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  • 1
    Language: English
    In: memo - Magazine of European Medical Oncology, 2018, Vol.11(4), pp.297-300
    Description: Previously assumed to be rare, the prevalence of aggressive variants of prostate cancer has increased rapidly. This histologically heterogeneous group of cancers, including different forms of the neuroendocrine carcinoma of the prostate, share a common clinical course associated with a poor response to androgen deprivation treatment and fatal prognosis. Currently, the most commonly used terms are aggressive variant of prostate cancer and treatment-related neuroendocrine prostate cancer. The best treatment of these tumors in clinical routine is still being debated. Here, we highlight the clinically most relevant aspects of this heterogeneous disease and summarize recommendations for clinical routine.
    Keywords: Prostate cancer ; Aggressive variant ; Anaplastic ; Neuroendocrine ; Small cell
    ISSN: 1865-5041
    E-ISSN: 1865-5076
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  • 2
    Language: English
    In: The Journal of Urology, April 2012, Vol.187(4), pp.e130-e130
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 3
    Language: English
    In: PLoS ONE, August 19, 2014, Vol.9(8)
    Description: Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.
    Keywords: DNA Polymerases – Growth ; Proteins – Growth
    ISSN: 1932-6203
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: PLoS ONE, Oct 15, 2014, Vol.9(10)
    Description: The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin [alpha] and [beta] subtypes, on integrin-linked kinase (ILK) and total and activated focal adhesion kinase (FAK) were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of [beta]1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of [beta]4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by [beta]1 or [beta]4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating [beta]1 or [beta]4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines) may depend upon the cancer cell type.
    Keywords: DNA Polymerases ; Collagen ; Integrins
    ISSN: 1932-6203
    Source: Cengage Learning, Inc.
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  • 5
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(8), p.e105590
    Description: Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 6
    Language: English
    In: PLoS ONE, Oct 15, 2014, Vol.9(10)
    Description: The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin [alpha] and [beta] subtypes, on integrin-linked kinase (ILK) and total and activated focal adhesion kinase (FAK) were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of [beta]1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of [beta]4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by [beta]1 or [beta]4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating [beta]1 or [beta]4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines) may depend upon the cancer cell type.
    Keywords: Dna Polymerases ; Collagen ; Integrins
    ISSN: 1932-6203
    Source: Cengage Learning, Inc.
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  • 7
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(1), p.e53100
    Description: Targeted drugs have significantly improved the therapeutic options for advanced renal cell carcinoma (RCC). However, resistance often develops, negating the benefit of these agents. In the present study, the molecular mechanisms of acquired resistance towards the histone deacetylase (HDAC) inhibitor valproic acid (VPA) in a RCC in vivo model were investigated. NMRI:nu/nu mice were transplanted with Caki-1 RCC cells and then treated with VPA (200 mg/kg/day). Controls remained untreated. Based on tumor growth dynamics, the mice were divided into "responders" and "non-responders" to VPA. Histone H3 and H4 acetylation and expression of cell signaling and cell cycle regulating proteins in the RCC mouse tumors were evaluated by Western blotting. Tumor growth of VPA responders was significantly diminished, whereas that of VPA non-responders even exceeded control values. Cdk1, 2 and 4 proteins were strongly enhanced in the non-responders. Importantly, Akt expression and activity were massively up-regulated in the tumors of the VPA non-responders. Chronic application (12 weeks) of VPA to Caki-1 cells in vitro evoked a distinct elevation of Akt activity and cancer cells no longer responded with cell growth reduction, compared to the short 2 week treatment. We assume that chronic use of an HDAC-inhibitor is associated with (re)-activation of Akt, which may be involved in resistance development. Consequently, combined blockade of both HDAC and Akt may delay or prevent drug resistance in RCC.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 8
    Language: English
    In: The Journal of Urology, April 2018, Vol.199(4), pp.e484-e485
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 9
    Language: English
    In: The Journal of Urology, September 2016, Vol.196(3), pp.664-671
    Description: Several nephrometry scores have been proposed to predict perioperative outcomes in renal surgery. We evaluated which nephrometry score correlates best with the MIC (margin, ischemia and complications) score and quantitative perioperative outcomes in nephron sparing surgery. Data on 188 patients undergoing nephron sparing surgery were retrospectively investigated for patient, operative and tumor characteristics. Nephrometry scores, including R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, hilar tumor touching the main renal artery or vein and location relative to polar lines), PADUA (preoperative aspects and dimensions used for an anatomical), C-index (concordance index) and DAP (diameter-axial-polar), were measured on preoperative computerized tomography or magnetic resonance imaging and coded continuously and categorically. Parameters pertaining to tumor margin, ischemia and complications were recorded as binary scores and classified as MIC achievement. Operative time, estimated blood loss, warm ischemia time and hospital stay were recorded as quantitative perioperative outcomes. The R.E.N.A.L. score correlated best with MIC and quantitative perioperative outcomes. The continuously coded R.E.N.A.L. score was predictive of MIC on univariate analysis (OR 0.75, 95% CI 0.58–0.97, p = 0.03) and it had the best predictive value on multivariate logistic regression analysis (OR 0.31, 95% CI 0.18–0.82, p = 0.03). The C-index but not the PADUA or the DAP score was predictive of MIC on univariate and multivariate logistic regression analysis. MIC achievement rates were significantly higher for low than for high complexity tumors as assessed by categorically coded R.E.N.A.L. score, C-index and DAP scores. Continuously coded R.E.N.A.L. and PADUA scores positively correlated with operative time, warm ischemia time and hospital stay. The C-index and the DAP score correlated with warm ischemia time. Of 4 nephrometry scores the R.E.N.A.L. score correlated best with MIC achievement and quantitative perioperative outcomes of nephron sparing surgery.
    Keywords: Kidney Neoplasms ; Ischemia ; Complications ; Prognosis ; Decision Support Techniques ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 10
    Language: English
    In: The Journal of Urology, April 2012, Vol.187(4), pp.e320-e321
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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