Aikyn Kali - Academia.edu (original) (raw)

Papers by Aikyn Kali

Research paper thumbnail of Improvement of myelopoiesis in a cyclophosphamide-induced myelodepression model by administration of a Newly Synthesized Pyrazolo- Piperidine β-Cyclodextrine complex compound

According to WHO, the acquired secondary form of hematopoietic-depressive states increases the ri... more According to WHO, the acquired secondary form of hematopoietic-depressive states increases the risk of death in people with cancer, infectious, and hormonal diseases. The choice of drugs that stimulate the proliferative activity of bone marrow cells is limited. The stimulus to the search for hematopoietic-stimulating compounds among pyridine derivatives was the manifestation of the activity of the cerebroprotective drug Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) to restore the granulocytes and B-lymphocytes homeostasis in clinical practice. The hematopoietic-stimulating activity of the newly synthesized compound Complex of 5-benzyl-7-(o-fluorobenzylidene)-2,3-bis(o-fluorophenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo [4,3-c]pyridine complex with β-cyclodextrin (BIV) was studied on a model of cyclophosphamide-induced myelodepression in C57BL6/J mouse line. The BIV compound demonstrated a stimulating effect on the process of restoring the level of Ly-6G+ Ly-6C+ granulocytes, m...

Research paper thumbnail of Influence of tumor cells on natural killer cell phenotype and cytotoxicity

International Journal of Biology, 2015

Natural Killer (NK) cells are known to lyse tumor cells lacking MHC-I and expressing ligands for ... more Natural Killer (NK) cells are known to lyse tumor cells lacking MHC-I and expressing ligands for activating receptors, thereby participating in cancer immune surveillance. However, their function and phenotype change significantly in cancer patients. The precise molecular mechanism(s) involved in this phenomenon remain unknown. The aim of the present study was to investigate changes of both receptor phenotype and cytotoxic activity of NK cells cocultured with K562 and HepG2 cells in dual-chamber Transwell® plates. A decrease of NK cell cytotoxicity against K562 cells was demonstrated. This effect was not a result of changes in perforin, granzyme or CD107a expression by NK cells or by production of cytokines (IFNγ, TNFα, IL-10, and TGFβ). No changes in the expression of a majority of NK cell receptors (CD16, CD69, 2B4, NKG2A, NKG2D, NKp30, NKp44, NKp46, and DNAM1) were observed. Only an increase in the percentage of NK cells bearing inhibitory receptor TIGIT was found as a result of ...

Research paper thumbnail of Fc Receptor is Involved in Nk Cell Functional Anergy Induced by Miapaca2 Tumor Cell Line

Immunological Investigations, 2020

Impaired NK cytotoxicity has been linked to poor cancer prognosis, but its mechanisms are not cle... more Impaired NK cytotoxicity has been linked to poor cancer prognosis, but its mechanisms are not clearly established. Increasing data demonstrate that NK cells lose cytotoxicity after interaction with NK cellsensitive tumor cells. In this paper, we provide evidence that the human adenocarcinoma cell line MiaPaCa2 and TNFα and TGFβtreated MiaPaCa2 cultures (MiaPaCa2-TT) induced functional anergy of NK cells via FGL2 protein. MiaPaCa2-TT cultures decreased expression of IFNγ, CD107a, DNAM-1, and stimulated expression of PD1 by NK cells, as well as inhibited their cytotoxic activity in a greater manner compared to the parental culture. More importantly, we found that cocultivation with anergized NK cells decreased expression of IFNγ and CD107a by naïve NK cells, which supports the hypothesis of NK cell functional anergy transmission. The obtained results suggest a mechanism by which tumor cells may inhibit cytotoxic functions of tumor-infiltrating and circulating NK cells in cancer.

Research paper thumbnail of Daunorubicin conjugated with alpha-fetoprotein selectively eliminates myeloid-derived suppressor cells (MDSCs) and inhibits experimental tumor growth

Cancer Immunology, Immunotherapy, 2017

Research paper thumbnail of TNFα and TGFβ-1 synergistically increase the cancer stem cell properties of MiaPaCa-2 cells

Oncology Letters, 2017

Increased serum concentrations of tumor necrosis factor α (TNFα) and transforming growth factor β... more Increased serum concentrations of tumor necrosis factor α (TNFα) and transforming growth factor β-1 (TGFβ-1) in the blood of patients with pancreatic cancer (PC) have previously been demonstrated. In addition, exogenous exposure to these cytokines promotes various cancer cell invasive and cancer stem cell (CSC) phenotypes. However, their importance in pancreatic CSCs remains elusive. In the present study, the effects of TNFα and TGFβ-1 on the human PC cell line MiaPaCa-2 were examined. Using flow cytometry, it was revealed that TNFα and TGFβ-1 synergistically increase cluster of differentiation (CD) 44v6, CD133 and ATP-binding cassette transporter G2 (ABCG2) expressing populations in adherent tumor cell culture conditions. Furthermore, a similar trend was observed in cells pretreated with these cytokines grown in sphere forming culture conditions. Similar to previous studies, TNFα treatment increased the proportion of epidermal growth factor receptor (EGFR) expressing cells in adherent culture, and this data was further supported by the results of the sphere formation assay, in which the subculture with a high proportion of EGFR expressing cells exhibited the most efficient sphere forming ability. However, the proportion of vascular endothelial growth factor receptor 1 (VEGFR1) expressing cells did not increase upon treatment with these cytokines individually or in combination. This data was subsequently supported by the results of the wound healing assay in which cytokine treatment did not increase the migration of cells. The MTT cell proli feration and cytotoxicity assay revealed that TNFα + TGFβ-1 treatment significantly increased cell proliferation and daunorubicin resistance, but not gemcitabine resistance. In conclusion, the data of the current study provide a mechanistic association between TNFα, TGFβ-1 and the CSC properties of MiaPaCa-2 cells. In addition, it suggests that targeting TNFα and TGFβ-1 is beneficial for improving the therapeutic efficacy of treatments for patients with PC.

Research paper thumbnail of Improvement of myelopoiesis in a cyclophosphamide-induced myelodepression model by administration of a Newly Synthesized Pyrazolo- Piperidine β-Cyclodextrine complex compound

According to WHO, the acquired secondary form of hematopoietic-depressive states increases the ri... more According to WHO, the acquired secondary form of hematopoietic-depressive states increases the risk of death in people with cancer, infectious, and hormonal diseases. The choice of drugs that stimulate the proliferative activity of bone marrow cells is limited. The stimulus to the search for hematopoietic-stimulating compounds among pyridine derivatives was the manifestation of the activity of the cerebroprotective drug Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) to restore the granulocytes and B-lymphocytes homeostasis in clinical practice. The hematopoietic-stimulating activity of the newly synthesized compound Complex of 5-benzyl-7-(o-fluorobenzylidene)-2,3-bis(o-fluorophenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo [4,3-c]pyridine complex with β-cyclodextrin (BIV) was studied on a model of cyclophosphamide-induced myelodepression in C57BL6/J mouse line. The BIV compound demonstrated a stimulating effect on the process of restoring the level of Ly-6G+ Ly-6C+ granulocytes, m...

Research paper thumbnail of Influence of tumor cells on natural killer cell phenotype and cytotoxicity

International Journal of Biology, 2015

Natural Killer (NK) cells are known to lyse tumor cells lacking MHC-I and expressing ligands for ... more Natural Killer (NK) cells are known to lyse tumor cells lacking MHC-I and expressing ligands for activating receptors, thereby participating in cancer immune surveillance. However, their function and phenotype change significantly in cancer patients. The precise molecular mechanism(s) involved in this phenomenon remain unknown. The aim of the present study was to investigate changes of both receptor phenotype and cytotoxic activity of NK cells cocultured with K562 and HepG2 cells in dual-chamber Transwell® plates. A decrease of NK cell cytotoxicity against K562 cells was demonstrated. This effect was not a result of changes in perforin, granzyme or CD107a expression by NK cells or by production of cytokines (IFNγ, TNFα, IL-10, and TGFβ). No changes in the expression of a majority of NK cell receptors (CD16, CD69, 2B4, NKG2A, NKG2D, NKp30, NKp44, NKp46, and DNAM1) were observed. Only an increase in the percentage of NK cells bearing inhibitory receptor TIGIT was found as a result of ...

Research paper thumbnail of Fc Receptor is Involved in Nk Cell Functional Anergy Induced by Miapaca2 Tumor Cell Line

Immunological Investigations, 2020

Impaired NK cytotoxicity has been linked to poor cancer prognosis, but its mechanisms are not cle... more Impaired NK cytotoxicity has been linked to poor cancer prognosis, but its mechanisms are not clearly established. Increasing data demonstrate that NK cells lose cytotoxicity after interaction with NK cellsensitive tumor cells. In this paper, we provide evidence that the human adenocarcinoma cell line MiaPaCa2 and TNFα and TGFβtreated MiaPaCa2 cultures (MiaPaCa2-TT) induced functional anergy of NK cells via FGL2 protein. MiaPaCa2-TT cultures decreased expression of IFNγ, CD107a, DNAM-1, and stimulated expression of PD1 by NK cells, as well as inhibited their cytotoxic activity in a greater manner compared to the parental culture. More importantly, we found that cocultivation with anergized NK cells decreased expression of IFNγ and CD107a by naïve NK cells, which supports the hypothesis of NK cell functional anergy transmission. The obtained results suggest a mechanism by which tumor cells may inhibit cytotoxic functions of tumor-infiltrating and circulating NK cells in cancer.

Research paper thumbnail of Daunorubicin conjugated with alpha-fetoprotein selectively eliminates myeloid-derived suppressor cells (MDSCs) and inhibits experimental tumor growth

Cancer Immunology, Immunotherapy, 2017

Research paper thumbnail of TNFα and TGFβ-1 synergistically increase the cancer stem cell properties of MiaPaCa-2 cells

Oncology Letters, 2017

Increased serum concentrations of tumor necrosis factor α (TNFα) and transforming growth factor β... more Increased serum concentrations of tumor necrosis factor α (TNFα) and transforming growth factor β-1 (TGFβ-1) in the blood of patients with pancreatic cancer (PC) have previously been demonstrated. In addition, exogenous exposure to these cytokines promotes various cancer cell invasive and cancer stem cell (CSC) phenotypes. However, their importance in pancreatic CSCs remains elusive. In the present study, the effects of TNFα and TGFβ-1 on the human PC cell line MiaPaCa-2 were examined. Using flow cytometry, it was revealed that TNFα and TGFβ-1 synergistically increase cluster of differentiation (CD) 44v6, CD133 and ATP-binding cassette transporter G2 (ABCG2) expressing populations in adherent tumor cell culture conditions. Furthermore, a similar trend was observed in cells pretreated with these cytokines grown in sphere forming culture conditions. Similar to previous studies, TNFα treatment increased the proportion of epidermal growth factor receptor (EGFR) expressing cells in adherent culture, and this data was further supported by the results of the sphere formation assay, in which the subculture with a high proportion of EGFR expressing cells exhibited the most efficient sphere forming ability. However, the proportion of vascular endothelial growth factor receptor 1 (VEGFR1) expressing cells did not increase upon treatment with these cytokines individually or in combination. This data was subsequently supported by the results of the wound healing assay in which cytokine treatment did not increase the migration of cells. The MTT cell proli feration and cytotoxicity assay revealed that TNFα + TGFβ-1 treatment significantly increased cell proliferation and daunorubicin resistance, but not gemcitabine resistance. In conclusion, the data of the current study provide a mechanistic association between TNFα, TGFβ-1 and the CSC properties of MiaPaCa-2 cells. In addition, it suggests that targeting TNFα and TGFβ-1 is beneficial for improving the therapeutic efficacy of treatments for patients with PC.