Jacek Otlewski
University of Wrocław
Binding siteBiophysicsMutantMolecular biologyCytotoxic T cellReceptorEnzymeChemistryPhage displayTrypsin inhibitorChymotrypsinTrypsinProtein structureBiochemistryStereochemistryFibroblast growth factorCrystallographyFibroblast growth factor receptorBiologyCell biologyCancer cell
Publications 152
#1Przemysław M. Jurek (UWr: University of Wrocław)H-Index: 2
#2Konrad Zabłocki (UWr: University of Wrocław)H-Index: 1
Last. Filip Jelen (UWr: University of Wrocław)H-Index: 13
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: Compounds that recognize and strongly bind to molecular targets are one of the cornerstones of modern pharmaceutics. Work has been ongoing for the past 25 years on the therapeutic use of aptamers, nucleic acid molecules, whose three-dimensional structure is the result of interactions between complementary base pairs. The aptamers selection methods allow the oligonucleotides which bind the molecular target in its native environment to be quickly isolated from a large library of random oligonucl...
21 CitationsSource
#1Anna M. Serwotka-Suszczak (UWr: University of Wrocław)H-Index: 2
#2Alicja M. Sochaj-Gregorczyk (UWr: University of Wrocław)H-Index: 3
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
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Antibody-drug conjugates (ADCs) have recently emerged as efficient and selective cancer treatment therapeutics. Currently, alternative forms of drug carriers that can replace monoclonal antibodies are under intensive investigation. Here, a cytotoxic conjugate of an anti-HER2 (Human Epidermal Growth Factor Receptor 2) diaffibody with monomethyl-auristatin E (MMAE) is proposed as a potential anticancer therapeutic. The anti-HER2 diaffibody was based on the ZHER2:4 affibody amino acid sequence. The...
10 CitationsSource
#1Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
#2Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
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Fibroblast growth factor receptors (FGFRs) are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1V), was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE), and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody–drug conjugates. The F...
17 CitationsSource
#1Alicja M. Sochaj-Gregorczyk (UWr: University of Wrocław)H-Index: 3
Last. Jacek OtlewskiH-Index: 44
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Abstract Targeted therapy is a new type of cancer treatment that most often uses biologically active drugs attached to a monoclonal antibody. This so called antibody-drug conjugate strategy allows the use of highly toxic substances that target tumor cells specifically, leaving healthy tissues largely unaffected. Over the last few years, antibody-drug conjugates have become a powerful tool in cancer treatment. We developed and characterized a novel cytotoxic conjugate against HER2 tumors in which...
15 CitationsSource
#1Joanna BoberH-Index: 3
#2Sjur Olsnes (University of Oslo)H-Index: 64
Last. Jacek OtlewskiH-Index: 44
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Besides its classical mode of action through activation of specific receptors at the cell surface, fibroblast growth factor 1 (FGF1) can also cross the cellular membrane and translocate into the cytosol and further to the nucleus. The mechanism of this translocation is described partially, but the role of FGF1 inside the cell remains unknown. The aim of our work was to identify novel binding partners of FGF1 to predict its intracellular functions. We combined three methods of identification of s...
9 CitationsSource
#1Magdalena Wezner-Ptasinska (UWr: University of Wrocław)H-Index: 2
#2Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
Variable lymphocyte receptors (VLRs) are non-immunoglobulin components of adaptive immunity in jawless vertebrates. These proteins composed of leucine-rich repeat modules offer some advantages over antibodies in target binding and therefore are attractive candidates for biotechnological applications. In this paper we report the design and characterization of a phage display library based on a previously proposed dVLR scaffold containing six LRR modules [Wezner-Ptasinska et al., 2011]. Our librar...
6 CitationsSource
#1Alicja M. Sochaj (UWr: University of Wrocław)H-Index: 1
#2Karolina Świderska (UWr: University of Wrocław)H-Index: 2
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
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Abstract Development of efficient and safe cancer therapy is one of the major challenges of the modern medicine. Over the last few years antibody–drug conjugates (ADCs) have become a powerful tool in cancer treatment with two of them, Adcetris® (brentuximab vedotin) and Kadcyla® (ado-trastuzumab emtansine), having recently been approved by the Food and Drug Administration (FDA). Essentially, an ADC is a bioconjugate that comprises a monoclonal antibody that specifically binds tumor surface antig...
96 CitationsSource
Heat shock proteins play an essential role in facilitating malignant transformation and they have been recognized as important factors in human cancers. One of the key elements of the molecular chaperones machinery is Hsp90 and it has recently become a target for anticancer therapeutic approaches. The potential and importance of Hsp90-directed agents becomes apparent when one realizes that disruption of Hsp90 function may influence over 200 oncogenic client proteins. Here, we described the selec...
1 CitationsSource
#1Katarzyna Pala (UWr: University of Wrocław)H-Index: 3
#2Piotr Jakimowicz (UWr: University of Wrocław)H-Index: 14
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 4 authors...
Conjugation of bioactive xenobiotics with innert particles often improves their efficacy and/or specificity. In this work we designed superparamagnetic ferric oxide nanoparticles (NPs) conjugated with a strong cytotoxic drug, monomethylauristatin E (MMAE), and evaluated their potential against cancer cells. Cytotoxicity tests showed that the conjugate was at least twice as toxic as the free drug. We then studied the cytotoxic potential of the conjugate at an elevated temperature achieved due to ...
1 CitationsSource
#1Marcela Buchtová (VFU: University of Veterinary and Pharmaceutical Sciences Brno)H-Index: 19
#2Radka Chaloupková (Masaryk University)H-Index: 24
Last. Pavel Krejci (Masaryk University)H-Index: 32
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Fibroblast growth factors (FGFs) deliver extracellular signals that govern many developmental and regenerative processes, but the mechanisms regulating FGF signaling remain incompletely understood. Here, we explored the relationship between intrinsic stability of FGF proteins and their biological activity for all 18 members of the FGF family. We report that FGF1, FGF3, FGF4, FGF6, FGF8, FGF9, FGF10, FGF16, FGF17, FGF18, FGF20, and FGF22 exist as unstable proteins, which are rapidly degraded in c...
32 CitationsSource