Biology subjects

Kudryashova, O.

Publications and source records attributed to Kudryashova, O..

3 recordsLinked to original sources

bioRxiv2024

Downregulation of Gankyrin/PSMD10 affects cancer cell growth and proliferation in glioblastoma: in vitro and in vivo study

AbstractThe oncoprotein Gankyrin/PSMD10 is upregulated in various cancers, including glioblastoma multiforme (GBM), the most difficult tumor to treat. The heterogeneity of this type of tumor requires a multi-targeted approach to overcome radio- and chemoresistance. Here we aim to investigate the effects of Gankyrin inhibition on glioma cell proliferation and its impact on sensitivity to chemotherapy both in vitro and in vivo. We have employed the RNA interference approach as a valuable tool to downregulate the expression of target genes. Small interfering RNA (siRNA) were formulated into lipid nanoparticles (LNP) to facilitate delivery and overcome challenges, including RNase activity. We demonstrate that knockdown of Gankyrin promotes cell growth arrest of murine (GL261, CT-2[A]) and human (U87, GBM23, GBM24) glioma cells and induces the generation of reactive oxygen species and apoptosis. Importantly, Gankyrin inhibition enhances the therapeutic effect of temozolomide in murine glioma cell lines and decreases the IC50 of doxorubicin and cisplatin for U87 and GL261 cells. The therapeutic potential of Gankyrin inhibition was shown in patient-derived glioblastoma stem cells, which are responsible for tumor initiation and resistance to therapy. We showed that downregulation of Gankyrin led to decreased cell proliferation in vitro and improved survival in xenograft glioma model mice. Our results suggest that harnessing siRNA against Gankyrin may serve as a novel therapeutic strategy for glioblastoma therapy in a multi-drug approach and address challenges in current treatment by sensitizing glioma cells to chemotherapy. HighlightsO_LIsiRNA-mediated knockdown of Gankyrin reduced cell proliferation of murine and human glioma cells, induced ROS generation and promoted apoptosis. C_LIO_LIInhibition of Gankyrin increased the therapeutic effect of temozolomide in resistant CT- 2A glioma cells and decreased the IC50 concentration of doxorubicin and cisplatin in U87 and GL261 cells. C_LIO_LIDownregulation of Gankyrin inhibited the growth of patient-derived glioma stem cells and increased the survival of NOD/SCID xenograft glioma model mice C_LI

cancer biology↗

bioRxiv2022

A Multi-scale, Multiomic Atlas of Human Normal and Follicular Lymphoma Lymph Nodes

Reference atlases, molecular and spatial maps of mammalian tissues, are critical resources for discovery efforts and translational research. Their utility is dependent on operationalizing the resulting data by identifying cell types, histological patterns, and predictive biomarkers underlying health and disease. The human lymph node (LN) offers a compelling use case because of its importance in immunity, structural and cellular diversity, and neoplastic involvement. One hematological malignancy, follicular lymphoma (FL), evolves from developmentally blocked germinal center B cells residing in and trafficking through these tissues. To promote survival and immune escape, tumor B cells undergo significant genetic changes and extensively remodel the lymphoid microenvironment. Here, we present an integrated portrait of healthy and FL LNs using multiple genomic and advanced imaging technologies. By leveraging the strengths of each platform, we identified several tumor-specific features and microenvironmental patterns enriched in individuals who experience early relapse, the most high-risk of FL patients.

cancer biology↗

bioRxiv2021

Immune microenvironment subtypes and association with tumor cell mutations and antigen expression in follicular lymphoma.

Follicular lymphoma (FL) is a B-cell lymphoma with a complex tumor microenvironment that is rich in non-malignant immune cells. We applied single-cell RNA-sequencing to characterize the diverse tumor and immune cell populations of FL and identified major phenotypic subsets of FL T-cells including a novel cytotoxic CD4 T-cell population. Their relative proportions of T-cells defined four major FL subtypes, characterized by differential representation or relative depletion of distinct T-cell subsets. By integrating exome sequencing, we observed that somatic mutations are associated with, but not definitive for, reduced antigen presentation on FL cells. In turn, expression of MHC class II genes by FL cells was associated with significant differences in the proportions and targetable immunophenotypic characteristics. This provides a classification framework of the FL microenvironment, their association with FL genotypes and antigen presentation, and informs different potential immunotherapeutic strategies based upon tumor cell MHC class II expression. Statement of significanceWe have characterized the FL-infiltrating T-cells, identified cytotoxic CD4 T-cells as an important component, showed that the abundance of these T-cell populations is associated with tumor-cell-intrinsic characteristics, and identified sets of targetable immune checkpoints on T-cells that differed between FLs with normal versus low antigen presentation.

cancer biology↗