Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268318 (ICP)
 10,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many conventional anticancer treatments kill cells irrespective of whether they are normal or cancerous, so patients suffer from adverse side effects due to the loss of healthy cells. Anticancer insights derived from cell cycle research has given birth to the idea of cell cycle G2 checkpoint abrogation as a cancer cell specific therapy, based on the discovery that many cancer cells have a defective G1 checkpoint resulting in a dependence on the G2 checkpoint during cell replication. Damaged DNA in humans is detected by sensor proteins (such as hHUS1, hRAD1, hRAD9, hRAD17, and hRAD26) that transmit a signal via ATR to CHK1, or by another sensor complex (that may include gammaH2AX, 53BP1, BRCA1, NBS1, hMRE11, and hRAD50), the signal of which is relayed by ATM to CHK2. Most of the damage signals originated by the sensor complexes for the G2 checkpoint are conducted to CDC25C, the activity of which is modulated by 14-3-3. There are also less extensively explored pathways involving p53, p38, PCNA, HDAC, PP2A, PLK1, WEE1, CDC25B, and CDC25A. This review will examine the available inhibitors of CHK1 (Staurosporin, UCN-01, Go6976, SB-218078, ICP-1, and CEP-3891), both CHK1 and CHK2 (TAT-S216A and debromohymenialdisine), CHK2 (CEP-6367), WEE1 (PD0166285), and PP2A (okadaic acid and fostriecin), as well as the unknown checkpoint inhibitors 13-hydroxy-15-ozoapathin and the isogranulatimides. Among these targets, CHK1 seems to be the most suitable target for therapeutic G2 abrogation to date, although an unexplored target such as 14-3-3 or the strategy of targeting multiple proteins at once may be of interest in the future.
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PMID:G2 checkpoint abrogators as anticancer drugs. 1507 95

The extensive regeneration potential of the liver makes use of hepatic re-sectioning and split liver transplantation for treating advanced liver diseases. Heavy metals such as cisplatin, carboplatin, and arsenic trioxide (ATO) are being practiced as chemotherapeutic agents for different cancers. Further, research is progressed on using different heavy metal nano-particles as a drug, drug carrier and diseases detective agent. Since liver is the chief organ metabolize ingested materials, the current study focuses on the involvement of ATO on acute liver injury regeneration using a partially hepatectomised (PHx) rat model. Scrutiny of serum liver markers such as albumin, AST, ALT & ALP and hepatic antioxidants like reduced glutathione, glutathione peroxidase, glutathione S-transferase, catalase & superoxide dismutase reveled ATO mediated hepatocyte injury and oxidative stress. Further, oxidative stress is confirmed with elevated TBARS and 8-OHdG in the hepatocyte nucleus in ATO supplemented healthy and regenerating liver and are co-relating with the H&E histological observations. It is noticed that ATO supplementation reduced liver regeneration potential as evidenced by reduced proliferative markers (Ki-67 and PCNA) and meanwhile increases apoptotic protein PARP-1. ICP-MS analysis displayed several-fold hiked serum and liver arsenic in ATO administrated normal and liver regenerating animals. This study concludes that ATO at a chemotherapeutic concentration augments oxidative stress and hepatocytes apoptosis, thereby delays liver regeneration potential and could affect the outcome of liver transplantation.
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PMID:Chemotherapeutic doses of arsenic trioxide delays hepatic regeneration by oxidative stress and hepatocyte apoptosis in partial hepatectomy rat. 3152 89