U radu se objavljuju dosad nepoznati nacrti planiranoga baroknog grada-tvrđave Novi Karlovac, čija je gradnja započela 1733. nedaleko od Karlovca, kao dio velike strateške cjeline novih ...gradova-tvrđava na jugoistočnoj granici Habsburške Monarhije. Grad je trebao površinom biti najveći grad-tvrđava u Hrvatskoj, no početkom Rata za nasljeđe poljske krune, a potom i smrću princa Eugena Savojskog 1736. gradnja je zaustavljena, a u posve novim okolnostima nakon smrti cara Karla VI. više nije nastavljena. Dotad izgrađeni zemljani nasipi pojedinih fortifikacijskih dijelova i opkopi uz njih ostali su očuvani do danas. Projekti utvrđenoga grada dio su opusa Nicolasa Doxata de Démoreta, glavnog projektanta gradova-tvrđava princa Eugena Savojskog, a pažnju posebno privlači i glavna gradska crkva koja je projektirana kao tlocrtna varijacija bečke Peterskirche.
Rad se temelji na arhivskim istraživanjima te otkriva nove podatke o povijesti urarstva u Karlovcu u 18. i 19. stoljeću. Donosi saznanja o dosad neobjavljenim satovima koji se čuvaju u fundusu ...Gradskog muzeja Karlovac, čime broj sačuvanih satova sa signaturama in C/Karlstadt raste na deset. Radi se o jedinim poznatim satovima s karlovačkom signaturom dvojice urara Marcusa Gohma (portalni sat) i J. Heckela (sat u okviru), te o podnom satu Lorenza Wilhelma Pehra.
The paper is based on archival research and provides new insights into the history of clockmaking in Karlovac in the 18th and 19th centuries. It also brings information about until now unpublished clocks in the City Museum of Karlovac, which increases the number of preserved clocks with signatures in C / Karlstadt to ten. These are the only known clocks with the Karlovac signature of two clockmakers Marcus Gohm (portal clock) and J. Heckel (frame clock), and the longcase clock of Lorenzo Wilhelm Pehr.
The paper is based on archival research and provides new insights into the history of clockmaking in Karlovac in the 18th and 19th centuries. It also brings information about until now unpublished ...clocks in the City Museum of Karlovac, which increases the number of preserved clocks with signatures in C / Karlstadt to ten. These are the only known clocks with the Karlovac signature of two clockmakers Marcus Gohm (portal clock) and J. Heckel (frame clock), and the longcase clock of Lorenzo Wilhelm Pehr.
Gradski muzej Karlovac na različite je načine predstavljao digitaliziranu građu u okviru svojih mrežnih stranica, a prvi projekt koji je sustavno obuhvatio veći broj predmeta baštine bio je Virtualni ...muzej karlovačke industrije 2014. godine.
Despite enzalutamide's efficacy in delaying the progression of metastatic castration-resistant prostate cancer (CRPC), resistance to this anti-androgen inevitably occurs. Several studies have ...revealed that the signal transducer and activator of transcription (STAT) 5 plays a role in tumour progression and development of drug resistance such as enzalutamide. Data mining revealed heterogeneous expression of STAT5 in enzalutamide-treated mCRPC patients and enzalutamide-resistant prostate cancer (PCa). Isobologram analysis revealed that the STAT5 inhibitor pimozide combined with enzalutamide has? additive and synergistic inhibitory effects on cell viability in the used models. Functional analysis with siRNA-mediated STAT5 knockdown yielded divergent results. The LNCaP-derived cell line MR49F could be resensitised to enzalutamide by siRNA-mediated STAT5b-knock-down. In contrast, neither STAT5a nor STAT5b knockdown resensitised enzalutamide-resistant LAPC4-EnzaR cells to enzalutamide. In conclusion, our results indicate that STAT5 may be a possible target in a subgroup of enzalutamide-resistant PCa. However, based on the data presented here, a general role of STAT5 in enzalutamide-resistance and its potential as a therapeutic target could not be shown.
Novel therapeutic strategies are urgently needed for advanced metastatic prostate cancer (PCa). Phytochemicals used in Traditional Chinese Medicine seem to exhibit tumor suppressive properties. ...Therefore, the therapeutic potential of artesunate (ART) on the progressive growth of therapy-sensitive (parental) and docetaxel (DX)-resistant PCa cells was investigated. Parental and DX-resistant PCa cell lines DU145, PC3, and LNCaP were incubated with artesunate (ART) 1-100 µM. ART-untreated and 'non-cancerous' cells served as controls. Cell growth, proliferation, cell cycle progression, cell death and the expression of involved proteins were evaluated. ART, dose- and time-dependently, significantly restricted cell growth and proliferation of parental and DX-resistant PCa cells, but not of 'normal, non-cancerous' cells. ART-induced growth and proliferation inhibition was accompanied by G0/G1 phase arrest and down-regulation of cell cycle activating proteins in all DX-resistant PCa cells and parental LNCaP. In the parental and DX-resistant PC3 and LNCaP cell lines, ART also promoted apoptotic cell death. Ferroptosis was exclusively induced by ART in parental and DX-resistant DU145 cells by increasing reactive oxygen species (ROS). The anti-cancer activity displayed by ART took effect in all three PCa cell lines, but through different mechanisms of action. Thus, in advanced PCa, ART may hold promise as a complementary treatment together with conventional therapy.
Resistance to antiandrogens and chemotherapy (Cx) limits therapeutic options for patients with hormone-sensitive and hormone-resistant prostate cancer (mCRPC). In this context, up-regulation of the ...glucocorticoid receptor has been identified as a potential bypass mechanism in mCRPC, and a combination of docetaxel and mifepristone (Doc + RU-486), an inhibitor of the glucocorticoid receptor, re-sensitized docetaxel-resistant cell models to Cx. This study was designed to elucidate the molecular mechanisms responsible for this phenomenon. RNA sequencing was performed in docetaxel-resistant prostate cancer cell models after Doc + RU-486 treatment with consecutive functional assays. Expression of selected proteins was verified in prostatic tissue from prostate cancer patients with progressive disease. Treatment with Doc + RU-486 significantly reduced cancer cell viability, and RNA sequencing revealed sterol regulatory element of binding transcription factor 1 (SREBF-1), a transcription factor of cholesterol and lipid biosynthesis, as a significantly down-regulated target. Functional assays confirmed that SREBF-1 down-regulation is partially responsible for this observation. In concordance, SREBF-1 knockdown and pharmacologic sterol regulatory element binding protein inhibition, together with other key enzymes in the cholesterol pathway, showed similar results. Furthermore, SREBF-1 expression is significantly elevated in advanced prostate cancer tissues, showing its potential involvement in tumor progression and emerging therapy resistance. Therefore, specific inhibition of cholesterol and lipid biosynthesis might also target Cx-resistant cancer cells and represents a potential additive future therapeutic option to improve mCRPC therapy.
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