Limits...
A framework for the in vitro evaluation of cancer-relevant molecular characteristics and mitogenic potency of insulin analogues.

Baricevic I, Jones DR, Roberts DL, Lutzen A, Lundby A, Worm J, Hansen BF, Renehan AG - Carcinogenesis (2015)

Bottom Line: Accordingly, there is a regulatory mandate for cancer-related pre-clinical safety evaluation during insulin analogue development, but currently, there is no standardized framework for such in vitro evaluation.The meta-analysis, adding data from five additional studies, supported the hypothesis that ligand mitogenic potency, relative to human insulin, increases with increasing cell-specific IGF-IR/IR ratio.This study established a framework for the in vitro evaluation of cancer-relevant bioassays for comparisons of insulin analogues, and specifically consolidated earlier studies that determination of the cell-specific IGF-IR/IR ratio is crucial for the interpretation of ranking relative biological activities.

View Article: PubMed Central - PubMed

Affiliation: Faculty Institute of Cancer Sciences, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK, Inositide Laboratory, Cancer Research UK Manchester Institute, Paterson Building, Manchester M20 4BX, UK and Diabetes Research Unit, Novo Nordisk A/S, Måløv, Denmark.

Show MeSH

Related in: MedlinePlus

Patterns of IR and IGF-IR expression in 17 human colonic adenocarcinomas (serial sections) (a). Quantification of immune expression of IR and IGF-IR using Definiens software (b). The expression of IGF-IR is relatively constant in the tumours, but the variation in the IGF-IR/IR ratio is mainly attributed to the variation in IR expression.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4552242&req=5

Figure 2: Patterns of IR and IGF-IR expression in 17 human colonic adenocarcinomas (serial sections) (a). Quantification of immune expression of IR and IGF-IR using Definiens software (b). The expression of IGF-IR is relatively constant in the tumours, but the variation in the IGF-IR/IR ratio is mainly attributed to the variation in IR expression.

Mentions: The immunohistochemical expressions of IR and IGF-IR in 17 colonic adenocarcinomas are shown in Figure 2. Three patterns emerged—low IR: high IGF-IR, medium IR: high IGF-IR and high IR: high IGF-IR. Quantification of the immune-expressions, using Definiens software, showed that the expression of IGF-IR is relatively constant across colonic adeocarcinomas, but the variation in the IGF-IR/IR ratio is attributed to varying expressions of IR.


A framework for the in vitro evaluation of cancer-relevant molecular characteristics and mitogenic potency of insulin analogues.

Baricevic I, Jones DR, Roberts DL, Lutzen A, Lundby A, Worm J, Hansen BF, Renehan AG - Carcinogenesis (2015)

Patterns of IR and IGF-IR expression in 17 human colonic adenocarcinomas (serial sections) (a). Quantification of immune expression of IR and IGF-IR using Definiens software (b). The expression of IGF-IR is relatively constant in the tumours, but the variation in the IGF-IR/IR ratio is mainly attributed to the variation in IR expression.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4552242&req=5

Figure 2: Patterns of IR and IGF-IR expression in 17 human colonic adenocarcinomas (serial sections) (a). Quantification of immune expression of IR and IGF-IR using Definiens software (b). The expression of IGF-IR is relatively constant in the tumours, but the variation in the IGF-IR/IR ratio is mainly attributed to the variation in IR expression.
Mentions: The immunohistochemical expressions of IR and IGF-IR in 17 colonic adenocarcinomas are shown in Figure 2. Three patterns emerged—low IR: high IGF-IR, medium IR: high IGF-IR and high IR: high IGF-IR. Quantification of the immune-expressions, using Definiens software, showed that the expression of IGF-IR is relatively constant across colonic adeocarcinomas, but the variation in the IGF-IR/IR ratio is attributed to varying expressions of IR.

Bottom Line: Accordingly, there is a regulatory mandate for cancer-related pre-clinical safety evaluation during insulin analogue development, but currently, there is no standardized framework for such in vitro evaluation.The meta-analysis, adding data from five additional studies, supported the hypothesis that ligand mitogenic potency, relative to human insulin, increases with increasing cell-specific IGF-IR/IR ratio.This study established a framework for the in vitro evaluation of cancer-relevant bioassays for comparisons of insulin analogues, and specifically consolidated earlier studies that determination of the cell-specific IGF-IR/IR ratio is crucial for the interpretation of ranking relative biological activities.

View Article: PubMed Central - PubMed

Affiliation: Faculty Institute of Cancer Sciences, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK, Inositide Laboratory, Cancer Research UK Manchester Institute, Paterson Building, Manchester M20 4BX, UK and Diabetes Research Unit, Novo Nordisk A/S, Måløv, Denmark.

Show MeSH
Related in: MedlinePlus