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)

Antitumor prostaglandins(PGs) such as Delta12-PGJ2 and Delta7-PGA1 possess a cyclopentenone or cross-conjugated dienone structures. Antitumor PGs are actively incorporated through cell membrane and control gene expression. Very recent studies clarified that P53 independent expression of p21 and gadd 45, activation of PPARgamma are involved in antitumor mechanism of these PGs. At the low concentration, these PGs exhibit physiological or pathological activity such as osteoblast calcification, promotion of colon cancer cell proliferation. COMPARE PROGRAM using human 38 tumor cell lines suggested that antitumor mechanism of Delta7-PGA1 and 13, 14-dihydro-15-deoxy-Delta7-PGA1 methyl ester (TEI-9826) are quite different from other anticancer agents which are clinically used. Lipid microspheres and Lipiodol formulation were examined as dosage form of the PGs and lipid microspheres were selected for further study. At first lipid microspheres integrated TEI-9038 (Lipo TEI-9038) was chosen as a candidate for clinical trial. However Lipo TEI-9038 failed to exhibit substantial antitumor effect because of its enzymatic instability and toxicity in vivo. Lipo TEI-9826 was then selected as promising candidate for clinical trial because of its stability in serum. Lipo TEI-9826 exhibited marked antitumor effect in several animal models including CDDP resistant nude mice model. Pharmacokinetic and toxicological studies using rats suggested that continuous infusion is the most suitable administration method for Lipo TEI-9826. New type emulsifier, Controlled High Pressure Process Homogenizer (De-BEE 2000 and mini De-BEE) was developed during the preclinical studies on manufacturing process of Lipo TEI-9826. These results warrant the clinical trial for Lipo TEI-9826 in CDDP resistant cancer.
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PMID:Preparation and evaluation of o/w type emulsions containing antitumor prostaglandin. 1110 98

Hepatocellular carcinoma remains a disease with a poor and dismal prognosis, and all forms of currently available conventional therapies are rarely beneficial. However, in recent years, combined targeting locoregional immunochemotherapy has been reported with very promising results. Adoptive immunotherapy with LAK cells (lymphokine-activated killer cells) and recombinant interleukin-2 is becoming one of the new modalities to reconstitute the depressed immune status of the tumor-bearing host. Interleukin-2, gamma-interferon, and interleukin-12 induce cytolytic activity of LAK and natural killer cells and are considered for cellular activation to locoregional immunotherapy before, after resection or even in unresectable hepatocellular carcinomas. Spleen is a suitable organ for LAK cell induction because it has densely packed lymphocytes. The strategy of administration of both interleukin-2 and gamma-interferon into the spleen for in vivo immunostimulation is based on the well-known synergism of the above cytokines. LAK cells have cytotoxic activity against a variety of tumor cells. In particular, LAK cells exhibit efficacy against lung and liver malignant lesions, as suggested by their trafficking pattern; activated killer cells injected i.v. into humans appeared in the lung early and were subsequently rapidly redistributed to the liver and spleen. Lipiodol-Urografin emulsion is probably an ideal cytokine/anti-cancer drug carrier suitable for the combined locoregional immunochemotherapy because during its preferential retention in the vascular network of the spleen and tumor, a gradual release of both immuno- and chemotherapeutical drugs bound to emulsion droplets is achieved ensuring a prolong half life for these drugs. Recent data point to the potential of considering intratumoral or intravascular use of adenovirus carrying interleukin-12 gene, and/or p53-based gene therapy as possible therapeutic strategies in patients with hepatocellular carcinoma.
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PMID:Locoregional immunochemotherapy in hepatocellular carcinoma. 1214 14