Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal growth factor receptor (EGFR) is commonly overexpressed in a number of epithelial malignancies and is often associated with an aggressive phenotype [e.g., non-small cell lung cancer (NSCLC) and bladder cancer]. EGFR is present in over 50% of cases of NSCLC, head and neck squamous cell carcinomas (HNSCC) and colon cancer. Several EGFR-targeting agents have been recently developed (C225, ABX-EGF, E7.6.3, EMD 55900, ICR62, ZD1839, CP358774, PD168393, CGP75166/PKI166, CGP59326A, BIBX1382). The two most advanced EGFR inhibitors in development are C225 and ZD1839. C225 is an antibody directed against the ligand-binding domain of human EGFR, which competes for receptor binding with EGF and other ligands. In vitro, C225 inhibits EGFR tyrosine kinase activity and proliferation of EGFR-overexpressing squamous cell carcinoma cell lines. Synergy was observed with doxorubicin, cisplatin and radiation in preclinical models. In phase I trials, major toxicity has been dermatological (rash and acneic skin reactions); allergic reactions have also been observed in about 3% of cases. This agent, administered intravenously once weekly, is presently in phase III trials in HNSCC and colon cancer. ZD1839, a synthetic molecule which targets the EGFR ATP binding site, is a very specific inhibitor of EGFR tyrosine kinase activity. Synergy has been observed with paclitaxel and cisplatin. In phase I trials, responses were seen in advanced NSCLC, and cutaneous toxicity and diarrhea were the most important side effects. Oral chronic daily administration is feasible. Two large randomized trials have been completed in advanced NSCLC in combination with chemotherapy. A large phase II study in second and third line has demonstrated a single agent activity of 18.5%. Another large phase II study in patients who received prior platinum and docetaxel obtained a response rate of 11%. There was no difference in response rate between the 250 and the 500 mg/day doses, but side effects were higher in patients who received the 500 mg dose. A very similar small molecule, OSI-774, has also shown activity in this setting. Two large randomized phase III studies of ZD1839 have recently been completed and analyzed in which two doses of ZD1839 (250 or 500 mg/day) or placebo were given in combination with two different chemotherapy regimens (carboplatin-paclitaxel or carboplatin-gemcitabine). These studies failed to demonstrate an increase in survival by adding ZD1839 together with chemotherapy in patients with advanced NSCLC.
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PMID:The epidermal growth factor receptor pathway and its inhibition as anticancer therapy. 1498 46

To date, precise roles of EMD (emerin) remain poorly described. In this paper, we investigated the role of EMD in the C16-ceramide autophagy pathway. Ceramides are bioactive signaling molecules acting notably in the regulation of cell growth, differentiation, or cell death. However, the mechanisms by which they mediate these pathways are not fully understood. We found that C16-ceramide induces EMD phosphorylation on its LEM domain through PRKACA. Upon ceramide treatment, phosphorylated EMD binds MAP1LC3B leading to an increase of autophagosome formation. These data suggest a new role of EMD as an enhancer of autophagosome formation in the C16-ceramide autophagy pathway in colon cancer cells.
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PMID:New role for EMD (emerin), a key inner nuclear membrane protein, as an enhancer of autophagosome formation in the C16-ceramide autophagy pathway. 2481 7

Tumour cell proliferation, invasion and apoptosis are crucial steps in tumour metastasis. We evaluated the effect of serum from patients undergoing colon cancer surgery receiving thoracic epidural and propofol anaesthesia on colon cancer cell biology. Patients were randomly assigned to receive propofol anaesthesia with a concomitant thoracic epidural (PEA, n = 20) or sevoflurane anaesthesia with opioid analgesia (SGA, n = 20). Venous blood was obtained before induction of anaesthesia and 24 hours postoperatively. The LoVo colon cancer cells were cultured with patient serum from both groups and the effects on proliferation, invasion and apoptosis were measured. Twenty-four hours after surgery, the absorbance value of LoVo cells at 10% serum concentration from PEA was decreased when compared with SGA (0.302 (0.026) vs 0.391 (0.066), p = 0.005). The inhibitory rate of LoVo cells at 10% serum concentration from PEA was higher than that from SGA (p = 0.004) 24 h after surgery. The number of invasive LoVo cells at 10% serum concentration from PEA was reduced when compared with SGA (44 (4) vs 62 (4), p < 0.001). Exposure of LoVo cells to postoperative serum from patients receiving PEA led to a higher luminescence ratio (apoptosis) than those receiving SGA (0.36 (0.04) vs 0.27 (0.05), p < 0.001). Serum from patients receiving PEA for colon cancer surgery inhibited proliferation and invasion of LoVo cells and induced apoptosis in vitro more than that from patients receiving SGA. Anaesthetic technique might influence the serum milieu in a way that affects cancer cell biology and, thereby, tumour metastastasis.
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PMID:Effects of anaesthesia on proliferation, invasion and apoptosis of LoVo colon cancer cells in vitro. 2666 60