Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Orientador: Fernandes Denardi / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-07-27T16:22:03Z (GMT). No. of bitstreams: 1 Matheus_WagnerEduardo_M.pdf: 9690090 bytes, checksum: c360620812517ab9e47fde081043552f (MD5) Previous issue date: 2001 / Resumo: o carcinoma urotelial superficial de bexiga é uma neoplasia que apresenta altas taxas de recorrência, se um tratamento complementar não for associado à ressecção completa do tumor. Dentre as alternativas terapêuticas, o BCG intravesicaltem sido o agente mais utilizado, com a finalidade de prevenir recidivas, progressão e aumentar a taxa de sobrevida dos pacientes com tumor de bexiga. o objetivo desse trabalho foi avaliar a eficácia, a longo prazo, da imunoterapia intravesical com BCG, descrever sua toxicidade, analisar fatores de risco do Carcinoma de Células Transicionais (CCT) superficial, tais como: tamanho tumoral, multifocalidade, estadiamento inicial e presença de carcinoma in situ (CIS), e também, correlacionar esses fatores de risco com recidiva tumoral, progressão histológica e realização de cistectomia radical. Nesse estudo, foram analisados 46 pacientes com diagnóstico de CCT superficial de bexiga e que foram submetidos ao tratamento de imunoterapia intravesical com BCG, no período de junho de 1988 a janeiro de 2000. Vinte e dois pacientes (48%) estavam livres de tumor, após o primeiro ciclo de BCG, 37 pacientes (80%), após o segundo ciclo, 41 pacientes (89%), após o terceiro ciclo, e 42 pacientes (91%), após o quarto ciclo. A taxa total de progressão para doença invasiva foi de 9% (4 pacientes). Complicações severas foram observadas em 4 pacientes (9%): 2 casos de hematúria, 1 de orquiepididimite e 1 de febre por mais de 24 horas. A presença de múltiplas lesões tumorais e o tamanho do tumor não apresentaram correlação com o prognóstico desses pacientes. Os tumores que evoluíram para cistectomia radical apresentaram estadiamentos iniciais PTIG2 ou PTIG3. A presença de carcinoma in situ indicou maior chance de recidiva, progressão e evolução para cistectomia radical. A análise dos resultados permitiu as seguintes conclusões: o BCG apresenta uma boa eficácia no tratamento complementar de CCT superficial; o uso do BCG está associado a um baixo índice de complicações severas; os fatores prognósticos mais importantes, na evolução clínica do tumor de bexiga, são estadiamento, grau histológico e carcinoma in situo / Abstract: The bladder superficial urotelial carcinoma is a neoplasy tOOthas shown high recurrence rates if a complementary treatment is not associated to the thorough resection of such tumor. BCG intravesical has been the most applied agent for the prevention either of the recurrences or progression and also for prolonging life of patients suffering ftom bladder cancer. Goal: Analysing effectiveness of the intravesical immunotherapy with BCG and describing its toxicity in the long termo Also analysing the risk factor of superficial CCT, such as: tumor sÍZe, multiplicity, initial staging and presence of cis, establishing a relationship among tumoral recurrences, histological progression and radical cistectomy. Methods and Material: 46 patients with b1adder superficial CCT diagnosis OOve been analysed prospectively and submitted to intravesical uno therapy treatment with BCG, ftom june 1988 to january 2000. Results: The number of patients without a tumor, afier the fust cycIe of BCG was 22 (48%), afier second was 37 (80%), afier third was 41 (89%), afier the forth was 42 (91%) and the total rate of advancing for invasive diasease was 4 (9%). Serious complications OOvebeen observed in 4 patients (9%). Two cases ofhematuria, 1 case of orchiepididymitis and 1 case of fever for over 24 hours. The presence of multiple tumorallesions and sÍZeof tumors OOd no correlation with the prognosis. Tumors which advanced to radical cistectomy showed initial staging pTIG2 or pTIG3. The presence of carcinoma in situ has indicated a greater chance of recurrences, progression and development to radical cistectomy. Conclusion: BCG has showed a good eifectiveness as a complementary treatment for superficial CCT and also a low toxicity. The most significant prognostic factors on the clinicaldevelopment ofbladder tumor are staging, histological grade and carcinoma in situo / Mestrado / Mestre em Cirurgia

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg in fulfilment of the requirements for the degree of Master of Science (Haematology) / The region Ilpl3-pl5 on the short arm of chromosome 11 (lip) has been implicated in the initiation or progression of several human malignancies including the embryonic rhabdomyosarcoma Wilms' tumour, bladder, renal cell and ovarian carcinoma. In this study, Fluorescence In Situ hybridisation (FISH) was used to identify the nature of a chromosome llp+ abnormality present in two ovarian carcinoma cell lines after conventional cytogenetic techniques had failed to elucidate the chromosomal origin of the abnormality. Using whole chromosome library probes, the abnormality in cell line UW0V2 was found to be composed entirely of chromosome 3 material representing the translocation t (3;11) (pl2-14;pl5). In the protein-free subline UW0V2(Sf), the abnormality was found to consist of the complex translocation t (3;8; 11) (pl2-14 ;q22-24;pl5) . It is possible that the involvement of chromosome 8 in this translocation was a cell culture phenomenon. Other structural and numerical abnormalities elucidated with FISH in cell line UW0V2(Sf) included lq+, +5, +7, 7q-, 8q+, +12, +14, 14q+, -15, 16q- and -18. Using FISH together with the gene probe pSB|5 and the CEPH YAC probes 892g9, 785e5, 847al2, 954f4, 966e8 and 845a3, the breakpoint region on chromosome 11 in the _ two cell lines was narrowed down and mapped to the region Ilpl4.3-pl5.1 lying between probes 966e8 (D11S902) and 845a3 (D11S899). This represents a physical distance of approximately 1 Mb. The breakpoint in the two cell lines appeared to involve the same region on llplS.l. In a separate study, three epithelial ovarian tumour specimens and four ascitic fluid specimens were obtained. Tumour specimens T2 and T4 and ascitic fluid specimens AF-1, AF-2 and AF-3 were all cytogenetically uninformative. Cytogenetic analysis of specimen T5 revealed a single clonal abnormality involving a deletion in the region 6q21. Ascitic fluid specimen AF-5 yielded cytogenetically normal metaphases. Both specimens were hypodiploid and revealed a cytogenetically normal chromosome 11. Using FISH and CEPH YAC probes 966e8 and 845a3, no abnormalities were detected in the region llpl4.3-pl5.1 in these two specimens but one cannot rule out the possibility of submicroscopic abnormalities lying within the region between these probes. From this study we speculate that chromosome 6 abnormalities may be important in the initiation of these tumours. From the results obtained with cell lines UW0V2 and UW0V2 (Sf) we speculate that the chromosome 3 abnormalities were an early event in the evolution of these tumours while the chromosome 11 abnormality was a later event. Little is known about the region llpl4.3-pl5.1 and very few disease loci have been assigned to this region, however, we may speculate that this region harbours a tumour suppressor gene or an oncogene whose disruption or activation is critical to the pathophysiology of ovarian carcinoma and other genitourinary cancers. / WHSLYP2017

In the past decades our knowledge concerning breast cancer progression from ductal carcinoma in situ (DCIS) to invasive cancer has grown rapidly. However, molecular factors driving the progression are still largely unknown. In the first study, we investigated tumor evolution in breast cancer by analyzing TP53 mutation status in tumors from various stages of the disease. Presence of the same TP53 mutations in both DCIS and invasive components from the same tumor indicates same cellular origin. The role of mutant TP53 in the progression of breast cancer is less clear and may vary between subtypes. In the second study, we studied the prognosis of basal-like DCIS in a large population-based cohort. Basal-like DCIS was associated with about doubled but not statistically significant risk for local recurrence compared with the other molecular subtypes. Molecular subtype was a better prognostic parameter than histopathological grade. In the third study, we studied markers in primary DCIS in relation to type of recurrence. Interestingly, recurrences after an ER-/HER2+, ER negative or EGFR positive primary DCIS were more often of the in situ type. The molecular subtype ER+/HER2+, FOXA1 positivity and FOXC1 positivity were risk factors for any recurrence. In the fourth study, we proposed a histological classification system for a new entity: neoductgenesis. We also evaluated histologic criteria for neoductgenesis. According to our criteria, good agreements among pathologists were achieved. Neoductgenesis was related to more aggressive tumor biology and to mammographic features. The result indicates potential benefits for women earlier considered having pure DCIS but later diagnosed as breast carcinoma with neoductgenesis, suggesting a need to develop appropriate treatment regiments. Our findings have to be repeated and the relation to prognosis warrants further studies.

Thesis (doctoral)--Lund University, 1992. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1992. / Added t.p. with thesis statement inserted.

<b>Introduction:</b> Almost 7,000 people are diagnosed with ductal carcinoma in situ (DCIS) in the United Kingdom each year, but there remains uncertainty regarding its natural history and optimal management. The aim of this thesis was to evaluate factors contributing to the epidemiology of DCIS and its outcomes. <b>Methods:</b> 1) A cohort study comparing risk factors for DCIS and invasive breast cancer (IBC) using UK Biobank; 2) A cohort study examining the accuracy of preoperative biopsy in DCIS using clinical records from the Netherlands Cancer Institute; 3) A cohort study examining the rate of invasive breast cancer following treatment for screen-detected DCIS in England using the National Health Service Breast Screening Programme (NHSBSP) audit; 4) A methodological study to develop an algorithm to identify invasive breast cancer recurrences, which in the future may used to identify DCIS recurrences, using all relevant routinely collected data stored within Public Health England (PHE). <b>Results:</b> (1) For both DCIS and IBC, postmenopausal BMI was associated with an increased risk of developing disease, and the number of live births was associated with a decreased risk of developing disease. However, the magnitude of the effect differed between DCIS and IBC. The increased risk from postmenopausal BMI &GE;35 kg/m² was larger for DCIS than for IBC (RR 2.35, 95% CI 1.14-4.82), and the trend of reduction in risk with each additional live birth was greater for DCIS than for IBC (p for trend = 0.03). (2) Consideration of mammographic lesion size and the absence of necrosis on biopsy may be helpful in selecting low-risk women for non-operative management of DCIS in the future, as may use of the 9G vacuum-assisted method of biopsy. (3) The cumulative risks of IBC at 5, 10 and 15 years after screen-detected DCIS in England were 3.5%, 7.1%, and 9.4% respectively. Women with clear surgical margins of 1-2 mm had a higher IBC rate than women with clear margins of 5+ mm (RR 1.85, 95% CI 1.20-2.84). Women given breast-conserving surgery (BCS) without radiotherapy had a higher ipsilateral IBC rate than women given BCS with radiotherapy (RR 1.63, 95% CI 1.27-2.10). Women given hormone therapy had a lower rate of any IBC compared with oestrogen receptor (ER) positive women not given hormone therapy (RR 0.76, 95% CI 0.63-0.93). (4) There was good agreement between the number of recurrences indicated by the developed algorithm using routinely collected data sources and the number of recurrences recorded in the test dataset. This finding supports the potential value of compiling recurrence information on a nationwide basis from routinely collected data, for use in future descriptive and epidemiological studies and in follow-up for randomised trials. <b>Conclusions:</b> Using a variety of methods these studies have all succeeded in adding to knowledge about the epidemiology of DCIS. This knowledge can be used to help the future management of women with DCIS. In addition, each of the studies has planned extensions and will continue to contribute further knowledge periodically into the future.

Orientadores : Luiz Carlos Zeferino, Maria Salete Costa Gurgel / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-11-09T15:57:30Z (GMT). No. of bitstreams: 1 Menezes_MarcusViniciusMartinsde_M.pdf: 4462397 bytes, checksum: 19e649c8f79ccdfab39e8019f7d69049 (MD5) Previous issue date: 2002 / Resumo: Este estudo teve como objetivo avaliar a associação entre a expressão das proteínas bcl-2, c-erbB-2 e p53 com o tecido mamário não-neoplásico, o carcinoma ductal in situ e o carcinoma invasivo da mesma mama, através da imuno-histoquímica, e verificar se há um padrão de variação identificável da expressão destas proteínas com a gravidade das lesões. Foram incluídas 56 mulheres que apresentaram na mesma mama carcinoma invasivo associado com carcinoma in situ. Foram utilizados anticorpos monoclocais específicos para bcl-2 (MxH, clone 124, DAKO, código M0887-1, diluição 1:40), c-erbB-2 (RxH, DAKO, código A0485-1, diluição 1 :300) e p53 (MxH, D0-7, DAKO, código M7001-1, diluição 1:100). Foi considerado como expressão positiva quando pelo menos 1% das células corou. A prevalência da expressão da proteína bcl-2 foi de 98%, 75% e 64%, respectivamente, no tecido não-neoplásico, carcinoma in situ e carcinoma invasivo e estas diferenças foram estatisticamente significantes. O odds ratio mostrou que a magnitude destas diferenças foi maior entre o tecido não-neoplásico e o carcinoma in situ. Não houve expressão da proteína c-erbB-2 no tecido não-neoplásico e a prevalência da expressão foi de 68% e 61%, respectivamente, para o carcinoma in situ e carcinoma invasivo. A diferença observada entre o tecido não-neoplásico e carcinoma in situ foi estatisticamente significante. A prevalência da expressão da proteína p53 foi de 2%, 18% e 16%, respectivamente, no tecido não-neoplásico, carcinoma in situ carcinoma invasivo e estas diferenças foram estatisticamente significantes entre os dois primeiros componentes. A expressão da proteína bcl-2 foi mais freqüente no carcinoma in situ do subtipo não-comedo e grau nuclear 1 ou 2 e no carcinoma invasivo grau nuclear 1 ou 2. A expressão da proteína c-erbB-2 foi mais freqüente no carcinoma in situ grau nuclear 3 e a expressão da proteína p53 foi mais freqüente no carcinoma invasivo grau nuclear 3. Sessenta e quatro porcento das mulheres apresentaram expressão da proteína bcl-2 nos três componentes e 23% apresentaram apenas no componente não-neoplásico. Sessenta e um porcento das mulheres apresentaram expressão da proteína cerbB- 2 apenas nos componentes carcinoma in situ e carcinoma invasivo e 32% não apresentaram expressão em nenhum dos componentes. Setenta e oito porcento das mulheres não apresentaram expressão da proteína p53 em nenhum dos componentes e 14% apresentaram apenas nos componentes in situe invasivo. Os resultados deste estudo permitem inferir que os genes Bcl-2, C-erbB-2 e P53 estão envolvidos nas fases mais iniciais da carcinogênese mamária, ou seja, na transformação do dueto não-neoplásico em carcinoma in situ. Uma vez instalada a lesão intra-epitelial, a progressão para a forma invasiva dependeria de outros genes / Abstract: The present study aims to evaluate the association among the expression of the proteins bcl2, c-erbB-2 and p53 and the non-neoplasic mammary tissue, the ductal carcinoma in situ and the invasive carcinoma of the same breast using the immunohistochemical technique. Through this evaluation it aims to find out if there is an identifiable pattern of variation of the expression of these proteins with the gravity of the lesions. Fifty six women were included in this study and ali of them had, in the same breast, the association between invasive carcinoma and carcinoma in situ. lt has been used specific monoclonal antibodies for bcl-2 (MxH, clone 124, DAKO, code M0887-1, dilution 1:40), cerbB- 2 (RxH, DAKO, code A0485-1, dilution 1:300) and p53 (MxH, D0-7, DAKO, code M7001-1, dilution 1:100). Positive expression has been considered when, at least 1% of the cells dyed. The prevalence of the expression of the protein bcl-2 was 98%, 75% and 64%, respectively in the non-neoplasic tissue, carcinoma in situ and invasive carcinoma and these differences were statistically significant. The odds ratio confirmed that the magnitude of these differences was higher between the non-neoplasic tissue and the carcinoma in situ. There was no expression of the protein c-erbB-2 in the non-neoplasic tissue and the prevalence of expression of this protein was 68% and 61%, respectively in carcinoma in situ and invasive carcinoma. The difference found between the non-neoplasic tissue and the carcinoma in situ was statistically significant. The prevalence of expression of protein p-53 was 2%, 18% and 16%, respectively in the non-neoplasic tissue, carcinoma in situ and invasive carcinoma and these differences were statistically significant between the two formers only. The expression of the protein bcl-2 was more frequent in carcinoma in situ noncomedo type, nuclear degrees 1 or 2 and in invasive carcinoma nuclear degrees 1 or 2. The expression of protein c-erbB-2 was more frequent in carcinoma in situ nuclear degree 3 and the expression of protein p53 was more frequent in invasive carcinoma nuclear degree 3. Sixty four per cent of women studied showed expression of protein bcl-2 in ali three components and 23% of women showed it only in the non-neoplasic component. Sixty one per cent of women showed expression of protein c-erbB-2 only in carcinoma in situ and invasive carcinoma and 32% did not show expression at ali. Sixty eight per cent of women did not show expression of protein p53 in none of the components and 14% showed it only in the components 'in situ' and 'invasive'. The results of the present study allow us to conclude that the genes Bcl-2, C-erbB-2 and P53 are linked to the initial stages of mammary carcinogenesis, in other words, they are linked to the transformation of the non-neoplasic duct in carcinoma in situ. Once the intra-epithelial lesion has started, the progression to invasive form would depend on other genes / Mestrado / Tocoginecologia / Mestre em Tocoginecologia

Orientador: Liliana Aparecida Lucci De Angelo Andrade / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-07-20T16:42:37Z (GMT). No. of bitstreams: 1 Marques_Terezinha_M.pdf: 5257490 bytes, checksum: a7ce79d4f8daa915ba77c12058973de4 (MD5) Previous issue date: 1995 / Resumo: Metaplasia tubária (MT) é uma lesão de natureza benigna que pode oferecer dificuldade para o diagnóstico diferencial com adenocarcinoma in situ (AIS) na endocérvice. Sua correta caracterização e identificação evita condutas terapêuticas inadequadas. Selecionamos IS casos de MT e 16 casos de AIS, morfologicamente característicos com o método hematoxilina-eosina. A seguir, examinamos por meio de reações histoquímicas e imuno-Mstoquímicas, para avaliar seu comportamento e tentar contribuir para o diagnóstico diferencial- Utilizamos colorações para mucinas, Alcian blue (AB), mucicarmim (MC), PAS e PAS com diastase (PASd), além de anticorpos anti-antígeno cárcino-embrionário (CEA) e anri-vimentína (VIM). Os métodos histoquírnicos não demonstraram diferença significativa entre as duas lesões. Apesar do CEA ser mais freqüente nos casos de adenocarcinoma in situ, o papel da vimentina foi decisivo no diagnóstico diferencial, porque resultou positiva em 78% dos casos de metaplasia tubária e negativa em todos os casos de adenocarcinoma in situ / Abstract: Endocervical tubal metaplasia, a benign lesion, is known to be frequently misdiagnosed as adenocarcinoma in situ. Its correct identification is needed in order to avoid inadequate managements. We selected 18 cases of endocervical tubal metaplasia and 16 of adenocarcinoma in situ. Only specimens that had morphologic appearences typical for either tubal metaplasia or adenocarcinoma in situ were chosen. All cases were analysed by hematoxilin-eosin, stains for mucin, Alcian blue pH 2.5, mucicarmine, PAS and PAS diastase, and submitted to immunoperoxidase reaction for carcinoembryonic antigen and vimentin. Statistical analysis demonstrated no signifficant difference in the reactions for mucins between the lesions. Whereas CEA was more frequently positive in AIS than in TM cases, VIM was negative in all cases of AIS and positive in 78% of TM cases and was therefore considered more useful for the differential diagnosis / Mestrado / Mestre em Ciências Médicas

Made available in DSpace on 2014-06-12T23:01:51Z (GMT). No. of bitstreams: 2 arquivo4255_1.pdf: 4065278 bytes, checksum: c0dabbd5dc05e703429eae598cc70d8d (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2009 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / As displasias da laringe são lesões precursoras do carcinoma escamocelular invasivo e constituem lesões pouco comuns, pois, a maior parte dos casos é diagnosticada como carcinoma invasor. Freqüentemente, utilizam-se os critérios de cérvix uterina para graduação das displasias na prega vocal. Todavia, existem diferenças histopatológicas, patogênicas e epidemiológicas entre as lesões intraepiteliais cervicais e laríngeas. O epitélio de transição na prega vocal pode ocasionar problemas diagnósticos. Os autores procuram caracterizar as displasias acentuadas/carcinoma in situ da prega vocal quanto aos aspectos histopatológicos, morfométricos (área do epitélio e diâmetro dos núcleos) e índice proliferativo (Ki-67), comparando estes dados com os obtidos no epitélio escamoso normal e de transição. Dentre 1400 casos de carcinoma de laringe (1994 a 2006), 5 casos (0,35%) de displasia acentuada/carcinoma in situ foram estudados. O grupo controle constituiu-se de dois indivíduos masculinos, não tabagistas e não etilistas de 52 e 78 anos. Observaram-se nos pacientes com displasia predomínio do sexo masculino, na 6º década e associação com tabagismo e etilismo. Comparando-se o epitélio displásico com o epitélio normal e de transição verificou-se que foi maior a área ocupada pelo primeiro, bem como o diâmetro do núcleo das células displásicas. O diâmetro dos núcleos por camada mostrou diferenças significativas no epitélio escamoso normal, mas não no epitélio displásico e de transição. O índice proliferativo foi maior no epitélio displásico que no escamoso normal e de transição com núcleos corados na camada basal/parabasal no epitélio escamoso normal e de transição e em todos os níveis no epitélio displásico