Wound Healing Is a First Response in a Cancerous Pathway: Hyperplasia Developments to 4n Cell Cycling in Dysplasia Linked to Rb-Inactivation  

作　　者：Kirsten H. Walen 

机构地区：[1]Cromos, Richmond, USA

出　　处：《Journal of Cancer Therapy》2015年第10期906-916,共11页癌症治疗（英文）

摘　　要：In a series of publications, the hypothesis of a special-type of endo-polyploidy, marked by 4-chromatid chromosomes (diplochromosomes), in the initiation of tumorigenesis has been presented from in vitro experiments. This review uses cellular happenings in benign pre-neoplasia to substantiate this idea, which appears to be linked to the wound-healing process of injured tissue. Rarer association between a wound healing process and a cancer occurrence has long been known. The wound healing multi-program-system involved a phase of tetraploidy that showed diplochromosomes. The hypothesis is that the inflammatory phase may not always be sufficient in getting rid of dead and damaged cells (by apoptosis and autophagy), such that cells with genomic damage (DNA breakage) may survive by genomic repair associated with change to diplochromosomal tetraploidy. In vitro data have shown division of these cells to be an orderly, mechanistic two-step, meiotic-like system, resulting in only two types of progeny cells: 4n/4C/G1 and 2n/2C/G1 pseudo-diploid cells with hyperplastic-like growth-morphology. In vivo damage to tissues can be from many sources for example, physical, toxic environment or from a disease as in Barrett’s esophagus (BE) with acid reflux into the esophagus. For this condition, it is acknowledged that damage of the esophagus lining is a pre-condition to hyperplastic lesions of pre-neoplasia. These initial lesions were from “diploid” propagating cells and, 4n cells with G2 genomic content (no mitosis) accumulated in these lesions before a change to dysplasia. Cell cycle kinetics put these 4n cells in G1, which with S-phase entry would lead to asymmetric tetraploid mitoses, characteristic for dysplastic lesions. This change in hyperplasia to dysplasia is the root-essential condition for a potential progression of pre-neoplasia to cancer. In BE the hyperplastic lesion showed increasing gains of cells with inactivated p53 and p16[ink4a] genes, which destroyed the retinoblastoma (Rb) protein-control over S-phase In a series of publications, the hypothesis of a special-type of endo-polyploidy, marked by 4-chromatid chromosomes (diplochromosomes), in the initiation of tumorigenesis has been presented from in vitro experiments. This review uses cellular happenings in benign pre-neoplasia to substantiate this idea, which appears to be linked to the wound-healing process of injured tissue. Rarer association between a wound healing process and a cancer occurrence has long been known. The wound healing multi-program-system involved a phase of tetraploidy that showed diplochromosomes. The hypothesis is that the inflammatory phase may not always be sufficient in getting rid of dead and damaged cells (by apoptosis and autophagy), such that cells with genomic damage (DNA breakage) may survive by genomic repair associated with change to diplochromosomal tetraploidy. In vitro data have shown division of these cells to be an orderly, mechanistic two-step, meiotic-like system, resulting in only two types of progeny cells: 4n/4C/G1 and 2n/2C/G1 pseudo-diploid cells with hyperplastic-like growth-morphology. In vivo damage to tissues can be from many sources for example, physical, toxic environment or from a disease as in Barrett’s esophagus (BE) with acid reflux into the esophagus. For this condition, it is acknowledged that damage of the esophagus lining is a pre-condition to hyperplastic lesions of pre-neoplasia. These initial lesions were from “diploid” propagating cells and, 4n cells with G2 genomic content (no mitosis) accumulated in these lesions before a change to dysplasia. Cell cycle kinetics put these 4n cells in G1, which with S-phase entry would lead to asymmetric tetraploid mitoses, characteristic for dysplastic lesions. This change in hyperplasia to dysplasia is the root-essential condition for a potential progression of pre-neoplasia to cancer. In BE the hyperplastic lesion showed increasing gains of cells with inactivated p53 and p16[ink4a] genes, which destroyed the retinoblastoma (Rb) protein-control over S-phase

关 键 词：MITOTIC SLIPPAGE Endotetraploidization Diplochromosomes Meiotic-Like Division 4n/4C/G1 PROGENY PROLIFERATIVE Advantage INACTIVATED p53 p16[ink4a] 

分 类 号：R73[医药卫生—肿瘤]