Emerging cohorts and basic studies have associated certain genetic modifications in cancer patients,such as gene mutation,amplification,or deletion,with the overall survival prognosis,underscoring patients’genetic ba...Emerging cohorts and basic studies have associated certain genetic modifications in cancer patients,such as gene mutation,amplification,or deletion,with the overall survival prognosis,underscoring patients’genetic background may directly regulate drug sensitivity/resistance during chemotherapies.Understanding the molecular mechanism underpinning drug sensitivity/resistance and further uncovering the effective drugs have been the major ambition in the cancer drug discovery.The emergence and popularity of CRISPR/Cas9 technology have reformed the entire life science research,providing a precise and simplified genome editing tool with unlimited editing possibilities.Furthermore,it presents a powerful tool in cancer drug discovery,which hopefully facilitates us with a rapid and reliable manner in developing novel therapies and understanding the molecular mechanisms of drug sensitivity/resistance.Herein,we summarized the application of CRISPR/Cas9 in drug screening,with the focus on CRISPR/Cas9 mediated gene knockout,gene knock-in,as well as transcriptional modification.Additionally,this review provides the concerns,cautions,and ethnic considerations that need to be taken when applying CRISPR in the drug discovery.展开更多
Objective To examine insulin resistance and high sensitivity C-reactive protein （hsCRP） association with clinical and angiographic severity of coronary artery disease （CAD） in patients with normal glucose toleranc...Objective To examine insulin resistance and high sensitivity C-reactive protein （hsCRP） association with clinical and angiographic severity of coronary artery disease （CAD） in patients with normal glucose tolerance. Methods In 638 consecutive patients with normal glucose tolerance, 221 had atypical chest pain and normal coronary artery （control group）, 279 had stable angina and CAD （SAP group ）, and 138 suffered acute myocardial infarction （ MI group）. The degree of CAD was further divided into borderline lesion （ lumen diameter narrowing 50% - 69% ）, significant 1-, 2- or 3-vessel disease （ luminal diameter narrowing 〉I 70% ）. Fasting serum glucose, insulin and hsCRP levels and lipid profiles were measured, and homeostasis model assessment for insulin resistance （ HOMA-IR ） was calculated. Multivariate analysis was performed to assess risk factors for 3-vessel disease or acute MI. Results Serum hsCRP, lipoprotein （a） levels, and insulin resistance index （IRI） were higher in AMI group than those in SAP and control groups. Serum hsCRP level and IRI were also higher in 3-vessel disease than those in other groups. Multivariate regression analysis revealed that insulin resistance, cigarette smoking, serum hsCRP, and lipoprotein （a） levels were independent risk factors for acute MI. Lipoprotein （ a ） elevation was an independent risk factor for 3-vessel disease. Conclusion Insulin resistance and high serum hsCRP level were associated with occurrence of acute MI and angiographic severity of coronary disease in patients with normal glucose tolerance.展开更多
基金This work was supported by the Start-Up funding from Anhui Medical University(KZ 0801033201),and the Doctoral Research Funding from the Cancer Society of Finland(KZ).
文摘Emerging cohorts and basic studies have associated certain genetic modifications in cancer patients,such as gene mutation,amplification,or deletion,with the overall survival prognosis,underscoring patients’genetic background may directly regulate drug sensitivity/resistance during chemotherapies.Understanding the molecular mechanism underpinning drug sensitivity/resistance and further uncovering the effective drugs have been the major ambition in the cancer drug discovery.The emergence and popularity of CRISPR/Cas9 technology have reformed the entire life science research,providing a precise and simplified genome editing tool with unlimited editing possibilities.Furthermore,it presents a powerful tool in cancer drug discovery,which hopefully facilitates us with a rapid and reliable manner in developing novel therapies and understanding the molecular mechanisms of drug sensitivity/resistance.Herein,we summarized the application of CRISPR/Cas9 in drug screening,with the focus on CRISPR/Cas9 mediated gene knockout,gene knock-in,as well as transcriptional modification.Additionally,this review provides the concerns,cautions,and ethnic considerations that need to be taken when applying CRISPR in the drug discovery.
文摘Objective To examine insulin resistance and high sensitivity C-reactive protein （hsCRP） association with clinical and angiographic severity of coronary artery disease （CAD） in patients with normal glucose tolerance. Methods In 638 consecutive patients with normal glucose tolerance, 221 had atypical chest pain and normal coronary artery （control group）, 279 had stable angina and CAD （SAP group ）, and 138 suffered acute myocardial infarction （ MI group）. The degree of CAD was further divided into borderline lesion （ lumen diameter narrowing 50% - 69% ）, significant 1-, 2- or 3-vessel disease （ luminal diameter narrowing 〉I 70% ）. Fasting serum glucose, insulin and hsCRP levels and lipid profiles were measured, and homeostasis model assessment for insulin resistance （ HOMA-IR ） was calculated. Multivariate analysis was performed to assess risk factors for 3-vessel disease or acute MI. Results Serum hsCRP, lipoprotein （a） levels, and insulin resistance index （IRI） were higher in AMI group than those in SAP and control groups. Serum hsCRP level and IRI were also higher in 3-vessel disease than those in other groups. Multivariate regression analysis revealed that insulin resistance, cigarette smoking, serum hsCRP, and lipoprotein （a） levels were independent risk factors for acute MI. Lipoprotein （ a ） elevation was an independent risk factor for 3-vessel disease. Conclusion Insulin resistance and high serum hsCRP level were associated with occurrence of acute MI and angiographic severity of coronary disease in patients with normal glucose tolerance.
