A novel canine B‐cell leukaemia cell line. Establishment, characterisation and sensitivity to chemotherapeutics

Pawlak, Aleksandra; Zioło, Ewa; Kutkowska, Justyna; Błażejczyk, Agnieszka; Wietrzyk, Joanna; Krupa, A.; Hildebrand, W.; Dzięgiel, Piotr; Dzimira, Stanisław; Obmińska-Mrukowicz, Bożena; Strządała, Leon; Rapak, Andrzej

doi:10.1111/vco.12257

Cited by 17 publications

(21 citation statements)

References 34 publications

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“…The canine cell line GL-1 (B cell leukemia) was obtained from Yasuhito Fujino and Hajime Tsujimoto from the University of Tokyo, Department of Veterinary Internal Medicine, Tokyo, Japan [ 46 ]. CLB70 line (B cell chronic leukemia) was established by one of the coauthors of the manuscript [ 47 ]. The human Jurkat cell line (T cell leukemia), coming from ATCC was kindly provided from the collection of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.…”

Section: Methodsmentioning

confidence: 99%

Preparation of Enantiomeric β-(2′,5′-Dimethylphenyl)Bromolactones, Their Antiproliferative Activity and Effect on Biological Membranes

et al. 2018

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Three novel enantiomeric pairs of bromolactones possesing a 2,5-dimethylphenyl substituent at the β-position of the lactone ring have been synthesized from corresponding enantiomeric (E)-3-(2′,5′-dimethylphenyl)hex-4-enoic acids (4) by kinetically controlled bromolactonization with N-bromosuccinimide (NBS). γ-Bromo-δ-lactones (5) were isolated as the major products. Absolute configurations of stereogenic centers of γ-bromo-δ-lactones (5) were assigned based on X-ray analysis; configurations of cis δ-bromo-γ-lactones (6) and trans δ-bromo-γ-lactones (7) were determined based on mechanism of bromolactonization. Synthesized compounds exhibited significant antiproliferative activity towards the four canine cancer cell lines (D17, CLBL-1, CLB70, and GL-1) and one human cancer line (Jurkat). Classifying the compounds in terms of activity, the most active were enantiomers of trans δ-bromo-γ-lactones (7) followed by enantiomers of cis isomer (6) and enantiomeric γ-bromo-δ-lactones (5). Higher activity was observed for all stereoisomers with S configuration at C-4 in comparison with their enantiomers with 4R configuration. Synthesized compounds did not induce hemolysis of erythrocytes. The results of the interaction of bromolactones with red blood cell membranes suggest that these compounds incorporate into biological membranes, concentrating mainly in the hydrophilic part of the bilayer but have practically no influence on fluidity in the hydrophobic region. The differences in interactions with the membrane between particular enantiomers were observed only for γ-lactones: stronger interactions were found for enantiomer 4R,5R,6S of cis γ-lactone (6) and for enantiomer 4S,5R,6S of trans γ-lactone (7).

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Section: Methodsmentioning

confidence: 99%

Preparation of Enantiomeric β-(2′,5′-Dimethylphenyl)Bromolactones, Their Antiproliferative Activity and Effect on Biological Membranes

et al. 2018

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“…The GL-1 (canine B-cell leukemia) was obtained from Yasuhito Fujino and Hajime Tsujimoto from the Department of Veterinary Internal Medicine University of Tokyo [27], the CLB70 (canine B-cell chronic leukemia) was described earlier by Pawlak et al [28]. The GL-1 cells were maintained in RPMI 1640 medium with 10% fetal bovine serum (FBS), 100 µg/mL streptomycin, 100 U/mL penicillin and 2 mM L-glutamine (Sigma-Aldrich, Stainheim, Germany).…”

Section: Antiproliferative Activitymentioning

confidence: 99%

Chemoenzymatic Synthesis of Enantiomeric, Bicyclic δ-Halo-γ-lactones with a Cyclohexane Ring, Their Biological Activity and Interaction with Biological Membranes

et al. 2020

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Starting from 1-acetyl-1-cyclohexene, three enantiomeric pairs (ee ≥ 99%) of bicyclic δ-halo-γ-lactones with cyclohexane ring were obtained in five-step synthesis. The key stereochemical steps were lipase-catalyzed kinetic resolution of racemic 1-(cyclohex-1-en-1-yl) ethanol followed by transfer of chirality to ethyl 2-(2-ethylidenecyclohexyl) acetate in the Johnson–Claisen rearrangement. Synthesized halolactones exhibited antiproliferative activity towards canine B-cell leukemia cells (GL-1) and canine B-cell chronic leukemia cells (CLB70) and the most potent (IC50 18.43 ± 1.46 μg/mL against GL-1, IC50 11.40 ± 0.40 μg/mL against CLB70) comparable with the control etoposide, was (1R,6R,1′S)-1-(1′-chloroethyl)-9-oxabicyclo[4.3.0]nonan-8-one (8b). All halolactones did not have a toxic effect on erythrocytes and did not change the fluidity of membranes in the hydrophobic region of the lipid bilayer. Only weak changes in the hydrophilic area were observed, like the degree of lipid packing and associated hydration. The racemic halolactones were also tested for their antimicrobial properties and found to exhibit selectivity towards bacteria, in particular, towards Proteus mirabilis ATCC 35659.

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“…In searching for tumour‐associated antigens expressed by CL cells, we established 2 hybridomas producing mAbs, which were designated as B5 and E11. These mAbs strongly stained the cell surface antigens present on canine B‐cell or T‐cell lymphoma cell lines CLBL‐1, CLB70, and CL‐1 and the ex vivo neoplasms of B‐cell and mixed B/T‐cell origin but were not reactive against the mixed‐type lymphoma GL1 and NK cell lymphoma CH89 (A. Rapak, unpublished) cell lines, where both the latter lacked the expression of DLA‐DR molecules. The PBMCs of healthy dogs were only weakly reactive with these mAbs (Figure A).…”

Section: Resultsmentioning

confidence: 99%

Development of novel monoclonal antibodies to dog leukocyte antigen DR displaying direct and immune‐mediated cytotoxicity toward canine lymphoma cell lines

Lisowska

Pawlak

Kutkowska

et al. 2018

Hematological Oncology

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Spontaneous canine lymphoma (CL) has become a promising, nonrodent model for advancing the therapeutic strategies of human hematological malignancies. As new resources for veterinary and comparative studies on CL-associated antigens, we developed 2 novel mouse monoclonal antibodies, denoted B5 and E11, that recognized the canine major histocompatibility Class II DR antigens (dog leukocyte antigen DR). Using flow cytometry and solid phase immunoenzymatic assays, we showed that the antigens recognized by B5 and E11 were strongly expressed in several CL cell lines and the ex vivo canine neoplastic cells of B and mixed B/T immunophenotypes. Additionally, we evaluated a minimal cross-reactivity of B5 and E11 with the human B-cell line, Raji. By the ectopic expression of the hybrid murine/canine I-E/DR dimers in the HEK293 cells, we demonstrated that the epitope of B5 was localized to the invariant DRα chain, whereas the epitope of E11 was collectively formed by the DRα and DRβ chains. Both epitopes were conformational and conserved in all the tested unrelated individuals of different dog breeds. In vitro treatment of 2 CL B-cell lines (CLBL1 and CLB70) with B5 and E11 rapidly induced a direct apoptotic cell death. Similarily, both mouse monoclonal antibodies efficiently killed the above cell lines through the mechanisms of complement-dependent and antibody-mediated cellular phagocytosis. Collectively, our data support the further development of B5 and E11 as novel tools for dog leukocyte antigen DR-targeted, preclinical trials involving CL.

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A novel canine B‐cell leukaemia cell line. Establishment, characterisation and sensitivity to chemotherapeutics

Cited by 17 publications

References 34 publications

Preparation of Enantiomeric β-(2′,5′-Dimethylphenyl)Bromolactones, Their Antiproliferative Activity and Effect on Biological Membranes

Preparation of Enantiomeric β-(2′,5′-Dimethylphenyl)Bromolactones, Their Antiproliferative Activity and Effect on Biological Membranes

Chemoenzymatic Synthesis of Enantiomeric, Bicyclic δ-Halo-γ-lactones with a Cyclohexane Ring, Their Biological Activity and Interaction with Biological Membranes

Development of novel monoclonal antibodies to dog leukocyte antigen DR displaying direct and immune‐mediated cytotoxicity toward canine lymphoma cell lines

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