ABSTRACT
Genomic reprogramming factors in the cytoplasm of germinal vesicle (GV) stage oocytes have been shown to improve the efficiency of producing cloned mouse offspring through the exposure of nuclei to a GV cytoplasmic extract prior to somatic cell nuclear transfer (SCNT) to enucleated oocytes. Here, we developed an extract of GV stage pig oocytes (GVcyto-extract) to investigate epigenetic reprogramming events in treated somatic cell nuclei. This extract induced differentiation-associated changes in fibroblasts, resulting in cells that exhibit pluripotent stem cell-like characteristics and that redifferentiate into three primary germ cell layers both in vivo and in vitro. The GVcyto-extract treatment induced large numbers of high-quality SCNT-generated blastocysts, with methylation and acetylation of H3-K9 and expression of Oct4 and Nanog at levels similar to in vitro fertilized embryos. Thus, GVcyto-extract could elicit differentiation plasticity in treated fibroblasts, and SCNT-mediated reprogramming reset the epigenetic state in treated cells more efficiently than in untreated cells. In summary, we provide evidence for the generation of stem-like cells from differentiated somatic cells by treatment with porcine GVcyto-extract.
Subject(s)
Cell Extracts/pharmacology , Cellular Reprogramming , Nuclear Transfer Techniques , Oocytes , Animals , Blastocyst/drug effects , Cell Differentiation/drug effects , Cell Nucleus/drug effects , Cell Nucleus/genetics , Cell Nucleus/metabolism , Epigenesis, Genetic , Fibroblasts/drug effects , Histones/metabolism , Homeodomain Proteins/biosynthesis , Induced Pluripotent Stem Cells , Methylation/drug effects , Octamer Transcription Factor-3/biosynthesis , Octamer Transcription Factor-3/genetics , Pluripotent Stem Cells , SwineABSTRACT
Gefitnib is an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, and it has a certain efficacy against non-small cell lung cancer. There are some reports that the non-small cell lung cancer patients who experienced disease progression after responding to gefitinib were again sensitive to re-administration of gefitinib following temporary cessation of gefitinib. This is the case report showing a remarkable effect of gefitinib re-treatment in a patient with metastatic invasive adenocarinoma who had experienced favorable results from the initial treatment with gefitinib.