Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decitabine [NSC 127716, DAC, dezocitidine, Aza dC, 2'-deoxy-5-azacytidine, Dacogen( trade mark )] is a deoxycytidine and cytarabine derivative with potent antileukaemic activity, originated by Pharmachemie. This antimetabolite is able to induce in vitro gene activation and cellular differentiation by a mechanism involving DNA hypomethylation. Decitabine has been studied in several phase II trials for solid tumours as well as in different types of leukaemia. The drug has been shown to have very limited efficacy against solid tumours. However, decitabine exhibits higher activity for the treatment of haematological malignancies. SuperGen announced that it had entered a Cooperative Research and Development Agreement (CRADA) with the US National Cancer Institute (NCI) in May 2000. SuperGen will supply decitabine to the NCI, which will initiate and sponsor clinical trials in patients with solid tumours and haematological malignancies. The NCI will also conduct studies on decitabine's mechanism of action. SuperGen had previously acquired worldwide rights to decitabine from Pharmachemie in the third quarter of 1999 for 4 million US dollars worth of SuperGen shares and income from manufacture upon the launch of decitabine. The drug is undergoing two phase II trials for the treatment of cytomegalovirus leukaemia (CML) in the US, one of which will assess the safety, response rate, duration of response, and survival of decitabine (injection) in combination with imatinib mesylate (oral). SuperGen initiated a phase II clinical study of decitabine in combination with imatinib mesylate in June 2003 that will be conducted under SuperGen's CRADA with the National Cancer Institute and will take place at the MD Anderson Cancer Center in the US. Approximately 80 patients with CML will be enrolled in the study. This followed on decitabine's orphan drug status for the same indication, which was granted by the US FDA in 2002. In addition, the European Commission has granted orphan drug status to decitabine for MDS treatment in February 2003. In March 2003, SuperGen announced that patient enrolment was completed for its open-label, phase III trial comparing decitabine with standard care therapy for treatment of advanced myelodysplastic syndrome, which was initiated in March 2001. The study will be conducted at 22 medical centres in the US and will enrol a total of 160 patients. A pivotal trial is also underway in Europe for the same indication and is aiming to enrol 220 patients. In addition, decitabine is undergoing phase II trials for the treatment of non-small cell lung cancer (NSCLC) in Canada and for prostate cancer in the US. In July 2003, SuperGen was issued a US patent relating to decitabine as part of a combination therapy with other anticancer agents to treat ovarian, breast, prostate, gastric, lung, pancreatic and colon cancers through the correction of DNA hypermethylation. SuperGen was issued a US patent (No. 6 191 119) in 2001 covering the use of decitabine in combination with rubitecan and antibiotic agents, including doxorubicin.
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PMID:Decitabine: 2'-deoxy-5-azacytidine, Aza dC, DAC, dezocitidine, NSC 127716. 1458 64

Two bombsin peptides, GRPR agonist [Aca-QWAVGHLM-NH(2)] and antagonist [fQWAVGHL-NHEthyl] were evaluated. We employed the highly sensitive Waters Q-Tof Premier MS coupled with a UPLC system to identify the metabolites produced by rat hepatocytes or PC-3 human prostate cancer cells; and we utilized the AB/MDS 4000 Q-Trap LC/MS/MS system with highly sensitive quantitative and qualitative performance, to quantitatively analyze the internalization of GRPR agonist and antagonist in PC-3 cells. The major metabolites of both GRPR agonist and antagonist were the result of peptide bond hydrolysis between W and A which was demonstrated by observation of the N-terminal fragment m/z 446 (Aca-QW-OH) for agonist and m/z 480 (fQW-OH) for antagonist. Both peptides were also hydrolyzed between A and V which formed peaks m/z 517 [Aca-QWA-OH] and m/z 555 (VGHLM-NH2) for the agonist and m/z 551 [fQWA-OH] and m/z 452 (VGHL-NHEthyl) for the antagonist. The peptide agonist also formed a unique metabolite that resulted from hydrolysis of the C-terminal amide. The antagonist showed significantly slower metabolism as compared to the agonist in both rat hepatocytes and PC-3 cells. The antagonist also showed significantly lower PC-3 cell internalization rate than that of the agonist. In conclusion, the metabolism profiles of both GRPR agonist and antagonist peptides were identified by LC/MS. The antagonist peptide was more stable than the agonist peptide in rat hepatocyte incubation. One major factor could be the hydrolysis-resistant C-terminal L-NHEthyl group compared with the unsubstituted amide of the agonist. Another factor could be different amino acid sequences of the agonist and antagonist that may also influence the enzymatic hydrolysis. The antagonist ligand is potentially more useful for receptor-targeted imaging due primarily to its higher metabolic stability.
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PMID:LC/MS evaluation of metabolism and membrane transport of bombesin peptides. 2067 5

Prostate cancer is the most common carcinoma of the elderly man and holds the third place in the ranking of cancer-specific mortality. However, mortality rates of 3 % are low, and half of the patients will die from intercurrent disease. Due to the significantly improved diagnostic methods and the increasing use of PSA screening, there has been a stage migration towards early tumour stages that are prognostically heterogeneous and require differentiated treatment. Based on the discussions of the Joint Federal Committee (G-BA) and the conceptual work of the MDS, the Competence Centre Oncology of the MDK, the IQWIG and the National Association of Statutory Health Insurance Funds (GKV-Spitzenverband), a prospective randomised multicentre trial was developed comparing the four treatments actually recommended by the German and European guidelines for localised prostate cancer (radical prostatectomy, percutaneous radiotherapy and permanent seed implantation and active surveillance) allowing a rejection of one or two treatment options. The trial is expected to start at the beginning of next year.
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PMID:[Localised prostate cancer: the PREFERE trial]. 2281 51