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Takeda, Kazuna. "MRI evaluation of residual tumor size after neoadjuvant endocrine therapy vs. neoadjuvant chemotherapy." Kyoto University, 2012. http://hdl.handle.net/2433/157449.
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Oliveira, Marcelo de Lima. "Ultrassonografia durante cirurgia para metástase cerebral: influência no índice de Karnofsky e volume do tumor residual." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-09082016-151729/.
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Introdução: Os principais objetivos do tratamento das metástases cerebrais (MC) são no auxílio do controle da doença no encéfalo e a melhora da qualidade de vida dos pacientes. A cirurgia convencional tem um importante papel no tratamento das MCs e os métodos de monitoração intraoperatória podem auxiliar na obtenção de resultados cirúrgicos melhores. Objetivos: Avaliar a influência da ultrassonografia encefálica durante cirurgia para ressecção de MC no índice de Karnofsky e no grau de ressecção do tumor. Métodos: Neste estudo prospectivo controlado e não randomizado, doentes com indicação de tratamento cirúrgico de MCs foram incluídos. A ultrassonografia intraoperatória (USIO) foi realizada por um neurossonologista. O índice de Karnofsky foi avaliado por equipe multidisciplinar de oncologia; o grau de dificuldade para ressecção cirúrgica do tumor foi avaliado pelo cirurgião e o volume tumoral foi avaliado pelo neurorradiologista por meio da RM realizada no pré e pós-operatório. Resultados: Dos 78 doentes, 40 homens e 38 mulheres com idade média de 53 anos, 35 foram submetidos a tratamento cirúrgico com auxílio da USIO. Não houve diferença estatística no KPS e volume tumoral pré-operatório entre os grupos. O KPS pós-operatório no grupo da USIO foi de 80 e no grupo-controle de 70 (p=0,045). Considerando-se a melhora do KPS no pós-operatório, a quantidade de doentes tiveram melhora do KPS foi superior no grupo da USIO (p=0,036) destacando-se os seguintes subgrupos: tumores com grau de dificuldade de ressecção < 4 (p=0,037), tumores nas áreas eloquentes (p=0,043), tumores não relacionados aos grandes vasos e nervos (p=0,007), e lesões únicas no leito cirúrgico (p=0,038). O tumor residual na RM pós-operatória foi menor no grupo da USIO: 9,5% no grupo da USIO e 30,8% no grupo-controle; 1,6 mm3 no grupo da USIO e 9 mm3 do grupo-controle; p=0,05. Considerando-se doentes com KPS >= 70, o número de doentes com volume de tumor residual inferior a 10% em relação ao volume pré-operatório foi superior no grupo da USIO (p=0,032 e OR de 3,8). Conclusão: Os achados deste estudo sugerem que a USIO encefálica pode influenciar na melhora do índice de Karnofsky e na redução do volume de tumor residualObject: The goals of treating a cerebral metastasis (CM) are to achieve local control of the disease and to improve patient quality of life. The aim of this study was to analyse the effect of using conventional surgery supported by intra-operative ultrasound (IOUS) to approach a CM. To perform this analysis, we determined Karnofsky post-operative scores (KPS) and tumour resection grades. Methods: Patients with CM who were eligible to undergo a surgical approach were included in this study. Surgical treatment was either supported or not supported by IOUS. A neural oncology team determined the pre- and post-operative KPS. A radiologist examined the tumour volume using pre- and post-operative magnetic resonance imaging. Before the surgery, the surgeon determined whether it was possible to perform a total CM resection. Results: A total of 78 patients with CM diagnosis were treated using a surgical approach (35 with and 43 without IOUS). The post-operative median KPS was higher in the IOUS group (80 versus 70, p=0.045). Within the IOUS group, KPS evolution was superior (p=0.036), especially in the following CM subgroups: a difficulty of tumour resection ranking score<4 (p=0.037), the tumour was in an eloquent area (p=0.043), the tumour was not associated with vessels or nerves (p=0.007), and solitary lesions (p=0.038). The volume of residual tumours was lower in the IOUS group (9.5% and 1.6 mm3 versus 30.8% and 9 mm3, p=0.05). In patients with a KPS >= 70, the residual tumour volume was categorized as < 10% or >= 10%, and 62% of patients had < 10% residual tumours (76% in the IOUS group and 45% in the non-IOUS group; p=0.032 and OR=3.8). Conclusion: This study suggests that IOUS can play a role in improving post-operative KPS and in decreasing residual tumours in CM surgeries
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Costa-Gurgel, Maria Salete 1956. "Aspectos histologicos relacionados com a persistencia de tumor residual apos conização em pacientes com carcinoma microinvasivo do colo uterino." [s.n.], 1994. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310012.
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Orientador: Aloisio José BedoneDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-07-19T18:28:24Z (GMT). No. of bitstreams: 1 Costa-Gurgel_MariaSalete_M.pdf: 1948436 bytes, checksum: 9652cc74f1c4e8abd0a8359398a304a0 (MD5) Previous issue date: 1994
Resumo: O tratamento do carcinoma microinvasivo do colo uterino é bastante controverso, sendo abordado diferentemente nos diversos Serviços. A histerectomia, acompanhada ou não de procedimentos mais radicais, é realizada na quase totalidade dos casos. Mais recentemente, tem-se observado uma tendência à adoção de condutas conservadoras, como a conização nos casos de invasão inicial, desde que se tenha segurança da retirada total da neoplasia. Através da revisão anatomopatológica dos 163 casos tratados no Ambulatório de Oncologia Ginecológica do Departamento de Tocoginecologia da FCM/UNICAMP, no período de 1967 a 1994, que foram submetidos à histerectomia simples ou radical após conização, procuramos estabelecer os fatores de risco para a persistência de tumor residual após esta cirurgia. Não houve influência das dimensões da microinvasão medidas pela profundidade e extensão horizontal da lesão, assim como do seu aspecto focal ou extenso e da presença de invasão vascular do estroma na ocorrência de neoplasia residual. Na análise inicial, o comprometimento das margens cirúrgicas da conização e a presença de sinais histológicos compatíveis com infecção pelo HPV demonstraram estar associados a um aumento significativo de neoplasia residual após conização uterina nos casos de carcinoma microinvasivo do colo uterino. No entanto, ao final do estudo, observou-se que houve interação entre os sinais de HPV e o comprometimento das margens cirúrgicas da conização na presença de tumor residual.
Abstract: The treatment of microinvasive carcinoma of the uterine cervix is controversial, with different approaches by different services. Hysterectomy in performed in almost all cases, associated or not with more radical procedures. Nowadays, there is a trend in adopting conservative conducts, such as conization in patients with early invasion, as long as there can be assured that the whole lesion was removed. Through histological review of 163 cases treated at the Gynecological Oncology Out patient Clinic if the Department of Gynecology and Obstetrics of the University of Campinas, from 1967 to 1994, ali of them undergone simple or radical hysterectomy after conization, it was tried to stablish the risk factors for persistency of residual tumor after conization. The microinvasion size measured by the depth and length of the lesion, its focal or extensive pattern and the presence of stromal vascular space involvement did not influence the occurrence of residual tumor. Initially the surgical margins involvement in conization and the presence of HPV histological signs were associated with on increased incidence of residual tumor after this procedure. Nonetheless, the statistical analysis showed that there was interaction between HPV histological signs and surgical margins involvement on residual tumor.
Mestrado
Mestre em Tocoginecologia
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Marighetti, P. "RESIDUAL DORMANT CANCER STEM CELL FOCI ARE RESPONSIBLE FOR TUMOR RELAPSE AFTER ANGIOGENIC METRONOMIC THERAPY IN HEPATOCELLULAR CARCINOMA XENOGRAFTS." Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/169919.
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Hepatocellular carcinoma (HCC) is the fifth most common solid tumor and the third leading cause of cancer-related death. Current available chemotherapeutic options are not curative due in part to their resistance to conventional therapies.
We have generated orthotopic HCC mouse models in immunodeficient NOD/SCID/IL2rγ null mice by injection of AFP- and/or luciferase-expressing HCC cell lines and primary cells from patients, where tumor growth and spread can be accurately monitored in a non-invasive way. Low dose metronomic administration of cyclophosphamide (LDM-CTX) causes in this model complete regression of the tumor mass with a significant increase in survival (p<0.0001), and reduction in aberrant angiogenesis, IL-6 and TNFα (but not VEGF) levels, hyperproliferation, and alteration of normal liver parenchyma, compared to untreated animals. However, the presence of residual circulating hAFP levels suggested that some tumor cells were still present in livers of treated mice. Immunohistochemistry revealed that those cells had a hAFP+/CD13+/PCNA- phenotype, suggesting that they were dormant cancer stem cells (CSC). Indeed, off-therapy mice developed rapidly tumor growth, which was still sensitive to LDM-CTX therapy. The capacity of developing hepatoshperes in vitro was drastically reduced upon LDM-CTX treatment, which resulted in selection of CD13+ cells, showing that these cells are particularly resistant to therapy. Co-treatment of the CD13-targeting drug bestatin with LDM-CTX resulted in a dramatic reduction in tumor burden.
Therefore, our results demonstrate the therapeutic efficacy of administering LDM-CTX and targeting the residual CD13+ CSC-like population in these novel orthotopic HCC models, and strongly suggests that this therapy could be implemented in clinical trials.
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Vu-Han, Tu-Lan [Verfasser], and Reinhard [Akademischer Betreuer] Schneppenheim. "Identifying Molecular Markers for the Sensitive Detection of Residual Atypical Teratoid Rhaboid-Tumor Cells / Tu-Lan Vu-Han. Betreuer: Reinhard Schneppenheim." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2016. http://d-nb.info/1082347604/34.
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Vu-Han, Tu-Lan Verfasser], and Reinhard [Akademischer Betreuer] [Schneppenheim. "Identifying Molecular Markers for the Sensitive Detection of Residual Atypical Teratoid Rhaboid-Tumor Cells / Tu-Lan Vu-Han. Betreuer: Reinhard Schneppenheim." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2016. http://nbn-resolving.de/urn:nbn:de:gbv:18-77221.
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Morales, Murillo Serafín. "Cáncer de mama: utilidad pronóstica de los Perfiles de Expresión Proteica en pacientes con tumor residual viable (>1.0cm.) tras Quimioterapia neoadyuvante." Doctoral thesis, Universitat de Lleida, 2015. http://hdl.handle.net/10803/401677.
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La identificació de marcadors moleculars en el tumor residual després de quimioteràpia neoadjuvant ( QTN ) en Càncer de Mama permet una millor caracterització pronostica . S'han seleccionat un total de 256 pacients amb QTN entre 1996 i 2011 , amb tumor residual ( > 1 cm ) . S'ha realitzat una matriu matricial de teixits i estudi inmunohistoquimic de l'expressió de 29 marcadors moleculars . L'anàlisi s'ha realitzat sobre l'aparició de metàstasi i la supervivència lliure de progressió a distància . El model multivariant ( mètode stepwise ) obté una signatura molecular amb sis marcadors de mal pronòstic : ER [ = 0 ] , cit - P65 [ < 85 ] , cit - HER4 [ > 75 ] , cit - PTEN [ = 0 ] , BCL2 [ < 78 ] i Ki67 [ > 20 ] . Una anàlisi en funció de l'expressió de receptors de estrògens identifica marcadors associats a mal pronòstic en RE -negatiu [ = 0 ] : ]: HER4-cit [>70] (p 0.01), P65-nuc [>37] (p 0.01), BP1 [>100] (p 0.001) p65-cit [<85] (p 0.04) E-Cad-cit [>80] (p 0.04) y GATA 3 [<145] (p 0,05), mentre que per RE - positiu [ > 0 ] : Ciclina D1-nuc [>145] (p 0.02) Ki67 [>24] (p 0.02) Survivina-nuc [<90] (p 0.02) i pAKT-cit [>145] (p 0.03)La identificación de marcadores moleculares en el tumor residual tras quimioterapia neoadyuvante (QTN) en Cáncer de Mama permite una mejor caracterización pronostica. Se han seleccionado un total de 256 pacientes con QTN entre 1996 y 2011, con tumor residual (> 1 cm). Se ha realizado un array matricial de tejidos y estudio IHQ de la expresión de 29 marcadores moleculares. El análisis se ha realizado sobre la aparición de metástasis y la supervivencia libre de progresión a distancia. El modelo multivariante (método stepwise) obtiene una firma molecular con seis marcadores de mal pronóstico: ER [= 0], cit-P65 [<85], cit-HER4 [> 75], cit-PTEN [= 0], BCL2 [<78] y KI67 [> 20]. Un análisis en función de la expresión de RE identifica marcadores asociados a mal pronostico en RE-negativo [=0]: HER4-cit [>70] (p 0.01), P65-nuc [>37] (p 0.01), BP1 [>100] (p 0.001) p65-cit [<85] (p 0.04) E-Cad-cit [>80] (p 0.04) y GATA 3 [<145] (p 0,05) , mientras que para RE-positivo [>0]: Ciclina D1-nuc [>145] (p 0.02) Ki67 [>24] (p 0.02) Survivina-nuc [<90] (p 0.02) y pAKT-cit [>145] (p 0.03) .
Identification of molecular markers in the residual tumor after neoadjuvant chemotherapy ( QTN ) in breast cancer allows better prognostic characterization . A total of a total of 256 patients between 1996 and 2011 QTN with residual tumor ( > 1 cm) have been selected . A tissue array and inmunohistochemistry study of expression of 29 molecular markers has been performed. The analysis was conducted on the occurrence of metastasis and progression-free survival distance. The multivariate model ( stepwise method ) obtained a molecular signature of six prognostic markers : ER [= 0] , cit - P65 [ < 85 ] , cit - HER4 [ > 75 ] , cit - PTEN [= 0] , BCL2 [ < 78 ] and Ki67 [ > 20 ] . An analysis based on the expression of estrogen receptor identifies markers associated with poor prognosis in ER - negative [= 0 ]: HER4-cit [>70] (p 0.01), P65-nuc [>37] (p 0.01), BP1 [>100] (p 0.001) p65-cit [<85] (p 0.04) E-Cad-cit [>80] (p 0.04) y GATA 3 [<145] (p 0,05) , whereas ER - positive [ > 0 ] : Ciclina D1-nuc [>145] (p 0.02) Ki67 [>24] (p 0.02) Survivina-nuc [<90] (p 0.02) y pAKT-cit [>145] (p 0.03).
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PEIRETTI, MICHELE. "Role of maximal primary cytoreductive surgery in patients with advanced epithelial ovarian and tubal cancer: surgical and oncological outcomes. single institution experience." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2010. http://hdl.handle.net/10281/8049.
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Objective. The objective of the present study was to determinate the impact of maximal cytoreductive surgery on progression free survival, overall survival rates and morbidity, in patients with advanced epithelial ovarian or fallopian tube cancer (stage IIIC-IV) treated in a referral cancer center.
Methods. After obtaining Institutional Review Board approval, we reviewed all medical records of patients with stage IIIC–IV epithelial ovarian cancer who were managed at our institution between January 2001 and December 2008. Individual records were reviewed and the following information collected: age at surgery, date of surgery, American Society of Anestesiology (ASA) class, primary site of disease, presence of peritoneal carcinomatosis, histologic type and tumor grade, pre-operative serum CA-125 level, location and size of the largest tumor mass, the initial ascites volume (if present), all surgical procedures performed, size of residual disease after surgery. The Kaplan–Meier method was used to estimate survival curves. Cox proportional hazards regression was performed to identify independent prognostic variables for overall survival by univariate and multivariate analysis.
Results. A total of 269 patients with advanced epithelial ovarian cancer were referred to our institution between January 2001 and December 2008, and of them 240 consecutive patients met inclusion criteria for the study. The median age was 58 years (range 22 to 77 years). After a median follow up of 29.8 months, the overall median survival (OS) and progression free survival (PFS) were 61.1 and 20.4 months respectively. On univariate analysis, factors significantly associated with decreased survival included: age grater than median (>60 years), presence of ascites >1000 cc, diffuse peritoneal carcinomatosis, omentum as anatomical location of the largest tumor mass, positive lymph-nodes and diameter of residual disease. On multivariate analysis confirmed the independent association of age grater than 60 years and residual disease > 5 mm with worse survival.
Conclusion. Our study seems to demonstrate that a more extensive surgical approach is associated with improved survival in patients with stages IIIC-IV epithelial ovarian cancer. Age grater than 60 years and residual tumor grater than 5 mm were independently associated with a worse prognosis.
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Milano, Jeronimo Buzetti. "Estudo das alterações em exames de ressonância magnética de pacientes em pós-operatório imediato de ressecção de tumores hipofisários por via transesfenoidal." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-22062010-125138/.
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Exames pós-operatórios de cirurgias intracranianas são difíceis de serem interpretados por apresentarem alterações morfológicas que simulam situações patológicas, como edema e tumores residuais. Com o advento de métodos de ressonância intraoperatória essa interpretação ganhou maior importância, pelo risco de re-intervenções desnecessárias. O presente estudo objetivou estabelecer as características de exames pós-operatórios normais após remoção de tumores hipofisários pela via transesfenoidal endonasal, bem como estabelecer parâmetros de remoção tumoral radical para otimização de exames intraoperatórios. Foram estudados 40 pacientes (22 microadenomas e 18 macroadenomas) operados consecutivamente no Instituto de Neurologia de Curitiba, portadores de adenomas hipofisários, pela via transesfenoidal endonasal, e que realizaram exame de ressonância magnética (RM) dinâmica no pré-operatório, pós-operatório imediato (primeiras 24horas após o término da cirurgia) e após três meses.Foram utilizadas sequências ponderadas em T1, com cortes coronais de 3mm antes da injeção de contraste (gadopentetato dimeglumina Gd-DTPA) e a cada 90 segundos após a injeção rápida do mesmo. Os achados de RM dinâmica no pós-operatório imediato foram analisados quanto ao deslocamento da haste hipofisária, presença de material hiperintenso intrasselar, deslocamento do diafragma selar superiormente (caracterizado pela classificação de Hardy para extensões suprasselares) e quanto ao padrão de captação de contraste na RM dinâmica. Os padrões de captação foram classificados como: 1. ausência de captação de contraste, 2. realce anelar periférico, 3. captação nodular e 4. padrão misto (periférico e nodular coexistentes). No exame pós-operatório tardio, ênfase foi dada na presença de tumor residual, confirmada por alteração hormonal ou re-operação com histopatologia.As alterações de imagem foram descritas em termos de prevalência de ocorrência (porcentagem), e correlacionadas com a existência ou não de tumores residuais no pós-operatório tardio. Observouse deslocamento da haste hipofisária em 95% dos casos (90,9% dos microadenomas e 100% dos macroadenomas). Material hiperintenso intrasselar ocorreu em 77,3% dos microadenomas e 100% dos macroadenomas (87,5% do total). O deslocamento cranial do diafragma selar manteve inalterado em 16 dos 18 casos (88,9%). A padrão de captação de contraste foi o tipo 1 em 90,9% dos microadenomas, com apenas 2 casos (9,1%) com captação periférica (tipo 2) neste grupo. Nos macroadenomas, 66,7% foram tipo 1, 5,5% tipo 2, 16,7% tipo 3 e 11,1% tipo 4. No pós-operatório tardio, o material hiperintenso desapareceu em todos os casos, com a haste hipofisária retornando à posição habitual em 81,8% dos casos. Cinco pacientes apresentavam tumores residuais, confirmados por alteração hormonal em dois casos e reoperação em três. Destes, três apresentavam padrão tipo 4 de captação de contraste, e dois do tipo 3. A correlação entre o padrão de captação nodular, isolado ou combinado, com a presença de tumor residual foi de 100%. Todos os outros achados devem ser considerados normais no pós-operatórioImaging after intracranial surgeries is difficult to evaluate because usual changes often simulates pathological findings, such as edema and residual tumors. Emerging technologies of intraoperative magnetic resonances lead to a greater interest on understanding usual findings, in order to avoid unnecessary revisions. The objective of this study was to establish normal postoperative findings on dynamic magnetic resonance imaging (dMRI) after resection of pituitary tumors through endonasal transsphenoidal approach, as well as determine parameters of radical resection, thus optimizing intraoperative images. Forty patients (22 microadenomas and 18 macroadenomas) operated on the Instituto de Neurologia de Curitiba for pituitary adenomas through endonasal transsphenoidal approach were evaluated by dMNRI before, within the first 24 hours and after three months of the surgery. T1-weighted images on coronal plane, 3mm slices were performed before and on every 90 seconds after rapid injection of the paramagnetic contrast (gadopentetate dimeglumine GdDTPA). Findings analyzed at early postoperative dMRI were: lateral displacement of the pituitary stalk, hyperintense intraselar material, position of the diafragma selae (as classified by Hardy, for supraselar extensions) and the pattern of contrast enhancement: 1. no enhancement, 2. peripheral ring, 3. nodular enhancement and 4. combined peripheral and nodular. At late postoperative MRI, the regression of early findings was noted, as well as the presence of a residual tumor. This late was confirmed by hormonal essay or hystopathological examination (reoperation). Findings were first described as prevalence (%), and then related to the presence or not of a residual tumor at late postoperative MRI. Displacement of the pituitary stalk was noted in 95% of cases (90,9% in microadenomas, and 100% in macroadenomas). Hyperintense intraselar material was found in 77,3% of microadenomas and 100% of macroadenomas (87,5% of all cases). Supraselar extension remained unaltered in 16 of 18 cases (88,9%). Pattern of enhancement was type 1 in 90,9% of the microadenomas, with only two cases (9,1%) with peripheral ring. Of the macroadenomas, 66,7% had type 1 pattern, 5,5% type 2, 16,7% type 3 and 11,1% type 4. At late postoperative MRI, the hyperintense material disappeared in all cases, with the pituitary stalk returning to the midline in 81,8% of the cases. Five patients had residual tumors, confirmed by hormonal essay in two cases, and re-operated (with hystopathological confirmation) in three. Of these, three had type 4 pattern of enhancement, and two had type 3. When the nodular enhancement, alone or combined, was correlated with the presence of a residual tumor, the association was of 100%. The other findings described should be considered normal findings
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Rick, Oliver. "Therapieoptimierungsverfahren bei Patienten mit rezidivierten oder progredienten Keimzelltumoren." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2004. http://dx.doi.org/10.18452/13921.
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Patienten mit metastasierten Keimzelltumoren, die einen Progress oder ein Rezidiv ihrer Erkrankung nach einer cisplatinhaltigen Vortherapie erleiden, haben eine schlechte Prognose. Unter Verwendung einer erneuten konventionellen Chemotherapie können maximal 15-30% dieser Patienten geheilt werden, so dass die Mehrzahl der Patienten an ihrer Erkrankung verstirbt. Aus diesem Grund ist die Optimierung der therapeutischen Möglichkeiten ein wesentliches Ziel. Unsere Daten zeigen, dass die Hochdosischemotherapie (HDCT) eine wesentliche therapeutische Verbesserung darstellt und mittels dieser Therapie mit einem ereignisfreien Überleben von 30-60% zu rechnen ist. Eine "matched-pair" Analyse konnte im Hinblick auf das ereignisefreie und das Gesamtüberleben einen Vorteil von mehr als 10% zu Gunsten der HDCT feststellen. Darüber hinaus hat die zunehmende Erfahrung und die Verwendung von peripheren Blutstammzellen und hämatopoetischen Wachstumsfaktoren, den Einsatz der HDCT deutlich sicherer gemacht. Aus den genannten Gründen sollte alle Patienten mit Rezidiv oder Progress eines Keimzelltumors der HDCT zugeführt werden. Die operative Entfernung von residuellen Tumormanifestationen (RTR) nach primärere Chemotherapie ist heute Standard bei Patienten mit metastasierten Keimzelltumoren. Zwar findet sich in der histologischen Aufarbeitung bei den meisten Patienten ausschließlich nekrotisches Gewebe, doch werden bei einem Teil der Patienten auch Anteile von reifem Teratom und vitalen differenzierten und undifferenzierten Karzinomen gefunden. Während die Resektion von Nekrose keinen therapeutischen Benefit für den Patienten darstellt, ist die komplette Entfernung von reifem Teratom oder Zellen eines Karzinoms für die Prognose entscheidend. In Bezug auf die HDCT konnten bisher keine vergleichbaren Daten erhoben werden. Zur Evaluierung des Stellenwertes der RTR nach HDCT analysierten wir unser eigenes Patientenkollektiv und fanden, dass vergleichbar zur Primärtherapie alle Patienten nach Salvage-HDCT, die eine partielle markernegative oder markerpositive Remission erreicht haben, einer RTR zugeführt werden sollten. Bis auf intrazerebrale Reste sollten alle residuellen Tumormanifestationen komplett reseziert werden. Neben der Optimierung der therapeutischen Möglichkeiten ist auch die Minimierung der chemotherapieassoziierten Toxizitäten ein wesentlicher Bestandteil meiner wissenschaftlichen Arbeit. Aus diesem Grund evaluierten wir die Wirksamkeit der Substanz Amifostin im Hinblick auf die Verringerung von Toxizitäten, die Wirkung auf die Mobilisierung von peripheren Blutstammzellen und den Einfluß auf die Rekonstitution des Immunstatus bei Patienten mit rezidivierten oder progredienten Keimzelltumoren, die mittels einer konventionellen Chemotherapie und anschließender HDCT behandelt wurden. Der Einsatz von Amifostin erbrachte in diesem Zusammenhang und in diesem Patientenkollektiv keinen therapeutischen oder prophylaktischen Nutzen, so dass dessen Verwendung bei Patienten mit Keimzelltumoren nicht generell empfohlen werden kann.Overall, patients with relapsed or progressive germ cell tumors (GCT) after cisplatin-based chemotherapy have a low chance of cure. Using conventional-dose chemotherapy as salvage treatment only 15-30% of the patients will become long-term survivors. It is well known that the majority of these patients will ultimately die of their disease. Therefore, improvment of standard treatment is clearly desirable. Our data has been established high-dose chemotherapy (HDCT) as an effective salvage modality with an event-free survival of 30-60%. A matched-pair analysis showed an advantage for HDCT compared with conventional-dose chemotherapy with improvement in event-free and overall survival of more than 10%. Furthermore, due to increasing clinical experience in the management of side-effects, the use of peripheral blood progenitor cells, and the availability of hematopoietic growth factors, HDCT has become relatively safe. In GCT patients with relapsed or rogressive disease HDCT has been demonstrated as a feasible and safe treatment concept which will be curative for a substantial proportion of these patients. Therefore, HDCT should be administered in patients with first relapse and unfavorable prognostic factors and as second or subsequent salvage treatment. Surgical resection of residual tumors (RTR) after first-line chemotherapy is recommended in patients with metastatic GCT. Necrosis will be the only histological finding in the majority of these patients. However, in others mature teratoma, viable cancer consisting of residual GCT, non germ-cell tumors, undifferentiated cancer or a combination of these histologies may be found. Whereas the resection of necrosis offers no therapeutic benefit, resection of mature teratoma or viable cancer adds to long-term event-free and overall survival in these patients. However, limited data exist on the results of surgery and the respective histologies in patients after first or subsequent salvage treatment with HDCT. To assess the contribution of RTR in this setting, we retrospectively analyzed a cohort of patients who had been treated with HDCT for relapsed or refractory GCT. Our data show that RTR contributes to the overall treatment outcome and should be offered to all patients with a partial remission after HDCT. Complete resections of all residual tumors outside the CNS should be attempted. Furthermore, we assessed the efficacy of amifostine for protection from chemotherapy-induced toxicities, for peripheral blood progenitor cell mobilization and for immune-reconstitution in patients treated with conventional-dose paclitaxel, ifosfamide, cisplatin (TIP) and high-dose carboplatin, etoposide and thiotepa (CET) followed by PBPC rescue. In conclusion, amifostine additional to conventional-dose chemotherapy or HDCT showed no unequivocal advantage in protection from treatment-related toxicities and had no effect neither on PBPC mobilization nor on immune-reconstitution.
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Mopin, Alexia. "Développement d’un modèle murin syngénique et immun de leucémie aiguë myéloïde et de maladie résiduelle mesurable surexprimant ou non le gène Wilms Tumor 1." Thesis, Lille 2, 2018. http://www.theses.fr/2018LIL2S035/document.
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Les leucémies aiguës myéloïdes (LAM) sont des hémopathies malignes hétérogènes déclenchées, dans la plupart des cas, par des anomalies génétiques (mutations, translocations ou inversions). Elles se caractérisent par un blocage de la différenciation de certains progéniteurs ou précurseurs hématopoïétiques (blastes) et leur prolifération clonale incontrôlée provoquant leur accumulation dans la moelle osseuse. Le traitement actuel de ces patients repose essentiellement sur l’utilisation d’agents de chimiothérapie (cytarabine associée à une anthracycline) permettant d’éliminer les cellules leucémiques et d’obtenir une rémission complète (RC) (définie morphologiquement comme une moelle osseuse normale avec moins de 5% de blastes). Cette RC est obtenue chez une majorité des patients mais plus d’un patient sur deux va rechuter quelques mois après l’arrêt du traitement. Ces rechutes attestent de la persistance de cellules leucémiques résiduelles après le traitement, que l’on appelle maladie résiduelle mesurable (MRD). Celle-ci a été mise en évidence grâce au développement de technologies performantes et sensibles tels que la cytométrie en flux multi-paramétrique et la PCR en temps réel (qPCR) permettant ainsi la détection de profils d’expression ou d’anomalies génétiques associés aux LAM. A ce jour, plusieurs mécanismes ont été décrits pour expliquer la présence de cette MRD. Celle-ci peut être causée par une résistance au traitement de certains sous-clones leucémiques (anomalies génétiques intrinsèques leur conférant une résistance ou un phénotype quiescent) ou par la présence de cellules souches leucémiques (naturellement quiescentes). Le système immunitaire pourrait également jouer un rôle en induisant la quiescence de certaines cellules les rendant résistantes aux chimiothérapies conventionnelles, ou en contrôlant leur croissance tumorale par l’établissement d’un état d’équilibre entre leur prolifération et leur lyse. Les modèles murins de LAM actuellement utilisés permettent d’étudier la leucémogenèse et l’efficacité thérapeutique de certains composés mais font abstraction du rôle de la réponse immunitaire dans ces processus du fait de leur immunodéficience. De plus, aucun modèle murin de MRD leucémique n’existe pour étudier les causes de la persistance cancéreuse après traitement par chimiothérapie. Ainsi, le but de cette thèse a été de développer un modèle murin syngénique et immunocompétent de MRD leucémique sur-exprimant ou non le gène Wilms’ Tumor 1 (WT1). WT1 est un des rares antigènes décrits dans les LAM et une réponse lymphocytaire cellulaire et humorale dirigée contre cette protéine a été décrite chez ces patients. La création de ce modèle sur-exprimant ou non WT1 permettra ainsi d’étudier le rôle de la réponse immunitaire spécifique de celui-ci dans la persistance leucémique. Pour développer ce modèle nous avons, dans un premier temps, caractérisé phénotypiquement et génotypiquement des sous-clones isolés de la lignée leucémique C1498 capable d’induire une LAM de type myélo-monocytaire chez des souris immunocompétentes C57BL/6J. Dans un deuxième temps, certains sous-clones ont été sélectionnés pour leur sensibilité à la cytarabine et transfectés de manière à exprimer stablement une protéine fluorescente (ZsGreen) en association ou non avec la protéine WT1. Enfin, ce modèle de MRD leucémique a été obtenu en modulant la quantité de cellules leucémiques injectée ainsi que la cinétique et la dose d’injection de la cytarabine. La MRD a été suivie par cytométrie en flux (expression ZsGreen) et par qPCR (expression ZsGreen et/ou de Wt1) dans le sang et la moelle osseuse des souris survivantes grâce au traitement [...]Acute myeloid leukemia (AML) is a genetic disorder leading to a blockade of differentiation and a clonal expansion of hematopoietic progenitors or precursors (called blasts) which accumulate in the bone marrow and then invade the blood stream. Conventional treatment relies on the use of chemotherapy agents (cytarabine in combination with an anthracycline) to eliminate leukemia cells and achieve complete remission (defined as normal bone marrow morphology with less than 5% blasts). This complete remission is achieved in a majority of patients but more than 50% of them will relapse several months after the treatment. These relapses indicate the presence of residual leukemic cells after treatment, known as measurable residual disease (MRD). It has been highlighted by the development of efficient and sensitive molecular biology technologies such as multi-parameter flow cytometry and real-time PCR allowing the detection of AML-associated expression patterns and genetic abnormalities. Several mechanisms have been described that can explain the presence of this MRD. It may be caused by the resistance to treatment of certain leukemic sub-clones (resistance-conferring mutations or quiescent phenotype) or the presence of leukemic stem cells. Finally, the immune system could also induce the quiescence of certain leukemic cells rendering them resistant to conventional chemotherapies, or control their growth leading to a state of equilibrium between their proliferation and lysis. Several AML mouse models allow the study of leukemogenesis and the testing of new therapeutic agents for leukemic cells eradication. However, they are mostly based on the transfer of human leukemic cells in immune-deficient mice and do not provide information about the role of the immune system in the leukemic cell survival, sub-clonal expansion or persistence. Moreover, there is still no available leukemia MRD mouse model allowing the study of leukemic cell persistence after chemotherapy treatment. According to these findings, the aim of this thesis was to develop a syngeneic and immune-competent mouse model of leukemia MRD overexpressing or not the Wilms' Tumor 1 (WT1) gene. The WT1 protein is described as an antigen associated with AML and is targeted by specific lymphocyte cellular and humoral responses in AML-affected patients. Creating a syngeneic and immune-competent leukemia MRD mouse model overexpressing or not this antigen will allow determining the role of this specific immune response in the cancer cell persistence. To set up this model, we first phenotyped and genotyped sub-clones isolated from the murine C1498 leukemic cell line able to induce a myelo-monocytic AML in immune-competent C57BL/6J mice. In a second step, certain sub-clones were selected for their sensitivity to cytarabine treatment and transfected to stably express the fluorescent ZsGreen protein with or without the WT1 antigen. Lastly, the MRD mouse model was obtained after modulation of various parameters such as the amount of leukemic cells administered, the kinetics and injection doses of chemotherapy. The leukemia MRD was monitored by flow cytometry (expression of the ZsGreen protein) and by real-time PCR (expression of the ZsGreen and/or Wt1 genes) in the peripheral blood and the bone marrow of treated and surviving mice. Thus, we generated a syngeneic and immune-competent leukemia MRD mouse model useful to study the immune mechanisms involved in the persistence of leukemic cell after treatment and to test new (immune)-therapeutic strategies targeting these residual cells
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Kuniyoshi, Renata Kelly. "Estudo do perfilamento gênico tumoral e de marcadores de doença residual mínima (CK19 e c-ErbB-2) através de RT-PCR quantitativo na fração mononuclear do sangue periférico em pacientes com câncer de mama durante o tratamento." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5167/tde-12022014-160250/.
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INTRODUÇÃO: De acordo com a estimativa de 2012 do INCA, eram esperados 52.680 novos casos de câncer de mama no Brasil, com um risco estimado de 52 casos a cada 100 mil mulheres. Estes dados mostram a necessidade da identificação de biomarcadores efetivos para rastreamento precoce e seguimento destas mulheres durante seu tratamento. Neste trabalho, para a avaliação de potenciais biomarcadores desta doença, foi idealizado um modelo laboratorial específico que avalie tanto a capacidade de um dado biomarcador rastrear um tumor inicial de mama, bem como testar o seu potencial valor para o seguimento de mulheres já diagnosticadas durante seu tratamento. Este modelo baseia-se na avaliação de células tumorais circulantes e perfilamento gênico tumoral. MÉTODOS: Amostras biológicas (sangue periférico e tumor) de 167 pacientes diagnosticadas com carcinoma mamário estadios I, II e III com indicação de quimioterapia adjuvante para: a) avaliação da presença de células tumorais circulantes através da expressão de CK19 e HER2 na Fração Mononuclear do Sangue Periférico (FMNSP) por RT-PCR quantitativo e b) perfilamento gênico tumoral através da análise da expressão de 21 genes relacionados a importantes processos de carcinogênese mamária em amostras de tecido parafinado por ensaio multiplex de RT-PCR quantitativo utilizando o sistema Plexor®. RESULTADOS: Foi observada uma correlação significativa entre CK19 e HER2 na primeira coleta e queda da concentração de HER2 no SP durante o tratamento; porém, não foi percebida queda significativa do CK19 ao longo do estudo. A expressão de HER2 na segunda coleta de pacientes positivas para HER2 na primeira coleta tendeu a se correlacionar significativamente com um pior Intervalo Livre de Doença (ILD). Através da padronização da pontuação em quartis das análises realizadas em multiplex pelo sistema Plexor, foi percebido que o quartil superior apresentava ILD significativa pior do que a de pacientes nos demais quartis. Também foi observada uma estratificação do estadio clínico II em pior ou melhor prognóstico de acordo com o quartil de pontuação do teste de perfilamento proposto neste estudo; além disso, verificou-se que pacientes submetidas a tratamento neoadjuvante com pontuações inferiores tenderam a responder melhor à quimioterapia. CONCLUSÃO: Pelas características do comportamento evolutivo no presente estudo, HER2 parece ser melhor como possível biomarcador de células tumorais circulantes do que o CK-19. Até o presente momento do seguimento das pacientes incluídas neste estudo, não foi possível criar um modelo com diversas variáveis para prever o prognóstico de pacientes com câncer de mama. Isto ocorreu principalmente pelas características preditivas prognósticas superiores do perfilamento genético do tumor que desloca fatores de prognóstico tais como células circulantes e estadio clínico, expressão hormonal do tumor e idade de um modelo multivariado. Por outro lado, foi padronizada uma tecnologia genômica complexa que poderá viabilizar seu uso para a população se estudos posteriores confirmarem seu valor em outras coortes de pacientes com câncer de mamaBACKGROUND: According to the estimate of 2012 INCA, were expected 52,680 cases of breast cancer in Brazil, with an estimated risk of 52 cases per 100 000 women. These data show the need for effective identification of biomarkers for early screening and follow-up of these women during their treatment. In this work, for the evaluation of potential biomarkers of this disease, a model laboratory was designed to evaluate both the specific capacity of a given biomarker trace an initial breast tumor, as well as test its potential value for the follow-up of women already diagnosed during their treatment. This model was based on the evaluation of circulating tumor cells and tumor gene profiling. METHODS: Biological samples (peripheral blood and tumor) of 167 patients diagnosed with breast cancer stages I, II and III with an indication for adjuvant chemotherapy: a) to evaluate the presence of circulating tumor cells through the expression of HER2 and CK19 in Peripheral Blood Mononuclear fraction (PBMN) by quantitative RT-PCR and b) tumor profiling gene by analyzing the expression of 21 genes related to important processes of mammary carcinogenesis in paraffinized tissue samples by multiplex assay for quantitative RT-PCR using the Plexor ® System. RESULTS: Was observed a significant correlation between HER2 and CK19 in the first collection and decrease in concentration of HER2 in PB during the treatment, but were not perceived significant decrease of CK19 along the study. The expression of HER2 in the second collection of patients positive for HER2 in the first test tended to correlate with a significantly worse disease-free interval (DFI). Through standardization of the scores in quartiles of the analyzes performed at multiplex Plexor system was seen that the upper quartile ILD had significantly worse than patients in the other quartiles. Also stratification was observed in clinical stage II in better or worse prognosis according to quartiles of test score profiling proposed in this study, in addition, it was found that patients submitted to neoadjuvant treatment with lower scores tended to better respond to chemotherapy. CONCLUSION: HER2 seems to be better as possible biomarker of circulating tumor cells than the CK-19. So far the monitoring of patients included in this study, it was not possible to create a model with multiple variables to predict the prognosis of patients with breast cancer. This occurred primarily due to the characteristics predictive prognostic upper genetic profiling of tumor that displaces prognostic factors such as circulating cells and clinical stage, tumor hormone expression and age in a multivariate model. In the other hand, was standardized complex genomic technology that may enable their use for the population if further studies confirm its value in other cohorts of patients with breast cancer
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Linhares, José Clemente. "Medida de qualidade de tumor residual como método preditivo da sobrevida após quimioterapia neoadjuvante no tratamento do câncer de mama : validação de uma nova metodologia / José Clemente Linhares ; coordenador, Luiz Carlos Von Bathen ; orientador, Flávio Daniel Saavedra Tomasich." reponame:Biblioteca Digital de Teses e Dissertações da PUC_PR, 2011. http://www.biblioteca.pucpr.br/tede/tde_busca/arquivo.php?codArquivo=2431.
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Dissertação (mestrado) - Pontifícia Universidade Católica do Paraná, Curitiba, 2011Bibliografia: f. 39-44
Introdução: Apesar dos significantes avanços no conhecimento no uso da quimioterapia primária ou neoadjuvante no tratamento do câncer da mama, ainda não se estabeleceu um método adequado para a quantificação da doença residual após o tratamento e a sua re
Introduction: Although we have had significant improvement in knowledge on the use of primary chemotherapy in breast cancer treatment, to the moment there is not an adequate method to evaluate the residual tumor burden after the treatment as well as its r
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Volpari, Tatiana. "Residual breast cancer metabolic phenotype after docetaxel treatment." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6710/.
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Despite improvements in early diagnosis and prevention, late stage breast cancer is often incurable due to metastasis, tumour relapse, resistance and incomplete response to treatments. Metabolic reprogramming has been recognised as a critical element for cancer cells to grow under hostile conditions and this is likely to contribute towards resistance against chemotherapeutics. This thesis therefore aimed at deciphering the metabolic phenotype of residual breast cancer which survived docetaxel treatment, in vitro and in vivo, quantifying polar metabolite levels and conducting pathway tracing and metabolic flux analysis using stable isotope (¹³C) labelled tracers. \(In\) \(vitro\) residual cells presented a hypermetabolic phenotype characterised by significant accumulation of essential and non-essential amino acids, together with an elicited Warburg effect and an increased antioxidant response based on glutathione production, while in growth arrest. A method to carry out in vivo tracer-based metabolic studies was successfully developed using a breast cancer mouse model. Although the metabolite accumulation outlined in vitro was not observed in vivo, a protective phenotype against oxidative stress was supported by increased flux through the oxidative branch of the pentose phosphate pathway. In conclusion, this thesis demonstrated that metabolic phenotyping is a valid approach to uncover key metabolic alterations in residual tumours both in vitro and in vivo, and could be further exploited to design personalised treatments aimed at restoring sensitivity to therapies.
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Dionne, Sara O. "Tumor-derived peptides modified at HLA-A*0201 binding residues elicit cytotoxic T lymphocyte responses." Diss., The University of Arizona, 2002. http://hdl.handle.net/10150/280126.
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The immunotherapy of cancer aims to activate both the humoral and cellular arms of the immune system to generate a specific and effective anti-tumor response. Tumor cells express self-antigens which masks these cells from recognition by the immune system. Tumor cells display antigen in the context of Human Leukocyte Antigen (HLA) molecules presented on the cell surface. Cytotoxic T lymphocyte (CTL) recognition of antigenic peptide/HLA complexes results in destruction of the target cell. CTL are educated to discriminate between foreign and self-antigens, however tumor cells frequently express self-antigens, rendering tumors poorly immunogenic. Several tumor-derived peptides have a weak affinity for HLA molecules and are therefore inefficiently presented to T cells. Peptides bind to HLA molecules through anchor residues on both the carboxy and amino termini. Modification of peptides at critical HLA-binding residues can (i) increase the affinity of a peptide for HLA molecules, therefore increasing the opportunity for peptide presentation to tumor-specific T cells and (ii) result in the generation of 'altered self' (altered peptide ligands) with the potential to activate CTL. It was hypothesized that the substitution of preferred HLA-A*0201-binding acids into tumor-derived peptides would increase the binding affinity of the peptides for HLA-A2 molecules (compared to wild type tumor peptide), resulting in activation of CTL specific for wild type tumor peptide. Altered peptide ligands (APL) were rationally designed for two tumor antigens, gp100 and Her-2/neu. Amino acid modifications were introduced into immunodominant, HLA-A*0201-binding nonamer peptides, gp100 (ITDQVPFSV, residues 209--217) and E75 (KIFGSLAFL, residues 369--377). Tumor APL were evaluated for HLA-A*0201 binding affinity and the ability to activate CTL specific for wild type tumor peptide. The work presented here demonstrates that APL with increased affinities for HLA molecules compared to wild type peptide stimulate CTL specific for wild type peptide from both cancer patients and normal HLA-A*0201 donors. These findings contribute to the development of peptide vaccines for immunotherapeutic treatment modalities.
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Hakenberg, Oliver W., P. Franke, Michael Fröhner, Andreas Manseck, and Manfred Wirth. "The Value of Conventional Urine Cytology in the Diagnosis of Residual Tumour after Transurethral Resection of Bladder Carcinomas." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-135153.
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Background: Transurethral resection leads to characteristic histological changes of tissue repair (’TUR cystitis‘), which also cause non-specific cytological changes. The aim of this study was to investigate the diagnostic sensitivity and specificity of conventional exfoliative urinary cytology in diagnosing residual urothelial carcinoma after differential transurethral resection. Patients and Methods: 417 urinary cytology specimens of all 374 patients undergoing primary (n = 326) or secondary (n = 91) transurethral resection of urothelial carcinoma of the bladder at our institution between June 1996 and December 1997 were examined. The cytology specimens were stained according to Papanicolaou’s method. The sensitivity and specificity of the cytologic diagnosis and of the tumour grading were compared with histological findings. Results: The overall sensitivity of urine cytology in tumour detection was 77.6% for primary lesions and 74.5% in the detection of residual carcinoma after transurethral resection. The diagnostic specificity was 77% and 84.3% respectively. The degree of sensitivity was dependent on tumour grade and was lower for well differentiated tumours. After transurethral resection, the sensitivity for grade 1 residual tumours was 11%, whereas it was 54% for grade 1 tumours before primary transurethral resection. Conclusions: The inflammatory changes following transurethral resection of primary bladder carcinoma cause reactive cytologic changes that make the diagnosis of well differentiated residual carcinoma more difficult. However, urinary cytology after transurethral resection has the same diagnostic accuracy for medium and poorly differentiated tumours as before primary resection and thus remains a very useful diagnostic toolHintergrund: Transurethrale Resektionen von Blasentumoren führen zu histologischen Veränderungen («TUR Zystitis») im Sinne regenerativer Veränderungen, welche urinzytologisch zu diagnostischen Fehleinschätzungen führen können. Das Ziel unserer Untersuchung war der Vergleich der diagnostischen Sensitivität und Spezifität der Urinzytologie vor transurethraler Resektion mit der bei der Diagnose von Residualtumoren nach transurethraler Resektion. Patienten und Methoden: Untersucht wurden 417 urinzytologische Präparate von allen 374 Patienten, die in unserer Einrichtung zwischen Juni 1996 und Dezember 1997 einer primären (n = 326) oder sekundären (n = 91) transurethralen Resektion von Urothelkarzinomen der Harnblase unterzogen wurden. Die zytologischen Präparate wurden nach Papanicolaou gefärbt. Sensitivität und Spezifität der zytologischen Diagnostik und des Tumorgradings wurden mit den histologischen Befunden verglichen. Ergebnisse: Die Sensitivität der Urinzytologie in der primären Tumorerkennung lag bei 77,6% und die für die Diagnose von Residualtumoren nach transurethraler Resektion bei 74,5%. Die diagnostische Spezifität lag bei 77% bzw. 84,3%. Die Sensitivität war abhängig vom Differenzierungsgrad der Urothelkarzinome und war bei gut differenzierten Tumoren am niedrigsten. Nach transurethraler Resektion betrug die Sensitivität der zytologischen Diagnose für G1-Residualtumore lediglich 11%, während sie für G1-Primärtumore bei 54% lag. Schlußfolgerungen: Die entzündlichenVeränderungen nach transurethraler Resektion verursachen Veränderungen exfoliierter Urothelzellen, welche die zytologische Diagnose von residualen G1-Tumoren erschweren. Die Diagnose mäßig und schlecht differenzierter residualer Urothelkarzinome nach transurethraler Resektion hat dagegen die gleiche Sensitivität und Spezifität wie die bei primärer Untersuchung, so daß die Urinzytologie auch bei der Diagnose von Residualtumoren ein wertvolles diagnostisches Verfahren darstellt
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Hakenberg, Oliver W., P. Franke, Michael Fröhner, Andreas Manseck, and Manfred Wirth. "The Value of Conventional Urine Cytology in the Diagnosis of Residual Tumour after Transurethral Resection of Bladder Carcinomas." Karger, 2000. https://tud.qucosa.de/id/qucosa%3A27624.
Full textAbstract:
Background: Transurethral resection leads to characteristic histological changes of tissue repair (’TUR cystitis‘), which also cause non-specific cytological changes. The aim of this study was to investigate the diagnostic sensitivity and specificity of conventional exfoliative urinary cytology in diagnosing residual urothelial carcinoma after differential transurethral resection. Patients and Methods: 417 urinary cytology specimens of all 374 patients undergoing primary (n = 326) or secondary (n = 91) transurethral resection of urothelial carcinoma of the bladder at our institution between June 1996 and December 1997 were examined. The cytology specimens were stained according to Papanicolaou’s method. The sensitivity and specificity of the cytologic diagnosis and of the tumour grading were compared with histological findings. Results: The overall sensitivity of urine cytology in tumour detection was 77.6% for primary lesions and 74.5% in the detection of residual carcinoma after transurethral resection. The diagnostic specificity was 77% and 84.3% respectively. The degree of sensitivity was dependent on tumour grade and was lower for well differentiated tumours. After transurethral resection, the sensitivity for grade 1 residual tumours was 11%, whereas it was 54% for grade 1 tumours before primary transurethral resection. Conclusions: The inflammatory changes following transurethral resection of primary bladder carcinoma cause reactive cytologic changes that make the diagnosis of well differentiated residual carcinoma more difficult. However, urinary cytology after transurethral resection has the same diagnostic accuracy for medium and poorly differentiated tumours as before primary resection and thus remains a very useful diagnostic tool.Hintergrund: Transurethrale Resektionen von Blasentumoren führen zu histologischen Veränderungen («TUR Zystitis») im Sinne regenerativer Veränderungen, welche urinzytologisch zu diagnostischen Fehleinschätzungen führen können. Das Ziel unserer Untersuchung war der Vergleich der diagnostischen Sensitivität und Spezifität der Urinzytologie vor transurethraler Resektion mit der bei der Diagnose von Residualtumoren nach transurethraler Resektion. Patienten und Methoden: Untersucht wurden 417 urinzytologische Präparate von allen 374 Patienten, die in unserer Einrichtung zwischen Juni 1996 und Dezember 1997 einer primären (n = 326) oder sekundären (n = 91) transurethralen Resektion von Urothelkarzinomen der Harnblase unterzogen wurden. Die zytologischen Präparate wurden nach Papanicolaou gefärbt. Sensitivität und Spezifität der zytologischen Diagnostik und des Tumorgradings wurden mit den histologischen Befunden verglichen. Ergebnisse: Die Sensitivität der Urinzytologie in der primären Tumorerkennung lag bei 77,6% und die für die Diagnose von Residualtumoren nach transurethraler Resektion bei 74,5%. Die diagnostische Spezifität lag bei 77% bzw. 84,3%. Die Sensitivität war abhängig vom Differenzierungsgrad der Urothelkarzinome und war bei gut differenzierten Tumoren am niedrigsten. Nach transurethraler Resektion betrug die Sensitivität der zytologischen Diagnose für G1-Residualtumore lediglich 11%, während sie für G1-Primärtumore bei 54% lag. Schlußfolgerungen: Die entzündlichenVeränderungen nach transurethraler Resektion verursachen Veränderungen exfoliierter Urothelzellen, welche die zytologische Diagnose von residualen G1-Tumoren erschweren. Die Diagnose mäßig und schlecht differenzierter residualer Urothelkarzinome nach transurethraler Resektion hat dagegen die gleiche Sensitivität und Spezifität wie die bei primärer Untersuchung, so daß die Urinzytologie auch bei der Diagnose von Residualtumoren ein wertvolles diagnostisches Verfahren darstellt.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Richter, Daniel [Verfasser], Marco [Akademischer Betreuer] Durante, and Gerhard [Akademischer Betreuer] Kraft. "Treatment planning for tumors with residual motion in scanned ion beam therapy / Daniel Richter. Betreuer: Marco Durante ; Gerhard Kraft." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2012. http://d-nb.info/1106117255/34.
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Dang, Raymond K. B. "Molecular detection of minimal residual disease in breast cancer and leukaemias using p53 tumour suppressor gene mutations as markers." Thesis, University of Edinburgh, 2000. http://hdl.handle.net/1842/22132.
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The use of peripheral blood progenitor cell (PBPC) transplantation is an important advance in the treatment of breast cancer and acute leukaemias, and these conditions are among the commonest indications for this procedure. Inevitably, there is concern that malignant cells may contaminate progenitor cell harvests and be re-infused during transplantation and cause disease relapse. Various methods are available for the detection of such minimal residual disease (MRD), and the key aim of this project was to evaluate the feasibility of using a tumour-specific marker, namely mutations within the p53 gene, for this purpose. This provided a useful model to assess the feasibility of using subtle genetic changes to detect MRD within PBPC harvests from patients with malignant diseases. The first step involved the use of denaturing gradient gel electrophoresis (DGGE) to screen original tumour tissues for mutations to be used as disease markers, in 5 individually PCR-amplified DNA fragments (A to E) covering exons 5 to 8 of p53. The technique was first optimised using cell lines known to contain p53 mutations in each fragment. Optimisation was performed with respect to electrophoresis temperature, time, voltage and polyacrylamide cross-linker. The sensitivity of DGGE in detecting a mutation in a mixed cell population was determined by diluting tumour cells in wild type (WT) cells. Although the presence of a mutation could be demonstrated when tumour cells occurred as 5% of total, a representation of at least 40% was required for the mutant homoduplex to be isolated for sequencing. Clinical samples studied were from 51 breast cancer patients, 38 of whom had metastatic disease or at high risk of metastasis, and 13 had high risk stage II/III disease randomised in a clinical study investigating PBPC transplantation and adjuvant therapy, and from 29 patients with acute leukaemias. A positive result was obtained in 14 of 51 primary breast cancer patients (1 was positive in 2 different fragments) and 3 of 29 patients with acute leukaemias.
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Araujo, Robyn Patrice. "Mathematical modelling of mechanical stresses and vascular collapse in solid tumours." Thesis, Queensland University of Technology, 2003. https://eprints.qut.edu.au/37156/6/37156_Digitised_Thesis.pdf.
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Nakamura, Kenichi. "Determination of the optimal cutoff percentage of residual tumors to define the pathological response rate for gastric cancer treated with preoperative therapy (JCOG1004-A)." Kyoto University, 2016. http://hdl.handle.net/2433/217718.
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Trilla, Herrera Enrique. "Estudio de factores pronósticos predictivos de la presencia de fibronecrosis en las masas residuales postquimioterapia en tumores de extirpe germinal." Doctoral thesis, Universitat de Barcelona, 2004. http://hdl.handle.net/10803/1223.
Full textAbstract:
HIPÓTESIS Y OBJETIVOS: La presencia de masas residuales postquimioterapia es una circunstancia relativamente frecuente (30-60%) en pacientes afectos de tumores germinales testiculares (TGT) metastásicos tras la finalización de la quimioterapia de inducción y en ausencia de elevación de marcadores tumorales. La resección quirúrgica constituye el tratamiento comúnmente aceptado en estos casos y en especial en los TGT no seminomatosos. La histología de dichas masas revelará hasta en un 40% la presencia de fibronecrosis, teratoma maduro en un 40% y tumor germinal viable en el 20% restante. La detección de tumor germinal viable en las masas resecadas es sumamente útil pues su presencia determinará la aplicación de nuevos ciclos de quimioterapia adyuvante. Así mismo la exéresis del teratoma, dado su carácter quimio-radio resistente y su potencial capacidad de crecimiento (síndrome del "Growing teratoma") determina que la cirugía sea la única alternativa en éstos casos. Por tanto y, a diferencia de las dos situaciones anteriores, la exéresis de masas residuales que contengan únicamente el componente histológico de fibronecrosis no va a tener valor terapéutico alguno y obliga a someter al paciente a una cirugía compleja con potenciales complicaciones y secuelas (disfunción eyaculatoria).
Por tanto nuestro estudio se propone identificar predictores objetivos de la histología de fibronecrosis en las masas residuales postquimioterapia que nos permitan omitir, en casos seleccionados,la práctica de la cirugía retroperitoneal. Se analizan la asociación y el valor predictivo global de las variables histológicas del tumor primario, variables clínico-biológicas y variables radiológicas respecto a la presencia de fibrosis-necrosis en las masas residuales postquimioterapia. Así mismo se analiza la morbilidad global de la serie estudiada.
MATERIAL Y MÉTODO:
Se realiza un estudio descriptivo y retrospectivo de una cohorte de 49 pacientes afectos de tumores germinales (46 testiculares y 3 extragonadales de localización retroperitoneal) con masa residual retroperitoneal postquimioterapia.pacientes afectos de TGT con masa residual de localización retroperitoneal. Se valoran diferentes variables histológicas (composición histológica cuantitativa, volumen tumoral, permeación linfo-vascular e invasión de estructuras testiculares), clínico-biológicas (edad, lateralidad, antecedente de maldescenso testicular, niveles prequimioterapia de alfa-feto proteína, beta-coriogonadotropina y lactato deshidrogenasa) y radiológicas (variaciones dimensionales y densitométricas en las masa residuales durante la aplicación de la quimioterapia). Se realiza un estudio descriptivo completo y un análisis estadístico uni y multivariante de los resultados obtenidos.
CONCLUSIONES:
La ausencia de elementos teratomatosos en el tumor primario se asoció a una mayor probabilidad de encontrar fibronecrosis en las masas residuales postquimioterapia en nuestra serie. La presencia del componente de teratoma en el tumor primario se correlaciona con una elevada probabilidad de contener dicho componente en las masas residuales. Los niveles de alfa-feto proteína, beta-coriogonadotropina y lactato deshidrogenasa previos a la cirugía retroperitoneal así como el resto de variables clínicas evaluadas no han resultado predictores de la histología de fibronecrosis en las masas residuales postquimioterapia en nuestra serie. Las masas residuales que presentan reducciones de volumen superiores o iguales al 90 % durante la administración de la quimioterapia estándar se asocian a una mayor probabilidad de contener fibronecrosis. Los enfermos que presentan asociación de elementos de teratoma maduro más reducciones volumétricas superiores o iguales al 90 % tras la quimioterapia, tienen más probabilidad de tener fibronecrosis en las masas residuales, si bien la probabilidad no es lo suficientemente elevada como para evitar la cirugía. La tasa global de complicaciones y mortalidad han sido bajas y equiparables a las series publicadas.
OBJECTIVE:
Up to 60% of patients with disseminated advanced germ cell tumors will have residual masses after completion of chemotherapy. Surgical resection is a generally accepted treatment for residual retroperitoneal masses after chemotherapy for metastatic germ cell tumors, particularly in testicular nonseminomatous germ cell tumors. After resection may reveal fibrosis/necrosis, diferenciated teratoma or viable cancer cells. The objective of surgery is to document the presence or absence of residual viable malignancy and to remove teratomatous components. Patients with complete necrotic or fibrosis residual tumor do not need surgical removal of the residual masses. Efforts have been made to identify these patients with a very high likelihood of fibrosis/necrosis to avoid retroperitoneal surgery.
PATIENTS AND METHODS:
The data set consisted of 49 patients with metastatic germ cell tumors (46 metastasic testicular cancer and 3 extragonadal retroperitoneal tumors) with postchemotherapy retroperitoneal residual masses. We evaluated histological primary tumor parameters, radiological characteristic of residual masses (changes in size and density during the course of chemotherapy) and clinical parameters like tumors markers (AFP, B-HCG and LDH) pre-chemotherapy, and all were correlated with the presence/absence of fibrosis/necrosis at retroperitoneal surgery.
CONCLUSIONS:
Patients with absence of teratomatous components in the primary tumor might be asociated with a very high likelihood of fibrosis/necrosis in postchemotherapy residual masses. Teratoma components in primary tumor was correlated with a high likelihood of teratoma in retroperitoneal surgical specimens. Prechemotherapy tumor marker levels (AFP, B-HCG and LDH) and other clinical parameters evaluated were not predictors of fibrosis/necrosis in postchemotherapy residual masses. A tumor shrinkage ≥ 90% during the course of medical treatment was correlated with a high likelihood of fibrosis/necrosis in postchemotherapy residual masses. Patients with asociation of tumor shrinkage ≥ 90% during the course of medical treatment and absence of teratomatous components in the primary tumor might be asociated with a very high likelihood of fibrosis/necrosis in postchemotherapy residual masses. Finally, morbidity was low and similar to other previous studies.
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Hamy, Anne-Sophie. "Identification of Factors Predicting Sensitivity or Resistance to Neoadjuvant Chemotherapy in Breast Cancer Neoadjuvant treatment : the future of patients with breast cancer Neoadjuvant treatment for intermediate/high-risk HER2-positive and triple-negative breast cancers: no longer an “option” but an ethical obligation Long-term outcome of the REMAGUS 02 trial, a multicenter randomised phase II trial in locally advanced breast cancer patients treated with neoadjuvant chemotherapy with or without celecoxib or trastuzumab according to HER2 status BIRC5 (survivin) : a pejorative prognostic marker in stage II/III breast cancer with no response to neoadjuvant chemotherapy Beyond Axillary Lymph Node Metastasis, BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy Pathological complete response and prognosis after neoadjuvant chemotherapy for HER2-positive breast cancers before and after trastuzumab era: results from a real-life cohort The presence of an in situ component on pre-treatment biopsy is not associated with response to neoadjuvant chemotherapy for breast cancer Chemosensitivity, tumor infiltrating lymphocytes (TILs), and survival of postpartum PABC patients treated by neoadjuvant chemotherapy Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma New insight for pharmacogenomics studies from the transcriptional analysis of two large-scale cancer cell line panels Biological network-driven gene selection identifies a stromal immune module as a key determinant of triple-negative breast carcinoma prognosis A Stromal Immune Module Correlated with the Response to Neoadjuvant Chemotherapy, Prognosis and Lymphocyte Infiltration in HER2-Positive Breast Carcinoma Is Inversely Correlated with Hormonal Pathways Stromal lymphocyte infiltration after neoadjuvant chemotherapy is associated with aggressive residual disease and lower disease-free survival in HER2-positive breast cancer Interaction between molecular subtypes, stromal immune infiltration before and after treatment in breast cancer patients treated with neoadjuvant chemotherapy COX2/PTGS2 Expression Is Predictive of Response to Neoadjuvant Celecoxib in HER2-negative Breast Cancer Patients Celecoxib With Neoadjuvant Chemotherapy for Breast Cancer Might Worsen Outcomes Differentially by COX-2 Expression and ER Status: Exploratory Analysis of the REMAGUS02 Trial Comedications influence immune infiltration and pathological response to neoadjuvant chemotherapy in breast cancer." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS129.
Full textAbstract:
La chimiothérapie néoadjuvante (CNA) est utilisée dans les cancers du sein agressifs ou localement avancés (CS). Au delà des bénéfices cliniques, elle représente une opportunité pour monitorer in vivo la sensibilité d’une tumeur à un traitement.A partir de l’analyse de sets de données de patients traités par CNA, nous souhaitons identifier des mécanismes associes à la résistance ou sensibilité au traitement. Dans la première partie, nous avons évalué des paramètres, cliniques, anatomopathologiques et transcriptomiques. Nous avons démontré que des éléments non explorés comme la présence d’embols après CNA revêtaient une information pronostique importante. Dans une 2ème partie, nous avons analysé l’impact de l’infiltrat immunitaire dans le cancer du sein, et avons décrit les changements observés entre des échantillons avant et après CNA. Nous avons montré que l’impact pronostique des TILs était différent avant et après CNA, et était opposé dans les CS triple négatif ou HER2-positif. Finalement, nous avons analysé l’impact des comédications pendant la CNA. Nous avons trouvé des effets positifs – via l’augmentation de l’infiltrat immunitaire et la réponse au traitement – et des effets négatifs avec des effets délétères dans certains sous groupes de patients. En conclusion, la situation néoadjuvante représente une plateforme pour générer et potentiellement valider des hypothèses de recherche. La mise à disposition de jeux de données de patients traités par chimiothérapie néoadjuvante constituerait une ressource majeure pour accélérer la recherche contre le cancer du seinNeoadjuvant chemotherapy (NAC i.e. chemotherapy before surgery) is increasingly being used for aggressive or locally advanced breast cancer (BCs). Beyond clinical benefits, it represents an opportunity to monitor in vivo sensitivity to treatment. Based on the analysis of datasets of BCs patients treated with NAC, we aimed at identifying mechanisms associated with resistance or sensitivity to treatment.In the first part, we evaluated biological, clinical, pathological and transcriptomic patterns. We demonstrated that unexplored pathological features such as post-NAC lymphovascular invasion may carried an important prognostic information.In a second part, we analyzed impact of imune infiltration in BC and we described extensively the changes of tumor infiltrating lymphocytes (TILs) between pre and post-NAC samples. We showed that the prognostic impact of TILs was different before and after NAC, and was opposite in TNBC and HER2-positive BCs. Finally, we investigated the impact of comedications use during NAC. We found both positive effects - while enhancing immune infiltration and response to treatment - and negative effects with deleterisous oncologic outcomes in specific patients subgroups. In conclusion, the neoadjuvant setting represents a platform to both generate and potentially validate research hypotheses aiming at increasing the efficacy of treatment. The public release of real-life datasets of BC patients treated with NAC would represent a major resource to accelerate BC research
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Chen, Yu-Hsiang. "Multi-Modality Plasma-Based Detection of Minimal Residual Disease in Triple-Negative Breast Cancer." Diss., 2019. http://hdl.handle.net/1805/20202.
Full textAbstract:
Indiana University-Purdue University Indianapolis (IUPUI)Triple-negative breast cancers (TNBCs) are pathologically defined by the absence of estrogen, progesterone, and HER2 receptors. Compared to other breast cancers, TNBC has a relatively high mortality. In addition, TNBC patients are more likely to relapse in the first few years after treatment, and experiencing a shorter median time from recurrence to death. Detecting the presence of tumor in patients who are technically “disease-free” after neoadjuvant chemotherapy and surgery as early as possible might be able to predict recurrence of patients, and then provide timely intervention for additional therapy. To this end, I applied the analysis of “liquid biopsies” for early detection of minimal residual disease (MRD) on early-stage TNBC patients using next-generation sequencing. For the first part of this study, I focused on detecting circulating tumor DNA (ctDNA) from TNBC patients after neoadjuvant chemotherapy and surgery. First, patient-specific somatic mutations were identified by sequencing primary tumors. From these data, 82% of the patients had at least one TP53 mutation, followed by 16% of the patients having at least one PIK3CA mutation. Next, I sequenced matched plasma samples collected after surgery to identify ctDNA with the same mutations. I observed that by detecting corresponding ctDNA I was able to predict rapid recurrence, but not distant recurrence. To increase the sensitivity of MRD detection, in the second part I developed a strategy to co-detect ctDNA along with circulating tumor RNA (ctRNA). An advantage of ctRNA is its active release into the circulation from living cancer cells. Preliminary data showed that more mutant molecules were identified after incorporating ctRNA with ctDNA detection in a metastatic breast cancer setting. A validation study in early-stage TNBC is in progress. In summary, my study suggests that co-detection of ctDNA and ctRNA could be a potential solution for the early detection of disease recurrence.
2021-08-05
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Bielčiková, Zuzana. "Cirkulující nádorové buňky u pacientek s karcinomem prsu." Doctoral thesis, 2017. http://www.nusl.cz/ntk/nusl-370957.
Full textAbstract:
Circulating tumor cells (CTCs) represent a systemic phase of the localised cancer disease. They can be distinguished and enriched from the peripheral blood and so from the surrounding leukocytes by either physical properties (e.g., density and size) or biological properties (e.g., expression of epithelial proteins such as EpCAM or cytokeratins) and are usually further characterized by immunostaining or RT-PCR assays. Selecting patients with the risk of disease relaps at the time of diagnosis is crucial for clinicians in deciding who should, and who should not, receive adjuvant chemotherapy. We know that CTCs are strong prognostic factor in patients with metastatic as well as localized breast cancer (BC). It is also known that the prognostic power of circulating tumor cells in women with BC is independent from the standard prognostic indicators. Testing of CTCs known recently as "liquid biopsy" could be informative not only as predictor of the disease relapse, but also as the predictor of therapy effectiveness. The clinical use of CTCs must be strictly encouraged by clinical trials results. Monitoring of CTCs in time could zoom in the mechanism of therapy resistance and/or may provide the identification of new druggable targets. The purpose of my work was therefore to assess the CTCs positivity rate...
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Kramarzová, Karolina. "Role genu WT1 a jeho izoforem v hematopoeze a leukemogenezi." Doctoral thesis, 2013. http://www.nusl.cz/ntk/nusl-321451.
Full textAbstract:
61 Summary Wilms' tumor gene 1 (WT1) is highly expressed in acute leukemia and other hematological malignancies. It has been therefore suggested as a potential universal marker of minimal residual disease (MRD), particularly in patients with acute myeloid leukemia (AML). Due to controversial results of some of the studies, the role of WT1 in MRD follow-up and WT1 prognostic significance remain unclear. WT1 protein is produced in more than 36 different isoforms. These variants have distinct, partially overlapping functions and their ratio is supposed to influence the final effect of WT1. However, despite the increasing number of studies, the clinical impact of WT1 and its isoforms in acute leukemia have not yet been elucidated. We established a unique qPCR method to assess the expression pattern of the main 4 WT1 isoforms. Using this method, we determined the ratio of WT1 variants in the samples of patients with AML, myelodysplastic syndrome (MDS) and healthy controls. Our data showed that this pattern can distinguish among particular hematological malignancies, but lacks a prognostic significance. Within our international study group we determined the prognostic significance of total WT1 expression in childhood AML. Based on our results of a large cohort of patients we can conclude that WT1 expression at...
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Richter, Daniel. "Treatment planning for tumors with residual motion in scanned ion beam therapy." Phd thesis, 2012. https://tuprints.ulb.tu-darmstadt.de/3071/1/thesis_dr_2012_09_05_pubweb.pdf.
Full textAbstract:
The treatment of mobile tumors with a scanned ion beam requires dedicated beam delivery and treatment planning
techniques. Interference effects (interplay) between beam and tumor motion can lead to clinically unacceptable dose distributions. Motion mitigation techniques, such as beam gating or irradiation under abdominal compression, can effectively reduce tumor motion but typically do not fully compensate motion-induced dose inhomogeneities. Further mitigation therefore is desirable.
In this work, the dosimetric impact of optimized treatment plan parameters on dose heterogeneities caused by residual tumor motion was investigated. For this purpose, a 4D treatment planning system (4DTPS) for the treatment of moving tumors with a scanned ion beam was developed based on previous efforts at GSI Helmholtz Center for Heavy Ion research (GSI). The system was validated in dedicated experiments, reaching an accuracy of (-1 ± 4)% for the typical beam configuration. The new software enabled extensive experiments, simulations, and treatment planning studies for liver cancer patients. The results show that an enlarged beam spot size can considerably mitigate motion-induced dose inhomogeneities for treatments with respiratory gating and under abdominal compression. Moreover, the 4DTPS allowed 4D dose reconstructions of the first treatments of liver tumors with a scanned ion beam at the Heidelberg Ion-Beam Therapy Center (HIT), revealing a
considerable degradation of the dose coverage in an exemplary case (V95=92.8%).
The 4DTPS is currently used as a basis for further research at GSI and by international collaborators. Results of this work have contributed to the world's first treatments of moving liver tumors with a scanned carbon ion beam at HIT.