In a series of publications a special, tetraploid diplochromosomal division system to only two types of progeny cells (4n/4C/G1 and 2n/4C para-diploid) has been suggested to initiate preneoplasia that can lead to a ca...In a series of publications a special, tetraploid diplochromosomal division system to only two types of progeny cells (4n/4C/G1 and 2n/4C para-diploid) has been suggested to initiate preneoplasia that can lead to a cancerous pathway. Colorectal and other preneoplasia are known with the pathogenic, histological phases of hyperplasia to arrested adenoma/nevi that can give rise to dysplasia with high risk for cancer development. The present theme is to find solutions to tumorigenic unsolved, biological problems (queries), explainable from the tetraploid 4n-system, which would support its operation in the cancerous pathway. Presently admitted, the mutational sequencing of the cancer genome (cancer chemistry) cannot discover so-called “dark matter”, which herein is considered to be the queries. The solutions from the 4n-system were largely supported by mutated APC-induced same type of tetraploidy from the mitotic slippage process. But importantly, these behaviors and consequences could be linked to the beginning of hyperplastic lesions and their development to the arrest-phase of preneoplasia (polyps/nevi). Function of HFSMs is mostly unknown, but for Barrett’s esophagus, HFSMs (p53, p16ink4a) caused inactivation of the Rb gene, leading to dysplasia with 4n, aneuploid, abnormal cell cycles. In vitro models of the 4n-system from normal human cells recapitulated preneoplasia-like histopathological changes. It was speculated that the “cancer-crucial” step to dysplasia could be therapy-vulnerable to CRISPR-caspase editing, and perhaps antibody treatment. Additionally, the 4n-system with spontaneous cell-behaviors together with preneoplasia molecular data promises construction of a more truthful cancer-paradigm than from sequencing data alone.展开更多
文摘In a series of publications a special, tetraploid diplochromosomal division system to only two types of progeny cells (4n/4C/G1 and 2n/4C para-diploid) has been suggested to initiate preneoplasia that can lead to a cancerous pathway. Colorectal and other preneoplasia are known with the pathogenic, histological phases of hyperplasia to arrested adenoma/nevi that can give rise to dysplasia with high risk for cancer development. The present theme is to find solutions to tumorigenic unsolved, biological problems (queries), explainable from the tetraploid 4n-system, which would support its operation in the cancerous pathway. Presently admitted, the mutational sequencing of the cancer genome (cancer chemistry) cannot discover so-called “dark matter”, which herein is considered to be the queries. The solutions from the 4n-system were largely supported by mutated APC-induced same type of tetraploidy from the mitotic slippage process. But importantly, these behaviors and consequences could be linked to the beginning of hyperplastic lesions and their development to the arrest-phase of preneoplasia (polyps/nevi). Function of HFSMs is mostly unknown, but for Barrett’s esophagus, HFSMs (p53, p16ink4a) caused inactivation of the Rb gene, leading to dysplasia with 4n, aneuploid, abnormal cell cycles. In vitro models of the 4n-system from normal human cells recapitulated preneoplasia-like histopathological changes. It was speculated that the “cancer-crucial” step to dysplasia could be therapy-vulnerable to CRISPR-caspase editing, and perhaps antibody treatment. Additionally, the 4n-system with spontaneous cell-behaviors together with preneoplasia molecular data promises construction of a more truthful cancer-paradigm than from sequencing data alone.
