125 results on '"Amler, Evzen"'
Search Results
102. INTRACELLULAR Ca2+ SIGNALS INDUCED BY ATP AND THAPSIGARGIN IN GLIOMA C6 CELLS. CALCIUM POOLS SENSITIVE TO INOSITOL 1,4,5- TRISPHOSPHATE AND THAPSIGARGIN
- Author
-
SABAłA, PAWEł, AMLER, EVZEN, and BARAŃSKA, JOLANTA
- Published
- 1997
- Full Text
- View/download PDF
103. Effect of triadimefon on lipids, sterols, and membrane fluidity in submerged cultures of claviceps purpurea
- Author
-
Pažoutová, Sylvie, Křen, Vladimír, Řezanka, Tomáš, Amler, Evžen, Flieger, Miroslav, Rylko, Viktor, and Sajdl, Přemysl
- Published
- 1989
- Full Text
- View/download PDF
104. Changes in Na +,K +-ATPase structure induced by cation binding Approach by Raman spectroscopy
- Author
-
Anzenbacher, Pavel, Mojzes, Peter, Baumruk, Vladimir, and Amler, Evžen
- Published
- 1992
- Full Text
- View/download PDF
105. Erythrosin 5′-isothiocyanate labels Cys 549 as part of the low-affinity ATP binding site of Na +/K +-ATPase
- Author
-
Linnertz, Holger, Kost, Holger, Obsil, Tomas, Kotyk, Arnost, Amler, Evzen, and Schoner, Wilhelm
- Published
- 1998
- Full Text
- View/download PDF
106. The isolated H 4-H 5 cytoplasmic loop of Na,K-ATPase overexpressed in Escherichia coli retains its ability to bind ATP
- Author
-
Obšil, Tomáš, Mérola, Fabienne, Lewit-Bentley, Anita, and Amler, Evžen
- Published
- 1998
- Full Text
- View/download PDF
107. Possible nystatin-protein interaction in yeast plasma membrane vesicles in the presence of ergosterol. A Förster energy transfer study
- Author
-
Opekarová, Miroslava, Urbanová, Petra, Konopásek, Ivo, Kvasnička, Peter, Strzalka, Kazimierz, Sigler, Karel, and Amler, Evžen
- Published
- 1996
- Full Text
- View/download PDF
108. Temperature-induced states of isolated F 1-ATPase affect catalysis, enzyme conformation and high-affinity nucleotide binding sites
- Author
-
Baracca, Alessandra, Amler, Evzen, Solaini, Giancarlo, Castelli, Giovanna Parenti, Lenaz, Giorgio, and Houstek, Josef
- Published
- 1989
- Full Text
- View/download PDF
109. Mg 2+-induced changes of lipid order and conformation of [formula omitted]
- Author
-
Amler, Evz̆en, Teisinger, Jan, and Svoboda, Petr
- Published
- 1987
- Full Text
- View/download PDF
110. Membrane lateral pressure as a modulator of glycerol-3-phosphate dehydrogenase activity
- Author
-
Amler, Evžen, Jasińska, Renata, Drahota, Zdeněk, and Zborowski, Józef
- Published
- 1990
- Full Text
- View/download PDF
111. Regulation of glycerol 3-phosphate oxidation in mitochondria by changes in membrane microviscosity
- Author
-
Amler, Evžen, Rauchová, Hana, Svobodová, Jaroslava, and Drahota, Zdeněk
- Published
- 1986
- Full Text
- View/download PDF
112. Polydatin Incorporated in Polycaprolactone Nanofibers Improves Osteogenic Differentiation
- Author
-
Stefania Lama, Amalia Luce, Giuseppe Bitti, Pilar Chacon-Millan, Annalisa Itro, Pasquale Ferranti, Giovanni D’Auria, Marcella Cammarota, Giovanni Francesco Nicoletti, Giuseppe Andrea Ferraro, Chiara Schiraldi, Michele Caraglia, Evzen Amler, Paola Stiuso, Lama, S., Luce, A., Bitti, G., Chacon-Millan, P., Itro, A., Ferranti, P., D'Auria, G., Cammarota, M., Nicoletti, G. F., Ferraro, G. A., Schiraldi, C., Caraglia, M., Amler, E., Stiuso, P., Lama, Stefania, Luce, Amalia, Bitti, Giuseppe, Chacon-Millan, Pilar, Itro, Annalisa, Ferranti, Pasquale, D'Auria, Giovanni, Cammarota, Marcella, Nicoletti, Giovanni Francesco, Ferraro, Giuseppe Andrea, Schiraldi, Chiara, Caraglia, Michele, Amler, Evzen, and Stiuso, Paola
- Subjects
osteosarcoma ,polydatin ,osteogenic differentiation ,mesenchymal stem cells ,polycaprolactone nanofibers ,Drug Discovery ,technology, industry, and agriculture ,Pharmaceutical Science ,Molecular Medicine ,equipment and supplies ,musculoskeletal system ,polycaprolactone nanofiber ,mesenchymal stem cell - Abstract
Polycaprolactone nanofibers are used as scaffolds in the field of tissue engineering for tissue regeneration or drug delivery. Polycaprolactone (PCL) is a biodegradable hydrophobic polyester used to obtain implantable nanostructures, which are clinically applicable due to their biological safety. Polydatin (PD), a glycosidic precursor of resveratrol, is known for its antioxidant, antitumor, antiosteoporotic, and bone regeneration activities. We aimed to use the osteogenic capacity of polydatin to create a biomimetic innovative and patented scaffold consisting of PCL-PD for bone tissue engineering. Both osteosarcoma cells (Saos-2) and mesenchymal stem cells (MSCs) were used to test the in vitro cytocompatibility of the PD-PCL scaffold. Reverse-phase (RP) HPLC was used to evaluate the timing release of PD from the PCL-PD nanofibers and the MTT assay, scanning electron microscopy, and alkaline phosphatase (ALP) activity were used to evaluate the proliferation, adhesion, and cellular differentiation in both osteosarcoma and human mesenchymal stem cells (MSCs) seeded on PD-PCL nanofibers. The proliferation of osteosarcoma cells (Saos-2) on the PD-PCL scaffold decreased when compared to cells grown on PLC nanofibers, whereas the proliferation of MSCs was comparable in both PCL and PD-PCL nanofibers. Noteworthy, after 14 days, the ALP activity was higher in both Saos-2 cells and MSCs cultivated on PD-PCL than on empty scaffolds. Moreover, the same cells showed a spindle-shaped morphology after 14 days when grown on PD-PCL as shown by SEM. In conclusion, we provide evidence that nanofibers appropriately coated with PD support the adhesion and promote the osteogenic differentiation of both human osteosarcoma cells and MSCs.
- Published
- 2022
113. Ipilimumab for the treatment of metastatic prostate cancer
- Author
-
Sabrina Rossetti, Lucio Quagliuolo, Mariarosaria Boccellino, Gaetano Facchini, Concetta Alaia, Michele Caraglia, Evzen Amler, Silvia Zappavigna, Alaia, Concetta, Boccellino, Mariarosaria, Zappavigna, Silvia, Amler, Evzen, Quagliuolo, Lucio, Rossetti, Sabrina, Facchini, Gaetano, and Caraglia, Michele
- Subjects
Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Immune checkpoint inhibitors ,medicine.medical_treatment ,Clinical Biochemistry ,Ipilimumab ,chemotherapy ,Cancer Vaccines ,Metastatic prostate cancer ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,vaccine ,Internal medicine ,Drug Discovery ,microRNA ,Humans ,Medicine ,CTLA-4 Antigen ,ipilimumab ,Pharmacology ,Clinical Trials as Topic ,Chemotherapy ,business.industry ,Drug Discovery3003 Pharmaceutical Science ,Prostatic Neoplasms ,social sciences ,Immunotherapy ,medicine.disease ,Combined Modality Therapy ,PDL1 inhibitor ,030104 developmental biology ,030220 oncology & carcinogenesis ,immunotherapy ,circulating tumour cell ,business ,medicine.drug - Abstract
Introduction: Immunotherapy with checkpoint inhibitors is beginning to be recognized as a valid weapon for the treatment of metastatic prostate cancer (PCa) when chemotherapy fails. Ipilimumab (ipi) is a fully humanized monoclonal antibody that blocks the activity of CTLA4. It also has a molecular weight of 148 kDa and is water-soluble at physiological pH. Ipi was first approved by the FDA for the treatment of malignant melanoma and is currently being studied in metastatic castration-resistant prostate cancer, with promising early results. Areas covered: The aim of this review is to collate the most significant preclinical and clinical studies available that look at ipi to propose new strategies for the future. Expert opinion: Additional studies are required to reduce toxicity and increase the activity of ipi in PCa. A possible strategy is to combine ipi with standard anti-cancer therapeutics such as vaccines, PDL1 inhibitors, antiandrogen drugs, and chemotherapy agents. Several initial results have suggested that combination strategies are useful to increase the activity in mCRPC, even if the toxicity of the treatment can increase. The activity of combined treatments is still not predictable, but considering the ongoing studies, we believe that they have good potential that will lead to the discovery of an optimal therapeutic strategy.
- Published
- 2017
- Full Text
- View/download PDF
114. Self-assembling nanoparticles encapsulating zoledronic acid inhibit mesenchymal stromal cells differentiation, migration and secretion of proangiogenic factors and their interactions with prostate cancer cells
- Author
-
Giuseppe De Rosa, Naike Casagrande, Nicola Normanno, Cinzia Borghese, Eliana Pivetta, Mariarosaria Boccellino, Alfonso Colombatti, Donatella Aldinucci, Michele Caraglia, Evzen Amler, Borghese, Cinzia, Casagrande, Naike, Pivetta, Eliana, Colombatti, Alfonso, Boccellino, Mariarosaria, Amler, Evzen, Normanno, Nicola, Caraglia, Michele, DE ROSA, Giuseppe, Aldinucci, Donatella, Amler, Ezven, and De Rosa, Giuseppe
- Subjects
0301 basic medicine ,Male ,Cell Survival ,Osteoclasts ,Cell Communication ,Zoledronic Acid ,Metastasis ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,DU145 ,Cell Movement ,Cell Line, Tumor ,Adipocytes ,Tumor Microenvironment ,Medicine ,Humans ,Tumor microenvironment ,Osteoblasts ,Diphosphonates ,business.industry ,self-assembling nanoparticles ,Mesenchymal stem cell ,Imidazoles ,Cancer ,Prostatic Neoplasms ,Cell Differentiation ,Mesenchymal Stem Cells ,medicine.disease ,prostate cancer ,030104 developmental biology ,Zoledronic acid ,Oncology ,030220 oncology & carcinogenesis ,mesenchymal stromal cell ,Immunology ,Cancer research ,Cytokines ,Nanoparticles ,Cytokine secretion ,Angiogenesis Inducing Agents ,business ,mesenchymal stromal cells ,self-assembling nanoparticle ,medicine.drug ,Research Paper - Abstract
// Cinzia Borghese 1, * , Naike Casagrande 1, * , Eliana Pivetta 1 , Alfonso Colombatti 1 , Mariarosaria Boccellino 2, 3 , Evzen Amler 4, 5 , Nicola Normanno 6 , Michele Caraglia 2, 3 , Giuseppe De Rosa 7 and Donatella Aldinucci 1 1 Molecular Oncology Unit, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, PN, Italy 2 Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy 3 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA 4 Indoor Environmental Quality, University Center for Energy Efficient Buildings, Czech Technical University in Prague, Bustěhrad, Czech Republic 5 Laboratory of Tissue Engineering, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic 6 Cell Biology & Biotherapy Unit, Istituto Nazionale Tumori “Fondazione G Pascale”-IRCCS, Naples, Italy 7 Department of Pharmacy, Federico II University of Naples, Naples, Italy * These authors have contributed equally to this work Correspondence to: Donatella Aldinucci, email: daldinucci@cro.it Keywords: zoledronic acid, self-assembling nanoparticles, mesenchymal stromal cells, prostate cancer, tumor microenvironment Received: January 21, 2017 Accepted: March 22, 2017 Published: April 19, 2017 ABSTRACT Zoledronic Acid (ZA) rapidly concentrates into the bone and reduces skeletal-related events and pain in bone metastatic prostate cancer (PCa), but exerts only a limited or absent impact as anti-cancer activity. Recently, we developed self-assembling nanoparticles (NPS) encapsulating zoledronic acid (NZ) that allowed a higher intratumor delivery of the drug compared with free zoledronic acid (ZA) in in vivo cancer models of PCa. Increasing evidence suggests that Bone Marrow (BM) Mesenchymal stromal cells (BM-MSCs) are recruited into the stroma of developing tumors where they contribute to progression by enhancing tumor growth and metastasis. We demonstrated that treatment with NZ decreased migration and differentiation into adipocytes and osteoblasts of MSCs and inhibited osteoclastogenesis. Treatment with NZ reduced the capability of MSCs to promote the migration and the clonogenic growth of the prostate cancer cell lines PC3 and DU145. The levels of Interleukin-6 and of the pro-angiogenic factors VEGF and FGF-2 were significantly reduced in MSC-CM derived from MSCs treated with NZ, and CCL5 secretion was almost totally abolished. Moreover, treatment of MSCs with supernatants from PC3 cells, leading to tumor-educated MSCs (TE-MSCs), increased the secretion of IL-6, CCL5, VEGF and FGF-2 by MSCs and increased their capability to increase PC3 cells clonogenic growth. Treatment with NZ decreased cytokine secretion and the pro-tumorigenic effects also of TE-MSCS. In conclusion, demonstrating that NZ is capable to inhibit the cross talk between MSCs and PCa, this study provides a novel insight to explain the powerful anticancer activity of NZ on PCa.
- Published
- 2017
115. Human DPSCs fabricate vascularized woven bone tissue: a new tool in bone tissue engineering
- Author
-
Vincenzo Desiderio, Alfredo De Rosa, Gianpaolo Papaccio, Serena Mazzoni, Virginia Tirino, Luigi Laino, Evzen Amler, Alessandra Giuliani, Francesca Paino, Marcella La Noce, Paino, Francesca, Noce, Marcella La, Giuliani, Alessandra, DE ROSA, Alfredo, Mazzoni, Serena, Laino, Luigi, Amler, Evzen, Papaccio, Gianpaolo, Desiderio, Vincenzo, and Tirino, Virginia
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_treatment ,Cell Separation ,hDPSCs ,Bone tissue ,Tissue engineering ,bone regeneration ,human Dental Pulp Stem Cell ,bone differentiation ,Osteogenesis ,PHASE CONTRAST IMAGING ,woven bone ,bone tissue engineering ,Research Articles ,Cells, Cultured ,Bone Transplantation ,PHASE CONTRAST MICROTOMOGRAPHY ,Medicine (all) ,Chemotaxis ,Stem Cells ,Cell Differentiation ,General Medicine ,holotomography ,medicine.anatomical_structure ,FRELON CAMERA ,Stem cell ,BONE ,Research Article ,PHASE CONTRAST ,Adult ,medicine.medical_specialty ,woven bon ,Osteocalcin ,Mice, Nude ,Neovascularization, Physiologic ,Biology ,human Dental Pulp Stem Cells ,03 medical and health sciences ,Young Adult ,Calcification, Physiologic ,stomatognathic system ,Dental pulp stem cells ,medicine ,Animals ,Humans ,Bone regeneration ,hDPSC ,Dental Pulp ,Cell Proliferation ,Tissue Engineering ,Growth factor ,Mesenchymal stem cell ,phc-microCT ,X-Ray Microtomography ,medicine.disease ,human serum ,030104 developmental biology ,BONE MINERALIZATION ,Bone Substitutes ,Calcification - Abstract
Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells that have been successfully used in human bone tissue engineering. To establish whether these cells can lead to a bone tissue ready to be grafted, we checked DPSCs for their osteogenic and angiogenic differentiation capabilities with the specific aim of obtaining a new tool for bone transplantation. Therefore, hDPSCs were specifically selected from the stromal-vascular dental pulp fraction, using appropriate markers, and cultured. Growth curves, expression of bone-related markers, calcification and angiogenesis as well as an in vivo transplantation assay were performed. We found that hDPSCs proliferate, differentiate into osteoblasts and express high levels of angiogenic genes, such as vascular endothelial growth factor and platelet-derived growth factor A. Human DPSCs, after 40 days of culture, give rise to a 3D structure resembling a woven fibrous bone. These woven bone (WB) samples were analysed using classic histology and synchrotron-based, X-ray phase-contrast microtomography and holotomography. WB showed histological and attractive physical qualities of bone with few areas of mineralization and neovessels. Such WB, when transplanted into rats, was remodelled into vascularized bone tissue. Taken together, our data lead to the assumption that WB samples, fabricated by DPSCs, constitute a noteworthy tool and do not need the use of scaffolds, and therefore they are ready for customized regeneration. Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells that have been successfully used in human bone tissue engineering. To establish whether these cells can lead to a bone tissue ready to be grafted, we checked DPSCs for their osteogenic and angiogenic differentiation capabilities with the specific aim of obtaining a new tool for bone transplantation. Therefore, hDPSCs were specifically selected from the stromal-vascular dental pulp fraction, using appropriate markers, and cultured. Growth curves, expression of bone-related markers, calcification and angiogenesis as well as an in vivo transplantation assay were performed. We found that hDPSCs proliferate, differentiate into osteoblasts and express high levels of angiogenic genes, such as vascular endothelial growth factor and platelet-derived growth factor A. Human DPSCs, after 40 days of culture, give rise to a 3D structure resembling a woven fibrous bone. These woven bone (WB) samples were analysed using classic histology and synchrotron-based, X-ray phase-contrast microtomography and holotomography. WB showed histological and attractive physical qualities of bone with few areas of mineralization and neovessels. Such WB, when transplanted into rats, was remodelled into vascularized bone tissue. Taken together, our data lead to the assumption that WB samples, fabricated by DPSCs, constitute a noteworthy tool and do not need the use of scaffolds, and therefore they are ready for customized regeneration.
- Published
- 2017
116. miR-125b Upregulates miR-34a and Sequentially Activates Stress Adaption and Cell Death Mechanisms in Multiple Myeloma
- Author
-
Amalia Luce, Alois Nečas, Massimo Donadelli, Carlo Irace, Pierosandro Tagliaferri, Giuseppe De Rosa, Michele Caraglia, Antonella Virgilio, Aldo Galeone, Angela Lombardi, Agostino Festa, Margherita Russo, Hiromichi Kawasaki, Evzen Amler, Gabriella Misso, Daniela Cristina Vuoso, Maria Teresa Di Martino, Mayra Rachele Zarone, Carmela Ferri, Alessia Maria Cossu, Pierfrancesco Tassone, Anna Grimaldi, Misso, G., Zarone, M. R., Lombardi, A., Grimaldi, A., Cossu, A. M., Ferri, C., Russo, M., Vuoso, D. C., Luce, A., Kawasaki, H., Di Martino, M. T., Virgilio, A., Festa, A., Galeone, A., DE ROSA, Giuseppe, Irace, C., Donadelli, M., Necas, A., Amler, E., Tagliaferri, P., Tassone, P., Caraglia, M., Misso, Gabriella, Zarone, Mayra Rachele, Lombardi, Angela, Grimaldi, Anna, Cossu, Alessia Maria, Ferri, Carmela, Russo, Margherita, Vuoso, Daniela Cristina, Luce, Amalia, Kawasaki, Hiromichi, Di Martino, Maria Teresa, Virgilio, Antonella, Festa, Agostino, Galeone, Aldo, De Rosa, Giuseppe, Irace, Carlo, Donadelli, Massimo, Necas, Aloi, Amler, Evzen, Tagliaferri, Pierosandro, Tassone, Pierfrancesco, and Caraglia, Michele
- Subjects
0301 basic medicine ,Programmed cell death ,autophagy ,senescence ,apoptosis ,miR-125b ,miR-34a ,miRNA therapeutics ,miRNome ,multiple myeloma ,next generation sequencing ,signal transduction ,Article ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,microRNA ,Viability assay ,STAT3 ,biology ,Chemistry ,lcsh:RM1-950 ,Autophagy ,miRNA therapeutic ,apoptosi ,Cell biology ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Apoptosis ,030220 oncology & carcinogenesis ,STAT protein ,biology.protein ,Molecular Medicine ,Signal transduction - Abstract
miR-125b, ubiquitously expressed and frequently dysregulated in several tumors, has gained special interest in the field of cancer research, displaying either oncogenic or oncosuppressor potential based on tumor type. We have previously demonstrated its tumor-suppressive role in multiple myeloma (MM), but the analysis of molecular mechanisms needs additional investigation. The purpose of this study was to explore the effects of miR-125b and its chemically modified analogs in modulating cell viability and cancer-associated molecular pathways, also focusing on the functional aspects of stress adaptation (autophagy and senescence), as well as programmed cell death (apoptosis). Based on the well-known low microRNA (miRNA) stability in therapeutic application, we designed chemically modified miR-125b mimics, laying the bases for their subsequent investigation in in vivo models. Our study clearly confirmed an oncosuppressive function depending on the repression of multiple targets, and it allowed the identification, for the first time, of miR-125b-dependent miR-34a stimulation as a possible consequence of the inhibitory role on the interleukin-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3)/miR-34a feedback loop. Moreover, we identified a pattern of miR-125b-co-regulated miRNAs, shedding light on possible new players of anti-MM activity. Finally, functional studies also revealed a sequential activation of senescence, autophagy, and apoptosis, thus indicating, for the first two processes, an early cytoprotective and inhibitory role from apoptosis activation. Keywords: miR-125b, multiple myeloma, apoptosis, autophagy, senescence, miRNome, miRNA therapeutics, miR-34a, next generation sequencing, signal transduction
- Published
- 2019
117. Testicular cancer from diagnosis to epigenetic factors
- Author
-
Michele Caraglia, Raffaele Piscitelli, Sisto Perdonà, Gelsomina Iovane, Carlo Buonerba, Paolo Muto, Sabrina Rossetti, Paolo Chieffi, Gaetano Facchini, Gerardo Botti, Carla Cavaliere, Rossella Di Franco, Alessandro Izzo, Daniela Vanacore, Evzen Amler, Carmine D'Aniello, Mariarosaria Boccellino, Giuseppe Di Lorenzo, Silvia Zappavigna, Boccellino, Mariarosaria, Vanacore, Daniela, Zappavigna, Silvia, Cavaliere, Carla, Rossetti, Sabrina, D'Aniello, Carmine, Chieffi, Paolo, Amler, Evzen, Buonerba, Carlo, Di Lorenzo, Giuseppe, Di Franco, Rossella, Izzo, Alessandro, Piscitelli, Raffaele, Iovane, Gelsomina, Muto, Paolo, Botti, Gerardo, Perdonà, Sisto, Caraglia, Michele, and Facchini, Gaetano
- Subjects
0301 basic medicine ,Homeobox protein NANOG ,Oncology ,medicine.medical_specialty ,endocrine system ,Epigenetic factor ,epigenetic factors ,Review ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,germ cell neoplasia ,medicine ,Epigenetic Profile ,Epigenetics ,seminoma ,Intratubular germ cell neoplasia ,biomarkers ,Seminoma ,Biomarker ,medicine.disease ,testicular cancer ,030104 developmental biology ,030220 oncology & carcinogenesis ,DNA methylation ,Cancer research ,Germ cell tumors ,Teratoma - Abstract
Testicular cancer (TC) is one of the most common neoplasms that occurs in male and includes germ cell tumors (GCT), sex cord-gonadal stromal tumors and secondary testicular tumors. Diagnosis of TC involves the evaluation of serum tumor markers alpha-fetoprotein, human chorionic gonadotropin and lactate dehydrogenase, but clinically several types of immunohistochemical markers are more useful and more sensitive in GCT, but not in teratoma. These new biomarkers are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells and they include PLAP, OCT3/4 (POU5F1), NANOG, SOX2, REX1, AP-2γ (TFAP2C) and LIN28. Gene expression in GCT is regulated, at least in part, by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation. There are different epigenetic modifications in TG-subtypes that reflect the normal developmental switch in primordial germ cells from an under- to normally methylated genome. The main purpose of this review is to illustrate the findings of recent investigations in the classification of male genital organs, the discoveries in the use of prognostic and diagnostic markers and the epigenetic aberrations mainly affecting the patterns of DNA methylation/histone modifications of genes (especially tumor suppressors) and microRNAs (miRNAs).
- Published
- 2017
118. Evidence of novel miR-34a-based therapeutic approaches for multiple myeloma treatment
- Author
-
Nicola Amodio, Michele Caraglia, Anna Grimaldi, Margherita Russo, Mayra Rachele Zarone, Silvia Zappavigna, Pierfrancesco Tassone, Pierosandro Tagliaferri, Maria Teresa Di Martino, Evzen Amler, Gabriella Misso, Zarone, Mayra Rachele, Misso, Gabriella, Grimaldi, Anna, Zappavigna, Silvia, Russo, Margherita, Amler, Evzen, Di Martino, Maria Teresa, Amodio, Nicola, Tagliaferri, Pierosandro, Tassone, Pierfrancesco, and Caraglia, Michele
- Subjects
0301 basic medicine ,Cell ,lcsh:Medicine ,Antineoplastic Agents ,Apoptosis ,Naphthols ,Zoledronic Acid ,Article ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,law ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,lcsh:Science ,Multidisciplinary ,biology ,Autophagy ,lcsh:R ,Cell Cycle ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Cell culture ,030220 oncology & carcinogenesis ,Benzamides ,Cancer research ,biology.protein ,Suppressor ,lcsh:Q ,Growth inhibition ,Multiple Myeloma ,Calreticulin - Abstract
MiR-34a acts as tumor suppressor microRNA (miRNA) in several cancers, including multiple myeloma (MM), by controlling the expression of target proteins involved in cell cycle, differentiation and apoptosis. Here, we have investigated the combination between miR-34a and γ-secretase inhibitor (γSI), Sirtinol or zoledronic acid (ZOL) in order to enhance the inhibitory action of this miRNA on its canonical targets such as Notch1 and SIRT1, and on Ras/MAPK-dependent pathways. Our data demonstrate that miR-34a synthetic mimics significantly enhance the anti-tumor activity of all the above-mentioned anti-cancer agents in RPMI 8226 MM cells. We found that γSI enhanced miR-34a-dependent anti-tumor effects by activating the extrinsic apoptotic pathway which could overcome the cytoprotective autophagic mechanism. Moreover, the combination between miR-34a and γSI increased the cell surface calreticulin (CRT) expression, that is well known for triggering anti-tumor immunological response. The combination between miR-34a and Sirtinol induced the activation of an intrinsic apoptotic pathway along with increased surface expression of CRT. Regarding ZOL, we found a powerful growth inhibition after enforced miR-34a expression, which was not likely attributable to neither apoptosis nor autophagy modulation. Based on our data, the combination of miR-34a with other anti-cancer agents appears a promising anti-MM strategy deserving further investigation.
- Published
- 2017
119. Can insulin-dependent diabetes mellitus be understood at the molecular level through Na +/K +-adenosine triphosphatase?
- Author
-
Amler, Evzen
- Published
- 1997
- Full Text
- View/download PDF
120. Flexible 3D nanofiber-based SERS biosensor for detection of miRNA-223-3p in early Laryngeal Cancer diagnosis.
- Author
-
Martino S, Yilmaz D, Tammaro C, Misso G, Esposito A, Falco M, Cossu AM, Lombardi A, Amler E, Divin R, Giannetti A, Scrima M, Dardano P, De Stefano L, Rea I, De Luca AC, and Caraglia M
- Abstract
MicroRNAs (miRNAs) are small non-coding RNAs (18-22 nucleotides) that regulate gene expression and are associated with various diseases, including Laryngeal Cancer (LCa), which has a high mortality rate due to late diagnosis. Traditional methods for miRNA detection present several drawbacks (time-consuming steps, high cost and high false positive rate). Early-stage diagnosis and selective detection of miRNAs remain challenging. This study proposes a 3D flexible biosensor that combines nanofibers (NFs), gold nanoparticles (AuNPs), and an inverse molecular sentinel (iMS) for enzyme-free, SERS-based detection of miRNA-223-3p, evaluated as a potential LCa biomarker. The electrospun flexible nanofibers decorated with AuNPs enhance Raman signal. Selective detection of miRNA-223-3p is achieved by immobilizing an iMS-DNA probe labeled with a Raman reporter (Cyanine 3) on the AuNPs. The iMS distinctive stem-and-loop structure undergoes a conformational change upon interaction with the miRNA-223-3p, producing an "on to off" SERS signal. The proposed sensor demonstrated a linear detection range from 10 to 250 fM, with a limit of detection (LOD) of 19.50 ± 0.05 fM. The sensor selectivity was confirmed by analyzing the SERS signal behaviour in the presence of both Non-complementary miRNA and miRNA with three mismatched base pairs. This easily fabricable sensor requires no amplification and offers key advantages, including sensitivity, flexibility, and cost-effectiveness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
- Full Text
- View/download PDF
121. Computer modelling reveals new conformers of the ATP binding loop of Na + /K + -ATPase involved in the transphosphorylation process of the sodium pump.
- Author
-
Tejral G, Sopko B, Necas A, Schoner W, and Amler E
- Abstract
Hydrolysis of ATP by Na
+ /K+ -ATPase, a P-Type ATPase, catalyzing active Na+ and K+ transport through cellular membranes leads transiently to a phosphorylation of its catalytical α -subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp369 to allow the transfer of ATP's terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the γ -phosphate group of ATP to the Asp369 is achieved, analogous molecular modeling of the M4 -M5 loop of ATPase was performed using the crystal data of Na+ /K+ -ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr338 and Ile760 of the α2 -subunit of Na+ /K+ -ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation; the first one close to Phe475 in the N-domain, the other one close to Asp369 in the P-domain. However, binding of Mg2+ •ATP to any of these sites in the "open conformation" may not lead to phosphorylation of Asp369 . Additional conformations of the cytoplasmic loop were found wobbling between "open conformation" <==> "semi-open conformation <==> "closed conformation" in the absence of 2Mg2+ •ATP. The cytoplasmic loop's conformational change to the "semi-open conformation"-characterized by a hydrogen bond between Arg543 and Asp611 -triggers by binding of 2Mg2+ •ATP to a single ATP site and conversion to the "closed conformation" the phosphorylation of Asp369 in the P-domain, and hence the start of Na+ /K+ -activated ATP hydrolysis., Competing Interests: The authors declare there are no competing interests.- Published
- 2017
- Full Text
- View/download PDF
122. Novel composite hyaluronan/type I collagen/fibrin scaffold enhances repair of osteochondral defect in rabbit knee.
- Author
-
Filová E, Jelínek F, Handl M, Lytvynets A, Rampichová M, Varga F, Cinátl J, Soukup T, Trc T, and Amler E
- Subjects
- Animals, Biomechanical Phenomena, Cell Survival, Cells, Cultured, Male, Materials Testing, Microscopy, Electron, Rabbits, Chondrocytes cytology, Collagen Type I, Fibrin, Hyaluronic Acid, Knee Injuries surgery, Prostheses and Implants
- Abstract
A new composite scaffold containing type I collagen, hyaluronan, and fibrin was prepared with and without autologous chondrocytes and implanted into a rabbit femoral trochlea. The biophysical properties of the composite scaffold were similar to native cartilage. The macroscopic, histological, and immunohistochemical analysis of the regenerated tissue from cell-seeded scaffolds was performed 6 weeks after the implantation and predominantly showed formation of hyaline cartilage accompanied by production of glycosaminoglycans and type II collagen with minor fibro-cartilage production. Implanted scaffolds without cells healed predominantly as fibro-cartilage, although glycosaminoglycans and type II collagen, which form hyaline cartilage, were also observed. On the other hand, fibro-cartilage or fibrous tissue or both were only formed in the defects without scaffold. The new composite scaffold containing collagen type I, hyaluronan, and fibrin, seeded with autologous chondrocytes and implanted into rabbit femoral trochlea, was found to be highly effective in cartilage repair after only 6 weeks. The new composite scaffold can therefore enhance cartilage regeneration of osteochondral defects, by the supporting of the hyaline cartilage formation.
- Published
- 2008
- Full Text
- View/download PDF
123. The hydrogen bonds between Arg423 and Glu472 and other key residues, Asp443, Ser477, and Pro489, are responsible for the formation and a different positioning of TNP-ATP and ATP within the nucleotide-binding site of Na(+)/K(+)-ATPase.
- Author
-
Lánský Z, Kubala M, Ettrich R, Kutý M, Plásek J, Teisinger J, Schoner W, and Amler E
- Subjects
- Adenosine chemistry, Amino Acid Sequence, Animals, Aspartic Acid chemistry, Binding Sites, Crystallography, X-Ray, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Genetic Vectors, Glutamic Acid chemistry, Glutathione Transferase metabolism, Hydrogen chemistry, Hydrogen Bonding, Hydrolysis, Kinetics, Ligands, Magnetic Resonance Spectroscopy, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Nucleotides chemistry, Point Mutation, Proline chemistry, Protein Binding, Protein Structure, Tertiary, Recombinant Fusion Proteins chemistry, Sequence Homology, Amino Acid, Serine chemistry, Software, Spectrophotometry, Temperature, Adenosine Triphosphate analogs & derivatives, Adenosine Triphosphate chemistry, Amino Acids chemistry, Arginine chemistry, Fluorescent Dyes chemistry, Sodium-Potassium-Exchanging ATPase chemistry
- Abstract
Mutation of Arg(423) at the N-domain of Na(+)/K(+)-ATPase resulted in a large decrease of both TNP-ATP and ATP binding. Thus, this residue, localized outside the binding pocket, seems to play a key role in supporting the proper structure and shape of the binding site. In addition, mutation of Glu(472) also caused a large decrease of both TNP-ATP and ATP binding. On the basis of our computer model, we hypothesized that a hydrogen bond between Arg(423) and Glu(472) supports the connection of two opposite halves of the ATP-binding pocket. To verify this hypothesis, we have also prepared the construct containing both these mutations. Binding of neither TNP-ATP nor ATP to this double mutant differed from binding to any of the single mutants. This strongly supported the existence of the hydrogen bond between Arg(423) and Glu(472). Similarly, the conserved residue Pro(489) seems to be substantial for the proper interaction of the third and fourth beta-strands of the N-domain, which both contain residues that take part in ATP binding. Mutation of Asp(443) affected only ATP, but not TNP-ATP, binding, suggesting that these ligands adopt different positions in the nucleotide-binding pocket. On the basis of a recently published crystal structure [Håkansson, K. O. (2003) J. Mol. Biol. 332, 1175-1182], we improved our model and computed the interaction of these two ligands with the N-domain. This model is in good agreement with all previously reported spectroscopic data and revealed that Asp(443) forms a hydrogen bond with the NH(2) group of the adenosine moiety of ATP, but not TNP-ATP.
- Published
- 2004
- Full Text
- View/download PDF
124. Eight amino acids form the ATP recognition site of Na(+)/K(+)-ATPase.
- Author
-
Kubala M, Teisinger J, Ettrich R, Hofbauerová K, Kopecký V Jr, Baumruk V, Krumscheid R, Plásek J, Schoner W, and Amler E
- Subjects
- Animals, Binding Sites, Brain enzymology, Cysteine chemistry, Dose-Response Relationship, Drug, Genetic Complementation Test, Genetic Vectors, Glutamic Acid chemistry, Glutamine chemistry, Hydrogen Bonding, Mice, Models, Molecular, Mutagenesis, Site-Directed, Phenylalanine chemistry, Point Mutation, Protein Binding, Protein Structure, Secondary, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins metabolism, Recombinant Proteins chemistry, Spectrophotometry, Infrared, Spectroscopy, Fourier Transform Infrared, Adenosine Triphosphate metabolism, Amino Acids chemistry, Sodium-Potassium-Exchanging ATPase chemistry
- Abstract
Point mutations of a part of the H(4)-H(5) loop (Leu(354)-Ile(604)) of Na(+)/K(+)-ATPase have been used to study the ATP and TNP-ATP binding affinities. Besides the previously reported amino acid residues Lys(480), Lys(501), Gly(502), and Cys(549), we have found four more amino acid residues, viz., Glu(446), Phe(475), Gln(482), and Phe(548), completing the ATP-binding pocket of Na(+)/K(+)-ATPase. Moreover, mutation of Arg(423) has also resulted in a large decrease in the extent of ATP binding. This residue, localized outside the binding pocket, seems to play a key role in supporting the proper structure and shape of the binding site, probably due to formation of a hydrogen bond with Glu(472). On the other hand, only some minor effects were caused by mutations of Ile(417), Asn(422), Ser(445), and Glu(505).
- Published
- 2003
- Full Text
- View/download PDF
125. Secondary and tertiary structure of nucleotide-binding domain of alphasubunit of Na+/K+-ATPase.
- Author
-
Hofbauerová K, Kopecký V Jr, Ettrich R, Ettrichová O, and Amler E
- Subjects
- Adenosine Triphosphate metabolism, Animals, Brain enzymology, Circular Dichroism, Escherichia coli metabolism, Mice, Models, Molecular, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Sodium-Potassium-Exchanging ATPase metabolism, Spectrum Analysis, Raman, Sodium-Potassium-Exchanging ATPase chemistry
- Abstract
The nucleotide-binding domain of the alpha subunit of mouse brain Na+/K+-ATPase was expressed and isolated from Escherichia coli cells. A model structure was constructed by comparative modeling with and without docked ATP. This was compared with the secondary structure determination from UV circular dichroism and Raman spectroscopy. Thus, we support the quality of the model and the correct folding of the recombinant protein. ATP binding was followed by Raman difference spectroscopy, and its influence on the secondary structure of the N domain seems to not be significant., (Copyright 2002 Wiley Periodicals, Inc.)
- Published
- 2002
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.