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Insights into platinum-induced peripheral neuropathy–current perspective

Neural Regeneration Research 2020年第9期15卷 1623-1630页

作者： andrijana lazić Jelena Popović Tatjana Paunesku Gayle EWoloschak Milena Stevanović Institute of Molecular Genetics and Genetic Engineering University of BelgradeBelgradeSerbia Feinberg School of Medicine Department of Radiation OncologyNorthwestern UniversityChicagoILUSA Faculty of Biology University of BelgradeBelgradeSerbia Serbian Academy of Sciences and Arts BelgradeSerbia

Cancer is a global health problem that is often successfully addressed by therapy, with cancer survivors increasing in numbers and living longer world around. Although new cancer treatment options are continuously explored, platinum based chemotherapy agents remain in use due to their efficiency and availability. Unfortunately, all cancer therapies affect normal tissues as well as cancer, and more than 40 specific side effects of platinum based drugs documented so far decrease the quality of life of cancer survivors. Chemotherapy-induced peripheral neuropathy is a frequent side effects of platinum-based chemotherapy agents. This cluster of complications is often so debilitating that patients occasionally have to discontinue the therapy. Sensory neurons of dorsal root ganglia are at the core of chemotherapy-induced peripheral neuropathy symptoms. In these postmitotic cells, DNA damage caused by platinum chemotherapy interferes with normal functioning. Accumulation of DNA-platinum adducts correlates with neurotoxic severity and development of sensation of pain. While biochemistry of DNA-platinum adducts is the same in all cell types, molecular mechanisms affected by DNA-platinum adducts are different in cancer cells and non-dividing cells. This review aims to raise awareness about platinum associated chemotherapy-induced peripheral neuropathy as a medical problem that has remained unexplained for decades. We emphasize the complexity of this condition both from clinical and mechanistical point of view and focus on recent findings about chemotherapy-induced peripheral neuropathy in in vitro and in vivo model systems. Finally, we summarize current perspectives about clinical approaches for chemotherapy-induced peripheral neuropathy treatment.

关键词： chemotherapy-induced peripheral neuropathy CIPN DNA-Pt adducts dorsal root ganglia DRG model systems molecular mechanisms neurotoxic platinum based chemotherapy Pt sensory neurons treatment side effects

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Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells

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BIOCELL 2021年第5期45卷 1355-1367页

作者： ISIDORA PETROVIC MILENA MILIVOJEVIC ANA ARSENIJEVIC andrijana laziC NATASA KOVACEVIC GRUJICIC MARIJA SCHWIRTLICH JELENA POPOVIC MILENA STEVANOVIC Institute of Molecular Genetics and Genetic Engineering University of BelgradeBelgradeSerbia Institute of Cell Biology School of Biological SciencesThe University of EdinburghEdinburghUK Department of Radiation Oncology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Faculty of Biology University of BelgradeBelgradeSerbia Serbian Academy of Sciences and Arts BelgradeSerbia

Genetic and molecular heterogeneity,together with intrinsic and acquired resistance to therapy,represent the major obstacles to the successful treatment of different types of breast *** evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade,poor prognosis,and therapy *** SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas,and these genes are recognized as potential antitumor *** aim was to evaluate the effect of retinoic acid(RA),a well-known cyto-differentiating agent,on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 *** applying various experimental approaches,we evaluated the effect of RA on basic cellular processes in SK-BR-3 and MCF7 breast carcinoma cell *** have shown that RA inhibits cell growth,reduces the number of Ki-67 positive cells,and causes cell-cycle *** effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression,including a higher decrease in cell viability,reduction in colony formation,and significant remodeling of cellular *** have shown that RA treatment led to the downregulation of SOX2 expression in MCF7 cells and to the reduction of SOX18 expression in both cell *** functional analysis,we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2,pointing to a SOX2-independent mechanism of *** ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from ***,our study shows that the response of breast carcinoma cell lines to RA treatment may vary,highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes.

关键词： Breast carcinoma Anti-proliferative activity Transcription factors MCF7 cell line SK-BR-3 cell line

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