A5015210894- Cancer, Hypoxia, and Metabolism
- Cancer Mechanisms and Therapy
- Protein Degradation and Inhibitors
- Chromatin Remodeling and Cancer
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Quinazolinone synthesis and applications
- Gene expression and cancer classification
- Advanced Proteomics Techniques and Applications
- Folate and B Vitamins Research
- PI3K/AKT/mTOR signaling in cancer
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Multiple Myeloma Research and Treatments
- Receptor Mechanisms and Signaling
- Melanoma and MAPK Pathways
- Metabolomics and Mass Spectrometry Studies
- Histone Deacetylase Inhibitors Research
- Biochemical and Molecular Research
Jagiellonian University
2021
Burkitt lymphoma (BL) is a rapidly growing tumor, characterized by high anabolic requirements. The MYC oncogene plays central role in the pathogenesis of this malignancy, controlling genes involved apoptosis, proliferation, and cellular metabolism. Serine biosynthesis pathway (SBP) couples glycolysis to folate methionine cycles, supporting certain amino acids, nucleotides, glutathione, methyl group donor, S-adenosylmethionine (SAM). We report that BLs overexpress SBP enzymes,...
Sepsis is the leading cause of death in intensive care units worldwide. Current treatments sepsis are largely supportive and clinical trials using specific pharmacotherapy for have failed to improve outcomes. Here, we used lipopolysaccharide (LPS)-stimulated mouse RAW264.7 cell line AlphaLisa assay TNFa as a readout perform supervised drug repurposing screen treatment with compounds targeting epigenetic enzymes, including kinases. We identified SCH772984 compound, an extracellular...
Triple-negative breast cancer (TNBC) is characterized by limited survival, poor prognosis, and high recurrence. Understanding the metabolic adaptations of TNBC could help reveal improved treatment regiments. Here we performed a comprehensive 1H NMR characterization MDA-MB-468 cell line, commonly used model TNBC, followed an analysis serum samples obtained from patients healthy controls. cells were cultured, changes in composition medium monitored for 72 h. Based on time courses, metabolites...
Abstract Mutations in isocitrate dehydrogenase 1 and 2 ( IDH1/2 ) genes occur about 20% patients with acute myeloid leukemia (AML), leading to DNA hypermethylation epigenetic deregulation. We assessed the prognostic significance of mutations + 398 AML normal karyotype (NK-AML), treated daunorubicine cytarabine (DA), DA cladribine (DAC), or fludarabine. IDH2 mutation was an independent favorable factor for 4-year overall survival (OS) total NK-AML population (p = 0.03, censoring at...
Abstract Over-activation of the serine synthesis pathway, upregulation SHMT2 has been described in over 20% solid tumors (e.g. breast, lung, colorectal cancers). Such cancer cells are highly dependent on serine. Serine hydroxymethyltransferase (SHMT) plays a key role so-called one-carbon group biochemical reactions involved amino acid metabolism. SHMT catalyzes conversion to glycine and also folate (vitamin B9) cycle. Antagonists metabolism or antifolates an established chemotherapy certain...
Abstract Many oncogenes modulate metabolic pathways and altered metabolism is one of the hallmarks cancer. In order to sustain proliferation, cell growth adopt a very specific tumor microenvironment, cancer cells have undergo reprogramming. Increased uptake glucose, consumed in anaerobic manner, allows maintain essential bioenergetic biosynthetic pathways. Various reports indicated that many cancers are crucially dependent on serine, which could be either imported or synthesized by serine...
Abstract Homozygous deletions of p16/CDKN2a (cyclin dependent kinase inhibitor 2A) locus are prevalent in cancer and often involve co-deletion adjacent genes. Metabolic gene MTAP (methylthioadenosine phosphorylase) is localized at the 9p21 chromosome close proximity to p16/CDKN2A tumor-suppressor locus. Co-deletion may be observed 80-90% all tumors harboring homozygous deletion CDKN2A, which represents 10 - 15% human tumors. Many these tumor types, such as non-small cell lung cancer,...
Abstract SWI/SNF is a multiprotein chromatin remodeler with ATP-dependent activities leading to selective gene expression, DNA repair, recombination and replication. Various sequencing efforts indicated that nearly 20% of cancers bear mutations in at least one subunit the complex. One crucial regulators complex SMARCA4, member family helicases ATPase activities, which are thought regulate transcription certain genes by altering structure. SMARCA4 mutated virtually all cases small cell...