O carcinoma verrucoso (CV), é considerado uma variante do carcinoma espinocelular (CEC) bem diferenciado, que se caracteriza por sua baixa agressividade e bom prognóstico e acomete principalmente a laringe e a boca. Um total de 1613 carcinomas espinocelulares primários de boca, cirurgicamente excisados entre 1980 e 2000, foram revisados dos arquivos dos Departamentos de Patologia e Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital do Câncer A.C. Camargo. Dez CVs foram identificados e analisados 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 também a expressão imuno-histoquímica e a hipermetilação da região promotora do gene da E-caderina, e os valores obtidos foram comparados com carcinomas espinocelulares bem diferenciados de boca sem (CEC-pN0) e com (CEC-pN+) comprometimento linfonodal. As probabilidades de sobrevidas, acumuladas nos períodos de cinco e dez anos para os grupos tumorais, foram calculadas pelo método de Kaplan-Meier. Os resultados demonstraram uma predileção dos CVs por pacientes do gênero masculino, tabagistas e etilistas, com idade superior a 67 anos, ocorrendo principalmente no lábio inferior. O tempo de história clínica foi maior que 16 meses e nenhum paciente com CV foi submetido à radioterapia e/ou quimioterapia pós-operatória. Microscopicamente as lesões eram bem características com intensa queratinização, padrão de invasão compressivo, pouca atipia e margens cirúrgicas livres. Uma maior expressão imunohistoquímica da E-caderina foi verificada nos carcinomas verrucosos quando comparados aos grupos de CEC-pN0 e CEC-pN+, sendo a diferença entre os grupos estatisticamente significativa (p= 0,016). O perfil de metilação do gene da E-caderina foi estatisticamente semelhante (p= 0,975) e superior a 50% nos três grupos de carcinomas de boca avaliados (CV, CEC-pN0 e CEC-pN+). A sobrevida global do grupo CV foi superior aos grupos de CECs bem diferenciados tanto em cinco quanto em dez anos (p= 0,012). Com base nestes resultados concluímos que o carcinoma verrucoso bucal apresenta um comportamento clínico e biológico relativo à expressão da E-caderina, mais favorável quando comparado carcinoma espinocelular bem diferenciado. A presença da hipermetilação do gene da E-caderina em neoplasias malignas com baixo potencial invasivo e metastático como o CV sugere que este evento epigenético ocorre precocemente nos mecanismos envolvidos na progressão tumoral. / Verrucous carcinoma (VC), is considered a variant of well differentiated squamous cell carcinoma, that is characterized by its low aggressiveness and good prognostic and arises most frequently in the larynx and oral cavity. A total of 1613 cases of surgically excised primary oral squamous cell carcinoma from the files of Otohinolaryngology, Head and Neck Surgery, and Pathology Departments of the A.C. Camargo Cancer Hospital, from 1980 to 2000, were retrospectively reviewed. Ten cases of CVs were identified and analyzed as for the gender, age, race, tobacco and alcohol abuse, localization, stage by the TNM-UICC, treatment, lymph nodes involvement, local and cervical recurrences, distant metastasis and second primary tumors. In addition, we investigated the immunohistochemical expression of the Ecadherin and the promoter region hypermethylation of the E-cadherin gene of VCs comparing with oral well differentiated squamous cell carcinoma without (SCC-pN0) and with (SCCpN+) lymph nodes involvement. The 5 and 10-year survival rates were calculated by Kaplan- Meyer method. The results demonstrated a predilection of VCs for patients of the masculine gender, with positive tobacco and alcohol history, with age older than 67 years and arise predominantly in the inferior lip. The clinical history was longer than 16 months and no patient with VC was submitted the radiotherapy and/or chemotherapy postoperative. The histopathologic analysis showed a heavily keratinized lesion with compressive invasion pattern, little atypia and free surgical margins. In comparison with SCC-pN0 and SCC-pN+, verrucous carcinoma showed a higher immunohistochemical expression of the E-cadherin score (p= 0,016). More than 50% of the tumors showed the hypermethylation of the Ecadherin gene and no statistically significant differences (p= 0,975) were found among VC, SCC-pN0 and SCC-pN+ groups. Verrucous carcinoma of the oral cavity had significantly better 5-year and 10-year overall survival rates than the well differentiated squamous cell carcinomas (p= 0,012). These results permit to conclude that the oral verrucous carcinoma presents more favorable clinical and biological behavior related to the immunohistochemical expression of the E-cadherin when compared with well differentiated squamous cell carcinoma. The presence of the hypermethylation of the E-cadherin gene in the malignant tumors with lower potential invasive and metastatic, such as VC, suggests that this epigenetic event happens early in the mechanisms involved in the tumoral progression.

O carcinoma verrucoso (CV), é considerado uma variante do carcinoma espinocelular (CEC) bem diferenciado, que se caracteriza por sua baixa agressividade e bom prognóstico e acomete principalmente a laringe e a boca. Um total de 1613 carcinomas espinocelulares primários de boca, cirurgicamente excisados entre 1980 e 2000, foram revisados dos arquivos dos Departamentos de Patologia e Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital do Câncer A.C. Camargo. Dez CVs foram identificados e analisados 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 também a expressão imuno-histoquímica e a hipermetilação da região promotora do gene da E-caderina, e os valores obtidos foram comparados com carcinomas espinocelulares bem diferenciados de boca sem (CEC-pN0) e com (CEC-pN+) comprometimento linfonodal. As probabilidades de sobrevidas, acumuladas nos períodos de cinco e dez anos para os grupos tumorais, foram calculadas pelo método de Kaplan-Meier. Os resultados demonstraram uma predileção dos CVs por pacientes do gênero masculino, tabagistas e etilistas, com idade superior a 67 anos, ocorrendo principalmente no lábio inferior. O tempo de história clínica foi maior que 16 meses e nenhum paciente com CV foi submetido à radioterapia e/ou quimioterapia pós-operatória. Microscopicamente as lesões eram bem características com intensa queratinização, padrão de invasão compressivo, pouca atipia e margens cirúrgicas livres. Uma maior expressão imunohistoquímica da E-caderina foi verificada nos carcinomas verrucosos quando comparados aos grupos de CEC-pN0 e CEC-pN+, sendo a diferença entre os grupos estatisticamente significativa (p= 0,016). O perfil de metilação do gene da E-caderina foi estatisticamente semelhante (p= 0,975) e superior a 50% nos três grupos de carcinomas de boca avaliados (CV, CEC-pN0 e CEC-pN+). A sobrevida global do grupo CV foi superior aos grupos de CECs bem diferenciados tanto em cinco quanto em dez anos (p= 0,012). Com base nestes resultados concluímos que o carcinoma verrucoso bucal apresenta um comportamento clínico e biológico relativo à expressão da E-caderina, mais favorável quando comparado carcinoma espinocelular bem diferenciado. A presença da hipermetilação do gene da E-caderina em neoplasias malignas com baixo potencial invasivo e metastático como o CV sugere que este evento epigenético ocorre precocemente nos mecanismos envolvidos na progressão tumoral. / Verrucous carcinoma (VC), is considered a variant of well differentiated squamous cell carcinoma, that is characterized by its low aggressiveness and good prognostic and arises most frequently in the larynx and oral cavity. A total of 1613 cases of surgically excised primary oral squamous cell carcinoma from the files of Otohinolaryngology, Head and Neck Surgery, and Pathology Departments of the A.C. Camargo Cancer Hospital, from 1980 to 2000, were retrospectively reviewed. Ten cases of CVs were identified and analyzed as for the gender, age, race, tobacco and alcohol abuse, localization, stage by the TNM-UICC, treatment, lymph nodes involvement, local and cervical recurrences, distant metastasis and second primary tumors. In addition, we investigated the immunohistochemical expression of the Ecadherin and the promoter region hypermethylation of the E-cadherin gene of VCs comparing with oral well differentiated squamous cell carcinoma without (SCC-pN0) and with (SCCpN+) lymph nodes involvement. The 5 and 10-year survival rates were calculated by Kaplan- Meyer method. The results demonstrated a predilection of VCs for patients of the masculine gender, with positive tobacco and alcohol history, with age older than 67 years and arise predominantly in the inferior lip. The clinical history was longer than 16 months and no patient with VC was submitted the radiotherapy and/or chemotherapy postoperative. The histopathologic analysis showed a heavily keratinized lesion with compressive invasion pattern, little atypia and free surgical margins. In comparison with SCC-pN0 and SCC-pN+, verrucous carcinoma showed a higher immunohistochemical expression of the E-cadherin score (p= 0,016). More than 50% of the tumors showed the hypermethylation of the Ecadherin gene and no statistically significant differences (p= 0,975) were found among VC, SCC-pN0 and SCC-pN+ groups. Verrucous carcinoma of the oral cavity had significantly better 5-year and 10-year overall survival rates than the well differentiated squamous cell carcinomas (p= 0,012). These results permit to conclude that the oral verrucous carcinoma presents more favorable clinical and biological behavior related to the immunohistochemical expression of the E-cadherin when compared with well differentiated squamous cell carcinoma. The presence of the hypermethylation of the E-cadherin gene in the malignant tumors with lower potential invasive and metastatic, such as VC, suggests that this epigenetic event happens early in the mechanisms involved in the tumoral progression.

Inaugural dissertation.--Universität Greifswald.

Note:

Note:

No description available.

A research report submitted to the faculty of Health Sciences University of Witwatersrand, in partial fulfilment for the degree of Master of Medicine (M.Med) Radiation Oncology. Johannesburg 2014 / Background Larynx preservation is the standard recommended treatment approach for cancer of the larynx. We looked at results of patient treated with larynx preserving approach at our institution. Objectives The study objectives included describing the demographics of the population in the study and comparing characteristics and outcomes for patients in the different treatment groups. We also assessed waiting time for treatment, treatment completion rates and overall treatment time for all the patients in the study group. Outcomes of patients at last follow up and survival for different stages of disease were described. Materials and Methods A retrospective study of patients with cancer of the larynx treated at Charlotte Maxeke Academic Hospital department of radiation oncology between the year 2007 and 2009. All patients who received radiotherapy including palliative and radical cases were assessed. Outcomes were measured from end of treatment to 1 year and 2 years follow up for survival. Results We identified 106 eligible patients. The mean age was 58.6 years (standard deviation of 10.051).Two thirds (67%) of the patients presented with stage IVa disease, 14% had stage IVb, 13% had stage III, and very few patients had stage I and II disease 4% and 2% respectively. One third of patients were treated with radical chemotherapy plus radiotherapy and majority of them received only 1 cycle of chemotherapy. The other 26 % of patients treated with radical intent received radiotherapy alone. A significant number of our patients (42 %) were treated with palliative intent of which 13 % were patients who had disease progression while awaiting treatment. The majority of patients (53%) had an improvement in symptoms while (5.7%) had died and (17%) were lost to follow-up. Conclusion Waiting time prior to radiotherapy is a major problem in our institution as our overall mean waiting time was 98.5 days. Patients who had disease progression as defined by change in the treatment intent from radical to palliative treatment (13%) had a mean waiting time of 187.9 days which was almost double our overall mean waiting time and significantly worse than that recommended by standard of care. Although this waiting time was not statistically significant when compared with other patients treated with radical intent, it is a concern for the department to have such long waiting time prior to therapy and is probably a reflection of inadequate statistical power. Of the radical cases those treated with chemotherapy and radiotherapy very few (2.9%) completed 3 cycles of chemotherapy therefore we had low treatment completion rates. Some patients did not receive their 2nd or 3rd cycle of chemotherapy due to low creatinine clearance other patients reasons for not completing chemotherapy was not documentation in their medical records. Although concurrent chemotherapy plus radiotherapy is the standard of care for larynx preservation, most of our patients received suboptimal treatment to the recommended schedule and a significant number of our patients were treated with palliative intent. Chemotherapy was not administered in some patients because of low CD4 count value. Unfortunately this was not recorded systematically and HIV status was not an entry or exclusion factor so no comparisons could be made. The chemotherapy schedule was not given to many patients at the recommended schedule of 3 cycles so we were not able to compare this with the literature. Resources constraints with regards to diagnostic and radiological facilities resulted in us not having measurable tumour volume increase to evaluate disease progression during waiting time and to evaluate response to treatment at follow-up. We have identified that patients are receiving inadequate treatment at the Department of Radiation Oncology with waiting times in excess of that recommended in the literature. Several reasons have been tentatively identified. Additional research in a form of prospective study is required in our department to assess if we could improve the number of patients treated with radical intent by giving induction chemotherapy during the waiting time for patients with advanced stage III & IV disease who have a good performance status. Protocols in our department need to be reviewed for patients with early disease to be treated with shorter regimen and a higher dose fractionation schedule of 2.25Gy as this will also reduce our overall treatment time and waiting time for treatment while improving local control.

Hepatocellular carcinoma (HCC) is now the first leading cause of male and the second of female cancer mortality in Taiwan. In a preliminary microarray data-mining, we identified that STMN1 was up-regulated in HCCs. This study was aimed to establish the STMN1 expression profiles in assorted cancer cell lines and HCC tissues. The STMN1 genomic DNA is 1.5 Kbp in length, mapped to the 1p36.1-p35 and encodes for an 18 KDa polypeptide in the human. STMN1 is a ubiquitous phosphoprotein that promotes microtubule catastrophe and spindle assembly during cell cycle. In addition, STMN1 protein is also a cofactor to regulate the angiogenesis, cell migration and invasion. The role of STMN1 in the onset or progression of HCC is still not clear. In this study, we firstly examined the STMN1 mRNAs expression profiles in several cancer cell lines and found its significant up-regulation in six HCC cell lines, HA22T, HCC36, Hep3B, Huh7, Malaru, SK-hep1, one breast tumor, BCM1 and one stomach tumor, SCM1. To further understand if any amplifications of genomic STMN1, the expression profile of STMN1 mRNA and STMN1 protein in HCC tissue specimens, 62 HCC tissues, in pair, that collected from Chi-Mei Medical Center (Tainan) were analyzed. Among 62 pairs of HCC tissues analyzed, 47 STMN1 mRNAs were significant higher in HCC tissues than in their normal counterparts. On the other hand, the STMN1 genomic DNA was amplification in 27 HCC tissues. Then, we have determined and compared the STMN1 protein in both HCC tissues and normal tissues by the Western blotting analysis. STMN1 protein expression was found to be higher in 30 tumor tissues than in their corresponding normal tissues. This result was 84% consistent with the quantitative RT-PCR results. Furthermore, STMN1 CDs were cloned from HCC cell line (Sk-hep1) and subcloned into various protein expression vectors for further examining STMN1 subcellular localization in HeLa and Sk-hep1 cell lines. The STMN1 protein locates in both cytoplasm and nucleus by immunofluorescence analysis. This result was different from the previously report that STMN1 located in cytoplasm. Furthermore, there were 7% of Sk-hep1 cells which STMN1 proteins were only located in nucleus.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Made available in DSpace on 2012-09-06T01:11:36Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 627.pdf: 1386418 bytes, checksum: 2e705d3dabbd982d0b2918fad161a251 (MD5) Previous issue date: 2003 / O presente trabalho procura descrever o perfil epidemiológico e a sobrevida de 1 e 5 anos em uma coorte de pacientes com carcinoma hepatocelular acompanhados no Instituto Nacional do Câncer (INCA), localizado no município do Rio de Janeiro. Foi realizado um estudo retrospectivo de 115 pacientes, matriculados no INCA-RJ no período de 1990 à 2000. Utilizou-se o método de Kaplan Meier e de Regressão de Cox para a análise e construção das curvas de sobrevida. O perfil da coorte estudada foi de pacientes sintomáticos (94 por cento) em estágio avançado de doença (41,3 por cento estadiamento IV), com média de idade de 53,6 anos, sem variação entre os sexos. A razão M/F encontrada foi de 1,3:1.A sobrevida de 1 ano foi de 30,5 por cento, com mediana de 4,6 meses. Pela análise univariada, os pacientes com melhor sobrevida foram aqueles submetidos a algum tratamento, com menos de 55 anos, com 1-3 nódulos menores que 10 cm e com nível de alfafetoproteína menor ou igual a 500 ng/ml, os quais apresentaram sobrevida de 1 ano de 44,9 por cento, 36,7 por cento, 46,5 por cento e 44,3 por cento, respectivamente. Apenas 3,4 por cento dos pacientes sobreviveram além de 5 anos. Na análise multivariada, foram construídos dois modelos: no primeiro observou-se uma Hazard Ratio (HR) de 3,92 (IC 95 por cento 1,79-8,61) para os pacientes com nódulos múltiplos, controlando as variáveis idade, cirrose e tratamento. No segundo modelo, a HR para os pacientes com nível sérico de alfafetoproteína > 500 ng/ml, foi de 2,02 (IC 95 por cento 1,17-3,49), controlando o efeito do tratamento. A média de idade observada tende a se aproximar dos valores descritos em regiões com alta incidência para o carcinoma hepatocelular, contudo a razão M/F foi inferior ao registrado em áreas com baixa incidência. Os pacientes submetidos a alguma intervenção terapêutica apresentaram melhor sobrevida em relação aos não tratados. Pacientes com alfafetoproteína elevada ou com nódulos múltiplos apresentaram pior prognóstico