Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2002. / Includes bibliographical references (leaves 74-85). Also available in electronic version. Access restricted to campus users.

Inaugural dissertation.--Universität Greifswald, 1899.

Proefschrift Maastricht. / Met lit. opg. - Met een samenvatting in het Nederlands.

RIOS, Maria Erivanda França. Estudo da atividade citotóxica e do potencial antitumoral do extrato acetônico das sementes de Annona muricata L.(AMSA), em modelos experimentais in vitro e in vivo. 2013. 122 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2013. / Submitted by denise santos (denise.santos@ufc.br) on 2013-08-05T13:45:37Z No. of bitstreams: 1 2013_dis_mefrios.pdf: 2626800 bytes, checksum: 0037c014fd2a250a03a2299014aa3a3a (MD5) / Approved for entry into archive by Erika Fernandes(erikaleitefernandes@gmail.com) on 2013-08-06T11:55:05Z (GMT) No. of bitstreams: 1 2013_dis_mefrios.pdf: 2626800 bytes, checksum: 0037c014fd2a250a03a2299014aa3a3a (MD5) / Made available in DSpace on 2013-08-06T11:55:05Z (GMT). No. of bitstreams: 1 2013_dis_mefrios.pdf: 2626800 bytes, checksum: 0037c014fd2a250a03a2299014aa3a3a (MD5) Previous issue date: 2013 / Annona muricata, popularly known as soursop, is a plant widely used in folk medicine as teas and infusions for the treatment of various diseases such as cancer. The aim of this study was to cytotoxicity evaluate the antitumor activity of the acetone extract of the seeds of Annona muricata. This study was conducted with a panel of four tumor cell lines, HL-60 cells, HCT-116, SF-295 and OVCAR-8 IC50 values obtained 0.1944 µg/ ml, 0.1488 µg/mL, 0.0601 µg/mL and 0.0987 µg/mL, respectively. In the analysis across from erythrocytes of mice obtained the IC50 of 9.23 µg/mL. The acute toxicity study was conducted in vivo and DL50 was 310.2 mg/kg. The study of hemolytic activity was performed using cell suspension from mice without causing lysis. The evaluation study antitumor doses (7.5, 15 and 30mg/kg/day orally) in mice transplanted with Sarcoma 180 showed activity at all doses, causing a reduction of 48.41% of tumor growth at the highest dose . Analyses of liver and kidney revealed that there were some changes in the liver, such as steatosis and focal necrosis suggesting liver toxicity in mice treated with acetone extract of the seeds of Annona muricata. These changes are, however, considered the possible reversal of the tissue with treatment discontinuation or dose adjustment. Biochemical analysis revealed an increase in serum creatinine at doses of 15 and 30 mg/kg/day. In haematological tests there were no changes in the groups treated with acetone extract of the seeds of Annona muricata. The results showed little change in physical parameters of the animal, biochemical and hematological showing that the extract is well tolerated and less toxic. / Annona muricata, conhecida popularmente como gravioleira, é uma planta usada amplamente na medicina popular na forma de chás e infusões para o tratamento de diversas doenças, como o câncer. O objetivo deste trabalho foi avaliar a citotoxicidade e a atividade antitumoral do extrato acetônico das sementes de Annona muricata. O presente estudo foi realizado frente a um painel de 4 linhagens de células tumorais, as células HL-60, HCT-116, SF-295 e OVCAR-8 obtiveram os valores de IC50 0,1944µg/mL, 0,1488µg/mL, 0,0601µg/mL e 0,0987 µg/mL respectivamente. Na análise frente a eritrócitos de camundongos obtivemos a IC50 de 9,23µg/mL. O estudo de toxicidade aguda foi realizado in vivo e a DL50 foi de 310,2 mg/kg. O estudo da atividade hemolítica foi feita utilizando suspensão de eritrócitos de camundongos não causando lise. O estudo da avaliação antitumoral nas doses (7,5; 15 e 30mg/kg/dia por via oral) em camundongos transplantados com Sarcoma 180 revelou atividade em todas as doses, causando uma redução de 48,41% do crescimento tumoral na maior dose. As análises do fígado e rins revelaram que houve algumas alterações no fígado, como esteatose e necrose focal sugerindo toxicidade hepática nos camundongos tratados com o extrato acetônico das sementes da Annona muricata. Essas alterações são, entretanto, consideradas de possível reversão do tecido com a descontinuidade do tratamento ou adequação da dose. As análises bioquímicas, revelaram um aumento nos níveis séricos da creatinina nas doses de 15 e 30 mg/kg/dia. Nos testes hematológicos não houve alterações nos grupos tratados com o extrato acetônico das sementes da Annona muricata. Os resultados mostraram poucas alterações dos animais nos parâmetros físicos, bioquímicos e hematológicos, mostrando que o extrato é bem tolerado e pouco tóxico.

OLIVEIRA, Cecília Carvalho de. Estudos toxicológicos pré-clínicos e antitumorais do extrato acetônico das folhas de Annona muricata L. 2012. 174 f. Tese (Doutorado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2012. / Submitted by denise santos (denise.santos@ufc.br) on 2013-08-21T12:49:59Z No. of bitstreams: 1 2012_tese_ccoliveira.pdf: 3134891 bytes, checksum: 3f41e7826048e965c13c6010512da2ff (MD5) / Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2013-08-21T13:17:04Z (GMT) No. of bitstreams: 1 2012_tese_ccoliveira.pdf: 3134891 bytes, checksum: 3f41e7826048e965c13c6010512da2ff (MD5) / Made available in DSpace on 2013-08-21T13:17:04Z (GMT). No. of bitstreams: 1 2012_tese_ccoliveira.pdf: 3134891 bytes, checksum: 3f41e7826048e965c13c6010512da2ff (MD5) Previous issue date: 2012 / Annona muricata, popularly known as soursop in Brazil, is a plant widely used in vernacular medicine as teas and infusions for the treatment of various diseases, including cancer. This study aimed to evaluate the toxicological, genotoxicological and antitumor profile of the acetone extract from the leaves of Annona muricata and test it using short-and long-term in vivo and in vitro assays. We initially assessed in vitro cytotoxicity against several human tumor cell lines. There was a toxic response to many of them, especially K-562, HCT-8, HCT-116 and SF-295 with average inhibitory concentration (IC50) of 0.1452 µg/mL, 0.2457 µg/mL, 0.2956 µg/ml and 0.2191 µg/mL respectively. Acute toxicity studies were performed in vivo and the average lethal dose (LD50) was 310.2 mg/kg. Chronic toxicity studies were performed using doses of 12.5 mg/kg, 25 mg/kg and 50 mg/kg of acetone extract. Results showed little change in animals’ physical, biochemical and hematological parameters, showing that the extract is well tolerated and not very toxic. Genotoxicity studies were performed in vivo. Animals were given three oral doses of the acetone extract (12.5 mg/kg, 25 mg/kg and 50 mg/kg). After 24 and 48 hours peripheral blood and bone marrow were collected. In the comet assay no high grade comet was detected and tested doses were statistically similar to the negative control. In the micronucleus test, none of the tested acetone extract doses induced the formation of micronuclei. They were statistically similar to the negative control, unlike what was observed in the positive control. Antitumor testing showed that the extract has tumor growth inhibitory activity, both in rats, in the Walker 256 carcinosarcoma model, and in mice, in the Sarcoma 180 model. All such results indicate that the acetone extract from the leaves of Annona muricata has little toxic action and significant activity inhibiting tumor growth in the models we tested. / Annona muricata, conhecida popularmente como gravioleira no Brasil, é uma planta usada amplamente na medicina popular na forma de chás e infusões para o tratamento de diversas doenças, incluindo o câncer. O trabalho teve como objetivo avaliar o perfil toxicológico, genotoxicológico e antitumoral do extrato acetônico das folhas de Annona muricata e foi realizado utilizando ensaios de curta e longa duração in vivo e in vitro. Inicialmente foi avaliada a citotoxicidade in vitro contra várias linhagens tumorais humanas, havendo resposta tóxica a muitas delas, principalmente K-562, HCT-8, HCT-116 e SF-295 com concentração inibitória média (CI50) de 0,1452 µg/mL, 0,2457 µg/mL, 0,2956 µg/mL e 0,2191 µg/mL respectivamente. Os estudos de toxicidade aguda foram realizados in vivo e a dose letal média (DL50) foi de 310,2 mg/Kg. Os estudos de toxicidade crônica foram realizados utilizando-se as doses 12,5 mg/Kg, 25 mg/Kg e 50 mg/Kg do extrato acetônico. Os resultados mostraram poucas alterações nos animais nos parâmetros fisiológicos, bioquímicos e hematológicos, mostrando que o extrato é bem tolerado e pouco tóxico. Os estudos de genotoxicidade foram realizados in vivo. Os animais foram tratados, por via oral, com três doses do extrato acetônico (12,5 mg/Kg, 25 mg/Kg e 50 mg/Kg). Após 24 h e 48 h, o sangue periférico e a medula óssea foram coletados. No ensaio do cometa não houve detecção de nenhum cometa de grau elevado, sendo as doses testadas estatisticamente semelhantes ao controle negativo. No ensaio do micronúcleo, todas as doses testadas do extrato acetônico não induziram a formação de micronúcleos, sendo semelhantes estatisticamente em relação ao controle negativo, ao contrário do observado no controle positivo. Os ensaios antitumorais mostraram que o extrato apresenta atividade inibidora do crescimento tumoral, tanto em ratos, no modelo do carcinossarcoma de Walker 256, como em camundongos, no modelo Sarcoma 180. Todos esses resultados indicam que o extrato acetônico das folhas de Annona muricata apresenta poucas ações tóxicas e significante atividade inibidora do crescimento tumoral nos modelos testados.

Made available in DSpace on 2014-06-11T19:33:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-04-29Bitstream added on 2014-06-13T19:44:12Z : No. of bitstreams: 1 silva_sr_dr_botfm.pdf: 1456327 bytes, checksum: a429186d37bfb5815b5f13088abac56f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Not available.

Orientador: Deilson Elgui de Oliveira / Banca: José Vassallo / Banca: Luisa Lina Villa / Banca: Sandra Cecília Botelho Costa / Banca: Claudio Sérgio Pannuti / Resumo: Não disponível. / Abstract: Not available. / Doutor

Orientador: Marcio Ajudarte Lopes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-06T02:39:06Z (GMT). No. of bitstreams: 1 Prado_FabioOrnellas_D.pdf: 1979883 bytes, checksum: 0895b272310133fed868ff45f0215c36 (MD5) Previous issue date: 2006 / Resumo: Os condrossarcomas são tumores malignos de etiologia desconhecida, em que as células tumorais formam tecido cartilaginoso. Embora a ocorrência seja rara, principalmente na região de cabeça e pescoço, é o segundo tumor ósseo primário maligno mais freqüente. O objetivo deste trabalho foi correlacionar os dados clinicopatológicos ao prognóstico dos pacientes portadores de condrossarcomas de cabeça e pescoço tratados no Departamento de Cabeça e Pescoço e Otorrinolaringologia do Hospital do Câncer A.C. Camargo. Foram selecionados 16 casos tratados no Hospital do Câncer A.C. Camargo entre 1953 e 2002. A idade média de acometimento no momento do diagnóstico foi de 36,5 anos, variando de 11 a 70 anos. Observou-se ligeira predileção pelo gênero masculino (56,2%). De acordo com a localização, 7 casos (43,8%) acometeram a maxila; 5 casos ocorreram em outros sítios (região etmoidal, fossa nasal [2 casos], fossa infra-temporal, região parietooccipital) e 4 pacientes (25,0%) desenvolveram condrossarcomas em mandíbula. A maioria dos casos foi tratada somente com cirurgia (6 casos, 40% do total). A sobrevida global, observada foi de 66,7% em 3 anos e 56,4% em 5 anos / Abstract: Chondrosarcomas are malignant tumors of unknown etiology, in which tumoral cells form cartilagenous tissue. Although rare in head and neck region, chondrosarcomas are the second primary osseous tumor in frequency. The aim of the present study was correlate clinicopathological data to prognostic of patients with head and neck chondrosarcomas treated in the Head and Neck and Otolaringology Department of the A.C. Camargo Cancer Hospital. There were 16 cases treated in the institution from 1953 to 2002. The mean age at diagnosis was 36.5 years, ranging from 11 to 70 years. A slight male preference was observed (56,2%). According to the location, 7 cases (43,8%) accomited maxilla; 5 cases occured at other sites (ethmoidal region, nasal fossa [2 cases], infratemporal fossa, parieto-occipital region) and 4 patients (25,0%) had mandibular lesions. Most of cases were treated with surgery alone (6 cases, 40%). The observed overall survival was 66,7% for 3-year and 56,4% for 5-year / Doutorado / Patologia / Doutor em Estomatopatologia

Osteosarcoma is a rare osteogenic cancer which is a predominantly pediatric/young adult disease but has a large adult population. Due to the skewed patient population, randomized clinical trials have focused on the younger osteosarcoma cases, and then applying these treatments to adults. Yet these treatments have not been tested in a prospective randomized clinical trial for adults for whether they achieve the same outcomes as those in the pediatric population. The purpose of this study is to compare outcomes of pediatric and adult osteosarcoma cases through a retrospective review of patients treated at two facilities, Dana-Farber Cancer Institute (DFCI) and Massachusetts General Hospital (MGH). A list of 2,263 potential patients was provided by the pathology departments of DFCI/MGH. Eligibility required: 1) the patient to be at least 18 YO at the time of diagnosis, 2) a pathology report confirming osteosarcoma, 3) the available follow-up data is greater than 1 year (unless the patient died within that year). The electronic charts were assessed for prognostic variables which includes; date of diagnosis, age at diagnosis, sex, primary disease site, tumor size, histologic response, and treatment course. The overall survival and metastasis free survival were based on the date of pathologic confirmation of osteosarcoma. The collected data was analyzed through the Kaplan-Meier method to produce overall survival and metastasis free survival curves. The 5-year OS and MFS rates were calculated with those alive at last follow-up censored from the analysis. The prognostic variables were tested for significant difference in OS and MFS by ANOVA and t-tests. Of potential patients, 177 were deemed eligible for this study and were found to have 5-year MFS and OS of 45.8% and 64.4%, respectively. When compared against results from a primarily pediatric/young adult study, our patient population had a significantly lower OS and MFS. This finding indicates that current treatment regimens have a shorter effect in adult osteosarcoma cases when compared to pediatric patients. Although pediatric patients have a sustained response to current treatment therapies, the adult cases of osteosarcoma have a significantly shortened outcome which needs to be addressed in future research.

Thesis (Ph.D. (Public Health))--University of the Witwatersrand, Faculty of Health Sciences, 2012 / Factors associated with the transmission of Kaposi’s sarcoma-associated herpesvirus (KSHV) are inconclusive. In countries where KS and KSHV are confined to men who have sex with other men (MSM), KSHV is associated with sexual risk factors. In countries where KSHV is endemic, it affects adults and children of all ages and irrespective of sexual orientation, suggesting the existence of non-sexual risk factors for KSHV infection. In this thesis, three distinct cross sectional studies aiming to define the seroprevalence of KSHV in South African populations and to identify plausible risk factors for KSHV infection were undertaken. The studies measured KSHV seropositivity in relation to sociodemographic factors and HIV status. In children, factors associated with horizontal mother to child transmission were also explored. In adults KSHV seropositivity was also measured in relation to sexually transmitted infections and/or measures of sexual behaviour. Calculated risk factors were expressed as odds ratios (95% confidence interval) for KSHV. Methods Mother to Child KSHV seroepidemiology Study: KSHV seroprevalence (reactive to either lytic K8.1 or latent Orf73) was measured in 1287 children and their 1179 biological mothers. Association between KSHV seropositivity in children was measured against KSHV seropositivity and HIV status of their mothers. KSHV seroepidemiology in women attending antenatal clinics: Antibodies to KSHV lytic K8.1 and latent Orf73 antigens were tested in 1740 pregnant women attending antenatal clinics in South Africa in 2001. Information on HIV and syphilis serology, age, education, residential area, gravidity, and parity was anonymously linked to evaluate risk factors for KSHV seropositivity. Clinics were grouped by municipal regions and their proximity to the two main river catchments defined. Carletonville Community KSHV seroepidemiology Study: Sera from 2103 South African individuals (862 miners, 95 sex workers, 731 female and 415 male township residents) were tested for antibodies to KSHV lytic K8.1 and latent Orf73, HIV gonococcus, herpes simplex virus type 2 (HSV-2), syphilis and chlamydia. Information on social, demographic and highrisk sexual behaviour was linked to laboratory data. Results Mother to Child KSHV seroepidemiology Study: KSHV seroprevalence (reactive to either lytic K8.1 or latent Orf73) was 15.9% (204 of 1287 subjects) in children and 29.7% (350 of 1179 subjects) in mothers. The risk of KSHV seropositivity was significantly higher in children of KSHV seropositive mothers compared with those of KSHV-seronegative mothers. The HIV status of mothers was marginally associated with an increased risk of KSHV seropositivity in their children (AOR = 1.6, 95% CI: 1.0 to 2.6; P = 0.07). KSHV seroprevalence was significantly higher in HIV-infected subjects (P = 0.0005), and HIV-infected subjects had significantly higher lytic and latent KSHV antibody levels than HIV-negative subjects. KSHV seroepidemiology in women attending antenatal clinics: KSHV seroprevalence was nearly twice that of HIV (44.6% vs. 23.1%). HIV and syphilis seropositivity was 12.7% and 14.9% respectively in women without KSHV, and 36.1% and 19.9% respectively in those with KSHV. Women who were KSHV seropositive were 4 times more likely to be HIV positive than those who were KSHV seronegative (AOR 4.1 95%CI: 3.4 - 5.7). Although, women with HIV infection were more likely to be syphilis seropositive (AOR 1.8 95%CI: 1.3 - 2.4), no association between KSHV and syphilis seropositivity was observed. Those with higher levels of education had lower levels of KSHV seropositivity compared to those with lower education levels. KSHV seropositivity showed a heterogeneous pattern of prevalence in some localities. Carletonville Community KSHV seroepidemiology Study: Overall KSHV and HIV prevalences were 47.5 and 40%, respectively (P<0.43). The risk of HIV infection was highest in sex workers followed by female residents and miners, compared with male residents (P<0.001). HSV-2 infection was highly prevalent (66%) and lower, but still substantial, prevalence (6–8%) was observed for other sexually transmitted infections (STI). No significant difference in KSHV infection was observed among the residential groups (P>0.05). KSHV was not associated with any of the STI or any measures of sexual behaviour. Conclusion The findings of these three studies contribute substantially to global KSHV seroepidemiology and show that in Southern African settings KSHV is associated with non-sexual mode of transmission. Firstly KSHV is common in very young children up to ten years of age and increases with age until adulthood. The high prevalence of KSHV in the South African populations remained evident in all populations. In children, the risk of acquisition of KSHV was higher among children of KSHV-seropositive mothers than if the mother was KSHV negative. The association between KSHV and HIV was also noted in the study of pregnant women attending antenatal clinics and in the mother to child study. However this association was not evident in the Carletonville population where both KSHV and HIV were highly prevalent. In both the adult studies the lack of association between KSHV and syphilis was evident. KSHV infection was also not associated with other sexually transmitted infections and measures of sexual behaviour. As expected, the pattern of HIV and STI in sex workers suggests high rates of high-risk sexual behaviour in this population; however KSHV seropositivity was the same amongst sexworkers and all the other community groups. This pattern of the lack of association with high-risk sexual behaviour, particularly in sex workers and with any markers of STI strongly suggests that the sexual mode does not play a significant role in KSHV transmission in this South African population. This may also suggest that KSHV transmission may involve geographical and cultural factors other than sexual transmission.