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Topic Review
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Topic Review
Aberrant
MET
Receptor Tyrosine Kinase Signaling in Glioblastoma
Despite therapeutic advances, the treatment of brain tumors, including glioblastoma (GBM), an aggressive primary brain tumor associated with poor prognosis and resistance to therapy, remains a significant challenge. Receptor tyrosine kinases (RTKs) are critical during development and in adulthood. Dysregulation of RTKs through activating mutations and gene amplification contributes to many human cancers and provides attractive therapeutic targets for treatment. Under physiological conditions, the Met RTK, the hepatocyte growth factor/scatter factor (HGF/SF) receptor, promotes fundamental signaling cascades that modulate epithelial-to-mesenchymal transition (EMT) involved in tissue repair and embryogenesis. In cancer, increased Met activity promotes tumor growth and metastasis by providing signals for proliferation, survival, and migration/invasion. Recent clinical genomic studies have unveiled multiple mechanisms by which MET is genetically altered in GBM, including focal amplification, chromosomal rearrangements generating gene fusions, and a splicing variant mutation (exon 14 skipping, METex14del). Notably, MET overexpression contributes to chemotherapy resistance in GBM by promoting the survival of cancer stem-like cells. This is linked to distinctive Met-induced pathways, such as the upregulation of DNA repair mechanisms, which can protect tumor cells from the cytotoxic effects of chemotherapy.
162
11 Mar 2024
Topic Review
ABCA1 and Atherogenesis
Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. ABCA1, ABCG1, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and HDL as a first RCT step. Molecular determinants of RCT efficiency that may possess diagnostic and therapeutic meaning remain largely unknown. Defects in the structure and function of ABCA1, ABCG1, and SR-BI are caused by changes in the gene sequence, such as single nucleotide polymorphism or various mutations. In the transcription initiation of transporter genes, in addition to transcription factors, long noncoding RNA (lncRNA), transcription activators, and repressors are also involved. Furthermore, transcription is substantially influenced by the methylation of gene promoter regions. Post-transcriptional regulation involves microRNAs and lncRNAs, including circular RNAs.
432
06 Jan 2022
Topic Review
A Journey to Produce Functional Beta Cells
Due to a pressing worldwide situation with diabetes, ideas to use direct differentiation from embryonic stem cells (ESCs) and pluripotent stem cells (PSCs) to produce beta cells have surfaced. Stem cells are thought to be an ideal source of all cell types including pancreatic beta cells.
400
28 Jun 2022
Topic Review
5-Methylcytosine
The human genome has additional regulation layers for the regulation of transcription. The DNA methylation is a key epigenetic process that sharp in functional regions in the genome. The 5-methylcytosine patterns in promoter regions are related to gene expression regulation.
874
08 Dec 2020
Topic Review
3D Modeling of Epithelial Tumors
The current statistics on cancer show that 90% of all human cancers originate from epithelial cells. Breast and prostate cancer are examples of common tumors of epithelial origin that would benefit from improved drug treatment strategies. About 90% of preclinically approved drugs fail in clinical trials, partially due to the use of too simplified in vitro models and a lack of mimicking the tumor microenvironment in drug efficacy testing. This entry focuses on the epithelial cancers, followed by experimental models designed to recapitulate the epithelial tumor structure and microenvironment. A specific focus is to put on novel technologies for cell culture of spheroids, organoids, and 3D-printed tissue-like models, utilizing biomaterials of natural or synthetic origins, and how the models could be utilized for nanotechnology-based drug delivery in the future.
705
24 Jun 2021
Topic Review
3D Culture Models of Exosomes in Breast Cancer
Breast cancer comes in different types, making it hard to treat effectively. One particularly aggressive type, called triple-negative breast cancer, is tough to target with current treatments. Scientists use advanced methods like 3D cultures, which mimic human tissue better than traditional lab methods, to study breast cancer. These 3D cultures help understand how tiny communication structures called exosomes affect cancer growth, spread, and response to therapy. Exosomes are like messengers between cells and can influence cancer’s behavior and response to therapy.
169
28 Feb 2024
Topic Review
3D Cell Cultures
The 3D cell cultures allow cells to growth and interact between them and with the extracellular matrix in three dimensions. This conforms a culture structure closer to physiological conditions than the cell monolayers (2D) traditionally employed in cell biology, and it can be achieved by using extracellular matrix hydrogels derived from decellularized tissues, bio-printed scaffolds made of different materials, or by forcing the cells to interact between each other without physical support. 3D culture models provide a powerful tool to understand cell-to-cell interactions when used in co-cultures, and to determine the involvement of extracellular vesicles as major key interactors in cellular crosstalk.
815
23 Feb 2021
Topic Review
3D Cell Culture in Micro-Bioreactors
Bioreactors have proven useful for a vast amount of applications. Besides classical large-scale bioreactors and fermenters for prokaryotic and eukaryotic organisms, micro-bioreactors, as specialized bioreactor systems, have become an invaluable tool for mammalian 3D cell cultures.
970
27 Jan 2021
Topic Review
3D Cell Culture in Brief
Three-dimensional (3D) cell culture represents a paradigm shift in cellular research. Unlike traditional two-dimensional (2D) cultures, it offers a more physiologically relevant environment for studying cells and tissues. In 3D culture, cells grow within complex three-dimensional structures that mimic the architecture of living organs and tissues. This approach allows researchers to explore cell behavior, disease mechanisms, and drug responses with greater accuracy. Methods like hydrogels, spheroids, and bioprinting enable the creation of 3D models that faithfully replicate in vivo conditions. These models find applications in diverse fields, including cancer research, neuroscience, infectious diseases, drug development, and tissue engineering. By improving disease modeling, drug screening, and tissue regeneration, 3D cell culture is driving advancements in biomedical research and offering new avenues for understanding and treating diseases. While challenges remain, ongoing innovations in 3D culture techniques are poised to reshape the landscape of cellular research.
262
11 Oct 2023
Topic Review
3C Protease as Ferroptosis Inducer
Regulated cell death (RCD) is a fundamental process common to nearly all living beings and essential for the development and tissue homeostasis in animals and humans. A wide range of molecules can induce RCD including a number of viral proteolytic enzymes. To date, numerous data indicate that picornaviral 3C proteases can induce RCD. In most reported cases, these proteases induce classical caspase-dependent apoptosis. In contrast, the human hepatitis A virus 3C protease (3Cpro) has recently been shown to cause caspase-independent cell death accompanied by previously undescribed features. In the current topic the results of the study where 3Cpro-induced cell death was characterized morphologically and biochemically are presented. It was found that dead cells demonstrated necrosis-like morphological changes including permeabilization of plasma membrane, loss of mitochondrial potential, as well as mitochondria and nuclei swelling. Additionally, it was shown that 3Cpro-induced cell death was efficiently blocked by ferroptosis inhibitors and was accompanied by intense lipid peroxidation. Taken together, these results indicate that 3Cpro induces ferroptosis upon its individual expression in human cells. This is the first demonstration that a proteolytic enzyme can induce ferroptosis, the recently discovered and actively studied type of RCD.
820
22 Sep 2021
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