Thyroid and androgen receptor signaling are antagonized by μ-Crystallin in prostate cancer
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01.02.2021 |
Aksoy O.
Pencik J.
Hartenbach M.
Moazzami A.A.
Schlederer M.
Balber T.
Varady A.
Philippe C.
Baltzer P.A.
Mazumder B.
Whitchurch J.B.
Roberts C.J.
Haitel A.
Herac M.
Susani M.
Mitterhauser M.
Marculescu R.
Stangl-Kremser J.
Hassler M.R.
Kramer G.
Shariat S.F.
Turner S.D.
Tichy B.
Oppelt J.
Pospisilova S.
Hartenbach S.
Tangermann S.
Egger G.
Neubauer H.A.
Moriggl R.
Culig Z.
Greiner G.
Hoermann G.
Hacker M.
Heery D.M.
Merkel O.
Kenner L.
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International Journal of Cancer |
10.1002/ijc.33332 |
0 |
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© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control. Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3′-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.
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Thyroid and androgen receptor signaling are antagonized by μ-Crystallin in prostate cancer
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01.02.2021 |
Aksoy O.
Pencik J.
Hartenbach M.
Moazzami A.A.
Schlederer M.
Balber T.
Varady A.
Philippe C.
Baltzer P.A.
Mazumder B.
Whitchurch J.B.
Roberts C.J.
Haitel A.
Herac M.
Susani M.
Mitterhauser M.
Marculescu R.
Stangl-Kremser J.
Hassler M.R.
Kramer G.
Shariat S.F.
Turner S.D.
Tichy B.
Oppelt J.
Pospisilova S.
Hartenbach S.
Tangermann S.
Egger G.
Neubauer H.A.
Moriggl R.
Culig Z.
Greiner G.
Hoermann G.
Hacker M.
Heery D.M.
Merkel O.
Kenner L.
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International Journal of Cancer |
10.1002/ijc.33332 |
0 |
Ссылка
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control. Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3′-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.
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Association of Hyponatremia With Survival in Patients With Castration-resistant Prostate Cancer: A Clinical Commentary
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01.12.2019 |
Stangl-Kremser J.
Kramer G.
Shariat S.
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Clinical Genitourinary Cancer |
10.1016/j.clgc.2019.08.001 |
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© 2019 Elsevier Inc. Hyponatremia has been associated with an increased risk of demise in several malignancies. The aim of the current study was to evaluate its prognostic value in patients with castration-resistant prostate cancer. In 186 patients planned for docetaxel chemotherapy, we detected an association between hyponatremia and decreased survival (P = .04). We suggest conducting further well-designed studies including full workup of hyponatremia.
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Prognostic Value of Lactate Dehydrogenase in Metastatic Prostate Cancer: A Systematic Review and Meta-analysis
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01.12.2019 |
Mori K.
Kimura S.
Parizi M.
Enikeev D.
Glybochko P.
Seebacher V.
Fajkovic H.
Mostafaei H.
Lysenko I.
Janisch F.
Egawa S.
Shariat S.
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Clinical Genitourinary Cancer |
10.1016/j.clgc.2019.07.009 |
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© 2019 The purpose of this study was to assess the prognostic value of lactate dehydrogenase (LDH) in patients with metastatic prostate cancer (PC). A systematic review and meta-analysis was performed in March 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with PC with high versus low LDH to determine the predictive value of LDH for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We performed a formal meta-analysis for both OS and PFS. A total of 59 articles with 14,851 patients were included in the systematic review and 45 studies with 12,224 patients for the qualitative assessment. High LDH was associated with both worse OS (pooled hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.75-2.44) and PFS (pooled HR, 1.08; 95% CI, 1.01-1.16). In subgroup analyses of both patients with castration-resistant prostate cancer (CRPC) and those with hormone-sensitive prostate cancer (HSPC), LDH was associated with OS (pooled HR, 2.02; 95% CI, 1.69-2.42 and pooled HR, 2.25; 95% CI, 1.78-2.84, respectively). In patients with CRPC, LDH was associated with OS in those treated with docetaxel systemic chemotherapy and androgen receptor–axis-targeting agents (pooled HR, 2.03; 95% CI, 1.37-3.00 and pooled HR, 1.79; 95% CI, 1.25-2.57, respectively). Elevated serum levels of LDH were associated with an increased risk of mortality and progression in patients with metastatic PC. LDH was independently associated with OS in both patients with CRPC and HSPC. LDH could be integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision-making process.
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Added value of diffusion-weighted MRI for nodal radiotherapy planning in pelvic malignancies
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01.10.2019 |
Sushentsev N.
Martin H.
Rimmer Y.
Barrett T.
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Clinical and Translational Oncology |
10.1007/s12094-019-02068-0 |
1 |
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© 2019, Federación de Sociedades Españolas de Oncología (FESEO). Purpose: To evaluate the added value of diffusion-weighted imaging (DWI) to T2-weighted imaging (T2WI) for improved identification of pelvic lymph nodes (LN) by radiation oncologists. Methods/patients: This retrospective study included 20 patients with histopathologically proven node-negative prostate cancer. All patients underwent 3T-MRI of the prostate; matched axial T2WI and DWI sequences were assessed by an experienced uro-radiologist as the reference standard. Consultant and specialist registrar radiation oncologists were asked to identify all LN first on T2WI alone (read 1) and then on T2WI and DWI combined (read 2); LN were measured in size and divided into true positives (TP), false positives (FP) and false negatives (FN). Sensitivity, positive predictive value (PPV) and false negative rate (FNR) were then calculated and compared using Pearson’s Chi square test. Results: A total of 177 LN comprised the reference standard. 16 TP, 16 FP and 161 FN LN (sensitivity 9.0%, PPV 50.0%, FNR 91.0%) and 124, 15 and 53 LN (70.1%, 89.2%, 30%) were identified by reader 1 on reads 1 and 2, respectively; χ2 (2, N = 385) = 137.8, p < 0.0001. 27, 21 and 150 LN (15.3%, 56.3%, 84.8%) and 120, 13 and 57 LN (67.8%, 90.2%, 32.2%) were identified by reader 2 on the two reads; χ2 (2, N = 388) = 102.4, p < 0.0001. Conclusions: Adding DWI to T2WI significantly improved identification of pelvic LN by radiation oncologists and can therefore be regarded as a useful LN contouring technique for RT planning in pelvic malignancies.
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Oncological safety of testosterone replacement therapy in prostate cancer survivors after definitive local therapy: A systematic literature review and meta-analysis
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01.10.2019 |
Kardoust Parizi M.
Abufaraj M.
Fajkovic H.
Kimura S.
Iwata T.
D'Andrea D.
Karakiewicz P.
Shariat S.
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Urologic Oncology: Seminars and Original Investigations |
10.1016/j.urolonc.2019.06.007 |
2 |
Ссылка
© 2019 Elsevier Inc. Aim: To evaluate the association between testosterone replacement therapy (TRT) in prostate cancer (CaP) patients who underwent definitive local therapy with curative intent with biochemical recurrence (BCR). Materials and methods: A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on November 2018 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta Analysis guidelines. The pooled BCR rate in CaP men treated with TRT after definitive local therapy with curative intent was calculated using a random effects model. Results: Twenty-one studies were eligible. The overall pooled BCR rate was 0.01 (95%CI 0.00–0.02) suggesting a lack of association between TRT and BCR; there was no heterogeneity among included studies (I2 = 24.34%, P = 0.15). In subgroup analyses, pooled BCR rates were 0.00 (95%CI 0.00–0.02) in patients treated with radical prostatectomy and 0.02 (95%CI 0.00–0.04) in patients treated with external beam radiation therapy, brachytherapy, cryotherapy, or high intensity focused ultrasound; there was no heterogeneity in the subgroup analyses (I2 = 19.88%, P = 0.18). Conclusions: In this systematic review and meta-analysis, we did not observe higher rate of BCR after TRT for nonmetastatic CaP patients after definitive local therapy. Based on these data, others and we have outlined a phase I/II trial assessing the safety and benefits of TRT in select men with secondary symptomatic hypogonadism who have no active disease after definitive local CaP therapy with curative intent.
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Surgical site infections after radical prostatectomy: A comparative study between robot-assisted laparoscopic radical prostatectomy and retropubic radical prostatectomy
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01.07.2018 |
Osmonov D.
Faddan A.
Aksenov A.
Naumann C.
Rapoport L.
Bezrukov E.
Tsarichenko D.
Jünemann K.
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Turkish Journal of Urology |
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Ссылка
© 2018 by Turkish Association of Urology. Objective: Surgical site infection (SSI) is defined as infection at or near surgical incisions within 30 days of an operative procedure and classified either incisional superficial and deep or organ/space. The aim of the study is to report and compare the incidence and management of SSIs after robot-assisted laparoscopic radical prostatectomy (RALP) and retropubic radical prostatectomy (RRP). Material and methods: Within the last 4 years, we identified 285 patients that underwent RRP, n=187 (66%) or RALP, n=98 (34%). We reviewed the frequency, types and way of management of SSI complications. Results: A significant difference was found between RALP and RRP (2/98, 2% vs. 27/187, 14.4%; p<0.0001) as for SSIs. The time interval between the time of surgery and diagnosis of SSIs was longer in RALP relative to RRP (median 13.5 vs. 12.9 days, p=0.761). Conclusion: All types of SSIs could be developed after RP, however RALP patients only experienced organ or space SSIs and have a lower rate of SSIs and shorter treatment time.
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Comparative results of cryoablation and laparoscopic radical prostatectomy in the treatment of localized prostate cancer
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01.05.2018 |
Chinenov D.
Rapoport L.
Shpot E.
Enikeev D.
Chernov Y.
Taratkin M.
Korolev D.
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Urologia |
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2 |
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AIM: To evaluate early prostate cancer cryoablation functional and oncological results in comparison with results of extraperitoneoscopic radical prostatectomy. MATERIALS AND METHODS: We analyzed early results of surgical treatment of 285 patients with prostate cancer: 42 of them had undergone total cryoablation (Group 1) while the rest of them had been treated by radical laparo- and extraperitoneoscopic prostatectomy. For comparative assessment of prostate cryoablation results, 42 patients from Group 2 randomized in accordance with their age, stage of disease, Gleason, prostate-specific antigen, and prostate volume were selected. In compliance with the results of pre-surgical examination, all the patients had low oncological risk and were not concerned in sexual function. Volume of prostate was from 22 to 65 cm3, prostate-specific antigen level was from 4.1 to 10 ng/mL, and level of neoplastic process differentiation using Gleason grading system was from 6 to 7a (3 + 4) scores. RESULTS: Patients after prostate cryoablation in early post-surgical period felt lower intensity of postoperative pain compared with those who had undergone prostatectomy. Follow-up period up to 12 months manifested significant true reduction of prostate-specific antigen level in both groups of patients. Frequency of stress-induced enuresis in Group 1 was not observed. CONCLUSION: Radical prostatectomy is still the traditional treatment of choice in the case of localized prostate cancer. But we can draw the conclusion that cryoablation is an effective low-invasive method for treatment of low oncological risk patients, which gives the opportunity both to achieve good oncological results and to preserve high life quality.
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Postoperative complications of minimally invasive therapies for prostate cancer
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01.01.2018 |
Enikeev D.
Rapoport L.
Amosov A.
Enikeev M.
Chinenov D.
Snurnitsyna O.
Gerasimov A.
Dzhalaev Z.
Gaas M.
Laukhtina E.
Taratkin M.
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Onkourologiya |
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© ABC-press Publishing House. All rights reserved. Prostate cancer is the most common cancer among men. Radical prostatectomy (open, laparoscopic, or robotic) remains the main method of surgical treatment for prostate cancer. However, minimally invasive therapies for prostate cancer are becoming increasingly popular in recent years, because they have similar efficacy as open surgery. The most studied minimally invasive therapies are cryoablation, high intensity focused ultrasound (HIFU), and brachytherapy. Despite the minimization of damage to neighboring structures, minimally invasive procedures can cause a number of complications, like any other surgical interventions. Each method has specific limitations and the most typical complications. Since multiple minimally invasive methods are currently available, we can ensure an individual approach to each particular patient, thus using the advantages of the methods and avoiding possible complications. This article covers the most frequent and severe complications of minimally invasive therapies for prostate cancer, as well as the methods of their prevention and treatment.
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Radical prostatectomy performed via robotic, transperitoneal and extraperitoneoscopic approaches: Functional and early oncological outcomes
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01.01.2018 |
Rapoport L.
Yossepowitch O.
Shpot E.
Chinenov D.
Chernov Y.
Yurova M.
Enikeev D.
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Central European Journal of Urology |
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0 |
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© 2018, Polish Urological Association. All rights reserved. Introduction Oncological remission along with high postoperative functionality [continence and erectile function (EF)] are the main aspects of prostate cancer (PCa) treatment. The aim of this study was to compare functional and oncological treatment results achieved after a nerve-sparing radical prostatectomy (RP) via transperitoneal (TPRP), extraperitoneal (EPRP) and robot-assisted (RARP) approach. Material and methods From March 2015 to March 2016, 507 RP were performed at the Institute for Urology and Reproductive Health (Moscow, Russia). A total of 264 patients with localized (cТ1а–2с) prostate cancer [prostate-specific antigen (PSA) <20 ng/ml, Gleason score ≤7], intact prostate capsule (according to MRI), International Index of Erectile Function (IIEF-5) ≥19 and a life expectancy >10 years were included into the retrospective study. All the surgeries were performed by a single surgeon. The outcomes were evaluated after urethral catheter removal and 3–6–12 months after RP. Results Nerve preservation (NP) was performed for 153 patients without significant distinctions in time (р = 0.064) and blood loss (р = 0.073). The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) score was lower for NP: 9.23 ±6.59 and 3.86 ±5.38 after 3 and 12 months respectively compared with continence after RP without nerve preservation (NP): 14.27 ±5.1 vs. 6.15 ±4.76 (р <0.001). Continent was 52.2% vs. 83.3% vs. 81.8% in TPRP, RARP and EPRP groups; р <0.001. IIEF-5 scores were 14.67 ±9.4, 4.2 ±4.26 and 4.0 ±2.07 after RARP, TPRP and EPRP respectively (р = 0.002). After 12 months the PSA: TPRP = 0.11 ±0.19, RARP = 0.03 ±0.05 and EPRP = 0.53 ±1.87 ng/ml (р <0.001). Outcomes depend on surgical approach and was better in the RARP-group (AUC = 0.768 ±0.034 (CI 95% 0,701–0.834; р <0.001). Conclusions We suggest RARP with NP as a method of choice for treatment of prostate cancer in patients interested in preservation of EF and quality of life in general.
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