1000 resultados para Cancer - Aspectos geneticos


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Since its discovery, radioactivity has brought numerous benefits to human societies. It has many applications in medicine, serving as a tool for non-invasive methods for diagnosis and therapies against diseases such as cancer. It also applies to technologies for energy in nuclear power plants with relatively low impacts on terms of perfect security. All applications, however, have risks, requiring maximum caution to drive processes and operations involving radioactive elements because, once released into the environment, they have extremely harmful effects on organisms affected. This paper presents fundamental concepts and principles of nuclear physics in order to understand the effects of radioactive elements released into the environment, culminating on the issue of radioactive contamination. Literature review allowed us to understand the radioactive contamination problem on living beings. Three major nuclear accidents have happened in the last thirty years, two of them in consecutive years. The nuclear accident at Chernobyl, Ukraine, in 1986, polluted large areas, condemning hundreds of thousands of people to live with consequences of the accident and effects of radiation, killing thousands of people throughout the years. In 1987, a major radiological accident occurred in Goiania (GO) when a source of radioactive cesium was violated, leading to the death of those who had direct or indirect contact with cesium. The most recent accident, in March, 2011, was located at the nuclear power plant in Fukushima Prefecture, Japan, after an earthquake and tsunami hit the region. There is no extensive and accurate knowledge about the consequences of the contamination entailed in that accident, although it is possible to verify signals on a global scale. An analysis of reports of contamination of large areas generated by nuclear plants with release of hazardous wastes suggests it is necessary to rethink the energy matrix of the various countries...

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Photodynamic Therapy (PDT) is a technique used to treat several types of lesions, such as cancer, microbial control, and esthetic dentistry cases. The performance of PDT involves the use of a photosensitizer (PS), which mainly will be located in cancer cells and is irradiated with visible light. This process, when it occurs in the presence of oxygen triggers the formation of reactive oxygen species that are cytotoxic to cells. These species cause cell death and subsequent tumor necrosis. The use of white light as a light source for multispectral Photodynamic Therapy and its consequences to the photodynamic effect is not yet completely established, and therefore there is interest in studying the parameters involved for analyzing the best conditions for applying treatment. The wavelength is crucial to improve the therapeutic effect, since both the optical properties of the biological tissue as the PS depend on these parameters. For FS studied in this work (Photogem®) are most often used wavelengths in the red region, due to their larger penetration depth in biological tissue. Thus, the light source becomes a fundamental aspect, their choice depends on the specific application and is based on the tumor location, light dose to be delivered and FS chosen. Despite all the advantages presented by lasers, the fact of having an emission spectrum essentially monochrome makes only one possible transition possible for the absorption of FS is used. Therefore, more extensive light sources such as light emitting diodes (LED), could be better used in some cases the laser, with the additional advantage of a reduced cost. Therefore, the choice of the white LED comes from an emission spectrum that still wider LED colors defined by allowing greater use of the several absorption bands and with varying depths of operation, according to the wavelength... (Complete abstract click electronic access below)

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The 131I (radioactive iodine) is one of the most used radionuclides in nuclear medicine for diagnosis and treatment. The present study evaluates the dosimetric aspects related to radioiodine therapy after thyroidectomy in patients with thyroid cancer. The samples were studied with 50 patients undergoing treatment, by assessing the exposures of workers (nursing assistants, staff hygiene, medical and physical), the general public (accompanying and family members) and on the environment. To evaluate the workers, was made a survey of the environmental conditions of the room radioiodine and routines adopted by them during the treatment period. Estimating the dose equivalent per month for each employee, we observed that the maximum levels obtained for nursing assistants, the team of hygiene, medical and physicians were considered low in relation to the extent permitted by law. In order to assess the public, some situations have been suggested for the calculation of equivalent doses in which it was possible to verify the fundamental importance of isolating the patient in the 2 days first. Regarding the environment, the radioactive waste generated by patient had volume of 1.0 m3 and activity estimated at 0.91 mCi, taking a decay time for eliminating them about 75 days to reach the allowable value of 2 μCi / kg system of collecting garbage. Therefore, all radioactive waste removed from the patient's room should be sent to the warehouse for temporary storage of radioactive waste, located away from normal work areas

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OBJETIVOS: conhecer os aspectos clínicos e patológicos dos casos de câncer de mama feminino cadastrados num serviço público de oncologia de Sergipe. MÉTODOS: procurou-se fazer uma associação do estadiamento com as características presentes nos tumores. A coleta de dados foi realizada em 165 prontuários de mulheres cadastradas no período de 2005 a 2008 no ambulatório de oncologia do Hospital Cirurgia, localizado em Aracaju-Sergipe, por meio de formulário de coleta de dados, em 2009. RESULTADOS: identificou-se o carcinoma ductal invasivo como o tipo de neoplasia mamária mais frequente com 80,8% dos casos; 76 (46,1%) neoplasias foram diagnosticadas em estádio avançado (IIB, III e IV) e a mastectomia prevaleceu como tipo de cirurgia utilizado no tratamento independente do estadiamento. Quanto aos receptores hormonais todos apresentaram associação com o grau do estádio e, ainda, notou-se que a positividade do estrogênio e progesterona é fator de proteção para um pior prognóstico. CONCLUSÃO: é notável que os casos de câncer de mama estudados apresentam maior agressividade biológica, cursando com pior prognóstico, considerando o estádio clínico. Fazem-se necessárias ações de detecção precoce voltadas ao câncer de mama na atenção básica de Sergipe para redução da morbi-mortalidade, melhora da sobrevida e qualidade de vida entre as mulheres acometidas por essa neoplasia.

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Squamous cell carcinoma of oral tongue shows high rates of morbidity and mortality in the population, therefore, great efforts are being made to classify morphological changes and identify biomarkers that have prognostic value and that are able to group patients in individualized therapeutic options. From this perspective, there is the heat shock factor 1 (HSF1), which is a heat shock factor transcription protein (HSPs) that allows the cancer to deal with stressors associated with malignancy, acting differently in tumor progression. This research aimed to perform a clinico-pathological analysis of 70 cases of oral tongue squamous cell carcinoma (OTSCC) and immunohistochemical study of the expression of HSF1 protein in OTSCC, comparing it with 30 specimens of normal oral mucosa (NOM), and correlating this immunostaining with clinico-pathological aspects of OTSCC. To analyze the association between immunoexpression of HSF1 and clinicophatoloical aspects, the cases were categorized in minor and major overexpression, based in the median immunostaining score. Regarding the cases of OTSCC, 57.1% showed clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998) and 47.1% as high risk of malignancy according to Brandwein-Gensler et al., (2005). A disease free survival rate of 47.84% and overall survival rate of 68.20% was observed in the analyzed cases, and the high degree of malignancy according to Bryne’s system (1998) (p=0.05), tumor size T3 or T4 (p=0.04), local recurrence (p=0.02), and perineural invasion (p=0.02) determined negative impacts in survival time. We observed also a statistically significant result (p<0.01) when comparing the immunoreactivity of HSF1 between NOM and OTSCC. This significantly increased expression of HSF1 in cases of OTSCC suggests that this protein acts, indeed, in the pathogenesis of this disease. However, there were no statistically significant associations between this overexpression and the clinico-pathological parameters analyzed. This finding may reflect the influence of epigenetic events on HSF1 gene or a possible stability of this protein expression throughout disease progression.

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Squamous cell carcinoma of oral tongue shows high rates of morbidity and mortality in the population, therefore, great efforts are being made to classify morphological changes and identify biomarkers that have prognostic value and that are able to group patients in individualized therapeutic options. From this perspective, there is the heat shock factor 1 (HSF1), which is a heat shock factor transcription protein (HSPs) that allows the cancer to deal with stressors associated with malignancy, acting differently in tumor progression. This research aimed to perform a clinico-pathological analysis of 70 cases of oral tongue squamous cell carcinoma (OTSCC) and immunohistochemical study of the expression of HSF1 protein in OTSCC, comparing it with 30 specimens of normal oral mucosa (NOM), and correlating this immunostaining with clinico-pathological aspects of OTSCC. To analyze the association between immunoexpression of HSF1 and clinicophatoloical aspects, the cases were categorized in minor and major overexpression, based in the median immunostaining score. Regarding the cases of OTSCC, 57.1% showed clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998) and 47.1% as high risk of malignancy according to Brandwein-Gensler et al., (2005). A disease free survival rate of 47.84% and overall survival rate of 68.20% was observed in the analyzed cases, and the high degree of malignancy according to Bryne’s system (1998) (p=0.05), tumor size T3 or T4 (p=0.04), local recurrence (p=0.02), and perineural invasion (p=0.02) determined negative impacts in survival time. We observed also a statistically significant result (p<0.01) when comparing the immunoreactivity of HSF1 between NOM and OTSCC. This significantly increased expression of HSF1 in cases of OTSCC suggests that this protein acts, indeed, in the pathogenesis of this disease. However, there were no statistically significant associations between this overexpression and the clinico-pathological parameters analyzed. This finding may reflect the influence of epigenetic events on HSF1 gene or a possible stability of this protein expression throughout disease progression.

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En este trabajo de grado presentado para optar al t?tulo de Licenciada en Educaci?n B?sica con ?nfasis en Ciencias Naturales y Educaci?n Ambiental y realizado en el marco general de la Ense?anza de la Ciencias Naturales con un enfoque de asuntos sociocient?ficos; se propuso analizar la construcci?n de explicaciones y los procesos de indagaci?n que realizan los estudiantes a trav?s de un estudio de casos ?C?ncer de mama? llev?ndome a comprender la importancia que juega la ense?anza (el quehacer pedag?gico y/o las intervenciones en los estudiantes) el cual, permita propiciar espacios de encuentro entre el conocimiento y a partir de ello establecer relaciones entre situaciones cotidianas, la ciencia, la sociedad, la cultura, lo ambiental y hasta la parte pol?tica, permitiendo contextualizar a un problema presente. Para tal efecto, se trabaj? con los aspectos metodol?gicos tales como: La observaci?n, grabaciones y cuestionarios referente al estudio de caso c?ncer de mama, el tipo de estudio de este trabajo es cualitativo con metodolog?a de investigaci?n acci?n. As? mismo, el inter?s por identificar, categorizar y analizar la construcci?n de explicaciones en torno a un problema contextualizado ?c?ncer de mama? y en ello se estableci? rejillas de an?lisis y mapas conceptuales para procesar la informaci?n y as? lograr establecer el an?lisis de resultados a trav?s de categor?as, el cual da como insumo algunas respuestas acerca de lo importante del que hacer pedag?gico y las intervenciones que como educadores llegamos hacer con los estudiantes, permitiendo construir explicaciones significativas o retoricas.

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The aim of the study was to analyze the frequency of epidermal growth factor receptor (EGFR) mutations in Brazilian non-small cell lung cancer patients and to correlate these mutations with response to benefit of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Our cohort consisted of prospective patients with NSCLCs who received chemotherapy (platinum derivates plus paclitaxel) at the [UNICAMP], Brazil. EGFR exons 18-21 were analyzed in tumor-derived DNA. Fifty patients were included in the study (25 with adenocarcinoma). EGFR mutations were identified in 6/50 (12 %) NSCLCs and in 6/25 (24 %) adenocarcinomas; representing the frequency of EGFR mutations in a mostly self-reported White (82.0 %) southeastern Brazilian population of NSCLCs. Patients with NSCLCs harboring EGFR exon 19 deletions or the exon 21 L858R mutation were found to have a higher chance of response to platinum-paclitaxel (OR 9.67 [95 % CI 1.03-90.41], p = 0.047). We report the frequency of EGFR activating mutations in a typical southeastern Brazilian population with NSCLC, which are similar to that of other countries with Western European ethnicity. EGFR mutations seem to be predictive of a response to platinum-paclitaxel, and additional studies are needed to confirm or refute this relationship.

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Radiotherapy (RT) is a risk factor for accelerated carotid artery atherosclerotic disease in subjects with head and neck cancer. However, the risk factors of RT-induced carotid artery remodeling are not established. This study aimed to investigate the effects of RT on carotid and popliteal arteries in subjects with head and neck cancer and to evaluate the relationship between baseline clinical and laboratory features and the progression of RT-induced atherosclerosis. Eleven men (age = 57.9 ± 6.2years) with head and neck cancer who underwent cervical bilateral irradiation were prospectively examined by clinical and laboratory analysis and by carotid and popliteal ultrasound before and after treatment (mean interval between the end of RT and the post-RT assessment = 181 ± 47 days). No studied subject used hypocholesterolemic medications. Significant increases in carotid intima-media thickness (IMT) (0.95 ± 0.08 vs. 0.87 ± 0.05 mm; p < 0.0001) and carotid IMT/diameter ratio (0.138 ± 0.013 vs. 0.129 ± 0.014; p = 0.001) were observed after RT, while no changes in popliteal structural features were detected. In addition, baseline low-density lipoprotein cholesterol levels showed a direct correlation with RT-induced carotid IMT change (r = 0.66; p = 0.027), while no other studied variable exhibited a significant relationship with carotid IMT change. These results indicate that RT-induced atherosclerosis is limited to the irradiated area and also suggest that it may be predicted by low-density lipoprotein cholesterol levels in subjects with head and neck cancer.

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To evaluate associations between polymorphisms of the N-acetyltransferase 2 (NAT2), human 8-oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing protein 1 (XRCC1) genes and risk of upper aerodigestive tract (UADT) cancer. A case-control study involving 117 cases and 224 controls was undertaken. The NAT2 gene polymorphisms were genotyped by automated sequencing and XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms were determined by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Slow metabolization phenotype was significantly associated as a risk factor for the development of UADT cancer (p=0.038). Furthermore, haplotype of slow metabolization was also associated with UADT cancer (p=0.014). The hOGG1 Ser326Cys polymorphism (CG or GG vs. CC genotypes) was shown as a protective factor against UADT cancer in moderate smokers (p=0.031). The XRCC1 Arg399Gln polymorphism (GA or AA vs. GG genotypes), in turn, was a protective factor against UADT cancer only among never-drinkers (p=0.048). Interactions involving NAT2, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms may modulate the risk of UADT cancer in this population.

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This study aimed to identify novel biomarkers for thyroid carcinoma diagnosis and prognosis. We have constructed a human single-chain variable fragment (scFv) antibody library that was selected against tumour thyroid cells using the BRASIL method (biopanning and rapid analysis of selective interactive ligands) and phage display technology. One highly reactive clone, scFv-C1, with specific binding to papillary thyroid tumour proteins was confirmed by ELISA, which was further tested against a tissue microarray that comprised of 229 thyroid tissues, including: 110 carcinomas (38 papillary thyroid carcinomas (PTCs), 42 follicular carcinomas, 30 follicular variants of PTC), 18 normal thyroid tissues, 49 nodular goitres (NG) and 52 follicular adenomas. The scFv-C1 was able to distinguish carcinomas from benign lesions (P=0.0001) and reacted preferentially against T1 and T2 tumour stages (P=0.0108). We have further identified an OTU domain-containing protein 1, DUBA-7 deubiquitinating enzyme as the scFv-binding antigen using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. The strategy of screening and identifying a cell-surface-binding antibody against thyroid tissues was highly effective and resulted in a useful biomarker that recognises malignancy among thyroid nodules and may help identify lower-risk cases that can benefit from less-aggressive management.

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Despite the remarkable improvements in breast cancer (BC) characterization, accurate prediction of BC clinical behavior is often still difficult to achieve. Some studies have investigated the association between the molecular subtype, namely the basal-like BC and the pattern of relapse, however only few investigated the association between relapse pattern and immunohistochemical defined triple-negative breast cancers (TNBCs). The aim of this study was to evaluate the pattern of relapse in patients with TNBC, namely the primary distant relapse site. One-hundred twenty nine (129) invasive breast carcinomas with follow-up information were classified according to the molecular subtype using immunohistochemistry for ER, PgR and Her2. The association between TNBC and distant relapse primary site was analyzed by logistic regression. Using multivariate logistic regression analysis patients with TNBC displayed only 0.09 (95% CI: 0.00-0.74; p=0.02) the odds of the non-TNBC patients of developing bone primary relapse. Regarding visceral and lymph-node relapse, no differences between in this cohort were found. Though classically regarded as aggressive tumors, TNBCs rarely development primary relapse in bone when compared to non-TNBC, a clinical relevant fact when investigating a metastasis of an occult or non-sampled primary BC.

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To analyze the prevalence of cervical cytopathological results for the screening of cervical cancer with regard to women's age and time since the last examination in Maceió and Rio de Janeiro, Brazil, among those assisted by the Brazilian Unified Health System. Cervical cytopathological results available in the Information System of Cervical Cancer Screening for the year 2011 were analyzed, corresponding to 206,550 for Rio de Janeiro and 45,243 for Maceió. In Rio de Janeiro, examination at one and two year intervals predominated, while in Maceió examination at one and three year intervals had a higher predominance. Women who underwent cervical smear screening in Maceió were older than those in Rio de Janeiro. The prevalence of invasive squamous cell carcinoma was similar for the two cities, but all the other results presented a higher prevalence in Rio de Janeiro: ASCUS (PR=5.32; 95%CI 4.66-6.07); ASCH (PR=4.27; 95%CI 3.15-5.78); atypical glandular cells (PR=10.02; 95%CI 5.66-17.76); low-grade squamous intraepithelial lesions (PR=6.10; 95%CI 5.27-7.07); high-grade squamous intraepithelial lesions (PR=8.90; 95%CI 6.50-12.18) and adenocarcinoma (PR=3.00; 95%CI 1.21-7.44). The rate of unsatisfactory cervical samples was two times higher in Maceió and that of rejected samples for analysis was five times higher in Maceió when compared to Rio de Janeiro. The prevalence rates of altered cervical cytopathological results was significantly higher in Rio de Janeiro than in Maceió. There is no objective information that may justify this difference. One hypothesis is that there may be a difference in the diagnostic performance of the cervical cancer screening, which could be related to the quality of the Pap smear. Thus, these findings suggest that it would be necessary to perform this evaluation at national level, with emphasis on the performance of cervical cancer screening in order to improve the effectiveness of cervical cancer control.

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Phase I trials use a small number of patients to define a maximum tolerated dose (MTD) and the safety of new agents. We compared data from phase I and registration trials to determine whether early trials predicted later safety and final dose. We searched the U.S. Food and Drug Administration (FDA) website for drugs approved in nonpediatric cancers (January 1990-October 2012). The recommended phase II dose (R2PD) and toxicities from phase I were compared with doses and safety in later trials. In 62 of 85 (73%) matched trials, the dose from the later trial was within 20% of the RP2D. In a multivariable analysis, phase I trials of targeted agents were less predictive of the final approved dose (OR, 0.2 for adopting ± 20% of the RP2D for targeted vs. other classes; P = 0.025). Of the 530 clinically relevant toxicities in later trials, 70% (n = 374) were described in phase I. A significant relationship (P = 0.0032) between increasing the number of patients in phase I (up to 60) and the ability to describe future clinically relevant toxicities was observed. Among 28,505 patients in later trials, the death rate that was related to drug was 1.41%. In conclusion, dosing based on phase I trials was associated with a low toxicity-related death rate in later trials. The ability to predict relevant toxicities correlates with the number of patients on the initial phase I trial. The final dose approved was within 20% of the RP2D in 73% of assessed trials.

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There is an increasing rate of papillary thyroid carcinomas that may never progress to cause symptoms or death. Predicting outcome and determining tumour aggressiveness could help diminish the number of patients submitted to aggressive treatments. We aimed to evaluate whether markers of the immune system response and of tumour-associated inflammation could predict outcome of differentiated thyroid cancer (DTC) patients. Retrospective cohort study. We studied 399 consecutive patients, including 325 papillary and 74 follicular thyroid carcinomas. Immune cell markers were evaluated using immunohistochemistry, including tumour-associated macrophages (CD68) and subsets of tumour-infiltrating lymphocytes (TIL), such as CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69 and CD25. We also investigated the expression of cyclooxygenase 2 (COX2) in tumour cells and the presence of concurrent lymphocytic infiltration characterizing chronic thyroiditis. Concurrent lymphocytic infiltration characterizing chronic thyroiditis was observed in 29% of the cases. Among all the immunological parameters evaluated, only the enrichment of CD8+ lymphocytes (P = 0·001) and expression of COX2 (P =0·01) were associated with recurrence. A multivariate model analysis identified CD8+ TIL/COX2 as independent risk factor for recurrence. A multivariate analysis using Cox's proportional-hazards model adjusted for the presence of concurrent chronic thyroiditis demonstrated that the presence of concurrent chronic thyroiditis had no effect on prognostic prediction mediated by CD8+ TIL and COX2. In conclusion, we suggest the use of a relatively simple pathology tool to help select cases that may benefit of a more aggressive approach sparing the majority of patients from unnecessary procedures.