子芃. "1.Mithramycin A inhibits human epithelial carcinoma cells 1.proliferation and migration involving downregulation of Eps8 expression 2.Mechanism of cell death induced by Caffeic acid on melanoma cells." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/99219699772727063271.
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博士中山醫學大學
生化暨生物科技研究所
100
Part1 Mithramycin A is an inhibitor of the binding of the Sp family transcription factor to the GC box. Many studies show that Mithramycin A may reduce the expression of many proto-oncogenes by inhibiting the mRNA and protein synthesis and it has been used as an antibiotic chemotherapy drug for a long time. Recently, Eps8 (EGFR pathway substrate 8) has been revealed to be a novel proto-oncogene related to cellular transformation, Rac activation and actin barbed-end-capping activity. Therefore, the aim of this study was to verify whether Eps8 might be regulated by Mithramycin. Results showed that Mithramycin could reduce the mRNA and protein levels of Eps8 in dose- and time-dependent manners in several cancer cell lines. Furthermore, cell growth and migration ability were also reduced significantly by Mithramycin A treatment. Since Src is a well-known Eps8 activity enhancer, a v-Src transfected IV5 cell line was subjected to Mithramycin A treatment and then analyzed to show that Src expression was unable to restore the Mithramycin-induced decrease in Eps8 expression, cell growth, and migration ability. To further confirm the above mentioned results, the expression of Eps8 was eliminated by a transient transfection with siRNA and subsequent analysis showed that silencing of Eps8 might also lead to a reduced growth and migration ability of cancer cells. These findings suggested that Eps8 was involved in the regulation of growth and motility of cancer cells and Mithramycin A might exert its anticancer ability via a pathway involving the downregulation of Eps8. Part2 Caffeic acid is an organic compound found in plants which also shows antioxidant, immunomodulatory, antiinflammtory and antitumor activities. Melanoma is tumorigenesis of melanocytes which produce melanin in the skin or other organs. It has a bad prognosis and difficult to treat when tumor become malignant. Studies has showed some chemicals or drugs reduced the proliferation of melanoma cells through inducing autophagy. We treat the melanoma cell line B16-F1 with Caffeic acid and find that cells go autophagy and the cell mobility diminished. The autophagy regulators p-Akt is down-regulated, and p-AMPK is up-regulated. FASN (Fatty acid synthase), a tumor related protein which can be activated by Akt and inhibited by AMPK is decreased. Beclin-1 and LC3, the autophagy regulated proteins, are express increasd. For investigate the roles of AMPK, we block the phosphorylation of AMPK by Compound C. Results show the effects of growth and migration abilities inhibited by Caffeic acid was recovery. Autophagy related proteins Beclin-1 and LC3 was recovery partially. It means that AMPK is one of the key regulator intermediate with Caffeic acid induced autophagy. It is worthy for the prophylaxis of melanoma to comprehend the death mechanisms regulated in cells. Our study shows Caffeic acid, the antioxidant ingredients conclude commonly in the plants, inhibit the cell mobility and decrease the cell growth of B16-F1 cells through autophagy. This mechnism is regulated by Akt and AMPK. Although it need more investigates to realize the factors involved, we still get an active principle for tumor inhibition and it is important for chemoprevention of melanoma.
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Kim, Edward. "P300 critically controls proliferation and survival of melanoma cells by transcriptionally regulating MITF." Thesis, 2017. https://hdl.handle.net/2144/27182.
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The p300 transcriptional coactivator has been implicated in the development of a large number of malignancies; however, the precise mechanism of p300-associated tumorigenesis remains unclear. Here, we demonstrate the functional impact of p300 in human melanomas using both genetic and chemical approach. Depletion of p300 in human melanoma cells was associated with cellular growth arrest and senescence. Microarray analysis identified the Microphthalmia-associated transcription factor (MITF), a critical lineage-specific transcription factor in melanocytes and melanomas, as a major downstream target of p300 in human melanoma. Ectopic expression of MITF in p300-depleted melanoma cells allowed rescue of the p300-silencing phenotype, suggesting a critical regulatory axis involving p300 and MITF. Chromatin immunoprecipitation studies revealed direct regulation of MITF transcription through p300 acetylation of proximal regulatory domains. Critically, we identified that Forkhead Box M1 (FOXM1), a potent pro-proliferation transcription factor, is a target of the p300-MITF signaling axis. Further evaluation of p300 regulation of melanoma cell growth was performed using a highly selective p300/CBP HAT inhibitor, 228-1. Inhibition of p300/CBP histone acetyltransferase (HAT) activity was found to significantly inhibit proliferation of multiple melanoma lines in an MITF-dependent fashion. Together, these data support the role of p300 as a promising therapeutic target in human melanoma and suggest particular therapeutic efficacy of small molecule inhibitors of p300 HAT activity in tumors expressing high levels of MITF.2018-12-14T00:00:00Z
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Hu, Wan-Ping, and 胡婉萍. "Study of Molecular Mechanisms in Helium-Neon Laser-induced Proliferation in Human Melanoma A2058 Cells." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/63476912342029661259.
Full textAbstract:
博士高雄醫學大學
醫學研究所博士班
95
Previous reports have shown that cellular functions could be influenced by visual light (400 - 700 nm). Recent evidence indicates that cellular proliferation could be triggered by the interaction of helium-neon laser (He-Ne laser, 632.8 nm) with the mitochondrial photoacceptor-cytochrome c oxidase. Our previous studies demonstrated that He-Ne irradiation induced an increase in cell proliferation, but not migration, in the melanoma cell line A2058 cell. The aim of this study was to investigate the underlying mechanisms involved in photostimulatory effects induced by an He-Ne laser. Using the A2058 cell as a model for cell proliferation, the photobiologic effects induced by an He-Ne laser were studied. He-Ne irradiation immediately induced an increase in mitochondrial membrane potential (ΔΨmt), ATP, and cAMP via enhanced cytochrome c oxidase activity and promoted phosphorylation of Jun N-terminal kinase (JNK) / activator protein-1 (AP-1) expressions. He-Ne irradiation-induced A2058 cell proliferation was significantly abrogated by the addition of ΔΨmt and JNK inhibitors. Moreover, treatment with an He-Ne laser resulted in delayed effects on interleukin-8 (IL-8) and transforming growth factor-β1 (TGF-β1) release from A2058 cells. These results suggest that He-Ne irradiation elicites photostimulatory effects in mitochondria processes, which involve JNK/AP-1 activation and enhanced growth factor release, and ultimately lead to A2058 cell proliferation.