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Bolander, Åsa. "Prognostic factors in malignant melanoma /." Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9511.
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Short, Candice, and Ryan Short. "Uveal Melanoma." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/7353.
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Short, Candice, and Ryan Short. "Uveal Melanoma." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/etsu-works/7357.
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Aliprandini, Eduardo. "Efeito da melanina e do oxigenio singlete na morte celular e fluxo de cálcio em células Melan-A e B16-F10." reponame:Repositório Institucional da UFPR, 2010. http://hdl.handle.net/1884/22552.
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Orientadora : Prof. Glaucia Regina MartinezDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Bioquímica. Defesa: Curitiba, 12/02/2010
Bibliografia: 65-74
Área de concentração: Bioquímica
Resumo
Resumo: O melanoma e um tipo de cancer bastante relevante ja que as opcoes de tratamento eficazes sao limitadas. A presenca da melanina protege os individuos de pele escura contra os efeitos da radiacao solar, a principal causa de formacao do melanoma pela geracao de especies reativas de oxigenio (ROS). Porem, a melanina tambem pode ter um papel duplo, que e a de gerar especies reativas durante sua sintese que podem prejudicar a celula. Portanto, o objetivo deste trabalho foi a avaliacao das caracteristicas de morte celular causadas por uma ROS, o oxigenio singlete (1O2), nas celulas de melanoma murino B16-F10 com e sem estimulo para producao de melanina e nas celulas de melanocito murino Melan-a. O estimulo para a sintese de melanina foi obtido incubando-se as celulas por 48 horas com meio RPMI 1640 enriquecido com 400 ƒÊmol/L de L-tirosina e 10 mmol/L de cloreto de amonio. A concentracao de melanina aumentou em mais de nove vezes nas celulas B16-F10 e as celulas Melan-a tiveram aumento de menos de duas vezes. Foi utilizado o endoperoxido DHPNO2 10 mmol/L por 2 horas para a geracao de 1O2. Essa condicao causou queda na viabilidade avaliada pelo metodo do MTT para 78,0% nas celulas B16-F10, 70,2% nas B16-F10 estimuladas (B16-F10 Y) e 79,3% nas Melan-a. O ensaio foi feito apos 24 horas do inicio do tratamento com DHPNO2 e a viabilidade caiu para 49,7% nas B16-F10, 53,3% nas B16- F10 Y e 72,5% nas Melan-a. A avaliacao da morte celular utilizando laranja de acridina e brometo de etidio mostrou que apos o tratamento por 2 horas, somente as celulas B16- F10 tiveram aumento significativo na quantidade de celulas em apoptose, e as B16-F10 Y tiveram leve queda na quantidade de celulas viaveis, com tendencia ao aumento de celulas em apoptose. As celulas Melan-a nao tiveram diferenca entre os tratamentos. A liberacao do citocromo c foi determinada por HPLC e mostrou-se que apos 2 horas, as celulas B16-F10 tratadas com 1O2 tiveram mais citocromo c liberado para o citoplasma comparado com o controle. Nos demais grupos, nao houve alteracao com o tratamento. Porem, as celulas controle com mais melanina tiveram maior liberacao de citocromo comparado com o controle das celulas nao estimuladas, mostrando que as celulas estavam sofrendo algum dano inerente da sintese de melanina. A analise da fragmentacao do DNA apos 2 e 24 horas mostrou que nao houve aparecimento de quebras caracteristicas de apoptose pelo tratamento com 1O2 em nenhum dos grupos testados. As celulas B16-F10 Y controle apresentaram DNA fragmentado inespecificamente, representado como um arraste no gel de agarose, que nao foi alterado pelo tratamento. A razao entre ADP e ATP foi quantificada para avaliar o estado energetico da celula, que pode refletir algumas caracteristicas de morte. Nenhuma das celulas teve diferenca estatistica apos o tratamento de 2 horas com 1O2, mas foi observado que as razoes ADP/ATP das celulas controle B16-F10 com e sem estimulo apresentaram valores acima do valor considerado para celulas viaveis/proliferativas. Os resultados da celula Melan-a foram bem proximos dos valores ditos normais. O fluxo de calcio tambem foi avaliado e o 1O2 foi capaz de liberar calcio das reservas intracelulares para o citoplasma nas celulas B16-F10, sendo que nas celulas estimuladas, o aumento do calcio citoplasmatico foi menor, indicando a possivel recaptacao do calcio pela melanina. As celulas Melan-a nao sofreram grandes alteracoes na quantidade de calcio liberado para o citoplasma. Nao houve diferenca na liberacao de AIF em nenhuma das celulas. Em conjunto, os resultados mostram que a sintese da melanina estimulada pela suplementacao do meio foi deleteria as celulas, pois causou fragmentacao no DNA, liberacao de citocromo c e aumentou a razao ADP/ATP para valores considerados de celula em apoptose. Por outro lado, a presenca da melanina parece ter protegido as celulas da acao do 1O2, pois alguns resultados indicam uma tendencia de melhora dos parametros avaliados.
Abstract: Melanoma is a relevant type of cancer since the options for efficient treatment are limited. The presence of melanin protects the dark-skinned people against the effects of solar radiation, the main cause for melanoma development by the generation of reactive species of oxygen (ROS). However, melanin may also have a role on the generation of reactive species during its synthesis, which may harm the cell. So, the objective of this work was the evaluation of the characteristics of cell death caused by a ROS, the singlet oxygen (1O2) on murine melanoma cells B16-F10 with or without stimulation for synthesis of melanin and on murine melanocytes cells Melan-a. The stimulus for the synthesis of melanin was obtained treating the cells for 48 hours with medium RPMI 1640 supplemented with 400 ìmol/L of L-Tyrosine and 10 mmol/L of ammonium chloride. The concentration of melanin increased more than nine times in the B16-F10 cells and the Melan-a cells increase was almost twice the amount of the control. It was used the endoperoxide DHPNO2 10 mmol/L for 2 hours for the generation of 1O2. This condition caused the decrease in the viability determined by the method of MTT to 78% in B16-F10, 70,2% in B16-F10 that were stimulated (B16-F10 Y) and 79,3% in Melana cells. The test was performed after 24 hours from the beginning of the treatment with DHPNO2 and the viability decreased to 49,7% in B16-F10, 53,3% in B16-F10 Y and 72,5 % in Melan-a. The evaluation of cell death using acridine orange and ethidium bromide showed that after the two-hour treatment, only the B16-F10 cells had a significant increase of the number of apoptotic cells, and the B16-F10 Y cells had a slight decrease of the amount of viable cells, with the tendency of the increase of apoptotic cells. Melan-a cells did not show difference among the treatments. The release of cytochrome c was determined by HPLC and it showed that after two hours, B16-F10 cells had more cytochrome c released to the cytoplasm compared to the control. There was not any alteration for other groups of cells with the treatment. However, the control cells that had more melanin showed increased cytochrome c release compared to the control of the not-stimulated cells, demonstrating that the previous cells were suffering some kind of damage from the melanin synthesis. The analysis of DNA fragmentation revealed the absence of typical apoptosis fragmentation in any of the groups. B16-F10 Y control cells displayed unspecific DNA damage observed as a smear in the agarose gel, which was not altered by 1O2 treatment. The same result was observed after the treatment for 2 and 24 hours. The ratio between ADP and ATP was quantified to evaluate the energetic state of the cell, which may reflect some characteristics of cell death. None of the cells showed results statistically significant after the two-hour treatment 1O2, but it was shown that the values of ADP/ATP ratio of the B16-F10 control cells with and without stimulation were above of the threshold accepted for viable/proliferative cells. The results of Melan-a cells were very close to the values considered normal. The calcium flux was also evaluated and it was evidenced that 1O2 was capable of releasing calcium from the intracellular stores to the cytoplasm in B16- F10 cells, and the release of calcium was lower in B16-F10 Y, indicating the possibility of the binding of the metal to melanin. The Melan-a cells did not showed much increase in the quantities of calcium released to the cytoplasm. There was no difference in the release of AIF in any group. Over all, the results support that the synthesis of melanin that was stimulated by the supplementation of the medium was deleterious to the cells, since it caused DNA fragmentation, release of cytochrome c and increase of the ratio ADP/ATP to values of cells in apoptosis. On the other hand, the presence of melanin seemed to protect the cells against the action of 1O2, because some results indicate a tendency of improvement in the parameters evaluated.
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Kohli, Jaskaren Singh. "Senescence and immortalisation in melanoma progression and multiple primary melanoma." Thesis, St George's, University of London, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706529.
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Multiple primary melanoma is defined as the gain of at least one additional independent melanoma and occurs in approximately 5% of melanoma patients. Germline mutations can be identified in genes in these patients, which are known to, or are predicted to result in an extension of melanocyte lifespan e.g. pl6, CDK4, and components of the telomere shelterin cap. We therefore hypothesised that 'normal' melanocytes from pl6 and CDK4 wild-type multiple primary melanoma patients have a statistically longer lifespan compared to those from single primary melanoma patients. Melanocytes from multiple primary melanoma patients did display a significantly extended culture lifespan, independently of donor age. Multiple primary melanoma is therefore commonly associated with a delay in normal melanocyte senescence. There is currently a shortage of diagnostic markers for melanoma and novel ones are needed for more accurate diagnosis and prognosis. TERT (the enzymatic component of telomerase) expression is the commonest route to telomere maintenance, required for melanoma immortality. TERT expression was tested via immunohistochemistry in a series of melanoma precursor and melanoma lesions, to analyse at which point in progression its expression is activated. The protein was found to be localised in either the nucleolus, the nucleoplasm (designated non-nucleolarTERT), or both. Only non-nucleolarTERT expression significantly increased with melanoma progression, suggesting this location is associated with immortality. As senescence likely needs to be bypassed for advanced melanoma development, microarrays were previously carried out comparing growing and senescent wild-type and pl6-null melanocyte lines to evaluate significantly up- or downregulated genes which could be used as future markers. In the present study, potential novel markers were authenticated using PCR and immunoblotting and validated genes were analysed via immunohistochemistry in a series of melanoma precursor and melanoma lesions. ETS1 was tested owing to recent findings that it can bind to and activate the mutant TERT promoter found commonly in melanomas. ETS1 was expressed at all stages from benign nevi onwards, perhaps owing to its link with the MAPK pathway.
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Wilson, Kenneth Scott. "Cutaneous malignant melanoma." Thesis, University of Edinburgh, 1994. http://hdl.handle.net/1842/27062.
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Epidemiology, clinical presentation, natural history, pathological features and treatment of cutaneous malignant melanoma have been studied in the British Columbia Cancer Agency [BCCA]. A retrospective review of 891 patients registered between 1972 and 1981 is presented. Age standardised incidence rates have increased significantly. Predominant primary sites were trunk for males and lower limb for females. Dominant growth patterns were superficial spreading [65%], nodular [25%], lentigo maligna [5%] and acral-lentiginous melanoma [2%]. Median primary tumor depth at presentation were 1.45mm for males and 1.10mm for females. No T 1 tumors were staged beyond the local area. Fifteen year survival was 55.5% for males and 70.3% for females. Multivariate analyses of prognostic factors in 556 clinical stage 1 patients showed that micrometer depth, pathological ulceration, primary site and type of initial surgery were principal prognostic factors. Elective lymph node dissections [ELND] were undertaken in 232 patients. Nodes examined after ELND were positive pathologically in 36 [16%] patients. Survival after ELND was compared with a concurrent group of patients not undergoing ELND and with other series. Multivariate analysis did not show ELND to be of independent significance. Survival after therapeutic LND was comparable with previous series. Adjuvant therapy with BCG and levamisole for 3 years was investigated in 76 patients from British Columbia as part of a National Cancer Institute of Canada Clinical Trials Group Study involving 543 patients. All patients were clinically disease-free after standard surgery for high risk primary or recurrent regional melanoma. Patients who received Levamisole alone experienced 30% fewer deaths than no immunotherapy control patients. Survival was worst in older patients in the control group and levamisole appeared to abolish the adverse prognostic significance of age.
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Wiguna, Arlina Permatasari. "Immunoregulation in melanoma." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2015. http://dx.doi.org/10.18452/17107.
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IL-10 und TGF-beta sind immunsupprimierende Zytokine, die in verschiedenen Tumoren, u.a. im Melanom, entdeckt wurden und als Hauptursache für das Versagen der Anti-Tumorimmunantwort angesehen werden. Allerdings wurden divergente Daten auch berichtet. Um diese Diskrepanz zu erklären, wurde die Expression dieser Zytokine mittels quantitativer RT-PCR im Melanom und in Haut gesunder Individuen verglichen. Weiterhin wurde die Induktion beider Zytokine in Kokulturexperimenten mit Dendritische Zellen und T-Zellen zusammen mit Tumorzellen sowie ihr Einfluß auf das Immunsystem untersucht. Beide Zytokine sowie deren Rezeptoren wurden im Melanom exprimiert, aber im Vergleich mit gesunder Haut auf signifikant geringerem Level. Dementsprechend waren die Expressionen von IL-10-induzierbare-SOCS-3 und auch TGF-beta-induzierbare-SMAD-7 im Tumor gering und in der gesunden Haut hoch. T-Zellen, die mit einer großen Zahl an Tumorzellen kokultiviert wurden, entwickelten einen anergischen Zustand, aber ohne mit dem IL-10 oder TGF-beta Level zu korrelieren. Dendritische Zellen, die zusammen mit Tumorzellen kokultiviert wurden, wiesen eine gemischte Population an vollständig und unvollständig differenzierten iDCs auf, produzierten hohe Level IL-10 und konnten die CD4 T Zellproliferation weniger effizient induzieren. Trotzdem konnten sie zur Reifung induziert werden, wobei die Blockierung von IL-10 nicht die Fähigkeit der resultierenden, reifen DCs veränderte, CD4 T-Zellproliferation zu induzieren. DCs, deren Reifung in der Gegenwart von Tumorzellen induziert wurde, produzierten erhöhte Level an IL-10, dagegen gleiche oder verminderte Level an TGF-beta und waren effizienter in der Induktion der CD4 T-Zellproliferation. Die fehlende Korrelation von IL-10 und TGF-beta mit den Immundefiziten in situ und in vitro legt den Schluß nahe, ihre Rolle bei Krebs neu zu überdenken.IL-10 and TGF-beta are immunosuppressive cytokines expressed in tumors including melanoma and, therefore, deemed major cause for failing anti-tumor immune responses. To re-evaluate their role, their expression was compared by quantitative RT-PCR in melanoma and skin of healthy individuals, their induction in dendritic cells and T cells co-cultured with tumor cells, and their effects on the immune cells were tested. Both cytokines as well as their receptors were expressed in melanoma at significantly lower levels than in healthy skin. Consequently, the expressions of IL-10-responsive SOCS-3 and TGF-beta-responsive Smad-7 were low in tumors but high in healthy skin. T cells co-cultured with tumor cells developed an anergic state but without increased IL-10 or TGF-beta expression. In vitro tumor-associated iDCs produced high IL-10 levels and were less efficient in inducing T cell proliferation. Nonetheless, they could be induced to mature, and blocking IL-10 did not alter the capacity of the resulting mDCs to induce T cell proliferation. mDCs co-cultured with tumor cells produced increased IL-10 but similar or decreased TGF-beta level and were more efficient in inducing T cell proliferation. The lack of correlation of IL-10 and TGF-beta with immune deficits in situ and in vitro suggests a necessity of re-evaluating their roles in cancer.
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Winklmeier, Andreas. "Rolle der Transkription und Aktivität von MIA ("Melanoma Inhibitory Activity") im malignen Melanom." kostenfrei, 2009. http://www.opus-bayern.de/uni-regensburg/volltexte/2009/1301/.
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Hering, Kathrin, Anke Bresch, Donald Lobsien, Wolf Müller, Rolf-Dieter Kortmann, and Clemens Seidel. "Primary intradural extramedullary spinal melanoma in the lower thoracic spine." Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-205904.
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Up to date, only four cases of primary intradural extramedullary spinal cord melanoma (PIEM) have been reported. No previous reports have described a case of PIEM located in the lower thoracic spine with long-termfollow-up. Purpose. Demonstrating an unusual, extremely rare case of melanoma manifestation. Study Design. Case report. Methods. We report a case of a 57-year-old female suffering from increasing lower extremity pain, left-sided paresis, and paraesthesia due to spinal
cord compression caused by PIEM in the lower thoracic spine. Results. Extensive investigation excluded other possible primary melanoma sites and metastases. For spinal cord decompression, the tumor at level T12 was resected, yet incompletely. Adjuvant radiotherapy was administered two weeks after surgery. The patient was recurrence-free at 104 weeks after radiotherapy but presents with unchanged neurological symptoms. Conclusion. Primary intradural extramedullary melanoma (PIEM) is extremely rare and its clinical course is unpredictable.
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Gilbert, Amy. "Humoral immune response to melanoma : discovery and evaluation of anti-melanoma antibodies." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/humoral-immune-response-to-melanoma-discovery-and-evaluation-of-antimelanoma-antibodies(34c0be73-e94a-4d3f-92b9-8888178c4cd2).html.
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Melanoma, a potentially lethal form of skin cancer, is widely thought to be immunogenic in nature. While numerous studies have examined T cell-mediated immune responses to melanoma and their therapeutic potential, there has been less focus on B cell-mediated immune responses and the tumor-reactive antibodies they produce. The aim of this work was three-fold: (1) to develop a methodology to detect antibodies secreted by human B cells that recognize melanoma cell surface proteins; (2) to evaluate the mature B cell repertoire of individuals with melanoma for antibody subclass composition and the presence and prevalence of anti-tumor antibodies; and (3) to study patient-derived antibodies and two engineered antibodies recognizing melanoma cells for their propensity to activate immune effector cells and their capacity to kill or restrict the growth of tumor cells. As part of this thesis, a novel tumor cell-based ELISA was developed for the detection of tumor-reactive antibodies. Utilizing this new assay, the presence and prevalence of melanoma-reactive IgG antibodies derived from ex vivo cultured peripheral blood B cells from a cohort of 21 patients with melanoma (Stage I, n=1; Stage II, n=8; Stage III, n=6; Stage IV, n=6) were compared to those from healthy volunteers (n=10). While B cells from melanoma patients secreted IgG antibody concentrations comparable to those from healthy volunteer B cell cultures, a significantly increased reactivity of antibodies derived from patients to primary and metastatic melanoma cells was measured compared to healthy volunteers (P<0.001). Interestingly, there was a significant reduction in antibody responses to melanoma with advancing disease stage that was not found to be solely due to a -ii-reduction in the B cell memory compartment size. Comparing IgG antibody subclass distribution among cutaneous tumors, patient lymph nodes and peripheral blood B cells all isolated from individuals with metastatic disease, elevated proportions of IgG4 subclass antibodies were observed in cutaneous tumors which present a novel finding of this thesis. These findings point to differentially polarized humoral immune responses in cutaneous tumor microenvironments. Lastly, an antibody derived from a patient was then selected and preliminary evaluations of reactivity and specificity to a range of melanoma cell lines and primary human melanocytes were conducted. Using a live cell imaging cytotoxicity assay, this patient-derived melanoma-specific antibody was observed to kill melanoma cells via antibody-mediated cellular cytotoxicity. Additionally, two engineered monoclonal antibodies recognizing a melanoma associated antigen were found to partially restrict tumor cell migration and adhesion and to kill melanoma cells via antibody-dependent cellular cytotoxicity or phagocytosis. In summary, examining the humoral immune response to melanoma and the effector function of antibodies targeting melanoma cells provides insight into the discovery of new therapeutic strategies for the treatment of melanoma.
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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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Tatzel, Jutta. "Bedeutung von MIA (Melanoma inhibitory activity) bei der Entstehung und Progression des malignen Melanoms." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975164775.
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Westerdahl, Johan. "Malignant melanoma risk factors /." Lund : Dept. of Surgery, Lund University, 1995. http://catalog.hathitrust.org/api/volumes/oclc/39204671.html.
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Reiniger, Ingrid. ""Melanoma Inhibitory Activity" (MIA)." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-34405.
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Robles, Espinoza Carla Daniela. "Drivers of melanoma susceptibility." Thesis, University of Cambridge, 2015. https://www.repository.cam.ac.uk/handle/1810/247224.
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Cutaneous melanoma is a cancer of melanocytes, the pigment-producing cells in our skin. It is one of the most aggressive human malignancies, constituting only about 2% of all dermatological cancers but being responsible for over 75% of all deaths from skin cancer. It has recently become a major public health problem, as it is now the fifth most common cancer in the United Kingdom after its incidence more than quadrupled in the last three decades. For these reasons, understanding the biological processes that are involved in its development is of great importance for devising novel treatments and for the management of patients in the clinic. The study of the genetic factors that influence melanoma risk can uncover mechanisms that are relevant in the transition from a benign melanocyte to a malignant melanoma. Approximately 10% of all melanoma cases are familial, and about half of these familial cases can be explained by pathogenetic variants in genes such as cyclin-dependent kinase inhibitor 2A (CDKN2A), cyclin-dependent kinase 4 (CDK4), breast cancer 2 (BRCA2), BRCA1-associated protein-1 (BAP1) and in the promoter of the telomerase reverse transcriptase (TERT). However, about 50% of all familial melanoma cannot be explained by mutations in known genes. In this dissertation, I detail the methodology I followed in an effort to uncover additional high-penetrance melanoma susceptibility genes. I analysed exome and genome sequence data from a total of 184 individuals that belong to 105 melanoma-prone families from the United Kingdom, The Netherlands and Australia that did not have any pathogenetic variants in known susceptibility genes. I applied different gene prioritisation strategies and developed novel software tools in order to devise a list of plausible melanoma susceptibility candidate genes; these analyses suggested that genes regulating telomere function could be influencing melanoma risk. After performing functional experimental analyses, our research team was able to determine that carriers of rare variants in the protection of telomeres (POT1) gene, a member of the shelterin complex that safeguards telomere integrity, are at high risk for developing melanoma. We successfully described the mechanism by which this happens, showing that the variants identified either disrupt POT1 mRNA splicing or abolish the ability of POT1 to bind to telomeres, and lead to increased telomere length in carriers when compared to melanoma cases with wild-type POT1. The main finding of the work described in this dissertation is the identification of telomere dysfunction as an important contributor to the risk of developing melanoma, and possibly other cancers. Our analyses suggest that POT1 is the second most commonly mutated high-penetrance melanoma susceptibility gene reported thus far, and moreover, that rare variants in this gene constitute the first hereditary mechanism for telomere lengthening in humans.
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Akhras, Victoria. "Lymphatic functions in melanoma." Thesis, St George's, University of London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546785.
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Pearl, Robert Ashley. "Molecular targets in melanoma." Thesis, University College London (University of London), 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497695.
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Pane, Anthony Robert. "Ocular melanoma in Queensland /." [St. Lucia, Qld.], 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16144.pdf.
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Caputo, Emilia. "Analisi molecolare del melanoma." Doctoral thesis, Università di Catania, 2012. http://hdl.handle.net/10761/1214.
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We have analyzed the proteomes of two human melanoma cell lines (A375 and 526), and of the human melanocytes, (FOM 78), by two-dimensional electrophoresis (2D-PAGE) and liquid chromatography¿tandem mass spectrometry (LC-MS/MS). Our comparative proteomic analysis revealed that six proteins were overexpressed in both melanoma cell lines as compared with melanocytes: galectin-1, inosine-5'-monophosphate dehydrogenase 2, serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A ¿ isoform, protein DJ-1, cyclophilin A and cofilin-1. We show, for the first time, that only specific isoforms of these molecules are overexpressed in melanoma. Different protein profiles were also found between each individual melanoma cell line and the melanocytes. s-Methyl-5-thioadenosine phosphorylase, ubiquitin and ribosomal protein S27 a precursor, the basic form of protein DJ-1, annexin a1, proliferation associatedvprotein 2g4, isoform alfa-enolase of alfa-enolase, protein disulfide-isomerase precursor and elongation factor 2 werevmore strongly expressed in A375 cells compared with melanocytes. In 526 cells, 60s acidic ribosomal protein p1 and calreticulin precursor were more highly expressed than in melanocytes. These molecular differences may help in better understanding melanoma development and its different responsiveness to therapies. The identified proteins could be exploited as biomarkers or therapeutic targets for melanoma.
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Martens, Kelly A. "Utilization of extreme drug resistance testing in malignant melanoma new is not always better." Gold Coast, QLD : Bond University, 2005. http://epublications.bond.edu.au/theses/martens.
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Thesis (DHlthSc) -- Bond University, 2005."A thesis submitted to Bond University in fulfillment of the requirements for the degree of Doctor of Health Sciences"-- t.p. Bibliography: pages 379-442. Also available via the World Wide Web.
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Seguin, Fabiana 1984. "Estudo do papel biológico da enzima ácido graxo sintase (FASN) em células endoteliais derivadas dos vasos sanguíneos." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290689.
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Orientador: Edgard GranerTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: A enzima ácido graxo sintase (FASN), cuja expressão e atividade estão elevadas em várias neoplasias malignas humanas, é responsável pela síntese endógena de ácidos graxos saturados de cadeia longa e, consequentemente, pela a produção de fosfolipídios das membranas celulares. A inibição de FASN com orlistat (Xenical), uma droga anti-obesidade, é descrita como tendo propriedades anti-neoplásicas nos cânceres de próstata, mama, bem como no melanoma. Este composto parece desempenhar também um papel anti-angiogênico, uma vez que foi descrito como inibidor da proliferação de células endoteliais e da neovascularização em ensaio ex vivo. Em trabalho recente, realizado por nosso grupo de pesquisa, foi demonstrado que o tratamento de camundongos portadores de melanomas intraperitoneais com orlistat reduziu em cerca de 50% o número de metástases para linfonodos mediastínicos. Em outro estudo, também realizado por nosso grupo, foi observado que a inibição da atividade de FASN pode ter um papel sobre a angiogênese induzida por melanomas experimentais, pois a densidade de vasos sanguíneos ao redor destes tumores foi significantemente reduzida pelo tratamento com orlistat. Considerando as evidências sugerindo um papel biológico relevante de FASN na disseminação metastática de melanomas, o presente trabalho de pesquisa teve como objetivo principal investigar as consequências da inibição da atividade de FASN em cultura de células endoteliais de vasos sanguíneos, através da análise do ciclo celular e das taxas de apoptose. A expressão dos diversos fatores da família VEGF foi avaliada por RT-PCR quantitativo em células de melanoma e carcinoma espinocelular bucal. Os resultados obtidos mostram que orlistat e cerulenina inibem a viabilidade, induzem a apoptose e reduzem in vitro a formação de vasos sanguíneos pelas células endoteliais RAEC. No entanto, o mesmo tratamento não reduz a viabilidade e nem reduzem a formação de vasos sanguíneos in vitro pelas células endoteliais HUVEC. A inibição de FASN nas células neoplásicas SK-MEL-25 e SCC-9 aumenta a expressão de RNAs mensageiros para VEGFA e que o meio condicionado por estas células com orlistat reduz a formação in vitro de vasos sanguíneos e a proliferação das células HUVEC. Nossos resultados sugerem que FASN parece ser importante para a sobrevivência das células RAEC e que a inibição de FASN modula a expressão das isoformas de VEGFA
Abstract: Fatty acid synthase (FASN) is the anabolic enzyme with high expression and activity in several human malignancies, which is responsible for the endogenous synthesis of saturated fatty acids and consequently of the phospholipids present in cell membranes. Inhibition of FASN with orlistat (Xenical), an anti-obesity drug, is described as having anti-neoplastic properties in breast and prostate cancers as well as in melanoma. An anti-angiogenic role, has been attributed to this drug, since it inhibits the proliferation of endothelial cells and the neovascularization in ex vivo both assays. In recent studies performed by our group, it was demonstrated that the treatment of mice bearing intraperitoneal melanoma with orlistat reduced by 50% the number of metastases to mediastinal lymph nodes. In another study, also conducted by our group, we observed that the inhibition of FASN reduces the angiogenesis induced by experimental melanomas, since the density of blood vessels around tumors was significantly decreased by the treatment with orlistat. In the present work investigated the consequences of the treatment with FASN inhibitors the proliferation and apoptosis cultured endothelial cells. The expression of the VEGF family of growth factors were assessed by quantitative RT-PCR in both melanoma and squamous cell carcinoma cells. The results show that orlistat and cerulenin inhibit the viability and induce apoptosis and reduce the formation of blood vessels by RAEC cells in vitro. However, the same treatment does not reduce the viability and not reduce the formation of blood vessels by HUVEC cells in vitro. The inhibition of FASN in neoplastic cells SK-MEL-25 and SCC-9 increases the expression of mRNAs for VEGF and the conditioned medium by these cells with orlistat reduces the formation of blood vessels in vitro and proliferation of HUVEC cells. Together, the experiments show that FASN seems to be important for the survival of RAEC cells and FASN inhibition modulates the expression of VEGF isoforms
Doutorado
Patologia
Doutor em Estomatopatologia
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Kmetiuk, Louise Nicolle Bach. "Desenvolvimento e avaliação comparativa do melanoma oral em camundongos, frente sua ocorrência espontânea em cães." Universidade Estadual de Ponta Grossa, 2016. http://tede2.uepg.br/jspui/handle/prefix/2761.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ntrodução: O Melanoma é a principal neoplasia em cavidade oral de cães domésticos. Ocorre principalmente em gengiva, e caracteriza-se pela progressão acelerada, altos índices de recidiva, metástase e resistência a terapias propostas. Tais aspectos impulsionaram o presente estudo, considerando a ausência de um modelo experimental para essa neoplasia, que possibilite a realização de ensaios pré-clínicos. Objetivos: Induzir a formação de melanoma oral murino em camundongos C57Bl/6J, e estudar suas características macroscópicas e histopatológicas. Método: trata-se de um estudo experimental. Trinta camundongos C57Bl/6J (Mus musculus) foram submetidos a indução tumoral através da injeção de células da linhagem de melanoma murino B16F10 em gengiva inferior direita porção vestibular, em duas concentrações celulares, originando dois grupos distintos: Grupo 1 (n=15) que receberam 0,1 ml contendo 1x104 células de melanoma murino B16F10; Grupo 2 (n=15) que receberam 0,1 ml contendo 5x104 células de melanoma murino B16F10. Para ambos os grupos foram realizadas eutanásias programadas aos sétimo, décimo quarto e vigésimoprimeiro dias de pós-operatório, com ressecção ex-vivo da hemicabeça direita. Após a exclusão dos indivíduos que foram a óbito antes do período determinado para eutanásia, obteve-se um número de indivíduos na amostra (n) de 21. Foi realizada análise macroscópica das formações tumorais. Para o estudo histológico comparativo, analisaram-se amostras de melanoma oral canino melânico no que tange aos aspectos morfométricos e morfológicos. Resultados: Houve diferença no desenvolvimento tumoral para cada concentração celular utilizada na indução. Notouse correlação positiva entre volume tumoral e número de células. Conclusão: A indução de melanoma oral em camundongos para fins de modelo de estudo pré-clínico para cães se mostrou uma alternativa útil, viável e reproduzível.
Introduction: Melanoma is the most common neoplasm in oral cavity of dogs. Melanoma has a predilection for the gum, and it is characterized by accelerated progression and high rates of relapse, metastasis and resistance to proposed therapies. Those factors inspires the present study, considering the lack of an experimental model for melanoma. Method: This is an experimental study. Thirty C57Bl / 6J mice (Mus musculus) were submitted to tumor induction by injecting murine melanoma B16F10 cells into the right lower gum using two different cell concentrations. Mice were divided in two groups: Group 1 (n = 15) received 1x104 murine melanoma B16F10 cells injection; Group 2 (n = 15) received 5x104 murine melanoma B16F10 cells injections. For both groups, euthanasia was scheduled at the 7th., 14th. and 21th. postoperative day, with post-mortem hemi-resection of the jaw. Individuals who died before the euthanasia period were excluded, leaving 21 mice. Macroscopic analysis of tumor formations was performed. For comparative histological study, oral canine melanoma samples were analyzed for morphological aspects. Data sete analyzed with BioStat 5.3 and submitted to non-parametric statistical tests. Results: Different tumor characteristics (tumor volume, presence of irregular margins, ulceration and dark coloration) were observed for each cell concentration used in the induction, as well perfect correlation between tumor volume and tumor growth. Conclusion: The induction of oral melanoma in mice for purposes of preclinical study model for dogs is an useful, viable and reproducible alternative.
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Beddingfield, Frederick Coston. "Melanoma a decision analysis to estimate the effectiveness and cost-effectiveness of screening and an analysis of the relevant epidemiology of the disease /." Santa Monica, CA : RAND, 2002. http://catalog.hathitrust.org/api/volumes/oclc/51441066.html.
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Lamberti, Arianna. "PRIMARY MELANOMA OF THE SKIN AND CUTANEOUS MELANOMA METASTASES: COMPARATIVE STUDY OF TUMOR MICROENVIRONMENT." Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1073036.
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Melanoma incidence is steadily increasing in the Western world. Surgery largely controls melanomas in early stages, whereas advanced disease is still a therapy challenge. Cutaneous melanoma comprises different subgroups according to epidemiology, biological behavior, prognostic features, and molecular profiles.
The tumor microenvironment rich in lymphocytes (TILs brisk) represents a complex signaling network with a controversial prognostic role. Notwithstanding the continuous crosstalk of melanoma cells with dendritic cells and T-cells in both peripheral blood and lymph nodes, the immune editing (intra and extra cellular signals interaction) is progressively lost. This event represents the main cause of the uncontrolled proliferation of tumor cells as well as of their migration capability to distant sites.
Our aim is to investigate the immune cell microenvironment of primary melanoma and their metastasis, to recognize early those patients with a higher risk of systemic recurrence. Skin primary melanomas and their own metastases of the last ten years with a minimum follow up of five years were included in the study. Sections were cut from the most representative paraffin block of each case. A large panel of antibodies is used to identify immune cell subsets (CD4; CD8; TIA-1; Granzyme B; CD25; FOXP3, CD20+, dendritic cells CD1aS100, CD68, CD15).
The comparison among these variables and to histopathological parameters (thickness, ulcer, mitosis) and tumor infiltrating immune cells grading (TI-ICs), was realized to define whether a specific immunological hallmark may explain a different behavior among various TI-ICs grades and if they may represent a useful prognostic tool to predict in early stage, high risk melanoma patients.
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Ragnarsson, Olding Boel. "Malignant melanoma of the vulva /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3567-X/.
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Bolander, Åsa. "Prognostic Factors in Malignant Melanoma." Doctoral thesis, Uppsala universitet, Enheten för onkologi, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9511.
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Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis. This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers. In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers. In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7. We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67. DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors. None of the investigated markers in study III and IV correlated with disease free survival or overall survival. In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.
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Foss, Alexander James Easterbrook. "The pathobiology of uveal melanoma." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337565.
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Li, Weiling. "Genetic changes in melanoma progression." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5595.
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Melanoma is a highly aggressive tumour with a poor prognosis for patients with advanced disease because it is resistant to current therapies. Therefore, the development of novel strategies for melanoma treatment is important. The characterization of the molecular mechanisms underlying melanoma proliferation, progression, and survival could help the development of novel targeted melanoma treatments. The MAPK and PI3K pathways both play important roles in melanoma progression. In the MAPK pathway, DUSP6, which acts as a phosphatase to negatively control the activation of ERK1/2, is involved in the development of human cancers. The MAPK pathway also regulates expression of the DNA repair gene ERCC1 following EGF treatment. ERCC1 is essential for nucleotide excision repair, which is one of the major systems for removal of cisplatin induced DNA lesions. The aims of this project were: 1, to investigate the molecular changes in our immortal mouse melanocyte cell lines that were needed for them to form tumours in a xenograft model; 2, to investigate whether the MAPK pathway regulates ERCC1 following cisplatin treatment and protects melanoma cells from death. Through comparison of the RAS/RAF/MEK/ERK (MAPK) and the PI3K/AKT (AKT) signalling pathways between our immortal mouse melanocyte cell lines and their tumour derivatives in our xenograft model, we identified a molecularly distinct subtype of mouse melanoma characterized by reduced ERK and AKT activity and increased expression of DUSP6. Functional analyses employing ectopic overexpression indicated that increased expression of DUSP6 enhanced anchorage independent growth ability and invasive ability in our mouse melanocytes, suggesting that increased DUSP6 expression may contribute to melanoma formation in the xenograft assay. We also demonstrated that higher expression of p-ERK suppressed invasion, but not anchorage independent growth, in our subtype of mouse melanoma by enforced expression of constitutively active MEK1 and MEK2. In addition, the role of DUSP6 in classical human melanoma was investigated in this Genetic changes in melanoma progression study. Inhibition of anchorage independent growth and invasion were observed after exogenous expression of DUSP6 in human melanoma cells. This suggested that DUSP6 played different roles in classic human melanoma than in our distinct subtype of mouse melanoma. Our study also investigated the phosphorylation level of ERK1/2 and the mRNA and protein level of ERCC1 and its partner XPF in the human melanoma cell line following cisplatin treatment. Significant increases in expression of p-ERK, ERCC1 and XPF were found in cisplatin treated cells. Moreover, a MEK inhibitor inhibited ERCC1 induction by cisplatin, but did not significantly affect XPF induction. This suggested that the MAPK pathway was involved in regulation of ERCC1 but not XPF. Furthermore, the DUSP6 level decreased after cisplatin treatment and overexpression of DUSP6 inhibited ERCC1 and XPF induction and reduced resistance to cisplatin. DUSP6 seems to play a crucial role in resistance of melanoma to cisplatin. In addition, a novel larger ERCC1 transcript was identified in human cell lines and was found to be upregulated by cisplatin. The ratio of larger ERCC1 transcript relative to the normal ERCC1 transcript increased following cisplatin treatment. The functions of this larger ERCC1 transcript in cisplatin resistance deserve further study.
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Lang, Julie M. S. "Genetics of cutaneous malignant melanoma." Thesis, University of Glasgow, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413378.
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Healy, Eugene. "Genetic changes in cutaneous melanoma." Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389573.
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Harries, Mark. "Enhancing anti-melanoma immune responses." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325539.
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Blessing, Karen. "Prognostic factors in malignant melanoma." Thesis, University of Aberdeen, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305319.
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Malignant melanoma is a relatively uncommon tumour in this country, but it accounts for most of the deaths attributable to skin cancer. Additionally, there is an established increasing incidence rate in every white population studied to date; it is therefore assuming greater importance. Despite the cutaneous location with the potential for early diagnosis, treatment and effective cure, the clinical behaviour of malignant melanoma still remains to a certain extent unpredictable. Today the Breslow measurement (thickness) of the tumour is regarded as the most sensitive prognostic indicator. Nonetheless, tumour thickness alone is not sufficient to predict the clinical outcome for the individual patient, with a 5-10% of 'thin' melanomas resulting in metastasis or death of the patient, and conversely it is recognised that a certain subgroup of 'thick' lesions will behave in a less aggressive than expected manner. Other features cited as influencing prognosis include patient age, sex, anatomical location, histogenetic type, mitotic counts, ulceration, vascular invasion, host response with a conflicting opinion on the role of regression. This thesis confirms the increasing incidence of melanoma in the Grampian Area, in keeping with other large studies and also that patients are presenting earlier with thin lesions. This thesis also confirms that some patients with thin melanomas develop metastasis and factors that may be important additional to the Breslow depth include lesion size, histological regression, Clark level and depth of the uninvolved dermis. Also, some thick melanomas do not metastasise and patients have a good disease free survival. Factors that appear to be important in this group of patients include anatomical location, vascular invasion and the nature of the lower tumour margin.
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Kernohan, Neil M. "Cutaneous malignant melanoma - immunophenotypic considerations." Thesis, University of Aberdeen, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305449.
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One of the principal themes of the prolific research on the subject of CMM has been to establish parameters that can predict the clinical outcome. The most useful of these prognostic parameters have been derived from histopathological studies, but none has been consistently reliable. Therefore, other parameters may be presumed to influence the clinical course and a body of evidence acquired from laboratory experimental, pathological and clinical studies suggests that host immune effector mechanisms may be relevant in this regard. Immunohistochemistry provides a means by which histopathologists can attempt to elucidate features of the interaction between tumour cells and host immune effector cells. Such an approach was adopted for the studies presented in this thesis. The T-cell infiltrate associated with CMM, although more intense than that associated with either lentigo maligna or nevocellular nevi, was qualitatively similar with regard to its immunophenotypic characteristics. Natural killer (NK) cells were, however, identified only in association with some cases of CMM. Interleukin-2 (IL-2) was localised principally within melanoma cell nuclei, the uptake of IL-2 by melanoma cells presumably being mediated by the β-chain of the IL-2 receptor which was selectively expressed by tumour cells. Contrary to most previous studies, expression of ICAM-1 and LFA-3 by melanoma and nevus cells was ubiquitous. Expression of these molecules therefore seems unlikely to aid the differential diagnosis of melanocytic lesions and is of doubtful independent prognostic significance. The role that these molecules may have in facilitating host immune responses against tumour cells is unclear; expression of these molecules correlated with neither the intensity of the host inflammatory cell infiltrate nor the presence of regression.
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Anbunathan, Hima. "Genomic landscape of uveal melanoma." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/58247.
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Uveal melanoma (UM) is the most common cancer of the adult eye which can manifest as a highly aggressive form approximately half of the time. Here a comprehensive landscape of genetic alterations in UMs is described. It was identified by integrating copy number alterations (CNAs), and transcriptomic and whole exome sequencing data from 207 primary UMs. Focal copy number analysis with the GISTIC algorithm refined the boundaries of chromosomal segments with chromosomal gains or losses and candidate cancer genes within these segments were identified. Chromosome 8q24.3 was the region most frequently amplified in UMs, being detected in 72% of tumours. A comparison of focal copy gains and losses with that described by a pan-cancer study revealed Plectin 1 as a candidate gene within the 8q24.3 amplicon. Integration of copy number and transcriptomic data also revealed enrichment of genes within pathways leading to activation of NF-kappa B, WNT signaling and RNA splicing. Using a complementary bioinformatics approach, additional novel mutations in known dominant UM driver genes (GNAQ, GNA11, BAP1, SF3B1, EIFIAX and CYSLTR2) were identified and an accurate estimate of the frequencies of mutations in each gene were obtained. Finally, integration of data obtained from CNAs with mutational and transcriptome data reveled homozygous deletions, protein damaging mutations and gene fusions that targeted chromatin modifiers, and specifically genes encoding components of the human SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. Genes from the BAF complex (ARID1A and ARID1B) and the PBAF complex (PHF10) were subjected to functional loss through CNAs, gene fusions and mutations. Two of these chromatin modifiers (ARID1B and PHF10) map to chromosome 6q whose loss is associated with metastasis in a subset of UMs, and an ARID1B fusion is found in a tumour with a BAP1 mutation that subsequently underwent metastasis. In conclusion, this study provides a comprehensive overview of the landscape of genomic alterations in UM, identifying candidate genes in regions of CNAs and providing further insights into the altered pathways of tumour development and progression.
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MacKenzie, Ross Alastair Dudley. "Overcoming senescence in melanoma development." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611085.
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Kayaga, Justina. "Allogenic tumour vaccines for melanoma." Thesis, St George's, University of London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394404.
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White, Nicholas. "Purinergic signalling in malignant melanoma." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1446032/.
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Malignant melanoma is an aggressive cancer that originates from melanocytes, the pigment producing cells of the skin. The incidence of melanoma is increasing and the outcome for patients with advanced disease remains poor. New therapies for melanoma are in urgently needed as no current systemic treatment is effective. Interactions between the nervous system and epidermal melanocytes have been suspected on the basis of their common embryological origin from the neural crest. Both melanocytes and melanomas are innervated by autonomic nerves with acetylcholine and noradrenaline acting as transmitter molecules. It is now well established that the purine nucleotide adenosine triphosphate (ATP) is a co-transmitter with noradrenaline in sympathetic nerves and with acetylcholine in parasympathetic nerves. ATP acts on extracellular receptors which have been characterised to consist of a number of subtypes. ATP acting on these receptors is involved with both rapid signalling in neurotransmission and also long term signalling in cell proliferation, differentiation and apoptosis.
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Robinson, June K., Katie Baker, and Joel J. Hillhouse. "New Approaches to Melanoma Prevention." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/73.
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Skin cancer is a major public health concern, and tanning remains a modifiable risk factor. Multidimensional influences, including psychosocial, individual, environmental, and policy-related factors, create the milieu for individuals to engage in tanning. Parents and physicians can modify the behavior of teens and young adults using strategies based on harm reduction. Environmental and policy-related factors similar to those used to limit smoking by restricting access of minors to cigarettes in the United States in the 20th century need to be created. Federal regulations can restrict direct advertising and the excise tax can be increased to a prohibitive amount. Social networking may assist with affect regulation.
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Medic, Sandra. "PAX3 and cutaneous malignant melanoma." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2006. https://ro.ecu.edu.au/theses/341.
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Cutaneous Malignant Melanoma (CMM) is the most aggressive form of skin cancer, with high mortality rate in patients with metastatic spread. The focus of recent research has been to find molecular markers of melanoma that can be used to detect metastatic cells in the blood of patients with CMM and to assist in diagnosis and staging as well as to predict the outcome of the disease. PAX3, a transcription factor encoding gene that regulates melanocyte migration, proliferation and differentiation during development is found to be highly expressed in melanomas and melanoma cells, particularly its alternate transcript PAX3d. Therefore, the aim of this study was to establish an assay that can be used to detect occult melanoma cells in peripheral blood of patients with CMM and to assess PAX3d as a melanoma cell marker.
We used staged formalin-fixed paraffin-embedded tissue and metastatic lymph node tissue to assess the expression of PAX3 transcripts in primary and metastatic melanoma tissue as well as in naevi and normal skin. Although problematic we were able to establish a technique for isolation of total RNA from archival formalin-fixed tissue slides. Furthermore, we perfected blood collection procedures and methods of total RNA isolation from peripheral blood. We also demonstrated that real time qRT-PCR provides a significantly higher marker detection rate relative to conventional gel-based RT-PCR and therefore suggest its use as a more sensitive and accurate detection method.
Analysis of PAX3 expression in peripheral blood of patients diagnosed with CMM showed significantly higher marker expression frequency in patient blood samples in contrast to no expression in blood from healthy volunteers. Results also showed that the alternate transcript PAX3d was detected at significantly higher frequencies in peripheral blood of melanoma patients than the PAX3c alternate transcript. Moreover PAX3d was more frequently expressed in patients diagnosed with metastatic disease compared to those diagnosed with in-situ and invasive melanoma.
Frequent expression of PAX3d in patients with in-situ melanoma even after more than one year since diagnosis was interesting, and suggests the presence of circulating melanoma cells even at this early stage of the disease. Since recent studies have found that melanoma cells with high metastatic potential have a different gene expression signature compared to highly proliferative cells with low metastatic potential, it is still to be clarified whether PAX3d is a marker of metastatic cells with low or high metastatic potential. Nevertheless, results presented here show that PAX3d is a sensitive and useful marker of melanoma cells in peripheral blood of melanoma patients.
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Ng, Kin Cheung Philip. "The expression of XAF1 in melanoma and the role of ILK in melanoma invasive behavior." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31801.
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The high metastatic potential and the resistance to apoptosis are common features of melanoma that make effective treatment difficult. The design of novel strategies for the treatment of this disease relies on the identification of key regulators of melanoma apoptosis and metastasis. In the current study, we characterized the protein expression of a novel tumor suppressor, XIAP-associated factor 1 (XAF1) in 70 primary melanomas and determined the role of integrin-linked kinase (ILK) in melanoma cell migration and invasion. Our first study shows that XAF1 mRNA expression was weak or undetectable in majority of melanoma cell lines. More importantly, XAF1 expression was significantly reduced in melanoma tissues compared with benign nevi in both nucleus and cytoplasm. Since XAF1 has been shown to inhibit the antiapoptotic activity of XIAP, the loss of XAF1 in melanoma may contribute to the impairment of apoptosis pathway and ultimately the malignant nature of melanoma. In the second study, we have determined the possible role of ILK as a regulator of melanoma progression. Inhibition of the kinase activity of ILK and depletion of endogenous ILK expression both significantly reduced melanoma cell migration. Moreover, melanoma cells stably expressing ILK short hairpin RNA resulted in a marked reduction in colony formation on soft agar and inhibition of invasion through Matrigel. In vivo data from melanoma xenograft indicated that mice inoculated with melanoma cells depleted of ILK expression showed a much slower tumor growth compared with mice inoculated with control melanoma cells. In summary, the loss of XAF1 expression in melanoma biopsies and the inhibition of cell migration and invasion through the inhibition of ILK suggest that both factors may play a prominent role in melanoma apoptosis pathway and invasion, respectively. Further study on the therapeutic value of ILK inhibition and proapoptotic function of XAF1 may help the development of effective therapy against metastatic melanoma.Medicine, Faculty of
Medicine, Department of
Experimental Medicine, Division of
Graduate
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Karlsson, Pia. "Cutaneous melanoma in children and adolescents and aspects of naevus phenotype in melanoma risk assessment." Doctoral thesis, Linköping : Univ, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-7703.
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Errico, Maria Cristina. "Melanoma stem-like cells and melanoma cell lines: main molecular pathways and possible microRNA involvement." Thesis, Universita' degli Studi di Catania, 2011. http://hdl.handle.net/10761/94.
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Cancer Stem Cells (CSCs) have been identified in several malignancies and indirect evidences support the existence of melanoma stem-like cells. Since microRNAs (miRs), an abundant class of small non-coding RNAs playing important roles in regulating gene expression, are involved in melanoma development and progression, we investigated their possible involvement also in melanoma stem-like cells. We identified a subset of melanoma cells, isolated from lung metastatic melanomas that, cultured in appropriate serum free conditions, were able to propagate as non adherent spheres (SC), whereas in the presence of serum they adhere to the plastic and acquire the typical morphologic features of differentiated cells (PC). These melanoma spheres are also capable of self-renewing and tumorigenesis in vivo. Here we analyzed a group of selected miRs by qReal Time PCR and among them miR-221/-222 had the most consistent and significant increased expression in PC cells. In these cells we confirmed the inverse correlation between microRNA-221/-222 and p27Kip1 and c-KIT receptor, already reported in melanoma development and progression. Moreover, looking for new miR-221/-222-dependent target genes, we selected the proto-oncogene ETS-1 because its functional role in melanoma development was not completely elucidated. In fact ETS-1 has been reported either as a valuable diagnostic/prognostic marker or as molecule without a clear association with clinical outcome. Here we demonstrated that in melanoma stem cells as well as in melanoma cell lines ETS-1 is a direct target of miR-222. Furthermore we showed the existence of an ETS1-mediated repression of miR-222 in melanoma cell lines, thus we suggest that in putative melanoma stem cells proliferating as spheres (Mel SC) in comparison to their adherent counterpart (Mel PC) may be active an ETS-1 miR-222 circuitry whose deregulation could be relevant for melanoma progression. Further studies are in progress to understand the function of miRNAs in the context of gene networks controlling cell differentiation and tumorigenicity in melanoma stem-like cells.
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Cho, Kenneth Kunhee. "Acral Melanoma: Epidemiology and Treatment Outcomes." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/25557.
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Acral melanomas are a subtype of melanoma which affect the palms, nails and soles of the feet. Acral melanomas are characterised by different mutation signatures, prognoses and treatment outcomes compared to other forms of melanoma. Given the non-UV mutation signature in acral melanomas, the aetiology is thought to be a distinct but unknown driving factor. These two systematic reviews and meta-analyses presented in this thesis aimed to investigate the association of chronic mechanical stress with acral melanoma of the lower limbs, and the treatment outcomes of patients with metastatic acral melanoma.
A systematic database search was performed using PubMed, EMBASE and MEDLINE, with the grey literature also comprehensively searched using Google Scholar and Google Search. The references of included articles were examined for relevant studies. Studies were included if they met pre-determined specified criteria. Study quality was assessed using published critical appraisal tools. Random-effects models were used to calculate prevalence and to estimate the summary event rate, 95% confidence intervals and heterogeneity. Publication bias was assessed using Egger’s regression test and funnel plots. All statistical analysis was performed with the software Comprehensive Meta-analysis (version 3.0), Biostat. Englewood, NJ (2014).
Our first study identified that melanoma had a predilection to affect certain locations on the plantar surface of the foot, and these areas appeared to correlate with areas of chronic mechanical stress. Subungual melanoma in the feet disproportionally affected the first toe, also an area of the foot most frequently exposed to acute and chronic trauma. These findings in combination suggest repetitive force may be a contributing factor in the pathogenesis of plantar melanoma. Our second study revealed that treatment outcomes for patients with metastatic acral melanoma were poorer than other forms of cutaneous melanomas (acral overall survival: median 15 months, 95% CI 13.7-16.3 months, non-acral cutaneous: median 24 months, 95% CI 22.6-25.4 months, p<0.001). Patients with acral melanoma treated using anti-PD-1 therapy had higher overall survival at 12 months (53%) compared with anti-CTLA-4 monotherapy (34%; p<0.001)
In conclusion, this study supports the evidence of acral melanoma being a distinct subtype, with chronic mechanical stress acting as a possible aetiological factor. In addition, the estimates of treatment response for metastatic acral melanoma, demonstrated low levels of responses to current approved therapy, including anti-PD-1, one of the most active treatments in melanoma to date.
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Veronez, Luciana Chain. "Atividade da fosfoetanolamina sintética em melanoma murino experimental." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/17/17147/tde-15122012-123717/.
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O desenvolvimento de novas estratégias terapêuticas ao melanoma é de particular importância devido à sua baixa resposta aos tratamentos tradicionais. No presente trabalho, utilizamos modelo de melanoma murino experimental para estudarmos os efeitos da fosfoetanolamina (PEA) sintética sobre o desenvolvimento deste tumor. Nossos resultados demonstram que o fosfomonoéster apresentou efeito inibidor da proliferação de células da linhagem B16F10 in vitro, induzindo apoptose após estimulação por 24 a 72h. In vivo, o tratamento (via oral) de animais portadores de melanoma com diferentes doses de PEA (10, 20 e 40mg/Kg), durante 10 ou 20 dias consecutivos, resultou em volumes tumorais pelo menos 70% menores que o de animais controle e diferenças macroscópicas consideráveis. PEA induziu, de maneira dose-dependente, aumento da apoptose e diminuição da proliferação de células tumorais. O tratamento resultou em alterações hematológicas como aumento do número de plaquetas, eritrócitos e leucócitos. Dentre os leucócitos, observou-se uma maior proporção de linfócitos e monócitos após 10 e 20 dias de tratamento, respectivamente. Em adição, PEA induziu uma maior produção da citocina pró-inflamatória IL-6 e das citocinas anti-inflamatórias IL-10 e TGF- e menores níveis da citocina pró-inflamatória IFN-. Os níveis de IL-1, IL-12p70 e IL-17 não foram alterados com o tratamento. Nossos resultados demonstram um papel inibidor da PEA sobre a progressão do melanoma, contribuindo para um melhor entendimento de sua atividade anti-tumoral.The low responsiveness of melanoma to traditional treatments together with its increasing incidence makes the development of new therapeutic strategies against this type of cancer extremely important. In this study, we used a murine melanoma model to evaluate the effects of synthetic phosphoethanolamine (PEA) on the development of this tumor. In vitro, PEA had an inhibitory effect on the proliferation of B16F10 cells, inducing apoptosis after 24 to 72h stimulation. In vivo, oral treatment of melanoma-bearing animals with different doses of PEA (10, 20 e 40mg/Kg) during 10 or 20 consecutive days resulted in reduced tumor volumes (at least 70% compared to the control) and in expressive macroscopic differences. PEA also induced a dose-dependent increase of apoptosis and decrease in tumor cell proliferation. The treatment also resulted in hematological changes, such as increased numbers of platelets, erythrocytes and leukocytes. Among leukocytes, we observed a higher proportion of lymphocytes and monocytes after 10 and 20 days of treatment, respectively. In addition, PEA induced higher levels of the pro-inflammatory cytokine IL-6 and of the anti-inflammatory cytokines IL-10 and TGF-, and it also induced a lower production of the pro-inflammatory cytokine IFN-. No differences were observed in the levels of IL-1, TNF-, IL-12p70 and IL-17 upon treatment. Our results demonstrate an inhibitory role of PEA in the development of melanoma, contributing to a better understanding of its antitumoral activity.
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Liu, Yuxi. "Anti-melanoma effects and mechanisms of action of a Chinese medicine formula Huai-Hua-Jin-Yin-Jiu." HKBU Institutional Repository, 2020. https://repository.hkbu.edu.hk/etd_oa/802.
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Huai-Hua-Jin-Yin-Jiu, a traditional Chinese medicine (TCM) formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos, was used for treating melanoma in ancient China. Our group has previously shown that an ethanolic extract of SL (SLE) possesses anti-melanoma effects, and that inhibiting STAT3 signaling contributes to the action mechanisms. STAT3 activation promotes the formation of an immunosuppressive microenvironment of melanoma. Regulation of the miR-let- 7/CCR7 pathway is a strategy for treating metastatic melanoma. Chrysoeriol is a flavonoid identified in SLE. The compound has anti-tumor properties, but there is no report about its effects on melanoma. The first aim of this study is to determine whether SLE inhibits melanoma progression by reprogramming tumor microenvironment; the second aim is to explore the involvement of miR-let-7a/f- CCR7 signaling in the anti-metastatic effects of SLE; and the third aim is to elucidate the anti-melanoma mode and mechanisms of action of chrysoeriol. Results showed that SLE suppresses melanoma growth and angiogenesis in mice. SLE inhibits STAT3 signaling, and alters immune cell compositions and molecules involved in STAT3 signaling in melanoma tissues. Cell co-culture experiments showed that SLE inhibits STAT3 signaling in melanoma cells and splenic lymphocytes. Over-activation of STAT3 in melanoma cells diminishes SLE's effects in altering compositions of immune cells and STAT3 signaling molecules in the co- culture system. Small RNA sequencing showed that SLE upregulates miR-let-7a/f levels in B16F10 melanomas. RT-qPCR analyses confirms these results. SLE elevates miR-let- 7a/f levels, and inhibits CCR7 (a target gene of miR-let-7a/f) signaling in melanoma cells. In a lung metastasis mouse model, SLE inhibits melanoma metastasis, elevates miR-let-7a/f levels, and suppresses CCR7 signaling. Knockdown of miR-let-7a/f diminishes the effects of SLE on CCR7 signaling and melanoma cell invasion; and overexpression of CCR7 lessens the effects of SLE on melanoma cell invasion. Chrysoeriol shows in vitro and in vivo anti-melanoma effects. Molecular dynamics and microscale thermophoresis assays demonstrate that chrysoeriol directly binds to Src. Chrysoeriol suppresses the Src/STAT3 pathway in melanoma cells and tissues. Chrysoeriol's anti-proliferative effects are diminished by STAT3 over- activation in melanoma cells. Chrysoeriol also has inhibitory effects in vemurafenib- resistant melanoma cell and animal models. RNA-seq analyses shows that syndecan-3 mRNA level is lower in vemurafenib-resistant cells than in vemurafenib-sensitive cells, and chrysoeriol reverses this vemurafenib resistance-associated downregulation. RT-qPCR and Western blotting analyses confirmed the results. In conclusion, we have demonstrated that reprograming immune microenvironment, partially mediated by inhibiting STAT3 signaling, contributes to the anti-melanoma mechanisms of SLE. Regulation of the miR-let-7a/f-CCR7 pathway is another mechanism underlying the anti-melanoma effects of SLE. Chrysoeriol is identified to be one of the active components responsible for the anti- melanoma effects of SLE. Inhibiting the Src/STAT3 pathway contributes to the anti- melanoma mechanisms of chrysoeriol. Chrysoeriol is able to overcome vemurafenib resistance in melanoma, and upregulation of syndecan-3 is involved in the action mechanisms. This study provides further pharmacological and chemical justifications for the use of the formula SL in treating melanoma, and suggests that SLE and SLE- derived compounds have the potential to be developed as modern alternative and/or complimentary agents for melanoma management
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Prado, Sara Santos Bernardes Real. "Estresse oxidativo e biomarcadores do metabolismo do ferro em pacientes com melanoma cutâneo e melanoma recidivado." Universidade Estadual de Londrina. Centro de Ciências Biológicas. Programa de Pós-Graduação em Patologia Experimental, 2014. http://www.bibliotecadigital.uel.br/document/?code=vtls000192063.
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Uma das correlações mais aceitas no prognóstico do melanoma cutâneo é a medida da espessura de Breslow, onde tumores mais espessos se relacionam fortemente com o risco de disseminação da doença e morte. O estresse oxidativo sistêmico em pacientes com câncer é reportado na literatura, porém seu papel no prognóstico de doenças malignas ainda é controverso. As ferritinas de cadeia pesada (FCP) e leve (FCL) são proteínas envolvidas no metabolismo do ferro, relacionadas a um pior prognóstico no câncer. O fator de crescimento tumoral beta-1 (TGF-β1) está intimamente relacionado com a iniciação, progressão e metástase tumoral, sendo os radicais livres capazes de regular sua atividade. A relação entre o estresse oxidativo e moléculas relacionadas, como as envolvidas no metabolismo do ferro e na resposta inflamatória, ainda não é bem caracterizado no melanoma. O objetivo deste trabalho foi caracterizar esses parâmetros em pacientes em diferentes estadiamentos dessa doença. A medida de espessura de Breslow e a presença ou não de recidivas foram utilizadas como parâmetros na divisão dos grupos. Um total de 83 pacientes foram recrutados no Hospital do Câncer de Londrina entre abril de 2011 e novembro de 2012. O grupo controle compreendeu 65 indivíduos saudáveis. O sangue venoso foi coletado e usado nas análises sistêmicas. Também foram selecionados aleatoriamente 70 blocos parafinizados de tumores de melanoma analisados no Departamento de Patologia do Hospital do Câncer de Londrina, a fim de estudar o estresse oxidativo e moléculas relacionadas no tecido tumoral por imuno-histoquímica. Quanto maior a espessura de Breslow e agressividade da doença (recidiva), mais evidentes foram as modificações oxidativas e inflamatórias sistêmicas, caracterizadas principalmente pelo aumento dos níveis de malondialdeído (MDA) e proteína C reativa (PCR). Além disso, tumores cutâneos com maior espessura de Breslow apresentaram maior concentração do produto de oxidação de proteínas 3-nitrotirosina nas análises de imunohistoquímica de células de melanoma e no tecido peritumoral quando comparados a tumores menores. Pacientes com recidiva e alto risco de recidiva, apresentaram aumento de FCP sistêmica, enquanto todos os pacientes com melanoma apresentaram aumento da relação FCP:FCL quando comparados a indivíduos saudáveis. O aumento dos níveis de FCP foi acompanhado do aumento do estresse oxidativo sistêmico, avaliado pela lipoperoxidação de hemácias. Células de melanoma apresentam aumento na marcação de FCP por imunohistoquímica porém em níveis iguais entre as diferentes classificações do tumor. A p53, proteína envolvida na proliferação celular, apresentou-se aumentada em tumores metastáticos quando comparados a tumores cutâneos com menores espessuras de Breslow. Pacientes com recidiva apresentaram baixos níveis sistêmicos de TGF-β1, acompanhados de altos níveis de MDA, lipoperoxidação de hemácias e de 3-nitrotirosina. Os resultados mostram o estresse oxidativo e moléculas relacionadas possuem perfis característicos nos diferentes estadiamentos do melanoma, acrescentando uma nova perspectiva sobre o estado redox e seu possível envolvimento com a evolução da doença.Surgical removal of cutaneous melanoma can cure most of the patients, however, the risk of recurrence remains for years. One of the most accepted correlation in cutaneous melanoma prognosis is Breslow thickness, where high tumor thickness values at diagnosis is strongly related to melanoma spread and high morbidity. Oxidative stress in patients with cancer is reported in literature, but their role in prognosis is still controversial. The ferritin heavy (FHC) and light chains (FLC) are proteins involved in iron metabolism, related to a poor prognosis in cancer. The inflammatory mediator transforming growth factor beta-1 (TGF-β1) is closely linked with initiation, progression and tumor metastasis, and free radicals are capable of regulating their activation. The relationship between oxidative stress and related molecules such as those involved in the iron metabolism and inflammatory response is still not well characterized in melanoma. The objective of this study was to characterize these parameters in patients in different stages of this disease. Breslow thickness and the presence or absence of recurrence was used as parameters for group division. A total of 83 patients were recruited at the Cancer Hospital of Londrina between April 2011 and November 2012. The control group comprised 65 healthy volunteers. Venous blood was collected and used in systemic analyzes. Moreover, 70 blocks of paraffin-embedded melanoma from patients treated between 2004 to 2012 were randomly selectedand analyzed at the Department of Pathology, Cancer Hospital of Londrina, in order to study oxidative stress and related molecules in tumor tissue by immunohistochemistry. The higher the Breslow thickness and aggressiveness of the disease (recurrence) the more evident were the systemic inflammatory and oxidative modifications, mainly evidenced by increased levels of malondialdehyde (MDA) and C-reactive protein (CRP). Furthermore, skin tumors with higher Breslow thickness showed increased labeling of the protein oxidation product 3-nitrotyrosine in melanoma cells and peritumoral tissue compared to smaller tumors. Recurrence and high risk recurrence patients showed increased FHC levels, while all patients with melanoma had increased FHC:FLC ratio when compared to healthy subjects. The increased levels of FHC were followed by the increased systemic oxidative stress, measured by red blood cells lipid peroxidation. Melanoma cells showed FHC expression, but the levels did not differ between tumor stages. The p53, a protein involved in cell proliferation, had increased labeling in metastatic tissue compared with thin Breslow thickness cutaneous tumor. Recurrence patients had low TGF-β1 systemic levels, accompanied by high levels of MDA, red blood cells lipid peroxidation and 3-nitrotyrosine in tumoral tissue. The results show that oxidative stress and related molecules have characteristic profiles in different melanoma stages, adding a new perspective on the redox state and their possible involvement in disease progression.
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Mendes, Rosemairy Luciene. "Morfologia e regimes de crescimento das linhagens celulares derivadas de melanoma murino B16F10, primário e metastático, em camundongos BALB/c." Universidade Federal de Viçosa, 2011. http://www.locus.ufv.br/handle/123456789/7113.
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Embora não esteja entre as neoplasias mais prevalentes é responsável pela quarta causa de morte entre os pacientes com câncer. A compreensão dos mecanismos envolvidos na gênese e progressão do melanoma é crucial para o seu tratamento. Modelos experimentais que representem as fases da progressão do melanoma ainda são raros, mas a cultura de células é uma ferramenta importante para tais investigações. Os objetivos deste trabalho foram: estabelecer um modelo de estudo do melanoma murino B16F10 por meio do estabelecimento de sublinhagens celulares que correspondem ao tumor primário e às metástases, após passagem dessas células in vivo em camundongos BALB/c; caracterizar morfologicamente por meio de microscopia óptica e eletrônica de transmissão (MET) e varredura (MEV) a linhagem B16F10 e as sublinhagens derivadas; e investigar as leis de escala que regem o crescimento das linhagens de células de melanoma. Nesse contexto, células de melanoma B16F10 foram injetadas subcutaneamente (sc.) em camundongo BALB/c e a linhagem derivada dos tumores primários foi denominada de B16F10B. A linhagem B16F10 e a sublinhagem B16F10B foram inoculadas endovenosamente (ev.) em camundongos BALB/c e as sublinhagens obtidas das metástases foram denominadas B16F10M e B16F10BM, respectivamente. A linhagem B16F10 e as sublinhagens B16F10B, -BM e -M foram analisadas em MO, MET e MEV, revelando uma grande heterogeneidade na morfologia dessas células e nos agregados por elas formados. As células B16F10 e B16F10B também revelaram à MET presença de partículas virais. Para a caracterização das leis de escala que regem os regimes de crescimento das células B16F10, -B, -BM e -M, as linhagens celulares foram cultivadas sobre lamínulas de vidro em placas de 24 poços e retiradas em intervalos de 24 horas, durante 7 dias. O número de células por agregado e o número total de agregados foram usados para determinar a função de distribuição de tamanho de agregados que sugerem uma transição nas funções de distribuição de um decaimento exponencial para um que segue lei de potência para as células B16F10B. As demais linhagens analisadas sempre exibiram um comportamento de lei de potência. A distribuição em leis de potência indica a ausência de um tamanho característico para os tamanhos dos agregados, podendo refletir na falta de mecanismos de controle da replicação celular aliada à estabilidade dos agregados. A transição no regime de crescimento exibido pelas células B16F10B sugere que o crescimento celular contínuo na cultura pode exercer forças seletivas que destroem os mecanismos de regulação, tais como a dependência de ancoragem e o crescimento de densidade-dependente. A caracterização morfológica, bem como do regime de crescimento das sublinhagens derivadas das células B16F10 mostrou que há diferenças e similaridades entre as mesmas, porém, para uma melhor caracterização dessas células, outras análises devem ser realizadas, tais como: resistência a drogas, integridade genômica e padrão de expressão de moléculas de adesão.
Melanoma is a malignant neoplasm derived from melanocytes, specialized pigmented cells that are found predominantly in the skin. Although it does not figure among the most prevalent cancer types, melanoma is responsible for the fourth leading cause of cancer patients death. Understanding of the mechanisms involved in the genesis and progression of melanoma is crucial for the cancer treatment. Experimental models that representing phases of melanoma progression are still rare, but the cell culture is an important tool for such investigations. The aims of the work were to determine a study model of murine melanoma B16F10 by the establishment of cell sublineages corresponding to the primary tumor and to the metastases, after passage of these cells in BALB/c mice; to characterize morphologically by optical microscopy (OM) and transmission electron (TEM) and scanning electron (SEM) the B16F10 lineage and sublineages derived from B16F10; to investigate the scaling laws that rule the growth of melanoma cell lines. In this context, B16F10 melanoma cells were injected subcutaneously (sc) in BALB/c mice and the subline derived from subcutaneous tumors was named B16F10B. The B16F10 lineage and the B16F10B sublineage were inoculated intravenous (iv) in BALB/c mice, and the sublineages of metastases obtained were named B16F10M and B16F10BM, respectively. The B16F10B lineage and the B16F10, -BM and -M sublineages were analyzed by OM, TEM and SEM, what revealed an extent heterogeneity in the morphology of these cells and clusters formed by them. B16F10 and B16F10B cells also disclosed to MET viral particles presence. To characterize the scaling laws that rule the growth regimes of the B16F10, -B, -BM and -M cells, the cells lineages were cultured on glass coverslips in 24-well plates and removed at intervals of 24 hours for 7 days. The number of cells per cluster and the total number of clusters were used to determine the cluster size functions. The results suggest distribution functions with a transition to an exponential decay that follows a power law for B16F10B cells. The other lineages analyzed always exhibits a power law behavior. The power law distribution indicates the absence of a characteristic size for the clusters sizes which, from the biological point of view, might reflect the lack of control mechanisms of cell replication allied to the stability of clusters. The transition in the growth regime exhibited by B16F10B cells suggests that the continued cell growth in culture may exert selective forces which destroy regulation mechanisms such as cell anchorage dependence and density-dependent growth.
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Rooij, Michaela Johanna Maria de. "Volunteer melanoma screening pros and cons /." [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 1997. http://arno.unimaas.nl/show.cgi?fid=5922.
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Bergman, Louise. "Uveal melanoma : epidemiological and clinical aspects /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-413-9/.
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Berg, Peter. "Malignant melanoma in children and adolescents /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-567-0/.
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