title: A guide for the analysis of long-term population growth in cancer.
abstract: Although cancer is a chronic disease, most of the in vitro experiments to assess the effectiveness of intervention are performed in hours or a few days. Moreover, none of the available methodologies to measure cell proliferation are adapted to provide information about the growth kinetic during and after treatment. Thus, the objective of this work is to provide a guide to assess long-term changes in cell population size to be used mainly in cancer research. Cumulative population doubling (CPD) graphs based on cell counting for in vitro or tumor volume for in vivo assays were used to calculate four parameters: relative end CPD (RendCPD), to quantify the end point analysis of proliferation; relative area under curve (rAUC), to describe the global chronic effect of a treatment; relative time to cross a threshold (RTCT), to indicate the delay in cell population recovery produced by a treatment; and relative proliferation rate (RPR), to describe the relative regrowth velocity of the cells that survived after treatment. These parameters describe not only the acute and chronic effects of a treatment but also the behavior of cells that are not eliminated by the treatment, providing crucial information about the growth kinetic of the surviving population. Moreover, the proposed analysis allowed the grouping of independent CPD experiments quantified at different time points and even the direct comparison of in vitro and in vivo experiments. Therefore, this new way to analyze long-term outcomes provides a global view of the effectiveness of an intervention, as an important tool for long-term studies.
authors.affiliation: Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Silva
authors.affiliation: Department of Clinical Analysis, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.
authors.forename: Karina B
authors.initials: KB
authors.lastname: Felipe
authors.affiliation: Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Emilly S
authors.initials: ES
authors.lastname: Villodre
authors.affiliation: Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Patricia L C
authors.initials: PL
authors.lastname: Lopez
authors.affiliation: Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. lenz@ufrgs.br.|Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. lenz@ufrgs.br.|Department of Biophysics, Building 43431 Lab. 115, Bento Gonçalves avenue, 9500, Porto Alegre, RS, 91501-970, Brazil. lenz@ufrgs.br.
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D049109:Cell Proliferation / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology*; D017408:Guidelines as Topic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008962:Models, Theoretical; D013997:Time Factors; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer resistance; Cell proliferation; Cell regrowth; Chronic effects; Cumulative population doubling; Long-term analysis