Subject(s)
Alaska Natives , Melanoma , SEER Program , Skin Neoplasms , Humans , Melanoma/epidemiology , Melanoma/ethnology , Female , SEER Program/statistics & numerical data , Skin Neoplasms/epidemiology , Skin Neoplasms/ethnology , Retrospective Studies , Male , Alaska Natives/statistics & numerical data , Middle Aged , United States/epidemiology , Aged , Sex Factors , Adult , Indians, North American/statistics & numerical data , Sex DistributionABSTRACT
Epithelial adenocarcinoma of the ovary and colon are associated with the highest rates of cancer-related deaths in women in the U.S. The literature supports the role of HDL-associated apolipoproteins in the treatment of cancer and other pro-inflammatory diseases. Previously, we developed a novel 20-amino acid mimetic peptide, HM-10/10, which potently inhibits tumor development and growth in colon and ovarian cancer. Here, we report the properties of HM-10/10 relative to its stability in vitro. The results demonstrated that HM-10/10 had the highest half-life in human plasma compared to plasma from other species tested. HM-10/10 demonstrated stability in human plasma and simulated gastric environment, increasing its promise as an oral pharmaceutical. However, under conditions modeling the small intestine, HM-10/10 demonstrated significant degradation, likely due to the peptidases encountered therein. Furthermore, HM-10/10 demonstrated no evidence of time-dependent drug-drug interactions, although it demonstrated CYP450 induction slightly above cutoff. As proteolytic degradation is a common limitation of peptide-based therapeutics, we are pursuing strategies to improve the stability properties of HM-10/10 by extending its bioavailability while retaining its low toxicity profile. HM-10/10 holds promise as a new agent to address the international women's health crisis of epithelial carcinomas of the ovary and colon.
Subject(s)
Neoplasms , Humans , Female , Neoplasms/drug therapy , Neoplasms/pathology , Peptides/pharmacology , Peptides/chemistry , Colon/pathologyABSTRACT
We prove the existence of free objects in certain subcategories of Banach lattices, including p-convex Banach lattices, Banach lattices with upper p-estimates, and AM-spaces. From this we immediately deduce that projectively universal objects exist in each of these subcategories, extending results of Leung, Li, Oikhberg and Tursi (Israel J. Math. 2019). In the p-convex and AM-space cases, we are able to explicitly identify the norms of the free Banach lattices, and we conclude by investigating the structure of these norms in connection with nonlinear p-summing maps.
