- Ap39, A Mitochondria-Targeting Hydrogen Sulfide (H2 s) Donor, Protects Against Myocardial Reperfusion Injury Independently Of Salvage Kinase Signalling. [Journal Article]
- BJBr J Pharmacol 2016 Dec 08
- CONCLUSIONS: AP39 protects against reperfusion injury independently of the cytosolic RISK pathway. Cardioprotection could be mediated by inhibiting PTP via cyclophilin D-independent mechanism. Thus, selective delivery of H2 S to mitochondria may be therapeutically applicable for harnessing the cardioprotective utility of H2 S. This article is protected by copyright. All rights reserved.
- Prognostic value of inflammation in prostate cancer progression and response to therapeutic: a critical review. [Review]
- JIJ Inflamm (Lond) 2016; 13:35
- Prostate is an immune-competent organ normally populated by inflammatory cells. Prostatic inflammation origin can be multi-factorial and there are some emerging evidences on its possible role as a fa...
Prostate is an immune-competent organ normally populated by inflammatory cells. Prostatic inflammation origin can be multi-factorial and there are some emerging evidences on its possible role as a factor involved in prostate cancer (PC) pathogenesis and progression. This review critically analyzes the role of inflammation as a prognostic factor for progression and aggressiveness of PC. We verified the last 10 years literature data on the association between inflammation and PC aggressiveness, or PC response to therapies. Several studies tried to correlate different inflammatory factors with the aggressiveness and metastatization of PC; all data sustain the role of inflammation in PC progression but they also produce confusion to identify a reliable clinical prognostic marker. Data on patients submitted to radical prostatectomy (RP) showed that cases with marked intraprostatic tissue inflammation are associated with higher rate of biochemical progression; systemic inflammation markers appear to have a significant prognostic value. Analyzing data on patients submitted to radiotherapy (RT) emerges a significant association between high neuthrophil to lymphocyte ratio (NLR) and decreased progression free survival and overall survival; also plateled to lymphocyte ratio (PLR) and C-reactive protein (CRP) have been proposed as significant prognostic factors for progression and overall survival. In patients submitted to androgen deprivation therapy (ADT), inflammation may drive castration resistant PC (CRPC) development by activation of STAT3 in PC cells. NLR has been proposed as independent predictor of overall survival in CRPC submitted to chemotherapy. Most of data are focused on markers related to systemic inflammation such as NLR and CRP, more than specifically to chronic prostatic inflammation. The suggestion is that these inflammatory parameters, also if not specific for prostatic inflammation and possibly influenced by several factors other than PC, can integrate with established prognostic factors.
- A Sensitive and Accurate LC-MS/MS Assay With the derivatization of 1Amino4methylpiperazine Applied To Serum Allopregnanolone, Pregnenolone and Androsterone in Pre- and Postmenopausal Women. [Journal Article]
- SSteroids 2016 Nov 29
- The concentrations of allopregnanolone (Allopreg), pregnenolone (Preg) and androsterone (ADT) are very low in the circulation, especially in postmenopausal women, resulting in a considerable challeng...
The concentrations of allopregnanolone (Allopreg), pregnenolone (Preg) and androsterone (ADT) are very low in the circulation, especially in postmenopausal women, resulting in a considerable challenge for their accurate measurements in serum or plasma. In this report, a sensitive and reliable LC-MS/MS assay method has been developed using a simple sample preparation and the 1-Amino-4-methylpiperazine (AMP) derivatization procedure. A 5pg/ml (0.1pg on column) of low limit of quantitation has been achieved for Allopreg, Preg and ADT, with a sensitivity comparable to data obtained with the commercial reagent. The major benefit of this reagent is to limit the matrix effect since the excess amount of reagent can be removed during the reaction. Multiple reaction monitoring (MRM) from the derivatization of AMP not only increases the detection of these compounds but also provides a good resolution for Allopreg, Preg and ADT from interferences, especially for Allopreg from its isomers. Within the calibration range of 5pg/ml to 2000pg/ml, a good linearity was obtained with R>0.99 where the weighing factor is 1/X. Bias and coefficients of variance are within 15% for all QC levels. The matrix effect has been evaluated, well meeting the acceptance criteria according to the FDA guidelines. With this method, the concentrations of Allopreg, Preg and ADT in postmenopausal serum are in the range of 6.4∼53.6pg/ml, 16.2∼68.0pg/ml and 23.9∼114.0pg/ml, respectively, while the ranges in premenopausal serum are 8.2pg/ml∼701.5pg/ml, 31.2∼135.2pg/ml and 47.8∼310.0pg/ml, respectively.
- The prognostic and predictive value of TMPRSS2-ERG gene fusion and ERG protein expression in prostate cancer biopsies. [Journal Article]
- DMDan Med J 2016; 63(12)
- CONCLUSIONS: The thesis has demonstrated that assessment of ERG protein expression is feasible in biopsy specimens, and a high concordance was found between the IHC assay and FISH assessment of ERG rearrangement. The low proportion of ERG reclassification between biopsies and prostatectomies supports the use of ERG assessment in biopsies to characterise the individual patient's ERG status. ERG status harbours important prognostic value in terms of tumour progression for patients managed on AS, whereas ERG expression has no predictive value for ADT response in men with advanced PCa undergoing first-line castration-based ADT. The overall conclusion of the thesis is that ERG protein expression provides valuable prognostic information in low-risk PCa managed observationally, and ERG expression might be used to personalise follow-up regimens in future AS programmes.
- Enzalutamide (New Therapeutic Indication) -- Benefit Assessment According to §35a Social Code Book [BOOK]
- BOOKInstitute for Quality and Efficiency in Health Care (IQWiG): Cologne, Germany
- The aim of the present report was to assess the added benefit of enzalutamide versus the appropriate comparator therapy (ACT) for treatment of adult men with metastatic castration-resistant prostate ...
The aim of the present report was to assess the added benefit of enzalutamide versus the appropriate comparator therapy (ACT) for treatment of adult men with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy (ADT) in whom chemotherapy is not yet clinically indicated. The G-BA specified the following options for the ACT:watchful waiting while maintaining ongoing conventional ADT; or, if applicable,combined maximal androgen blockade with a non-steroidal anti-androgen (flutamide, bicalutamide); or: abiraterone acetate while maintaining ongoing ADT. The company concurred with the G-BA’s specification and chose watchful waiting while maintaining conventional ADT from the options mentioned. The present benefit assessment was conducted in comparison with the option chosen by the company from the options of ACT specified by the G-BA. The assessment was conducted based on patient-relevant outcomes and on the evidence provided by the company in the dossier.
- Inherited Variants in Wnt Pathway Genes Influence Outcomes of Prostate Cancer Patients Receiving Androgen Deprivation Therapy. [Journal Article]
- IJInt J Mol Sci 2016 Nov 26; 17(12)
- Aberrant Wnt signaling has been associated with many types of cancer. However, the association of inherited Wnt pathway variants with clinical outcomes in prostate cancer patients receiving androgen ...
Aberrant Wnt signaling has been associated with many types of cancer. However, the association of inherited Wnt pathway variants with clinical outcomes in prostate cancer patients receiving androgen deprivation therapy (ADT) has not been determined. Here, we comprehensively studied the contribution of common single nucleotide polymorphisms (SNPs) in Wnt pathway genes to the clinical outcomes of 465 advanced prostate cancer patients treated with ADT. Two SNPs, adenomatous polyposis coli (APC) rs2707765 and rs497844, were significantly (p ≤ 0.009 and q ≤ 0.043) associated with both prostate cancer progression and all-cause mortality, even after multivariate analyses and multiple testing correction. Patients with a greater number of favorable alleles had a longer time to disease progression and better overall survival during ADT (p for trend ≤ 0.003). Additional, cDNA array and in silico analyses of prostate cancer tissue suggested that rs2707765 affects APC expression, which in turn is correlated with tumor aggressiveness and patient prognosis. This study identifies the influence of inherited variants in the Wnt pathway on the efficacy of ADT and highlights a preclinical rationale for using APC as a prognostic marker in advanced prostate cancer.
- Androgen deprivation causes selective deficits in the biomechanical leg muscle function of men during walking: a prospective case-control study. [Journal Article]
- JCJ Cachexia Sarcopenia Muscle 2016 Aug 02
- CONCLUSIONS: Testosterone deprivation selectively decreases lower-limb muscle function, predominantly affecting muscles that support body weight, accelerate the body forwards during walking, and mediate balance. Future exercise and pro-myogenic interventional studies to mitigate ADT-associated sarcopenia should target these deficits.
- Investigational serine/threonine kinase inhibitors against prostate cancer metastases. [Journal Article]
- EOExpert Opin Investig Drugs 2016 Nov 28
- CONCLUSIONS: Inhibitors for different STKs have been developed but clinical trials in PCa are comparatively rare and few exhibit satisfactory 'drug-like' properties. It is, however, necessary to intensify, when possible, the number of clinical trials with these drugs in order to insert new therapies or combinations with standard hormone- and chemo-therapies in the treatment guidelines of the mPCA.
- Functional and Structural Signatures of the Anterior Insula are associated with Risk-taking Tendency of Analgesic Decision-making. [Journal Article]
- SRSci Rep 2016 Nov 28; 6:37816
- In a medical context, decision-making is associated with complicated assessment of gains, losses and uncertainty of outcomes. We here provide novel evidence about the brain mechanisms underlying deci...
In a medical context, decision-making is associated with complicated assessment of gains, losses and uncertainty of outcomes. We here provide novel evidence about the brain mechanisms underlying decision-making of analgesic treatment. Thirty-six healthy participants were recruited and completed the Analgesic Decision-making Task (ADT), which quantified individual tendency of risk-taking (RPI), as the frequency of choosing a riskier option to relieve pain. All the participants received resting-state (rs) functional magnetic resonance imaging (MRI) and structural MRI. On rs-functional connectome, degree centrality (DC) of the bilateral anterior insula (aINS) was positively correlated with the RPI. The functional connectivity between the aINS, the nucleus accumbens and multiple brain regions, predominantly the medial frontal cortex, was positively correlated with the RPI. On structural signatures, the RPI was positively correlated with grey matter volume at the right aINS, and such an association was mediated by DC of the left aINS. Regression analyses revealed that both DC of the left aINS and participants' imagined pain relief, as the utility of pain reduction, could predict the individual RPI. The findings suggest that the functional and structural brain signature of the aINS is associated with the individual differences of risk-taking tendency in the context of analgesic decision-making.
New Search Next
- Functional Outcomes and Quality of Life After Radical Prostatectomy Only Versus a Combination of Prostatectomy with Radiation and Hormonal Therapy. [Journal Article]
- EUEur Urol 2016 Nov 22
- CONCLUSIONS: Patients who received RP + RT had a 4% higher overall incontinence rate 3 yr after surgery, and 1% higher rate for severe incontinence (>3 pads/24h) compared to matched RP-only patients. ADT further increased the overall and severe incontinence rates by 4% and 3%, respectively, compared to matched RP + RT patients. RP + RT was associated with an 18% lower rate of potency compared to RP alone, while RP + RT + ADT was associated with a further 17% reduction compared to RP + RT. Additional RT reduced QoL by 10% and additional ADT by a further 12% compared to RP only and RP + RT, respectively. The timing of RT after RP had no influence on continence, but adjuvant compared to salvage RT was associated with significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%). Limitations of our study include the observational study design and potential for selection bias in the treatments received.Secondary RT and ADT after RP have an additive negative influence on urinary function, potency, and QoL. Patients with high-risk disease should be counseled before RP on the potential net impairment of functional outcomes due to multimodal treatment.