Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-05-11T14:56:08Z No. of bitstreams: 1 DIS_LUCAS_POITEVIN_BANDINELLI_PARCIAL.pdf: 719523 bytes, checksum: ea7e36f5e671ac6c3ddd0bad0608d569 (MD5) / Made available in DSpace on 2017-05-11T14:56:08Z (GMT). No. of bitstreams: 1 DIS_LUCAS_POITEVIN_BANDINELLI_PARCIAL.pdf: 719523 bytes, checksum: ea7e36f5e671ac6c3ddd0bad0608d569 (MD5) Previous issue date: 2017-01-18 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Introduction: Early life stress (ELS) has an important role in the response of psychoneuroimmunoendocrine systems and in the face of a situation as a major life stressor event such as the diagnosis of breast cancer, women with a history of childhood maltreatment may react diferente then others. Objective: To investigate the role of stress before its impact within the systems that regulate biological and psychological responses in the treatment of breast cancer. Method: The empirical study was an exploratory and correlational study with women newly diagnosed with breast cancer, where scales and tests were used for behavioral assessment and verification of the history of child maltreatment, as well as collection of peripheral blood To evaluate the expression of inflammatory markers. This dissertation was also composed by a narrative review, with a hypothesis proposal on the accumulation of stress throughout life and outcomes in the treatment of breast cancer. Results: There were 18 newly diagnosed women with breast cancer, mean age 45.2 (8.3). There were no significant differences between the group of patients and the control group, regarding cognitive scores and depression and anxiety. However, as women with breast cancer who score higher on the child abuse assessment scale had more traumatic symptoms, such as avoidance and hypervigilance. Similarly, women with higher traumatic symptoms had lower rates of inflammatory markers, such as IL-2 and IL-4. Conclusion: Women with a history of childhood maltreatment with more extreme traumatic reactions with respect to the impact of breast cancer discovery, as well as lower expression of inflammatory markers. The construction of the hypothesis was important for the data obtained in empirical research, taking into account the psychological and immunological impact in women with breast cancer who have a history of childhood maltreatment. / Introdu??o: O estresse precoce possui um papel importante na resposta dos sistemas psiconeuroimunoend?crinos e, diante de uma situa??o estressora como o diagn?stico do c?ncer de mama, avalia-se que respostas comportamentais e imunol?gicas diferentes podem ocorrer em mulheres com o diagn?stico de c?ncer de mama com o hist?rico de maus-tratos na inf?ncia. Objetivo: Investigar o papel do estresse precoce e o impacto no mesmo dentro dos sistemas que regulam as respostas biol?gicas e psicol?gicas frente ao tratamento do c?ncer de mama. M?todo: Realizou-se um estudo explorat?rio e correlacional com mulheres rec?m diagnosticadas com c?ncer de mama, onde utilizou-se escalas e testes para avalia??o comportamental e verifica??o de hist?rico de maus-tratos infantis, bem como coleta de sangue perif?rico para avalia??o dos n?veis plasm?ticos de marcadores inflamat?rios. Esta disserta??o tamb?m foi composta de uma revis?o narrativa, com a proposta de uma hip?tese sobre o ac?mulo de estresse ao longo da vida e desfechos no tratamento do c?ncer de mama. Resultados: Avaliou-se 18 mulheres, com m?dia de idade 45.2 (8.3). N?o houve diferen?as significativas entre o grupo de pacientes e grupo controle no que diz respeito a escores cognitivos e de depress?o e ansiedade. Contudo, as mulheres com c?ncer de mama que possu?am maiores escores na escala de avalia??o de maus-tratos infantis apresentaram mais sintomas traum?ticos, como evita??o e hipervigil?ncia. Da mesma forma, mulheres com maiores sintomas traum?ticos apresentaram n?veis plasm?ticos reduzidos de marcadores inflamat?rios, como a IL-2 e IL-4. Conclus?o: Mulheres com hist?rico de maus-tratos infantis possuem rea??es traum?ticas mais extremas no que diz respeito ao impacto da descoberta do diagn?stico do c?ncer de mama, bem como uma redu??o nos n?veis plasm?ticos de marcadores inflamat?rios. A constru??o da hip?tese se mostrou importante para compreender os dados obtidos na pesquisa emp?rica, levando em considera??o o impacto psicol?gico e imunol?gico nas mulheres com c?ncer de mama que possuem o hist?rico de maus-tratos na inf?ncia.

Submitted by PPG Gerontologia Biom?dica (geronbio@pucrs.br) on 2018-09-26T11:04:34Z No. of bitstreams: 1 Trintinaglia_Lauren_Dis.pdf: 3983976 bytes, checksum: 466d953c5edcd91085fcab766ad7abd9 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-09-27T12:52:20Z (GMT) No. of bitstreams: 1 Trintinaglia_Lauren_Dis.pdf: 3983976 bytes, checksum: 466d953c5edcd91085fcab766ad7abd9 (MD5) / Made available in DSpace on 2018-09-27T12:59:22Z (GMT). No. of bitstreams: 1 Trintinaglia_Lauren_Dis.pdf: 3983976 bytes, checksum: 466d953c5edcd91085fcab766ad7abd9 (MD5) Previous issue date: 2018-03-07 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Introduction: Individuals who have experienced childhood maltreatment (CM) present a higher sensitive profile to stress. This profile have been associated with dysregulation of the immune system, characterized by reactivation of herpesvirus and increased cellular senescence markers. New traumatic or stressful experiences, such as breast cancer diagnosis, in those sensitized individuals can trigger an increase in stress levels possibly leading to important immunological changes. Here we investigate the presence of immunosenescence markers in women newly diagnosed with breast cancer with and without history of CM. Methods: Twenty-nine women newly diagnosed with breast cancer, without start the treatment, were recruited. Fifteen with history of CM (CM+) and fourteen without history of CM (CM-). Twenty-seven women without breast cancer and CM were selected as the control group. Peripheral blood was assessed by lymphocyte subsets by flow cytometry (B cells, CD4+, CD8+, NK cells, activated T cell, regulatory T cell, early and intermediated T cell, senescent and exhaustion T cells. CMV serology was determinate by ELISA method. Results: The groups CM+ and CM- present similar cancer stage and family history of breast cancer. In peripheral lymphocyte subpopulations we found significantly reduced Early-differentiated T cell (p <0.0001), while intermediate-differentiated T cell (p<0.0001), senescence T cell (p<0.0001) and exhaustion t cells (p<0.0001) were increased in CM+ and CM? patients. The mean fluorescent intensity (MFI) was analyzed and the CD27 expression on CD4 T cells was found lower in controls as compared to CM+ and CM? groups (p = 0.002).There was no difference of CMV IgG levels between CM + and CM? groups (p=0.24), but between controls and CM groups, this association becomes significant (p= 0.008) . Conclusion: Our findings suggest that the presence of CM is not directly related with immunosenescence in women newly diagnosed with breast cancer. However, when evaluated women with breast cancer and healthy controls, this senescent profile is evident. Future longitudinal studies are necessary to explore the role of senescent cells in the disease progression and treatment response. / Introdu??o: Indiv?duos que foram expostos a maus tratos na inf?ncia apresentam um perfil de sensibilidade ao estresse mais acentuado, quando comparado a aqueles que cresceram em um ambiente adequado. Esse perfil est? relacionado com a desregula??o do sistema imunol?gico, sendo caracterizado pela presen?a de um aumento de marcadores de senesc?ncia celular e reativa??es de infec??es virais latentes. O acontecimento de novas experi?ncias traum?ticas, como o diagn?stico do c?ncer de mama, pode acarretar em um aumento dos n?veis relacionados ao estresse, provocando altera??es imunol?gicas importantes. Nesse estudo n?s investigamos a presen?a de marcadores de imunossenesc?ncia em mulheres rec?m diagnosticadas com c?ncer de mama com ou sem hist?rico de c?ncer de mama. M?todos: Vinte e nove pacientes rec?m diagnosticadas com c?ncer de mama foram recrutadas para esse estudo, sendo que quinze mulheres reportaram presen?a de maus tratos na inf?ncia (CM+), enquanto quatorze n?o vivenciaram situa??es envolvendo abuso ou neglig?ncia nesse mesmo per?odo (CM-). Para compor o grupo controle, foram selecionadas vinte e sete mulheres sem c?ncer de mama e que negaram a presen?a de maus tratos. Os linf?citos foram isolados das c?lulas mononucleares do sangue perif?rico (PBMCs), e imunofenotipados por citometria de fluxo para investigar a presen?a dos seguintes subgrupos: c?lulas B, CD4+, CD8+, c?lulas NK, c?lulas T ativadas, c?lulas T reguladoras, c?lulas T rec?m diferenciadas, c?lulas T intermedi?rias, c?lulas T senescentes e com perfil de exaust?o. A sorologia IgG para citomegalov?rus (CMV) foi realizada atrav?s do m?todo ELISA. Resultados: Os grupos CM+ e CM- n?o apresentaram diferen?as significativas em rela??o ao estadiamento da doen?a ou hist?rico familiar. Nas subpopula??es de linf?citos encontramos uma redu??o significativa de c?lulas T rec?m diferenciadas (p <0.0001), nos grupos CM+ e CM-, enquanto c?lulas T intermedi?rias (p <0.0001), senescentes (p <0.0001) e de exaust?o (p <0.0001) apresentaram-se aumentadas nos mesmos grupos. Ao analisar a m?dia da intensidade de fluoresc?ncia (MFI) encontramos uma express?o diminu?da de CD27 em c?lulas T CD4 nos controles quando comparado as mulheres com c?ncer de mama expostas e n?o expostas a maus tratos (p = 0.002). N?o observamos diferen?as entre os grupos CM+ e CM- em rela??o a sorologia IgG para citomegalov?rus entre os grupos CM + e CM - (p=0.24), entretanto foi presenciado entre os controles e indiv?duos com maus tratos (p= 0.008). Conclus?o: nossos achados sugerem que a presen?a de maus tratos n?o est? diretamente associada com um perfil de imunossenesc?ncia em mulheres rec?m diagnosticada com c?ncer de mama. Entretanto, quando avaliamos mulheres com c?ncer de mama e indiv?duos saud?veis esse perfil senescente torna-se evidente. Logo, torna-se necess?rio a realiza??o de novos estudos para explorar o impacto da presen?a de marcadores de senesc?ncia no tratamento e progn?stico do c?ncer de mama.