Background: Colorectal cancer(CRC) is the third most commonly diagnosed cancer in males and the second in females worldwide in 2012. In the past 20 years, strong evidence suggests that cancer stem cells are the main c...Background: Colorectal cancer(CRC) is the third most commonly diagnosed cancer in males and the second in females worldwide in 2012. In the past 20 years, strong evidence suggests that cancer stem cells are the main culprit of cancer metastasis,chemotherapy resistance, and relapse.Methods: To further understand the unique biological properties of cancer stem cells and uncover novel molecular targets to eradicate them, we first established a panel of patient-derived xenograft(PDX) tumor models using tumors surgically removed from human colorectal cancer patients. We then isolated CRC cancer stem cells based on their ALDH activity using fluorescent-activated cell sorting(FACS)and characterized their metabolic properties.Results: Interestingly, we found that the CRC cancer stem cells(ie, CRC cells with higher ALDH activity, or ALDH+) express higher level of antioxidant genes and have lower level of reactive oxygen species(ROS) than non-CRC cancer stem cells(ie, CRC cells with lower ALDH activity, or ALDHà). The CRC cancer stem cells also possess more mitochondria mass and show higher mitochondrial activity. More intriguingly,we observed higher AMP-activated protein kinase(AMPK) activities in these CRC cancer stem cells. Inhibition of the AMPK activity using 2 AMPK inhibitors, Compound C and Iodotubercidin, preferentially induces cell death in CRC cancer stem cells.Conclusion: We propose that AMPK inhibitors may help to eradicate the CRC cancer stem cells and prevent the relapse of CRCs.展开更多
Objective： To explore the neuroprotective effects of electroacupuncture （EA） on hypoxic-ischemic encephalopathy （HIE） and to further investigate the role of glial cell line-derived neurotrophic factor （GDNF） fa...Objective： To explore the neuroprotective effects of electroacupuncture （EA） on hypoxic-ischemic encephalopathy （HIE） and to further investigate the role of glial cell line-derived neurotrophic factor （GDNF） family receptor member RET （rearranged during transfection） and its key downstream phosphatidylinositol 3 kinase （PI-3K）/protein kinase B （Akt） pathway in the process. Methods： A total of 220 seven-day-old SD rats （of either sex, from 22 broods） were randomly divided into two groups, one （30 rats） for sham-surgery group and the other （190 rats） for HIE model group. The HIE model was established using the left common carotid artery ligation method in combination with hypoxic treatment. The successfully established rats were randomly divided into five groups, including control model group, EA group, sham-EA group, antagonist group and antagonist plus electroacupuncture group, with 35 rats in each group. Baihui （GV 20）, Dazhui （GV 14）, Quchi （LI 11） and Yongquan （KI 1） acupoints were chosen for acupuncture. EA was performed at Baihui and Quchi for 10 min once a day for continuous 1, 3, 7 and 21 days, respectively. The rats were then killed after the operation and injured cerebral cortex was taken for the measurement of neurologic damage by hematoxylin-eosin （HE） staining and the degenerative changes of cortical ultrastructure by transmission electron microscopy. RET mRNA level and Akt protein level were detected by real-time reverse-transcription polymerase chain reaction （RT-PCR） and western blot analysis, respectively. Results： EA could ameliorate neurologic damage of the first somatic sensory area （SITr） and alleviate the degenerative changes of ultrastructure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex. Conclusion： EA has neuroprotective effects on HIE and could be a potential therapeutic strategy for HIE in the neonate. Activation of RET/Akt signaling pathway might be involved in this process.展开更多
文摘Background: Colorectal cancer(CRC) is the third most commonly diagnosed cancer in males and the second in females worldwide in 2012. In the past 20 years, strong evidence suggests that cancer stem cells are the main culprit of cancer metastasis,chemotherapy resistance, and relapse.Methods: To further understand the unique biological properties of cancer stem cells and uncover novel molecular targets to eradicate them, we first established a panel of patient-derived xenograft(PDX) tumor models using tumors surgically removed from human colorectal cancer patients. We then isolated CRC cancer stem cells based on their ALDH activity using fluorescent-activated cell sorting(FACS)and characterized their metabolic properties.Results: Interestingly, we found that the CRC cancer stem cells(ie, CRC cells with higher ALDH activity, or ALDH+) express higher level of antioxidant genes and have lower level of reactive oxygen species(ROS) than non-CRC cancer stem cells(ie, CRC cells with lower ALDH activity, or ALDHà). The CRC cancer stem cells also possess more mitochondria mass and show higher mitochondrial activity. More intriguingly,we observed higher AMP-activated protein kinase(AMPK) activities in these CRC cancer stem cells. Inhibition of the AMPK activity using 2 AMPK inhibitors, Compound C and Iodotubercidin, preferentially induces cell death in CRC cancer stem cells.Conclusion: We propose that AMPK inhibitors may help to eradicate the CRC cancer stem cells and prevent the relapse of CRCs.
基金Supported by the 45th China Postdoctoral Science Foundation(No.20090450856)
文摘Objective： To explore the neuroprotective effects of electroacupuncture （EA） on hypoxic-ischemic encephalopathy （HIE） and to further investigate the role of glial cell line-derived neurotrophic factor （GDNF） family receptor member RET （rearranged during transfection） and its key downstream phosphatidylinositol 3 kinase （PI-3K）/protein kinase B （Akt） pathway in the process. Methods： A total of 220 seven-day-old SD rats （of either sex, from 22 broods） were randomly divided into two groups, one （30 rats） for sham-surgery group and the other （190 rats） for HIE model group. The HIE model was established using the left common carotid artery ligation method in combination with hypoxic treatment. The successfully established rats were randomly divided into five groups, including control model group, EA group, sham-EA group, antagonist group and antagonist plus electroacupuncture group, with 35 rats in each group. Baihui （GV 20）, Dazhui （GV 14）, Quchi （LI 11） and Yongquan （KI 1） acupoints were chosen for acupuncture. EA was performed at Baihui and Quchi for 10 min once a day for continuous 1, 3, 7 and 21 days, respectively. The rats were then killed after the operation and injured cerebral cortex was taken for the measurement of neurologic damage by hematoxylin-eosin （HE） staining and the degenerative changes of cortical ultrastructure by transmission electron microscopy. RET mRNA level and Akt protein level were detected by real-time reverse-transcription polymerase chain reaction （RT-PCR） and western blot analysis, respectively. Results： EA could ameliorate neurologic damage of the first somatic sensory area （SITr） and alleviate the degenerative changes of ultrastructure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex. Conclusion： EA has neuroprotective effects on HIE and could be a potential therapeutic strategy for HIE in the neonate. Activation of RET/Akt signaling pathway might be involved in this process.
