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Se realizo un estudio retrospectivo en un total 23 pacientes de cáncer renal con presencia de trombo tumoral en la vena renal atendidos y tratados quirúrgicamente en el Hospital Nacional Edgardo Rebagliatti Martins en el período de 1995 – 2001. El presente trabajo se ha realizado se realizo con el objetivo de conocer los resultados del tratamiento quirúrgico empleado en pacientes con cáncer renal y compromiso por trombo tumoral en la vena renal. Se encontró que el sexo masculino (67%) es el mas afectado en una proporción de 2:1 , la edad mas frecuente es en mayores de 50años (89,4%). Asi mismo se encontró que no existe relación entre el tamaño tumoral y la presencia de compromiso por trombo tumoral en la vena cava, el estadio 3b fue el mas frecuente con 87%. La sobrevida de los pacientes fue a 1 año de 78% y a 5 años de 42% Las complicaciones postoperatorias más frecuentes fueron la infección de herida operatoria (8,7%), neumonia (4,4%). El mayor tiempo de estancia hospitalaria fue de 5 – 7 dias (73,9%). Por los resultados obtenidos vemos que el tratamiento quirúrgico del trombo tumoral en la vena cava por cáncer renal es un tratamiento efectivo y que ofrece a dichos pacientes una mejor sobrevida.

A number of amino acid deprivations have been tested in our laboratory, for the selective eradication of tumour cells in vitro. Withdrawal of the essential amino acid, L-arginine, produced the greatest differential effect on cell proliferation. Normal cells ceased to proliferate and remained viable in G, of the cell cycle, while tumour cells attempted to proliferate in conditions unfavourable for growth, resulting in rapid cell death. Of the six tumour cell lines studied here, four displayed the latter response, while the other two responded in an apparently similar manner to normal cells. Most tumour cells cannot arrest in G1 and are therefore defective in G1 cell cycle control (particularly at the R-point). Analysis of a normal cell line, and the two tumour cell lines that survived arginine deprivation, revealed that cdk4 was downregulated, and the cells were found to possess functional p53. The other four tumour cell lines had dysfunctional p53 and did not downregulate cdk4 upon arginine withdrawal, or relied upon cdk6 for pRb phosphorylation. Arginine is required for histone synthesis during S phase. Histone synthesis in the absence of arginine was compared in a normal and a tumour cell line. Normal fibroblasts synthesise histones to support previously initiated DNA synthesis for the first 24 h of arginine deprivation until the cells reach the R-point. However, HeLa cells cannot synthesise adequate amounts of histone proteins, despite continued DNA synthesis and this is to their detriment. A novel cancer therapy has been developed which exploits the differential response of normal and tumour cells to arginine deprivation. Extracorporeal dialysis was used to reduce blood arginine levels in normal and tumour-bearing dogs. Arginine was successfully reduced to <10 M within the first 12 h of dialysis and this low level was maintained for up to 5 days, but arginine was not reduced for a long enough period of time to see significant tumour regression.

Master of Science - Biology / á-catenin plays a crucial role in cell adhesion. Expression levels of á-catenin have been shown to be decreased in almost all tumours studied. The levels of the epidermal growth factor receptor (EGFR) were shown to be increased in oesophageal squamous cell carcinoma (OSCC) cell lines. á-catenin therefore, may play a part in linking the EGF pathway or other signal transduction pathways, bringing about some of the changes in the OSCC cell lines. The á-catenin gene from five OSCC cell lines was sequenced. Three out of five OSCC cell lines studied were found to harbour mutations. One of the mutations resulted in a change in the amino acid sequence of á-catenin. It was concluded that this alteration may not have affected the functioning of á-catenin. á-catenin was largely expressed at the plasma membrane with some weaker cytoplasm/nuclear expression occurring in all of the OSCC cell lines. Treatment of the OSCC cells with EGF for a 12 hour period resulted in no noticeable change in the expression levels of á- catenin. The results obtained from this study indicated that á-catenin could play a role in signal transduction pathways in the OSCC cell lines.

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O carcinoma escamoso basalóide (CEB) tem sido considerado uma das variantes mais agressivas do carcinoma espinocelular (CEC), acometendo preferencialmente a base da língua, a hipofaringe e a laringe. Um total de 776 carcinomas espinocelulares primários de boca, cirurgicamente excisados entre 1970 e 2000, foram revisados dos arquivos dos Departamentos de Patologia e de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital do Câncer A.C. Camargo. Dezessete CEBs foram identificados e analisados comparativamente a 27 CECs pouco diferenciados com estadiamento e localização equivalentes, quanto ao gênero, idade, raça, tabagismo, etilismo, localização do tumor primário, classificação pelo sistema TNM, tratamento, ocorrência de recidiva tumoral, metástases em linfonodos regionais, a distância e de segundo tumor primário. Analisaram-se a morfologia tumoral e a expressão dos marcadores de proliferação celular e apoptose: PCNA, p53, Bax e Bcl-X. As probabilidades de sobrevida, acumuladas nos períodos de 5 e 10 anos para ambos grupos tumorais, foram calculadas pelo método de Kaplan-Meier, sendo a influência das variáveis clínicas e microscópicas no prognóstico avaliada pelo modelo de regressão de Cox. Morfologicamente, a maioria dos CEBs apresentou configuração tumoral sólida/lobular, disposição em paliçada das células periféricas, espaços císticos, comedonecrose, hialinização intra e peritumoral, disjunção epitélio tumoral/conjuntivo e associação com o componente escamoso. Nenhuma diferença estatística foi detectada entre os grupos CEB e CEC quanto às características demográficas, clínicas e quanto à expressão dos marcadores PCNA, p53 e Bcl-X. O CEB apresentou, comparativamente ao CEC, maior expressão da proteína Bax (p=0,031). As probabilidades de sobrevida global, sobrevida específica e sobrevida livre de doença acumuladas em 5 e 10 anos para os pacientes com CEB e com CEC foram semelhantes. O estadiamento clínico N constituiu um fator prognóstico independente para os pacientes com carcinoma escamoso basalóide e carcinoma espinocelular pouco diferenciado na mucosa bucal. A morfologia tumoral, bem como a expressão dos anticorpos PCNA, p53, Bax e Bcl-X, não foram fatores prognósticos significativos. Estes resultados sugerem que, o CEB e o CEC pouco diferenciado com localização e estadiamento clínico equivalentes na boca, apresentam comportamento clínico e biológico similares. Assim sendo, os pacientes acometidos por estes tumores podem ser submetidos aos mesmos protocolos terapêuticos. / Basaloid squamous cell carcinoma (BSCC) has been recognized as an agressive variant of conventional squamous cell carcinoma (SCC), that arises predominantly in the base of the tongue, hypopharynx and larynx. A total of 776 cases of surgically excised primary oral squamous cell carcinomas from the files of Otohinolaryngology, Head and Neck Surgery, and Pathology Departments of the Cancer Hospital A.C. Camargo, from 1970 to 2000 were retrospectively reviewed. Seventeen cases of BSC were identified and clinically compared with 27 poorly differentiated SCC, with equivalent localization and clinical stage using the following parameters: patient gender, age, race, tobacco and alcohol abuse, stage by the TNM-UICC, localization, lymph nodes involvement, treatment, local and cervical recurrences, distant metastasis and second primary tumors. In addition, we investigated the morphologic features and the expression of proliferative and apoptose markers: PCNA, p53, Bax and Bcl-X. The 5 and 10-year survival rates were calculated by Kaplan-Meier method and the prognostic value of the clinical and microscopic variables was obtained by Cox regression models. The histopathologic analysis showed that BSCC was arranged in solid lobules with abundant comedo-type necrosis, peripheral cells with nuclear palisading, microcystic spaces, stromal and intratumoral hialinosis, tumor/stroma disruption and association with squamous cell component. No statistically significant differences were found between group BSSC and SCC, with regard to clinical features and immunohistochemical reactivity for antibodies PCNA, p53 and Bcl-X. In comparison with SCC, BSCC group showed higher Bax score (p=0,031). The 5-year and 10-year overall survival, cancer specific survival and disease free survival rates showed no significant differences between BSC and SCC groups. The N clinical stage presented an independent prognostic factor for the oral BSC and SCC patients. The histological features and immunohistochemical markers: PCNA, p53, Bax , and Bcl-X, showed no prognostic value. These results suggest that the clinical and biologic course of BSCC is similar to the SCC when clinical stage, site and treatment are matched. In this way, patients presenting these tumors can undergo the same therapeutical protocols.

O adenoma pleomorfo é o tipo de tumor de glândula salivar mais comum e caracteriza-se pela diversidade morfológica. Sua transformação maligna origina os carcinomas ex-adenomas pleomorfos. A molécula ?-catenina participa nas junções celulares e tem sido intensamente associada à carcinogênese das neoplasias humanas, sua atividade metastática e ainda à transformação maligna de adenomas em carcinomas de alguns órgãos como, por exemplo, o estômago. O objetivo deste trabalho foi traçar o perfil clínico e morfológico de todos os adenomas pleomorfos e carcinomas ex-adenomas pleomorfos dos arquivos do Departamento de Estomatologia, Disciplina de Patologia da Faculdade de Odontologia de Bauru - USP compreendendo o período de 1963 até 2003. Em seguida, marcar imunohistoquimicamente e comparar a expressão da ?-catenina em dez glândulas salivares normais, 16 adenomas pleomorfos e três carcinomas ex-adenomas pleomorfos no intuito de observar sua importância na patogênese das lesões e estabelecer correlações com os aspectos microscópicos. A técnica padrão do complexo estreptavidina-biotina-peroxidase foi utilizada para marcação do anticorpo monoclonal ?-catenina. Como resultados, o gênero mais afetado pelo adenoma pleomorfo e carcinoma ex-adenoma pleomorfo foi o feminino, com faixa etária da 3ªa 5ª e 6ª a 7ª décadas de vida, respectivamente. A localização mais freqüente foi no palato para ambos, assim como as características microscópicas representativas foram o estroma fibroialino, as estruturas epiteliais em ilhotas, cordões e ductos para os adenomas e nos carcinomas a metaplasia escamosa, as estruturas ductais, acinares, e as células claras. Observou-se a diminuição estatisticamente significante (p=0,008)da expressão da proteína nos adenomas pleomorfos em comparação às glândulas. Estes resultados sugerem a participação da ?-catenina no desenvolvimento dos adenomas pleomorfos. / Pleomorphic adenomas (PAs) are the most frequent type of salivary gland neoplasms, and their malignant counterpart, the carcinoma in pleomorphic adenomas(CPAs) arises much less commonly. ß-catenin was originally identified on the basis of its association with cadherin adhesion molecules and has been implicated in carcinogenesis because it is frequently absent in human epithelial cancers. ß-catenin also is significantly associated with the invasion and metastasis of carcinoma in the head and neck, esophagus and other organ. In this study we evaluated the morphological and clinical features of all the PAs and CPAs of the archives of the Department of Pathology at the Bauru Dental School of the University of São Paulo since 1963 until 2003. We also realized immunohistochemical analysis in formalinfixed, paraffin embedded specimens of 10 salivary glands, 16 PAs and 3 CPAs by the avidin-biotin-peroxidase complex method. Our results showed that in both lesions the predominant gender was the feminine with age ranging between 3ª and 5ª decades in PA and 6ª and 7ª in CPA. The most commonly glands affected were located in the palate in both types of tumours. The more significant histopathological features in PAs were fibrohialine stroma with epithelial cells organized in clusters and islands or ductal structures. In CPAs, squamous cell carcinomas were originated in all the cases. In the benign counterpart, there was fibrohialine stroma with clear cells, squamous metaplasia, epithelial cells organized in clusters or acinic or ductal structures. All specimens have membranous and cytoplasmic immunostaining. Higher ß-catenin index rates were seen mainly in ductal structures. The loss of expression of the protein in PAs was statistically significant when comparing with salivary glands (p=0,008) and there was cytoplasmic accumulation of the ß-catenin in CPAs. Our experiment showed that the loss of ß-catenin participates in the development of pleomorphic adenoma and that the cytoplasmic accumulation of the molecule takes part in the malignant transformation of the PA into CPA.

by Tim-tak Kwok. / Bibliography: leaves 157-171 / Thesis (M.Phil.)--Chinese University of Hong Kong, 1982

Kwan Suet-ming. / Bibliography: leaves 75-94 / Thesis (M.Ph.)--Chinese University of Hong Kong, 1984

Mok Chi Ho, Samuel. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1987. / Includes bibliographical references.