Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amongst cancers with poor prognosis those originating from breast commonly metastasise to the skeleton for the high affinity of breast cancer cells to bone. A(3) adenosine receptor (A(3)AR) agonists were found to be potent anti-tumour agents even if their effect on bone-residing breast cancer has not yet been investigated. An animal model of surgery-induced metastasis was used to mimic the human condition in an attempt to develop a novel effective treatment strategy. Sprague-Dawley rats receiving intra-tibial injections of syngeneic MRMT-1 rat mammary gland carcinoma cells developed cancer-associated osteolytic lesions and structural damage that were monitored by microcomputed tomography imaging and histological analysis. To address the involvement of A(3)ARs in tumour-related signalling pathway, A(3)AR expression and functional role were analysed in MRMT-1 cells. The effect of chronic treatment with an A(3)AR agonist, 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyl-uronamide (Cl-IB-MECA) in comparison with cisplatin, was evaluated on rat tumour growth and bone cancer pain. A(3)ARs were expressed in MRMT-1 cells and their activation reduced NF-kB, increased p53 expression and apoptosis, inhibited tumour cell proliferation and migration. In vivo Cl-IB-MECA administration, started on day 1 after tumour cell injection, produced a significant reduction in tumour growth and cancer pain. Cl-IB-MECA treatment, performed on days 5 and 10 after the tumour cell inoculation, revealed the capability of A(3)AR stimulation to partially reduce tumour progression. Our findings highlighted the effectiveness of A(3)AR stimulation in the inhibition of breast tumour-derived bone metastasis growth strongly suggesting that targeting A(3)ARs may have promising therapeutic value in the treatment of bone-residing breast cancer.
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PMID:The stimulation of A(3) adenosine receptors reduces bone-residing breast cancer in a rat preclinical model. 2277 Aug 90

BACKGROUND Compound Kushen injection (CKI) is a traditional Chinese medicine preparation for clinical treatment of cancer pain or treatment of various types of solid tumors. The purpose of this study was to identify the main active compounds from CKI and to investigate its anti-cancer mechanisms via drug target biological network pharmacology construction and prediction. MATERIAL AND METHODS Constituents of CKI were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease targets were collected in the Human Gene (Gene Cards) and Human Mendelian Inheritance (OMIM) databases. "Ingredients-protein targets-pathway" networks were constructed using Cytoscape. STRING database platform to construct enrichment of protein-protein interactions (PPI), related diseases and pathways network. Gene Ontology (GO) biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of were performed to investigate by using Bioconductor tool for analysis. RESULTS The results indicated that 60 constituents of absorption, distribution, metabolism, and excretion (ADME) filtration resulted in 33 constituents exhibiting significant correlations with anti-cancer and CKI may target 113 proteins, including IL6, EGFR, CASP3, VEGFA, MYC, and ESR1. GO and KEGG enrichment analysis results show that 129 biological processes and 93 signal pathways associated with cancer. It mainly involves cancers such as prostate cancer, bladder cancer, hepatocellular carcinoma, colorectal cancer, breast cancer, etc. Active ingredients might also induce apoptosis in cancer cells via the p53 and PI3K-Akt signaling pathway mechanism. CONCLUSIONS This study was based on pharmacological networks results for the prediction of the multi-constituent, multi-target, and multi-pathway mechanisms of CKI, which might be a promising potential therapeutic and prevention candidate for anti-cancer. However, based on computer data mining and analysis, this study still needs to be further verified by in vivo/in vitro experiments, and the safety of CKI needs to be evaluated.
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PMID:Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Compound Kushen Injection in Anti-Cancer Effect. 3189 93