AIM: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer. METHODS: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochem...AIM: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer. METHODS: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochemistry in pancreatic cancer and chronic pancreatitis samples. Enzyme-linked immunosorbent assay was used to detect the serum IL-8 levels in pancreatic cancer patients. Human pancreatic cancer tissues were heterotopically transplanted to the immune-deficiency mice to evaluate the effect of serum IL-8 on the tumorigenesis of the cancer samples.RESULTS: IL-8 and CXCR1 proteins were both overexpressed in pancreatic adenocarcinoma samples (55.6% and 65.4%, respectively) compared with the matched para-cancer tissues (25.9% and 12.3%, P < 0.01), or chronic pancreatitis (0% and 25%, P < 0.05). Serum IL-8 levels in pancreatic cancer patients (271.1 ± 187.7 ng/mL) were higher than in other digestive system tumors, such as gastric cancer (41.77 ± 9.11 ng/mL, P = 0.025), colorectal carcinoma (78.72 ± 80.60 ng/mL, P = 0.032) and hepatocellular carcinoma (59.60 ± 19.80 ng/mL, P = 0.016). In vivo tumorigenesis analysis further proved that tumor tissues from patients with higher serum IL-8 levels grew faster than those with lower IL-8 levels. CONCLUSION: IL-8 can be a fine serum marker for predicting the prognosis pancreatic cancer.展开更多
Drug metabolism as a discipline plays an important role in drug discovery and development and the effects of drug metabolism on pharmacokinetics(PK), pharmacodynamics(PD), and safety should be carefully considered. Th...Drug metabolism as a discipline plays an important role in drug discovery and development and the effects of drug metabolism on pharmacokinetics(PK), pharmacodynamics(PD), and safety should be carefully considered. This communication provides an overview of common strategies in the area of drug metabolism for improving PK/PD and safety profiles of drug candidates; these include, but are not limited to, collaboration with medicinal chemists on structure–activity relationships(SAR) to overcome high clearance, using deuterium replacement to further optimize a lead, prodrug approaches to circumvent formulation and delivery difficulties, and addressing issues such as species differences in metabolism,drug–drug interactions(DDI) and formation of reactive metabolites.展开更多
Cancer stem cells(CSCs)have received considerable attention from the research community since they were first reported in human acute myeloid leukemia 15 years ago.Accumulating evidence suggests that CSCs are responsi...Cancer stem cells(CSCs)have received considerable attention from the research community since they were first reported in human acute myeloid leukemia 15 years ago.Accumulating evidence suggests that CSCs are responsible for tumor initiation and progression,drug resistance,and metastasis in both liquid and solid tumors.These findings lead to the development of novel compounds targeting CSC populations that is becoming increasingly important for eradicating CSCs in heterogeneous tumor masses and to cure the cancer.Since 2003,we have participated in CSC studies and encountered crucial early events in the field.This article reviews the history of CSC biology,clarifies the term and its definition,and further addresses the issue of how to utilize CSCs in therapeutic target discovery and drug development based on our substantial experience.展开更多
基金Supported by The National Key Project of Scientific and Technical Supporting Programs of China, No. 2006BAI02A14National Natural Science Foundation of China, No. 30770996 and No. 30901776
文摘AIM: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer. METHODS: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochemistry in pancreatic cancer and chronic pancreatitis samples. Enzyme-linked immunosorbent assay was used to detect the serum IL-8 levels in pancreatic cancer patients. Human pancreatic cancer tissues were heterotopically transplanted to the immune-deficiency mice to evaluate the effect of serum IL-8 on the tumorigenesis of the cancer samples.RESULTS: IL-8 and CXCR1 proteins were both overexpressed in pancreatic adenocarcinoma samples (55.6% and 65.4%, respectively) compared with the matched para-cancer tissues (25.9% and 12.3%, P < 0.01), or chronic pancreatitis (0% and 25%, P < 0.05). Serum IL-8 levels in pancreatic cancer patients (271.1 ± 187.7 ng/mL) were higher than in other digestive system tumors, such as gastric cancer (41.77 ± 9.11 ng/mL, P = 0.025), colorectal carcinoma (78.72 ± 80.60 ng/mL, P = 0.032) and hepatocellular carcinoma (59.60 ± 19.80 ng/mL, P = 0.016). In vivo tumorigenesis analysis further proved that tumor tissues from patients with higher serum IL-8 levels grew faster than those with lower IL-8 levels. CONCLUSION: IL-8 can be a fine serum marker for predicting the prognosis pancreatic cancer.
文摘Drug metabolism as a discipline plays an important role in drug discovery and development and the effects of drug metabolism on pharmacokinetics(PK), pharmacodynamics(PD), and safety should be carefully considered. This communication provides an overview of common strategies in the area of drug metabolism for improving PK/PD and safety profiles of drug candidates; these include, but are not limited to, collaboration with medicinal chemists on structure–activity relationships(SAR) to overcome high clearance, using deuterium replacement to further optimize a lead, prodrug approaches to circumvent formulation and delivery difficulties, and addressing issues such as species differences in metabolism,drug–drug interactions(DDI) and formation of reactive metabolites.
文摘Cancer stem cells(CSCs)have received considerable attention from the research community since they were first reported in human acute myeloid leukemia 15 years ago.Accumulating evidence suggests that CSCs are responsible for tumor initiation and progression,drug resistance,and metastasis in both liquid and solid tumors.These findings lead to the development of novel compounds targeting CSC populations that is becoming increasingly important for eradicating CSCs in heterogeneous tumor masses and to cure the cancer.Since 2003,we have participated in CSC studies and encountered crucial early events in the field.This article reviews the history of CSC biology,clarifies the term and its definition,and further addresses the issue of how to utilize CSCs in therapeutic target discovery and drug development based on our substantial experience.
