O câncer de cólon e reto atinge pessoas no mundo todo e está entre os cinco tipos de câncer mais incidentes no Brasil. O impacto da doença e seu tratamento na vida do paciente pode causar alterações física, psicológica, social e conseqüentemente na qualidade de vida. O presente estudo é uma revisão integrativa da literatura, cujo objetivo foi buscar e avaliar as evidências disponíveis na literatura sobre o conhecimento científico produzido relacionado à qualidade de vida do paciente adulto com câncer de cólon e reto. Para a seleção dos artigos, utilizamos as bases de dados LILACS, CINAHL e MEDLINE e a amostra constituiu-se de 24 artigos, das quais apenas uma publicação foi escrita em português e as demais em inglês. Os autores principais, em sua maioria, foram médicos (62,5%), os enfermeiros contribuíram com 8,3% das publicações. De todos os artigos, 79,1% estiveram vinculados a universidades; a maioria foi sediada em países desenvolvidos; e entre 20 periódicos levantados, apenas 15% foram revistas de enfermagem. Em relação ao design dos artigos analisados, 23 são estudos quantitativos e um é qualitativo; a maioria (70,8%) é de delineamento não-experimental, estudos descritivos que juntamente com o qualitativo possuem um fraco nível de evidência, 16,7% são estudos coortes e apenas 12,5% tem nível forte de evidências, são ensaios clínicos randomizados controlados. Na análise de conteúdo, estabelecemos seis categorias temáticas relacionadas à qualidade de vida: sobrevivência a curto-prazo, sobrevivência a longo-prazo, influência da atividade física, do seguimento por exames, avaliação psicossocial e aspectos inerentes ao paciente. O resultado da análise apontou que o diagnóstico e o tratamento do câncer afeta as funções física, emocional, mental e social, desempenho de papel e estado de saúde global e causa vários sintomas em diferentes graus; que a qualidade de vida também é influenciada por fatores como presença de co-morbidades, estilo de vida, sedentarismo, idade, sexo, estado nutricional, estágio do tumor ao diagnóstico, tipo de tratamento, remissão e recorrência da doença. Encontramos que a prática de exercícios, o aumento da aptidão física, o estado de boa nutrição e a presença de suporte psicossocial favorecem uma qualidade de vida melhor. Essa Revisão Integrativa demonstrou o nível do conhecimento produzido nesta temática e apontou que são evidências fracas e com pouca produção por parte do profissional enfermeiro. Portanto, sugerimos o preparo dos enfermeiros, desde a graduação com a educação permanente depois de formado, na área da pesquisa e o desenvolvimento de pesquisas de intervenção para que as evidências extraídas dos estudos clínicos possam auxiliar o enfermeiro no planejamento de ações que possibilitem a reabilitação e melhoria na qualidade de vida do paciente com câncer de cólon e reto. / Colon and rectal cancer affects people throughout the world and is among the five most common types of cancer in Brazil. The impact of the disease and its treatment in the patient\'s life may cause physical, psychological, and social changes, thus affecting his quality of life. This study is an integrative literature review with the purpose to identify and assess the evidence available in the literature about the produced scientific knowledge regarding the quality of life of adult patients with colon and rectal cancer. The articles were selected using the databases LILACS, CINAHL, and MEDLINE, and the sample comprised 24 articles. Only one of the selected articles was written in Portuguese; the others were published in English. The authors were mostly physicians (62.5%), and nurses contributed with 8.3% of the publications. Of all articles, 79.1% are related to universities; most took place in developed countries; and among 20 surveyed serials, only 15% were nursing journals. As to their design, 23 of the analyzed articles are quantitative studies and one is qualitative; most (70.8%) are of a non-experimental outline, descriptive studies that along with the qualitative offer weak evidence level, 16.7% are cohort studies, and only 12.5% have strong evidence level, they are controlled randomized clinical trials. Content analysis established six thematic categories related quality of life: short term survival, long term survival, influence from physical activity, influence from follow-up exams, psychosocial evaluation, and aspects inherent to the patient. Result analysis revealed that cancer diagnosis and treatment affects physical, emotional, mental, social and role functioning, and global health. Furthermore, it causes several symptoms at different levels. In addition, it showed that quality of life is also affected by factors such as the presence of co-morbidities, lifestyle, leading a sedentary life, age, gender, nutritional condition, stage of the tumor at diagnosis, type of treatment, disease remission and recurrence. It was found that the practice of exercises, the increase of physical fitness, nutritional condition, and the presence of psychosocial support benefit a better quality of life. This integrative review showed the level of knowledge produced about this subject and pointed out that the evidence is weak, with a low production by nurses. Hence, we suggest that nurses be better prepared, as of the undergraduate course, with permanent education after graduating, in the pertinent field of research and the development of intervention research so that the evidence extracted from clinical studies can help nurses to plan actions that make it possible to rehabilitate and improve the quality of life of patients with colon and rectal cancer.

Este estudo teve como objetivo interpretar os significados que os homens inseridos na classe popular atribuem à condição de serem portadores de estoma intestinal por câncer colorretal, com base nos pressupostos sócio-antropológicos de masculinidade. Para tal compreensão foram utilizados os referenciais teóricos da antropologia interpretativa de Clifford Geertz e de Arthur Kleinman e o método etnográfico. Participaram do estudo dezesseis homens portadores de estomas intestinais temporários e/ou definitivos por câncer colorretal, moradores de Ribeirão Preto e região. A coleta de dados ocorreu no período de junho a dezembro de 2007 no Ambulatório de Proctologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto e nas residências dos informantes. Foram respeitadas as questões éticas e os informantes assinaram um Termo de Consentimento Livre e Esclarecido para participarem do estudo. Realizou-se entrevistas semi-estruturadas gravadas, observações participantes e anotações em um diário de campo. A análise dos dados apoiou-se nos pressupostos da sócio-antropologia de masculinidade de Connell e outros autores. Identificou-se os códigos que apontaram o sentido da experiência para os informantes e que, posteriormente, serviram de guia para as unidades de sentidos e a construção dos significados. Da análise surgiram dois núcleos de significados: \"A descoberta da doença e da necessidade do tratamento: a vida em jogo\"; \"Ser homem com estoma intestinal: ajustando a vida com resignação à sua nova masculinidade\". No primeiro tema, foi possível apreender que os sintomas do câncer colorretal surgem gradativamente, integram-se ao cotidiano dos homens e a sua gravidade é percebida quando a doença já está avançada. Influenciados por padrões sócio-culturais hegemônicos da masculinidade, os homens demoram em procurar recursos profissionais. A precariedade dos serviços de saúde e a dificuldade para a definição do diagnóstico os levam a idas e vindas aos ambulatórios e exames. O diagnóstico de câncer, a quimioterapia, a radioterapia e a cirurgia mutiladora que resulta na construção do estoma intestinal, rompem seus projetos de vida. O segundo tema aborda as dificuldades iniciais no pós-operatório, as alterações da imagem corporal, o estoma, a bolsa coletora, a dieta, a sexualidade e os laços sociais. Essas dificuldades foram interpretadas como dimensões de masculinidades de subordinação, marginalização e cumplicidade. Influenciados por padrões de masculinidade(s), os homens não se entregam, lutam pela sobrevivência e pela manutenção dos seus papéis sociais, estipulados pela visão hegemônica da masculinidade. Sobreviver ao CCR exige um ajustamento à nova condição, à nova identidade de homem; requer uma resignação com a situação para re-significar o viver. Nesse sentido, apreendemos a influência das dimensões da masculinidade nos diversos momentos de desafio ao ajustamento ao câncer, em se ter um estoma e nas conseqüências limitadoras em relação ao estilo de vida anterior. Os achados desse estudo oferecem subsídios para o cuidar, levando-se em consideração a perspectiva cultural. / This study had as objective to interpret the meanings that the men inserted in the popular class they attribute to the condition of they be bearers of intestinal stoma for cancer colorectal, with base in the partner-anthropological presuppositions of manliness. For such understanding were used the Clifford Geertz and Arthur Kleinman\'s theoretical references of interpretative anthropology and the method ethnographic. Sixteen men participated in the study bearers of temporary and/or definitive intestinal stoma for cancer colorectal, residents from Ribeirão Preto and region. The collection of data happened in the period of june to december of 2007 in the Clinic of Proctology of the Hospital of the Clinics of University of Medicine of Ribeirão Preto and in the informers\' residences. The ethical subjects were respected and the informers signed a Term of Free Consent and Illustrious to participate in the study. It took place interviews semi-structured recorded, participant observations and annotations in a field diary. The analysis of the data supported in the presuppositions of the partner-anthropology of manliness of Connell and other authors. It was identified the codes that pointed the sense of the experience for the informers and that, later, they served as guide for the units of senses and the construction of the meanings. Of the analysis two nuclei of meanings appeared: \"The discovery of the disease and of the need of the treatment: the life in game\"; \"To be man with intestinal stoma: adjusting the life with resignation to his new manliness\". In the first theme, it was possible to apprehend that the symptoms of the cancer colorectal appear gradually, they integrate into the daily of the men and his gravity is noticed when the disease is already advanced. Influenced by patterns partner-cultural hegemonic of the manliness, the men delay in seeking professional resources. The precariousness of the services of health and the difficulty for the definition of the diagnosis take them to go and come to the clinics and exams. The diagnosis of cancer, the chemotherapy, the radiotherapy and the surgery of mutilation that results in the construction of the intestinal stoma, they break their life projects. The second theme approaches the initial difficulties in the postoperative, the alterations of the corporal image, the stoma, the bag collect, the diet, the sexuality and the social ties. These difficulties were interpreted as dimensions of manliness of subordination, marginalization and complicity. Influenced by patterns of manliness, the men don\'t surrender, they struggle for the survival and for the maintenance of their social roles, stipulated by the vision hegemonic of the manliness. To survive to CCR demands an adjustment to the new condition, to the new man identity; it requests a resignation with the situation to redefinition of living. In that sense, we apprehended the influence of the dimensions of the manliness in the several moments of challenge to the adjustment to the cancer, in having a stoma and in the consequences of limitation in relation to the previous lifestyle. The discoveries of that study offer subsidies for taking care, being taken into account the cultural perspective.

O câncer colorretal é o segundo tipo que mais causa mortes no Brasil. Podem ser utilizados vários tratamentos para esses casos, tais como a quimioterapia, radioterapia e cirurgias, dentre as quais, a colostomia. Apesar de trazer sobrevida, a colostomia pode acarretar mudanças físicas e psicológicas que impactam diretamente os doentes. Pesquisas na área da Psico-oncologia são consideradas importantes nesses casos, pois estudam as dimensões psicológicas do câncer sob diferentes aspectos. Na presente dissertação, foi realizado estudo de caso instrumental com dois sujeitos cada qual se relacionando em regime de união estável com o objetivo de analisar as questões psicodinâmicas envolvidas na vivência da própria sexualidade após a colostomia. Para atingir tal objetivo, foram realizadas entrevistas semiestruturadas e o teste psicológico HTP. Os resultados foram analisados sob enfoque psicanalítico e indicaram: queda na autoestima; autoimagem corporal negativa; isolamento social e dificuldades na aceitação do uso da bolsa coletora; luto pela perda do corpo saudável; vergonha e receio de que os outros percebam sua condição de colostomizado. A dinâmica psíquica de cada entrevistado impactou a maneira de experienciar esse processo. Com personalidades e formas de enfrentamento distintas, foram encontradas diferenças na forma de lidar com seus próprios relacionamentos afetivos. A despeito dessas questões, a colostomia emergiu como a principal culpada pelo distanciamento ocorrido entre as partes, em relação a ambos os casais, embora muitos reveses já estivessem presentes na rotina conjugal antes mesmo da cirurgia. Além disso, a falta de apoio conjugal, indiferença por parte do companheiro e dificuldades na convivência colaboraram para o surgimento de barreiras entre o casal, contribuindo para a derrocada da vida sexual. Os pacientes não foram encaminhados para acompanhamento psicológico, embora considerem a psicoterapia importante. Não encontraram oportunidade em serviços públicos de saúde para dirimir dúvidas e abordar questões de ordem pessoal, conjugal ou sexual / Colorectal is the second type of cancer that causes death in Brazil. There are some kinds of treatment for this disease, including chemotherapy, radiotherapy and surgeries, such as the colostomy. Although this surgery increases survival rates, colostomy might bring physical and psychological changes which impact directly patients on this condition. Researches in the field of psycho-oncology are important on this cases, considering it comprehends psychological dimensions of cancer by differents perspectives. An instrumental study was carried out, with two participants, both living in a common-law marriage. The goal of this research was to analyze psychodynamic aspects involved on their sexual experience after colostomy. In order to accomplish this goal, semi-structured interviews were conducted as well as the application of the psychological test HTP. The results were analyzed by the psychoanalytical approach and indicated self-esteem decrease; negative self-body perception; social isolation and difficulties in accepting the use of the colostomy bag; mourning over the lost healthy body; shame and concerns about others realize they are carrying a colostomy bag. Each personal patients psycho dynamic impacted the way of dealing with this process. Having distinct personalities and coping strategies, differences were found on the way of dealing with their own relationships. Despite these questions, colostomy had emerged as the main reason for the emotional distance in the relationship, even though a lot of setbacks were already part of their daily routine before the surgery. Furthermore, lack of conjugal support, partners indifference and cohabitation adversities cooperated for the emergence of barriers between the couple and all of that contributed to decadence of sexual life. The patients were not referred to psychological support, despite considering psychotherapy important. They have not found any opportunity to dispel doubts about personal, conjugal or sexual subjects on public health care system

O objetivo deste estudo foi interpretar os significados atribuídos à qualidade de vida pelo paciente com câncer colorretal no contexto da quimioterapia antineoplásica. Utilizamos o referencial teórico da antropologia médica, derivada da antropologia interpretativa, que conceitualmente integra cultura e doença, com utilização do método etnográfico, e análise temática indutiva. Realizaram-se entrevistas em profundidade (CEP-EERP-USP 1412/2011) com dezesseis participantes com câncer colorretal, que realizavam quimioterapia antineoplásica em um hospital público universitário. Foram construídas três unidades de sentidos e dois núcleos temáticos. As unidades de sentido \"Itinerário terapêutico: do diagnóstico aos tratamentos\", \"A quimioterapia antineoplásica e seus efeitos adversos\" e \"Qualidade de vida durante a quimioterapia antineoplásica\", mostraram que a construção do itinerário terapêutico perpassa pelo reconhecimento da anormalidade do corpo, busca pelo sistema profissional de saúde e pela necessidade de tratamentos especializados. A primeira indicação terapêutica é a cirurgia, que traz sofrimento e solução parcial do problema, logo substituída pela quimioterapia. A doença é percebida como uma dimensão incontrolável, e os acontecimentos vivenciados fornecem uma nova identidade social, as marcas corporais representam sua vulnerabilidade e os efeitos adversos denunciam sua condição de doente oncológico. Há o sofrimento social, a necessidade de ter resiliência para aderir ao tratamento, de adaptações e transformações individuais, familiares e sociais, que resultaram na adoção de novas ideias, conceitos, valores e crenças, acrescentando novos elementos na sua identidade social, pois percebe a perda de suas capacidades e a impossibilidade de cura. A esperança da retomada da normalidade da vida anterior é prejudicada pela confirmação da impossibilidade de cura, sendo substituída pelo direito de uma morte digna. A pessoa tem a sua condição oncológica visivelmente denunciada e, apesar da consciência de sua finitude, não abre mão da sua esperança de cura. Nos núcleos temáticos \"A experiência moral atribuída ao câncer colorretal e a quimioterapia antineoplásica\" e \"Qualidade de vida de pessoas com câncer colorretal em quimioterapia antineoplásica - a retomada da normalidade\" foi evidenciada que a quimioterapia é uma etapa liminar para a cura, no processo da experiência moral de ter câncer colorretal, que está relacionada às consequências das atitudes morais e sociais no cotidiano, com busca da preservação de sua autoestima e do senso de normalidade, rejeitando que as possibilidades de cura acabaram. O significado de qualidade de vida é construído, de acordo com as relações desenvolvidas com as pessoas, incluindo o julgamento pessoal sobre sua vida, experiências e expectativas de futuro, relacionados ao contexto de adoecimento, onde a quimioterapia é mais uma etapa do tratamento, que mesmo com suas reações limitantes, ainda é a expectativa de alcance de cura. Há evidências que os participantes não possuem qualidade de vida, pois ocorreu a \"perda do controle da vida\", a percepção que a terapêutica não garante a sua cura, permanecendo a incerteza do futuro, mesmo com o sofrimento e a experiência moral. Deve ocorrer a ampliação do foco da qualidade de vida pelos enfermeiros, incluindo as referências socioculturais das pessoas que vivem o processo de adoecimento e do tratamento, ultrapassando a dimensão biológica e tecnológica do cuidar / The aim of this study was to interpret the meanings attributed to quality of life for patients with colorectal cancer in the context of antineoplasic chemotherapy. We use the theoretical framework of medical anthropology, derived from interpretive anthropology, which conceptually integrates culture and disease with use of ethnographic methods, and inductive thematic analysis. There were in-depth interviews (CEP- EERP- USP 1412/2011) with sixteen participants with colorectal cancer who were undergoing cancer chemotherapy in a public university hospital. Three units of meaning and two thematic groups were constructed. The units of \"Therapeutic itinerary meaning: from the diagnosis to treatment\",\"The antineoplasic chemotherapy and its adverse effects\" and \"Quality of life during cancer chemotherapy\", showed that the construction of the therapeutic itinerary runs through the recognition of body abnormality, the search for professional health care system and the need for specialized treatments. The first therapeutic indication is the surgery, which brings suffering and partial solution of the problem, soon replaced by chemotherapy. The disease is perceived as an uncontrollable dimension, and the experienced events provide a new social identity, the body marks represent their vulnerability and the adverse effects report their condition of cancer patients. There is the social suffering, the need for resilience to adhere to treatment, individual, familiar and social adaptations and transformations, which resulted in the adoption of new ideas, concepts, values and beliefs, adding new elements in their social identity, because they realize the loss of their capabilities and the healing impossibility. The hope of normality of life recovery is impaired by the confirmation of the healing impossibility, being replaced by the right of a dignified death. The person has their oncologic condition visibly exposed and, despite the knowledge of their finitude, does not give up their hope of cure. In thematic groups \"The moral experience attributed to colorectal cancer and cancer chemotherapy\" and \"Quality of life of people with colorectal cancer receiving antineoplasic chemotherapy - normality recovery\" was evidenced that chemotherapy is a preliminary step to healing in the process of moral experience of having colorectal cancer, which is related to the consequences of moral and social attitudes in everyday, with the pursuit of preserving their self-esteem and sense of normality, rejecting that the possibilities of cure have ended. The meaning of quality of life is constructed according to the relations developed with people, including personal judgment about life, experiences and expectations of future related to the context of disease where chemotherapy is one more step of the treatment, that even with their limiting reactions, is still the expectation to reach the cure. There is evidence that participants do not have quality of life, because of the \"loss of control of their lives,\" the perception that the therapy does not ensure healing, remaining the uncertainty of the future, even with the suffering and moral experience. Expanding the focus of quality of life should occur by nurses, including socio-cultural references of people who live the process of illness and treatment, exceeding the biological and technological dimension of care

Eukaryotic translation elongation factor-2 (EEF2) is regulated through phosphorylation by a specific kinase known as eukaryotic elongation factor-2 kinase (EEF2K), leading to translational down regulation. Currently, it has been reported that EEF2K could promote the autophagic survival in breast and glioblastoma cell lines. However, the precise function of EEF2K in cancer as well as the related mechanism is still poorly understood. Colorectal cancer is the third common malignant disease worldwide and more than half of the patients with colorectal cancer require chemotherapy after surgery. However, de novo or acquired resistance to the agents is common. Discovery of novel targets for the chemotherapeutic intervention or treatment of colorectal cancer is highly warranted. In this study, the role of EEF2K as well as the underlying mechanism involved was evaluated in HT-29 and HCT-116 human colon cancer cells. Contrary to the reported autophagy-promoting activity of EEF2K in certain cancer cells, EEF2K is shown to negatively regulate autophagy in colon cancer cells as indicated by the increase of LC3-II levels, the accumulation of LC3 dots per cell, and the promotion of autophagic flux in EEF2K silenced cells. Moreover, the silencing of EEF2K promotes the cell viability, clonogenicity, cell proliferation and cell size in colon cancer cells. The silencing of BECN1 and ATG7 significantly reduce silencing of EEF2K induced LC3-II accumulation and cell survival. However, autophagy induced by EEF2K silencing does not potentiate the anticancer efficacy of the AKT inhibitor MK-2206. In addition, EEF2K overexpression decreases the cell survival and potentiates the antitumor efficacy of oxaliplatin. Autophagy induced by silencing of EEF2K is attributed to induction of protein synthesis, which results in ATP consumption and then actives AMPK-ULK1 pathway. This process appears independent of the suppression of MTOR activity and ROS generation. Silencing of AMPK or ULK1 significantly decreases EEF2K silencing-induced autophagy as well as cell survival in colon cancer cells. In conclusion, EEF2K negatively regulates autophagic survival through the AMPK-ULK1 pathway in colon cancer cells. This study provide useful information in understanding the role of EEF2K in colon cancer cells and suggests that upregulation of EEF2K activity may be developed a novel approach for the treatment of human colon cancer. / 真核延伸因子2激酶 (EEF2K) 通過磷酸化修飾真核延伸因子2 (EEF2) 來調控其活性，進而下調蛋白質翻譯延伸的速度。目前，有研究表明在乳腺癌和多形性膠質母細胞瘤中，EEF2K能夠誘導細胞自噬，並且這種類型的細胞自噬有助於細胞生存。然而，對於EEF2K在腫瘤中的精確作用以及它所涉及的分子機理仍然知之甚少，有待於進一步的研究。結直腸癌是全球第三大惡性腫瘤疾病，約有半數以上的患者需要手術後進行化學藥物治療。然而，患者對目前已有藥物的耐藥性十分普遍，因此，研發新的化學藥物靶點或者新的治療方法十分必要。在本課題研究中，EEF2K的功能及其所涉及的分子機理在人結腸癌細胞系HT-29和HCT-116上進行了闡釋。與在某些特定種類腫瘤細胞中EEF2K能夠誘導細胞自噬產生的現象相反，在EEF2K表達下調的人結腸癌細胞中，細胞自噬標記物LC3-II表達上升， 細胞中LC3斑點的聚集增多，並且細胞自噬流增強的現象，都表明EEF2K在這類腫瘤細胞中負調控細胞自噬。在結腸癌細胞中，EEF2K表達下調能夠增強細胞的活力，單細胞克隆的形成，細胞增殖以及細胞大小。此外，沈默BECN1和ATG7基因的表達都能夠減少EEF2K下調引發的LC3-II積累以及細胞增殖。然而，降低EEF2K表達所引發的細胞自噬並不能夠增強AKT抑制劑MK-2206抗腫瘤的效果。EEF2K的過表達能夠減少細胞增殖並且加強oxaliplatin的抗腫瘤藥效。沈默EEF2K引發的細胞自噬是通過誘導蛋白質的合成，導致ATP的消耗進而激活AMPK-ULK1細胞通路，與MTOR活性的抑制及ROS的產生無關。在結腸癌細胞中，降低AMPK或者ULK1的表達能夠消除EEF2K沈默所引起的LC3-II表達升高，細胞中LC3斑點聚集增多以及細胞增殖加強等現象。綜上所述，在人結腸癌細胞中，沈默EEF2K基因表達能夠通過激活AMPK-ULK1細胞通路，誘導有助於細胞存活的自噬現象產生。本課題研究對理解EEF2K在結腸癌細胞中的功能提供了有用的信息並且表明增強EEF2K的活性可以作為一種潛在的新的治療人結腸癌的方法。 / Liu, Xiaoyu. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 116-131). / Abstracts also in Chinese. / Title from PDF title page (viewed on 16, November, 2016). / Detailed summary in vernacular field only.

by Lai Mei Yi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 130-136). / Abstracts in English and Chinese. / Acknowledgment --- p.i / Abstract --- p.ii / 論文撮耍 --- p.v / List of Figures --- p.viii / List of Tables --- p.xi / Abbreviations --- p.xii / Table of content --- p.xiii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Facilitative glucose transporters --- p.1 / Chapter 1.1.1 --- Predicted Secondary structure of Glutl --- p.1 / Chapter 1.1.2 --- The tissue-specific distribution of glucose transporters --- p.2 / Chapter 1.2 --- Increase of glucose uptake in cancer cells --- p.5 / Chapter 1.3 --- Antisense oligonucleotide therapeutics --- p.7 / Chapter 1.3.1 --- Chemical modifications of oligonucleotides --- p.7 / Chapter 1.3.2 --- Cellular Uptake of Oligonucleotide --- p.11 / Chapter 1.3.3 --- Mechanism of action --- p.13 / Antisense-mediated RNA Cleavage --- p.14 / """Occupancy-only"" mediated mechanism" --- p.15 / Chapter 1.3.4 --- Antisense treatment in vivo --- p.17 / Chapter 1.4.5 --- Human Studies of Antisense Treatment --- p.18 / Chapter Chapter 2 --- Materials & Methods --- p.20 / Chapter 2.1 --- Materials --- p.20 / Chapter 2.2 --- Cell Culture --- p.21 / Chapter 2.2.1 --- Human colon adenocarcinoma cell Line (Caco-2) --- p.21 / Chapter 2.3 --- General Methodology for treatment of cells with antisense oligonucleotides --- p.22 / Chapter 2.3.1 --- Treatment of cells with oligonucleotides --- p.22 / Chapter 2.4 --- Cytotoxicity Assay --- p.23 / Chapter 2.4.1 --- MTT assay --- p.23 / Chapter 2.4.2 --- 3H-thymidine incorporation --- p.23 / Chapter 2.5 --- RNA extraction --- p.24 / Chapter 2.6 --- Competitive Reverse-transcription polymerase chain reaction (RT-PCR) of glucose transporters --- p.25 / Chapter 2.7 --- Measurement of 2-deoxy-D-glucose and Fructose transport --- p.27 / Chapter 2.8 --- Western blotting --- p.28 / Chapter 2.9 --- Flow cytometry --- p.30 / Chapter 2.9.1 --- Measurement of cellular accumulation of fluorophore-labeled oligonucleotide --- p.30 / Chapter 2.10 --- Design of antisense oligonucleotide --- p.31 / Chapter 2.11 --- ATP assay --- p.34 / Chapter 2.12 --- Animals studies --- p.35 / Chapter Chapter 3 --- Optimization of phosphorothioate antisense oligonucleotide delivery by Lipofectin --- p.36 / Chapter 3.1 --- Introduction --- p.36 / Chapter 3.2 --- Measurement of oligonucleotide uptake --- p.38 / Chapter 3.2.1 --- Lipofectin as a delivery system for the oligonucleotide uptake --- p.39 / Chapter 3.2.2 --- Effect of Lipofectin ratio on the oligonucleotide uptake --- p.41 / Chapter 3.2.3 --- Effect of oligonucleotide concentration on the oligonucleotide uptake --- p.41 / Chapter 3.2.4 --- Effect of incubation time on the oligonucleotide uptake --- p.44 / Chapter 3.2.5 --- Effect of oligonucleotide length on cellular uptake --- p.44 / Chapter 3.3 --- Effect of Lipofectin on cell viability --- p.47 / Chapter Chapter 4 --- In vitro effect of Antisense Oligonucleotides against glucose transporters on Caco-2 Cell --- p.49 / Chapter 4.1 --- Introduction --- p.49 / Chapter 4.2 --- Design of Antisense Oligonucleotides against Glucose Transporters gene --- p.50 / Chapter 4.3. --- Antisense effect of different regions of antisense oligonucleotide --- p.52 / Chapter 4.4 --- Antisense and Sense effect of oligonucleotide against start codon (G5 7015) on Caco-2 cells --- p.59 / Chapter 4.4.1 --- Effect of oligonucleotide to Lipofectin ratio on cell viability --- p.59 / Chapter 4.4.2 --- Dose-Response Study: effect of concentration of antisense - oligonucleotide on cell viability --- p.61 / Chapter 4.4.3 --- Effect of length´ؤof oligonucleotide on cell viability --- p.61 / Chapter 4.4.4 --- Time-Response Study: effect of antisense oligonucleotide on cell viability --- p.66 / Chapter 4.5 --- "The effect of antisense oligonucleotide against Glut1, Glut3 and Glut5 on cell viability of Caco-2 cells" --- p.70 / Chapter 4.6 --- Analysis of ATP content in Caco-2 cells by using antisense oligonucleotide flanking start codon (G5 7015) --- p.72 / Chapter 4.7 --- Effect of G5 7015 on HepG2 cells --- p.72 / Chapter Chapter 5 --- Effect of antisense oligonucleotides against Glut5 on mRNA and Protein levels of Glut5 gene --- p.76 / Chapter 5.1 --- Introduction --- p.76 / Chapter 5.2 --- RT-PCR of Glut isoform in Caco-2 cells --- p.77 / Chapter 5.3 --- Effect of antisense oligonucleotides against Glut 5 on mRNA level in Caco-2 cells --- p.77 / Chapter 5.3.1 --- Effect of oligonucleotides targeted different region of Glut5 gene on Glut5 message level --- p.77 / Chapter 5.3.2 --- Reduction in expression of mRNA level of Glut5 by using antisense oligonucleotides targeting start codon (G5 7015) --- p.81 / Chapter 5.3.3 --- Study of the dose and time dependence on inhibition of mRNA expression in G5 7015 treated Caco-2 cells --- p.83 / Chapter 5.3.4 --- Cross-Inhibition of antisense targeting glucose transporter isoforms --- p.83 / Chapter 5.4 --- Reduction in Glut5 protein level using G5 7015 antisense oligonucleotide --- p.86 / Chapter 5.5 --- Inhibition of Glut5 activity using G57015 oligonucleotide --- p.88 / Chapter 5.6 --- Inhibition of Glut5 mRNA level in vivo --- p.93 / Chapter Chapter 6 --- The possible role for Glucose Transporters in the Modification of Multidrug Resistance in Tumor cells --- p.95 / Chapter 6.1 --- Introduction --- p.95 / Chapter 6.2 --- Materials & Methods --- p.97 / Chapter 6.2.1 --- Cell culture --- p.97 / Chapter 6.2.2 --- Chemicals --- p.98 / Chapter 6.2.3 --- Measurement of doxorubicin uptake --- p.99 / Chapter 6.3 --- The expression of P-glycoprotein and Doxorubicin resistance of R-HepG2 cells --- p.99 / Chapter 6.4 --- Comparison of H3-2-deoxyglucose uptake between HepG2 and R-HepG2 cells --- p.99 / Chapter 6.5 --- Quantification of Glut1 and Glut3 expression by RT-PCR --- p.102 / Chapter 6.6 --- Comparison of doxorubicin between HepG2 and R-HepG2 cells cultured accumulation in glucose free medium --- p.104 / Chapter 6.7 --- The time course of doxorubicin accumulation in R-HepG2 cells culturing in glucose free medium --- p.106 / Chapter 6.8 --- "Cell viability of R-HepG2 cells after treatment of glucose transporter inhibitors, phloretin (PT), cytochalasin B (CB) and mitochondrial inhibitor，2,4-Dinitrophenol (DNP)" --- p.106 / Chapter 6.9 --- "Effect of glucose transporter inhibitors (PT, CB) and mitochondrial inhibitor (DNP) on doxorubicin accumulationin R-HepG2" --- p.110 / Chapter 6.10 --- Effect of antisense oligonucleotide against Glutl on doxorubicin accumulation in R-HepG2 cell --- p.113 / Chapter 6.11 --- "Analysis of ATP content and 3H-2-deoxy-D-glucose uptakein R-HepG2 after treatments of PT, CB and DNP" --- p.115 / Chapter Chapter 7 --- Discussion --- p.117 / Chapter 7.1 --- Antisense oligonucleotide against glucose transportersin Caco-2 cell --- p.117 / Chapter 7.2 --- Cellular uptake of oligonucleotide --- p.119 / Chapter 7.3 --- In vitro study of using antisense oligonucleotide against Glut5 --- p.121 / Chapter 7.4 --- In vivo study of using antisense oligonucleotide against Glut5 --- p.126 / Chapter 7.5 --- Possible role of inhibition of glucose transport in reversing P- gp --- p.127 / Chapter Chapter 8 --- References --- p.130

He, Jun. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 136-156). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

越來越多證據表明了煙酰胺腺嘌呤核苷酸磷酸（nicotinamide adenine dinucleotide phosphate, NADPH）代謝對腫瘤細胞增殖和生存的重要性。最近一項研究證實了一個p53調節基因，TP53誘導的糖酵解和凋亡調節因數（TP53-inducible glycolysis and apoptosis regulator, TIGAR），在抑制凋亡和誘導NADPH產生方面的作用。抗凋亡蛋白B細胞淋巴瘤2（B-cell lymphoma 2, Bcl-2）之前被報導能夠通過還未確定的機制誘導NADPH的產生。在這篇論文研究中，我們假設Bcl-2與TIGAR耦合從而調節NADPH的產生和細胞生存，並且TIGAR可能成為一個促進細胞生長的新生存因數。這篇論文研究的目的是：1）檢測在NADPH代謝中Bcl-2與TIGAR間的生物聯繫；2）探究在哺乳動物系統中TIGAR調節的分子機制；3）研究TIGAR在體外和體內調節正常及腫瘤細胞生存的作用。 / 這篇論文的第一部分結果顯示在正常小鼠胚胎成纖維細胞（MEFs）和缺少功能性p53的人非小細胞肺癌（NSCLC）細胞中存在Bcl-2/TIGAR/NADPH這樣一個新的信號通路軸，重要抗凋亡蛋白Bcl-2與TIGAR耦合後，以一個特有並持久的方式調節NADPH代謝和細胞生長。用特異的小干擾RNA（siRNA）靶向抑制Bcl-2能夠在NSCLC細胞中抑制TIGAR/NADPH/生長信號軸。用小分子抑制劑ABT-737對Bcl-2進行藥理學抑制也能夠顯示相似的作用，而這個作用能夠通過過表達TIGAR被部分逆轉。而且，敲除TIGAR能夠降低Bcl-2誘導的NADPH產生和細胞生長，表明了TIGAR在介導TIGAR/NADPH/生長信號軸中的關鍵作用。 / 為了第二個目的，我們研究了Bcl-2對TIGAR的機制調節。我們發現過表達Bcl-2不能改變TIGAR的mRNA水平，但是能誘導轉錄後的TIGAR蛋白累積。有趣的是，TIGAR似乎能通過一個正反饋回路誘導Bcl-2的表達，這進一步促進了由Bcl-2誘導的TIGAR表達上調。除了Bcl-2，許多致癌基因或生長調節因數也被證實參與了TIGAR的調節，包括信號轉導和轉錄啟動因數3（signal transducer and activator of transcription 3, STAT3, Bcl-2的上有調節因數），表皮生長因數受體（epidermal growth factor receptor, EGFR）和肝細胞生長因數受體（hepatocyte growth factor receptor, c-Met）。 / 這篇論文的第三部分證實了TIGAR在缺少功能性p53細胞模型中的致癌作用。TIGAR過表達能夠誘導一些癌症的標誌性特徵，包括細胞代謝調節異常，細胞生長增加和凋亡減少。重要的是，TIGAR的過表達在MEFs和缺少功能性p53的NSCLC細胞中直接促成了腫瘤形成，促進了腫瘤的生長。但是功能性p53的存在無論在體外還是體內都能夠消除TIGAR這種生長促進和成瘤的作用。這些發現表明當p53功能消失時TIGAR能成為一個致癌基因，促進腫瘤形成。 / 總的來說，我們發現了在腫瘤中Bcl-2/TIGAR/NADPH這樣一條新的信號通路。Bcl-2通過增加TIGAR蛋白累積的轉錄後機制調節TIGAR。我們也證實了TIGAR受到多種致癌基因或生長調節因數的調節，包括STAT3，EGFR和c-Met。並且，我們闡明了當p53功能消失時TIGAR能成為一個致癌基因，促進細胞轉化和腫瘤形成。 / Emerging evidences reveal the importance of nicotinamide adenine dinucleotide phosphate (NADPH) metabolism for cancer cell proliferation and survival. A recent study demonstrated the role of a p53-regulated gene, TP53-inducible glycolysis and apoptosis regulator (TIGAR), in inhibiting apoptosis and inducing NADPH production. The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) has previously been reported to induce NADPH generation through undefined mechanism. In this thesis study, we hypothesized that Bcl-2 is coupled to TIGAR for regulation of NADPH production and cell survival, and that TIGAR may serve as a novel survival factor contributing to cell growth. The objectives of the thesis study are: 1) to examine the biologic relationship between Bcl-2 and TIGAR in NADPH metabolism; 2) to investigate the molecular mechanisms of TIGAR regulation in mammalian systems; and 3) to examine the role of TIGAR in regulating normal and cancer cell survival in vitro and in vivo. / Findings in first part of the thesis revealed a novel signaling axis of Bcl-2/TIGAR/NADPH in normal mouse embryonic fibroblasts (MEFs) and human non-small cell lung cancer (NSCLC) cells lacking functional p53, coupling the major anti-apoptotic protein Bcl-2 to TIGAR regulation for NADPH metabolism and cell growth in a specific and sustained manner. Targeting of Bcl-2 by specific siRNA inhibited TIGAR/NADPH/growth axis in NSCLC cells. Pharmacologic inhibition of Bcl-2 by small molecule inhibitor ABT-737 also exhibited similar effects, which was partially reversed by the overexpression of TIGAR. In addition, TIGAR knockdown reduced Bcl-2-induced NADPH production and cell growth, implicating a critical role of TIGAR in mediating Bcl-2/NADPH/growth signaling axis. / For the second objective, we studied the mechanistic regulation of TIGAR by Bcl-2. We found that overexpression of Bcl-2 did not alter TIGAR mRNA expression but induced TIGAR protein accumulation post-transcriptionally. Interestingly, TIGAR seemed to induce Bcl-2 expression via a positive feedback loop, which may further contribute to the upregulation of TIGAR expression induced by Bcl-2. In addition to Bcl-2, a number of oncogene/growth regulators were demonstrated to be involved in TIGAR regulation, including signal transducer and activator of transcription 3 (STAT3, an upstream regulator of Bcl-2), epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met). / The third part of the thesis demonstrated the oncogenic role of TIGAR in cell models lacking functional p53. TIGAR overexpression induced several hallmark features of cancer including deregulated cell metabolism, increased cell growth and inhibited apoptosis. Strikingly, overexpression of TIGAR directly drove tumor formation and promoted tumor growth in MEFs and NSCLC cells lacking functional p53. The growth stimulatory and tumorigenic activities of TIGAR were abolished in the presence of functional p53 both in vitro and in vivo. These findings revealed TIGAR as an oncogene capable of driving tumorigenesis when p53 function is lost. / In summary, we have identified a novel signaling pathway of Bcl-2/TIGAR/NADPH in cancer. TIGAR is regulated by Bcl-2 via a post-transcriptional mechanism by enhancing TIGAR protein accumulation. We also demonstrated the regulation of TIGAR by multiple oncogene/growth regulators including STAT3, EGFR and c-Met. Furthermore, we have demonstrated TIGAR as an oncogene capable of driving cell transformation and tumorigenesis when p53 function is lost. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Lam, Kai Yee. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 158-176). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Abstract --- p.i / 摘要 --- p.iv / Declaration --- p.vi / Acknowledgements --- p.vii / Publications --- p.viii / Table of Content --- p.ix / List of Illustrations --- p.xii / List of Abbreviations --- p.xv / Chapter Chapter 1: --- Introduction / Chapter 1.1 --- Overview of tumor metabolism --- p.1 / Chapter 1.1.1 --- Glucose metabolism --- p.4 / Chapter 1.1.2 --- Glutamine metabolism --- p.6 / Chapter 1.1.3 --- De novo fatty acid synthesis --- p.7 / Chapter 1.1.4 --- Advantages of metabolic reprogramming in tumor cells --- p.8 / Chapter 1.2 --- Mechanisms regulating metabolic reprogramming in cancers --- p.11 / Chapter 1.2.1 --- Tumor suppressor p53 --- p.11 / Chapter 1.2.2 --- Hypoxia-inducible factor 1 (HIF-1) --- p.13 / Chapter 1.2.3 --- PI3K/Akt/mTOR signaling pathway --- p.15 / Chapter 1.2.4 --- Oncogenic Myc --- p.16 / Chapter 1.2.5 --- Oncogenic Ras --- p.18 / Chapter 1.3 --- TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) --- p.22 / Chapter 1.3.1 --- TIGAR and oxidative stress --- p.25 / Chapter 1.3.2 --- TIGAR and carcinogenesis --- p.29 / Chapter 1.3.3 --- TIGAR and other diseases --- p.32 / Chapter 1.4 --- Hypotheses and Aims --- p.36 / Chapter Chapter 2: --- Materials and Methods / Chapter 2.1 --- Materials --- p.38 / Chapter 2.1.1 --- Chemicals and reagents --- p.38 / Chapter 2.1.2 --- Drugs --- p.41 / Chapter 2.1.3 --- Commercial detection kits --- p.41 / Chapter 2.1.4 --- Antibodies --- p.42 / Chapter 2.2 --- Cell culture --- p.43 / Chapter 2.3 --- Plasmids --- p.44 / Chapter 2.4 --- Transfection --- p.46 / Chapter 2.5 --- Retrovirus infection --- p.47 / Chapter 2.6 --- Drug treatment --- p.47 / Chapter 2.7 --- Cell viability assay --- p.48 / Chapter 2.8 --- Trypan blue exclusion assay --- p.49 / Chapter 2.9 --- NADPH assay --- p.49 / Chapter 2.10 --- Cell death detection ELISA --- p.50 / Chapter 2.11 --- Western blotting --- p.50 / Chapter 2.12 --- Reverse TranscriptionPolymerase Chain Reaction (RT-PCR) --- p.51 / Chapter 2.13 --- Cell cycle analysis --- p.52 / Chapter 2.14 --- Transwell migration and matrigel invasion assays --- p.53 / Chapter 2.15 --- In vivo studies --- p.54 / Chapter 2.16 --- Histology and immunohistochemistry --- p.55 / Chapter 2.17 --- Statistical analysis --- p.56 / Chapter Chapter 3: --- Indentification of Novel Bcl-2/TIGAR/NADPH Signaling Axis / Chapter 3.1 --- Introduction --- p.57 / Chapter 3.2 --- Results --- p.60 / Chapter 3.2.1 --- Bcl-2-induced NADPH production and cell growth is associated with TIGAR upregulation in p53-null MEFs --- p.60 / Chapter 3.2.2 --- Identification of Bcl-2/TIGAR/NADPH signaling axis in p53-negative NSCLC cells --- p.63 / Chapter 3.2.3 --- Bcl-2 targeting reduces TIGAR expression and NADPH production in MEFs and NSCLC cells --- p.66 / Chapter 3.2.4 --- Pharmacologic intervention of Bcl-2 alters TIGAR levels in MEFs and NSCLC cells --- p.71 / Chapter 3.2.5 --- Bcl-2 targeting inhibits TIGAR expression, NADPH production and cell growth in Bcl-2-amplified small cell lung cancer (SCLC) cells --- p.76 / Chapter 3.2.6 --- Bcl-2-induced TIGAR expression is highly specific compared to other pro-survival proteins --- p.78 / Chapter 3.2.7 --- Bcl-2/TIGAR/NADPH signaling axis is functionally intact in p53-positive NSCLC cells --- p.80 / Chapter 3.3 --- Discussion --- p.83 / Chapter Chapter 4: --- Mechanisms of TIGAR Regulation / Chapter 4.1 --- Introduction --- p.88 / Chapter 4.2 --- Results --- p.90 / Chapter 4.2.1 --- Bcl-2 regulates TIGAR by post-transcriptional mechanism --- p.90 / Chapter 4.2.2 --- Bcl-2-induced TIGAR expression is associated with upregulation of other pro-survival proteins --- p.94 / Chapter 4.2.3 --- STAT3 activation can serve as a biological signal for TIGAR induction --- p.97 / Chapter 4.2.4 --- Tyrosine kinase receptors contributes to TIGAR regulation --- p.100 / Chapter 4.2.5 --- The existence of TIGAR/Bcl-2 positive feedback loop --- p.102 / Chapter 4.3 --- Discussion --- p.104 / Chapter Chapter 5: --- TIGAR is Oncogenic / Chapter 5.1 --- Introduction --- p.107 / Chapter 5.2 --- Results --- p.109 / Chapter 5.2.1 --- Overexpression of TIGAR alters several hallmark features of cancer --- p.109 / Chapter 5.2.2 --- TIGAR drives tumor formation in vivo --- p.114 / Chapter 5.2.3 --- Tumorigenic activity of TIGAR is functionally counteracted by functional p53 --- p.123 / Chapter 5.3 --- Discussion --- p.134 / Chapter Chapter 6: --- Summary --- p.138 / Chapter Chapter 7: --- Future Prospective --- p.143 / Appendices --- p.148 / References --- p.158

A Quimioterapia antineoplásica (QtA) adjuvante para câncer colorretal (CCR) traz consequências fisiológicas e psicossociais como os eventos adversos (EA) gastrintestinais e dermatológicos, que podem trazer dificuldades na utilização de equipamentos para os pacientes com estomia intestinal. Este estudo teve por objetivos analisar a produção científica nacional e internacional sobre os EA gastrintestinais e dermatológicos para pacientes com CCR em QtA adjuvante; e estabelecer as recomendações em relação à indicação de equipamentos coletores e adjuvantes para os pacientes com estomia intestinal por CCR, assim como para os cuidados com a estomia intestinal e o manejo destes equipamentos durante a QtA, com base nas evidências científicas. Trata-se de uma Revisão Integrativa, fundamentada na Prática Baseada em Evidências, cuja pergunta formulada foi: Quais os EA gastrintestinal e dermatológico decorrentes da quimioterapia adjuvante em pacientes com câncer colorretal? Os descritores utilizados para as buscas foram Neoplasias Colorretais, Quimioterapia, Toxicidade, Efeitos adversos, nas bases de indexação eletrônica PubMed, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Cumulative Index to Nursing and Allied Health (CINAHL), e Excerpta Médica (EMBASE), mediante os critérios de inclusão: estudos que abordassem a ocorrência e o tratamento de EA gastrintestinais ou dermatológicos em pacientes com CCR em QtA adjuvante; e estudos publicados em inglês, português ou espanhol, sem corte temporal de publicação; obtidos na íntegra via Biblioteca Central do Campus de Ribeirão Preto da Universidade de São Paulo; e os critérios de exclusão que foram estudos em modelo animal e modelo in vitro; estudos sobre metástases associadas ao tumor primário colorretal. Do total de 4.021 artigos científicos, resultantes das buscas, foram selecionados mediante os critérios de inclusão e exclusão, 20 estudos que constituíram a amostra final, sendo que todos foram publicados em inglês, com níveis de evidência pouco fortes em 65% (IV e VI) e cujos aspectos abordados foram categorizados em quatro temáticas: Diarreia e demais EA gastrintestinais; Diarreia e EA Gastrodermatológicos; EA Gastrintestinais; e EA Dermatológicos. No tema Diarreia e demais EA gastrintestinais evidenciou-se diarreia, náusea, perda de apetite e constipação, vinculados à QtA adjuvante com 5-FU, capecitabina e irinotecano. No tema Diarreia e EA Gastrodermatológicos evidenciou-se síndrome palmar-plantar, outras afecções cutâneas (eritema, úlcera, descamação, prurido, eritema, bolha), estomatite, edema das mãos/face/boca, e hipersensibilidade por capecitabina e oxaliplatina. No tema EA Gastrintestinais verificamos que náusea e vômito foram mais frequentes e relacionados à oxaliplatina. No tema EA Dermatológicos, evidenciou-se rash cutâneo, rubor, prurido, reações alérgicas, síndrome palmar-plantar nos esquemas com 5-FU, capecitabina, oxaliplatina e irinotecano. Considerando estas evidências e a necessidade de utilização de equipamentos coletores do paciente com estomia intestinal por CCR em QtA adjuvante, a assistência de enfermagem especializada deve assegurar a demarcação de estoma, ensino do autocuidado sobre EA e seu manejo, indicação e fornecimento de equipamentos coletores e adjuvantes, que atendam as suas necessidades, assim como o desenvolvimento de protocolos para avaliação dos EA gastrintestinais e dermatológicos durante a QtA adjuvante / The antineoplastic chemotherapy for adjuvant colorectal cancer (ACC) brings physiological and psychosocial consequences such as gastrointestinal and dermatologic adverse events (AE), which can cause difficulties in using equipment for patients with ostomy. This study aimed to analyze the national and international scientific literature on the gastrointestinal and dermatological EA for patients with CRC in adjuvant chemotherapy; and establish recommendations regarding the indication of equipment supplies and also aid for patients with ostomy by CRC, as well as for ostomy care and management of this equipment during the chemotherapy, based on scientific evidence. This is an integrative review, based on the evidence-based practice, whose question was: What are the gastrointestinal and dermatological EA resulting from adjuvant chemotherapy in patients with colorectal cancer? The descriptors used for the search were Colorectal neoplasms, Drug therapy, Toxicity, and Adverse effects, in electronics PubMed indexing bases, Latin American and Caribbean Health Sciences (LILACS), Cumulative Index to Nursing and Allied Health (CINAHL) and Excerpta Medical (EMBASE) by the inclusion criteria: studies that addressed the occurrence and treatment of gastrointestinal or dermatological EA in patients with CRC in adjuvant chemotherapy; and studies published in English, Portuguese or Spanish, without temporal cutting time publication; obtained in entirety at Ribeirão Preto Campus Central Library of the University of São Paulo; and the exclusion criteria were studies in animal models and in vitro model; studies on colorectal metastases associated with primary tumor. Of the total of 4,021 scientific articles resulting from the searches, they were selected by the inclusion and exclusion criteria, 20 studies which formed the final sample, all of which have been published in English, with little strong evidence levels 65% (IV and VI) and whose addressed aspects were categorized into four themes: Diarrhea and other gastrointestinal EA; Diarrhea and gastrointestinal and dermatologic EA; Gastrointestinal EA; Dermatologic EA. In the subject Diarrhea and other gastrointestinal EA became evident diarrhea, nausea, loss of appetite and constipation linked with adjuvant 5-FU, capecitabine, and irinotecan. On the topic diarrhea and Gastrointestinal and dermatologic EA showed up hand-foot syndrome, other skin disorders (erythema, ulcers, peeling, itching, erythema, and bubble), and stomatitis, swelling of the hands / face / mouth, and hypersensitivity oxaliplatin and capecitabine. On the topic Gastrointestinal EA were found that nausea and vomiting were more frequent and related to oxaliplatin. On the topic of Dermatological EA, evidence of skin rash, redness, itching, allergic reactions and palmar-plantar syndrome in the schemes with 5-FU, capecitabine, oxaliplatin and irinotecan. Considering this evidence and the need for equipment supplies in patients with ostomy by CRC in chemotherapy, specialized nursing care to ensure the demarcation of stoma, self-care education on EA and its management, display and supply collectors equipment and adjuvants that meet their needs, as well as the development of protocols for evaluation of gastrointestinal and dermatological EA during adjuvant chemotherapy.

Resumo: Este estudo objetivou interpretar o significado do primeiro ano de pós- operatório para pessoas com estoma intestinal por câncer colorretal, em seguimento ambulatorial. Utilizamos o referencial teórico da Sociologia da Saúde, que integra ações das pessoas às estruturas sociais em um contexto, com utilização do método etnográfico e análise temática indutiva. Foram realizadas entrevistas em profundidade (Parecer no. 184.720 - CEP/EERP-USP) com treze participantes com estoma intestinal por câncer colorretal, no primeiro ano de pós-operatório em um hospital público universitário, em seguimento de controle oncológico. Foram construídas três unidades de sentidos e dois núcleos temáticos. As unidades de sentido \"Adoecimento oncológico: da suspeita à constatação\", \"Gerenciamento do adoecimento e do tratamento oncológico\" e \"Convivendo com o câncer, com a estomia intestinal e com o eu diferente, mostraram a decisão pelo itinerário terapêutico perpassa pelo reconhecimento do acontecimento de algo grave com o corpo destas pessoas, busca pelo sistema profissional de saúde e a luta pela acessibilidade aos exames especializados e dos tratamentos oncológicos, em busca de cura. O gerenciamento das consequências do tratamento cirúrgico como a estomização intestinal e dos tratamentos adjuvantes como a fadiga levam à reflexividade sobre as mudanças do corpo e as repercussões na vida destas pessoas, contrapondo a normalidade anterior e após o adoecimento oncológico, além do enfrentamento do estigma da doença e do estoma intestinal. Contudo, a vida destas pessoas ficou mais restrita aos acontecimentos clínicos e ao contexto de assistência à saúde, às expectativas de respostas aos tratamentos e as possibilidades de recidiva e de metástase, mas com busca de uma normalidade nesta etapa de sobrevivência. Na perspectiva da Reconfiguração do self os dois temas construídos: \"A etapa de sobrevivência da pessoa com estoma intestinal no seguimento oncológico\" e \"Estomização por CCR no primeiro ano de pós-operatório: o eu reconfigurado\", trouxeram os desafios e sofrimentos vividos por estas pessoas na busca pelo direito à acessibilidade ao exame de colonoscopia e aos tratamentos oncológicos, assim como a demanda de suas necessidades de cuidados no período do seguimento de controle e os limites do sistema profissional. O significado do primeiro ano de pós-operatório das pessoas com estoma intestinal por CCR em seguimento oncológico foi construída mediante o Referencial teórico da Reconfiguração do self na perspectiva da Sociologia Compreensiva, considerando as ações e interações destas pessoas para a mediação da experiência de perdas corporais, dos limites e de sofrimentos em decorrência deste câncer, dos resultados com o tratamento oncológico e da estomização, cuja reflexividade sobre o sentido da vida e do viver, culmina o \"eu diferente\", representado por ter câncer e estoma intestinal, em \"eu reconfigurado\", representado pelo processo de estomização por câncer colorretal, ou seja, estas mudam as suas expectativas de cura para expectativas de se manterem vivas por mais um dia / Abstract: This study aimed to interpret the meaning of the first year after surgery for people with intestinal stoma for colorectal cancer. We use the theoretical framework Sociology of health, integrating actions of those social structures in context, using the ethnographic method and inductive thematic analysis. In-depth interviews were conducted (opinion No. 184,720 - CEP/EERP-USP) with thirteen participants with intestinal stoma for colorectal cancer, in the first year after surgery in a public hospital in outpatient follow-up for cancer control. Three units of meaning and two thematic units were built. The sense units \"cancer Illness: from suspicion to finding\", \"Managing illness and cancer treatment\" and \" Living with cancer, with ostomy and with a different me,\", showed the decision by therapeutic itinerary runs through the recognition of a serious event happening with the body of these people, search for professional health system and the struggle for accessibility to specialized tests and cancer treatments, for healing. The management of the consequences of surgical treatment as the intestinal stomatization and adjuvant treatments as fatigue lead to reflexivity about body changes and the impact on the lives of these people, opposed to normal life before and after the illness, cancer beyond the coping of the stigma of the disease and intestinal stoma. However, their lives became more restricted to clinical events and the health care context, the expectations of treatment response and chances of recurrence and metastasis, but with finding a normal life in this survival stage. From the perspective of self Resetting the two themes built: \"A person\'s survival stage with intestinal stoma following cancer\" and \"stomatization by CRC in the first year after surgery: the self reconfigured\", brought the challenges and sufferings experienced by these people searching for the right to accessibility to colonoscopy and cancer treatments, as well as the demand for their care needs in control of follow-up period and limits of the professional system. The meaning of the first year after surgery for people with intestinal stoma by CRC in oncological was built by the Theoretical framework of self reconfiguration in the perspective of Comprehensive Sociology, considering the actions and interactions of these people to the mediation of the experience of bodily losses, the limits and suffering as a result of this cancer, the consequences with the cancer treatment and stomatization whose reflexivity about the meaning of life and living, culminates the \"me different,\" represented by having cancer and intestinal stoma, on \"I reconfigured\" represented by stomatization process colorectal cancer, so, they change their expectations for curing expectations remain alive for another day