京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20224号 / 医博第4183号 / 新制||医||1019(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 武藤 学, 教授 羽賀 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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A substância P (SP) é um neuropeptídeo da família das taquicininas que regula numerosas funções biológicas por meio da ligação ao seu receptor altamente específico neuroquinina-1 (NK-1R). Este complexo SP/NK-1R está envolvido em diversos processos relacionados à oncogênese, como a mitogênese, angiogênese, migração celular e metástase. O objetivo deste trabalho foi investigar a expressão de substância P e de seu receptor NK-1 e sua correlação com o índice de proliferação celular em 73 pacientes portadores de 90 carcinomas espinocelulares de boca, diagnosticados e tratados no Hospital General e Hospital de La Princesa, Jaen, Espanha, durante o período de 1995 a 2008. Todos os tumores foram corados pela técnica imunoistoquímica da estreptavidina-biotina-peroxidase com os anticorpos anti-SP, anti-NK-1R e anti-Ki-67. As alterações celulares epiteliais das margens cirúrgicas livres de doença também foram registradas. A expressão imunoistoquímica da substância P e do seu receptor neurokinina-1 foi avaliada na membrana, no citoplasma e no núcleo das células epiteliais malignas e do epitélio da mucosa bucal adjacente ao tumor, nos linfócitos e nos vasos sanguíneos dos tumores. O índice de proliferação celular tumoral foi determinado pela expressão imunoistoquímica de Ki-67 identificada no núcleo das células neoplásicas. As correlações entre as diversas localizações da SP, de seu receptor NK-1R e do índice de proliferação tumoral determinado pelo Ki-67 foram determinadas estatísticamente utilizando-se o Crosstab, Regress e Descript de SUDAAN. A expressão de SP foi identificada no estroma de 77% dos tumores, na membrana de 71% das células malignas e no citoplasma de 81,2% dos tumores. A maioria dos tumores apresentou altas taxas de proliferação das células neoplásicas com mais de 50% das células imunopositivas para o Ki-67. Ao analisar as margens cirúrgicas livres de doença, observou-se expressão da SP, sobretudo no terço inferior e médio, tanto no núcleo, como no citoplasma e na membrana celular. A expressão concomitante de substância P e do receptor neurokinina-1 no citoplasma das células neoplásicas ocorreu mais frequentemente nas células tumorais em proliferação. Verificou-se que expressão de SP no câncer bucal ocorre juntamente com o aumento da expressão de NK-1R, sugerindo que as células neoplásicas epiteliais bucais podem utilizar esta via para tornarem-se mais susceptíveis aos estímulos mediados pela SP. A expressão de substância P nos linfócitos do infiltrado inflamatório e vasos sanguíneos intratumorais e peritumorais se associaram a tumores de menor tamanho, menor estádio clínico e com menor frequência metástase ganglionar. Concluiu-se que as células neoplásicas epiteliais bucais podem utilizar a via substância P/NK-1R para tornarem-se mais susceptíveis aos estímulos mediados pela SP, particularmente aqueles associados à proliferação celular. Além disso, a expressão epitelial, citoplasmática e nuclear da substância P é um evento precoce na carcinogênese bucal podendo ser considerado um marcador da presença e intensidade de displasia epitelial. / The substance P (SP) is a neuropeptide of the tachykinin family that regulates multiple biological functions by binding to the highly specific receptor neurokinin-1. This complex SP/NK-1 is involved in several processes related to oncogenesis, such as mitogenesis, angiogenesis, cell migration and metastasis. This study investigated the expression of substance P and its receptor NK-1 and its correlation with the cell proliferation index in 73 patients with oral squamous cell carcinoma, diagnosed and treated at the General Hospital and Princess Hospital at Jaen, Spain, during the period 1995 to 2008. All tumors were stained immunohistochemically by the streptavidin-biotin-peroxidase technique using the antibodies anti-SP, anti-NK-1R and anti-Ki-67. The epithelial cell alterations on the disease-free surgical margins were registered. The immunohistochemical expression of SP and its receptor neurokinin-1 were evaluated on the membrane, cytoplasm and nucleus of malignant epithelial cells and cells of healthy oral mucosa adjacent to the tumor, as well as on the infiltrating lymphocytes and peritumoral or intratumoral blood vessels. The tumor cell proliferation index was determined by the immunohistochemical expression of Ki- 67 identified on the malignant cell nucleus. The correlations between the distinct localizations of SP, its receptor NK-1 and the proliferation index Ki-67 were statistically analyzed using the Sudaan Crosstab, Regress and Descript tests. The SP expression was identified on the stroma of 77% of tumors, on the membrane of 71% of malignant cells and cytoplasm of 81.2% of tumors. Most tumors presented high proliferation rates of neoplastic cells, with more than 50% of cells immunopositive for Ki-67. Analysis of the disease-free surgical margins revealed SP expression especially on the lower and medium third, both on the nucleus, cytoplasm and cell membrane. The simultaneous expression of substance P and its receptor NK-1 on the cytoplasm of neoplastic cells occurred more frequently in proliferating malignant cells. The expression of SP in oral cancer occurred simultaneously to an increased expression of NK-1R, suggesting that the oral malignant epithelial cells might use this pathway to become more susceptible to the stimuli mediated by the SP. The substance P expression on infiltrating lymphocytes and intratumoral or peritumoral blood vessels was associated with tumors of small size, lower clinical stage and less frequent node metastasis. It was concluded that the oral neoplastic epithelial cells may use the pathway SP/NK-1R to become more susceptible to the stimuli mediated by the SP, particularly those associated with cell proliferation. Additionally, the epithelial, cytoplasmic and nuclear expression of substance P is an early event in oral carcinogenesis and may be considered a marker of the presence and intensity of epithelial dysplasia.

Introduction et objectifs : Les méningiomes sont des tumeurs intracrâniennes pour la plupart de bas grade, dont les récidives sont cependant fréquentes. Le premier objectif de cette étude est d'évaluer la valeur pronostique de marqueurs de prolifération dans une série de 60 méningiomes. HuR (ELAV-like 1) est une protéine pro-oncogène pouvant stimuler la prolifération et la survie cellulaire. Dans la seconde partie de cette étude, nous analysons l'expression de HuR et les effets de l'inhibition de HuR sur la prolifération, l'apoptose et la résistance à l'hypoxie. Résultats : Il existe une corrélation significative entre le grade histologique et l'expression nucléaire de MCM6 (p<0,001), Ki-67 (p<0,001) et PHH3 (p<0,001), et une corrélation inverse entre ces marqueurs et la survie sans récidive (Cox ; MCM6 : p<0,001 ; Ki-67 : p=0,003 ; PHH3 : p=0,037). L'expression cytoplasmique de HuR est corrélée négativement avec la survie sans récidive (p=0,028), et positivement avec le grade (I vs II : p=0,0007), l'indice mitotique (p=0,0001), Ki-67 (p=0,0007) et MCM6 (p=0,0009). In vitro, l'inhibition de HuR (siRNA) entraîne une diminution de la croissance cellulaire (p=0,0004) et de la prolifération (Ki-67, p=0,0004), et une augmentation de l'apoptose (caspase 3 clivée, p=0,002), ces différents effets étant significativement augmentés en hypoxie. L'inhibition de HuR entraîne également une diminution de SIRT1 en normoxie (p=0,01) et en hypoxie (p=0,0006). Conclusion : MCM6 est un marqueur efficace pour identifier les méningiomes à haut risque de récidive. HuR est un marqueur de mauvais pronostic, dont l'inhibition permet de diminuer la prolifération cellulaire et d'augmenter l'apoptose / Introduction and objectives: Meningiomas are frequent and in most of cases low grade intracranial tumors, with frequent recurrences. The first objective of this study was to evaluate the prognostic value of proliferation and cell cycle markers in a series of 60 meningiomas. HuR (ELAV-like 1) is a pro-oncogenic protein that stimulates cell proliferation and survival. In the second part of this study, the objective was to evaluate HuR expression, and the effects of HuR inhibition on proliferation, apoptosis and resistance to hypoxia. Results: We found a significant correlation between histological grade and nuclear staining for MCM6 (p<0.001), Ki-67 (p<0.001) and PHH3 (p<0.001), and an inverse correlation between these markers and reccurence free survival (Cox; MCM6: p<0.001; Ki-67: p=0.003; PHH3: p=0.037). Cytoplasm staining for HuR was significantly stronger in atypical meningiomas (grades I vs II: p=0.0007), inversely correlated with progression free survival (p=0.028), and was positively correlated with mitotic index (p=0.0001), Ki-67 (p=0.0007) and MCM6 (p=0.0009). In vitro, HuR inhibition (siRNA) led to a significant decrease of cell growth (p=0.0004) and proliferation (Ki-67, p=0.0004), and an increase of apoptosis (cleaved caspase 3, p=0.002). These effects were significantly increased under hypoxia, comparing with normoxia. When HuR was inhibited, SIRT1 was decreased, both under normoxia (p=0.01) and hypoxia (p=0.0006). Conclusion: In conclusion, MCM6 is an efficient marker to identify meningiomas with high risk of recurrence. HuR is correlated with a poor prognosis. Its inhibition allows to decrease cell proliferation and to increase apoptosis

A substância P (SP) é um neuropeptídeo da família das taquicininas que regula numerosas funções biológicas por meio da ligação ao seu receptor altamente específico neuroquinina-1 (NK-1R). Este complexo SP/NK-1R está envolvido em diversos processos relacionados à oncogênese, como a mitogênese, angiogênese, migração celular e metástase. O objetivo deste trabalho foi investigar a expressão de substância P e de seu receptor NK-1 e sua correlação com o índice de proliferação celular em 73 pacientes portadores de 90 carcinomas espinocelulares de boca, diagnosticados e tratados no Hospital General e Hospital de La Princesa, Jaen, Espanha, durante o período de 1995 a 2008. Todos os tumores foram corados pela técnica imunoistoquímica da estreptavidina-biotina-peroxidase com os anticorpos anti-SP, anti-NK-1R e anti-Ki-67. As alterações celulares epiteliais das margens cirúrgicas livres de doença também foram registradas. A expressão imunoistoquímica da substância P e do seu receptor neurokinina-1 foi avaliada na membrana, no citoplasma e no núcleo das células epiteliais malignas e do epitélio da mucosa bucal adjacente ao tumor, nos linfócitos e nos vasos sanguíneos dos tumores. O índice de proliferação celular tumoral foi determinado pela expressão imunoistoquímica de Ki-67 identificada no núcleo das células neoplásicas. As correlações entre as diversas localizações da SP, de seu receptor NK-1R e do índice de proliferação tumoral determinado pelo Ki-67 foram determinadas estatísticamente utilizando-se o Crosstab, Regress e Descript de SUDAAN. A expressão de SP foi identificada no estroma de 77% dos tumores, na membrana de 71% das células malignas e no citoplasma de 81,2% dos tumores. A maioria dos tumores apresentou altas taxas de proliferação das células neoplásicas com mais de 50% das células imunopositivas para o Ki-67. Ao analisar as margens cirúrgicas livres de doença, observou-se expressão da SP, sobretudo no terço inferior e médio, tanto no núcleo, como no citoplasma e na membrana celular. A expressão concomitante de substância P e do receptor neurokinina-1 no citoplasma das células neoplásicas ocorreu mais frequentemente nas células tumorais em proliferação. Verificou-se que expressão de SP no câncer bucal ocorre juntamente com o aumento da expressão de NK-1R, sugerindo que as células neoplásicas epiteliais bucais podem utilizar esta via para tornarem-se mais susceptíveis aos estímulos mediados pela SP. A expressão de substância P nos linfócitos do infiltrado inflamatório e vasos sanguíneos intratumorais e peritumorais se associaram a tumores de menor tamanho, menor estádio clínico e com menor frequência metástase ganglionar. Concluiu-se que as células neoplásicas epiteliais bucais podem utilizar a via substância P/NK-1R para tornarem-se mais susceptíveis aos estímulos mediados pela SP, particularmente aqueles associados à proliferação celular. Além disso, a expressão epitelial, citoplasmática e nuclear da substância P é um evento precoce na carcinogênese bucal podendo ser considerado um marcador da presença e intensidade de displasia epitelial. / The substance P (SP) is a neuropeptide of the tachykinin family that regulates multiple biological functions by binding to the highly specific receptor neurokinin-1. This complex SP/NK-1 is involved in several processes related to oncogenesis, such as mitogenesis, angiogenesis, cell migration and metastasis. This study investigated the expression of substance P and its receptor NK-1 and its correlation with the cell proliferation index in 73 patients with oral squamous cell carcinoma, diagnosed and treated at the General Hospital and Princess Hospital at Jaen, Spain, during the period 1995 to 2008. All tumors were stained immunohistochemically by the streptavidin-biotin-peroxidase technique using the antibodies anti-SP, anti-NK-1R and anti-Ki-67. The epithelial cell alterations on the disease-free surgical margins were registered. The immunohistochemical expression of SP and its receptor neurokinin-1 were evaluated on the membrane, cytoplasm and nucleus of malignant epithelial cells and cells of healthy oral mucosa adjacent to the tumor, as well as on the infiltrating lymphocytes and peritumoral or intratumoral blood vessels. The tumor cell proliferation index was determined by the immunohistochemical expression of Ki- 67 identified on the malignant cell nucleus. The correlations between the distinct localizations of SP, its receptor NK-1 and the proliferation index Ki-67 were statistically analyzed using the Sudaan Crosstab, Regress and Descript tests. The SP expression was identified on the stroma of 77% of tumors, on the membrane of 71% of malignant cells and cytoplasm of 81.2% of tumors. Most tumors presented high proliferation rates of neoplastic cells, with more than 50% of cells immunopositive for Ki-67. Analysis of the disease-free surgical margins revealed SP expression especially on the lower and medium third, both on the nucleus, cytoplasm and cell membrane. The simultaneous expression of substance P and its receptor NK-1 on the cytoplasm of neoplastic cells occurred more frequently in proliferating malignant cells. The expression of SP in oral cancer occurred simultaneously to an increased expression of NK-1R, suggesting that the oral malignant epithelial cells might use this pathway to become more susceptible to the stimuli mediated by the SP. The substance P expression on infiltrating lymphocytes and intratumoral or peritumoral blood vessels was associated with tumors of small size, lower clinical stage and less frequent node metastasis. It was concluded that the oral neoplastic epithelial cells may use the pathway SP/NK-1R to become more susceptible to the stimuli mediated by the SP, particularly those associated with cell proliferation. Additionally, the epithelial, cytoplasmic and nuclear expression of substance P is an early event in oral carcinogenesis and may be considered a marker of the presence and intensity of epithelial dysplasia.

Die Entwicklung von Dickdarmkrebs wird durch eine Reihe von Lebens- und Essgewohnheiten sowie Umweltfaktoren begünstigt. Den letzteren beiden sind Substanzen zuzurechnen, die bei der Zubereitung der Nahrung entstehen und mit ihr aufgenommen werden. Zu diesen Verbindungen gehört das 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridin (PhIP) aus der Substanzklasse der heterozyklischen aromatischen Amine. Es entsteht bei der Erhitzung zahlreicher proteinhaltiger Nahrungsmittel und die Zielorgane in Nagerstudien stimmen mit der Häufung von Krebsinzidenzen in westlichen Industrienationen überein. Dieser Zusammenhang konnte jedoch bis heute nicht endgültig bewiesen werden. Fütterungsversuche mit Ratten wurden mit Konzentrationen der Substanz durchgeführt, die weit über der menschlichen Exposition liegen. Durch das Verfüttern einer humanrelevanten Dosis PhIP sollte geklärt werden, ob auch geringe Konzentrationen dickdarmkrebstypische Mutationen, präneoplastische Läsionen oder Tumore induzierten. Die mit humanrelevanten Dosen gefütterten Tiere wiesen weniger Läsionen als die Hoch-Dosis-PhIP-Gruppe auf, in der allerdings keinerlei maligne Tumoren des Dickdarms auftraten. Hinweise auf dickdarmkrebstypische Mutationen fanden sich ebenfalls in beiden Gruppen, wobei hier keine Dosisabhängigkeit beobachtet werden konnte. Die Sequenzierung ergab ein deutlich von Literaturdaten abweichendes Spektrum. In Bezug auf das verwendete Tiermodell wurden erhebliche Abweichungen in der Empfindlichkeit der Tiere gegenüber der Substanz im Vergleich zu ähnlichen Studien festgestellt. Beide Fütterungsgruppen zeigten deutlich weniger Läsionen; als mögliche Gründe wurden Unterschiede in der Futterzusammensetzung und –zubereitung sowie in der Tierhaltung und –herkunft ausgemacht. Es konnte erstmalig ein Zusammenhang zwischen PhIP in niedrigen Dosen in der Nahrung und der Induktion von Entzündungen gezeigt werden. Diese waren sowohl makroskopisch als auch histologisch sichtbar, der genaue Mechanismus ihrer Entstehung ist jedoch unbekannt.<br><br> Die zusammenfassende Betrachtung aller Ergebnisse lässt vermuten, dass PhIP allein über lange Zeiträume aber in geringen Dosen verabreicht nicht für die hohe Zahl an Krebserkrankungen in westlichen Industrienationen ursächlich ist. / The development of colon cancer is associated with several nutritional, life style, and environmental factors. Among the environmental factors probably involved are substances formed during food processing and taken up with food. One of these substances is the heterocyclic aromatic amine (HAA) 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is formed during the heating of proteinaceous food such as meat and fish. In rodent studies the target organs for HAA-derived cancer development are identical with human organs showing high tumor incidences in western countries. Whether there is an association between exposure to PhIP and high tumor incidences in humans is still uncertain. The amount of PhIP administred to rodents in several studies was far above the levels of human exposure towards HAA. Thus, the aim of this study was to elucidate whether low concentrations of the substance are able to induce finger-print colon cancer gene mutations, preneoplastic lesions or tumors in rats. Animals fed with high amounts of PhIP developed fewer lesions than animals fed with a human-relevant concentration of PhIP. However none of the groups developed tumors of the colon. Both groups showed finger-print mutations for colon cancer, but not in a dose-dependent manner. Sequencing showed that the mutations were different from the known mutation spectum of PhIP. The susceptibility of the F344 rats to PhIP used in this study differed from that in previous feeding studies, with both groups showing much less lesions of the colon. Differences in composition and processing of the animal diets as well as animal maintenance and –origin may explain this discrepancy. For the first time an association between low doses of PhIP in the diet and induction of inflammation was shown. Signs of inflammation were observed macroscopically as well as in histological slices, but the mechanism of its induction remains to be clarified.<br><br> Taken together the results suggest that a chronical exposure to low doses of PhIP alone is not sufficient to explain the high incidences of colon cancer in western countries.

O tema da pesquisa da presente dissertação é investigar a poética narrativa do cineasta sulcoreano Kim Ki Duk a partir dos elementos nomeados labirintos imagéticos presentes na narrativa fílmica Time (Shigan)-2006. O ponto de partida do estudo é a análise da narrativa focalizando o trânsito entre textos e os jogos de significantes no discurso amoroso e na criação de corpos orgânicos, imagéticos, simbólicos e ficcionais. Sendo assim, foram explorados os labirintos do discurso amoroso e os labirintos do corpo como os responsáveis pela formação dos labirintos imagéticos que permeiam a narrativa fílmica em análise. Ao longo do estudo do objeto híbrido— narrativa fílmica, pontuaram-se questionamentos sobre Intertextualidade, Interdisciplinaridade, Imagem, Olhar e o objeto a. Pretendo estabelecer diálogos entre Teoria Literária, Psicanálise, Antropologia, Filosofia, Estudos Intermídias e Estudos Culturais, uma vez que a narrativa fílmica do cineasta Kim Ki Duk é tecida e mediada por elementos de uma poética dos limiares, de jogos vertiginosos das imagens e de provocação dos limites da linguagem, oscilando entre a presença e a ausência de significantes. / The theme of this thesis is discuss the visual poetic in narratives of South Korean filmmaker Kim Ki Duk through elements named mazes imagistic in film narrative Time (Shigan) -2006. The starting point of the study is the analysis of narrative focusing on transit between texts and significants in love speech also in the constructions of organic bodies, imagery, symbolic and fictional. Thereby, the labyrinths of love's speech and the labyrinths of the body were exploited, as responsible for the formation of imagistic mazes that permeate the film narrative in analysis. Throughout the study of hybrid object- film narrative, some questions emerged about Intertextuality, Interdisciplinary, Image, Gaze and the object a. I intend to establish dialogues between Literary Theory, Psychoanalysis, Anthropology, Philosophy, Intermídias Studies and Cultural Studies, since the film narrative filmmaker Kim Ki Duk create elements of a poetics of the transit of images and limits of language, through oscillations between the presence and the absence of significants.

O tema da pesquisa da presente dissertação é investigar a poética narrativa do cineasta sulcoreano Kim Ki Duk a partir dos elementos nomeados labirintos imagéticos presentes na narrativa fílmica Time (Shigan)-2006. O ponto de partida do estudo é a análise da narrativa focalizando o trânsito entre textos e os jogos de significantes no discurso amoroso e na criação de corpos orgânicos, imagéticos, simbólicos e ficcionais. Sendo assim, foram explorados os labirintos do discurso amoroso e os labirintos do corpo como os responsáveis pela formação dos labirintos imagéticos que permeiam a narrativa fílmica em análise. Ao longo do estudo do objeto híbrido— narrativa fílmica, pontuaram-se questionamentos sobre Intertextualidade, Interdisciplinaridade, Imagem, Olhar e o objeto a. Pretendo estabelecer diálogos entre Teoria Literária, Psicanálise, Antropologia, Filosofia, Estudos Intermídias e Estudos Culturais, uma vez que a narrativa fílmica do cineasta Kim Ki Duk é tecida e mediada por elementos de uma poética dos limiares, de jogos vertiginosos das imagens e de provocação dos limites da linguagem, oscilando entre a presença e a ausência de significantes. / The theme of this thesis is discuss the visual poetic in narratives of South Korean filmmaker Kim Ki Duk through elements named mazes imagistic in film narrative Time (Shigan) -2006. The starting point of the study is the analysis of narrative focusing on transit between texts and significants in love speech also in the constructions of organic bodies, imagery, symbolic and fictional. Thereby, the labyrinths of love's speech and the labyrinths of the body were exploited, as responsible for the formation of imagistic mazes that permeate the film narrative in analysis. Throughout the study of hybrid object- film narrative, some questions emerged about Intertextuality, Interdisciplinary, Image, Gaze and the object a. I intend to establish dialogues between Literary Theory, Psychoanalysis, Anthropology, Philosophy, Intermídias Studies and Cultural Studies, since the film narrative filmmaker Kim Ki Duk create elements of a poetics of the transit of images and limits of language, through oscillations between the presence and the absence of significants.

Existe-t-il une histoire du cinéma à Taiwan, une île qui connaît une longue et riche histoire coloniale, qui échapperait aux diverses formes imposées par les colonisateurs ? N’y a-t-il pas un cinéma résistant et indigénisé qui pourrait, en réaction aux contraintes sociales, politiques et culturelles, proposer une stratégie esthétique participant à l'émergence d'un sentiment national ? Ou faut-il attendre l'avènement d'un Nouveau Cinéma Taïwanais pour connaître un cinéma indigénisé dit “national” ?Afin de nourrir cette réflexion, la présente étude propose un retour sur l'une des formes originelles du cinéma taïwanais, au travers du personnage du benshi, en vue d’établir une histoire figurative. Deux autres figures, tâng-ki et kuso, nous permettent de développer la théorie du corps médiumnique. Cette dernière a pour objectif de construire une stratégie afin de résister aux troubles identitaires, autant dans l’espace public que dans l’espace privé. En conséquence, benshi, tâng-ki et kuso mettent en lumière une histoire cachée, une esthétique survivante, les bases d'une stratégie de résistance pour le cinéma taiwanais. / In Taiwan, the island of Formosa, where it holds a long history of colonization, is it possible for a history of cinema to escape from the various forms imposed by the colonists ? Could there be a resistant and indigenousized cinema, which offers an aesthetic strategy responding to the social, political and cultural issues ? At the meantime, also evokes a national sentiment ? Do we have to wait for the arrival of New Taiwan Cinema, which is known as indigenousized cinema to form a national cinema ?In order to explore these ideas, we will trace back to one of the original forms of Taiwan cinema, through the role of Benshi, to establish a figurative history. The other two roles, Tâng-ki and Kuso, will also allow us to develop the theory of mediumistic body, which will build a strategy responding to the identity crisis, both in public and private spaces. As a conclusion, Benshi, Tâng-ki and Kuso, which surface a previously hidden history and the surviving esthetics, become the funding bases of the resistance against colonization for Taiwan cinema.

O tema da pesquisa da presente dissertação é investigar a poética narrativa do cineasta sulcoreano Kim Ki Duk a partir dos elementos nomeados labirintos imagéticos presentes na narrativa fílmica Time (Shigan)-2006. O ponto de partida do estudo é a análise da narrativa focalizando o trânsito entre textos e os jogos de significantes no discurso amoroso e na criação de corpos orgânicos, imagéticos, simbólicos e ficcionais. Sendo assim, foram explorados os labirintos do discurso amoroso e os labirintos do corpo como os responsáveis pela formação dos labirintos imagéticos que permeiam a narrativa fílmica em análise. Ao longo do estudo do objeto híbrido— narrativa fílmica, pontuaram-se questionamentos sobre Intertextualidade, Interdisciplinaridade, Imagem, Olhar e o objeto a. Pretendo estabelecer diálogos entre Teoria Literária, Psicanálise, Antropologia, Filosofia, Estudos Intermídias e Estudos Culturais, uma vez que a narrativa fílmica do cineasta Kim Ki Duk é tecida e mediada por elementos de uma poética dos limiares, de jogos vertiginosos das imagens e de provocação dos limites da linguagem, oscilando entre a presença e a ausência de significantes. / The theme of this thesis is discuss the visual poetic in narratives of South Korean filmmaker Kim Ki Duk through elements named mazes imagistic in film narrative Time (Shigan) -2006. The starting point of the study is the analysis of narrative focusing on transit between texts and significants in love speech also in the constructions of organic bodies, imagery, symbolic and fictional. Thereby, the labyrinths of love's speech and the labyrinths of the body were exploited, as responsible for the formation of imagistic mazes that permeate the film narrative in analysis. Throughout the study of hybrid object- film narrative, some questions emerged about Intertextuality, Interdisciplinary, Image, Gaze and the object a. I intend to establish dialogues between Literary Theory, Psychoanalysis, Anthropology, Philosophy, Intermídias Studies and Cultural Studies, since the film narrative filmmaker Kim Ki Duk create elements of a poetics of the transit of images and limits of language, through oscillations between the presence and the absence of significants.