Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic studies in mice and humans have shown that the transforming growth factor-beta (TGF-beta) type-I receptor activin receptor-like kinase 1 (ALK1) and its co-receptor endoglin play an important role in vascular development and angiogenesis. Here, we demonstrate that ALK1 is a signalling receptor for bone morphogenetic protein-9 (BMP-9) in endothelial cells (ECs). BMP-9 bound with high affinity to ALK1 and endoglin, and weakly to the type-I receptor ALK2 and to the BMP type-II receptor (BMPR-II) and activin type-II receptor (ActR-II) in transfected COS cells. Binding of BMP-9 to ALK2 was greatly facilitated when BMPR-II or ActR-II were co-expressed. Whereas BMP-9 predominantly bound to ALK1 and BMPR-II in ECs, it bound to ALK2 and BMPR-II in myoblasts. In addition, we observed binding of BMP-9 to ALK1 and endoglin in glioblastoma cells. BMP-9 activated Smad1 and/or Smad5, and induced ID1 protein and endoglin mRNA expression in ECs. Furthermore, BMP-9 was found to inhibit basic fibroblast growth factor (bFGF)-stimulated proliferation and migration of bovine aortic ECs (BAECs) and to block vascular endothelial growth factor (VEGF)-induced angiogenesis. Taken together, these results suggest that BMP-9 is a physiological ALK1 ligand that plays an important role in the regulation of angiogenesis.
 ...
PMID:BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis. 1731 49

Demethyl fruticulin A (SCO-1) is a compound found in Salvia corrugata leaves. SCO-1 was reported to induce anoikis in cell lines via the membrane scavenging receptor CD36. However, experiments performed with cells lacking CD36 showed that SCO-1 was able to induce apoptosis also via alternative pathways. To gain some insight into the biological processes elicited by this compound, we undertook an unbiased genomic approach. Upon exposure of glioblastoma tumor initiating cells (GBM TICs) to SCO-1 for 24 h, we observed a deregulation of the genes belonging to the glutathione metabolism pathway and of those belonging to the biological processes related to the response to stress and to chemical stimulus. On this basis, we hypothesized that the SCO-1 killing effect could result from the induction of reactive oxygen species (ROS) in the mitochondria. This hypothesis was confirmed by flow cytometry using MitoSOX, a mitochondria-selective fluorescent reporter of ROS, and by the ability of N-acetyl cysteine (NAC) to inhibit apoptosis when co-administered with SOC-1 to the GBM TICs. We further show that NAC also protects other cell types such as HeLa, MG-63, and COS-7 from apoptosis. We therefore propose that ROS production is the major molecular mechanism responsible for the pro-apoptotic effect induced by SCO-1. Consequently, SCO-1 may have a potential therapeutic value, which deserves further investigation in animal models.
 ...
PMID:Demethyl fruticulin A (SCO-1) causes apoptosis by inducing reactive oxygen species in mitochondria. 2068 4

Fluorescence nanoscopy has become an indispensable tool for studying organelle structures, protein dynamics, and interactions in biological sciences. Single-molecule localization microscopy can now routinely achieve 10-50 nm resolution through fluorescently labeled specimens in lateral optical sections. However, visualizing structures organized along the axial direction demands scanning and imaging each of the lateral imaging planes with fine intervals throughout the whole cell. This iterative process suffers from photobleaching of tagged probes, is susceptible to alignment artifacts and also limits the imaging speed. Here, we focused on the axial plane super-resolution imaging which integrated the single-objective light-sheet illumination and axial plane optical imaging with single-molecule localization technique to resolve nanoscale cellular architectures along the axial (or depth) dimension without scanning. We demonstrated that this method is compatible with DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) and exchange-PAINT by virtue of its light-sheet illumination, allowing multiplexed super-resolution imaging throughout the depth of whole cells. We further demonstrated this proposed system by resolving the axial distributions of intracellular organelles such as microtubules, mitochondria, and nuclear pore complexes in both COS-7 cells and glioblastoma patient-derived tumor cells.
 ...
PMID:Axial plane single-molecule super-resolution microscopy of whole cells. 3201 May 28

Novel lanthanide (Ln) compounds [Ln(L)2]Cl.xH2O (Ln = La3+, Ce3+, Sm3+) containing aromatic N,O-chelate ligands [HL1 = 4-amino-2-(1H-benzimidazol-2-yl)phenol; HL2 = 5-amino-2-(1H-benzimidazol-2-yl)phenol] have been synthesized and structurally characterized by elemental analysis, NMR and IR spectroscopy, molar conductance measurements, and mass spectrometry (MS). The spectroscopic data suggested that the benzimidazolyl-phenol ligands act as N,O-chelate ligands through the iminic nitrogen and phenolic oxygen atoms. Elemental analysis indicated that lanthanide compounds were formed in a 1:2 stoichiometry (metal:ligand). In vitro biological evaluation was carried out using these complexes, exhibiting moderate cytotoxicity against six different human tumor cell lines (U251, human glioblastoma; HCT-15, colorectal carcinoma; MCF-7, breast epithelial adenocarcinoma; PC-3, prostate cancer; K562, myelogenous leukemia; SKLU-1, lung carcinoma) and lower toxicity against a non-cancerous cell line (COS-7, primate kidney). In addition, the antibacterial activity of the compounds was assessed against two gram-positive strains (Staphylococcus aureus ATCC 25923, Listeria monocytogenes ATCC 19115) and two gram-negative strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27583) using the microdilution method. The results obtained show that the metal complexes exhibit higher biological activity than the free ligands, confirming a synergistic effect. Further benzimidazolyl-phenol derivatives were explored for the detection of bacteria using fluorescence imaging studies. Interestingly, the fluorescent properties of these compounds make them potential candidates to monitor the morphology of bacteria at different compound concentrations. Hence, the interaction of the ligand and complexes with model membranes mimicking those of bacteria was studied by using differential scanning calorimetry (DSC) and molecular dynamics (MD), showing that both compounds decreased the enthalpy of transition in two model membranes as the concentration of the compounds increased. In addition, the main transition temperature was slightly reduced as a result of these interactions.
 ...
PMID:Synthesis, biological evaluation and model membrane studies on metal complexes containing aromatic N,O-chelate ligands. 3254 26


<< Previous 1 2