BACKGROUND： Pancreatic cancer（PC） is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Rec...BACKGROUND： Pancreatic cancer（PC） is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identified groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecular mechanisms of PC metastasis.DATA SOURCES： Relevant articles on PC metastasis were searched in MEDLINE via Pub Med prior to April 2015. The search was limited in English publications.RESULTS： PC metastatic cascades are multi-factorial events including both intrinsic and extrinsic elements. This review highlights the most important genetic alterations and other mechanisms that account for PC invasion and metastasis, with particular regard to epithelial-mesenchymal transition, inflammation, stress response, and circulating tumor cells.CONCLUSIONS： Analyses of relevant gene functions and signaling pathways are needed to establish the gene regulatory network and to define the pivotal modulators. Another promising area of study is the genotyping and phenotyping of circulating tumor cells, which could lead to a new era of personalized therapy by identifying specific markers and targets.展开更多
Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal malignancies with a five-year survival rate of approximately 5%. Several target agents have been tested in PDAC, but almost all have failed to demonstra...Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal malignancies with a five-year survival rate of approximately 5%. Several target agents have been tested in PDAC, but almost all have failed to demonstrate efficacy in late phase clinical trials, despite the better understanding of PDAC molecular biology generated by large cancer sequencing initiatives in the past decade. Eroltinib(a small-molecule tyrosine-kinase inhibitor of epidermal growth factor receptor) plus gemcitabine is the only schedule with a biological agent approved for advanced pancreatic cancer, but it has resulted in a very modest survival benefit in unselected patients. In our work, we report a summary of the main clinical trials(closed and ongoing) that refer to biological therapy evaluation in pancreatic cancer treatment.展开更多
Lobetyolin(LBT)is a polyacetylene glycoside found in diverse medicinal plants but mainly isolated from the roots of Codo-nopsis pilosula,known as Radix Codonopsis or Dangshen.Twelve traditional Chinese medicinal prepa...Lobetyolin(LBT)is a polyacetylene glycoside found in diverse medicinal plants but mainly isolated from the roots of Codo-nopsis pilosula,known as Radix Codonopsis or Dangshen.Twelve traditional Chinese medicinal preparations containing Radix Codonopsis were identified;they are generally used to tonify spleen and lung Qi and occasionally to treat cancer.Here we have reviewed the anticancer properties of Codonopsis extracts,LBT and structural analogs.Lobetyolin and lobetyolinin are the mono-and bis-glucosylated forms of the polyacetylenic compound lobetyol.Lobetyol and LBT have shown activi-ties against several types of cancer(notably gastric cancer)and we examined the molecular basis of their activity.A down-regulation of glutamine metabolism by LBT has been evidenced,contributing to drug-induced apoptosis and tumor growth inhibition.LBT markedly reduces both mRNA and protein expression of the amino acid transporter Alanine-Serine-Cysteine Transporter 2(ASCT2).Other potential targets are proposed here,based on the structural analogy with other anticancer compounds.LBT and related polyacetylene glycosides should be further considered as potential anticancer agents,but more work is needed to evaluate their efficacy,toxicity,and risk-benefit ratio.展开更多
Ferroptosis is a novel type of regulated cell death(RCD)involving iron accumulation and lipid peroxidation.Since its discovery in 2012,various studies have shown that ferroptosis is associated with the pathogenesis of...Ferroptosis is a novel type of regulated cell death(RCD)involving iron accumulation and lipid peroxidation.Since its discovery in 2012,various studies have shown that ferroptosis is associated with the pathogenesis of various diseases.Ferroptotic cell death has also been linked to intestinal dysfunction but can act as either a positive or negative regulator of intestinal disease,depending on the cell type and disease context.The continued investigation of mechanisms underlying ferroptosis provides a wealth of potential for developing novel treatments.Considering the growing prevalence of intestinal diseases,particularly colorectal cancer(CRC)and inflammatory bowel disease(IBD),this review article focuses on potential therapeutics targeting the ferroptotic pathway in relation to CRC and IBD.展开更多
基金supported by grants from the National Natural Science Foundation of China(81272767 and 81201734)
文摘BACKGROUND： Pancreatic cancer（PC） is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identified groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecular mechanisms of PC metastasis.DATA SOURCES： Relevant articles on PC metastasis were searched in MEDLINE via Pub Med prior to April 2015. The search was limited in English publications.RESULTS： PC metastatic cascades are multi-factorial events including both intrinsic and extrinsic elements. This review highlights the most important genetic alterations and other mechanisms that account for PC invasion and metastasis, with particular regard to epithelial-mesenchymal transition, inflammation, stress response, and circulating tumor cells.CONCLUSIONS： Analyses of relevant gene functions and signaling pathways are needed to establish the gene regulatory network and to define the pivotal modulators. Another promising area of study is the genotyping and phenotyping of circulating tumor cells, which could lead to a new era of personalized therapy by identifying specific markers and targets.
文摘Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal malignancies with a five-year survival rate of approximately 5%. Several target agents have been tested in PDAC, but almost all have failed to demonstrate efficacy in late phase clinical trials, despite the better understanding of PDAC molecular biology generated by large cancer sequencing initiatives in the past decade. Eroltinib(a small-molecule tyrosine-kinase inhibitor of epidermal growth factor receptor) plus gemcitabine is the only schedule with a biological agent approved for advanced pancreatic cancer, but it has resulted in a very modest survival benefit in unselected patients. In our work, we report a summary of the main clinical trials(closed and ongoing) that refer to biological therapy evaluation in pancreatic cancer treatment.
文摘Lobetyolin(LBT)is a polyacetylene glycoside found in diverse medicinal plants but mainly isolated from the roots of Codo-nopsis pilosula,known as Radix Codonopsis or Dangshen.Twelve traditional Chinese medicinal preparations containing Radix Codonopsis were identified;they are generally used to tonify spleen and lung Qi and occasionally to treat cancer.Here we have reviewed the anticancer properties of Codonopsis extracts,LBT and structural analogs.Lobetyolin and lobetyolinin are the mono-and bis-glucosylated forms of the polyacetylenic compound lobetyol.Lobetyol and LBT have shown activi-ties against several types of cancer(notably gastric cancer)and we examined the molecular basis of their activity.A down-regulation of glutamine metabolism by LBT has been evidenced,contributing to drug-induced apoptosis and tumor growth inhibition.LBT markedly reduces both mRNA and protein expression of the amino acid transporter Alanine-Serine-Cysteine Transporter 2(ASCT2).Other potential targets are proposed here,based on the structural analogy with other anticancer compounds.LBT and related polyacetylene glycosides should be further considered as potential anticancer agents,but more work is needed to evaluate their efficacy,toxicity,and risk-benefit ratio.
基金the NIGMS funded Academic Science Education and Research Training(ASERT,K12-GM088021)Program at the University of New Mexico Health Sciences CenterXiang Xue received partial funding support from the National Institutes of Health(P20 GM130422)+4 种基金a Research Scholar Grant from the American Cancer Society(RSG-18-050-01-NEC)Environmental Health and Toxicology Pilot Awards from UNM Center for Native Environmental Health Equity Research(P50 MD015706)New Mexico Integrative Science Program Incorporating Research in Environmental Sciences(NM-INSPIRES,1P30ES032755)Xiang Xue also acknowledges funding support from a Research Program Support Pilot Project Award from UNM comprehensive cancer center(P30CA118100)the Cardiovascular and Metabolic Disease Research Program Pilot Project Grant from UNMHSC Office of Research Signature Programs。
文摘Ferroptosis is a novel type of regulated cell death(RCD)involving iron accumulation and lipid peroxidation.Since its discovery in 2012,various studies have shown that ferroptosis is associated with the pathogenesis of various diseases.Ferroptotic cell death has also been linked to intestinal dysfunction but can act as either a positive or negative regulator of intestinal disease,depending on the cell type and disease context.The continued investigation of mechanisms underlying ferroptosis provides a wealth of potential for developing novel treatments.Considering the growing prevalence of intestinal diseases,particularly colorectal cancer(CRC)and inflammatory bowel disease(IBD),this review article focuses on potential therapeutics targeting the ferroptotic pathway in relation to CRC and IBD.
