Publications by authors named "K E Jenns"
AXL+ Siglec-6+ dendritic cells (ASDC) are novel myeloid DCs which can be subdivided into CD11c+ and CD123+ expressing subsets. We showed for the first time that these two ASDC subsets are present in inflamed human anogenital tissues where HIV transmission occurs. Their presence in inflamed tissues was supported by single cell RNA analysis of public databases of such tissues including psoriasis diseased skin and colorectal cancer.
View Article and Find Full Text PDFOncology nurses and patients identify nausea and vomiting as the two most distressing side effects of chemotherapy. The onset and duration of nausea and vomiting in patients receiving chemotherapy may vary. Inadequate control of emesis in the first 24 h following chemotherapy can lead to anticipatory nausea and vomiting and poor control in subsequent cycles of treatment.
View Article and Find Full Text PDFThe dose limiting toxicities of the short infusion trial of the dacarbazine analog, CB10-277, were nausea and vomiting which appeared to be related to the peak plasma level of the parent drug. In addition, based on mouse studies, these dose limiting toxicities occurred at a less than optimal level of the monomethyl metabolite, the presumed species required for antitumour activity. An alternative schedule that would avoid the parent drug peak plasma levels of short infusion, while possibly allowing an increase in the amount of monomethyl metabolite produced was considered.
View Article and Find Full Text PDFArticle Synopsis
- The pharmacokinetics of anthrapyrazole CI-941 were studied during a Phase I trial, using a starting dose of 5 mg/m² based on safety data from mice.
- A target plasma concentration area (AUC) was set at 110 microM x min, linked to the drug's toxicity profile in mice, and was achievable in human participants at a higher dose of 40 mg/m².
- Results indicated significant variability in drug clearance among patients, which hindered the use of a pharmacokinetics-based dosing strategy, but the recommended Phase II dose was established at 50 mg/m².
Article Synopsis
- The development of new anticancer drugs relies on animal studies for efficacy and toxicity before proceeding to early human trials.
- Recent proposals suggest that preclinical pharmacokinetic data from mice could enhance the efficiency of phase I trials, exemplified by the anthrapyrazole CI-941.
- In a phase I trial involving 44 patients, leucopenia emerged as the primary dose-limiting toxicity, with other manageable side effects; however, the intended pharmacokinetically guided dose adjustment was impractical due to significant variability in patient response, leading to no observable tumor responses.