CONTEXT: Recent randomized controlled trials (RCTs) examined the role of adding androgen receptor signaling inhibitors (ARSIs), including abiraterone acetate (ABI), apalutamide, darolutamide (DAR), and enzalutamide (ENZ), to docetaxel (DOC) and androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). OBJECTIVE: To analyze the oncologic benefit of triplet combination therapies using ARSI + DOC + ADT, and comparing them with available treatment regimens in patients with mHSPC. EVIDENCE ACQUISITION: Three databases and meetings abstracts were queried in April 2022 for RCTs analyzing patients treated with first-line combination systemic therapy for mHSPC. The primary interests of measure were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were conducted to assess the differential outcomes in patients with low- and high-volume disease as well as de novo and metachronous metastasis. EVIDENCE SYNTHESIS: Overall, 11 RCTs were included for meta-analyses and network meta-analyses (NMAs). We found that the triplet combinations outperformed DOC + ADT in terms of OS (pooled hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.65-0.84) and PFS (pooled HR: 0.49, 95% CI: 0.42-0.58). There was no statistically significant difference between patients with low- and high-volume disease in terms of an OS benefit from adding an ARSI to DOC +ADT (both HR: 0.79; p = 1). Based on NMAs, triplet therapy also outperformed ARSI + ADT in terms of OS (DAR + DOC + ADT: pooled HR: 0.74, 95% CI: 0.55-0.99) and PFS (ABI + DOC + ADT: HR: 0.68, 95% CI: 0.51-0.91, and ENZ + DOC + ADT: HR: 0.70, 95% CI: 0.53-0.93). An analysis of treatment ranking among de novo mHSPC patients showed that triplet therapy had the highest likelihood of improved OS in patients with high-volume disease; however, doublet therapy using ARSI + ADT had the highest likelihood of improved OS in patients with low-volume disease. CONCLUSIONS: We found that the triplet combination therapy improves survival endpoints in mHSPC patients compared with currently available doublet treatment regimens. Our findings need to be confirmed in further head-to-head trials with longer follow-up and among various patient populations. PATIENT SUMMARY: Our study suggests that triplet therapy with androgen receptor signaling inhibitor, docetaxel, androgen deprivation therapy prolongs survival in patients with metastatic hormone-sensitive prostate cancer compared with the current standard doublet therapy.

• Klíčová slova
• Androgen receptor signaling inhibitor, Docetaxel, Metastatic hormone-sensitive prostate cancer,
• MeSH
• androgenní receptory MeSH
• androgeny terapeutické užití   MeSH
• antagonisté androgenů * škodlivé účinky   MeSH
• docetaxel terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty * patologie   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• androgenní receptory MeSH
• androgeny MeSH
• antagonisté androgenů * MeSH
• docetaxel MeSH
• enzalutamide MeSH Prohlížeč

(1) Background: Several phase II studies, including randomized controlled trials (RCTs), assessed the efficacy of adding androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) as a neoadjuvant treatment in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). Summarizing the early results of these studies could help in designing phase III trials and patient counseling. (2) Methods: We queried three databases in January 2023 for studies that included PCa patients treated with neoadjuvant ARSI-based combination therapy before RP. The outcomes of interest were oncologic outcomes and pathologic responses, such as pathologic complete response (pCR) and minimal residual disease (MRD). (3) Results: Overall, twenty studies (eight RCTs) were included in this systematic review. Compared to ADT or ARSI alone, ARSI + ADT was associated with higher pCR and MRD rates; this effect was less evident when adding a second ARSI or chemotherapy. Nevertheless, ARSI + ADT resulted in relatively low pCR rates (0-13%) with a high proportion of ypT3 (48-90%) in the resected specimen. PTEN loss, ERG positive, or intraductal carcinoma seem to be associated with worse pathologic response. One study that adjusted for the effects of possible confounders reported that neoadjuvant ARSI + ADT improved time to biochemical recurrence and metastasis-free survival compared to RP alone. (4) Conclusions: Neoadjuvant ARSI + ADT combination therapy results in improved pathologic response compared to either alone or none in patients with non-metastatic advanced PCa. Ongoing phase III RCTs with long-term oncologic outcomes, as well as biomarker-guided studies, will clarify the indication, oncologic benefits, and adverse events of ARSI + ADT in patients with clinically and biologically aggressive PCa.

• Klíčová slova
• androgen receptor signaling inhibitors, neoadjuvant therapy, prostate cancer, radical prostatectomy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Enzalutamide is an androgen receptor (AR) inhibitor approved for therapy of metastatic castration resistant prostate cancer. However, clinical application revealed that 30 to 40% of patients acquire resistance after a short period of treatment. Currently, the molecular mechanisms underlying such resistances are not completely understood, partly due to a lack of model systems. In the present study we established three different cellular models of enzalutamide resistance including a cell line with wild type AR (LAPC4), DuCaP cells which overexpress wild-type AR, as well as a cell which has been adapted to long term androgen ablation (LNCaP Abl) and harbors the AR T878A mutation. After 10 months of cultivation, sustained growth in the presence of enzalutamide was achieved. When compared to controls, resistant cells exhibit significantly decreased sensitivity to enzalutamide as measured with 3[H]thymidine incorporation and WST assay. Moreover, these cell models exhibit partly re-activated AR signaling despite presence of enzalutamide. In addition, we show that enzalutamide resistant cells are insensitive to bicalutamide but retain considerable sensitivity to abiraterone. Mechanistically, enzalutamide resistance was accompanied by increased AR and AR-V7 mRNA and protein expression as well as AR gene amplification, while no additional AR mutations have been identified.

• Klíčová slova
• AR gene amplification, AR-V7, androgen receptor, enzalutamide resistance, prostate cancer,
• MeSH
• androgenní receptory genetika   metabolismus   MeSH
• androsteny farmakologie   MeSH
• anilidy farmakologie   MeSH
• benzamidy MeSH
• chemorezistence účinky léků   genetika   MeSH
• fenylthiohydantoin analogy a deriváty   farmakologie   MeSH
• lidé MeSH
• mutace MeSH
• nádorové buněčné linie MeSH
• nádory prostaty genetika   metabolismus   patologie   MeSH
• nitrily farmakologie   MeSH
• proliferace buněk účinky léků   genetika   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• signální transdukce účinky léků   genetika   MeSH
• tosylové sloučeniny farmakologie   MeSH
• viabilita buněk účinky léků   genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• abiraterone MeSH Prohlížeč
• androgenní receptory MeSH
• androsteny MeSH
• anilidy MeSH
• benzamidy MeSH
• bicalutamide MeSH Prohlížeč
• enzalutamide MeSH Prohlížeč
• fenylthiohydantoin MeSH
• nitrily MeSH
• tosylové sloučeniny MeSH

BACKGROUND: Androgen-receptor signaling inhibitors (ARSIs) significantly improve survival in systemic therapy for advanced/metastatic prostate cancer (PCa) patients; however possible central nervous system (CNS) toxicity is an unaddressed concern. We aimed to assess and compare the incidence of CNS-related adverse events (AEs) secondary to the treatment of PCa patients with different ARSIs. MATERIALS: In August 2023, a comprehensive seach was conducted in three databases for randomized controlled trials (RCTs) of PCa patients receiving ARSIs plus ADT. The primary endpoints included mental impairment, cognitive impairment, seizure, fatigue, and falls. RESULTS: Twenty-six RCTs, comprising 20,328 patients, were included in meta-analyses and network meta-analyses (NMAs). ARSIs increased the risk of mental impairment (RR: 1.72; 95% CI, 1.09-2.71), cognitive impairment (RR: 2.25; 95% CI, 1.78-2.86), seizure (RR: 2.20, 95% CI, 1.09-4.45), fatigue (RR: 1.31, 95% CI, 1.20-1.43), and falls (RR: 2.07, 95% CI, 1.60-2.67) compared to standard of care (SOC). Based on NMAs, Enzalutamide showed a significant increase in risk for all assessed CNS-related AEs, while Abiraterone demonstrated significant risk increases in cognitive impairment, fatigue, and falls. Conversely, Darolutamide did not exhibit significant increases in risk for any CNS-related AEs, except for fatigue. CONCLUSIONS: The addition of ARSIs to ADT increased all examined CNS-related AEs compared to SOC. Each ARSI is associated with a distinct profile of CNS-related AEs. Careful patient selection and monitoring for CNS sequelae is necessary to achieve the best quality of life in patients on ARSI + ADT for PCa.

• Klíčová slova
• ARSI, Central Nervous System, Meta-analysis, Network Meta-analysis, Prostate Cancer,
• MeSH
• antagonisté androgenních receptorů * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• benzamidy MeSH
• fenylthiohydantoin škodlivé účinky   aplikace a dávkování   MeSH
• lidé MeSH
• nádory prostaty * farmakoterapie   patologie   MeSH
• nemoci centrálního nervového systému chemicky indukované   MeSH
• nitrily MeSH
• pyrazoly MeSH
• randomizované kontrolované studie jako téma MeSH
• síťová metaanalýza * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• antagonisté androgenních receptorů * MeSH
• benzamidy MeSH
• darolutamide MeSH Prohlížeč
• enzalutamide MeSH Prohlížeč
• fenylthiohydantoin MeSH
• nitrily MeSH
• pyrazoly MeSH

The bulbocavernosus (BC) is a sexually dimorphic muscle observed only in males. Androgen receptor knockout mouse studies show the loss of BC formation. This suggests that androgen signaling plays a vital role in its development. Androgen has been known to induce muscle hypertrophy through satellite cell activation and myonuclei accretion during muscle regeneration and growth. Whether the same mechanism is present during embryonic development is not yet elucidated. To identify the mechanism of sexual dimorphism during BC development, the timing of morphological differences was first established. It was revealed that the BC was morphologically different between male and female mice at embryonic day (E) 16.5. Differences in the myogenic process were detected at E15.5. The male BC possesses a higher number of proliferating undifferentiated myoblasts. To identify the role of androgen signaling in this process, muscle-specific androgen receptor (AR) mutation was introduced, which resulted in no observable phenotypes. Hence, the expression of AR in the BC was examined and found that the AR did not colocalize with any muscle markers such as Myogenic differentiation 1, Myogenin, and paired box transcription factor 7. It was revealed that the mesenchyme surrounding the BC expressed AR and the BC started to express AR at E15.5. AR mutation on the nonmyocytic cells using spalt-like transcription factor 1 (Sall1) Cre driver mouse was performed, which resulted in defective BC formation. It was revealed that the number of proliferating undifferentiated myoblasts was reduced in the Sall1 Cre:AR(L-/Y) mutant embryos, and the adult mutants were devoid of BC. The transition of myoblasts from proliferation to differentiation is mediated by cyclin-dependent kinase inhibitors. An increased expression of p21 was observed in the BC myoblast of the Sall1 Cre:AR(L-/Y) mutant and wild-type female. Altogether this study suggests that the nonmyocytic AR may paracrinely regulate the proliferation of myoblast possibly through inhibiting p21 expression in myoblasts of the BC.

• MeSH
• androgenní receptory genetika   metabolismus   MeSH
• časové faktory MeSH
• embryo savčí embryologie   metabolismus   MeSH
• imunohistochemie MeSH
• inhibitor p21 cyklin-dependentní kinasy metabolismus   MeSH
• mikroskopie elektronová rastrovací MeSH
• mutace MeSH
• myoblasty cytologie   metabolismus   MeSH
• myši inbrední ICR MeSH
• myši knockoutované MeSH
• myši transgenní MeSH
• myši MeSH
• perineum embryologie   MeSH
• proliferace buněk MeSH
• sexuální faktory MeSH
• svaly embryologie   metabolismus   ultrastruktura   MeSH
• těhotenství MeSH
• transkripční faktory genetika   metabolismus   MeSH
• vývoj svalů genetika   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• androgenní receptory MeSH
• inhibitor p21 cyklin-dependentní kinasy MeSH
• Sall1 protein, mouse MeSH Prohlížeč
• transkripční faktory MeSH

PURPOSE: There is strong epidemiologic evidence indicating that estrogens may not be the sole steroid drivers of breast cancer. We hypothesize that abundant adrenal androgenic steroid precursors, acting via the androgen receptor (AR), promote an endocrine-resistant breast cancer phenotype. EXPERIMENTAL DESIGN: AR was evaluated in a primary breast cancer tissue microarray (n = 844). Androstenedione (4AD) levels were evaluated in serum samples (n = 42) from hormone receptor-positive, postmenopausal breast cancer. Levels of androgens, progesterone, and estradiol were quantified using LC/MS-MS in serum from age- and grade-matched recurrent and nonrecurrent patients (n = 6) before and after aromatase inhibitor (AI) therapy (>12 months). AR and estrogen receptor (ER) signaling pathway activities were analyzed in two independent AI-treated cohorts. RESULTS: AR protein expression was associated with favorable progression-free survival in the total population (Wilcoxon, P < 0.001). Pretherapy serum samples from breast cancer patients showed decreasing levels of 4AD with age only in the nonrecurrent group (P < 0.05). LC/MS-MS analysis of an AI-sensitive and AI-resistant cohort demonstrated the ability to detect altered levels of steroids in serum of patients before and after AI therapy. Transcriptional analysis showed an increased ratio of AR:ER signaling pathway activities in patients failing AI therapy (t test P < 0.05); furthermore, 4AD mediated gene changes associated with acquired AI resistance. CONCLUSIONS: This study highlights the importance of examining the therapeutic consequences of the steroid microenvironment and demonstrable receptor activation using indicative gene expression signatures.

• MeSH
• androgenní receptory fyziologie   MeSH
• androstendion krev   fyziologie   MeSH
• chemorezistence MeSH
• inhibitory aromatasy terapeutické užití   MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buňky kultivované MeSH
• nádory prsu krev   farmakoterapie   etiologie   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• androgenní receptory MeSH
• androstendion MeSH
• AR protein, human MeSH Prohlížeč
• inhibitory aromatasy MeSH
• ligandy MeSH

Members of the bcl-2 gene family and endogenous inhibitors of cyclin-dependent kinases participate in the regulation of apoptosis and cell cycle in a diverse range of cell types and are implicated in the development of hormone refractory prostate cancer and resistance to anti-cancer therapy. The expression of several of these genes can be regulated by steroid hormones and related agents via their nuclear receptors. However, insufficient information considering the protein expression after the treatment by hormone antagonists is available. The aim of this study was to evaluate the expression of anti- and pro-apoptotic proteins, (Bcl-2, Bax), and to correlate this with the appearance of some nuclear receptors and cell cycle related proteins in androgen sensitive and androgen insensitive prostate cancer cell lines, LNCaP and DU-145, after the treatment by androgen antagonist bicalutamide. Our results revealed that androgen receptor (AR) expression in LNCaP cells decreased, however in DU-145 cells AR slightly increased following anti-androgen treatment. The same agent stimulated expression of p21Waf1/Cip5 and p27Kip1 in LNCaP, as well as in DU-145 cell lines. Bcl-2 level increased slightly in LNCaP cells and, in DU-145 cells was almost undetectable. Bax expression was not changed in LNCaP but significantly decreased in DU-145 cells. Similarly, retinoid X receptor beta (RXRbeta) level was significantly down regulated after 24 hours in DU-145 and also in LNCaP cells after 72 hours. These results confirm that androgen withdrawal therapy employing anti-androgens may elicit different signalling pathways in various types of prostate cancer that may be dependent on AR status and AR sensitivity.

• MeSH
• androgeny farmakologie   MeSH
• anilidy farmakologie   MeSH
• antagonisté androgenů farmakologie   MeSH
• buněčné dělení MeSH
• buněčné jádro metabolismus   MeSH
• buněčný cyklus účinky léků   MeSH
• časové faktory MeSH
• down regulace MeSH
• lidé MeSH
• nádorové buňky kultivované MeSH
• nádory prostaty farmakoterapie   MeSH
• nitrily MeSH
• protein X asociovaný s bcl-2 MeSH
• protoonkogenní proteiny c-bcl-2 metabolismus   MeSH
• protoonkogenní proteiny metabolismus   MeSH
• signální transdukce MeSH
• tosylové sloučeniny MeSH
• viabilita buněk MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• androgeny MeSH
• anilidy MeSH
• antagonisté androgenů MeSH
• BAX protein, human MeSH Prohlížeč
• bicalutamide MeSH Prohlížeč
• nitrily MeSH
• protein X asociovaný s bcl-2 MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• protoonkogenní proteiny MeSH
• tosylové sloučeniny MeSH

Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 µM for MXC and 126 µM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC via mechanisms involving rapid activation of PC-PLC occurring independently of ER- or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors.

• Klíčová slova
• endocrine disruptors, epigenetic toxicity, gap junctional intercellular communication, mitogen-activated protein kinases, non-genomic signaling., phosphatidylcholine-specific phospholipase C,
• MeSH
• androgenní receptory metabolismus   MeSH
• buněčné linie MeSH
• insekticidy toxicita   MeSH
• játra cytologie   účinky léků   metabolismus   MeSH
• kmenové buňky účinky léků   metabolismus   MeSH
• konexin 43 metabolismus   MeSH
• krysa rodu Rattus MeSH
• MAP kinasový signální systém účinky léků   MeSH
• methoxychlor toxicita   MeSH
• mezerový spoj účinky léků   MeSH
• mezibuněčná komunikace účinky léků   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• oxazoly toxicita   MeSH
• potkani inbrední F344 MeSH
• receptory pro estrogeny metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• androgenní receptory MeSH
• insekticidy MeSH
• konexin 43 MeSH
• methoxychlor MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• oxazoly MeSH
• receptory pro estrogeny MeSH
• vinclozolin MeSH Prohlížeč

BACKGROUND: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified. OBJECTIVE: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs. METHODS: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC). RESULTS: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92). CONCLUSIONS: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Steroids with a nitrogen-containing heterocycle in the side chain are known as effective inhibitors of androgen signaling and/or testosterone biosynthesis, thus showing beneficial effects for the treatment of prostate cancer. In this work, a series of 3β-hydroxy-5-ene steroids, containing an isoxazole fragment in their side chain, was synthesized. The key steps included the preparation of Weinreb amide, its conversion to acetylenic ketones, and the 1,2- or 1,4-addition of hydroxylamine, depending on the solvent used. The biological activity of the obtained compounds was studied in a number of tests, including their effects on 17α-hydroxylase and 17,20-lyase activity of human CYP17A1 and the ability of selected compounds to affect the downstream androgen receptor signaling. Three derivatives diminished the transcriptional activity of androgen receptor and displayed reasonable antiproliferative activity. The candidate compound, 24j (17R)-17-((3-(2-hydroxypropan-2-yl)isoxazol-5-yl)methyl)-androst-5-en-3β-ol, suppressed the androgen receptor signaling and decreased its protein level in two prostate cancer cell lines, LNCaP and LAPC-4. Interaction of compounds with CYP17A1 and the androgen receptor was confirmed and described by molecular docking.

• Klíčová slova
• CYP17A1, LAPC-4, LNCaP, Weinreb amide, androgen receptor, androgen signaling, isoxazoles, molecular docking, prostate cancer,
• MeSH
• androgenní receptory metabolismus   MeSH
• antitumorózní látky * chemie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prostaty * farmakoterapie   metabolismus   MeSH
• simulace molekulového dockingu MeSH
• steroid-17-alfa-hydroxylasa metabolismus   MeSH
• steroidy farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• androgenní receptory MeSH
• antitumorózní látky * MeSH
• steroid-17-alfa-hydroxylasa MeSH
• steroidy MeSH