Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the concept that transfer of the human carboxylesterase (CE) gene will overcome the drug resistance of a solid tumor to CPT-11 (irinotecan), we used an adenovirus vector (AdCMV.CE) carrying human CE cDNA to infect CPT-11-resistant A549 human adenocarcinoma cells (A549/CPT) in vitro and in vivo and evaluated cell growth over time. The A549/CPT cells, selected by stepwise and continuous exposure of parental A549 cells to CPT-11 over 10 months, had a 6-fold resistance to CPT-11 and 42% CE activity in comparison with parental A549 cells. AdCMV.CE infection resulted in an increase in functional CE protein in resistant cells in vitro that was sufficient to convert CPT-11 to its active metabolite, SN-38, and effectively suppressed resistant cell growth in vitro in the presence of CPT-11. When AdCMV.CE was directly injected into established s.c. resistant A549-based tumors in nude mice receiving CPT-11, there was a 1.8-fold reduction in tumor size at day 20 compared to that of controls (P < 0.05). These observations suggest that adenovirus-mediated gene transfer of the human CE gene and concomitant administration of CPT-11 may have potential as a strategy for local control of acquired CPT-11 resistance of solid tumors.
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PMID:Reversal of CPT-11 resistance of lung cancer cells by adenovirus-mediated gene transfer of the human carboxylesterase cDNA. 976 66

Pembrolizumab, a potent antibody against programmed death 1 (PD-1) receptor, has shown robust antitumor activity and manageable safety in patients with advanced solid tumors. Its pharmacokinetic (PK) properties were analyzed with population PK modeling using pooled data from the KEYNOTE-001, -002, and -006 studies of patients with advanced melanoma, non-small cell lung cancer (NSCLC), and other solid tumor types. Pembrolizumab clearance was low and the volume of distribution small, as is typical for therapeutic antibodies. Identified effects of sex, baseline Eastern Cooperative Oncology Group performance status, measures of renal and hepatic function, tumor type and burden, and prior ipilimumab treatment on pembrolizumab exposure were modest and lacked clinical significance. Furthermore, simulations demonstrated the model has robust power to detect clinically relevant covariate effects on clearance. These results support the use of the approved pembrolizumab dose of 2 mg/kg every 3 weeks without dose adjustment in a variety of patient subpopulations.
CPT Pharmacometrics Syst Pharmacol 2017 01
PMID:Model-Based Characterization of the Pharmacokinetics of Pembrolizumab: A Humanized Anti-PD-1 Monoclonal Antibody in Advanced Solid Tumors. 2786 86

We describe an extremely rare case of advanced pure primary ovarian squamous cell carcinoma (SCC), treated by adjuvant chemotherapy with dose-dense paclitaxel combined with carboplatin (dd-TC) plus the combination chemotherapy with irinotecan and cisplatin (CPT-P), with long-term recurrence-free survival. A 71-year-old woman complaining of lower abdominal pain was referred to our hospital and a 7-cm-diameter solid tumor was identified. She was diagnosed with a left ovarian tumor that was highly suspicious for malignancy based on ultrasonography, magnetic resonance imaging, and contrast-enhanced computed tomography. Bilateral salpingo-oophorectomy, low-anterior colon resection, and colostomy were performed. Intra- and post-operative histopathological diagnosis revealed International Federation of Gynecology and Obstetrics stage IIIc well-differentiated pure ovarian SCC. As adjuvant chemotherapy, 2 courses of dd-TC were administered, followed by 3 courses of CPT-P; the patient then underwent 4 additional courses of dd-TC. Both regimens were effective and there has been no recurrence or metastasis thus far in the 5 years since the operation.
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PMID:Long-term recurrence-free survival of a patient with advanced pure primary ovarian squamous cell carcinoma treated with dose-dense paclitaxel combined with carboplatin. 2918 68