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ANÁLISE DO POLIMORFISMO GENÉTICO DO CÓDON 72 DO GENE P53 EM PACIENTES COM CARCINOMA ESCAMOSO DE BASE DA LÍNGUABorges Filho, Francisco Pereira 05 May 2009 (has links)
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Previous issue date: 2009-05-05 / INTRODUCTION: The polymorphism at codon 72, proline (p53P) or arginine (p53R) is
involved in the ability of p53 to interact with cellular proteins. Several authors have
shown that the presence of genotype p53RR confers greater risk of developing
tumors. OBJETIVE: To assess the allelic frequency of genetic polymorphism in
codon 72 in TP53 gene in samples obtained from patients diagnosed with squamous
carcinoma of base of the tongue treated at the Hospital Araújo Jorge and Associação
de Combate ao Câncer em Goiás (ACCG)between 1990 and 2006. Evaluate the
genetic predisposition for Base of Tongue Cancer linked of TP53 polimorphism, by
identififyin of the presence or absence of the alleles p53R and/or p53P alleles in
patients with this pathology. MATERIALS AND METHODS: This study is a casecontrol
retrospective in nature, was conducted at Núcleo de Pesquisas Replicon of
the Universidade Católica de Goiás in conjunction with the Hospital Araújo Jorge. We
evaluated 54 patients with squamous carcinoma of the base of the tongue and 186
individuals without cancer. These were matched regarding gender, age, and the
group of cases was evaluated clinical stage and smoking, alcohol consumption. The
genotypes p53R and p53P were determined by PCR, using specific primers.
RESULTS: The allele frequencies for p53R in cases and controls were 75.9% and
74.2%, while the p53P were 24.1% and 25.8% respectively. There was no statistically
significant difference (p = 0.79) in allele frequencies between the two groups,
suggesting that the polymorphism of codon 72 of TP53 is not a risk factor for
susceptibility to squamous cell carcinoma of the tongue base. CONCLUSION: The
study does not find relationship between p53R and CCO carcinogenesis when
compared sex, age and color. / INTRODUÇÃO: O polimorfismo no códon 72, prolina (p53P) ou arginina (p53R) está
envolvido na habilidade da p53 em interagir com as proteínas celulares. Vários
autores têm demonstrado que a presença do genótipo p53RR confere maior risco de
desenvolvimento de tumores. OBJETIVO: Avaliar a freqüência alélica do
polimorfismo genético no códon 72 do gene p53 em amostras obtidas de pacientes
diagnosticados com Carcinoma Escamoso de Base de Língua atendidos no Hospital
Araújo Jorge, da Associação de Combate ao Câncer em Goiás (ACCG), entre os
anos de 1999 e 2006. Avaliar a predisposição genética do câncer de base da língua
relacionada ao polimorfismo de TP53, através da identificação da presença ou não
dos alelos p53R e/ou p53P nos pacientes com esta patologia. MATERIAIS E
METODOS: O presente estudo é do tipo caso-controle de caráter retrospectivo, foi
realizado no Núcleo de Pesquisas Replicon da Universidade Católica de Goiás em
conjunto com o Hospital Araújo Jorge. Foram avaliados 54 pacientes com carcinoma
escamoso de base da língua e em 186 indivíduos sem câncer. Estes foram pareados
quanto ao sexo, idade e no grupo caso, foram avaliados o estádio clínico e hábitos
de etilismo e tabagismo. A genotipagem dos alelos p53R e p53P foi determinada por
PCR, utilizando-se primers específicos. RESULTADOS: As freqüências alélicas para
p53R nos casos e controles foram de 75,9% e 74,2%, enquanto que de p53P foram
de 24,1% e 25,8%, respectivamente. Não houve diferença estatisticamente
significativa (p = 0,79) nas freqüências alélicas entre os dois grupos analisados,
sugerindo que o polimorfismo do códon 72 de TP53 não seja um fator de risco de
susceptibilidade ao carcinoma escamoso de base da língua. CONCLUSÃO: Não foi
observada associação entre a variante p53R e o desenvolvimento da carcinogênese
de CCO de base da língua, segundo o sexo, idade e etnia.
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Long-term outcome research on PDR brachytherapy with focus on breast, base of tongue and lip cancerJohansson, Bengt January 2010 (has links)
Brachytherapy (BT) with continuous low dose rate (LDR) has been used for 100 years and is considered as the radiotherapy method able to deliver a dose in the shortest time with high efficacy and low risk of side effects. The drawbacks are need for patient isolation and radiation exposure of the staff during the treatment. Brenner and Hall published the radiobiology concept for pulsed dose rate (PDR) in 1991. Short (10-20 minutes), hourly pulses of high dose rate (HDR) given to the same dose, with same overall treatment time will virtually simulate continuous LDR. At the same time new afterloading machine technology became available, where a single millimetre sized radiation 192Iridium source sequentially moves through the applicator in small individually timed steps. The advantages are that the radiation dose can be optimized along the applicator and with no radiation exposure of the staff and no need for patient isolation more than during the pulse. This work deals with four different aspects of PDR BT An experimental comparison of measured absorbed doses outside a left sided breast target on a body equivalent Alderson phantom was made. Five external beam radiotherapy (EBRT) whole breast treatments to 50 Gy versus five accelerated partial breast irradiations (APBI) by PDR BT to 50 Gy were studied. The absorbed doses were measured in 67 different positions inside the body phantom by thermoluminescence dosimeters. The result shows that dose points distant to the left breast will have 1-1.4 % of the prescribed dose with no difference between EBRT and PDR BT. Organs at risk in short distance (<5 cm) to the target (such as parts of the left lung, heart muscle and the right breast) will have significantly less dose by PDR BT. In conclusion PDR BT has dosimetric advantages close to the target compared to EBRT and cannot do more damage to remote organs. PDR APBI as the adjuvant RT treatment to breast conserving surgery after early breast cancer was studied. Between 1994-2004 we treated 50 women and 51 breasts. The median age of the population was 53 (40-72) years. The cases were radically resected, unifocal T1-2N0-1M0 tumours. PDR BT was given to a dose of 50 Gy for 5 days directed to the operated sector of the breast. The median treated volume was 160 cm3, constituting in median 31 % of the breast volume. The treatment is called accelerated because total treatment time is 5 days compared to 5 weeks for EBRT. After a median follow-up of 130 months (>10 years) we noted 5 (10 %) local recurrences in the treated breast. Four of these recurrences were outside the treated volume. Three women (6 %) developed cancers in the other breast. Early side effects were mild and less than with EBRT. As late side effects we found mild to moderate local fibroses in the treated volume. A cosmetic evaluation was done by both the patient and a nurse and was found to be lower than in other published data (56 % = good to excellent). The 10 years local failure rate is similar to the result from a large Swedish randomized study on whole breast radiotherapy to 50 Gy. The study indicates that PDR BT is highly effective. A combination of EBRT (40.8 Gy) and PDR boost (35 Gy) to T1-4N0-3M0, base of tongue (BOT) cancer, treated during 1994-2007 was analyzed. The study is the first with PDR and second largest with BT worldwide. A number of 83 patients with a median age of 60 (38-82) years were included. BT was given to a mean volume of 58 ccm 2 days after the neck dissection. Median follow-up was 54 months. At 5 years we found 89 % local tumour control, 95 % neck control, 80 % disease free survival and an overall survival of 65 %. Late side effects were 13 % minor transient soft tissue necrosis and 12 % long lasting or permanent soft tissue- or osteoradio-necrosis. The results are among the best published worldwide. An extensive quality of life analysis was done on 45 patients at last follow-up and showed limited, persistent xerostomia and dysphagia. The global quality of life was rated good in 75 % of the patients. The last study presented was PDR mono-brachytherapy (55-60 Gy) to cancer of the lip (T1-3N0M0). The study included 43 patients with a median age of 74 (37-92) years. The treatment time was 5.5-6 days and the mean treated volume was 15 ccm. The median follow-up time was 54 (1-158) months. Five year Kaplan-Meier data showed, local control 94 %, disease free survival 86 % and overall survival 59 %. An early side effect was a strong radiation mucositis and dermatitis, which healed in 1 month. Late side effects were uncommon and the cosmetic appearance and the lip function were found to be normal. Our data in total and per T-stage was compared to a European survey from 1993 on 2794 patients treated by LDR BT. The results are similar and are a strong indication of equal efficacy between PDR and LDR.
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