BACKGROUND Hepatic neuroendocrine neoplasm(hNEN) is a highly heterogeneous tumor. The exact identification of the source and malignant degree of hNEN is important.However, there is a lack of information regarding diag...BACKGROUND Hepatic neuroendocrine neoplasm(hNEN) is a highly heterogeneous tumor. The exact identification of the source and malignant degree of hNEN is important.However, there is a lack of information regarding diagnosis of hNEN with imaging. In addition, no studies have compared the imaging between hNEN and hepatocellular carcinoma(HCC) and among different sources and malignant degrees of hNEN.AIM To compare the ultrasound characteristics between hNEN and HCC and among different sources and malignant degrees of hNEN.METHODS A total of 55 patients with hNEN were recruited and defined as the hNEN group.Among them, 35 cases of hNET were defined as the hNET group. Twenty cases of hepatic neuroendocrine carcinoma(hNEC) were defined as the hNEC group.Among the 55 lesions, 29 were transferred from the pancreas, 20 were from the gastrointestinal tract, and six were from other sites. In total, 55 patients with HCC were recruited and defined as the HCC group. The characteristic differences of Bmode ultrasound and contrast-enhanced ultrasound(CEUS) between hNEN and HCC and among different sources and malignant degrees of hNEN were compared.RESULTS In the hNEN group, the proportions of multiple liver lesions, unclear borders,and high echo lesions were higher than those in the HCC group. The proportions of non-uniform echo and peripheral acoustic halo were lower than those in the HCC group(P < 0.05). The washout to iso-enhancement time and washout to hypo-enhancement time were lower than those in the HCC group(P < 0.05). The characteristics of B-ultrasound and CEUS among different sources of hNEN were similar, and the differences were not statistically significant(P > 0.05). B-mode ultrasound characteristics of hNET and hNEC were similar. The proportions of low enhancement at portal venous phase, non-uniform enhancement forms, and combined tumor vasculature in the hNEC group were larger than those in the hNEN group(P < 0.05).CONCLUSION Compared with HCC, hNEN showed multiple intrahepatic lesions, uniform high echo, uniform high enhancement at arterial phase, and rapid washout. Low enhancement at portal venous phase, overall non-uniform enhancement form,and the proportion of combined tumor vasculature in hNEC were larger than those in hNET.展开更多
BACKGROUND Breast cancer is a common malignant tumor that seriously threatens women’s health.Breast cancer stem cell(CSC)-like cell population may be the main factor for breast cancer metastasis.Therefore,targeted th...BACKGROUND Breast cancer is a common malignant tumor that seriously threatens women’s health.Breast cancer stem cell(CSC)-like cell population may be the main factor for breast cancer metastasis.Therefore,targeted therapy for CSCs has great potential significance.Hypoxia-inducible factor is a transcription factor widely expressed in tumors.Studies have shown that down-regulation of the hypoxia signaling pathway inhibits tumor stem cell self-renewal and increases the sensitivity of stem cells to radiotherapy and chemotherapy mediated by hypoxiainducible factor-2α(HIF-2α).However,the specific mechanism remains unclear and further research is necessary.AIM To investigate the effect of HIF-2αdown-regulation on stem cell markers,microsphere formation,and apoptosis in breast cancer cell line MDA-MB-231 under hypoxia and its possible mechanism.METHODS Immunohistochemistry was used to detect the expression of HIF-2αand CD44 in triple-negative breast cancer(TNBC)and non-TNBC tissues.Double-labeling immunofluorescence was applied to detect the co-expression of HIF-2αand CD44 in MDA-MB-231 cells and MCF-7 cells.HIF-2αwas silenced by RNA interference,and the expression of CD44 and transfection efficiency were detected by real-time fluorescent quantitative PCR.Further,flow cytometry,TdT-mediated X-dUTP nick end labeling,and mammosphere formation assays were used to evaluate the effect of HIF-2αon CSCs and apoptosis.The possible mechanisms were analyzed by Western blot.RESULTS The results of immunohistochemistry showed that HIF-2αwas highly expressed in both TNBC and non-TNBC,while the expression of CD44 in different molecular types of breast cancer cells was different.In in vitro experiments,it was found that HIF-2αand CD44 were expressed almost in the same cell.Compared with hypoxia+negative-sequence control,HIF-2αsmall interfering ribonucleic acid transfection can lower the expression of HIF-2αand CD44 mRNA(P<0.05),increase the percentage of apoptotic cells(P<0.05),and resulted in a reduction of CD44+/CD24−population(P<0.05)and mammosphere formation(P<0.05)in hypoxic MDA-MB-231 cells.Western blot analysis revealed that phosphorylated protein-serine-threonine kinase(p-AKT)and phosphorylated mammalian target of rapamycin(p-mTOR)levels in MDA-MB-231 decreased significantly after HIF-2αsilencing(P<0.05).CONCLUSION Down-regulation of HIF-2αexpression can inhibit the stemness of human breast cancer MDA-MB-231 cells and promote apoptosis,and its mechanism may be related to the CD44/phosphoinosmde-3-kinase/AKT/mTOR signaling pathway.展开更多
文摘BACKGROUND Hepatic neuroendocrine neoplasm(hNEN) is a highly heterogeneous tumor. The exact identification of the source and malignant degree of hNEN is important.However, there is a lack of information regarding diagnosis of hNEN with imaging. In addition, no studies have compared the imaging between hNEN and hepatocellular carcinoma(HCC) and among different sources and malignant degrees of hNEN.AIM To compare the ultrasound characteristics between hNEN and HCC and among different sources and malignant degrees of hNEN.METHODS A total of 55 patients with hNEN were recruited and defined as the hNEN group.Among them, 35 cases of hNET were defined as the hNET group. Twenty cases of hepatic neuroendocrine carcinoma(hNEC) were defined as the hNEC group.Among the 55 lesions, 29 were transferred from the pancreas, 20 were from the gastrointestinal tract, and six were from other sites. In total, 55 patients with HCC were recruited and defined as the HCC group. The characteristic differences of Bmode ultrasound and contrast-enhanced ultrasound(CEUS) between hNEN and HCC and among different sources and malignant degrees of hNEN were compared.RESULTS In the hNEN group, the proportions of multiple liver lesions, unclear borders,and high echo lesions were higher than those in the HCC group. The proportions of non-uniform echo and peripheral acoustic halo were lower than those in the HCC group(P < 0.05). The washout to iso-enhancement time and washout to hypo-enhancement time were lower than those in the HCC group(P < 0.05). The characteristics of B-ultrasound and CEUS among different sources of hNEN were similar, and the differences were not statistically significant(P > 0.05). B-mode ultrasound characteristics of hNET and hNEC were similar. The proportions of low enhancement at portal venous phase, non-uniform enhancement forms, and combined tumor vasculature in the hNEC group were larger than those in the hNEN group(P < 0.05).CONCLUSION Compared with HCC, hNEN showed multiple intrahepatic lesions, uniform high echo, uniform high enhancement at arterial phase, and rapid washout. Low enhancement at portal venous phase, overall non-uniform enhancement form,and the proportion of combined tumor vasculature in hNEC were larger than those in hNET.
文摘BACKGROUND Breast cancer is a common malignant tumor that seriously threatens women’s health.Breast cancer stem cell(CSC)-like cell population may be the main factor for breast cancer metastasis.Therefore,targeted therapy for CSCs has great potential significance.Hypoxia-inducible factor is a transcription factor widely expressed in tumors.Studies have shown that down-regulation of the hypoxia signaling pathway inhibits tumor stem cell self-renewal and increases the sensitivity of stem cells to radiotherapy and chemotherapy mediated by hypoxiainducible factor-2α(HIF-2α).However,the specific mechanism remains unclear and further research is necessary.AIM To investigate the effect of HIF-2αdown-regulation on stem cell markers,microsphere formation,and apoptosis in breast cancer cell line MDA-MB-231 under hypoxia and its possible mechanism.METHODS Immunohistochemistry was used to detect the expression of HIF-2αand CD44 in triple-negative breast cancer(TNBC)and non-TNBC tissues.Double-labeling immunofluorescence was applied to detect the co-expression of HIF-2αand CD44 in MDA-MB-231 cells and MCF-7 cells.HIF-2αwas silenced by RNA interference,and the expression of CD44 and transfection efficiency were detected by real-time fluorescent quantitative PCR.Further,flow cytometry,TdT-mediated X-dUTP nick end labeling,and mammosphere formation assays were used to evaluate the effect of HIF-2αon CSCs and apoptosis.The possible mechanisms were analyzed by Western blot.RESULTS The results of immunohistochemistry showed that HIF-2αwas highly expressed in both TNBC and non-TNBC,while the expression of CD44 in different molecular types of breast cancer cells was different.In in vitro experiments,it was found that HIF-2αand CD44 were expressed almost in the same cell.Compared with hypoxia+negative-sequence control,HIF-2αsmall interfering ribonucleic acid transfection can lower the expression of HIF-2αand CD44 mRNA(P<0.05),increase the percentage of apoptotic cells(P<0.05),and resulted in a reduction of CD44+/CD24−population(P<0.05)and mammosphere formation(P<0.05)in hypoxic MDA-MB-231 cells.Western blot analysis revealed that phosphorylated protein-serine-threonine kinase(p-AKT)and phosphorylated mammalian target of rapamycin(p-mTOR)levels in MDA-MB-231 decreased significantly after HIF-2αsilencing(P<0.05).CONCLUSION Down-regulation of HIF-2αexpression can inhibit the stemness of human breast cancer MDA-MB-231 cells and promote apoptosis,and its mechanism may be related to the CD44/phosphoinosmde-3-kinase/AKT/mTOR signaling pathway.