Purpose Both oncogenic viruses and cell cycle control proteins are fast growth research areas. More and more evidence indicates that virus infection and replication are often associated with apoptosis and interfer...Purpose Both oncogenic viruses and cell cycle control proteins are fast growth research areas. More and more evidence indicates that virus infection and replication are often associated with apoptosis and interfere with cell cycle pathways. To understand the mechanisms by which viral proteins regulate apoptosis and target the cellular pathways may lead to the development of new remedies for some cancers.Data sources English literature searched by MEDLINE from January 1995 to August 1998.Study selection and data extraction More than one hundred research papers published in these areas over the past three years. Only new and important breakthroughs in these papers are selected. The review focuses on DNA viruses associated with the development of human cancers.Results and conclusions Some DNA viruses contain oncogenic proteins which transform normal cells in vitro and induce tumors in animals. These viral proteins target the cellular pathways and block apoptosis induced by receptors or in response to signal transduction. Viral interference with host cell apoptosis leads to enhanced viral replication and may promote carcinogenesis. Oncogenes and tumor suppressor genes, such as Retinoblastoma (RB) and p53, play important roles in regulation of these interactions.展开更多
The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. F...The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair. The NBS1 protein is a component of the MRE11/RAD50/NBS 1 complex （MRN） that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity. Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome （NBS）, a hereditary disorder that imparts an increased predisposition to development of malignancy. The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks. Here, we review the current knowledge of the role of NBS1 in the DNA damage response. Emphasis is placed on the role of NBS1 in the DNA double strand repair, modulation of the DNA damage sensing and signaling, cell cycle checkpoint control and maintenance oftelomere stability.展开更多
Colorectal cancer (CRC) has an apparent hereditary component, as evidenced by the well-characterized genetic syndromes and family history associated with the increased risk of this disease. However, in a large fractio...Colorectal cancer (CRC) has an apparent hereditary component, as evidenced by the well-characterized genetic syndromes and family history associated with the increased risk of this disease. However, in a large fraction of CRC cases, no known genetic syndrome or family history can be identified, suggesting the presence of “missing heritability” in CRC etiology. The genome-wide association study (GWAS) platform has led to the identification of multiple replicable common genetic variants associated with CRC risk. These newly discovered genetic variations might account for a portion of the missing heritability. Here, we summarize the recent GWASs related to newly identified genetic variants associated with CRC risk and clinical outcome. The findings from these studies suggest that there is a lack of understanding of the mechanism of many single nucleotide polymorphisms (SNPs) that are associated with CRC. In addition, the utility of SNPs as prognostic markers of CRC in clinical settings remains to be further assessed. Finally, the currently validated SNPs explain only a small fraction of total heritability in complex-trait diseases like CRC. Thus, the “missing heritability” still needs to be explored further. Future epidemiological and functional investigations of these variants will add to our understanding of CRC pathogenesis, and may ultimately lead to individualized strategies for prevention and treatment of CRC.展开更多
文摘Purpose Both oncogenic viruses and cell cycle control proteins are fast growth research areas. More and more evidence indicates that virus infection and replication are often associated with apoptosis and interfere with cell cycle pathways. To understand the mechanisms by which viral proteins regulate apoptosis and target the cellular pathways may lead to the development of new remedies for some cancers.Data sources English literature searched by MEDLINE from January 1995 to August 1998.Study selection and data extraction More than one hundred research papers published in these areas over the past three years. Only new and important breakthroughs in these papers are selected. The review focuses on DNA viruses associated with the development of human cancers.Results and conclusions Some DNA viruses contain oncogenic proteins which transform normal cells in vitro and induce tumors in animals. These viral proteins target the cellular pathways and block apoptosis induced by receptors or in response to signal transduction. Viral interference with host cell apoptosis leads to enhanced viral replication and may promote carcinogenesis. Oncogenes and tumor suppressor genes, such as Retinoblastoma (RB) and p53, play important roles in regulation of these interactions.
文摘The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair. The NBS1 protein is a component of the MRE11/RAD50/NBS 1 complex （MRN） that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity. Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome （NBS）, a hereditary disorder that imparts an increased predisposition to development of malignancy. The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks. Here, we review the current knowledge of the role of NBS1 in the DNA damage response. Emphasis is placed on the role of NBS1 in the DNA double strand repair, modulation of the DNA damage sensing and signaling, cell cycle checkpoint control and maintenance oftelomere stability.
基金Supported by A start-up grant from Thomas Jefferson Universityand National Cancer Institute Grant,CA162201
文摘Colorectal cancer (CRC) has an apparent hereditary component, as evidenced by the well-characterized genetic syndromes and family history associated with the increased risk of this disease. However, in a large fraction of CRC cases, no known genetic syndrome or family history can be identified, suggesting the presence of “missing heritability” in CRC etiology. The genome-wide association study (GWAS) platform has led to the identification of multiple replicable common genetic variants associated with CRC risk. These newly discovered genetic variations might account for a portion of the missing heritability. Here, we summarize the recent GWASs related to newly identified genetic variants associated with CRC risk and clinical outcome. The findings from these studies suggest that there is a lack of understanding of the mechanism of many single nucleotide polymorphisms (SNPs) that are associated with CRC. In addition, the utility of SNPs as prognostic markers of CRC in clinical settings remains to be further assessed. Finally, the currently validated SNPs explain only a small fraction of total heritability in complex-trait diseases like CRC. Thus, the “missing heritability” still needs to be explored further. Future epidemiological and functional investigations of these variants will add to our understanding of CRC pathogenesis, and may ultimately lead to individualized strategies for prevention and treatment of CRC.
