Thesis (M.S. in biochemistry)--Washington State University, May 2006. / Includes bibliographical references (leaves 81-86).

Thesis (doctoral)--University of Tartu, 2005.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2007. / Includes bibliographical references. Also available in electronic version.

Thesis (Ph. D.)--Ohio State University, 2007. / Full text release at OhioLINK's ETD Center delayed at author's request

Aline Borba Sbardelotto. Estudo do mecanismo de citotóxicidade da oncocalixona-A em leucemia promiolocítica humana – linhagem HL-60. 2013. 103 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2013. / Submitted by denise santos (denise.santos@ufc.br) on 2015-01-27T11:21:47Z No. of bitstreams: 1 2013_dis_absbardelotto.pdf: 2256619 bytes, checksum: 5769a859b286e70e7de75a9e8b9ddbd5 (MD5) / Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2015-01-27T11:23:29Z (GMT) No. of bitstreams: 1 2013_dis_absbardelotto.pdf: 2256619 bytes, checksum: 5769a859b286e70e7de75a9e8b9ddbd5 (MD5) / Made available in DSpace on 2015-01-27T11:23:29Z (GMT). No. of bitstreams: 1 2013_dis_absbardelotto.pdf: 2256619 bytes, checksum: 5769a859b286e70e7de75a9e8b9ddbd5 (MD5) Previous issue date: 2013 / Auxemma oncocalyx Taub. belongs to the Boraginaceae family. It is known as “pau branco” and is frequently found in the State of Ceará. The skin of that tree is an astringent and is commonly used as a medicine for wounds. Oncocalyxone A (Onco-A) is a quinone isolated from the ethanolic extract of A. oncocalyx, it has exhibited a series of pharmacological properties, such as analgesic, anti-inflammatory, antioxidant, cytotoxic and antitumor properties. The present study tried to provide a basic set of data on the cytotoxic effects of Onco-A against human promyelocytic leukemia cell line HL-60. The cytotoxic potential of Onco-A was evaluated by the MTT assay, colorimetric analysis, after 24 hours exposure in HL-60 cells with increasing concentrations (8, 16,5 e 33 µM). After the cells were exposure, there were performed experiments to identify the mecanisms of action in vitro (flow cytometry) by the cellular viability, phosphatidyl externalization, internucleosomal DNA fragmentation, identifying apoptotic pathway; the experiments to morphological analysis were made with tripan blue, May-Grunwald-Giemsa, and acridine orange/ethidium bromide; DNA integrity’s test by cometa assay; and the avaliation of interection of enzyme topoisomerase with Onco-A. Results: according to MTT test results, Onco-A showed a significant cytotoxic activity against HL-60 cells (IC50 11 µM). In addition, morphological analysis of cells treated with lower concentration of Onco – A demonstrated that there were reduction in cell’s volume, formation of apoptotic bodies, chromatin condensation, phosphatidylserine externalization, also reduction of cell viability and DNA fragmentation. The Onco-A caused mitochondrial depolarization, activated caspase starters -9 and -8, and the effectors -3 and -7, cleaved Poly ADP-Ribose polymerase – intrinsic and extrinsic pathways. Although our results had shown that none of the doses was able to generate Reactive Oxigen Species, after pre-treated for 1 hour with N-acetylcysteine, the cytotoxicity of Onco-A was changed, an increase in membrane integrity, decreased DNA fragmentation, drag on the G2/M cell cycle phase and low levels of DNA damage. Besides the Onco-A does not interact with the enzyme topoisomerase, the data suggest that their target as Michael acceptor, can be the DNA. These results suggest that apoptosis is one of the major forms of cell’s death caused by Onco-A, and reinforces the compound may be a prototype for cancer therapy. / Auxemma oncocalyx Taub pertence a família das Boraginaceae, é conhecida como “pau branco” e frequentemente encontrada no estado do Ceará. A casca da árvore é um adstringente e popularmente utilizado no tratamento de feridas. Oncocalixona A (Onco-A), uma quinona isolada do extrato etílico da A. oncocalyx, possui uma série de propriedades farmacológicas, tais como: analgésica, anti-inflamatória, antioxidante, citotóxica e antitumoral. O presente estudo foi realizado para avaliar os efeitos citotóxicos da Onco-A na linhagem tumoral promielocítica, HL-60. O potencial citotóxico foi avaliado pelo teste colorimétrico de análise indireta, MTT, depois de 24 horas de exposição das células HL-60 às concentrações crescentes (8, 16,5 e 33 µM) da Onco-A. Após o tratamento, os procedimentos experimentais realizados para identificar os mecanismos de ação in vitro (no citômetro de fluxo) foram de viabilidade celular, externalização da fosfatildiserina, fragmentação do DNA intercucleossomal, identificação da via apoptótica, geração de espécie reativa de oxigênio; os experimentos de análise morfológica foram com azul de tripan, May-Grunwald-Giemsa, e laranja de acridina/ brometo de etídio; a integridade do DNA pelo teste cometa e também avaliado a interação da Onco-A com enzima topoisomerase. Resultados: de acordo com o teste do MTT, Onco-A apresentou significante citotoxicidade nas linhagem HL-60 (IC50 11 µM). As análises dos experimentos demonstraram que as células tratadas com a menor concentração de Onco-A tiveram redução no volume celular, formação de corpos apoptóticos, condensação da cromatina, externalização de fosfatildiserina, redução da viabilidade celular e fragmentação do DNA. Onco-A causou despolarização mitocondrial, ativou caspase iniciadoras -9 e -8, e as efetoras -3 e -7, clivou a proteína Poli ADP-Ribose polimerase – via intrínseca e extrínseca. Apesar de nossos resultados demonstrem que nenhuma das doses foi capaz de gerar espécies reativas de oxigênio, depois de pré-tratadas por 1 hora com N-Acetilcisteína, a citotoxicidade da Onco-A foi alterada, apresentando aumento na integridade da membrana, diminuição na fragmentação do DNA, parada na fase do ciclo celular G2/M e baixo nível de dano no DNA. Embora a Onco-A não interaja com as enzimas topoisomerases, os dados apresentados sugerem que seu alvo, como aceptor de Michael, pode ser a molécula de DNA. Esses resultados sugerem que a apoptose é uma importante forma de morte celular causada pela Onco-A, e reforça que o composto pode ser um protótipo para o tratamento do câncer.

by Royal Alfred McGraw. / Vita. / Thesis (M.S.)--Florida State University. / Bibliography: leaves 42-43.

Typescript. / Thesis (Ph. D.)--Florida State University, 1970. / Includes bibliographical references.

Typescript. / Thesis (M.S.)--Florida State University, 1969. / Includes bibliographical references.

Spermatogenesis in Cancer productus Randall was studied to determine the availability of cells and chromosomes suitable for the localization of crab dAT. It was found that throughout most of the year the reproductive tract contained resting spermatogdnial cells and a few residual spermatophores. Between April and July there was a burst of meiotic activity observed both cytologically and by the incorporation of a radioactive DNA precursor, tritiated-thymidine. The mean haploid chromosome number for C. productus was found to be 47.0 ± 4.1, lower than the previously reported number of 58. / Science, Faculty of / Zoology, Department of / Graduate