| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 8.14 MB | Adobe PDF |
Advisor(s)
Abstract(s)
As neoplasias urológicas, nomeadamente o cancro da bexiga, são muito comuns em países ocidentais e a sua incidência tem vindo a aumentar. Em 2013, registaram-se 2,1 milhões de novos casos, e as mortes associadas aumentaram cerca de 1,6 vezes desde 1990. Apesar dos avanços recentes na terapêutica destes tumores, existe ainda a necessidade de ferramentas de diagnóstico precoce, assim como testes não invasivos e de baixo custo para o seu rastreio e vigilância atempada e precisa, de forma a otimizar os resultados dos tratamentos. Neste contexto, os marcadores moleculares agregam um grande potencial no suporte da decisão clínica. Embora se recorra ao PSA como marcador de diagnóstico e auxiliar de recidiva de cancro da próstata, este ainda possui algumas limitações na sua aplicabilidade clínica. No caso do cancro da bexiga, ainda é necessário um biomarcador de rotina, e, dada a sua elevada taxa de recorrência, o seguimento é realizado por citoscopia, um exame caro e que exige muitos recursos, tornando-o o cancro mais caro para tratar por cada caso incidente. Deste modo, os ácidos nucleicos detetados em fluidos biológicos podem fornecer informação acerca do tumor e proporcionar uma fonte acessível de material tumoral. Vários estudos indicam que estes ácidos nucleicos advêm de processos de morte de células tumorais. Estudos recentes têm evidenciado o potencial da deteção de DNA circulante no sangue periférico de doentes oncológicos, mas a literatura acerca do seu potencial uso na urina de doentes com cancros urológicos é escassa. Enquanto que o sangue é naturalmente homeostático, a amostra de urina tende a refletir alterações no seu ambiente, e pode ser obtida através de procedimentos não invasivos. O objetivo deste estudo consistiu na aplicação de um teste simples, que pudesse ser utilizado como ferramenta de diagnóstico complementar não invasiva. Para tal, estudaram-se 36 doentes com cancro da bexiga e 40 indivíduos-controlo. O DNA livre foi extraído de urina e plasma com recurso a um kit comercial, e quantificaram-se os seus níveis, através da amplificação do gene hTERT, pela metodologia de PCR em tempo real. Os resultados foram sujeitos à análise estatística apropriada. Os resultados obtidos permitem observar um aumento de [ucfDNA] com o avançar do estadio tumoral, bem como uma concentração elevada de cfDNA no estadio T2. Apesar de não possuírem significância estatística, estes resultados são promissores, uma vez que poderá ser possível obter informação mais rápida, precisa e de modo mais inócuo do que a obtida pelos métodos atuais. Para validar estas descobertas, seria necessário ampliar a amostra, de um modo a obter uma maior representação de cada um dos estadios da doença.
Urological neoplasms, particularly bladder cancer, are very common in western countries and their incidence is increasing. In 2013, 2.1 million new cases were registered, with an increased of 1.6 fold in the associated deaths since 1990. Despite the technological advancements on those tumors therapeutics, there's still a need for early diagnosis tools, as well as non-invasive and low cost test, for a more precise and early screening and surveillance, as to optimize the treatment outcomest. In this context, molecular markers aggregate a huge potential in supporting clinical decision. Even though PSA is used as a diagnostic and complementary relapse marker for prostate cancer it still possesses some hidrances on its clinical applicability. As for bladder cancer, there is still a need for a routine biomarker, and, considering its recurrence rate, the follow-up is done by cystoscopy, an expansive and resource-wasting exam, making it the most expensive cancer to treat, per incident case. Thereby, nucleic acids deteced biological fluids can provide information about the tumor ans act as an accessible source of tumor material. Several studies indicate that these nucleic acids originat from death processes of tumor cells. Recent studies have highlighted the potencial of circulating DNA detection in peripheral blood of oncologic patientes, but theres´s a lack of research about this potential in urologic patient´s urine. while blood is homeostatic, urine samples tend to demonstrate changes in its composition, and they can be harvested by non-invasive procedures. The objective of this study consisted on the application of a simple test, that could be used as a complementary non-invasive diagnostic tool. To this end, 36 patientes with bladder cancer and 40 healthy individuals were studied. Free DNA was extracted from urine and plasma using a commercial kit, and its levels were quantified, through the amplification of the hTERT gene, by real-time PCR. The resuts were subjected to the appropriate statistical analysis. Our results show an increase of [ucfDNA] with the development of tumor stage, as well as a high cfDNA concentration in T2 stage. Even though the results don´t possess statistical significance, they are still promising, since they could be possibly be used to obtain faster and precise information, in a more innocuous manner than the one provide by current methods. To validate this discoveries, it would be necessary to increase the study sample, as to obtain a bigger representation of each of bladder cancer´s stages.
Urological neoplasms, particularly bladder cancer, are very common in western countries and their incidence is increasing. In 2013, 2.1 million new cases were registered, with an increased of 1.6 fold in the associated deaths since 1990. Despite the technological advancements on those tumors therapeutics, there's still a need for early diagnosis tools, as well as non-invasive and low cost test, for a more precise and early screening and surveillance, as to optimize the treatment outcomest. In this context, molecular markers aggregate a huge potential in supporting clinical decision. Even though PSA is used as a diagnostic and complementary relapse marker for prostate cancer it still possesses some hidrances on its clinical applicability. As for bladder cancer, there is still a need for a routine biomarker, and, considering its recurrence rate, the follow-up is done by cystoscopy, an expansive and resource-wasting exam, making it the most expensive cancer to treat, per incident case. Thereby, nucleic acids deteced biological fluids can provide information about the tumor ans act as an accessible source of tumor material. Several studies indicate that these nucleic acids originat from death processes of tumor cells. Recent studies have highlighted the potencial of circulating DNA detection in peripheral blood of oncologic patientes, but theres´s a lack of research about this potential in urologic patient´s urine. while blood is homeostatic, urine samples tend to demonstrate changes in its composition, and they can be harvested by non-invasive procedures. The objective of this study consisted on the application of a simple test, that could be used as a complementary non-invasive diagnostic tool. To this end, 36 patientes with bladder cancer and 40 healthy individuals were studied. Free DNA was extracted from urine and plasma using a commercial kit, and its levels were quantified, through the amplification of the hTERT gene, by real-time PCR. The resuts were subjected to the appropriate statistical analysis. Our results show an increase of [ucfDNA] with the development of tumor stage, as well as a high cfDNA concentration in T2 stage. Even though the results don´t possess statistical significance, they are still promising, since they could be possibly be used to obtain faster and precise information, in a more innocuous manner than the one provide by current methods. To validate this discoveries, it would be necessary to increase the study sample, as to obtain a bigger representation of each of bladder cancer´s stages.
Description
Keywords
Bexiga Cancro urológico Urina DNA circulante Diagnóstico precoce Bladder cancer Early diagnosis Urine Circulating DNA