Browsing by Subject "eturauhassyöpä"
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(2021)Eturauhassyöpä koskettaa yhä useampaa miestä ja sen diagnostiikkaan on kehitetty useita kuvantamismenetelmiä. Positroniemissiotomografia tietokonetomografiaan yhdistettynä on rutiinikäytössä oleva kuvantamistapa, jossa yhdistyy tietokonetomografilla saatava anatominen tarkkuus positroniemissiotomografian kykyyn kuvantaa metabolisten prosessien tai eri substraattien pitoisuuksien vaihteluita. Retrospektiivisen tutkimuksen tekohetkellä HUS:n Kliinisen fysiologian ja isotooppilääketieteen yksikössä oli siirrytty eturauhassyövän ja eturauhassyövän kemiallisen relapsin PET/TT-kuvantamisessa 18F-koliinista 68Ga-PSMA-merkkiaineeseen, eikä näiden kahden merkkiaineen välillä oltu vielä tehty vertailua. Tutkimukseen valittiin 143 potilasta, joista noin puolet oli kuvattu 18F-koliinilla ja puolet 68Ga-PSMA:lla. PET-kuvantamisen tuloksia verrattiin TT-kuvantamisen tuloksiin ja tuloksista laskettiin tilastollisissa suureita: p-arvo, sensitiivisyys/spesifisyys ja PPV/NPV. Tuloksista nähdään, että PET:lla todetaan tarkemmin leesioita ja metastaaseja kuin TT:lla. Merkkiaineiden välillä ei pystytty tekemään suoraa vertailua, koska potilaat oli jaettu kahteen ryhmään missä kummassakin käytettiin vain yhtä merkkiainetta. Epäsuorasta vertailusta nähtiin, että 18F-koliini tuotti hieman varmemmin luotettavia tuloksia 68Ga-PSMA:aan verrattuna.
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(2016)Extracellular vesicles are cell-derived vesicles which consist of two lipid layers. Extracellular vesicles involve in intercellular communication, maintaining of homeostase and development of pathophysiological states in human body. Extracellular vesicles are promising biomarkers and drug carriers in future. The aim of this study was to develop a method based on time resolved fluorescence microscopy and autologous extracellular vesicles labelled with environmentally sensitive fluorescent probes for studying the distribution of mitose-inhibitor paclitaxel in prostate cancer cells (PC-3) carried by extracellular vesicles. The efficacy of paclitaxel loaded extracellular vesicles was compared to synthetic liposomes. The two subpopulations of extracellular vesicles, exosome -and microvesicle-enriched, were isolated from the PC-3 cell media by differential ultracentrifugation. The size distribution and particle concentration of extracellular vesicles was determined by nanoparticle tracking analysis. DSPC-Cholesterol liposomes were prepared by reverse-phase evaporation method and the size distribution of the liposomes was determined by dynamic laser diffraction and nanoparticle tracking analysis. Paclitaxel was loaded into the liposomes in hydration phase and into the extracellular vesicles by incubating vesicles and paclitaxel. Unbound paclitaxel was removed from samples by ultracentrifugation. The the dose-dependent sytotoxicity of paclitaxel loaded extracellular vesicles and liposomes was evaluated with Alamar Blue viability assay. The release and distribution of paclitaxel from extracellular vesicles in living PC-3 cells was investigated by confocal microscopy and time-resolved fluorescence microscopy. The exosomes had approximately 50 nm smaller diameter than microvesicles and exosome particle concentrations were significantly higher compared to microvesicles. According to viability assays conducted with wide range of concentrations, paclitaxel loaded in microvesicles were slightly more effective than paclitaxel loaded in exosomes. The time-resolved fluorescence microscopy was useful method for investigating the release and distribution of extracellular vesicle bound paclitaxel, since we succesfully detected changes in Paclitaxel-OregonGreen fluorescence lifetime in different phases of the drug delivery process. With confocal microscopy we detected that paclitaxel loaded extracellular vesicles were already uptaken inside the cells after two hours of incubation and after few hours, paclitaxel was detected in microtubules of PC-3 cells and killed PC-3 cells. Extracellular vesicles may improve the accumulation of paclitaxel into tumor cells thus preventing the side-effects of paclitaxel. Nevertheless, PC-3 cell derived extracellular vesicles have ability to increase the PC-3 cell viability, which limits their potential use as drug carrier due to safety issues. In addition, extracellular vesicles characterization and isolation methods lack standardization and the isolation of exosomes and microvesicles is impossible due to this fact. Extracellular vesicles involvement in physiological and pathophysiological states should be investigated throughoutly and their safety as drug carriers should be examined both in animal and human.
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(2013)Prostate cancer is the most common cancer among men in Finland. Today, new prostate cancers are diagnosed in an early phase of the disease when the cancer is still local and effectiveness of the treatments good. There are many effective treatment options for localised prostate cancer but all of them cause multiple side effects. No comprehensive information about prostate cancer patients' experiences, treatment consequences and outcomes has been available. National Institute for Health and Welfare (THL) carried out a nationwide survey to prostate cancer patients diagnosed in 2004. The questionnaire was sent by mail in 2009. Patients were asked to report their experiences during the diagnosis and treatment selection (prostatectomy, hormone therapy, external beam radiation, brachytherapy, surveillance). They were asked about amount and harmfulness of side effects and satisfaction with outcome of the treatment. An association between the side effects and satisfaction with the treatment outcome was also studied. A total of 1239 responses were accepted for the study (response rate 73%). All treatments caused several side effects, and up to half of the patients had some adverse effect still present at the time of the survey. Most of the side effects concerned urinary or sexual dysfunction, in external beam radiation also bowel dysfunction. All treatments caused sexual dysfunction, but radiation therapy less than the other treatments. Side effects caused by hormone therapy were specific for this treatment, like hot flashes and mood disturbances. Patients treated with prostatectomy were least satisfied with the outcome of the treatment and dissatisfaction was mostly associated with sexual and urinary dysfunction. Patients treated with radiation therapy were most satisfied with the outcome. Urinary and bowel dysfunction impaired the satisfaction in patients treated with external beam radiation. All prostate cancer treatments cause plenty of potentially harmful side effects that may be challenging for psychological and psychosocial well-being of the patients. Thus, both treatment modalities and means to support well-being of the patients should be developed further. Actions that enhance well-being and prevent and relieve side effects should be an essential part of standard clinical procedures for every prostate cancer patient.
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(2010)Prostate cancer is one of the most common cancers in the developed countries. Prostate cancer is slowly progressing cancer but can transform into aggressive disease and metastasize. Metastases are the major cause of mortality. Androgens play an important role in the pathogenesis of prostate cancer and prostate tumors are usually dependent on androgens. Thus the aim of the treatment is to eliminate testicular androgens by surgical or medical castration and/or block the effect of androgens on the prostate with antiandrogens. Prostate cancer and new therapies to treat the disease are being investigated vigorously. Numerous in vivo models of prostate cancer have been developed. Androgen responsive animal models mimic prostate cancer more closely. There are many animal species that may be used to model prostate cancer but mouse is no doubt the most useful. Tumor models can be created by inoculating human cancer cells or solid parts of tumors into immune deficient mice. Orthotopic prostate tumor models reflect the abnormal cancer cell-stroma interactions occuring in prostate cancer. Transgenic mouse models are becoming more and more common in the research of prostate cancer. Transgenic models are able to model the initiation and progression of the disease more realistically. Growth of the orthotopic tumor is difficult to monitor without measuring serum prostate specific antigen (PSA) concentrations or using specific imaging methods. Imaging techniques, such as optical imaging, are being utilized in different in vivo models of prostate cancer. The objective of the experimental part of this thesis was to optimize bioluminescence imaging method in androgen responsive cell line LNCaP-luc2 in orthotopic model of prostate cancer. Bioluminescence imaging is based on a reaction catalyzed by a luciferase which is expressed by the tumor cells. In the ATP-dependent reaction luciferase enzyme oxidizes its substrate, luciferin, and produces light. In addition, the purpose of this study was to examine the effects of medical therapy and castration on tumor growth. Bioluminescence imaging enabled noninvasive, real-time and longitudinal monitoring of the growth of prostate tumors in this model. Quantification of the tumors with bioluminescence measurement was faster than with ultrasound sonography. It was also possible to monitor the growth of the tumors more often with bioluminescence imaging than with PSA measurements. Bioluminescence imaging was found to correlate better with serum PSA concentrations than with the actual size of the tumor. However prostate tumor size was noted to correlate better with PSA concentrations than with bioluminescence imaging in this study. Medical treatment or castration was found to have no effect on the size of the tumors when measured with bioluminescence imaging. The larger size of the tumors than expected was the probable reason for this. Bioluminescence imaging is not suitable for large or necrotic tumors because this imaging method can only be applied in living cells. In addition, a successful luciferin injection is essential for the proper utilization of bioluminescence imaging in this model. More studies are needed to validate the model for example in proving the effects of the medical therapies.
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(2011)Eturauhassyöpä on miesten yleisin syöpä länsimaissa. Suomessa se aiheuttaa vuosittain noin 800 kuolemaa ja uusia eturauhassyöpiä diagnosoidaan vuosittain yli 4 000 kappaletta. Eturauhassyövän tarkasteleminen tilastotieteen keinoin on lähtökohtaisesti kannattavaa, koska eturauhassyövän diagnosoinnista ja hoidosta kerätään laajoja ja kattavia tietoaineistoja. Aineistojen otoskoot ovat lisäksi sairauden yleisyydestä johtuen verrattain suuria, mikä edesauttaa tilastollisia analyyseja. Tässä tutkielmassa analysoidaan tilastollisesti suomalaisesta eturauhassyövän seulontatutkimuksesta peräisin olevaa aineistoa ($n$=1 608) elinaika-analyysin keinoin. Elinaika-analyysi on tilastotieteen osa-alue, jonka tehtävänä on antaa vastauksia kysymyksiin, jotka liittyvät tiettyjen kiinnostavien tapahtumien ilmenemiseen ja selittävien tekijöiden vaikutukseen tapahtumien ilmenemiseen. Elinaika-analyysin menetelmistä sovelletaan regressiomalleihin kuuluvaa Coxin suhteellisten riskitiheyksien mallia ja Kaplan-Meierin estimaattoreita. Sovelletut menetelmät ovat yleisesti sovellettuja eturauhassyövän tilastollisessa analyysissa. Analyysin tulokset osoittavat, että diagnoosihetkellä määritetyt muuttujat selittävät eturauhassyöpäkuolleisuutta tilastollisesti merkitsevällä tavalla. Merkittävä osa kuolleisuudesta jää kuitenkin selittämättä, minkä vuoksi saatujen tulosten sovellettavuus rajoittuu väestötason tarkasteluun; yksittäisiä potilaita koskevien hoitopäätösten teko vaatii diagnoosihetkellä määritettyjen muuttujien lisäksi muita tutkimuksia. Analyysiin sisältyvät diagnostiset tarkastelut eivät paljasta merkittäviä poikkeamia sovellettuihin tilastollisiin menetelmiin sisältyvistä oletuksista.
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(2023)Kartiokeilatietokonetomografia eli KKTT on tyypillisimmin käytetty kuvausmodaliteetti kuvantaohjatussa sädehoidossa ja sitä käytetään pääasiassa potilaan asemointiin ja sädehoidon kohdistamiseen. KKTT-kuvantaminen perustuu röntgensäteilyyn ja sen käytön haittapuolena potilas saa ylimääräistä säteilyannosta sekä hoidettavalle alueelle että sitä ympäröiville terveille kudoksille. Eturauhassyöpä on miesten yleisin syöpätyyppi Suomessa ja paikallista eturauhassyöpää voidaan hoitaa esimerkiksi sädehoidolla. Ionisoivan säteilyn käyttö lisää terveiden kudosten syöpäriskiä ja siksi KKTT-kuvantamisen aiheuttaman säteilyannoksen määritys ja optimointi on tärkeää. Tämän työn tarkoituksena on selvittää yhdeksässä suomalaisessa sairaalassa käytettäviä KKTT-kuvantamisen kuvausparametreja ja kuvauskäytäntöjä sekä laskennallisesti määrittää kuvantamisen aiheuttamia potilasannoksia ja optimoinnin vaikutuksia. Laskenta tehdään käyttäen Monte Carlo menetelmään perustuvaa ImpactMC-ohjelmaa, ICRP:n vokselitestikappaletta ja suomalaisten sairaaloiden käyttämiä kuvantamisen parametreja. Tulosten esittämiseen käytetään riskielinten kokonais- ja elinannoksia, isodoosipiirroksia xy- ja xz-tasoissa, riskielinten annostilavuushistogrammeja sekä annosprofiileja xy- ja xz-tasoissa. Tässä työssä lasketut riskielinten elinannokset ovat yhdellä kuvauskerralla noin mGy:n luokkaa ja kokonaissäteilyannokset riippuvat vahvasti kuvausfraktioiden määrästä. Symmetrisen keilan geometriassa säteilyannokset ovat pienempiä kuin epäsymmetrisen keilan geometriassa. Kuvantamisessa käytettävä kuvausalueen pituus, kuvausputken aloituskulma ja kuvausputken kiertosuunta vaikuttavat symmetrisessä geometriassa myös eri riskielimien saamaan säteilyannokseen ja säteilyn jakautumiseen xz-tasossa. Tuloksista havaitaan, että sekä symmetrisen että epäsymmetrisen keilan tapauksissa kuvausparametrien optimointi esimerkiksi putkivirtaa laskemalla pienentää eturauhasen, peräsuolen, reisiluun punaista luuydintä sisältävän osan ja virtsarakon saamaa elinannosta. Kuvausparametrien optimointi pienentää annostasoja myös kaikissa muissa lasketuissa tapauksissa kuten isodoosipiirroksissa ja annosprofiileissa.
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(2012)Prostate cancer is the most common cancer in men in Finland. Health care costs increase annually and cost of cancer is significant to the society. Because resources are scarce more information is needed about the costs of diseases as well as treatment effectiveness. In addition to clinical effectiveness it is important to assess the value of healthcare technologies from the patient's point of view by measuring the treatment's effect on patients' quality of life. In this thesis a literature review was made on the following topics: cost of treating prostate cancer, prostate cancer patients' quality of life and cost-effectiveness of prostate cancer. The aim of the research was to determine what the drug costs are in relation to the total cost of treatment for prostate cancer in different stages of the disease and assess how the quality of life changes during the first year of treatment depending on the form of treatment. Drug costs were calculated from the health care payer's perspective in a six month cross-sectional study. The study population included a total of 629 prostate cancer patients treated in the Helsinki and Uudenmaa hospital district (HUS). The quality of life study population (N=367) was different of that used to calculate drug costs. The quality of life was measured according to an ongoing cost-effectiveness research at HUS. It was measured with 15D-instrument before receiving cancer treatment and three, six and twelve months after the beginning of treatment. Drug costs in relation to the total cost of prostate cancer treatment were significant. In patients with meta-static cancer drugs were 53 % of the total cost of cancer treatment. In remission patients the total costs of cancer treatment were the lowest compared to other diseases stages, but drug costs were still 30 % of the total costs. For patients receiving palliative treatment, local or relapse cancer patients, and patients whose cancer was just diagnosed, the total drug costs were 19%, 13% and 0%, respectively. Policlinic visits and policlinic procedures were also a significant cause of the total costs. Quality of life of prostate cancer patients is incredibly good compared to age-standardized population. However the patients' quality of life decreases statistically and clinically significantly during the first year of treatment. Before treatment 15D score was 0,91 and after 12 months it was 0,88. When assessed in different treatment groups the quality of life decreased the least in patients treated with waiting. The largest statistically significant change occurred in patients treated with radiation. The strength of the study is that the costs were calculated per patient according to real resource use. The study also had limitations. The costs of primary care were not included in the calculations. Also cancer related pain medication, depression and erectile dysfunction drugs should be included in the drug costs. The follow-up time of measuring quality of life was too short. In the future it would be important to study the cost-effectiveness of medication as well as the cost-effectiveness of the different forms of treatment in prostate cancer.
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(2019)Johdanto: Eturauhassyöpä on miesten yleisin syöpä. Radikaaliprostatektomia on ainoa hoito, jonka on osoitettu lisäävän elinaikaa paikallisessa eturauhassyövässä pelkkään seurantaan verrattuna. Robottiavusteinen kirurgia on lisääntynyt eturauhassyöpäleikkauksissa nopeasti, vaikka satunnaistettu tutkimusnäyttö robotin eduista on vähäistä. Robotin käyttöön liittyviä lisäkustannuksia on perusteltu muun muassa lyhyemmillä sairaalahoitojaksoilla sekä mahdollisesti vähemmillä komplikaatioilla. Tavoitteet: Tutkimuksen tarkoituksena oli vertailla retropubisesti (avoimesti) ja robottiavusteisesti leikattujen eturauhassyöpäpotilaiden sairaalassaoloaikoja. Tutkimuksessa arvioitiin primaarileikkaukseen liittyvää sairaalahoitoa sekä kotiutumisen jälkeisten komplikaatioiden aiheuttamia sairaalahoitojaksoja. Lisäksi selvitettiin näihin vaikuttavia tekijöitä. Menetelmät: Analysoimme 7520 Suomessa vuosina 2007-2014 leikatun radikaaliprostektomiapotilaan Terveyden ja hyvinvoinnin laitokselta saadut hoitoilmoitustiedot. Tarkasteltuja muuttujia olivat leikkaustekniikka, imusolmukedissektio, tulotaso, asuinkunnan koko, ikä leikkaushetkellä, tehtiinkö leikkaus yliopistosairaalassa vai keskussairaalassa, leikkausvuosi, sekä CCI-luokka. Tulokset: Robottiavusteisesti leikatuille potilaille kertyi vähemmän sairaalapäiviä sekä leikkauksen yhteydessä että yhden ja kolmen kuukauden seurannassa. Robottiavusteisesti leikatut potilaat palasivat myös harvemmin sairaalahoitoon. Imusolmukedissektion tekeminen lisäsi merkittävästi sekä sairaalahoidon kestoa että uusien sairaalahoitojaksojen riskiä. Molemmilla tekniikoilla sairaalahoidon kesto ja uusia sairaalahoitoja tarvitsevien potilaiden suhteellinen osuus pienenivät seuranta-aikana. Pohdinta: Avokirurgia sekä imusolmukedissektion tekeminen altistavat potilaat pitemmälle hoitoajalle sekä uusille sairaalahoidoille. Seuranta-ajan aikana tapahtunut hoitoaikojen lyheneminen ja sairaalahoitoon palaamisen vähentyminen johtuu todennäköisesti tekniikoiden kehittymisestä sekä yleisestä muutoksesta sairaaloiden hoitokäytännöissä. Tutkimustulokset vaikuttaisivat olevan linjassa aiemman tutkimusnäytön kanssa, jonka mukaan robotin käyttöön liittyy vähemmän komplikaatioita ja lyhyemmät sairaalahoitoajat. Leikkaustekniikan ja imusolmukedissektion vaikutus sairaalahoitoon palaamiseen olivat aineistossamme suuremmat kuin aiemmassa kirjallisuudessa. (213 sanaa)
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(2023)Metastatic prostate cancer is often fatal disease stage. Mechanism causing prostate cancer remains unknown, but possible mechanism relies on hormones. Testosterone may activate spontaneous cell division of oncogenes. Prostate cancer cells require androgen cell stimulation of AR to grow in early stages of prostate cancer, approximately 80-90% of prostate cancer cases are androgen dependent. 3bHSD1, encoded by HSD3B1, catalyzes the conversion of dehydroepiandrosterone to androstenedione and further to T and DHT. SNP (1245A to C) in HSD3B1 changes asparagine to threonine in position 367 resulting the enzyme accumulation and increased function. With androgen deprivation therapy castrate levels of testosterone are often achieved and it induces positive response in most PCa patients, but the polymorphism of 1245C is related with lower survival rate and higher probability for PCa to develop into CRPC. The aim of this study was to find out the effect of SNP in 3bHSD1 to androgen levels in patients treated with ADT. 32 patients were first genotyped based on SNP in the HSD3B1 gene (rs1047303) with 96.9 % success rate. 21 patients represented genotype AA, 9 AC and 1 patient CC. Other mutation in rs6203 was also detected. Genotyping was done by isolating DNA from blood samples and preparing it further for Sanger sequencing. Steroid analysis was performed by using LC/MS, using liquid-liquid extraction as sample preparation method. Altogether 21 steroids were analyzed from serum samples. Samples were taken every 3 months, during 33 months period for longest. The concentrations of T and DHT were reduced in AA genotype group after ADT as was expected to happen in all of the groups. In fact, the only significant changes were seen in AA genotype with for example the concentrations of previously mentioned T, DHEA and also A4. The changes in measured androgen levels cannot be generalized to concern especially the CC genotype, as there was only one patient homozygote with the mutation. Even though these results gave promising data of possible androgen synthesis pathways, a similar study must be rerun with larger patient data to be sure of the characteristics of different genotypes. Also, the effect of SNP in rs6203 remains still unknown.
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(2023)Metastatic prostate cancer is often fatal disease stage. Mechanism causing prostate cancer remains unknown, but possible mechanism relies on hormones. Testosterone may activate spontaneous cell division of oncogenes. Prostate cancer cells require androgen cell stimulation of AR to grow in early stages of prostate cancer, approximately 80-90% of prostate cancer cases are androgen dependent. 3bHSD1, encoded by HSD3B1, catalyzes the conversion of dehydroepiandrosterone to androstenedione and further to T and DHT. SNP (1245A to C) in HSD3B1 changes asparagine to threonine in position 367 resulting the enzyme accumulation and increased function. With androgen deprivation therapy castrate levels of testosterone are often achieved and it induces positive response in most PCa patients, but the polymorphism of 1245C is related with lower survival rate and higher probability for PCa to develop into CRPC. The aim of this study was to find out the effect of SNP in 3bHSD1 to androgen levels in patients treated with ADT. 32 patients were first genotyped based on SNP in the HSD3B1 gene (rs1047303) with 96.9 % success rate. 21 patients represented genotype AA, 9 AC and 1 patient CC. Other mutation in rs6203 was also detected. Genotyping was done by isolating DNA from blood samples and preparing it further for Sanger sequencing. Steroid analysis was performed by using LC/MS, using liquid-liquid extraction as sample preparation method. Altogether 21 steroids were analyzed from serum samples. Samples were taken every 3 months, during 33 months period for longest. The concentrations of T and DHT were reduced in AA genotype group after ADT as was expected to happen in all of the groups. In fact, the only significant changes were seen in AA genotype with for example the concentrations of previously mentioned T, DHEA and also A4. The changes in measured androgen levels cannot be generalized to concern especially the CC genotype, as there was only one patient homozygote with the mutation. Even though these results gave promising data of possible androgen synthesis pathways, a similar study must be rerun with larger patient data to be sure of the characteristics of different genotypes. Also, the effect of SNP in rs6203 remains still unknown.
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