Radostina Alexandrova - Academia.edu (original) (raw)
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Papers by Radostina Alexandrova
Infection and drug resistance, Mar 1, 2024
Dokladi na Bʺlgarskata akademiâ na naukite, Jan 29, 2024
Despite undoubted success in early diagnosis and treatment of breast cancer, it remains one of th... more Despite undoubted success in early diagnosis and treatment of breast cancer, it remains one of the most common and lethal neoplastic diseases in the world among women. Adequate model systems, including cell cultures, can help us better understand breast cancer biology as well as for the discovery of new diagnostic, prognostic and therapeutic strategies. This review summarizes some of the main characteristics of cell cultures (primary cell cultures and immortal cell lines; 2D and 3D cell cultures) used in current biomedical research and their strengths and weaknesses.
Journal of Inorganic and Organometallic Polymers and Materials, Dec 1, 2018
Four complexes of Co(II), Ni(II), Cu(II), and Zn(II) with isoxicam (H2ISO) as ligand, namely [Co(... more Four complexes of Co(II), Ni(II), Cu(II), and Zn(II) with isoxicam (H2ISO) as ligand, namely [Co(HISO)2(H2O)2]⋅3H2O (Co–Iso), [Ni(HISO)2(H2O)2]⋅0.5H2O (Ni–Iso), [Cu(HISO)2(H2O)] (Cu–Iso), [Zn(HISO)2(H2O)2]⋅0.5H2O (Zn–Iso), have been synthesized and characterized by FT-IR, UV–Vis–NIR, 1H NMR, TG/DSC, elemental analysis, magnetic and conductivity measurements. The following permanent cell lines were used to evaluate the cytotoxic activity of the compounds: LSCC-SF-Mc29, strain E7 (transplantable chicken hepatoma induced by the myelocytomatosis virus Mc29), LSR-SF-SR (transplantable sarcoma in rat, induced by Rous sarcoma virus, strain Schmidt-Ruppin), MCF-7 (luminal A type breast cancer), HeLa (human carcinoma of the uterine cervix) and Lep-3 (human non-tumor embryonal fibroblastoid cells). Short term experiments (24–72 h) with monolayer cultures were performed by MTT test, neutral red uptake cytotoxicity assay and double staining with acridine orange and propidium iodide as well as long term experiments (20 days) with 3D cancer cell colonies in semi-solid medium. The results obtained reveal that: (i) applied at a concentration range of 5–500 µg mL−1 the compounds investigated decrease in a time- and concentration-dependent manner viability and/or proliferation of the treated cells; (ii) metal complexes are more pronounced cytotoxic agents as compared to isoxicam; (iii) cell-specific response was observed—Cu–Iso expresses the highest cytotoxic activity in LSCC-SF-Mc29 (strain E7) cells, whereas Zn–Iso is the most effective compound in LSR-SF-SR and Lep-3 cells, and Co–Iso—in HeLa cells; (iv) in general, human non-tumor Lep-3 embryonic fibroblastoid cells are relatively less sensitive to the cytotoxic activity of the complexes as compared to human cancer MCF-7 and HeLa cells.
Materials, methods & technologies, May 31, 2015
PubMed, Sep 1, 2009
Gene therapy is a new and innovative approach to the treatment of malignant neoplasms, although i... more Gene therapy is a new and innovative approach to the treatment of malignant neoplasms, although it is still not capable of eradicating cancer in humans. Selection of the appropriate vector with maximal efficiency and minimal toxicity is crucial for gene therapy and numerous viral and non-viral (synthetic) methods for gene transfer have been developed. There are different gene therapy approaches for cancer treatment such as: 1) gene correction; 2) molecular chemotherapy; 3) proapoptotic gene therapy; 4) antiangiogenic gene therapy; 5) immune gene therapy; and 6) modulation of drug resistance/sensitivity. Cancer gene therapy represents one of the most rapidly developing areas in preclinical and clinical research. However, some problems need to be solved to make sure this strategy is safe, effective and long-lasting before it becomes routinely adopted in clinical practice.
Inorganica Chimica Acta, May 1, 2011
![Research paper thumbnail of Metal [Zn(II), Co(II), Ni(II)] complexes with kojic acid: do they help us to fight against cancer](https://attachments.academia-assets.com/119655155/thumbnails/1.jpg)
](HAL (Le Centre pour la Communication Scientifique Directe), 2020
Gels
The study reports the synthesis and characterization of novel triple stimuli responsive interpene... more The study reports the synthesis and characterization of novel triple stimuli responsive interpenetrating polymer network (IPN) based on two polyzwitterionic networks, namely of poly(carboxybetaine methacrylate) and poly(sulfobetaine methacrylate). The zwitterionic IPN hydrogel demonstrates the ability to expand or shrink in response to changes in three “biological” external stimuli such as temperature, pH, and salt concentration. The IPN hydrogel shows good mechanical stability. In addition, other important features such as non-cytotoxicity and antibiofouling activity against three widespread bacteria as P. Aeruginosa, A. Baumanii, and K. Pneumoniae are demonstrated. The in vivo behavior of the novel zwitterionic IPN hydrogel suggests that this smart material has very good potential as a biomaterial.
Scripta scientifica medica, Oct 10, 2017
Scripta scientifica medica, Oct 10, 2017
Drug resistance and toxic side effects are among the main obstacles preventing successful treatme... more Drug resistance and toxic side effects are among the main obstacles preventing successful treatment of neoplastic diseases. Development and application of agents that have the capability to interact selectively with two or more macromolecular targets is a promising strategy to overcome these challenges. The identification of compounds with anticancer potential requires a complex approach based on a wide spectrum of model systems and methods with different molecular/cellular targets and mechanisms of action. The optimization and introduction of such an approach in our laboratory was the aim of the study presented. The cytotoxic activity of various synthetic compounds with different structure and physico-chemical characteristics (cisplatin, disulfiram, Cu(II) complexes with Schiff bases, etc.) was evaluated in short-term (24-72h, with monolayer cultures) and long-term (30-45 days, with 3D cancer cell colonies) experiments by the MTT test, neutral red uptake cytotoxicity assay, crystal violet staining, trypan blue dye exclusion technique, lactate dehydrogenase activity assay, double staining with acridine orange and propidium iodide, Annexin V/FITC assay, Comet assay and colony-forming method. The investigations were performed using permanent cell lines established from chicken (hepatoma), rat (sarcoma) and human (breast cancer, cervical carcinoma, liver cancer, non-small cell lung cancer, glioblastoma multiforme) cancers of different etiology, histological type and expression of hormonal receptors (in the case of breast cancer). The conditions for carrying out these methods were optimized and their advantages and disadvantages were specified. Information regarding the influence of the compounds investigated on cell survival and proliferation was obtained. Our results indicate that in order to obtain adequate experimental data, the approach described above has to be adapted to each individual “cell line – compound” system. Acknowledgements: This study was supported by Grant -DCOST 01/16 from 17.08.2017, COST Action CA15135 and a bilateral project between the Bulgarian Academy of Sciences and the Romanian Academy.
European Journal of Cancer, Sep 1, 2015
Results: EGFR signaling was inhibited in pancreatic carcinoma cell lines by all the small EGFR in... more Results: EGFR signaling was inhibited in pancreatic carcinoma cell lines by all the small EGFR inhibitors tested. The effects of the EGFR inhibitors AG1478, erlotinib, geficitinib and cetuximab have been determined in pancreatic carcinoma cell lines (IMIM-PC-1, IMIM-PC-2, RWP-1 and PANC-1). Our results show that all cell lines were resistant to the antiproliferative effect of cetuximab (only IMIM-PC-1 cell line shows a slightly decrease in proliferation) as determined by MTT analysis as well as by cell cycle analysis using flow cytometry. Meanwhile, all cell lines were sensitive to at least one of the EGFR tyrosin-kinase activity inhibitors (AG-1478, erlotinib and geficitinib). We have found that IMIM-PC-2 cell line was sensitive to all the EGFR-TK inhibitors, RWP-1 cells were sensitive to geficitib and erlotinib but they were quite resistant to AG-1478, IMIM-PC-1 cells were sensitive to geficitinib and to a lesser extent to erlotinib and, finally PANC-1 cells were only moderately sensitive to geficitinib. The discrepancies found between the differential effects of cetuximab versus EGFR-TK inhibitors as well as the differences observed in the effects of the different TK-inhibitors upon the same cell lines, suggest that the EGFR inhibitors act in these pancreatic carcinoma cell lines not only trough inhibition of EGFR but also through differential effects on secondary targets. For identification of the putative secondary targets, we have determined by DNA arrays, the level of expression of tyrosin-kinases in the four pancreatic cell lines. Differential expression of several kinases has been found in our cell lines that could be related to the effects observed with the EGFR inhibitors in the pancreatic carcinoma cell lines. Inhibitory peptides designed against PTK6 as well as specific siRNas for this kinase, are able to potentiate the effects of EGFR inhibitors in pancreatic carcinoma cell lines. Conclusion: PTK6 and in lesser extension TNK2 kinases are able to potentiate the effects of EGFR inhibitors on pancreatic carcinoma cell lines No conflict of interest.
Infection and drug resistance, Mar 1, 2024
Dokladi na Bʺlgarskata akademiâ na naukite, Jan 29, 2024
Despite undoubted success in early diagnosis and treatment of breast cancer, it remains one of th... more Despite undoubted success in early diagnosis and treatment of breast cancer, it remains one of the most common and lethal neoplastic diseases in the world among women. Adequate model systems, including cell cultures, can help us better understand breast cancer biology as well as for the discovery of new diagnostic, prognostic and therapeutic strategies. This review summarizes some of the main characteristics of cell cultures (primary cell cultures and immortal cell lines; 2D and 3D cell cultures) used in current biomedical research and their strengths and weaknesses.
Journal of Inorganic and Organometallic Polymers and Materials, Dec 1, 2018
Four complexes of Co(II), Ni(II), Cu(II), and Zn(II) with isoxicam (H2ISO) as ligand, namely [Co(... more Four complexes of Co(II), Ni(II), Cu(II), and Zn(II) with isoxicam (H2ISO) as ligand, namely [Co(HISO)2(H2O)2]⋅3H2O (Co–Iso), [Ni(HISO)2(H2O)2]⋅0.5H2O (Ni–Iso), [Cu(HISO)2(H2O)] (Cu–Iso), [Zn(HISO)2(H2O)2]⋅0.5H2O (Zn–Iso), have been synthesized and characterized by FT-IR, UV–Vis–NIR, 1H NMR, TG/DSC, elemental analysis, magnetic and conductivity measurements. The following permanent cell lines were used to evaluate the cytotoxic activity of the compounds: LSCC-SF-Mc29, strain E7 (transplantable chicken hepatoma induced by the myelocytomatosis virus Mc29), LSR-SF-SR (transplantable sarcoma in rat, induced by Rous sarcoma virus, strain Schmidt-Ruppin), MCF-7 (luminal A type breast cancer), HeLa (human carcinoma of the uterine cervix) and Lep-3 (human non-tumor embryonal fibroblastoid cells). Short term experiments (24–72 h) with monolayer cultures were performed by MTT test, neutral red uptake cytotoxicity assay and double staining with acridine orange and propidium iodide as well as long term experiments (20 days) with 3D cancer cell colonies in semi-solid medium. The results obtained reveal that: (i) applied at a concentration range of 5–500 µg mL−1 the compounds investigated decrease in a time- and concentration-dependent manner viability and/or proliferation of the treated cells; (ii) metal complexes are more pronounced cytotoxic agents as compared to isoxicam; (iii) cell-specific response was observed—Cu–Iso expresses the highest cytotoxic activity in LSCC-SF-Mc29 (strain E7) cells, whereas Zn–Iso is the most effective compound in LSR-SF-SR and Lep-3 cells, and Co–Iso—in HeLa cells; (iv) in general, human non-tumor Lep-3 embryonic fibroblastoid cells are relatively less sensitive to the cytotoxic activity of the complexes as compared to human cancer MCF-7 and HeLa cells.
Materials, methods & technologies, May 31, 2015
PubMed, Sep 1, 2009
Gene therapy is a new and innovative approach to the treatment of malignant neoplasms, although i... more Gene therapy is a new and innovative approach to the treatment of malignant neoplasms, although it is still not capable of eradicating cancer in humans. Selection of the appropriate vector with maximal efficiency and minimal toxicity is crucial for gene therapy and numerous viral and non-viral (synthetic) methods for gene transfer have been developed. There are different gene therapy approaches for cancer treatment such as: 1) gene correction; 2) molecular chemotherapy; 3) proapoptotic gene therapy; 4) antiangiogenic gene therapy; 5) immune gene therapy; and 6) modulation of drug resistance/sensitivity. Cancer gene therapy represents one of the most rapidly developing areas in preclinical and clinical research. However, some problems need to be solved to make sure this strategy is safe, effective and long-lasting before it becomes routinely adopted in clinical practice.
Inorganica Chimica Acta, May 1, 2011
HAL (Le Centre pour la Communication Scientifique Directe), 2020
Gels
The study reports the synthesis and characterization of novel triple stimuli responsive interpene... more The study reports the synthesis and characterization of novel triple stimuli responsive interpenetrating polymer network (IPN) based on two polyzwitterionic networks, namely of poly(carboxybetaine methacrylate) and poly(sulfobetaine methacrylate). The zwitterionic IPN hydrogel demonstrates the ability to expand or shrink in response to changes in three “biological” external stimuli such as temperature, pH, and salt concentration. The IPN hydrogel shows good mechanical stability. In addition, other important features such as non-cytotoxicity and antibiofouling activity against three widespread bacteria as P. Aeruginosa, A. Baumanii, and K. Pneumoniae are demonstrated. The in vivo behavior of the novel zwitterionic IPN hydrogel suggests that this smart material has very good potential as a biomaterial.
Scripta scientifica medica, Oct 10, 2017
Scripta scientifica medica, Oct 10, 2017
Drug resistance and toxic side effects are among the main obstacles preventing successful treatme... more Drug resistance and toxic side effects are among the main obstacles preventing successful treatment of neoplastic diseases. Development and application of agents that have the capability to interact selectively with two or more macromolecular targets is a promising strategy to overcome these challenges. The identification of compounds with anticancer potential requires a complex approach based on a wide spectrum of model systems and methods with different molecular/cellular targets and mechanisms of action. The optimization and introduction of such an approach in our laboratory was the aim of the study presented. The cytotoxic activity of various synthetic compounds with different structure and physico-chemical characteristics (cisplatin, disulfiram, Cu(II) complexes with Schiff bases, etc.) was evaluated in short-term (24-72h, with monolayer cultures) and long-term (30-45 days, with 3D cancer cell colonies) experiments by the MTT test, neutral red uptake cytotoxicity assay, crystal violet staining, trypan blue dye exclusion technique, lactate dehydrogenase activity assay, double staining with acridine orange and propidium iodide, Annexin V/FITC assay, Comet assay and colony-forming method. The investigations were performed using permanent cell lines established from chicken (hepatoma), rat (sarcoma) and human (breast cancer, cervical carcinoma, liver cancer, non-small cell lung cancer, glioblastoma multiforme) cancers of different etiology, histological type and expression of hormonal receptors (in the case of breast cancer). The conditions for carrying out these methods were optimized and their advantages and disadvantages were specified. Information regarding the influence of the compounds investigated on cell survival and proliferation was obtained. Our results indicate that in order to obtain adequate experimental data, the approach described above has to be adapted to each individual “cell line – compound” system. Acknowledgements: This study was supported by Grant -DCOST 01/16 from 17.08.2017, COST Action CA15135 and a bilateral project between the Bulgarian Academy of Sciences and the Romanian Academy.
European Journal of Cancer, Sep 1, 2015
Results: EGFR signaling was inhibited in pancreatic carcinoma cell lines by all the small EGFR in... more Results: EGFR signaling was inhibited in pancreatic carcinoma cell lines by all the small EGFR inhibitors tested. The effects of the EGFR inhibitors AG1478, erlotinib, geficitinib and cetuximab have been determined in pancreatic carcinoma cell lines (IMIM-PC-1, IMIM-PC-2, RWP-1 and PANC-1). Our results show that all cell lines were resistant to the antiproliferative effect of cetuximab (only IMIM-PC-1 cell line shows a slightly decrease in proliferation) as determined by MTT analysis as well as by cell cycle analysis using flow cytometry. Meanwhile, all cell lines were sensitive to at least one of the EGFR tyrosin-kinase activity inhibitors (AG-1478, erlotinib and geficitinib). We have found that IMIM-PC-2 cell line was sensitive to all the EGFR-TK inhibitors, RWP-1 cells were sensitive to geficitib and erlotinib but they were quite resistant to AG-1478, IMIM-PC-1 cells were sensitive to geficitinib and to a lesser extent to erlotinib and, finally PANC-1 cells were only moderately sensitive to geficitinib. The discrepancies found between the differential effects of cetuximab versus EGFR-TK inhibitors as well as the differences observed in the effects of the different TK-inhibitors upon the same cell lines, suggest that the EGFR inhibitors act in these pancreatic carcinoma cell lines not only trough inhibition of EGFR but also through differential effects on secondary targets. For identification of the putative secondary targets, we have determined by DNA arrays, the level of expression of tyrosin-kinases in the four pancreatic cell lines. Differential expression of several kinases has been found in our cell lines that could be related to the effects observed with the EGFR inhibitors in the pancreatic carcinoma cell lines. Inhibitory peptides designed against PTK6 as well as specific siRNas for this kinase, are able to potentiate the effects of EGFR inhibitors in pancreatic carcinoma cell lines. Conclusion: PTK6 and in lesser extension TNK2 kinases are able to potentiate the effects of EGFR inhibitors on pancreatic carcinoma cell lines No conflict of interest.