Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-ki...Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways have been widely investigated. Their aberrant expression or mutation has been significantly associated with advanced stage or poor prognosis of gastric cancer. Recently, aberrations of immune checkpoints including programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) have been suggested as an important step in the formation of a microenvironment favorable for gastric cancer. Accomplishments in basic research have led to the development of novel agents targeting these signaling pathways. However, phase III studies of selective anti-HGF/c-MET antibodies and mTOR inhibitor failed to show significant benefits in terms of overall survival and progression-free survival. Few agents directly targeting STAT3 have been developed. However, this target is still critical issue in terms of chemoresistance, and SH2-containing protein tyrosine phosphatase 1 might be a significant link to effectively inhibit STAT3 activity. Inhibition of PD-1/PD-L1 showed durable efficacy in phase I studies, and phase III evaluation is warranted. Therapeutic strategy to concurrently inhibit multiple tyrosine kinases is a reasonable option, however, lapatinib needs to be further evaluated to identify good responders. Regorafenib has shown promising effectiveness in prolonging progression-free survival in a phase II study. In this topic highlight, we review the biologic roles and outcomes of clinical studies targeting these signaling pathways.展开更多
Although multiple advances have been made in systemic therapy for renal cell carcinoma(RCC),metastatic RCC remains incurable.In the current review,we focus on the underlying biology of RCC and plausible mechanisms of ...Although multiple advances have been made in systemic therapy for renal cell carcinoma(RCC),metastatic RCC remains incurable.In the current review,we focus on the underlying biology of RCC and plausible mechanisms of metastasis.We further outline evolving strategies to combat metastasis through adjuvant therapy.Finally,we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.展开更多
AIM： To study the expression level and localization of insulin-like growth factor -Ⅰ receptor （IGF-IR） in HepG2 cells and Chang liver cells, and to observe the effect of anti-IGF-IR monoclonal antibody （αIR3） o...AIM： To study the expression level and localization of insulin-like growth factor -Ⅰ receptor （IGF-IR） in HepG2 cells and Chang liver cells, and to observe the effect of anti-IGF-IR monoclonal antibody （αIR3） on the growth of HepG2 cells. METHODS： The expression of IGF-IR in HepG2 cells and Chang liver cells was detected by immunohistochemistry. The influences of αIR3 on proliferation and apoptosis were examined by the 3- （4, 5-dimethylthiazol-2-yl）-2, 5- diphenyltetrazolium bromide （MTT） assay and electron microscopy, respectively. Flow cytometry （FCM） was applied for the analysis of cell cycle and apoptosis was observed under electron microscope. RESULTS： IGF-IR was located in the membranes of both HepG2 and Chang liver cell lines, and the expression level of IGF-IR was higher in HepG2 cells than in Chang liver cells. Treated with 0.1 μg/mL αIR3 for 48 h in vitro, the cell growth index （GI） of HepG2 cells was significantly higher than that of control （103.41% ys 100%, P 〈 0.01）. However, the αIR3 for 24 h at final concentration of 4.0 μg/mL made the GI of HepG2 cells lower than that of control （93.37% vs 100%, P 〈 0.01）. Compared with control, treated with αIR3 for 48 h at final concentrations ranging from 2.0 μg/mL to 4.0 μg/mL markedly reduced the GIs of HepG2 cells （97.63%, 97.16%, 95.13%, 92.53% vs 100%, P 〈 0.05 or P 〈 0.01）, treated with αIR3 for 72 h at final concentrations ranging from 0.2 μg/mL to 4.0 μg/mL decreased the GIs of HepG2 cells obviously （95%, 91.63%, 90.77%, 89.84%, 88.51% vs 100%, P 〈 0.01）, and treated with αIR3 for 96 h at final concentrations ranging from 0.5 μg/mL to 4.0 μg/mL made GIs of HepG2 cells lower significantly （88.86%, 83.97%, 79.81%, 77.24%, 70.51% vs 100%, P 〈 0.05or P 〈 0.01）. Moreover, treated with αIR3 from 24 h to 96 h at final concentrations ranging from 0.2 μg/mL to 4.0 μg/mL reduced the GI of HepG2 cells from 97.63% to 70.51% in a dose- and time-dependent manner. Also, αIR3 treatmen展开更多
文摘Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways have been widely investigated. Their aberrant expression or mutation has been significantly associated with advanced stage or poor prognosis of gastric cancer. Recently, aberrations of immune checkpoints including programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) have been suggested as an important step in the formation of a microenvironment favorable for gastric cancer. Accomplishments in basic research have led to the development of novel agents targeting these signaling pathways. However, phase III studies of selective anti-HGF/c-MET antibodies and mTOR inhibitor failed to show significant benefits in terms of overall survival and progression-free survival. Few agents directly targeting STAT3 have been developed. However, this target is still critical issue in terms of chemoresistance, and SH2-containing protein tyrosine phosphatase 1 might be a significant link to effectively inhibit STAT3 activity. Inhibition of PD-1/PD-L1 showed durable efficacy in phase I studies, and phase III evaluation is warranted. Therapeutic strategy to concurrently inhibit multiple tyrosine kinases is a reasonable option, however, lapatinib needs to be further evaluated to identify good responders. Regorafenib has shown promising effectiveness in prolonging progression-free survival in a phase II study. In this topic highlight, we review the biologic roles and outcomes of clinical studies targeting these signaling pathways.
文摘Although multiple advances have been made in systemic therapy for renal cell carcinoma(RCC),metastatic RCC remains incurable.In the current review,we focus on the underlying biology of RCC and plausible mechanisms of metastasis.We further outline evolving strategies to combat metastasis through adjuvant therapy.Finally,we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.
基金Supported by the Gansu Province's Natural Science Fund, No.ZS021-A25-079-Y
文摘AIM： To study the expression level and localization of insulin-like growth factor -Ⅰ receptor （IGF-IR） in HepG2 cells and Chang liver cells, and to observe the effect of anti-IGF-IR monoclonal antibody （αIR3） on the growth of HepG2 cells. METHODS： The expression of IGF-IR in HepG2 cells and Chang liver cells was detected by immunohistochemistry. The influences of αIR3 on proliferation and apoptosis were examined by the 3- （4, 5-dimethylthiazol-2-yl）-2, 5- diphenyltetrazolium bromide （MTT） assay and electron microscopy, respectively. Flow cytometry （FCM） was applied for the analysis of cell cycle and apoptosis was observed under electron microscope. RESULTS： IGF-IR was located in the membranes of both HepG2 and Chang liver cell lines, and the expression level of IGF-IR was higher in HepG2 cells than in Chang liver cells. Treated with 0.1 μg/mL αIR3 for 48 h in vitro, the cell growth index （GI） of HepG2 cells was significantly higher than that of control （103.41% ys 100%, P 〈 0.01）. However, the αIR3 for 24 h at final concentration of 4.0 μg/mL made the GI of HepG2 cells lower than that of control （93.37% vs 100%, P 〈 0.01）. Compared with control, treated with αIR3 for 48 h at final concentrations ranging from 2.0 μg/mL to 4.0 μg/mL markedly reduced the GIs of HepG2 cells （97.63%, 97.16%, 95.13%, 92.53% vs 100%, P 〈 0.05 or P 〈 0.01）, treated with αIR3 for 72 h at final concentrations ranging from 0.2 μg/mL to 4.0 μg/mL decreased the GIs of HepG2 cells obviously （95%, 91.63%, 90.77%, 89.84%, 88.51% vs 100%, P 〈 0.01）, and treated with αIR3 for 96 h at final concentrations ranging from 0.5 μg/mL to 4.0 μg/mL made GIs of HepG2 cells lower significantly （88.86%, 83.97%, 79.81%, 77.24%, 70.51% vs 100%, P 〈 0.05or P 〈 0.01）. Moreover, treated with αIR3 from 24 h to 96 h at final concentrations ranging from 0.2 μg/mL to 4.0 μg/mL reduced the GI of HepG2 cells from 97.63% to 70.51% in a dose- and time-dependent manner. Also, αIR3 treatmen
