Tissue Expression of Androgen Receptor Splice Variant 7 at Radical Prostatectomy Predicts Risk of Progression in Untreated Nonmetastatic Prostate Cancer

Sciarra, Alessandro; Maggi, Martina; Salciccia, Stefano; Nicolai, Ambra; Tortorella, Elisabetta; Giantulli, Sabrina; Magliocca, Fabio Massimo; Silvestri, Ida; Taglieri, Ludovica; Cattarino, Susanna; Scarpa, Susanna

doi:10.1159/000512445

Cited by 13 publications

(14 citation statements)

References 10 publications

(13 reference statements)

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“…This variation of enzymatic activity is analogous to the one we have generated in our cell and mouse models. The Ala variant of this polymorphism has been consistently associated with prostate cancer risk and increased aggressiveness either alone or when the antioxidant intake is low [ 11 , 14 , 35 , 36 , 37 ], indicating that higher levels of SOD2 activity might help prostate cancer progression similarly to our results obtained in a study of a cohort of patients [ 12 ]. Moreover, redox-related metabolism can be induced by different environmental factors such as anti-tumor therapy, diet, or lifestyle factors [ 38 ].…”

Section: Discussionsupporting

confidence: 85%

“…One of the most interesting aspects is the ability to reduce androgen signaling [ 9 ]. Androgens are essential to keep the tissue homeostasis in the prostate, and disarrangements in androgen signaling including receptor overexpression and splicing variants have a strong impact on prostate cancer progression [ 14 ], metabolism [ 15 ], and redox profile [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Androgen-Dependent Prostate Cancer Cells Reprogram Their Metabolic Signature upon GLUT1 Upregulation by Manganese Superoxide Dismutase

et al. 2022

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Prostate cancer is the second leading cause of cancer in men across the globe. The prostate gland accounts for some unique glycolytic metabolic characteristics, which causes the metabolic features of prostate tumor initiation and progression to remain poorly characterized. The mitochondrial superoxide dismutase (SOD2) is one of the major redox metabolism regulators. This study points out SOD2 as one major regulator for both redox and glycolytic metabolism in prostate cancer. SOD2 overexpression increases glucose transporter GLUT-1 and glucose uptake. This is not an insulin-mediated effect and seems to be sex-dependent, being present in male mice only. This event concurs with a series of substantial metabolic rearrangements at cytoplasmic and mitochondrial level. A concomitant decrease in glycolytic and pentose phosphate activity, and an increase in electron transfer in the mitochondrial electronic chain, were observed. The Krebs Cycle is altered to produce amino-acid intermediates by decreasing succinate dehydrogenase. This in turn generates a 13-fold increase in the oncometabolite succinate. The protein energy sensor AMPK is decreased at basal and phosphorylated levels in response to glucose deprivation. Finally, preliminary results in prostate cancer patients indicate that glandular areas presenting high levels of SOD2 show a very strong correlation with GLUT-1 protein levels (R2 = 0.287 p-value < 0.0001), indicating that in patients there may exist an analogous phenomenon to those observed in cell culture and mice.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Androgen-Dependent Prostate Cancer Cells Reprogram Their Metabolic Signature upon GLUT1 Upregulation by Manganese Superoxide Dismutase

et al. 2022

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“…However, several systematic reviews, meta-analyses [ 2 , 4 , 30 , 31 ] and randomized trials [ 32 , 33 ] have underlined that the different approaches to RP yielded similar post-operative results, so that EAU guidelines [ 5 ] recommend informing patients that no surgical approach to RP has clearly shown superiority in terms of both functional and oncologic outcomes. Independently to the surgical approach, several variables have been analyzed as possible predictors and factors able to influence oncologic and functional results after surgery [ 11 – 19 , 28 – 35 ]. Only few data are present in the literature regarding the correlation between blood loss during RP and surgical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Influence of operative time and blood loss on surgical margins and functional outcomes for laparoscopic versus robotic-assisted radical prostatectomy: a prospective analysis

Salciccia

Rosati

Viscuso

et al. 2021

Cent european J Urol

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Introduction The aim of this article was to analyze whether operative time and blood loss during radical prostatectomy (RP) can significantly influence surgical margins (SM) status and post-operative functional outcomes. Material and methods We prospectively analyzed prostate cancer (PC) patients undergoing RP, using robot-assisted (RARP) or laparoscopic (LRP) procedures. Blood loss was defined using the variation in hemoglobin (Hb, g/dl) values from the day before surgery and no later than 4 hours after surgery. Results From a whole population of 413 cases considered for RP, 67% underwent LRP and 33.0% RARP. Positive SM (SM+) were found in 33.9% of cases. Mean surgical operative time was 172.3 ±76 min (range 49–485), whereas blood loss was 2.3 ±1.2 g/dl (range 0.3–7.6). Operative time and blood loss at RP were not significantly correlated (r = -0.028275; p = 0.684). SM+ rates significantly (p = 0.002) varied by operative time; a higher SM+ rate was found in cases with an operative time <120 min (41.2%) and >240 min (53.4%). The risk of SM+ significantly increased 1.70 and 1.94 times in cases with an operative time <120 min and >240 min, respectively, independently to the surgical approach. The rate of erectile disfunction (ED) varied from 22.4% to 60.3% between <120 min and >240 min procedures (p = 0.001). According to blood loss, SM+ rates slightly but significantly (p = 0.032) varied; a higher rate of SM+ was found in cases with a Hb variation between 2–4 g/dl (35.9%). Conclusions Independently to the surgical approach, operative time, more than blood loss at RP, represents a significant variable able to influence SM status and post-operative ED.

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“…In recent years, new urinary and serum biomarkers have been developed, with the goal of overcoming the current limitations of PSA, mainly represented by a low specificity, which has led to unnecessary biopsies and over-diagnosis and over-treatment of indolent PC cases [ 10 , 11 , 12 ]. Ideally, to be useful in clinical practice, a tumor biomarker should present the following characteristics: first and most importantly, it should be relatively specific for PC, and not affected by other benign conditions; second, it should be useful in all steps of the natural history of the disease (i.e., from diagnosis to follow-up after initial and subsequent therapy) and, in this context, it should be accurate in distinguishing csPC from indolent cases.…”

Section: Role Of Different Bio-fluids On Pc Biomarkersmentioning

confidence: 99%

Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes

Salciccia

Capriotti

Laganà

et al. 2021

IJMS

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Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. To overcome the current limitations of PSA, new urinary and serum biomarkers have been developed in recent years. Although several biomarkers have been explored in various scenarios and patient settings, to date, specific guidelines with a high level of evidence on the use of these markers are lacking. Recent advances in metabolomic, genomics, and proteomics have made new potential biomarkers available. A number of studies focused on the characterization of the specific PC metabolic phenotype using different experimental approaches has been recently reported; yet, to date, research on metabolomic application for PC has focused on a small group of metabolites that have been known to be related to the prostate gland. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers. Thanks to a general improvement of the technical equipment to analyze exosomes, we are able to obtain reliable quantitative and qualitative information useful for clinical application. Although some pilot clinical investigations have proposed potential PC biomarkers, data are still preliminary and non-conclusive.

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Tissue Expression of Androgen Receptor Splice Variant 7 at Radical Prostatectomy Predicts Risk of Progression in Untreated Nonmetastatic Prostate Cancer

Cited by 13 publications

References 10 publications

Androgen-Dependent Prostate Cancer Cells Reprogram Their Metabolic Signature upon GLUT1 Upregulation by Manganese Superoxide Dismutase

Androgen-Dependent Prostate Cancer Cells Reprogram Their Metabolic Signature upon GLUT1 Upregulation by Manganese Superoxide Dismutase

Influence of operative time and blood loss on surgical margins and functional outcomes for laparoscopic versus robotic-assisted radical prostatectomy: a prospective analysis

Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes

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