A5078797562- Protein Degradation and Inhibitors
- MicroRNA in disease regulation
- Melanoma and MAPK Pathways
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Pituitary Gland Disorders and Treatments
- Circular RNAs in diseases
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- RNA Research and Splicing
- DNA Repair Mechanisms
- Dendrimers and Hyperbranched Polymers
- Histone Deacetylase Inhibitors Research
- HER2/EGFR in Cancer Research
- Adrenal and Paraganglionic Tumors
- Acute Myeloid Leukemia Research
- Blood groups and transfusion
- Cancer Cells and Metastasis
- Multiple Myeloma Research and Treatments
- Amino Acid Enzymes and Metabolism
- Neutropenia and Cancer Infections
- CAR-T cell therapy research
- FOXO transcription factor regulation
- Cytokine Signaling Pathways and Interactions
- Chronic Myeloid Leukemia Treatments
Polish Academy of Sciences
2021-2025
John H. Stroger, Jr. Hospital of Cook County
2024
National Institutes of Health
2024
National Cancer Institute
2019-2024
Medical University of Warsaw
2017-2023
Institute of Molecular Physics of the Polish Academy of Sciences
2023
Center for Cancer Research
2022
University of Warsaw
2018-2021
Gdańsk Medical University
2019
Warsaw University of Technology
2019
MCM7 (minichromosome maintenance complex component 7), a DNA replication licensing factor, is host gene for the oncogenic miR-106b~25 cluster. It has been recently revealed as relevant prognostic biomarker in variety of cancers, including pituitary adenomas. The purpose this study was to assess whether and levels correlate with tumor invasiveness cohort ACTH-immunopositive adenomas.Tissue samples were obtained intraoperatively from 25 patients adenoma. Tumor assessed according Knosp grading...
miR-410-3p plays opposite roles in different cancers and may act as an oncomiR or tumor suppressor miR. The purpose of this study was to assess the role somatotroph, gonadotroph, corticotroph pituitary adenomas. Tissue samples were obtained from 75 patients with adenoma. expression assessed using qRT-PCR performed on RNA isolated fresh frozen samples. In vitro experiments cell lines derived somatotroph (GH3), gonadotroph (RC-4B/C), (AtT-20) tumors. Cells transfected synthetic mimic...
Proteasome inhibitors (PIs), used in the treatment of plasma cell myeloma (PCM), interfere with degradation misfolded proteins leading to activation unfolded protein response (UPR) and death. However, despite initial strong antimyeloma effects, PCM cells eventually develop acquired resistance PIs. The pleiotropic role ʟ-glutamine (Gln) cellular functions makes inhibition Gln metabolism a potentially good candidate for combination therapy. Here, we show that cells, both sensitive resistant...
Abstract Background and Aims Inflammatory bowel diseases are linked to an increased risk of developing colorectal cancer [CRC]. Previous studies suggested that the H2B ubiquitin ligase RING finger protein-20 [RNF20] inhibited inflammatory signaling mediated by nuclear factor kappa-light-chain-enhancer activated B cells [NF-κB]. However, role RNF40, obligate heterodimeric partner RNF20, in context inflammation CRC has not been addressed. Here, we examined effect RNF40 loss on vitro vivo....
Triple-negative breast cancer (TNBC) is associated with poor prognosis because of the lack effective therapies. Mixed-lineage protein kinase 3 (MLK3) a that often upregulated in TNBC and involved driving tumorigenic potential cells. Here, we present selective MLK3 degrader, CEP1347-VHL-02, based on pan-MLK inhibitor CEP1347 ligand for E3 ligase von Hippel–Lindau (VHL) by employing proteolysis-targeting chimera (PROTAC) technology. Our compound effectively targeted degradation via...
Abstract Mixed-lineage kinase 3 (MLK3) is a member of the MLK family serine/threonine kinases. MLK3 well-known to regulate MAPK signaling by acting upstream ERK, JNK, and p38 pathways. In addition its canonical role in activating cascades, regulates activity various proteins pathways, including NF-κB, Wnt/β-catenin, PAK1. Previous studies demonstrated that can promote proliferation, invasive growth, metastatic potential human cancers. Triple-negative breast cancer (TNBC) subtype...
Abstract Chemoresistance constitutes a major challenge in the treatment of triple-negative breast cancer (TNBC). Mixed-Lineage Kinase 4 (MLK4) is frequently amplified or overexpressed TNBC where it facilitates aggressive growth and migratory potential cells. However, functional role MLK4 resistance to chemotherapy has not been investigated so far. Here, we demonstrate that promotes chemoresistance by regulating pro-survival response DNA-damaging therapies. We observed knock-down inhibition...
PIM kinases have important pro-tumorigenic roles and mediate several oncogenic traits, including cell proliferation, survival, chemotherapeutic resistance. As a result, multiple inhibitors been pursued as investigational new drugs in cancer; however, response to solid tumors has fallen short of expectations. We found that inhibition kinase activity stabilizes protein levels all three isoforms (PIM1/2/3), this can promote resistance chemotherapy. To overcome effect, we designed proteolysis...
Background/Aim: The post-transcriptional regulation of matrix metalloproteinases (MMPs) via microRNAs (miRNAs) has been recently described in numerous human malignancies. However, the exact mechanisms miRNA-mediated MMPs deregulation endometrial cancer (EC) remain unclear. Herein, we aimed to analyze expression MMP2, MMP16 and TIMP2 identify miRNAs that modulate their expression. Materials Methods: Protein was assessed by immunohistochemistry formalin-fixed paraffin-embedded EC samples....
Metastasis to distant organs is a major cause for solid cancer mortality, and the acquisition of migratory invasive phenotype key factor in initiation malignancy. In this study we investigated contribution Mixed-Lineage Kinase 4 (MLK4) aggressive breast cells. Our TCGA genomic data analysis revealed that amplification or mRNA upregulation MLK4 occurred 23% carcinoma cases. To find association between expression specific subtype cancer, performed transcriptomic multiple datasets, which showed...
Abstract Mixed Lineage Kinase 4 (MLK4) is a serine/threonine kinase that plays role in variety of cellular processes, including migration, apoptosis and proliferation. It belongs to the family MAP3 kinases, which regulate activity specific MAPKs (mitogen-activated protein kinases). MLK4 least described member it was proved act as functional activates JNK, ERK NFκB pathways. The rationale this project based on recent data showing gene amplification mRNA upregulation invasive breast carcinoma...
Abstract Resistance to chemotherapy leads high rates of relapse and poor outcomes in patients with triple-negative breast cancer (TNBC). Therefore, there is a need identify novel molecular targets that could be exploited overcome TNBC chemoresistance. Mixed-lineage kinase 4 (MLK4) member MLK family serine/threonine kinases. Large-scale genomic transcriptomic data indicated MLK4 gene (MAP3K21/KIAA1804) amplified overexpressed approximately 50% tumors. We have recently demonstrated promotes...