Colorectal cancer (CRC), with an estimated 1.2 million new cases annually, is the third leading cause of cancer incidence and death worldwide. Generally, the majority of CRC patients are diagnosed at the advanced stages with poor prognosis and unfavorable response to multiple therapeutic drugs. In spite of increasing knowledge of the molecular mechanism for the tumorigenesis in CRC patients, the translation from basic science into clinical therapy has been limited for quite a long time. In order to develop novel treatment strategies against CRC, intensive and extensive attempts have been made in the past decades. / The epithelial to mesenchymal transition (EMT) is a multi-step process characterized by the loss of cell polarity, decreased cell-cell adhesion as well as enhanced migration and invasion capacity. It is well documented that EMT is essential for a variety of cellular biological events ranging from embryogenesis to tumor progression. The field of lncRNA is developing rapidly and currently it is one of the most intensively studied fields in the biomedical sciences. Emerging evidence indicates that the majority of human genome encodes thousands of non-protein-coding RNA transcripts, nevertheless, the function of long non-coding RNAs (lncRNAs) in orchestrating EMT progression remains elusive. Historically, the lncRNA H19 was the first identified imprinted non-coding RNA transcript in human, and the H19/IGF2 locus acted as an ideal paradigm for the investigation of genomic imprinting genes. In recent years, the expression profiling and functional characterization of the H19 gene in a variety of human diseases has been extensively studied. / In our studies, H19 was characterized as a novel regulator of EMT in colon cancer. We first observed significant mesenchymal characteristics in the methotrexate-resistant HT-29 cells. Interestingly, significant upregulation of H19 was observed in mesenchymal-like MTX resistant HT-29 cells. We subsequently demonstrated that after treatment of TGF-β1, one of the most widely used EMT inducers, H19 presented dramatic increase during the EMT progression. To further investigate the functional role of H19 in EMT, we generated the stable cell lines overexpressing H19 in colon cancer cells using retroviral infection. Stable overexpression of H19 significantly promoted EMT progression in two epithelial colon cancer cell lines HT-29 and HCT-116. However, overexpression of H19 did not affect cell proliferation as well as cell cycle progression. Further proteomics studies screened out that ectopic expression of H19 upregulated the protein level of Vimentin, a vital biomarker for mesenchymal cells. By using the bioinformatics study in combination with luciferase reporter assays, we demonstrated that H19 potentiated the expression of several core marker genes essential for mesenchymal cells by serving as a competing endogenous RNA(ceRNA), which builds up the missing link between the regulatory miRNA network and EMT progression. According to the results from xenograft tumor model and soft agar assay, stable expression of H19 reinforced the in vitro and in vivo tumor growth. Moreover, the investigation of clinical specimens verified that H19 RNA level was significantly increased in colon cancer tissues compared with corresponding adjacent normal tissues. Taken together, the above observations imply that the lncRNA H19, by acting as a competing endogenous RNA, is an important regulator which tightly modulated the expression of multiple important genes involved in EMT and it could probably serve as a novel therapeutic target against colon cancer. / 大腸癌每年有一百二十萬新增個案，是世界第三大癌症殺手。通常情況下，大部分大腸癌病人發現時已經處於晚期，該時期的癌症病人對多種臨床治療藥物已無法治愈。盡管關於大腸癌發病的分子生物學機制已經不斷完善，但如何從基礎研究轉化為臨床治療手段在很長一段時間內不可實現。為了進一步研究新的抗擊大腸癌治療手段，廣泛且深入的研究已經不斷開展。 / 上皮間充質轉化是一個多步驟的過程，該過程的典型特徵為失去細胞的極性，細胞間粘連減弱以及細胞爬行遷移能力的不斷加強。目前科學家已經知道上皮間充質轉化對於從胚胎發育到腫瘤發展都起著重要的作用。近年來，長非編碼RNA的研究不斷快速發展，已然成為醫學研究中最激烈的領域之一。眾多證據表明人體基因組編碼數以千計不編碼蛋白質的RNA轉錄體。然而，這些RNA轉錄體在上皮間充質轉化中的功能依然所知甚少。長非編碼RNA H19是人體內第一個被鑒別出來參與到基因印記的非編碼RNA。資料表明H19/IGF2位點是一個非常理想的研究基因印記的位點。近年來，H19在眾多癌症中的表達以及功能學研究已不斷湧現，同時也不斷取得令人鼓舞的研究成果。 / 在我們的研究中，H19被鑒定為大腸癌裏上皮間充質轉化過程中一個重要的參與者。通過研究甲氨蝶呤耐藥大腸癌HT-29細胞株，我們發現該HT-29耐藥細胞株有著顯著的間充質細胞特性。有趣的是，H19在該細胞株中有著顯著升高。我們隨後用經典的上皮間充質轉化誘導劑TGF-β1處理兩株大腸癌細胞，處理後H19亦有著顯著升高。為了進一步研究H19在上皮間充質轉化，通過使用逆轉錄病毒，我們建立H19的穩定表達細胞株。穩定表達H19顯著地促進了HT-29以及SW620大腸癌細胞株的上皮間充質轉化。然後，高水平表達(過表達)H19並不影響細胞的生長以及細胞周期的進程。進一步的蛋白質組學研究表明，過表達H19能促進間充質細胞一個重要標記基因Vimentin的表達。通過生物信息學以及熒光素酶報告基因實驗，我們證明了H19通過其競爭內源性RNA的作用，能夠促進間充質細胞所需的幾個重要基因的表達。該發現建立起了miRNA網絡以及上皮間充質轉化進程的交流網絡。通過異位移植以及軟瓊脂實驗，我們發現過表達H19能夠促進腫瘤細胞的生長。而在臨床大腸癌病人組織中，我們更發現H19在大腸癌病人組織中高表達。綜上所述，我們的結果證明H19這一長非編碼RNA，能夠通過其競爭內源性RNA的作用機制，從而調控上皮間充質轉化過程中的關鍵基因。同時H19亦有可能成為治療大腸癌的臨床新靶點。 / Liang, Weicheng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 95-124). / Abstracts also in Chinese. / Title from PDF title page (viewed on 24, October, 2016). / Liang, Weicheng.

O tratamento quimioterápico do câncer de cólon e reto pode provocar efeitos adversos que limitam a efetividade da terapia e tem grande impacto nos resultados finais do tratamento, sendo a neutropenia a toxicidade hematológica mais comum decorrente do tratamento quimioterápico. O presente estudo teve como objetivos identificar a ocorrência de neutropenia em pacientes com câncer de cólon e reto submetidos a tratamento quimioterápico adjuvante do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP) e avaliar o risco para o desenvolvimento de neutropenia febril (NF) de acordo com o índice de risco da Associação Multinacional de Cuidados de Assistência ao Câncer (MASCC), em pacientes que apresentaram neutropenia durante o tratamento quimioterápico. Trata-se de um estudo descritivo e retrospectivo, realizado por meio da revisão de 60 prontuários de pacientes com diagnóstico de câncer de cólon e reto submetidos ao tratamento quimioterápico com 5-fluorouracil, ácido folínico e oxaliplatina (FLOX), seguidos no ambulatório de Coloproctologia deste referido hospital, entre os anos de 2010 a 2017. Foi realizada a avaliação dos resultados laboratoriais a cada semana do tratamento quimioterápico nos pacientes elegíveis para este estudo. A idade média dos participantes foi de 63,8 anos. 34 pacientes (56,7%) eram do sexo masculino. A maioria 50 (83,3%) era da raça branca. Quanto ao estado civil 37 (61,7%) eram casados. O tipo de neoplasia mais frequente foi o adenocarcinoma de reto, representado por 38 (63,3%) pacientes, seguido pelo adenocarcinoma de cólon com 22 (36,7%). Os estadiamentos clínicos mais observados foram o IIIb em 18 (30%) pacientes, seguido do IVa em 16 (26,7%). Foi analisado um total de 146 ciclos de quimioterapia com uma média de 2,5 ciclos por paciente, e 876 semanas de tratamento quimioterápico. Dos 60 pacientes participantes no estudo, 41,7% apresentaram neutropenia em algum momento do tratamento quimioterápico. Entre estes 60 pacientes, 21,6% apresentaram um episódio de neutropenia, dois episódios foram observados em 13,3%, quatro episódios em 3,4% e, 3,4% dos pacientes desenvolveram seis episódios de neutropenia. No total, foram identificados 49 episódios de neutropenia. Registrou-se 67 atrasos entre as semanas de tratamento com uma média de 5,02 dias. A redução de doses foi utilizada em 30 pacientes, com um total de 40 ciclos e 218 semanas de tratamento reduzidos, e a suspensão do tratamento ocorreu em 21 pacientes, totalizando 57 semanas de tratamento com suspensão de 27 ciclos. A neutropenia neste estudo esteve entre os principais motivos para os atrasos, reduções de dose e suspensão do tratamento quimioterápico. Quanto a avaliação de risco para o desenvolvimento de NF, 23 pacientes (84%) apresentaram baixo risco, 2 (8%) apresentaram alto risco e 2 (8%) apresentaram baixo e/ou alto risco concomitantemente. Os resultados deste estudo evidenciam que a neutropenia em pacientes com câncer de cólon e reto em tratamento quimioterápico tem uma incidência relativamente baixa em seus diferentes graus, possui baixo risco para o desenvolvimento de NF, e sugere a elaboração e implantação de instrumentos nos serviços de saúde que forneçam o melhor registro de informações da incidência de neutropenia, evitando sua subnotificação / The chemotherapeutic treatment of colon and rectal cancer can entail adverse effects that limit the effectiveness of the therapy and have a great impact on the final results of the treatment, where neutropenia is the most common hematological toxicity resulting from the chemotherapeutic treatment. This study was aimed to identify the occurrence of neutropenia in patients with colon and rectal cancer who underwent adjuvant chemotherapeutic treatment at the Clinical Hospital of the Ribeirão Preto Medical School, which belongs to the University of São Paulo (HCFMRP-USP), and to assess the development of febrile neutropenia (FN), according to the risk index of the Multinational Association for Supportive Care in Cancer (MASCC), in patients who had neutropenia during the chemotherapeutic treatment. This is a descriptive and retrospective study, which was performed through the review of 60 medical charts of patients diagnosed with colon and rectal cancer who underwent chemotherapeutic treatment with 5-fluorouracil, folinic acid and oxaliplatin (FLOX) and were monitored at the outpatient clinic of Coloproctology of this hospital between 2010 and 2017. We performed the assessment of the laboratory results of the chemotherapeutic treatment in patients allowable for this study on a weekly basis. The average age of participants was 63.8 years. A total of 34 patients (56.7%) were male. Most, 50, (83.3%) were white. As for marital status, 37 (61.7%) were married. The most frequent type of neoplasm was rectal adenocarcinoma, represented by 38 (63.3%) patients, followed by colon adenocarcinoma with 22 (36.7%). The most observed clinical staging were IIIb, 18 (30%) patients, followed by IVa, 16 (26.7%). We analyzed a total of 146 chemotherapeutic cycles, with an average of 2.5 cycles per patient, and 876 weeks of chemotherapeutic treatment. Of the 60 patients participants in the study, 41.7% had neutropenia at some time over the chemotherapeutic treatment. Among these 60 patients 21.6% had one episode of neutropenia, two episodes were observed in 13.3%, four episodes in 3.4%, and 3.4% of the patients developed six episodes of neutropenia. Altogether, 49 episodes of neutropenia were identified. We noted 67 delays among the treatment weeks, with an average of 5.02 days. Dose reduction was used in 30 patients, with a total of 40 cycles and 218 weeks of treatment reduced, and treatment suspension happened to 21 patients, totaling 57 treatment weeks with 27 suspension cycles. In this study, neutropenia was among the main reasons for the delays, dose reductions, and suspension of chemotherapeutic treatment. As for the risk assessment for the development of FN, 23 patients (84%) showed low risk, 2 (8%) showed high risk and 2 (8%) showed low and/or high risk concomitantly. The results of this study highlight that neutropenia in patients with colon and rectal cancer undergoing chemotherapeutic treatment has a relatively low incidence in its different stages, has low risk for the development of FN, in addition to suggesting the preparation and implementation of instruments capable of providing the best record of information on the incidence of neutropenia in health services, thus avoiding its underreporting

INTRODUÇÃO: A ressecção hepática é o único tratamento potencialmente curativo para as metástases hepáticas de câncer colorretal (MHCCR), porém com taxas de recidiva entre 60 e 70%. Desta forma, faz-se necessário um melhor entendimento das vias de disseminação e recidiva da doença. Os brotamentos tumorais (BT) e grupamentos pouco diferenciados (GPD), relacionados à transição epitélio-mesenquimal, são fatores prognósticos para o câncer colorretal; entretanto sua presença e importância nas MHCCR ainda não estão estabelecidas. Os objetivos deste trabalho foram avaliar a presença dos BT e GPD nas MHCCR, determinar sua importância prognóstica e sua relação com outros fatores patológicos conhecidos. MÉTODOS: Foram avaliados, retrospectivamente, 229 pacientes submetidos a ressecção de MHCCR com intuito curativo, entre janeiro de 2004 e junho de 2014. Nos espécimes cirúrgicos das MHCCR ressecadas, foi realizada análise anatomopatológica através de lâminas coradas em hematoxilina e eosina (HE), para avaliação dos BT, GPD, infiltrado inflamatório peritumoral, presença de pseudocápsula e tipo de borda; e por imuno-histoquímica, por meio de anticorpos anti-AE1/AE (BT e GPD), anti-D2-40 (invasão linfática) e anti-CD34 (invasão venosa portal). Também foram analisadas as variáveis clínicas relacionadas ao prognóstico. RESULTADOS: O seguimento médio após a hepatectomia foi de 43 meses. As taxas de sobrevida global e livre de doença em 1, 3 e 5 anos foram de, respectivamente, 94,1%, 66,7% e 45,5% e 53,6%, 31,5% e 29,6%. Os BT estiveram presentes em 61,1% dos pacientes na avaliação pelo AE1/AE3 e em 48,9% pelo HE, enquanto os GPD estiveram presentes em 42,8% dos pacientes na avaliação pelo AE1/AE3 e em 49,3% pelo HE. Na análise univariada, os BT e os GPD grau 3 ( > 9 GPD) mostraram significância prognóstica, tanto na avaliação pelo AE1/AE3 quanto pelo HE. Na análise múltipla, os fatores independentes para sobrevida global foram: a presença de GPD grau 3 (pelo HE), presença de pseudocápsula, invasão venosa portal e presença de 4 ou mais nódulos. Os fatores independentes para sobrevida livre de doença foram: GPD grau 3 (pelo HE), quimioterapia prévia, presença de 4 ou mais nódulos, infiltrado inflamatório peritumoral ausente ou leve, invasão venosa portal e borda infiltrativa. Os BT e GPD não estiveram associados à recidiva hepática. Os BT foram associados a: GPD, MHCCR sincrônicas, tumores de até 5 cm, ausência de pseudocápsula, borda infiltrativa, e presença de invasão venosa portal. Os GPD foram associados a: BT, infiltrado inflamatório peritumoral ausente ou leve, ausência de pseudocápsula e borda infiltrativa. CONCLUSÕES: Os BT e os GPD são frequentes nas MHCCR e ambos, na análise univariada, são fatores de pior prognóstico na sobrevida global e livre de doença, estando associados à recidiva extra-hepática. A presença de GPD grau 3 avaliada pelo HE é fator prognóstico independente na sobrevida global e livre de doença, sugerindo que este é um importante mecanismo de disseminação tumoral na MHCCR / INTRODUCTION: The only potentially curative treatment for colorectal liver metastases is surgical resection. However, about 60 to 70% of patients will recur, showing the necessity of a better knowledge regarding spread and disease recurrence pathways. Tumor budding and poorly differentiated clusters, markers related to epithelial-mesenchymal transition, are prognostic factors for colorectal cancer, but their presence and significance in colorectal liver metastases is not yet established. The aims of this study were to evaluate the presence of tumor budding and poorly differentiated clusters in colorectal liver metastases, to determine their prognostic value and to relate them to other known pathological factors. METHODS: A total of 229 patients that underwent hepatic resection for colorectal liver metastases between January 2004 and June 2014 were retrospectively evaluated. Resected specimens of colorectal liver metastases were submitted to pathological evaluation by hematoxilin and eosin staining, to analyze tumor budding, poorly differentiated clusters, peritumoral inflammatory infiltrate, presence of tumor pseudocapsule and tumor growth pattern; and by immunohistochemical staining with antibodies anti- AE1/AE3 (tumor budding and poorly differentiated clusters), anti-D2-40 (lymphatic invasion) and anti-CD-34 (portal vein invasion). Clinical variables related to prognosis were also evaluated. RESULTS: Mean follow up after hepatectomy was 43 months. Overall and disease-free survival rates at 1, 3 and 5 years were 94.1%, 66.7% and 45.5% and 53.6%, 31.5% and 29.6%, respectively. Tumor budding was present in 61.1% of patients in the evaluation by AE1/AE3 staining and in 48.9% by hematoxilin and eosin, while poorly differentiated clusters were present in 42.8% of patients by AE1/AE3 staining and 49.3% by hematoxilin and eosin. At univariate analysis, tumor budding and poorly differentiated clusters grade 3 ( > 9 poorly differentiated clusters) by AE1/AE3 and hematoxilin and eosin staining showed prognostic significance. On multiple analysis, independent factors for overall survival were: presence of poorly differentiated clusters grade 3 (by hematoxilin and eosin), presence of tumor pseudocapsule, portal vein invasion and presence of 4 or more nodules. Independent factors for disease-free survival were: poorly differentiated clusters grade 3 (by hematoxilin and eosin), preoperative chemotherapy, portal vein invasion, presence of 4 or more nodules, none/mild peritumoral inflammatory infiltrate and infiltrative tumor border. Tumor budding and poorly differentiated clusters were not related to hepatic recurrence. Tumor budding was associated with: presence of poorly differentiated clusters, synchronous colorectal liver metastases, tumor size up to 5 cm, absence of tumor pseudocapsule, infiltrative tumor border and presence of portal vein invasion. Poorly differentiated clusters were associated with: presence of tumor budding, none/mild peritumoral inflammatory infiltrate, absence of tumor pseudocapsule and infiltrative tumor border. CONCLUSIONS: Tumor budding and poorly differentiated clusters are frequent in colorectal liver metastases and, on univariate analysis, are prognostic factors for overall and disease-free survival, being associated to extrahepatic recurrence. Presence of poorly differentiated clusters grade 3 stained by hematoxilin and eosin is an independent prognostic factor for overall and disease-free survival, suggesting that it is an important spread pathway in colorectal liver metastases

A 24-hour fermentation of the optimized synbiotic composed of B. longum and EPR was performed to give a cell-free fermentation broth (S24). S24 was co-cultured with two colon cancer cell lines (Caco-2 and SW620) and normal colon cells (FHC). S24 significantly inhibited cell proliferation for both colon cancer cells but promoted FHC cell growth by 10-25% as shown by MTT and BrdU arrays. Primary DNA damage analysis by alkaline comet assay showed S24 caused DNA damage to a comparable extent as the positive control of 10 mM H2O2 (treated for 1 hour) for both cancer cells. Dynamic analysis on DNA damage-associated DNA repair showed the two colon cancer cells had different response pattern to S24. Flow cytometric analysis showed that both Caco-2 and SW620 when treated with S24 (IC 50=3.66 mM of acetate) were arrested initially at G2/M and subsequently at S phase accompanied with large sub-G1 peaks. Dual staining with PI/AnnexinV further proved the appearance of apoptosis. Live cell imaging analysis on Caco-2 cells treated with S24 showed the following events: mitochondria were rapidly destroyed within the first two-hour treatment, the cells bubbled and the nucleus condensed after the mitochondrial had shrunken, followed by apoptosis. / Despite active research on synbiotic on anti-carcinogenesis of colon cancer by synbiotics, the underlying mechanism still remains unclear. This study investigated a novel synbiotic composed of non-digestible carbohydrates (NDCs) extracted from mushroom sclerotia as prebiotics and Bifidobacteria as probiotics. Preliminary results on incubation of two probiotics ( Bifidobacterium longum and Lactobacillus brevis) and one pathogenic bacterium (Clostridium celatum) separately with 3 NDCs extracted from mushroom sclerotia [Poria cocos (PC), Polyporus rhinocerus (PR) and Pleurotus tuber-regium (PT)] indicated that the growth of B. longum and L. brevis was stimulated more preferentially than C. celatum after 72-hour fermentation. The short-chain fatty acid (SCFA) profile was dominated by acetate (> 98% of total SCFAs) with very little butyrate (< 2.0% of total SCFAs) and the organic matter disappearance (OMD) during fermentation was consistent with the bacterial growth. Among the synbiotic combinations, NDC from PR and B. longum gave the largest amount of acetate (2.47+/-0.232 mmol/g of organic matter disappearance). / Results obtained from human pathway finder RT2 Profiler(TM) PCR Array indicated that S24 could modulate the proliferation of colon cancer cells mainly by various pathways such as cell cycle and DNA damage repair, apoptosis and cell senescence, etc. In SW620 cells, PCR Array of Human Cell Cycle further revealed that the modulated genes mainly belonged to the gene cluster of S phase and DNA replication as well as G2 and G2/M transition. While for Caco-2 cells, the cell-cycle modulated genes mainly belonged to the cluster of G2 and G2/M transition. Immuno-blotting on the pivotal upstream regulators showed that phosphorylation of ATM at Serine 1981 was significantly increased in both cancer cells. Site-specific phosphorylation of pRB was decreased and phosphorylation of Chk1 was increased in both cancer cells while Chk2 were increased in SW620 cells. Cdc25A was phosphorylated at serine17 in both cancer cells. It can be proposed that the blockage of DNA synthesis or DNA damage was due to the down-regulation of some pivotal DNA replication related proteins such as RPA3, PCNA and MCMs, detected by ATM-Chk1/Chk2-Cdc25A pathway. This would cause the prolonged staying of cells at the G1/S checkpoint which further moved on to S phase arrest for SW620 cells. Moreover the sharply up-regulated p21, an important inhibitor of Cdk2 would further hinder the cells passing the G1/S checkpoint in SW620 cells. / The tumor suppressor p53 was detected phosphorylated at various sites in SW620 but not in Caco-2 cells. In SW620 cells, G2/M arrest was caused by the inhibition of CDK1/CDC2 due to increased expression of GADD45A and p21 and phosphorylation of Cdc25A, while for Caco-2, the G2/M arrest was caused by degradation of Cdc25A due to the absence of p53-activated GADD45A and p21 expression as shown in the pathway finder results. Some apoptosis-related proteins of Bax, Apaf-1 and PARP were modulated as shown by immuno-blotting in both colon cancer cells. (Abstract shortened by UMI.) / Gao, Shane. / Adviser: Peter Chi-Keung Cheung. / Source: Dissertation Abstracts International, Volume: 72-11, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 55-94). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Findings from this pioneer study demonstrate that CF, which is unique to rice bran oil, is capable of triggering apoptosis in CRC cells at early stages of carcinogenesis. Furthermore, CF enhances TRAIL-induced apoptosis in metastatic CRC cells. This study provides clear evidence that the health-beneficial properties of whole grain consumption are not only limited by the presence of dietary fiber but also other molecules that can either act as a chemopreventive agent to directly induce tumor regression or a sensitizer to enhance TRAIL-induced apoptosis in metastatic cancer cells. / High intake of whole grain food has been suggested as an important factor for reducing the risk of colon cancer, owing to the abundance of indigestible fiber. Rice bran, which is a component of raw rice after removal of starchy endosperm in milling process, has been shown to be a rich source of some health-beneficial compounds for preventing cancer, hyperlipidaemia, fatty liver, hypercalciuria, kidney stones, and heart disease (Jariwalla, 2001). In the present study, proliferation-inhibitory effects of some rice bran polyphenolic compounds were investigated on a panel of human colorectal cancer (CRC) cell lines, including SW480 (stage B), SW620 (stage C) and Colo-201 (stage D) with increasing metastatic potential according to the Dukes' classification system. / Results from the MTT study revealed that, among the polyphenolic compounds tested, cycloartenyl ferulate (CF) showed the most prominent proliferation inhibition on the CRC cells. CF is one of the typical ferulic acid esters of triterpene alcohols present in rice bran oil. The cancer cell proliferation was reduced by 62, 31 and 21% of their control levels after 72 h of 200 muM CF treatment, respectively. CF seemed to possess higher ability to control proliferation of tumor cells at early stages of cancer development. In meanwhile, results from Toxilight study showed that CF had low toxicity on normal colon CCD-18-Co cells. The anticancer activity of CF was further illustrated by its ability to induce significant regression of SW480 xenograft in nude mice. CF was found to induce apoptosis in SW480 cells in vitro. DNA flow cytometric studies demonstrated that CF elevated dose- and time-dependently the sub G1 or apoptotic cells with fragmented DNA. The pro-apoptotic effect of CF was further confirmed using immunoblotting study showing cleavage of poly(ADP-ribose) polymerase (PARP), which is a hallmark feature of apoptosis. Besides, the executioner procaspase-3, -6 and -7 were found to be processed and activated. On the other hand, administration of pan-caspase inhibitor Z-VAD-FMK completely rescued the cells from PARP cleavage, indicating that CF elicited solely caspase-dependent apoptosis. Elevation of death receptors DR4 and DR5 with the CF treatment seems to originate the upstream activation of the initiator procaspase-8 and -10 of the extrinsic apoptosis pathway. Flow cytometric JC-1 studies further demonstrated that CF significantly altered the mitochondrial membrane potential in a dose-dependent manner together with cytochrome c and smac/DIABLO but not AIF release from mitochondria into the cytosol, as well as the activation of procaspase-9 of the intrinsic apoptosis pathway. Depletion of anti-apoptotic Bcl-2 and elevation of pro-apoptotic Bak were observed; meanwhile, Bid was found to be cleaved by caspase-8, so that the death receptor pathway might be exaggerated by the mitochondrial apoptosis pathway. / Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising candidate for cancer therapeutics due to its ability to induce apoptosis selectively in cancer cells (Gura, 1997). Result from MTT study illustrated that SW620 was more resistant than SW480 to TRAIL treatment. It is recognized that SW620 is the metastatic form of SW480 derived from the same patient at a later time, so it is important to develop agents that are able to sensitize the cancer cells to TRAIL, or to recover TRAIL sensitivity. We show for the first time that CF sensitizes SW620 cells to TRAIL-induced apoptosis and the mechanisms involved at least elevation of DR4, enhanced activation of caspase-8 and -3, as well as increase in DNA fragmentation. / Kong, Ka Lai. / Adviser: Wong Yum Shing. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 119-136). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

INTRODUÇÃO: A ressecção de metástases hepáticas (MH) do câncer colorretal (CCR) é considerada segura e potencialmente curativa. Apesar dos avanços no diagnóstico e nas estratégias cirúrgicas até 70% dos pacientes operados vão apresentar recidiva. Os critérios prognósticos clínico-patológicos disponíveis são insuficientes e a utilidade de modelos prognósticos é considerada inconsistente. Deste modo, torna-se necessário o desenvolvimento de novos critérios que se apoiam em outras variáveis biológicas. A disseminação intra-hepática de metástases de câncer colorretal pode ocorrer através de diferentes vias: linfática, sanguínea (vasos portais), através dos sinusóides ou de ductos biliares. Embora estas vias tenham sido bem descritas, o valor prognóstico de cada uma após a ressecção hepática não está completamente definido. O adenocarcinoma colorretal mucinoso (ACM) é um subtipo de carcinoma colorretal com importante produção mucina, e que está associado clinicamente a tumores proximais, estágio avançado no momento do diagnóstico, instabilidade de microssatélites e mutação do gene BRAF. Há controvérsias sobre o impacto prognóstico da histologia mucinosa nos tumores colorretais primitivos e o seu papel nas lesões metastáticas hepáticas permanece desconhecido. O objetivo do nosso estudo foi determinar a frequência e elucidar o impacto prognóstico de quatro vias diferentes de disseminação intra-hepática assim como da histologia mucinosa em uma série consecutiva de pacientes operados por MH de CCR. PACIENTES E MÉTODOS: Os prontuários de 132 pacientes submetidos à ressecção cirúrgica de MH de CCR entre dezembro de 1999 e janeiro de 2010 foram revisados. Os pacientes que faleceram por complicações pós-operatórias (n= 3), aqueles com ressecções incompletas (R2; n= 2), ou nos quais não havia material disponível para o estudo (n= 14) foram excluídos. Os 113 pacientes restantes tiveram suas variáveis clínico-patológicas e resultados (recidiva e sobrevida) avaliados. Os espécimes cirúrgicos foram submetidos à avaliação histológica de rotina e agrupados de acordo com o conteúdo mucinoso da maior lesão hepática da seguinte forma: ACM >50 %; adenocarcinoma mucinoso intermediário (AIM) com componente mucinoso < 50 %; não-MAC (NMA) se ausência de componente mucinoso. A disseminação intra-hepática foi analisada por hematoxilina e eosina e imuno-histoquímica através dos anticorpos anti-D2-40 (vasos linfáticos), anti-CD34 (vasos sanguíneos), anti-CK-7 (epitélio biliar) e anti-CK-20 (epitélio colorretal). RESULTADOS: O tempo médio de seguimento após a ressecção foi de 37 meses. Recidivas foram observadas em 76 pacientes, com um intervalo médio de 13 meses após a ressecção. As porcentagens de sobrevida global e de sobrevida livre de doença (SLD) após a hepatectomia em 3 e 5 anos foram de 62 e 56 %, e 26% e 24%, respectivamente. A disseminação intra-hepática foi classificada em quatro categorias distintas avaliadas separadamente: invasão da veia porta, invasão dos sinusóides, através dos ductos biliares, e através dos vasos linfáticos/espaço perineural. Encontrou-se invasão microscópica intravenosa portal em 49 pacientes, sinusoidal em 43, biliar em 20 e linfática em 33 pacientes. A disseminação intra-hepática através dos vasos linfáticos foi a única via de disseminação independentemente associada ao risco de recidiva hepática (OR= 2,75) e de menor SLD (p= 0,006). Os focos tumorais de invasão angiolinfática intra-hepática foram detectados em um raio de 2mm de distância da lesão principal. As lesões com componente mucinoso (MAC e AIM) estiveram relacionadas à localização proximal do tumor primário e ao sexo feminino. A análise multivariada revelou que as lesões de tipo ACM apresentavam prognóstico desfavorável (RR= 3,13; IC95% 1,30 - 6,68; p= 0,011) quando comparadas às lesões de componente mucinoso < 50% (NMA e AIM). CONCLUSÃO: A presença de invasão angiolinfática intra-hepática é um importante fator prognóstico após a ressecção de MH de CCR. As outras vias de disseminação intra-hepática, embora observadas com freqüência, não estão relacionadas à recidiva da doença ou sobrevida, sugerindo que o sistema linfático possa ser a principal via de disseminação de MH de CCR. Além disso, o uso da imuno-histoquímica na detecção da invasão angiolinfática intra-hepática parece trazer benefícios na prática clínica. As MH de CCR com componente mucinoso > 50% (ACM) estão associadas a um pior prognóstico quando comparadas às lesões sem componente mucinoso (NMA). A presença de mucina pode, em um futuro próximo, influenciar a estratégia terapêutica e deve se tornar um ponto importante para discussão e investigação futuras / BACKGROUND: Resection of colorectal cancer liver metastases (CRCLM) is generally accepted as a safe and potentially curative treatment. Despite advances in diagnosis and surgical strategies, up to 70% of patients will present recurrence of the disease after resection of CRCLM. Clinicopathological prognostic factors are inadequate to determine disease prognosis and the utility of prognostic models on general population is considered highly inconsistent. Herein, future attempts to develop prognostic scores may include additional biologic variables. Intrahepatic spread from CRLM may take place through four different routes: lymphatic vessels, portal vessels, sinusoids and biliary ducts. Although these routes have been well described, their prognostic value after hepatectomy is not completely understood. Colorectal mucinous adenocarcinoma (MAC) is a subtype of colorectal adenocarcinoma with prominent mucin production associated with tumor proximal location, advanced stage at diagnosis, microsatellite instability, and BRAF mutation. There are controversies about the prognostic impact of mucinous histology on colorectal cancer and the prognostic implication of MAC in CRCLM is unknown. The purpose of our study was to determine the frequency and elucidate the prognostic implication of four different routes for intrahepatic dissemination and the mucinous histology in a consecutive series of resected CRCLM. METHODS: Medical records of 132 patients who underwent a first resection of CRCLM between December 1999 and January 2010 were reviewed. Patients who died from postoperative complications (n=3), those with incomplete resections (R2; n=2), or no available tissue for the study (n=14) were excluded. The remaining 113 patients had their clinicopathologic variables and outcome parameters evaluated. Resected specimens were submitted to routine histological evaluation and were grouped according to metastasis mucinous content: > 50%, MAC; < 50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Intrahepatic dissemination was analyzed by H&E and immunohistochemical staining with D2-40 (lymphatic vessels), CD34 (blood vessels), CK-7 (biliary epithelium), and CK-20 (CRC cells). RESULTS: Mean follow-up after resection was 37 months. Tumor recurrence was observed in 76 patients, with a median interval of 13 months after resection. Overall survival and disease-free survival (DFS) rates after hepatectomy were 62 and 56%, and 26 and 24% at 3 and 5 years, respectively. Intrahepatic spread was classified into discreet categories that were evaluated separately: invasion of the portal vein, sinusoids, bile duct, and lymphatic/perineural space. Intrahepatic microscopic invasion included portal vein in 49 patients, sinusoidal in 43 patients, biliary in 20 patients, and lymphatic in 33 patients. Intra-hepatic lymphatic invasion was the only route of dissemination independently associated with the risk of hepatic recurrence (OR=2.75) and shorter DFS (P= 0.006). All tumor foci of intrahepatic lymphatic invasion were detected within 2mm away from tumor edge. Tumors with mucinous component (AIM and MAC) were related to proximal location of the primary tumor and were more frequently observed in females. Multivariate analysis revealed that MAC was an independent negative prognostic factor (hazard ratio= 3.13; 95% CI, 1.30-6.68; P= 0.011) compared with non-MAC (NMA and AIM). CONCLUSION: Intrahepatic lymphatic invasion is a significant prognostic factor. Other mechanisms of invasion, although frequently observed, are not related to disease recurrence or survival, suggesting that the lymphatic system is the main route for dissemination of CRCLM. Furthermore, immunohistochemical detection of intrahepatic lymphatic invasion might be of value in clinical practice. MAC has an adverse prognostic impact compared with NMA, which may influence therapeutic strategy raising an important subject for discussion and future investigation

Cheung, Wing Ki. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 100-112). / Abstracts in English and Chinese. / Acknowledgments / Abbreviations / Abstract 一 English --- p.i / - Chinese --- p.iii / Chapter Chapter 1 --- General Introduction / Chapter 1.1. --- Colon Cancer / Chapter 1.1.1. --- Colon cancer statistic in Hong Kong --- p.1 / Chapter 1.1.2. --- Development of Colon cancer --- p.1 / Chapter 1.1.3. --- Treatment --- p.2 / Chapter 1.2. --- Chemistry of ascorbates / Chapter 1.2.1. --- Sodium-L-ascorbate --- p.3 / Chapter 1.2.2. --- "Sodium 5,6-benazylidene-L-ascorbate" --- p.4 / Chapter 1.3. --- "Reactive oxygen species and reactive nitrogen species, and their biological consequences" --- p.5 / Chapter 1.4. --- Cell cycle --- p.7 / Chapter 1.5. --- Autophagy --- p.8 / Chapter 1.6. --- Human colon cancer HT29 cells for anti-tumor study --- p.9 / Chapter 1.7 --- Aim of study --- p.10 / Chapter Chapter 2 --- Comparative studies of cytotoxicity of SAA and SBA in short term treatment / Chapter 2.1. --- Introduction --- p.11 / Chapter 2.2. --- Materials and Methods --- p.14 / Chapter 2.3. --- Results --- p.17 / Chapter 2.4. --- Discussion --- p.26 / Chapter Chapter 3 --- Comparative studies of SAA and SBA in oxidative stress induction and their corresponding ROS inhibitors / Chapter 3.1. --- Introduction --- p.28 / Chapter 3.2. --- Materials and Methods --- p.31 / Chapter 3.3. --- Results --- p.35 / Chapter 3.4. --- Discussion --- p.42 / Chapter Chapter 4 --- "Effects of SAA and SBA treatments on cell cycle regulatory proteins and the induction of transient cell cycle arrests in Gl, S and G2 phases Cell Cycle" / Chapter 4.1. --- Introduction --- p.45 / Chapter 4.2. --- Materials and Methods --- p.49 / Chapter 4.3. --- Results --- p.53 / Chapter 4.4. --- Discussion --- p.69 / Chapter Chapter 5 --- Autophagy induction during SBA treatment and autophagy inhibition during SAA treatment / Chapter 5.1. --- Introduction --- p.72 / Chapter 5.2. --- Materials and Methods --- p.74 / Chapter 5.3. --- Results --- p.77 / Chapter 5.4. --- Discussion --- p.91 / Chapter Chapter 6 --- General Discussion --- p.93 / References --- p.100

Lectins (hemagglutinins) are a type of proteins that could recognize different sugar structures and specifically initiate reversible binding with them. Though they have been universally found in a variety of organisms, they are exceptionally abundant in legumes. From the initial finding of agglutinating red blood cells to the discovery of recognizing carbohydrates on cell membranes, multiple functions of lectins have been gradually unveiled by numerous researchers across a century. Based on its carbohydrate-binding property, lectins have found great value in the study of glycomics. Many lectin-based biological tools, like lectin affinity chromatography, lectin blotting, lectin histochemistry, lectin microarray and lectin-based biosensor have been developed and applied to the study of glycoproteins. Besides, lectins are also reported to be potential agents for anti-insect, anti-fungi, anti-HIV, anti-bacterial and anti-tumor applications. / The present study focuses on the isolation of a new hemagglutinin from an edible legume, exploration of its anti-colorectal cancer effect and mechanisms, its cytokine inducing function and anti-HIV activities. The protein was purified by liquid chromatography techniques which entailed affinity chromatography on Affi-Gel Blue Gel, ion exchange chromatography on Mono Q and gel filtration on Superdex 75 with an FPLC system. The hemagglutinating activity of this hemagglutinin was demonstrated to be ion-dependent and stable over a wide range of temperatures (20-60℃) and pH (2-11) values. Like most of the lectins or hemagglutinins, this novel hemagglutinin could also attenuate the activity of HIV-1 reverse transcriptase. / This hemagglutinin could potently suppress the proliferation of colorectal carcinoma HCT116 cells and colorectal adenocarcinoma HT29 cells. It induced cell cycle arrest in G0/G1 phase, downregulated the expression of Cyclin D1 and upregulated P21expression. The protein initially bound on the cell membranes most probably through glycoproteins and subsequently entered the cytoplasm, which was achieved as early as 3h post treatment. The hemagglutinin was found to be preferentially localized in Golgi apparatus and initiated aggregation of the Golgi apparatus, which may possibly attenuate its protein processing capacity by reducing total superficial area or even partially blocking the transportation of proteins from the endoplasmic reticulum (ER). The impaired protein reception ability of Golgi apparatus may lead to the protein accumulation in the ER and induce cell apoptosis. Accordingly, two ER stress sensors (IRE1α and ATF6) and one late product of ER stress (CHOP) were found to up-regulated. Apoptosis-inducing effect of this hemagglutinin on HT29 and HCT116 cells were further confirmed using methods based on different principles. Cells treated with the hemagglutinin were observed to undergo obvious chromatin condensation, mitochondrial membrane depolarization and phosphatidylserine exposure. An apoptosis initiator (Apaf-1) and one important indicator (cleaved PARP) of cell apoptosis were accordingly detected. Besides, intraperitoneal administration of this hemagglutinin to colorectal tumor bearing nude mice could slow down the growth of tumors. / At last, this hemagglutinin exerted an immunomodulatory function on splenocytes by stimulating the mRNA expression level of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), interferon- gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α). Secretion of IL-1β and IL-2 from splenocytes also increased with the concentration of this hemagglutinin. / In a short conclusion, we have isolated a new hemagglutinin with anti-HIV RT, anti-colorectal cancer and immunomodulatory activities. / 凝集素（血凝素）是一类能够识别不同糖结构并能和它们发生可逆性结合的蛋白。虽然他们在许多生物体内均有发现，但这类蛋白在豆科植物中的含量尤其丰富。经过一个多世纪来众多研究者的努力，从最初认识到其具有红血细胞凝集功能到糖类识别作用，凝集素的诸多功能已被逐步挖掘。基于其独特的糖结构识别特性，凝集素在糖组学的研究中具有重大意义。许多基于凝集素的生物方法，如凝集素亲和层析法，凝集素印迹法，凝集素组织化学，凝集素生物芯片以及基于凝集素的生物传感器已被研究出来, 并用于研究糖蛋白。除此之外，研究表明，凝集素还具有抗虫，抗真菌，抗HIV，抗细菌和抗癌等活性。 / 该凝集素可以极大抑制结肠直肠癌HCT116细胞和结直肠腺癌HT29细胞增殖，引发细胞周期停滞，分别下调和上调Cyclin D1和P21的表达。该蛋白极有可能首先通过和细胞表面的糖蛋白结合而附在细胞膜上，然后进入细胞内。该过程可在往细胞培养液内加入该蛋白后的3小时内完成。该凝集素优先与细胞内的高尔基体结合，随后引发高尔基体聚集。该聚集作用可能会通过减少高尔基体总表面积甚至阻塞内质网和高尔基体间的蛋白运输，进而减弱高尔基体处理蛋白质的能力。当高尔基体接受蛋白的能力降低时，蛋白可能会堆积在内质网上并进一步引发细胞程序性死亡。相应地，两个内质网应激感受蛋白IRE1α和 ATF6以及内质网应激后期产物CHOP均被发现上调。该凝集素对HT29细胞和HCT116细胞的凋亡诱导作用采用不同的方法进行了进一步的确认，这些方法都是基于不同检测原理进行的。结果表明，该凝集素可导致细胞产生明显的染色质凝缩，线粒体膜电位去极化和磷脂酰丝氨酸外翻。与此相应地，凋亡启动蛋白Apaf-1和凋亡后期蛋白(被剪切的PARP)可在处理后的细胞中检测到。通过腹腔注射的方法给接种大肠癌细胞的裸鼠给药可降低肿瘤的生长速度。 / 本研究的工作包括：从一种可食用豆类中提取一种新的凝集素；检测其抗大肠癌的作用和机制；研究其细胞素诱导作用以及抗HIV活性。该蛋白采用液相色谱法分离提纯，其中包括亲和层析柱Affi-Gel Blue Gel, 离子交换层析柱Mono Q 和凝胶层析柱Superdex 75，后两种层析法在FPLC系统上操作。该蛋白的红血细胞凝集作用具有金属阳离子依赖性，并在20-60℃和pH2-11范围内保持活性稳定。像许多其它的凝集素一样，该蛋白也可以削弱HIV逆转录酶活性。 / 最后，该蛋白还具有免疫调节作用，它可促进白细胞介素-2，白细胞介素-6，白细胞介素-1β，干扰素-γ和肿瘤坏死因数-α在mRNA水平上的表达并刺激白细胞介素-2和细胞介素-1β的分泌。 / 综上所诉，本研究分离提纯了一种新凝集素，它具有抗HIV，抗大肠癌和免疫调节作用。 / Dan, Xiuli. / Thesis Ph.D. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 153-170). / Abstracts also in Chinese. / Title from PDF title page (viewed on 05, October, 2016). / 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.

O câncer colorretal (CCR) é o quarto tipo mais incidente mundialmente e a taxa de mortalidade ocupa a terceira posição. Apresenta desenvolvimento lento e bom prognóstico quando diagnosticado em estadio inicial. Apesar de ser um câncer que pode ter rastreamento populacional, as políticas públicas não têm conseguido estabelecer estratégicas efetivas de prevenção e diagnóstico precoce. Este estudo teve como objetivo geral caracterizar o perfil epidemiológico da coorte dos pacientes diagnosticados com CCR, atendidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), no período de janeiro de 2000 a dezembro de 2010. Estudo de coorte retrospectivo, longitudinal, baseado em dados secundários do Registro Hospitalar de Câncer (RHC) do HCFMRP-USP. As análises foram realizadas com o auxílio do Programa Excel 2010 da Microsoft e o Software R 3.0.1. Para análise da sobrevida, foi utilizado o método não paramétrico de Kaplan-Meier e para as associações foi aplicado o teste de Fisher e Qui-quadrado. Estudo aprovado pelo Comitê de Ética da Escola de Enfermagem de Ribeirão Preto- USP, nº 224.448/2012, Resolução CNS 466/2012. A população foi composta por 926 pacientes e os resultados evidenciaram prevalência do sexo masculino, com idade de 70 anos ou mais, 38,9% analfabetos/baixa escolaridade, 54,2% foram diagnosticados com o estadio III e IV e a localização predominante do tumor foi cólon e reto. O tempo médio entre a primeira consulta e o diagnóstico foi de 19,8 dias e entre o diagnóstico e o tratamento, foi de 27,8 dias. Observou-se igual sobrevida para homens e mulheres, sendo que o tempo médio entre o início do tratamento e a ocorrência do óbito foi de 626,3 dias. Conclui-se que há necessidade de investir na prevenção primária do CCR, com ações que minimizem os fatores de riscos conhecidos e na prevenção secundária com testes efetivos, como a pesquisa de sangue oculto nas fezes. Destaca-se ainda a urgente necessidade de políticas públicas mais direcionadas e investimento na educação permanente dos profissionais de saúde, principalmente o enfermeiro, que tem papel primordial na geração de conhecimento para esta população / Colorectal cancer (CCR) is the fourth most incident cancer worldwide and is the third leading cause of cancer-related deaths. It develops slowly and has a good prognosis when identified in early stages. Even though it can be screened in the population, public policies have not established effective preventive measures or early diagnosis strategies. This study\'s general objective was to characterize the epidemiological profile of a cohort of patients diagnosed with CCR cared for by the Hospital das Clinicas at University of São Paulo at Ribeirão Preto, Medical School (HCFMRP-USP) from January 2000 to December 2010. This longitudinal, retrospective cohort was based on secondary data from the Cancer Hospital Record from HCFMRP-USP. Analyses were performed using Excel 2010, Microsoft and R software 3.0.1. For the analysis of survival, Kaplan-Meier non-parametric method was used and the Fisher\'s test and Chi-square were used for associations. The study was approved by the Institutional Review Board at the College of Nursing at Ribeirão Preto, USP according to CNS Resolution 466/2012 (No. 224,448/2012). The population was composed of 926 patients and the results show a prevalence of 70 years old or older males, 38.9% were illiterate or had low level of education, 54.2% were diagnosed at stages III and IV, while the predominant sites were colon and rectum. The average time between the first consultation and diagnosis was 19.8 days and 27.8 days between diagnosis and treatment. Equal survival rates were observed for both men and women while the average time between the beginning of treatment and death was 626.3 days. There is a need to invest in CCR primary prevention with actions that minimize known risks and secondary prevention with effective tests such as fecal occult blood test. We also highlight the urgent need of public policies focused on this condition and investment on the permanent education of healthcare professionals, especially nurses who play an essential role in transmitting knowledge to this population

Introdução: Muitos pacientes desenvolvem recidiva de câncer colorretal (CCR), que possui importância epidemiológica devido ao diagnóstico tardio e à dificuldade de acessibilidade à assistência de saúde. Objetivos: analisar as evidências científicas sobre a deiscência de anastomose intestinal em cirurgias por laparotomia e laparoscopia em pacientes com CCR, a recidiva de câncer colorretal e a assistência de enfermagem para pacientes com recidiva de CCR em tratamento cirúrgico; e realizar proposição de assistência de enfermagem perioperatória para esta clientela, com base nestas evidências científicas. Materiais e método: trata-se de revisão integrativa (RI), fundamentada na Prática Baseada em Evidências, realizada com as etapas de elaboração da pergunta e definição das estratégias de busca; elaboração de critérios de inclusão e exclusão; utilização de um instrumento para a coleta de dados da amostra; análise crítica dos estudos com avaliação do rigor e das características da amostra; síntese e interpretação dos resultados; e apresentação da RI. Para a busca da literatura científica utilizou-se os descritores colorectal neoplasms, laparoscopy, laparotmy e anastomoticleak; recurrence e colorectal neoplasm; nas base de dados Cumulative Index to Nursing and Allied Health Literature (CINAHL), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), Biblioteca virtual COCHRANE, Índice Bibliográfico Español de Ciencias de la Salud (IBECS) e biblioteca virtual National Library of Medicine National Institutes of Health (PUBMED), mediante os critérios de inclusão e de exclusão, com seleção de oito e quatro artigos científicos, respectivamente; e com os descritores colorectal neoplasms, recurrence e nursing, seis artigos científicos. Resultados e discussão: a ocorrência de deiscência de anastomose, foi analisada em relação ao uso de novas técnicas cirúrgicas e maior densidade tecnológica para as terapêuticas adjuvantes, farmacológicas e os exames diagnósticos, que comprometem a mortalidade e sobrevida desta clientela. Em geral, os pacientes apresentam estadiamento avançado da doença, com realização de cirurgia tradicional pela condição clínica associada à comorbidades, maior risco cirúrgico e ampla ressecção intestinal, o que comprometem a sua recuperação fisiológica e psicossocial, além de maior possibilidade de recidiva ou metástases. Para a assistência à saúde desta clientela há necessidade de equipe multidisciplinar, priorizando-se a complexidade clínica, utilização de maior densidade tecnológica e seguimento especializado ao longo da sobrevivência. Há escassez de produção científica, sobre aspectos clínicos, terapêuticos e preventivos, principalmente da enfermagem. Conclusão: O enfermeiro deve ter domínio sobre fisiopatologia, terapêuticas e suas consequências, além de prognósticos e aspectos preventivos do CCR, para prestar assistência de enfermagem perioperatória para pacientes com CCR e familiares, com planejamento de intervenções procedimentais, educativas e psicossociais / Background: Many patients develop colorectal cancer recurrence (CCR), with epidemiological importance due to late diagnosis and the difficult access to health care. Objectives: To analyse scientific evidence on bowel anastomosis dehiscence in laparotomy and laparoscopy surgeries in patients with CCR, the colorectal cancer recurrence and the nursing care for patients with CCR relapse undergoing surgical treatment; and make the perioperative nursing care proposal to these patients, based on the scientific evidences cited. Method and materials: An integrated review (IR), grounded on the Evidence-Based Practice, developed in the following phases: creation of the question and definition of search strategies; creation of inclusion and exclusion criteria; the use of an instrument to collect sample data; critical analysis of the study and assessment of the rigor and characteristics of the sample; summary and interpretation of the results; and IR presentation. In the search for scientific literature, the descriptors colorectal neoplasms, laparoscopy, laparotomy and anastomotic leak; recurrence and colorectal neoplasm were used on the following databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), LatinAmerican and Caribbean Literatures on health Science (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), COCHRANE virtual library, Español de Ciencias de la Salud (IBECS) bibliographic index and National Library of Medicine National Institutes of Health (PUBMED) virtual library, using the inclusion and exclusion criteria, selecting 8 and 4 scientific articles, respectively; and 6 scientific articles with the descriptors colorectal neoplasms, recurrence e nursing. Results and discussion: the occurrence of anastomosis dehiscence was analysed in relation to the use of new surgical techniques and greater technological density for the therapeutics adjuvants, pharmacological and the diagnostic tests that affect the mortality and the survival of such patients. In general, patients present advanced staging of the disease with the practice of traditional surgery due to clinic condition associated to comorbidities, greater surgical risk and extensive intestinal resection, which impair their physiological and psychosocial recovery, in addition to a greater possibility of recurrence or metastasis. For the health care of such patients, it is necessary a multidisciplinary team, prioritising the clinical complexity, the use of higher technological density and specialised assistance throughout the survival. There is a shortage of scientific production on clinical, therapeutic and preventive aspects, particularly in nursing. Conclusion: Nurses shall master pathophysiology, therapeutics and their consequences, as well as the prognosis and preventive aspects of CCR in order to provide perioperative nursing care for patients with CCR and their family, with procedural, educational and psychosocial interventions