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Lundström, K.-J., Söderstrom, L., Jernow, H., Stattin, P. & Nordin, P. (2019). Epidemiology of hydrocele and spermatocele; incidence, treatment and complications. Scandinavian journal of urology, 53(2-3), 134-138
Öppna denna publikation i ny flik eller fönster >>Epidemiology of hydrocele and spermatocele; incidence, treatment and complications
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2019 (Engelska)Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, nr 2-3, s. 134-138Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objectives: To estimate the incidence of men seeking specialized care and receiving treatment for hydro or spermatocele complaints. Also, to determine the risk of complications of treatment.

Materials and methods: The total number of men living in Sweden each year from 2005 to 2014 was used to calculate incidence and age distribution of adult (≥18 years) men seeking specialized healthcare with either hydro or spermatocele. This was done by using nationwide registries, mandatory by law. They contain information on primary or discharge diagnosis, procedure codes and antibiotic prescriptions. Also, complication rates comparing aspiration (with or without sclerotherapy) and conventional surgery were analysed.

Results: The incidence of men with either hydro or spermatocele diagnosis in specialized healthcare was ∼100/100,000 men. The treatment incidence was 17/100,000 men. Orchiectomy was used as primary treatment in 2.4% of cases. The risk of experiencing a complication was clinically and statistically significantly increased with conventional surgery as compared with aspiration, 17.5% (1607/9174) vs 4.6% (181/3920), corresponding to relative risk of 3.79 (95% CI = 3.27–4.40). Hematoma and infections were the most common complications.

Conclusion: Hydro and spermatoceles are common, affecting elderly men. Aspiration seems advantageous with respect to complications and can be recommended due to the benign course of the disease. The indication for conventional surgery might be questioned such as the use of orchiectomy as primary treatment.

Ort, förlag, år, upplaga, sidor
Taylor & Francis, 2019
Nyckelord
Testicular hydrocele, spermatocele, incidence, postoperative complications
Nationell ämneskategori
Urologi och njurmedicin
Identifikatorer
urn:nbn:se:umu:diva-158954 (URN)10.1080/21681805.2019.1600582 (DOI)000465949700001 ()30990342 (PubMedID)
Tillgänglig från: 2019-05-27 Skapad: 2019-05-27 Senast uppdaterad: 2019-10-10Bibliografiskt granskad
Matejcic, M., Saunders, E. J., Dadaev, T., Brook, M. N., Wang, K., Sheng, X., . . . Sanchez, M. (2019). Germline variation at 8q24 and prostate cancer risk in men of European ancestry (vol 9, 4616, 2018). Nature Communications, 10, Article ID 382.
Öppna denna publikation i ny flik eller fönster >>Germline variation at 8q24 and prostate cancer risk in men of European ancestry (vol 9, 4616, 2018)
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2019 (Engelska)Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, artikel-id 382Artikel i tidskrift (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
NATURE PUBLISHING GROUP, 2019
Identifikatorer
urn:nbn:se:umu:diva-155954 (URN)10.1038/s41467-019-08293-z (DOI)000455955100001 ()30655571 (PubMedID)
Anmärkning

Correction to: Nature Communications; https://doi.org/10.1038/s41467-018-06863-1, published online 5 November 2018.

Tillgänglig från: 2019-02-08 Skapad: 2019-02-08 Senast uppdaterad: 2019-02-08Bibliografiskt granskad
Fritz, J., Bjorge, T., Nagel, G., Concin, H., Manjer, J., Häggström, C., . . . Ulmer, H. (2019). Insulin resistance measured by the triglyceride-glucose index and risk of obesity-related cancers: An epidemiological investigation in more than 500,000 individuals.. Paper presented at Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), MAY 31-JUN 04, 2019, Chicago, IL. Journal of Clinical Oncology, 37(15), 1552-1552
Öppna denna publikation i ny flik eller fönster >>Insulin resistance measured by the triglyceride-glucose index and risk of obesity-related cancers: An epidemiological investigation in more than 500,000 individuals.
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2019 (Engelska)Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, nr 15, s. 1552-1552Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
Abstract [en]

Background: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. We aimed to determine to what extent insulin resistance measured as the logarithmized triglyceride glucose product (TyG index) mediates the effect of BMI on risk of obesity-related cancers. Methods: A total of 510,471 individuals from six European cohorts with a mean age of 43.1 years were included in the study. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with ten common obesity-related cancer sites, and quantified the proportion of the effect of BMI mediated through TyG index. Results: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney (hazard ratio (HR) per one standard deviation increase 1.13, 95% confidence interval: 1.07-1.20), liver (1.13, 1.04-1.23), pancreas (1.12, 1.06-1.19), colon (1.07, 1.03-1.10), and rectum (1.09, 1.04-1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%), and colon (20%); smaller proportions for kidney (15%) and liver (11%); none for endometrium, ovary and breast (postmenopausal). Conclusions: In this pooled cohort study including more than 500,000 individuals, insulin resistance measured as the logarithmized triglyceride glucose product significantly mediated the effect of overweight and obesity on risk of cancers of the kidney, liver, pancreas, colon, and rectum. In contrast, insulin resistance did not mediate the risk for cancers of the endometrium, ovary and breast. Our results confirm a promoting role of insulin resistance in the pathogenesis of gastrointestinal cancers. Although often claimed, insulin resistance does not appear to connect excess body weight with cancers of the female reproductive organs.

Ort, förlag, år, upplaga, sidor
American Society of Clinical Oncology, 2019
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-164084 (URN)10.1200/JCO.2019.37.15_suppl.1552 (DOI)000487345804348 ()
Konferens
Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), MAY 31-JUN 04, 2019, Chicago, IL
Anmärkning

Supplement: S (May 20, 2019)

Meeting Abstract: 1552

Tillgänglig från: 2019-10-14 Skapad: 2019-10-14 Senast uppdaterad: 2019-10-14Bibliografiskt granskad
Crawley, D., Garmo, H., Rudman, S., Stattin, P., Zethelius, B., Holmberg, L., . . . Van Hemelrijck, M. (2018). Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer. BJU International, 121(2), 209-216
Öppna denna publikation i ny flik eller fönster >>Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer
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2018 (Engelska)Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, nr 2, s. 209-216Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.

Subjects and Methods: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate-(T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20 ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow-up, was calculated both for men with T2DM only and for men with T2DM and PCa.

Results: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69-0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and high-risk PCa who did and did not receive curative treatment, respectively.

Conclusions: Men with T2DM were less likely to receive curative treatment for localized intermediate-and high-risk PCa. Men with T2DM and high-risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under-nor overtreated.

Ort, förlag, år, upplaga, sidor
WILEY, 2018
Nyckelord
diabetes, curative treatment, prostatectomy, external beam radiotherapy, #ProstateCancer, #PCSM
Nationell ämneskategori
Urologi och njurmedicin
Identifikatorer
urn:nbn:se:umu:diva-144946 (URN)10.1111/bju.13880 (DOI)000424029800012 ()28418195 (PubMedID)
Tillgänglig från: 2018-02-23 Skapad: 2018-02-23 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
FitzGerald, L. M., Zhao, S., Leonardson, A., Geybels, M. S., Kolb, S., Lin, D. W., . . . Stanford, J. L. (2018). Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: an analysis of 12,082 prostate cancer cases. Prostate Cancer and Prostatic Diseases, 21(2), 228-237
Öppna denna publikation i ny flik eller fönster >>Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: an analysis of 12,082 prostate cancer cases
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2018 (Engelska)Ingår i: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 21, nr 2, s. 228-237Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed. Methods Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach. Results Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT (rs2308327; HR 0.90; p-value = 3.5 x 10(-2)) and IL4 (rs2070874; HR 1.22; p-value = 1.1 x 10(-3)) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 x 10(-2)). Conclusions This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2018
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-150859 (URN)10.1038/s41391-017-0029-2 (DOI)000437334500010 ()29298992 (PubMedID)2-s2.0-85040017696 (Scopus ID)
Tillgänglig från: 2018-09-07 Skapad: 2018-09-07 Senast uppdaterad: 2018-09-07Bibliografiskt granskad
Van Hemelrijck, M., Ulmer, H., Nagel, G., Peter, R. S., Fritz, J., Myte, R., . . . Stocks, T. (2018). Longitudinal study of body mass index, dyslipidemia, hyperglycemia, and hypertension in 60,000 men and women in Sweden and Austria. PLoS ONE, 13(6), Article ID e0197830.
Öppna denna publikation i ny flik eller fönster >>Longitudinal study of body mass index, dyslipidemia, hyperglycemia, and hypertension in 60,000 men and women in Sweden and Austria
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2018 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 6, artikel-id e0197830Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Obesity is suggested to underlie development of other metabolic aberrations, but longitudinal relationships between metabolic factors at various ages has not been studied in detail. Methods: Data from 27,379 men and 32,275 women with in total 122,940 health examinations in the Västerbotten Intervention Project, Sweden and the Vorarlberg Health Monitoring and Prevention Programme, Austria were used to investigate body mass index (BMI), mid-blood pressure, and fasting levels of glucose, triglycerides, and total cholesterol at baseline in relation to 10-year changes of these factors and weight. We included paired examinations performed 10 +/- 2 years apart and used them for longitudinal analysis with linear regression of changes between the ages 30 and 40, 40 and 50, or 50 and 60 years. Results: Higher levels of BMI were associated with increases in glucose and mid-blood pressure as well as triglycerides levels, and, to a lesser extent, decreases in cholesterol levels. For instance, per 5 kg/m(2) higher BMI at age 40, glucose at age 50 increased by 0.24 mmol/l (95%Cl:0.22-0.26) and mid-blood pressure increased by 1.54 mm Hg (95%Cl: 1.35-1.74). The strongest association observed was between BMI at age 30 and mid-blood pressure, which was 2.12 mm Hg (95% CI: 1.79-2.45) increase over ten years per 5 kg/m(2) higher BMI level. This association was observed at an age when blood pressure levels on average remained stable. Other associations than those with BMI at baseline were much weaker. However, triglyceride levels were associated with future glucose changes among individuals with elevated BMI, particularly in the two older age groups. Conclusion: BMI was most indicative of long-term changes in metabolic factors, and the strongest impact was observed for increases in blood pressure between 30 and 40 years of age. Our study supports that lifestyle interventions preventing metabolic aberrations should focus on avoiding weight increases.

Ort, förlag, år, upplaga, sidor
Public Library Science, 2018
Nationell ämneskategori
Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
Identifikatorer
urn:nbn:se:umu:diva-150785 (URN)10.1371/journal.pone.0197830 (DOI)000435090700031 ()29897925 (PubMedID)
Tillgänglig från: 2018-08-20 Skapad: 2018-08-20 Senast uppdaterad: 2018-08-20Bibliografiskt granskad
Ventimiglia, E., Folkvaljon, Y., Carlsson, S., Bratt, O., Montorsi, F., Volz, D., . . . Stattin, P. (2018). Nationwide, population-based study of post radical prostatectomy urinary incontinence correction surgery. Journal of Surgical Oncology, 117(2), 321-327
Öppna denna publikation i ny flik eller fönster >>Nationwide, population-based study of post radical prostatectomy urinary incontinence correction surgery
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2018 (Engelska)Ingår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 117, nr 2, s. 321-327Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

ObjectivesTo assess the use of post radical prostatectomy (RP) urinary incontinence (PPI) surgery and to investigate factors related to its use. MethodsCohort study in Prostate Cancer database Sweden (PCBaSe) of men who underwent primary RP between 1998 and 2012. PPI correction procedures were identified in the Patient Registry. Hazard ratios (HR) and 95% confidence intervals (CIs) of PPI surgeries were estimated. ResultsSeven hundred eighty-two out of 26280 (3%) men underwent PPI surgery at a median time of 3 years after RP. There was an eightfold increase in the absolute number of PPI surgeries during 2000-2014 and a threefold increase in the number per 1000 RPs performed. Factors associated with high use PPI surgery were age >70, HR 1.96 (1.54-2.50), and high hospital RP volume (>100 RPs/year), HR 0.81 (0.66-0.99). There was a 10-fold difference in use of PPI surgery per 1000 RPs between the county with the highest versus lowest use. In a subgroup of men with Patient-Reported Outcome Measures (PROM); severe PPI was reported by 7% of men and 24% of them underwent PPI surgery. ConclusionsThree percent of all men received PPI surgery, with a 10-fold variation among health care providers. Only a quarter of men with severe PPI underwent PPI surgery, suggesting that PPI surgery remains underutilized.

Ort, förlag, år, upplaga, sidor
WILEY, 2018
Nyckelord
artificial urinary sphincter, population based, post radical prostatectomy urinary incontinence, PROM
Nationell ämneskategori
Omvårdnad
Identifikatorer
urn:nbn:se:umu:diva-145787 (URN)10.1002/jso.24816 (DOI)000426165700026 ()28876467 (PubMedID)
Tillgänglig från: 2018-03-22 Skapad: 2018-03-22 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Gnanapragasam, V. J., Bratt, O., Muir, K., Lees, L. S., Huang, H. H., Stattin, P. & Lophatananon, A. (2018). The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study. BMC Medicine, 16, Article ID 31.
Öppna denna publikation i ny flik eller fönster >>The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study
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2018 (Engelska)Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, artikel-id 31Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer.

Methods: We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality.

Results: The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n =3D 20,586), C-index 0.77 vs. 074; radiotherapy (n =3D 11,872), C-index 0.73 vs. 0.69; and conservative management (n =3D 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001).

Conclusions: This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

Ort, förlag, år, upplaga, sidor
BioMed Central, 2018
Nyckelord
Prostate cancer, Prognostic prediction, Cancer-specific mortality, Cambridge Prognostic Groups, Non-metastatic disease, Stratification, All-cause mortality, Competing risks, Improved treatment section, Treatment selection
Nationell ämneskategori
Urologi och njurmedicin Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-146163 (URN)10.1186/s12916-018-1019-5 (DOI)000426402000003 ()29490658 (PubMedID)
Tillgänglig från: 2018-05-16 Skapad: 2018-05-16 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Lycken, M., Drevin, L., Garmo, H., Stattin, P., Adolfsson, J., Lissbrant, I. F., . . . Bill-Axelson, A. (2018). The use of palliative medications before death from prostate cancer: Swedish population-based study with a comparative overview of European data. European Journal of Cancer, 88, 101-108
Öppna denna publikation i ny flik eller fönster >>The use of palliative medications before death from prostate cancer: Swedish population-based study with a comparative overview of European data
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2018 (Engelska)Ingår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 88, s. 101-108Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Symptoms of terminal cancer have previously been reported as under-treated. The aim of this study was to assess the use of palliative medications before death from prostate cancer.

Methods: This Swedish register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer.

Results: We included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.47-0.66 for > 85 years versus < 70 years) and (OR 0.78, 95% CI: 0.66-0.92 for unmarried without children versus married with children).

Conclusion: Our results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer. 

Ort, förlag, år, upplaga, sidor
Elsevier, 2018
Nyckelord
Anxiety, Cancer pain, Castration, Depression, Fatigue, Observational study, Opioids, Palliative medicine, Prostate cancer, Sleep disorders
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-143628 (URN)10.1016/j.ejca.2017.10.023 (DOI)000418290800012 ()29216521 (PubMedID)
Tillgänglig från: 2018-01-29 Skapad: 2018-01-29 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Licciardello, M. P., Ringler, A., Markt, P., Klepsch, F., Lardeau, C.-H., Sdelci, S., . . . Kubicek, S. (2017). A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor. Nature Chemical Biology, 13(7), 771-778
Öppna denna publikation i ny flik eller fönster >>A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor
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2017 (Engelska)Ingår i: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 13, nr 7, s. 771-778Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for gamma-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2017
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-137623 (URN)10.1038/nchembio.2382 (DOI)000403673700014 ()28530711 (PubMedID)
Tillgänglig från: 2017-07-19 Skapad: 2017-07-19 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
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