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Att leva med icke-malign prostataförändring : en litteraturöversikt / Living with a non-malignant prostatic condition : a literature reviewStåhl, Joanna, Ericzon, Moa January 2019 (has links)
Bakgrund Icke-maligna prostataförändringar är ett utbrett samhällsproblem och en vanlig anledning till att människor söker sjukvård. Prostatit och benign prostatahyperplasi är två icke-maligna förändringar som kan te sig på olika sätt och kan orsaka lidande hos de drabbade, ofta genom ”lower urinary tract symptoms” och smärta som är vanliga symtom. Att lindra lidande är vårdens uppgift och en sjuksköterskas ansvar. Syfte Syftet med denna litteraturöversikt var att belysa hur det är att leva med en icke-malign prostataförändring. Metod Metoden som användes var icke-systematisk litteraturöversikt där 18 artiklar analyserades. Resultat Resultatet efter att ha analyserat de inkluderad studierna visade att icke-maligna prostataförändringar kan ha inverkan på samliv och relationer, ge upphov till känslor av skam, rädsla och oro, att det finns faktorer som kan vara mer eller mindre gynnsamma vid dessa tillstånd samt att det finns rum för förbättring vid mötet med sjukvården. Slutsats Resultatet i denna litteraturöversikt visar på att leva med icke-maligna prostataförändringar och symtomen de ger upphov till kan ha en tydlig inverkan på drabbade personers liv och livskvalitet i ett flertal aspekter / Background Non-malignant prostatic conditions are a prevalent problem in society and a common reason as to why people seek medical care. Prostatitis and benign prostatic hyperplasia are two examples of non-malignant conditions that can appear in different ways and that could cause the afflicted person suffering, oftentimes through symptoms like pain and lower urinary tract symptoms. Alleviating suffering is an undertaking of health-care professionals’ and a nurse’s responsibility. Aim The aim of this literature review was to illuminate what it is like to live with a non-malignant prostatic condition. Method Non-systematic literature review where 18 articles were analyzed. Results The results of the included and analyzed studies show that non-malignant prostatic conditions can influence intimate relationships, cause feelings of shame, fear and worry, that there are factors that can be more or less favourable in relation to these conditions and that there is room for improvement in the meeting with healthcare professionals. Conclusions The results in this non-systematic literature review show that living with non-malignant prostatic conditions, and the symptoms they cause, can have a significant influence on the affected persons’ lives and quality of life in several aspects.
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Benign Prostatahyperplasi. Upplevelser och livskvalitet hos män med benign prostatahyperplasiGunnarsson, Jenny, Lundin, Madeleine January 2009 (has links)
Benign prostatahyperplasi (BPH) är ett tillstånd som drabbar nästintill samtliga män över 80 år och vilket medför urologiska besvär som kan ha inverkan på livs¬kvaliteten och det dagliga livet. Syftet med denna litteraturstudie var att redogöra för hur män med benign prostatahyperplasi upplever sitt dagliga liv samt hur deras livskvalitet påverkas. En litteraturstudie gjordes utifrån ett systematiskt tillväga¬gångssätt. Litteratursökningen utfördes i databaserna Cinahl, PsycInfo, PubMed samt The Cochrane Library. Både kvantitativa och kvalitativa studier inkluderades vilka kvalitetsgranskades av båda författarna oberoende av varandra med hjälp av ett modifierat granskningsprotokoll. Resultatet visar på att män med BPH har en störd sömn på grund av nykturi, begränsar sitt sociala liv och upplever genans över de urologiska symtomen och en negativ påverkan på det sexuella samlivet. Män med BPH tycks också utveckla copingstrategier för att bemästra sin vardag som att t ex reducera vätskeintaget, prata om besvären och acceptera tillståndet. Det verkar också vara vanligt förekommande att livskvaliteten hos män med BPH är sämre än hos män utan BPH. Fler studier med både kvalitativ och kvantitativ metodansats behövs för att finna en djupare förståelse för män med BPH och för att stärka evidensen avseende livskvalitet och dagligt liv. / Benign prostatic hyperplasia (BPH) is a condition which causes urology bother that might have an impact on quality of life and daily living in almost all men over the age 80. The aim of this study was to report on how men with benign prostatic hyperplasia experiencing their daily lives and how their quality of life is affected. A systematic review was made in accordance to a systematic procedure. The literature searching was made in the databases CINAHL, PsycInfo, PubMed and The Cochrane Library. Both quantitative and qualitative studies were included and the quality was assessed by both authors independently of each other using a modified audit protocol. The results show that men with BPH have disturbed sleep due to nocturia, limiting their social lives and experiencing embarrassment over the urological symptoms and a negative impact on the sexual life. Men with BPH also seems to develop coping strategies to overcome their daily lives such as reducing fluid intake, talk about the complaint and accept the condition. It also seems that it is more common for men with BPH to rank their quality of life lower than men without BPH. More studies using both qualitative and quantitative approach are needed to find a deeper understanding of men with BPH and to strengthen evidences about quality of life and daily life.
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Utveckling av automatiserad urinflödesmätare / Development of an Automated Urine Flow MeterMohamed, Abdirahman January 2021 (has links)
Detta kandidatexamensarbete som utförts på uppdrag av ST-läkare i urologi Per Nordlund hade målet att bygga en urinflödesmätare. Eftersökta mätvärden att registrera var tidpunkt för miktionstillfället, mängden urin per tidsenhet (ml/s), flödesmönster, total mikterad volym (ml) samt miktionstid (sek). Urinflödesmätaren syftar till att förbättra initial bedömning samt uppföljning av personer med vattenkastningssvårigheter, en vanlig orsak till sjukvårdskontakt hos svenska män. För utvärdering av patienters vattenkastning ombeds patienten idag själv registrera och mäta urinvolym, en metod som ofta innebär besvär för patienten och kan innehålla inkomplett och felaktig data. Vid urologmottagningar ges möjligheten att elektroniskt mäta urinflöde och volym. Då en stor variation över dygn och miktionstillfälle föreligger kan en felaktig bild över symtom presenteras. Detta har gett upphov till idén att skapa en urinflödesmätare vars uppgift är att automatisera mätningsprocessen i hemmet. Arbetet utfördes genom att programmera en Arduino mikrokontroller samt användning av en flödessensor. Flödessensorns konstruktion bestod av en magnet, halleffektsensor samt en turbin. Halleffektsensorns uppgift var att mäta det elektriska fältet som uppstår då magneten som sitter på flödessensorns turbin roterar. Genom att utnyttja turbinrotationen kan bland annat volym beräknas. Arbetet har även inneburit användning av Python med syftet att spara det mätvärde från mikrokontrollern i en CSV fil som kan öppnas av en vårdgivare med applikationer som Excel. / This bachelor's degree project which was carried out on behalf of Per Nordlund, urology resident, had the goal of building a urine flow meter. The sought-after values to register each time of the micturition; the amount of urine per unit time (ml/ s), flow pattern, total micturized volume (ml) and micturition time (sec). The urine flow meter aims to improve initial assessment and follow-up of people with urination difficulties, a common cause of medical contact in Swedish men. Today, when evaluating patients urination, the patient is asked to register and measure urine volume themselves, a method that often causes problems for the patient and may contain incomplete and incorrect data. At urology clinics, individuals are given the opportunity to electronically measure urine flow and volume. When there is a large variation over day and occasion of micturition, an incorrect picture of symptoms can be presented. This has given rise to the idea of creating a urine flow meter whose task is to automate the measurement process in the home. The work was performed by programming an Arduino microcontroller and using a flow sensor. The design of the flow sensor consisted of a magnet, a hall-effect sensor and a turbine. The task of the hall-effect sensor was to measure the electric field that arises when the magnet attached on the flow sensor's turbine rotates. By utilizing the turbine rotation, volume can be calculated. The work has also involved the use of Python with the aim of saving the output values from the microcontroller in a CSV file that can be opened by a healthcare provider with applications such as Excel.
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Screening kandidátních genů u karcinomu prostaty a močového měchýře / Candidate genes screening for prostate cancerSemaneková, Viera January 2013 (has links)
Prostate carcinoma is considered to be one of the main medical problem in male population. Prostate carcinoma is the most frequently diagnosed malignancy in men and the death rate has the second position within all diagnosed malignancies in Czech Republic (ÚZIS). There is only one reliable diagnostic tool: PSA (prostate specific antigen). Level of PSA is often elevated in men with prostate carcinoma. This diploma thesis is focused on study of changes in gene expression in prostate carcinoma. Three candidate genes were analyzed: VCL (vinculin), SHB (Src homology 2 binding protein) and OCT3 (organic cation transporter 3). According to recent publications, these genes are related to tumor progression and they could have prognostic significance. In this thesis the following methodological approaches were used: 82 prostatic specimens were collected from patients and mRNA was isolated from these specimens; then RT-PCR was used to obtain cDNA, fragments were detected by electrophoresis. At the end statistical methods were used for evaluation. Relative expression of the genes in prostate carcinoma tissue was compared to relative expression of the genes in BPH (benign prostatic neoplasia) tissue. Results showed higher expression of genes SHB and OCT3 in prostate carcinoma tissue in compariscon to BPH...
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Exprese kandidátních genů karcinomu prostaty / Expression of candidate genes for prostate cancerKrupicová, Daniela January 2013 (has links)
4 Abstract Prostate cancer is one of the major medical problems within the male population in the Czech Republic and in the world. It is on second place among cancer illnesses with respect to mortality in czech male population. Its incidence strongly increases with age. Prostate cells have a unique ability to accumulate zinc in high concentrations compared to other tissues of human body. It is necessary for the proper physiological function of the prostate. There was detected loss of this accumulation ability in prostate cancer cells, which seems to be a condition to carcinogenesis in prostate cells. In this thesis was investigated the expression of four genes involved in the maintenance of homeostasis of zinc in prostate cells. Genes ZIP1 and ZIP7 encode zinc transporters, genes MT1-F and MT2 encode metallothioneins. There was collected 90 biopsy specimens from patients with prostate cancer or with benign prostatic hyperplasia. mRNA was isolated from these samples, cDNA was obtained by RT-PCR. This cDNA was detected by gel electrophoresis and the results were statistically evaluated. Several correlations was found between gene expression and the clinical data of patients. The most important result, there was found lower levels of expression of genes MT1- F and ZIP1 in samples of patients with cancer...
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Efeitos do uso da finasterida sobre o volume prostático e dosagem sérica do PSA em pacientes jovens / Effects of the use of finasteride on prostate volume and serum PSA in young patientsTacino, Rafael Bozzo 22 October 2015 (has links)
A indicação de biópsia para o diagnóstico precoce do câncer prostático baseia-se na dosagem sérica do PSA e nos achados do toque retal. O PSA é uma kalecreina estando seus genes reguladores ligados aos andrógenos. Drogas que afetam o metabolismo dos andrógenos podem afetar a produção de PSA. A finasterida é uma droga sintética que inibe a conversão de testosterona em DHT pela enzima 5 AR. O uso da finasterida na dose de 5mg/dia para o tratamento da HPB causa redução do volume prostático de 20 a 30% e diminuição dos valores dos PSA em aproximadamente 50% do seu valor inicial após 6 meses. O uso da finasterida na dose de 1mg/dia para o tratamento da AAM foi aprovado pelo FDA em 1997. Um estudo realizado em 2007 avaliou a alteração do nível do PSA em homens com mais de 40 anos fazendo uso de finasterida 1mg/dia para tratamento da AAM. Os resultados revelaram redução dos valores do PSA semelhante à verificada nos pacientes portadores de HPB. Não existem estudos prospectivos sobre o tema incluindo pacientes mais jovens. O objetivo do nosso trabalho foi verificar as alterações da dosagem do PSA, da testosterona sérica total e do volume prostático em indivíduos com menos de 40 anos de idade com em uso de finasterida 1mg/dia. Selecionamos 52 pacientes que após avaliação inicial preenchiam os critérios de inclusão. Foram dosados os níveis séricos do PSA e da testosterona, e mensurado o volume prostático através da ultrassonografia transabdominal, no início do estudo (T0) e um ano após o uso da finasterida (T2). No intervalo, 6 meses após o início da droga, foi solicitada apenas nova dosagem de PSA (T1). O valor médio na avaliação inicial (T0) da dosagem do PSA, da testosterona total plasmática e do volume prostático mensurado pela ultrassonografia transabdominal foi de 0,398 ng/ml (0,14- 0,78); 735,77 ng/dl (548-927) e 21,35 ml (15-31ml) respectivamente. Foi observada uma redução do valor médio do PSA de 9,21% após 6 meses do uso da droga (p=0,001). Após 12 meses do uso da finasterida verificamos uma redução de 10,51% do valor do PSA em relação à dosagem inicial (p<0,001) e uma diminuição do valor médio do volume prostático 21,37 ml para 20,03 ml (p<0,001). Não foi detectada alterações nos níveis de testosterona. Diferentemente de estudos anteriores em que, em homens fazendo uso de finasterida 1mg/dia, houve redução de 40% e 50% dos valores do PSA nas faixas etárias de 40 a 49 anos e 50 a 59 anos, nosso trabalho revelou reduções inferiores. Nosso estudo traz importantes questionamentos em relação a como deve ser feita a correção dos valores do PSA nos pacientes que começaram a utilizar finansterida 1mg antes dos 40 anos de idade e que se apresentam para avaliação prostática. Outro ponto de interesse é se a hiperplasia do componente epitelial observada durante envelhecimento masculino poderia ser inibida pelo uso da finasterida desde a juventude, pois sabemos que indivíduos portadores de deficiência congênita de 5AR não apresentam alopecia e nem tão pouco desenvolvem HPB. / The indication of biopsy for early diagnosis of prostate cancer is based on serum PSA levels and digital rectal examination findings. PSA is a kalecreine and its regulatory genes are modulating by androgens. Drugs affecting the androgens metabolism can affect the production of PSA. Finasteride is a synthetic drug, which inhibits the conversion of testosterone to DHT by the enzyme 5 AR. There are two subtypes of 5AR enzymes, Type 1 that predominates in non-prostatic tissues such as liver and skin, and Type 2, which predominates in the prostate and scalp but is also expressed in other tissues. The use of Finasteride 5mg / day for the treatment of BPH is well known. After six months we observe a decrease in prostate volume by 20 to 30% and also a decrease in total serum PSA concentration of approximately 50%. The use of Finasteride at 1mg / day for the treatment of MAA has been approved by the FDA in 1997. In 2007 a study evaluated the change in total serum PSA concentration in men over 40 years taking Finasteride 1 mg / day to treat MAA. The results showed a reduction in PSA values similar to that observed in patients treated of BPH. There are no prospective studies including younger patients. The aim of our study was to assess the changes in total serum PSA concentration, total serum testosterone concentration and prostate volume in patients younger than 40 years of age in use of Finasteride 1mg / day for MAA. We prospectively selected 52 patients with MAA and indication for treatment with Finasteride who met the inclusion criteria. Serum levels of total PSA and total testosterone and prostate volume, measured by transabdominal ultrasound, were obtained at baseline (T0) and one year after started the drug (T2). In the interval, 6 months after started drug, only serum total PSA concentration was measured (T1). The median value at baseline (T0), for total PSA, total testosterone and prostate volume was 0.398 ng / ml (0.14 to 0.78); 735.77 ng / dl (548-927) and 21.35 ml (15-31ml) respectively. A reduction of 9.21% on total PSA concentration was detected 6 months after started the drug (p = 0.001). After 12 months we observed a 10.51% decrease in total serum PSA concentration, when compared with the baseline value, (p <0.001). A reduction in the median value of prostate volume from 21.37 ml to 20.03 ml (p < 0.001) was also detected at the same period. There were no detectable changes in testosterone levels. They reported a decrease of 40% and 50% in total PSA concentration for groups between 40-49 and 50-59 of age respectively. In our study we observed lower reductions. Our finding may be explained by the fact that the epithelial component of the prostate gland has not yet started the hyperplasia process, so the conversion of testosterone into DHT by blocking 5AR by Finasteride would cause less impact. The fact that the values of plasma testosterone not have changed is not surprising since Finasteride is not considered an anti androgenic drug, it means that the synthesis of the testosterone is not affected by its use. Our study highlights important questions about how the adjustment of PSA values should be done in patients who began taking Finasteride 1mg / day before 40 years of age and present for prostate evaluation. Another point of interest is whether the hyperplasia of the epithelial component, observed during the aging process, could be inhibited by the use of Finasteride. This hypothesis can be corroborate by the fact that individuals with congenital deficiency of 5AR do not present alopecia or develop BPH. In conclusion the use of Finasteride 1mg /day reduces the total serum PSA value by 10,51% after one year. Prostate volume is also reduced by 6,3% in the same period.
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Sleep and quality of life in men with lower urinary tract symptoms : and their partnersMarklund-Bau, Helén January 2009 (has links)
Aims: The overall aim was to determine how lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) affect sleep, health related quality of life and disease specific quality of life, and how the men’s urinary symptoms affect their partners. Subjects and methods: In papers I–II, a descriptive design with a pre-test and post-test was used and in papers III-IV the design was descriptive and comparative. The method was self-administered questionnaires. In papers I- II: The questionnaires were translated in the ethnographic mode. In paper I the reliability of the questionnaire was tested in 122 patients with LUTS/ BPO. The disease specific quality of life was studied before and after intervention in 572 consecutive patients with BPO, aged 45-94 yrs. In paper II, the partner specific quality of life was studied in partners to men with BPO before and after TURP. The reliability and the responsiveness of the questionnaire were tested in two groups with 51 partners each. Papers III-IV: A study of 239 men with LUTS, aged 45-80 yrs, and their partners (n=126) who were compared to randomly selected men from the population (n=213) and their partners (n=131). The men had an extra control group, men with inguinal hernia (n=200). Sleep and health related quality of life was studied in both men and their partners. The partners’ specific quality of life was also studied and the men with LUTS answered questions about urinary symptoms and disease specific quality of life. Results: Papers I-II: All the tested questionnaires showed an acceptable reliability and responsiveness. I: Before and after intervention the prevalence of urinary incontinence was 46 % and 16 % respectively. II: Partners were affected by the patients’ BPO symptoms before and improved after the patients TURPs. III: Most sleep variables were significantly impaired in men with LUTS compared to one or both of the control groups. The men with LUTS had a significantly higher prevalence of insomnia (40 %) than both control groups and significantly lower sleep efficiency (49 %) than men with hernia. The men with LUTS were significantly impaired in most domains of the health related quality of life compared to men in the population. IV: There were no significant differences between the two partner groups regarding the quantity and quality of sleep or the health related quality of life. Conclusions: All tested questionnaires showed an acceptable reliability and responsiveness. The prevalence of urinary incontinence before and after intervention was higher than earlier reported. Men with LUTS had significantly poorer sleep quality, reduced sleep efficiency and a higher prevalence of insomnia than men in the population and men with inguinal hernia. The HRQOL is impaired in men with LUTS compared to men in the population and men with inguinal hernia. Partners are affected by the patients’ symptoms, and it is emotional rather than practical aspects that affect them most. Partners of men with LUTS did not differ significantly from partners in the population with regard to sleep and health related quality of life.
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Is There a Relationship between the Amount of Tissue Removed at Transurethral Resection of the Prostate and Clinical Improvement in Benign Prostatic HyperplasiaHakenberg, Oliver W., Helke, Christian, Manseck, Andreas, Wirth, Manfred P. 21 February 2014 (has links) (PDF)
Objective: To assess in a prospective trial the influence of the amount of tissue resected at transurethral resection of the prostate (TURP) for benign prostatic enlargement on the symptom improvement as assessed by symptom scores.
Methods: Between December 1996 and August 1998 a total of 138 men (mean age 68.2, range 53–89) with symptomatic benign prostatic enlargement who underwent TURP participated in this prospective study. Patients were assessed preoperatively with the International Prostate Symptom Score (IPSS), the American Urological Association Bother Score (AUA–BS) and the Benign Prostatic Hyperplasia Impact Index (BPH–II) as well as urinary flow rate measurements (Qmax) and prostate volume (PV) and residual urine determination by ultrasound. The amount of tissue resected was weighed. Patients were followed with reevaluation of Qmax, residual urine and the symptom and bother scores at 3 and 6 months.
Results: A close correlation between preoperative PV (mean 49.0 ml, SD 22.0, range 13–140) and the resected tissue weight (RTW, mean 24.7 g, SD 18.0, range 6–128) was seen (r = 0.75, p<0.001). Age was correlated with preoperative PV (r = 0.23, p<0.05). While significant mean improvements in Qmax, residual volume and IPSS, AUA–BS and BPH–II were found 3 and 6 months postoperatively, a negative correlation was seen between the RTW and the IPSS, the AUA–BS and the BPH–II 3 months after TURP (r = –0.23, p<0.024; r = –0.23, p<0.025; r = –0.20, p = 0.05). No statistically significant correlation was seen between symptom change and the percentage of PV removed or the residual prostatic weight. Classification of the patients into groups depending on preoperative PV (<30, 31–50, 51–70 and >70 ml) showed a tendency for patients with larger PV to gain more symptom improvement postoperatively.
Conclusions: Early symptom improvement after TURP will depend on the amount of tissue removed but the relationship is weak and affected by several other confounding factors. Apparently, the symptomatic improvement after TURP is not primarily dependent on the relative completeness of the resection. Patients with larger prostates and larger RTW tend to gain more symptomatic benefit from TURP than do patients with smaller prostates. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Diagnostic Significance of Prostate-Specific Antigen Velocity at Intermediate PSA Serum Levels in Relation to the Standard Deviation of Different Test SystemsManseck, Andreas, Pilarsky, Christian, Froschermaier, Stefan E., Menschikowski, Mario, Wirth, Manfred P. 17 February 2014 (has links) (PDF)
Serial prostate-specific antigen (PSA) measurements (PSA velocity) as an additional instrument to detect prostatic cancer was introduced in 1992. It has previously been reported that PSA increase per year differed in the last 5 years prior to diagnosis in patients with benign prostatic hyperplasia (0.18 ng/ml/year), locally confined (0.75 ng/ml/year) and metastasized (4.4 ng/ml/year) cancer of the prostate (CaP) in contrast to healthy men (0.04 ng/ml/year). The ability of PSA velocity to detect organ-confined CaP in patients with intermediate PSA serum values depends therefore on a reliable and reproducible PSA result. The present study comprised 85 men with PSA values between 3 and 8 ng/ml (Abbott IMx). PSA measurements were repeated with Abbott IMx (n = 85 patients) and Hybritech Tandem-E (n = 59 patients) assays. The PSA serum values differed from one examination to the other from 0.02 to 2.74 ng/ml with the Abbott IMx. Standard deviation amounted to 0.35 ng/ml with the Abbott IMx PSA assay. Using the Hybritech Tandem-E assay, mean standard deviation was 1.15 ng/ml and therefore higher than with the Abbott IMx assay. The difference from one test to the other ranged from 0.05 to 4.05 ng/ml with the Hybritech Tandem-E. Using the Abbott IMx assay, 10.6% of all repeat measurements exceeded 1 ng/ml whereas in the Hybritech Tandem-E assay 62.7% of the second measurements differed >1 ng/ml from the first PSA result. An increase in PSA serum values may therefore be due to intratest variation, physiological day-to-day variation as well as prostatic disease. It is important to notice that the intra-assay variation may be greater than the PSA increase per year in a patient with CaP. Therefore, PSA velocity seems to be of limited value. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Desenvolvimento de aplicações tecnológicas da metodologia de phage display no diagnóstico do câncer de próstataFreschi, Ana Paula Peres 28 November 2006 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Prostate cancer is the second cause of death in men by tumor, surpassed
only by lung cancer. Its occurrence is estimated to be 51 to 100,000 cases per
year. The increasing incidence levels observed may be partially explained by the
evolution of diagnostic methods, quality of information systems and longer life
expectancy. The identification of new cancer specific antigens and genes may
provide important biomarkers for diagnosis and instruments for the development of
new treatment strategies. The Phage Display technology may be able to select
peptides with different aims, such as the discovery of mimetic antigens that are
recognized by specific antibodies. Selected peptides may become potential tumor
biomarkers for prostate cancer diagnosis. It could be possible to use this
technology to identify proteins that are able to detect cancer earlier than the
conventional methods, to predict disease staging, and to develop new treatment
strategies based on more efficient biological targets.
The immunization of SPF (specific pathogen free) male chickens with total
proteins of tissues of prostate cancer has generated polyclonal specific IgY sera,
which were used in biopanning procedures against random peptide libraries.
Selected phages were characterized by sequencing and bioinformatics, and
subsequently by dot immunoblotting and ELISA to validate their specificity.
Selected peptides were mimotopes of putative proteins involved in the
carcinogenesis process. These peptides were further tested for their possible use
in the immune response diagnostics associated with tumor processes.
In this work, we have also successfully developed a general immunosensor
for diagnostics, performed on an exclusion liquid chromatography system based
on a micro column resin separation, using the selected bacteriophages as carriers
of antigens and antibodies. These phage are coupled to colored latex beads,
which are activated with different chemical groups. The presence of phage in the
process is of fundamental importance, once they favor the formation of the antigen-antibody complex, peptide-protein or peptide-substrate, amplifying the
optical detection during chromatographic separation or by micro-agglutination in
slides for optical microscopy detection. The new technology is practical and
simple, and may also be used for detection of other biomolecules or chemical
substances associated with infectious and genetic diseases, with high precision,
sensitivity, specificity, and rapidity, using low sample volumes and presenting a
low cost. / O câncer de próstata é a segunda causa de óbitos por câncer em homens,
sendo superado apenas pelo câncer de pulmão. A ocorrência estimada é de 51
casos novos para cada 100 mil homens por ano para este tipo de câncer. O
aumento observado nas taxas de incidência pode ser parcialmente justificado pela
evolução dos métodos diagnósticos, pela melhoria na qualidade dos sistemas de
informação do país e pelo aumento na expectativa de vida do brasileiro. A
identificação de novos antígenos ou genes específicos do câncer de próstata
pode prover novos biomarcadores e também fornecer instrumentos para o
desenvolvimento de novas modalidades de tratamento. A tecnologia de Phage
Display é capaz de selecionar peptídeos com diversas finalidades, como
mimetizar antígenos reconhecidos por anticorpos. Peptídeos selecionados por
esta técnica são potenciais marcadores tumorais para o diagnóstico do câncer de
próstata. Por meio desta metodologia pode ser possível identificar proteínas
capazes de detectar a resposta imune contra o tumor mais precocemente do que
os métodos tradicionais, predizer o estadio atual do tumor, além de permitir o
desenvolvimento de tratamentos mais eficientes.
Pela imunização de galos SPF (livre de patógenos específicos) com
proteínas totais de tecidos tumorais da próstata, foram obtidas IgY policlonais
específicas que foram utilizadas no biopanning contra uma biblioteca de
peptídeos recombinantes randômicos. Os fagos selecionados foram
caracterizados por seqüenciamento e subsequentemente testados por dot
immunoblotting e ELISA para validar a especificidade dos mesmos. Selecionou-se
peptídeos que mimetizam proteínas prostáticas, possivelmente proteínas
envolvidas no processo de tumorigênese. Esses peptídeos foram testados quanto
a sua possível utilização no diagnóstico da resposta imune associada a processos
tumorais.
Neste trabalho, também foi desenvolvido com sucesso um imunossensor
para diagnóstico que tem como base de detecção um sistema de cromatografia
líquida por exclusão em micro colunas cromatográficas com bacteriófagos
filamentosos carreadores de antígeno(s) e/ou anticorpo(s), selecionados por
phage display, acoplados microesferas de látex coloridas, ativadas com diferentes
grupamentos químicos. A presença do fago é de grande importância no processo,
pois favorece a formação dos complexos antígeno-anticorpo, peptídeo-proteína
ou peptídeo-substrato, ampliando a detecção ótica durante a separação por
cromatografia ou por microaglutinação em microscopia ótica. A nova tecnologia
pode também ser usada para a detecção de biomoléculas ou substâncias
químicas associados a doenças infecciosas, parasitárias e genéticas, com
rapidez, precisão, sensibilidade e reprodutibilidade, utilizando-se pequenos
volumes de amostras e reagentes, apresentando praticidade e baixos custos. / Doutor em Genética e Bioquímica
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