Parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer
Female breast cancer, according to current estimates, is still reaching a very high level of incidence and prevalence in Brazil and Pará. The need for studies that expand knowledge about therapeutic options and mitigate the damage suffered by cancer becomes innovative in our region. Thus, we aim to...
| Autor principal: | SIQUEIRA, Maria Lúcia Souza |
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| Grau: | Tese |
| Idioma: | por |
| Publicado em: |
Universidade Federal do Pará
2022
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| Acesso em linha: |
http://repositorio.ufpa.br:8080/jspui/handle/2011/15083 |
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ir-2011-15083 |
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ir-2011-150832024-09-16T15:17:39Z Parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer SIQUEIRA, Maria Lúcia Souza MONTEIRO, Marta Chagas http://lattes.cnpq.br/6710783324317390 SOUZA, Givago da Silva http://lattes.cnpq.br/5705421011644718 https://orcid.org/0000-0002-3328-5650 https://orcid.org/0000-0002-4525-3971 Mamas - câncer Neoplasias da mama Metabolismo dos lipídeos Tamoxifeno Antineoplásicos CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CANCEROLOGIA BIOLOGIA CELULAR Biologia Celular Female breast cancer, according to current estimates, is still reaching a very high level of incidence and prevalence in Brazil and Pará. The need for studies that expand knowledge about therapeutic options and mitigate the damage suffered by cancer becomes innovative in our region. Thus, we aim to determine and assess metabolic and visual health parameters in patients diagnosed with breast cancer exposed to anti-cancer therapies. The specific objectives were divided into three sections: Section I: determine lipid, anthropometric, oxidative stress and pro-inflammatory cytokine markers to assess metabolic health; Section II: determine tamoxifen metabolites (4-hydroxy tamoxifen and endoxifen) and correlate with blood lipids to assess drug interaction and metabolism with lipids; Section III: Perform visual tests to assess the effect of anticancer therapies on retinal thickness. Research approved by the ethics committee with opinion number 1.915.051 (CEP-HOL) and 1.897.057 (CEP-ICS-UFPA) from March 2017 to September 2019. It consisted of 40 women diagnosed with breast cancer (Ductal Carcinoma Grade II and III) in a public cancer reference hospital in Belém of Pará and who consented to participate in the research. A group of 20 patients formed the chemotherapy group (GQt), 20 patients the tamoxifen hormone therapy group (GTam) and another group of women without cancer was constituted as a comparative control (GC) based on the inclusion criteria. For the determination of biochemical markers, the automated method was used; anthropometry followed the Ministry of Health manual; for oxidative stress the colorimetric method; for the measurement of cytokines the ELISA method; for the determination of tamoxifen and metabolites in plasma, High Performance Liquid Chromatography (HPLC) was used; for retinal analyses, optical coherence tomography (OCT) was used. The results obtained showed that the patients were predominantly women aged between 40 and 50 years, brown, with an income of 1 to 3 minimum wages, were in pre- and post-menopause; were overweight/obese with high BMI, between 25 to 29.9 kg/m2, waist circumference above 80 cm and did not perform regular physical activity; the mean levels of lipids were altered in both groups studied, but with emphasis on the chemotherapy group with elevation of total cholesterol, LDL and triglycerides and low levels of HDL cholesterol, (p<0.05); the antioxidant parameters (TEAC, GSH, CAT and SOD) showed low levels of GSH and high CAT activity for the chemotherapy group and less activity for the tamoxifen group compared to the control (p<0.01); the pro-oxidant parameters (MDA and NO) showed that chemotherapy patients had a higher level of lipid peroxidation than tamoxifen patients compared to control (p<0.05); the GSH/MDA ratio showed greater sensitivity to oxidative damage for chemotherapy patients (p<0.01); as for cytokines, TNF-α and IL-6, they were elevated both in the chemotherapy group and in the tamoxifen group (p<0.05). Mean plasma concentrations of tamoxifen, 4-hydroxy tamoxifen, and endoxifen were 62 ng/mL, 1.04 ng/mL and 8.79 ng/mL; triglyceride levels ranged from 59 to 352 mg/dL, total cholesterol from 157 to 321 mg/dL, LDL-c from 72 mg/dL to 176 mg/dL and HDL-c from 25.1 mg/dL to 62.8 mg/dL; there was no significant association between tamoxifen and metabolites with cholesterol and triglyceride levels; there was a weak association between tamoxifen and its active metabolites with HDLc, LDLc and VLDLc. Mean retinal macular thickness revealed no significant difference between patients who received chemoradiotherapy and control tamoxifen (p>0.05); regional macular thickness revealed that only one macular field showed a significant difference between two groups; in the external nasal macular field, the chemoradiotherapy patients showed thinner retinal thickness compared to the control. We conclude that breast cancer patients exposed to chemotherapy and hormone therapy presented: unfavorable lipid profile with high levels of total cholesterol, LDL, triglycerides and low HDL, overweight and obesity, lower antioxidant capacity for patients who received chemotherapy and systemic levels of inflammatory cytokines, TNF-α and IL-6, elevated; there was a weak association between plasma concentrations of tamoxifen and its active metabolites with levels of HDL-c, LDL-c and VLDL-c, with a low impact of lipoprotein levels on exposure to tamoxifen, 4-hydroxytamoxifen and endoxifen; a macular field was altered in the chemotherapy group, which had a thinner retina compared to the control group, however the retinal structure was sensitive to the presence of tamoxifen metabolites. O câncer de mama feminino, segundo as estimativas atuais, ainda vem atingindo um nível de incidência e prevalência bem elevado no Brasil e no Pará. A necessidade por estudos que venham ampliar o conhecimento sobre as opções terapêuticas e mitigar os danos sofridos pelo câncer, torna-se inovador em nossa região. Desta forma, objetivamos determinar e avaliar parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama expostas a terapias anticâncer. Os objetivos específicos foram divididos em três seções: Seção I: determinar marcadores lipídicos, antropométricos, estresse oxidativo e citocinas pró-inflamatórias para avaliar a saúde metabólica; Seção II: determinar os metabólitos de tamoxifeno (4-hidroxitamoxifeno e endoxifeno) e correlacionar com lipídios sanguíneos para avaliar a interação e metabolismo da droga com lipídios; Seção III: realizar testes visuais para avaliar o efeito das terapias anticâncer na espessura da retina. Pesquisa aprovada pelo comitê de ética com parecer no 1.915.051 (CEP-HOL) e 1.897.057 (CEP-ICS-UFPA) no período de março de 2017 a setembro de 2019. Foi constituída por 40 mulheres diagnosticadas com câncer de mama (Carcinoma Ductal Grau II e III) em um hospital público de referência oncológica em Belém do Pará e que consentiram participar da pesquisa. Um grupo de 20 pacientes formaram o grupo que estavam em quimioterapia (GQt), 20 pacientes o grupo em hormonioterapia com tamoxifeno (GTam) e um outro grupo de mulheres sem câncer foi constituído como controle comparativo (GC) a partir dos critérios de inclusão. Para a determinação dos marcadores bioquímicos, foi utilizado o método automatizado; a antropometria seguiu o manual do Ministério da Saúde; para o estresse oxidativo o método colorimétrico; para a dosagem de citocinas o método de ELISA; para a determinação do tamoxifeno e metabólitos no plasma foi utilizado a Cromatografia Líquida de Alta Eficiência (CLAE); para as análises da retina, foi utilizado a tomografia de coerência óptica (TCO). Os resultados obtidos, mostraram que as pacientes eram mulheres predominantemente com idade entre 40 a 50 anos, pardas, com renda de 1 a 3 salários mínimos, estavam na pré e pós-menopausa; apresentaram sobrepeso/ obesidade com IMC elevado, entre 25 a 29,9 kg/m2, circunferência abdominal acima de 80 cm e não realizavam atividade física regular; os níveis médios de lipídios mostraram-se alterados em ambos os grupos estudados, mas com destaque para o grupo quimioterápico com elevação do Colesterol total, LDL e Triglicerídeos e baixos níveis de HDL colesterol, (p<0,05); os parâmetros antioxidantes (TEAC, GSH, CAT e SOD) mostraram baixos níveis de GSH e elevada atividade da CAT, para o grupo quimioterápico e em menor atividade para o grupo de tamoxifeno em relação ao controle (p<0,01); os parâmetros pró-oxidantes (MDA e NO), mostraram que pacientes de quimioterapia apresentaram maior nível de peroxidação lipídica diferente das pacientes de tamoxifeno comparado ao controle (p<0,05); a razão GSH/MDA mostrou maior sensibilidade aos danos oxidantes para as pacientes de quimioterapia (p<0,01); quanto as citocinas,TNF- α e IL-6, mostraram-se elevadas tanto no grupo de quimioterapia quanto no grupo tamoxifeno (p<0,05). As concentrações plasmáticas médias de tamoxifeno, 4-hidroxitamoxifeno e endoxifeno foram 62 ng/mL, 1.04 ng/mL and 8.79 ng/mL; níveis de triglicerídeos variaram de 59 a 352 mg/dL, Colesterol total de 157 a 321 mg/dL, LDL-c de 72 mg/dL a 176 mg/dL e HDL-c de 25.1 mg/dL a 62.8 mg/dL; não houve associação significativa entre tamoxifeno e os metabólitos com os níveis de colesterol e triglicerídeos; houve fraca associação entre tamoxifeno e seus metabólitos ativos com HDLc, LDLc e VLDLc. A média da espessura macular da retina revelou não ter diferença significativa entre as pacientes que receberam quimioradioterapia e tamoxifeno com controle (p>0,05); a espessura macular regional revelou que somente um campo macular apresentou diferença significativa entre dois grupos; no campo macular nasal externo, as pacientes de quimioradioterapia mostraram a espessura da retina mais fina em relação ao controle. Concluímos que pacientes de câncer de mama, expostas a quimioterapia e hormonioterapia, apresentaram: perfil lipídico desfavorável com níveis elevados de colesterol total, LDL, triglicerídeos e baixo HDL, sobrepeso e obesidade, menor capacidade antioxidante para as pacientes que receberam quimioterapia e níveis sistêmicos de citocinas inflamatórias, TNF-α e IL-6, elevados; houve fraca associação entre as concentrações plasmáticas de tamoxifeno e seus metabólitos ativos com os níveis de HDL-c, LDL-c e VLDL-c, com baixo impacto dos níveis de lipoproteínas na exposição ao tamoxifeno, 4-hidroxitamoxifeno e endoxifeno; um campo macular foi alterado no grupo quimioterápico, que apresentou retina mais fina em comparação com o grupo controle, no entanto a estrutura da retina mostrou-se sensível à presença dos metabólitos do tamoxifeno no sangue. UFPA - Universidade Federal do Pará 2022-12-13T15:40:02Z 2022-12-13T15:40:02Z 2021-09 Tese SIQUEIRA, Maria Lúcia Souza. Parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer. Orientadora: Marta Chagas Monteiro. 2021. 116 f. Tese (Doutorado em Genética e Biologia Molecular) - Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, 2022. Disponível em: http://repositorio.ufpa.br:8080/jspui/handle/2011/15083. Acesso em:. http://repositorio.ufpa.br:8080/jspui/handle/2011/15083 por Acesso Aberto Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ application/pdf Universidade Federal do Pará Brasil Instituto de Ciências Biológicas UFPA Programa de Pós-Graduação em Genética e Biologia Molecular Disponível na internet via correio eletrônico: biblicb.420@gmail.com |
| institution |
Repositório Institucional - Universidade Federal do Pará |
| collection |
RI-UFPA |
| language |
por |
| topic |
Mamas - câncer Neoplasias da mama Metabolismo dos lipídeos Tamoxifeno Antineoplásicos CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CANCEROLOGIA BIOLOGIA CELULAR Biologia Celular |
| spellingShingle |
Mamas - câncer Neoplasias da mama Metabolismo dos lipídeos Tamoxifeno Antineoplásicos CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CANCEROLOGIA BIOLOGIA CELULAR Biologia Celular SIQUEIRA, Maria Lúcia Souza Parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer |
| topic_facet |
Mamas - câncer Neoplasias da mama Metabolismo dos lipídeos Tamoxifeno Antineoplásicos CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CANCEROLOGIA BIOLOGIA CELULAR Biologia Celular |
| description |
Female breast cancer, according to current estimates, is still reaching a very high level of incidence and prevalence in Brazil and Pará. The need for studies that expand knowledge about therapeutic options and mitigate the damage suffered by cancer becomes innovative in our region. Thus, we aim to determine and assess metabolic and visual health parameters in patients diagnosed with breast cancer exposed to anti-cancer therapies.
The specific objectives were divided into three sections: Section I: determine lipid, anthropometric, oxidative stress and pro-inflammatory cytokine markers to assess metabolic health; Section II: determine tamoxifen metabolites (4-hydroxy tamoxifen and endoxifen) and correlate with blood lipids to assess drug interaction and metabolism with lipids; Section III: Perform visual tests to assess the effect of anticancer therapies on retinal thickness. Research approved by the ethics committee with opinion number 1.915.051 (CEP-HOL) and 1.897.057 (CEP-ICS-UFPA) from March 2017 to September 2019. It consisted of 40 women diagnosed with breast cancer (Ductal Carcinoma Grade II and III) in a public cancer reference hospital in Belém of Pará and who consented to participate in the research. A group of 20 patients formed the chemotherapy group (GQt), 20 patients the tamoxifen hormone therapy group (GTam) and another group of women without cancer was constituted as a comparative control (GC) based on the inclusion criteria. For the determination of biochemical markers, the automated method was used; anthropometry followed the Ministry of Health manual; for oxidative stress the colorimetric method; for the measurement of cytokines the ELISA method; for the determination of tamoxifen and metabolites in plasma, High Performance Liquid Chromatography (HPLC) was used; for retinal analyses, optical coherence tomography (OCT) was used. The results obtained showed that the patients were predominantly women aged between 40 and 50 years, brown, with an income of 1 to 3 minimum wages, were in pre- and post-menopause; were overweight/obese with high BMI, between 25 to 29.9 kg/m2, waist circumference above 80 cm and did not perform regular physical activity; the mean levels of lipids were altered in both groups studied, but with emphasis on the chemotherapy group with elevation of total cholesterol, LDL and triglycerides and low levels of HDL cholesterol, (p<0.05); the antioxidant parameters (TEAC, GSH, CAT and SOD) showed low levels of GSH and high CAT activity for the chemotherapy group and less activity for the tamoxifen group compared to the control (p<0.01); the pro-oxidant parameters (MDA and NO) showed that chemotherapy patients had a higher level of lipid peroxidation than tamoxifen patients compared to control (p<0.05); the GSH/MDA ratio showed greater sensitivity to oxidative damage for chemotherapy patients (p<0.01); as for cytokines, TNF-α and IL-6, they were elevated both in the chemotherapy group and in the tamoxifen group (p<0.05). Mean plasma concentrations of tamoxifen, 4-hydroxy tamoxifen, and endoxifen were 62 ng/mL, 1.04 ng/mL and 8.79 ng/mL; triglyceride levels ranged from 59 to 352 mg/dL, total cholesterol from 157 to 321 mg/dL, LDL-c from 72 mg/dL to 176 mg/dL and HDL-c from 25.1 mg/dL to 62.8 mg/dL; there was no significant association between tamoxifen and metabolites with cholesterol and triglyceride levels; there was a weak association between tamoxifen and its active metabolites with HDLc, LDLc and VLDLc. Mean retinal macular thickness revealed no significant difference between patients who received chemoradiotherapy and control tamoxifen (p>0.05); regional macular thickness revealed that only one macular field showed a significant difference between two groups; in the external nasal macular field, the chemoradiotherapy patients showed thinner retinal thickness compared to the control. We conclude that breast cancer patients exposed to chemotherapy and hormone therapy presented: unfavorable lipid profile with high levels of total cholesterol, LDL, triglycerides and low HDL, overweight and obesity, lower antioxidant capacity for patients who received chemotherapy and systemic levels of inflammatory cytokines, TNF-α and IL-6, elevated; there was a weak association between plasma concentrations of tamoxifen and its active metabolites with levels of HDL-c, LDL-c and VLDL-c, with a low impact of lipoprotein levels on exposure to tamoxifen, 4-hydroxytamoxifen and endoxifen; a macular field was altered in the chemotherapy group, which had a thinner retina compared to the control group, however the retinal structure was sensitive to the presence of tamoxifen metabolites. |
| author_additional |
MONTEIRO, Marta Chagas |
| author_additionalStr |
MONTEIRO, Marta Chagas |
| format |
Tese |
| author |
SIQUEIRA, Maria Lúcia Souza |
| title |
Parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer |
| title_short |
Parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer |
| title_full |
Parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer |
| title_fullStr |
Parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer |
| title_full_unstemmed |
Parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer |
| title_sort |
parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer |
| publisher |
Universidade Federal do Pará |
| publishDate |
2022 |
| url |
http://repositorio.ufpa.br:8080/jspui/handle/2011/15083 |
| _version_ |
1811330062622916608 |
| score |
11.675608 |