Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysyl oxidase (EC 1.4.3.13), a copper-dependent enzyme which catalyses the formation of aldehyde cross-links, and acts primarily on collagen and elastin, is known to be increased during wound healing and in fibrotic disorders including liver cirrhosis and atherosclerosis, and to be decreased in some hereditary connective tissue diseases and in malignant cell lines. A recent study showed that lysyl oxidase might possess tumour suppressor activity as an antioncogene for ras. Little is known about the localization of this enzyme in human skin. In this study, we determined immunohistochemically the localization of lysyl oxidase in normal skin of young and elderly subjects obtained from sun-exposed and unexposed regions of the body. All skin samples tested had similar distributions of lysyl oxidase. The enzyme was present both extracellularly and intracellularly. Extracellularly, a few granular aggregates of immunoreactants were observed along collagen and elastic fibres. These granules were more common in the adventitial portion of the dermis than in the reticular portion. Of all sun-exposed and unexposed regions studied, the skin of the face displayed the greatest amount of extracellular immunoreactants. Immunopositive granules were observed intracellularly in fibroblasts, vascular endothelial cells, sweat glands, sebaceous glands, arrector pili muscles and some keratinocytes. These findings provide evidence that, as suggested in recent reports, lysyl oxidase may have a variety of intracellular functions.
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PMID:Immunohistochemical localization of lysyl oxidase in normal human skin. 791 5

Acetaldehyde has been classified as a carcinogen in experimental animal research. Acetaldehyde is highly toxic, mutagenic and carcinogenic. Acetaldehyde causes point mutations, sister chromatid exchanges and gross chromosomal aberrations. In the liver, acetaldehyde binds to DNA and the formation of stable adducts represents one mechanism by which acetaldehyde could trigger the occurrence of replication errors and/or mutations in oncogenes or tumour suppressor genes. In experimental colorectal carcinogenesis the inhibition of acetaldehyde dehydrogenase with elevated acetaldehyde levels results in an acceleration of cancer development. The production of acetaldehyde is reduced when germ-free animals are studied, emphasizing the role of bacteria in the generation of colorectal acetaldehyde. Acetaldehyde levels in the colorectum correlate with crypt cell production rate and result in hyper-regeneration, a precancerous condition. Genetic linkage studies give further evidence for acetaldehyde as a carcinogen. Individuals who accumulate acetaldehyde due to polymorphism and/or mutations in the genes coding for enzymes responsible for acetaldehyde generation and detoxification have an increased cancer risk. This is true for Asians with low acetaldehyde dehydrogenase 2 and for Caucasians with alcohol dehydrogenase 1C*1/1. In conclusion, there is an enormous body of evidence from in vitro studies, animal experiments and genetic linkage studies, that acetaldehyde is the major factor responsible for tumour development in alcohol-associated carcinogenesis of the gastrointestinal tract.
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PMID:The role of acetaldehyde in alcohol-associated cancer of the gastrointestinal tract. 1759 Sep 90

The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs-a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor)-provides outstanding capability to synergistically abrogate tumours. Conjugation of RNA triple helices to dendrimers allows the formation of stable triplex nanoparticles, which form an RNA-triple-helix adhesive scaffold upon interaction with dextran aldehyde, the latter able to chemically interact and adhere to natural tissue amines in the tumour. We also show that the self-assembled RNA-triple-helix conjugates remain functional in vitro and in vivo, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.
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PMID:Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment. 2664 Oct 16