| 1. |
- Dahlman, Anna K, et al.
(författare)
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Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3.
- 2010
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 13, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the effects of short-term neoadjuvant and long-term androgen deprivation therapies (ADTs) on beta-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) expression in prostate cancer patients. We also studied if MSMB expression was related to genotype and epigenetic silencing. Using an Affymetrix cDNA microarray analysis, we investigated the expression of MSMB, CRISP3, androgen receptor (AR), KLK3 and Enhancer of Zeste Homologue-2 (EZH2) in tissue from prostate cancer patients receiving (n=17) or not receiving (n=23) ADT before radical prostatectomy. MSMB, CRISP3 and AR were studied in tissue from the same patients undergoing TURP before and during ADT (n=16). MSMB genotyping of these patients was performed by TaqMan PCR. MSMB and KLK3 expression levels decreased during ADT. Expression levels of AR and CRISP3 were not affected by short-term ADT but were high in castration-resistant prostate cancer (CRPC) and metastases. Levels of EZH2 were also high in metastases, where MSMB was low. Genotyping of the MSMB rs10993994 polymorphism showed that the TT genotype conveys poor MSMB expression. MSMB expression is influenced by androgens, but also by genotype and epigenetic silencing. AR and CRISP3 expression are not influenced by short-term ADT, and high levels were found in CRPC and metastases.Prostate Cancer and Prostatic Diseases advance online publication, 3 August 2010; doi:10.1038/pcan.2010.25.
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| 2. |
- Kellokumpu-Lehtinen, P-L, et al.
(författare)
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Toxicity in patients receiving adjuvant docetaxel plus hormonal treatment after radical radiotherapy for intermediate or high-risk prostate cancer : a preplanned safety report of the SPCG-13 trial
- 2012
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 15:3, s. 303-307
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Radical radiotherapy (RD combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). METHODS: The inclusion criteria are the following: men > 18 and <= 75 years of age, WHO/ECOG performance status 0-1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4 + 3), PSA > 10; T2, Gleason 8-10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mg m(-2) d 1. cycle 21 d) or no docetaxel after radical RI (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). RESULTS: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3-4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3-4 toxicities at 12 weeks after the randomization. CONCLUSIONS: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.
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| 3. |
- Li, Xinjun, et al.
(författare)
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Neighborhood deprivation and prostate cancer mortality: a multilevel analysis from Sweden.
- 2012
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 15, s. 128-134
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Tidskriftsartikel (refereegranskat)abstract
- Background:The objective was to analyze the association between neighborhood deprivation and prostate cancer mortality, after adjusting for individual characteristics.Methods:This study was designed as a follow-up study of prostate cancer mortality between 1 January 1990 and 31 December 2008 in patients aged 25-74 years (a total of 73 159 patients). Multilevel logistic regression analyses were performed with individual-level characteristics at the first level and level of neighborhood deprivation at the second level.Results:The age-standardized prostate cancer mortality rate was 1.5 times higher in men living in high-deprivation neighborhoods than in those living in the most affluent neighborhoods. Mortality rates were also associated with certain individual-level characteristics, that is, age, marital status, family income, educational attainment, immigration status, urban/rural status, mobility and comorbidity. For example, there was a strong relationship between prostate cancer mortality and being unmarried, having a low income or educational attainment, and hospitalization for chronic obstructive pulmonary disease. In the full model, the risk of prostate cancer mortality was 25% higher in men living in the most deprived neighborhoods than in those living in the most affluent neighborhoods.Conclusions:High level of neighborhood deprivation independently predicts prostate cancer mortality. This raises important clinical and public health concerns. Both individual- and neighborhood-level approaches are important in healthcare policies.Prostate Cancer and Prostatic Diseases advance online publication, 11 October 2011; doi:10.1038/pcan.2011.46.
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| 4. |
- Lippolis, Giuseppe, et al.
(författare)
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A high-density tissue microarray from patients with clinically localized prostate cancer reveals ERG and TATI exclusivity in tumor cells.
- 2013
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 16:2, s. 145-150
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Tidskriftsartikel (refereegranskat)abstract
- Background:Prostate cancer (PCa) is characterized by high tumor heterogeneity. In 2005, the fusion between the androgen-regulated gene TMPRSS2 and members of the ETS family was discovered in prostate cancer. In particular, fusion of TMPRSS2 with ERG was found in approximately 50% of prostate cancers and considered as an early event in the onset of the disease. The prognostic value of this fusion is still contradictory. Bioinformatics showed that overexpression of SPINK1 gene in a subset of fusion-gene-negative prostate cancers was associated with a poor prognosis. In theory, overexpression of the tumor-associated trypsin inhibitor (TATI) protein encoded by SPINK1 in fusion-gene-negative tumor cells opens the way to selected treatments for genotypically different cases. However, their expression has never been assessed at the cellular level in the same tissue samples.Methods:As ERG expression has been shown to be a surrogate of fusion gene occurrence in prostate cancer, we have used double immunohistochemical staining to assess expression of ERG and TATI on a large tissue microarray comprising 4177 cases of localized prostate cancer.Results:We did not detect any co-expression of ERG and TATI in the same cancer cells, which confirms previous suggestions from in silico studies. ERG was associated with Gleason score (GS), surgical margins and pathological stage, but had no prognostic value in this cohort. TATI was weakly associated with pathological stage but had no significant association with outcome.Conclusions:We here provide a morphological basis for ERG and TATI exclusivity in prostate cancer cells. Future therapies should be based on a combination of different targets in order to eradicate tumor cells with gene fusions and cells expressing other tumor-associated antigens. Further studies are needed to understand why ERG and TATI are not co-expressed in the same prostatic tumor cells.Prostate Cancer and Prostatic Disease advance online publication, 5 March 2013; doi:10.1038/pcan.2013.7.
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| 5. |
- Peng, Z., et al.
(författare)
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An expression signature at diagnosis to estimate prostate cancer patients' overall survival
- 2014
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 17:1, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study aimed to identify biomarkers for estimating the overall and prostate cancer (PCa)-specific survival in PCa patients at diagnosis. METHODS: To explore the importance of embryonic stem cell (ESC) gene signatures, we identified 641 ESC gene predictors (ESCGPs) using published microarray data sets. ESCGPs were selected in a stepwise manner, and were combined with reported genes. Selected genes were analyzed by multiplex quantitative polymerase chain reaction using prostate fine-needle aspiration samples taken at diagnosis from a Swedish cohort of 189 PCa patients diagnosed between 1986 and 2001. Of these patients, there was overall and PCa-specific survival data available for 97.9%, and 77.9% were primarily treated by hormone therapy only. Univariate and multivariate Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis, and a k-nearest neighbor (kNN) algorithm for estimating overall survival. RESULTS: An expression signature of VGLL3, IGFBP3 and F3 was shown sufficient to categorize the patients into high-, intermediate- and low-risk subtypes. The median overall survival times of the subtypes were 3.23, 4.00 and 9.85 years, respectively. The difference corresponded to hazard ratios of 5.86 (95% confidence interval (CI): 2.91-11.78, P<0.001) for the high-risk subtype and 3.45 (95% CI: 1.79-6.66, P<0.001) for the intermediate-risk compared with the low-risk subtype. The kNN models that included the gene expression signature outperformed the one designed on clinical parameters alone. CONCLUSIONS: The expression signature can potentially be used to estimate overall survival time. When validated in future studies, it could be integrated in the routine clinical diagnostic and prognostic procedure of PCa for an optimal treatment decision based on the estimated survival benefit.
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| 6. |
- Rueenauver, K., et al.
(författare)
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Prognostic significance of YWHAZ expression in localized prostate cancer
- 2014
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 17:4, s. 310-314
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PCa) patients are often over-treated because of the lack of biomarkers needed to distinguish the lethal from the indolent form of PCa. YWHAZ was recently identified as a potential therapeutic target in castration-resistant PCa (CRPC). Therefore, this study focused on determining the prognostic significance of YWHAZ in localized PCa.METHODS: YWHAZ expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded tissue from 213 men who underwent radical prostatectomy. Kaplan-Meier analysis and Cox proportional-hazards models were, used to assess the prognostic value of YWHAZ intensity.RESULTS: High YWHAZ expression was strongly associated with high Gleason score at the time of diagnosis (P<0.001) and PSA relapse (P=0.001). Importantly, patients with high expression of YWHAZ had a higher risk of CRPC development (P=0.002) and reduced survival time (P=0.002).CONCLUSIONS: Our findings indicate that YWHAZ could serve as a promising prognostic biomarker in localized PCa to predict poor prognosis and to identify a subgroup of tumors, which might benefit from earlier adjuvant or YWHAZ-targeted therapy.
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| 7. |
- Shore, N. D., et al.
(författare)
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New considerations for ADT in advanced prostate cancer and the emerging role of GnRH antagonists
- 2013
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 16:1, s. 7-15
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Forskningsöversikt (refereegranskat)abstract
- Androgen deprivation therapy (ADT) is first-line treatment for metastatic prostate cancer (PCa). Gonadotrophin-releasing hormone (GnRH) agonists are the most commonly used ADT but have several theoretical physiologic disadvantages (e.g. initial testosterone surge, potential microsurges upon repeat administration). Testosterone surge delays the intended serologic endpoint of testosterone suppression and may exacerbate clinical symptoms. GnRH antagonists were developed with a view toward overcoming these potential adverse physiologic events. This review evaluates GnRH agonists and antagonists, assessing the potential future role of antagonists in PCa and strategies to minimize ADT adverse events (AEs). Evidence was identified via PubMed search (by GnRH agent and other ADT-related terms), from review article bibliographies, and authors' therapy area knowledge, with articles included by author consensus. Degarelix shows similar efficacy to a GnRH agonist in achieving and maintaining castration, with faster onset and without testosterone surge/microsurges. Phase III data showed that, in the first treatment year, degarelix displayed a lower risk of PSA failure or death (composite endpoint), lower levels of the bone marker serum alkaline phosphatase (in baseline metastatic disease), and fewer musculoskeletal AEs than the agonist leuprolide. Also, crossing over from leuprolide to degarelix after 1 year reduced the risk of PSA failure or death. ADT displays an AE spectrum which can impact quality of life as well as causing significant morbidities. Strategies to improve ADT tolerability have become increasingly important including: a holistic management approach, improved diet and exercise, more specific monitoring to detect and prevent testosterone depletion toxicities, and intermittent ADT allowing hormonal recovery between treatment periods. Clinical studies suggest possible benefits of GnRH antagonists over agonists based on different mechanisms of action. GnRH antagonists should now be considered as an alternative first-line ADT option in advanced PCa. Intermittent ADT and a holistic treatment approach are promising strategies to improve ADT tolerability. Prostate Cancer and Prostatic Diseases (2013) 16, 7-15; doi:10.1038/pcan.2012.25; published online 3 July 2012
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| 8. |
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| 9. |
- Pösö, Tomi, et al.
(författare)
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Volatile rapid sequence induction in morbidly obese patients
- 2011
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Ingår i: European Journal of Anaesthesiology. - : Lippincott Williams & Wilkins. - 0265-0215 .- 1365-2346. ; 28:11, s. 781-787
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: The interest in bariatric surgery is growing. Morbidly obese patients have an increased risk of hypoxia and decreased blood pressure during rapid sequence induction (RSI). Alternate RSI methods that provide cardiovascular and respiratory stability are required. With this in mind, we evaluated a method for volatile RSI in morbidly obese patients.Design: Observational study.Methods: Thirty-four patients with mean BMI 42.4 kg m(-2) undergoing bariatric surgery (morbidly obese group) and 22 patients with mean BMI 25.6 kg m(-2) as a control group were included in the study. Anaesthesia was induced with sevoflurane, propofol, suxamethonium and alfentanil, designed to avoid respiratory and haemodynamic adverse events and to minimise depressing effect on the brain respiratory centre under ongoing RSI. Peripheral oxygen saturation (SpO(2)) and mean arterial blood pressure were registered before and after endotracheal intubation. In addition, two time periods were measured during RSI: spontaneous breathing time (SBT) and apnoea time.Results: We found no significant differences between the groups. No periods of desaturation were detected. SpO(2) was 100% before and after endotracheal intubation in all patients. Mean arterial pressure was maintained at a stable level in both groups. Mean SBT and apnoea time were 65.6 and 45.8 s in the morbidly obese group, and 70.7 and 47.7 s in the control group, respectively.Conclusion: A combination of sevoflurane, propofol, suxamethonium and alfentanil is a suitable method for RSI which maintains cardiovascular and respiratory stability in both morbidly obese and lean patients.
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