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
The extent and aggression of colorectal cancer is a worldwide public health threat.Extensive research has been conducted on the pre-requisites leading to this fatal cancer.An array of genes along with their mutations ...The extent and aggression of colorectal cancer is a worldwide public health threat.Extensive research has been conducted on the pre-requisites leading to this fatal cancer.An array of genes along with their mutations and the signal transduction pathways leading to the cellular transformation into the cancerous cells have been investigated.Based on the knowledge gained so far,present review shortly discussed the role of the major genes especially those are involved in instigating abnormalities in the cellular cycles,cellular proliferation and differentiation.A simple but novel molecular scheme of the colorectal cancer development has also been plotted.展开更多
Gout is an independent risk factor for hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease and cerebral infarction.At present,the studies on the mechanism of gout at home and abroad have mainly focuse...Gout is an independent risk factor for hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease and cerebral infarction.At present,the studies on the mechanism of gout at home and abroad have mainly focused on immune inflammation,gene polymorphism and related studies.Uric acid deposition or crystal precipitation activates phagocytes,fibroblasts and mast cells in synovium,produces IL-1β,TNF and chemokine IL-8(CXCL8),thereby activating neutrophils,urate crystal polyanion surface can be coated with immunoglobulins and other serum proteins as substrates for complement activation,complement substitution pathways and classical complement pathways to activate complements.Uric acid crystals activate inflammation-related signal transduction pathways including the activation of inflammation-related signal transduction pathway by uric acid crystals and TLRS/MyD88 signal transduction pathways.Gene polymorphism is related to inflammation and signaling pathway,EGF gene is closely related to gout inflammation,which may be involved in the regulation of gout inflammation,among which NLRP3 inflammatory signaling pathway and gene polymorphism have been deeply studied in the pathogenesis of gout,which is the main therapeutic target of anti-inflammatory and uric acid lowering.展开更多
Chemotherapy is one of the important methods to treat cancer,and the emergence of multidrug resistance(MDR)is one major cause for the failure of cancer chemotherapy.Almost all anti-tumor drugs develop drug resistance ...Chemotherapy is one of the important methods to treat cancer,and the emergence of multidrug resistance(MDR)is one major cause for the failure of cancer chemotherapy.Almost all anti-tumor drugs develop drug resistance over a period of time of application in cancer patients,reducing their effects on killing cancer cells.Chemoresistance can lead to a rapid recurrence of cancers and ultimately patient death.MDR may be induced by multiple mechanisms,which are associated with a complex process of multiple genes,factors,pathways,and multiple steps,and today the MDR-associated mechanisms are largely unknown.In this paper,from the aspects of protein–protein interactions,alternative splicing(AS)in pre-mRNA,non-coding RNA(ncRNA)mediation,genome mutations,variance in cell functions,and influence from the tumor microenvironment,we summarize the molecular mechanisms associated with MDR in cancers.In the end,prospects for the exploration of antitumor drugs that can reverse MDR are briefly discussed from the angle of drug systems with improved targeting properties,biocompatibility,availability,and other advantages.展开更多
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.
文摘The extent and aggression of colorectal cancer is a worldwide public health threat.Extensive research has been conducted on the pre-requisites leading to this fatal cancer.An array of genes along with their mutations and the signal transduction pathways leading to the cellular transformation into the cancerous cells have been investigated.Based on the knowledge gained so far,present review shortly discussed the role of the major genes especially those are involved in instigating abnormalities in the cellular cycles,cellular proliferation and differentiation.A simple but novel molecular scheme of the colorectal cancer development has also been plotted.
基金Supported by Six Peak Talents Projects in Jiangsu Province on Clinical Application of HuRAT1 Combined with ABCG2 Gene Detection in Predicting Hyperuricemia/Gout Susceptibility(2015-WSN-089)Research Projects of Traditional Chinese Medicine of Wuxi Municipal Health Commission on Mechanisms of Bixie Drink on Neutrophils and Inflammatory Signal Transduction Pathway of NLRP3 in Gout Model Rats(ZYZL201803).
文摘Gout is an independent risk factor for hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease and cerebral infarction.At present,the studies on the mechanism of gout at home and abroad have mainly focused on immune inflammation,gene polymorphism and related studies.Uric acid deposition or crystal precipitation activates phagocytes,fibroblasts and mast cells in synovium,produces IL-1β,TNF and chemokine IL-8(CXCL8),thereby activating neutrophils,urate crystal polyanion surface can be coated with immunoglobulins and other serum proteins as substrates for complement activation,complement substitution pathways and classical complement pathways to activate complements.Uric acid crystals activate inflammation-related signal transduction pathways including the activation of inflammation-related signal transduction pathway by uric acid crystals and TLRS/MyD88 signal transduction pathways.Gene polymorphism is related to inflammation and signaling pathway,EGF gene is closely related to gout inflammation,which may be involved in the regulation of gout inflammation,among which NLRP3 inflammatory signaling pathway and gene polymorphism have been deeply studied in the pathogenesis of gout,which is the main therapeutic target of anti-inflammatory and uric acid lowering.
基金the National Natural Science Foundation of China(21877113,81971983)the Natural Science Foundation of Fujian Province(2020I0036,China).
文摘Chemotherapy is one of the important methods to treat cancer,and the emergence of multidrug resistance(MDR)is one major cause for the failure of cancer chemotherapy.Almost all anti-tumor drugs develop drug resistance over a period of time of application in cancer patients,reducing their effects on killing cancer cells.Chemoresistance can lead to a rapid recurrence of cancers and ultimately patient death.MDR may be induced by multiple mechanisms,which are associated with a complex process of multiple genes,factors,pathways,and multiple steps,and today the MDR-associated mechanisms are largely unknown.In this paper,from the aspects of protein–protein interactions,alternative splicing(AS)in pre-mRNA,non-coding RNA(ncRNA)mediation,genome mutations,variance in cell functions,and influence from the tumor microenvironment,we summarize the molecular mechanisms associated with MDR in cancers.In the end,prospects for the exploration of antitumor drugs that can reverse MDR are briefly discussed from the angle of drug systems with improved targeting properties,biocompatibility,availability,and other advantages.
