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Showing posts from September, 2020

Note for Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

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Note for Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review) Doi: 10.3892/ijo.2020.5099 Overview Anticancer peptide; Physicochemical properties Amino acid composition Addition of chemical group These three properties – affect Conformation Net charge Orientation of secondary structure Thus, affecting specificity and ACP-cell interaction (peptide penetrating capability, stability, efficacy) Introduction Anticancer peptide advantage High selectivity High penetration Easy modifications Membrane properties of cancer vs normal cells Membrane fluidity of cancer cells higher than healthy cells Contain more abundant microvilli compare with healthy cells Negatively charge but normal cell – neutrality Thus, making cancer cells more prone to ACP Three enzymes involved in contribution of lipid types in the cell membrane Flippase (phosphatidylserine and phosphatidylethanolamine – outer to inner mb) Floppase (phosphatidychlorine and cholesterol f...

Note for: A Proposal Regarding Reporting of In Vitro Testing Results

Note for: A Proposal Regarding Reporting of In Vitro Testing Results Doi: 10.1158/1078-0432.CCR-13-0043 Failure to translate to clinical research examples; Sorafenib Vorinostat Metformin They ask reviewer to limit the publications which reported the concentrations were not related to clinical level, to prevent the failure rate at the clinical levels. The key point for the successfulness in term of translation from in vitro to clinical –  Testing with multiple cell lines Giving wide variation of sensitivity Only small portion of cell will be extremely sensitive at very low concentration This subgroup has special molecular feature which is targetable for particular drug Suggestion Cells – heterogeneity Test with many different types of cells Picking up the cell with show sensitivity with very low drug concentration Finding feature at the molecular level and tracing back to clinical level How to get rid of bad data Author proposed “desk reject” the MS which the concentrations are not ...

Note for: Clinically Relevant Concentrations of Anticancer Drugs: A Guide for Nonclinical Studies

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Note for: Clinically Relevant Concentrations of Anticancer Drugs: A Guide for Nonclinical Studies Doi: 10.1158/1078-0432.CCR-16-3083 Aim of this paper; Giving a guideline for setting up the in vitro experiment on cell line, esp. concentrations by which it makes some sense when translated back to clinical level. Extraction; For doing experiment with FDA-approved drug – it is better to search for pharmacokinetics as well as toxicity of particular drug. Thus, we can design the experiment which will be more clinically relevant.  Guiding dose and concentration selection – providing comprehensive compilation of human plasma exposures for drug-approved by the FDA for used in oncology. Sources of FDA-approved drug NCI – cross-checked with MediLexicon and Centerwatch Pharmacokinetic search through databases – original literature or conference abstract Using Cmax (maximum plasma concentration) and the integrated area under the plasma concentration–time curve (AUC) associated with the highest...