Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The accumulation of amino acid and dipeptide derivatives of DNR has been studied in vitro on L1210 cells. Only Leu-DNR reaches accumulation levels close to DNR, while Val-DNR, Ile-DNR, and Leu-Leu-DNR reach intermediate values. Intracellular DNR was found when the L1210 cells were incubated in the presence of DNR, Leu-Leu-DNR, Leu-Ala-DNR, and Leu-DNR. The cytostatic activity of the derivatives in vitro on L1210 cells cannot be correlated with their uptake or conversion into DNR. At equitoxic doses given iv on the iv inoculated form of L1210 leukemia, all the derivatives are less active than DNR. When given iv on the sc inoculated L1210 leukemia, Leu-DNR, Ala-Leu-DNR and Leu-Leu-DNR are much more active than DNR with a striking increase in ILS and reduction of tumor progression. The superiority of those compounds could be due to their greater hydrophobicity and to their hydrolysis in situ by enzymes secreted by tumor cells or present on the tumor cells surface.
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PMID:Amino acid and dipeptide derivatives of daunorubicin. 2. Cellular pharmacology and antitumor activity on L1210 leukemic cells in vitro and in vivo. 745 66

Cediranib is a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor that affects tumor angiogenesis and is under investigation in clinical studies on ovarian cancer. Using a panel of eleven patient-derived ovarian cancer xenografts (EOC-PDX) growing orthotopically in the peritoneal cavity of nude mice we investigated the effect of cediranib as monotherapy or in combination with chemotherapy on overall survival (primary endpoint, at euthanasia), and tumor dissemination and metastasis in the peritoneal cavity (secondary endpoint, interim analysis). The response of EOC-PDX to cediranib varied (increment of lifespan, ILS between 12 and 85 %) in the different EOC-PDX, independently from tumor responsiveness to cisplatin (DDP). Cediranib combined with DDP and in maintenance regimen prolonged the survival of mice bearing EOC-PDX with different responsiveness to DDP (ILS between 34 and 224 % with only DDP and between 135 and 337 % with DDP plus Cediranib); survival was extended with the addition of paclitaxel to chemotherapy (50-77 % complete remissions). Cediranib reduced ascites of advanced EOC-PDX, but had limited effect on tumor dissemination; only combined with chemotherapy, ascites and metastases were both reduced. The reduction of tumor dissemination was associated to the increase of overall survival. In conclusion, the response to cediranib differs in the various EOC-PDX, reproducing the heterogeneous response of cancer patients to angiogenesis inhibitors. Cediranib potentiated chemotherapy, significantly inhibiting tumor progression and dissemination to metastatic organs, even in tumors poorly responsive to DDP. EOC-PDX preclinical models with different responsiveness to Cediranib may help in identifying determinants of response to cediranib and mechanisms of adaptation to antiangiogenic treatments.
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PMID:Cediranib combined with chemotherapy reduces tumor dissemination and prolongs the survival of mice bearing patient-derived ovarian cancer xenografts with different responsiveness to cisplatin. 2618 56