This investigation was concerned with characterizing effects of this tumor line on lipid metabolism in DBA/lJ mice and serum protein levels and cellular changes in DBA/lJ and Swiss white mice. Total lipids, lipid phosphorus, neutral lipids, and changes in fatty acids were determined in liver, spleen, skin, and tumor of DBA/lJ mice bearing the lymphosarcoma at various days after injection of tumor cells.

Thesis (M.Med.Sc.)--University of Hong Kong, 2003. / Includes bibliographical references (leaves 40-47). Also available in print.

The role of protein kinases in modulating cell proliferation was examined. Studies characterized the regulation of cell proliferation by adenosine 3':5'-monophosphate-dependent protein kinase (cA-PK). Calcium/calmodulin-dependent myosin light chain kinase (MLCK) was isolated and examined as a potential substrate regulated by cA-PK in the rapidly proliferating.

The investigation was concerned with characterizing effects of this tumor line on lipid metabolism in DBA/1J mice and serum protein levels and cellular changes in DBA/1J and Swiss white mice. Total lipids, lipid phosphorus, neutral lipids, and changes in fatty acids were determined in liver, spleen, skin and tumor of DBA/1J mice bearing the lymphosarcoma at various days after injection of tumor cells.

This study examined differences in psychosocial adjustment and sexual function between female survivors of Hodgkin's disease and a control group of recently diagnosed but untreated cancer patients. The Hodgkin's disease survivors were assigned to one of two groups depending on whether they had retained ovarian functioning following their cancer therapy. Differences among the three groups were examined on variables consisting of the principal components derived from scores on the: Derogatis Sexual Functioning Inventory (DSFI); Brief Symptom Inventory (BSI); and Psychosocial Adjustment to Illness Scale (PAIS). These variables included: DSFI (General background and sexual functioning, Attitudes and feelings, and Information and Drive); BSI (General distress, and Somatic anxiety); and PAIS (General social functioning, and Health care orientation). No statistically significant differences in psychosocial adjustment and sexual function were found among the three groups. Additional analyses suggested that women who required therapeutic abortions to terminate pregnancies (existing at their diagnosis or occurring while they were receiving cancer treatment) had greater problems in psychosocial adjustment and sexual function than those who did not require abortions.

This investigation was concerned with characterizing a tumor line induced and maintained in this laboratory. Various chemical assays, cell counts, and electron microscopy were the methods employed to characterize the blood of mice bearing the tumor at days 3, 6, 9, and 12 after injection of the 1.2 x 10^8 tumor cells.

The purpose of this investigation was (1) to isolate and purify glyoxalase I from the livers of normal DBA/lJ mice and the livers from mice bearing a lymphosarcoma tumor; and (2) to determine, at least with respect to glyoxalase I, if the tumor has an effect on the chemical properties or structure of macromolecules in an organ removed from tumor locale and not histologically affected by its presence.

The problem with which this investigation is concerned is that of determining the nature of events leading to the change. of normal cells into malignant cells. The design of the study is multi-phasic: (A) to establish the presence or absence of an oncogenic virion, (B) to demonstrate by use of the electron microscopy any ultracellular alteration in malignant or transformed tissues, (C) to investigate the nature of the transforming agent in the murine lymphosarcoma, and (D) to employ various methods to demonstrate cellular transformations in vivo and in vitro. It is concluded that the transforming and tumorinducing agent in this' investigation was not a virion, but an infectious ribonucleic acid genome or a segment of a viral genome which had become integrated into the genome of the mouse cells. The vision has lost its ability to form a protein coat; therefore it is not demonstrable as a virion. But the ribonucleic acid is able to infect other cells and transform them from normal to neoplastic tissues.

Orientador: Deilson Elgui de Oliveria / Banca: Lígia Niéro-Melo / Banca: Daniel Onofre Vidal / Banca: Alexandrona Sartori / Banca: Otávio Cesar Carvalho Guimarães Baiocchi / Resumo: Linfoma de Hodgkin clássico (LHc) é uma neoplasia maligna que apresenta um padrão aberrante de expressão de citocinas, incluindo IL-10 e TNF-a. Polimorfismos de nucleotídeo único (SNPs) nos genes codificadores de IL-10 e TNF-a ou de suas proteínas regulatórias, como NFkB, podem interferir na patobiologia do LHc. No presente estudo, SNPs nas regiões promotoras dos genes de IL-10 (SNP/pIL-10 -592, rs1800872; e SNP/pIL-10 -1082, rs1800896) e TNF-a (SNP/pTNF-a -238, rs361525; e SNP/pTNF-a -862, rs1800630), assim como na região intrônica do gene NFkB1 (SNP/iNFkB1, rs1585215) foram genotipados em 73 pacientes com LHc e avaliados em relação à sua associação com parâmetros prognósticos clínicos e laboratoriais da doença. SNPs/pIL-10 AA foram significativamente associados a maiores contagens de leucócitos e menores valores de linfócitos ao diagnóstico. No caso de TNF-a, SNP/pTNF-a -238 AG foi associado à presença de infecção pelo EBV enquanto SNP/pTNF-a -862 CC apresentou-se mais frequentemente com leucocitose. SNP/iNFkB1 AA associaramse à doença em estádio IV e padrão extranodal de apresentação. Entretanto, nenhum dos SNPs avaliados teve efeito no desfecho do tratamento. Esse estudo mostrou que alguns genótipos de SNPs nos genes de IL-10 e TNF-a estão associados a parâmetros prognósticos no LHc. Adicionalmente, pela primeira vez foram descritas associações entre SNP/iNFkB1 (rs1585215) e aspectos clínicos da doença / Abstract: Classic Hodgkin lymphoma (cHL) is a malignant lymphoid neoplasia that shows aberrant expression of cytokines, including IL-10 and TNF-a. Single nucleotide polymorphisms (SNPs) in genes encoding IL-10 and TNF-a or their regulatory proteins, such as NFkB, may impact cHL pathobiology. In this study, SNPs in the promoter regions of genes encoding for IL-10 (SNP/pIL-10 -592, rs1800872; and SNP/pIL-10 -1082, rs1800896), and TNF-a (SNP/pTNF-a -238, rs361525; and SNP/pTNF-a -862, rs1800630), as well as in the intronic region of the NFkB1 gene (SNP/iNFkB1, rs1585215) were genotyped in 73 patients with cHL and evaluated against clinical and laboratory prognostic parameters for the disease. SNPs/pIL-10 AA were significantly associated with higher leukocyte and lower lymphocyte counts at diagnosis. In case of TNF-a, SNP/pTNF-a -238 AG was associated with EBV infection while SNP/pTNF-a -862 CC presented more frequently with leukocytosis. SNP/iNFkB1AA generally had stage IV and extranodal disease at diagnosis. Nonetheless, none of the studied SNPs had effect on on treatment outcome. This study shows that some SNPs genotypes for IL-10 and TNF-a genes are associated with prognostic parameters in cHL; furthermore, this is the first time that the SNP/iNFkB1 (rs1585215) was implicated in clinical features of the disease / Doutor

Na radioterapia, o planejamento é parte fundamental do tratamento de um paciente. Para que o planejamento seja bem sucedido, o físico deve utilizar parâmetros físicos baseados na interação da radiação com a matéria para determinar a dose no volume alvo. Esses parâmetros são obtidos a partir de campos com dimensões bem definidas (geralmente quadrados), porém, na radioterapia é comum aparecer campos irregulares. Para resolver este problema, utilizam-se métodos que convertem esses campos irregulares em equivalentes de campos quadrados. Quando se tem campos pequenos, a aproximação de Sterling (algoritmo que permite a obtenção do campo quadrado equivalente a partir da razão entre quatro vezes a área efetiva de irradiação pelo perímetro que a envolve) é bem sucedida, porém quando o campo é muito grande e irregular, esta relação mais tão eficiente. Para tal caso, tem-se um método conhecido por Método de Clarkson. O método de Clarkson é um algoritmo que utiliza valores obtidos a partir de funções que relacionam a interação da radiação com a matéria, tais como, Razão Espalhamento Ar (SAR) e Razão Tecido Ar (TAR), para determinar especialmente campos quadrados equivalentes de campos irregulares e de grandes dimensões ou para calcular a dose de radiação em um ponto do paciente. A utilização deste método é muito trabalhosa, pois exige muitas horas de trabalho manual de um profissional especializado. Este trabalho desenvolveu um programa que analisa uma magem digital de um campo irregular, como os campos encontrados frequentemente no tratamento de linfomas do tipo Hodgking (manto), e determina um campo regular equivalente a este. As incertezas entre o método de Clarkson manual e o programado foram de ( -0,52 ± 0,60 )% e validam o programa desenvolvido. / Radiotherapy has a fundamental part that is the patient treatment planning. For its success, the medical physicist has to use physical parameters based on the radiation interaction with the matter, in this case the patient; in order to determine the radiation absorbed dose in the selected target volume. The physical parameters normally are related to regular radiation field sizes, although irregular fields can be also used in some treatments. To overcome this problem there are methods that convert irregular fields in regular fields, such as a square one. For small fields the Sterling\'s Method (technique to calculate equivalent square fields making use of ratio four times the effective area of irradiation by is perimeter) can be used. However, this method is not adequate for large irregular field. In this case, the Clarkson\'s Method is used. The Clarkson\'s Method uses values functions, such as Scattering-Air Ratio (SAR) and Tissue-Air Ratio (TAR), related with radiation interaction of with matter, to determine equivalent square fields from those large irregular ones or to calculate the radiation absorbed dose in the point of interest in a patient The application this method takes time, once it needs a considerable time from the medical physicist attention and also from the equipment. In this work, a software was developed to analyse digital images of large irregular fields, such as fields found in treatment of Hodgkin\'s disease (mantle) correlating them to regular equivalent fields. The uncertainty between the manual Clarkson and the programmed was inferred as ( -0,52 ± 0,60 )%, what can validate the program developed.