Prostate cancer is the most common cancer among men in the United States and is one of the leading causes of cancer death among men of all races. However, African-American men are at particularly high risk. These men are diagnosed more often with prostate cancer, are diagnosed later, and are more than twice as likely to die from prostate cancer than are Caucasian men. A strategy to address this inequity was to develop a community based program that would reach this at risk population. The goal of the project was to develop an evidence-based, theory-supported education and referral program to promote prostate cancer prevention screening among African-American men utilizing New York community church settings. The resultant scholarly project aims to motivate the target population towards prostate cancer prevention screening as appropriate through the development of an evidence-based, theory-supported, community-focused education and referral program using self-efficacy theory. This project provides a program, grounded in self-efficacy, that will educate African-American men about prostate cancer, empower them with knowledge regarding risk, motivate them to seek preventative screenings, and obtain care if needed. An evaluation strategy was developed incorporating a post-test questionnaire to measure participant knowledge and self-efficacy along with a process for measuring referrals to local screening and treatment programs. The program will bring about positive social change through empowerment of a population of men suffering from disparate access to care resulting in increased morbidity and mortality. Dissemination of the project will include presentations to the community church leaders and Caribbean healthcare professionals, as well as publication in Parish nursing journals.

In 2016, prostate cancer was the second leading cause of fatality in the United States. However, the population in this study 'Black American men, ages 40 and older, in selected counties in Fulton, DeKalb, Gwinnett, Clayton and Atlanta metropolitan areas' tended to underutilize prostate cancer care. The purpose of this quantitative, nonexperimental descriptive study was to determine whether socio-economic barriers and perceptions of Black American men about prostate cancer reduce their ability to access quality care in this county in Georgia. The Health Belief Model (HBM) was used to inform the predictive validity of perceptions, attitudes, and belief on individual health behaviors. Data were collected from 303 men through online and mailed researcher-made surveys that had been piloted using the demographic/medical background instrument; data from these surveys were then analyzed using frequency distribution and analysis of variance, coupled with Tukey's honest significant difference test. According to the results, 90% of the respondents stated that early detection and treatment were a perceived benefit of undergoing prostate cancer screening, and respondents perceived early detection, early treatment, and the reduced chance of dying from prostate cancer as the main reasons for undergoing the screening. A potential social significance to this study is that it provides information to health care providers and policy makers to better understand the patterns of Black American men and their motivation to seek early prostate cancer screening. Early screening could reduce costs, both economically and socially, associated with late diagnosis of this disease.

Les bisphénols et les phtalates sont des contaminants environnementaux ubiquitaires du fait de leur utilisation massive dans la fabrication de divers produits de consommation. L’exposition à ces molécules est liée à de nombreuses pathologies, dont les cancers hormono-dépendants, mais les mécanismes moléculaires exacts par lesquels elles induisent leurs effets restent largement inconnus.Au cours de ce travail, nous avons étudié l’implication de la sérine thréonine kinase PKD1 dans l’effet de quatre bisphénols : bisphénol A (BPA), bisphénol AF (BPAF), bisphénol F (BPF) et bisphénol S (BPS) et deux phtalates (DEHP et MEHP) sur des cellules du cancer du sein et de la prostate.Nous avons ainsi montré que le BPAF, BPF, BPS, DEHP et MEHP stimulent de manière dose-dépendante la prolifération, la clonogénicité et la croissance indépendante de l’ancrage des cellules MCF-7 et que ces processus sont dépendants de l’expression de PKD1. En revanche, nous avons mis en évidence l’absence d’effet pro-prolifératif du BPA dans trois lignées de cancer de la prostate (LNCaP, PC3 et DU145). D’autre part, nous avons pu identifier que le BPA induit la phosphorylation de PKD1 dans les mitochondries. Enfin, nous avons démontré qu’il existe un effet cumulatif de certaines combinaisons de traitement de bisphénols et de phtalates et mis en évidence que le BPAF induit la transition épithélio mésenchymateuse des cellules MCF-7.Nos résultats permettent ainsi d’identifier PKD1 comme étant une cible moléculaire de certains bisphénols et phtalates dans les cellules MCF-7 fournissant de nouvelles connaissances sur les mécanismes d’action de ces molécules. / Bisphenols and phthalates are ubiquitous environmental contaminants due to their extensive use in the production of a variety of consumer products. Exposure to these molecules is linked to multiple pathologies including hormone-dependent cancers. However, the exact molecular mechanisms by which they exert their effects remain largely unknown.In our study, we analyzed the implication of the serine threonine kinase PKD1 in the effect of four bisphenols : bisphenol A (BPA), bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol S (BPS) and two phthalates (DEHP and MEHP) on breast and prostate cancer cells.We thus showed that BPAF, BPF, BPS, DEHP and MEHP induce, in a dose-dependent manner, the proliferation, clonogenicity and anchorage independent growth of MCF-7 breast cancer cells, via a PKD1-dependent pathway. On the other hand, we showed that BPA does not have a pro-proliferative effect in three prostate cancer cell lines (LNCaP, PC3 and DU145). Furthermore, we determine that BPA induced the phosphorylation of PKD1 into the mitochondria. Finally, we demonstrated that BPAF stimulates epithelial to mesenchymal transition of MCF-7 cells and that co-exposure to combinations of bisphenols and phthalates induces cumulative proliferation effects in MCF-7 cells.Our results characterize PKD1 as a molecular target for bisphenols and phthalates in MCF-7 cells, providing new elements in the knowledge of the mechanisms of action of these molecules.

Prostate Cancer (PCa) is the second most diagnosed cancer in men across the world; it is considered the fifth leading cause of cancer related death according to cancer statistics 2012. Being a member of the internal parts in males reproductive system, testing any abnormality with the prostate gland remains both troublesome and inconvenient, and foremost inaccurate. The diagnostic practice starts with prostate-specific antigen (PSA) level testing, which in return is highly indecisive, provoking an over diagnosis and treatment. Genomic alteration and Single Nucleotide Variants (SNV s) are assumed to play a role during PCa progression. On behalf of the RIBOLUTION project, a project with the aim of finding diagnostic biomarkers from RNA sequences, SNV s in RNA sequences were analysed to pinpoint potential candidate genes in PCa. The fact that the cohort provides whole-transcriptome data of pro- static tissue promotes the possibility to obtain comprehensive knowledge of the cancerous changes. The advantage of detecting SNV s in RNA sequences relies in focusing on only those, which could be relevant to the gene’s func- tion. However, methods for detecting and analysing SNV s solely in RNA sequences are currently not yet established. This study aimed to (1) establish fitting and applicable assays to identify, inspect and conclude the potential role of SNV s in RNA sequences, (2) use the obtained knowledge to single out the genes that are potentially relevant for PCa. SNV s in the RIBOLUTION cohort were investigated. Prostate tissue was obtained from 40 PCa patients, and then RNA was sequenced using Next Generation Sequencing. In 16 patients, a pairwise prostatic tissue was taken, one a confirmed tumor tissue and the second a tumor-free tissue. As a control, samples from 8 men with benign prostatic hyperplasia were likewise sequenced. Different computational pipelines were established and successfully fulfilled the aim. The CVR Module (Calling Variants in RNA-Seq) is a computer- based pipeline intended to identify SNV s and discriminate between false positive and true positive calls. Validating the SNV s reported by the accomplished Module has shown high sensitivity (> 80% validated SNV s). Much as novel SNV s that had ∼ 101% higher median calling quality in comparison to SNV s found in dbSNP, the Single Nucleotide Polymorphism Database. In agreement with current knowledge, novel SNV s was observed in tumor samples with slight but significant increase vs. tfree tissue (P < 0.05, testing on proportion). On top of that, positive correlation between non-silent effect and novel SNV in tumor samples was also observed (P < 0.05, r = 0.33, Pearson’s correlation). Moreover, more than 40% of the candidate genes were found in COSMIC, the Catalog Of Somatic Mutations In Cancer; some of them are confirmed somatic mutation (cancer associated). About 11% were also reported in studies to be disease associated or observed in other diseases, mostly heredity related. Potential PCa associated genes were identified via combination of three different systematic methods: mutational clustering, mutational functional bias, and covariates of the mutated genes. The first method (mutational clustering), however, did not reveal any significant insight. The top candidate genes were then selected in accordance with the latter methods. The list of top candidate genes includes > 50% genes with direct association with PCa; > 80% genes previously reported in other cancer types, while ∼ 35% that are in- volved in PCa associated complexes. Besides well known and validated PCa biomarker (alpha-methylacyl-CoA racemase (AMACR)), we identify for the first time, from mutational prospective, 22% of the genes to be potentially associated with PCa. Among those, one of the most promising candidate genes is NWD1 (NACHT and WD repeat domain containing 1). This gene was mentioned in a previous study to be a potential player in PCa prognosis. We add to this our novel observation, NWD1 was found significantly mutated in the entire tumor samples. These significant findings were proven to be tumor-specific when they were compared to the available control and tumor-free (P < 0.05, non-parametric ranking). We conclude that analyzing SNV s from RNA is as useful and informative as DNA-based ones, and accomplish further benefits that could be gained once the suggested methods are adapted.

京都大学 / 0048 / 新制・課程博士 / 博士(薬学) / 甲第18218号 / 薬博第808号 / 新制||薬||238(附属図書館) / 31076 / 京都大学大学院薬学研究科医療薬科学専攻 / (主査)教授 佐治 英郎, 教授 橋田 充, 教授 髙倉 喜信 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

No description available.

Targeted radionuclide therapy is becoming a widely used cancer treatment strategy. By radiolabeling receptor-specific peptides, cancer cells overexpressing the receptor can be selectively targeted, and the cytotoxic radionuclide can be delivered to the target cell or tissue for therapeutic or diagnostic purposes. Bombesin analogues have been previously developed and utilized to target the gastrin-releasing peptide receptor (GRPR), a receptor commonly overexpressed in prostate cancer cells. The RM26 analogue derived from the native bombesin is an antagonistic ligand of GRPR and a possible candidate for targeted radiotherapy. Prolonging the half-life of the molecule is an important aspect of developing a new protein therapeutic. Using albumin binding domain (ABD) for this purpose is an emerging strategy in recent years. ABD is able to bind to serum albumin and thus remains in the blood circulation for a long period of time. It is also a scaffold for protein engineering efforts and by coupling receptor-specific ligands to ABD, the target-specific binding along with extended in vivo halflife can be achieved. In this project, an RM26 analogue with a PEG linker and ABD with a DOTA chelator for future radiolabeling were synthesized with solid phase peptide synthesis (SPPS), conjugated, purified by RP-HPLC and analyzed by mass spectrometry. The binding properties of the conjugate were evaluated by SPR-based biosensory studies, and further experiments are planned for the testing the product and its potential application in radionuclide therapy. / Riktad radioterapi är en allt vanligare metod för behandling av cancer. Genom att radioinmärka receptor-specifika peptider kan dessa selektivt levereras till tumörceller som uttrycker receptorn. Radioterapi kan användas för diagnostik eller terapi, beroende på kopplad radionuklid. Bombesinanaloger har utvecklats och använts för att selektivt binda gastrinfrisättande peptidreceptor (gastrin-releasing peptide receptor, GRPR), en receptor som ofta är överuttryckt i prostatacancer. Bombesinanalogen RM26, som har sitt ursprung från nativt bombesin, är en antagonist till GRPR och kan möjligen användas för riktad radioterapi av prostatacancer. Vid utvecklingen av nya proteinläkemedel är halveringstiden i serum en viktig aspekt. En nyligen utvecklad strategi för att förlänga halveringstiden i serum är fusion av det  tumörspecifika proteinet till en albumin-bindande domän (ABD). ABD binder till albumin, ochsåledes kan fusionsproteinet bevaras i blodcirkulationen under en längre tid. I detta projekt, har både RM26 med en PEG-linker, och ABD med en DOTA kelator syntetiserats med fastfaspeptidsyntes (solid phase peptide synthesis, SPPS). RM26-PEG och DOTA-ABD har därefter konjugerats, renats med RP-HPLC och analyserats med massspektrometri. Bindning till albumin har utvärderats med ytplasmonresonans (surface plasmon resonance, SPR). Vidare studier planeras för att utvärdera peptid-proteinkonjugatet och dess potential för riktad radioterapi.

Syftet med denna systematiska litteraturstudie var att undersöka hur patienter medprostatacancer uppfattade den givna informationen om sin sjukdom ochbehandlingen av den. Författarna har utgått från Willman m fl (2006)evidensbaserade metod. De vetenskapliga artiklarna som legat till grund förstudien granskades i protokoll av Carlsson & Eiman m fl (2003), modifierade avförfattarna. Studien innefattar tolv vetenskapliga artiklar. Författarna kom iresultatet fram till tre olika temaområden: informationsmaterial och hjälpmedel,informatörer och stödgivare samt behov av information. I många studier utrycktepatienterna missnöje med informationen, den ansågs inte vara tillräcklig. Demetoder som visade sig framgångsrika var rådgivning och uppföljning via telefonav en sjuksköterska efter utskrivning. Även de patienter som försågs medutbildningspaket var väldigt nöjda med informationen. Kontakt med andra mänmed erfarenhet av prostatacancer ansågs också vara viktig. / The aim of this systematic literature review was to look at how patients withprostate cancer regarded the information they received about their condition andits treatments. The authors have used Willman et al (2006) evidence basedmethod. The results of this study are based on twelve articles. The articles that areincluded were examined with a protocol by Carlsson & Eiman et al (2003),modified by the authors. The results are divided into three themes; informationmaterial and aids, informant and support and need for information. In many of thestudies patients expressed dissatisfaction with the information, they felt that it wasnot considered sufficient. The successful methods for giving information weretelephone guidance and a follow-up by a nurse after discharge. Also patients whoreceived an education package were very pleased with the information. Contactwith other men with experience of prostate cancer was also considered veryhelpful.

No description available.

Prostate cancer in the United States shows great disparities among race and socioeconomic status. Disparities in cancer rates in South Carolina are severe. Cancer control policies are lacking in ways to identify reasons for high risk populations and cost-effective ways to do so. An innovative spatial visualization program called the GeoViz Toolkit was used to determine areas of high Prostate Cancer incidence and mortality in South Carolina (rates obtained from the South Carolina Central Cancer Registry) compared with socioeconomic variables (education, income, lack of health insurance, and living in rural areas) and race. From there, recommendations were made using the South Carolina Cancer Alliance's "South Carolina Comprehensive Cancer Control Plan" objectives for Prostate Cancer for the top counties that were determined to have the highest need of intervention. These 11 counties include Colleton, Hampton, Allendale, Barnwell, Fairfield, Dillon, Marion, Marlboro, Williamsburg, Bamberg, and Orangeburg.