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Topic Review
Signaling and Transcriptional Regulation of Muscle Catabolic Genes
Cancer cachexia (CC) is a multifactorial syndrome characterized by a significant reduction in body weight that is predominantly caused by the loss of skeletal muscle and adipose tissue. Although the ill effects of cachexia are well known, the condition has been largely overlooked, in part due to its complex etiology, heterogeneity in mediators, and the involvement of diverse signaling pathways. For a long time, inflammatory factors have been the focus when developing therapeutics for the treatment of CC. Despite promising pre-clinical results, they have not yet advanced to the clinic. Developing new therapies requires a comprehensive understanding of how deregulated signaling leads to catabolic gene expression that underlies muscle wasting.
  • 375
  • 19 Sep 2022
Topic Review
Targeting Strategies against Radioresistant Tumors
A radiosensitizer is a drug that makes cancer cells more sensitive to radiation therapy. These compounds apparently promote the scavenging of free radicals produced by radiation damage on the molecular level. Radiation therapy generally affects DNA; mainly, it leads to DNA DSBs. Therefore, many radiosensitizing agents have been formulated to target the clinically developed DNA DSB repair pathways. Other agents instead target different pathways, e.g., DNA-PKcs, ATM, and ATR signaling cascades. More than seven PARP inhibitors, for example, are currently being developed considering their role in DNA repair, especially for tumors with DNA repair defects, such as BRCA mutation, because of their synthetic lethality.
  • 376
  • 16 Sep 2022
Topic Review
Subcellular Localization of Membrane-Type-1 Matrix Metalloproteinase
Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Membrane-type-1 matrix metalloproteinase (MT1-MMP), a transmembrane protein, is first known to localize to the cell membrane.
  • 515
  • 15 Sep 2022
Topic Review
Extracellular Matrix Environment of ccRCC
The extracellular matrix (ECM) controls fundamental properties of tumors, including growth, blood vessel investment, and invasion. The ECM defines rigidity of tumor tissue and individual ECM proteins have distinct biological effects on tumor cells. The most frequent initiating genetic mutation in ccRCC (clear cell renal cell carcinoma) inactivates the VHL gene, which plays a direct role in organizing the ECM.
  • 495
  • 15 Sep 2022
Topic Review
BRAF and MEK Inhibitors in Pediatric CNS Tumors
BRAF is a component of the MAPK and PI3K/AKT/mTOR pathways that play a crucial role in cellular proliferation, differentiation, migration, and angiogenesis. Pediatric central nervous system tumors very often show mutations of the MAPK pathway, as demonstrated by next-generation sequencing (NGS), which now has an increasing role in cancer diagnostics.
  • 446
  • 13 Sep 2022
Topic Review
Development, Phenotype and Macrophage Niche of Kupffer Cells
Macrophages are key participants in the maintenance of tissue homeostasis under normal and pathological conditions, and implement a rich diversity of functions. The largest population of resident tissue macrophages is found in the liver. Hepatic macrophages, termed Kupffer cells, are involved in the regulation of multiple liver functionalities. Kupffer cells (KCs), the resident liver macrophages, constitute a crucially important component of the mononuclear-monocytic system. KCs have a wide variety of responsibilities at both local and systemic level, notably the barrier function preventing various pathogens and their toxic by-products (e.g., endotoxin, also known as bacterial lipopolysaccharide (LPS)) from entering systemic circulation.
  • 674
  • 13 Sep 2022
Topic Review
Eosinophil Structure and Biology
Eosinophils are granulocytes with unique biology. The fact that these cells have been largely preserved during evolution strongly suggests that they play relevant physiological functions. Eosinophils have traditionally been classified as effector cells with prevalent cytotoxic activity, although recent evidence indicates that these cells may play a role in a wide range of homeostatic and regulatory functions.
  • 4.0K
  • 09 Sep 2022
Topic Review
The Proteasome Activator PA200/PSME4
Proteasomes comprise a family of proteasomal complexes essential for maintaining protein homeostasis. Accordingly, proteasomes represent promising therapeutic targets in multiple human diseases. Several proteasome inhibitors are approved for treating hematological cancers. Their side effects impede their efficacy and broader therapeutic applications. Therefore, understanding the biology of the different proteasome complexes present in the cell is crucial for developing tailor-made inhibitors against specific proteasome complexes. 
  • 412
  • 09 Sep 2022
Topic Review
SUMOylation in Skeletal Development and Disease
The modification of proteins by small ubiquitin-related modifier (SUMO) molecules, SUMOylation, is a key post-translational modification involved in a variety of biological processes, such as chromosome organization, DNA replication and repair, transcription, nuclear transport, and cell signaling transduction. Emerging evidence has shown that SUMOylation regulates the development and homeostasis of the skeletal system.
  • 365
  • 09 Sep 2022
Topic Review
TNF Receptor Associated Factor-2 in Immune Signaling Pathways
Tumor necrosis factor (TNF) receptor associated factor-2 (TRAF2) is an intracellular adapter protein with E3 ligase activity, which interacts with a plethora of other signaling proteins, including plasma membrane receptors, kinases, phosphatases, other E3 ligases, and deubiquitinases. TRAF2 is involved in various cancer-relevant cellular processes, such as the activation of transcription factors of the NFκB family, stimulation of mitogen-activated protein (MAP) kinase cascades, endoplasmic reticulum (ER) stress signaling, autophagy, and the control of cell death programs. In a context-dependent manner, TRAF2 promotes tumor development but it can also act as a tumor suppressor.
  • 455
  • 07 Sep 2022
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