Objective：To assess the diagnostic accuracy of whole-body MRI using diffusion-weighted sequence（WB-DWI）to determine the peritoneal cancer index（PCI）in correlation with surgical and histopathological findings.Meth...Objective：To assess the diagnostic accuracy of whole-body MRI using diffusion-weighted sequence（WB-DWI）to determine the peritoneal cancer index（PCI）in correlation with surgical and histopathological findings.Methods：Twenty-seven patients underwent preoperative WB-MRI,followed by cytoreductive surgery for primary tumors of the appendix（n=15）,colorectum（n=12）,and associated peritoneal disease.A total of 351 regions were retrospectively reviewed.The sensitivity,specificity,and accuracy were calculated at 13 anatomical sites.The WB-DWI PCI and PCI type were compared with surgical and histopathological findings.Results：No statistical difference was found between the WB-DWI PCI and surgical PCI（P=0.574）.WB-DWI correctly predicted the PCI type in 24 of 27 patients with high accuracy（88.9%）,including 10 of 10 patients with small-volume tumor,12 of 14 with moderate-volume tumor,and 2 of 3 with large-volume tumor.WB-DWI correctly depicted tumors in 163 of 203 regions,with 40false-negative and 23 false-positive regions.The overall sensitivity,specificity,and accuracy of WB-DWI for the detection of peritoneal tumors were 80.3%,84.5%,and 82.1%,respectively.For lesions＆lt;0.5 cm in diameter,WB-DWI demonstrated good sensitivity（69.4%）.Conclusions：WB-DWI accurately predicted PCI before surgery in patients undergoing evaluation for cytoreductive surgery.展开更多
Background:Abnormal expression of protein tyrosine phosphatases(PTPs)has been reported to be a crucial cause of cancer.As a member of PTPs,protein tyrosine phosphatase receptor type O(PTPRO)has been revealed to play t...Background:Abnormal expression of protein tyrosine phosphatases(PTPs)has been reported to be a crucial cause of cancer.As a member of PTPs,protein tyrosine phosphatase receptor type O(PTPRO)has been revealed to play tumor suppressive roles in several cancers,while its roles in colorectal cancer(CRC)remains to be elucidated.Hence,we aimed to explore the roles and mechanisms of PTPRO in CRC initiation and progression.Methods:The influences of PTPRO on the growth and liver metastasis of CRC cells and the expression patterns of different lipid metabolism enzymes were evaluated in vitro and in vivo.Molecular and biological experiments were conducted to uncover the underpinning mechanisms of dysregulated de novo lipogenesis and fatty acidβ-oxidation.Results:PTPRO expression was notably downregulated in CRC liver metastasis compared to the primary cancer,and such a downregulation was associated with poor prognosis of patients with CRC.PTPRO silencing significantly promoted cell growth and liver metastasis.Compared with PTPRO wild-type mice,PTPROknockout mice developed more tumors and harbored larger tumor loads under treatment with azoxymethane and dextran sulfate sodium.Gene set enrichment analysis revealed that PTPRO downregulation was significantly associated with the fatty acid metabolism pathways.Blockage of fatty acid synthesis abrogated the effects of PTPRO silencing on cell growth and liver metastasis.Further experiments indicated that PTPRO silencing induced the activation of the AKT serine/threonine kinase(AKT)/mammalian target of rapamycin(mTOR)signaling axis,thus promoting de novo lipogenesis by enhancing the expression of sterol regulatory element-binding protein 1(SREBP1)and its target lipogenic enzyme acetyl-CoA carboxylase alpha(ACC1)by activating the AKT/mTOR signaling pathway.Furthermore,PTPRO attenuation decreased the fatty acid oxidation rate by repressing the expression of peroxisome proliferator-activated receptor alpha(PPARα)and its downstream enzyme peroxisomal acyl-coenzyme A oxidase 1(ACOX1)via activating the p38/extracellular signal-regulated kinase(ERK)mitogen-activated protein kinase(MAPK)signaling pathway.Conclusions:PTPRO could suppress CRC development and metastasis via modulating the AKT/mTOR/SREBP1/ACC1 and MAPK/PPARα/ACOX1 pathways and reprogramming lipid metabolism.展开更多
Cancer cells are usually characterized by hyperactive glucose metabolism,which can often lead to glucose scarcity;thus,alternative pathways to rewire cancer metabolism are required.Here,we demonstrated that GLUT3 was ...Cancer cells are usually characterized by hyperactive glucose metabolism,which can often lead to glucose scarcity;thus,alternative pathways to rewire cancer metabolism are required.Here,we demonstrated that GLUT3 was highly expressed in colorectal cancer(CRC)and negatively linked to CRC patient outcomes,whereas GLUT1 was not associated with CRC prognosis.Under glucoselimiting conditions,GLUT3 expedited CRC cell growth by accelerating glucose input and fuelling nucleotide synthesis.Notably,GLUT3 had a greater impact on cell growth than GLUT1 under glucose-limiting stress.Mechanistically,low-glucose stress dramatically upregulated GLUT3 via the AMPK/CREB1 pathway.Furthermore,high GLUT3 expression remarkably increased the sensitivity of CRC cells to treatment with vitamin C and vitamin C-containing regimens.Together,the results of this study highlight the importance of the AMPK/CREB1/GLUT3 pathway for CRC cells to withstand glucose-limiting stress and underscore the therapeutic potential of vitamin C in CRC with high GLUT3 expression.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81501437)the Shanghai Municipal Planning Commission of Science and Research Fund(Grant No.JGGG1401)
文摘Objective：To assess the diagnostic accuracy of whole-body MRI using diffusion-weighted sequence（WB-DWI）to determine the peritoneal cancer index（PCI）in correlation with surgical and histopathological findings.Methods：Twenty-seven patients underwent preoperative WB-MRI,followed by cytoreductive surgery for primary tumors of the appendix（n=15）,colorectum（n=12）,and associated peritoneal disease.A total of 351 regions were retrospectively reviewed.The sensitivity,specificity,and accuracy were calculated at 13 anatomical sites.The WB-DWI PCI and PCI type were compared with surgical and histopathological findings.Results：No statistical difference was found between the WB-DWI PCI and surgical PCI（P=0.574）.WB-DWI correctly predicted the PCI type in 24 of 27 patients with high accuracy（88.9%）,including 10 of 10 patients with small-volume tumor,12 of 14 with moderate-volume tumor,and 2 of 3 with large-volume tumor.WB-DWI correctly depicted tumors in 163 of 203 regions,with 40false-negative and 23 false-positive regions.The overall sensitivity,specificity,and accuracy of WB-DWI for the detection of peritoneal tumors were 80.3%,84.5%,and 82.1%,respectively.For lesions＆lt;0.5 cm in diameter,WB-DWI demonstrated good sensitivity（69.4%）.Conclusions：WB-DWI accurately predicted PCI before surgery in patients undergoing evaluation for cytoreductive surgery.
基金National Natural Science Foundation of China,Grant/Award Numbers:81871958,82103554Science and Technology Commission of Shanghai Municipality,Grant/Award Numbers:19140902100,16401970502,17411951100。
文摘Background:Abnormal expression of protein tyrosine phosphatases(PTPs)has been reported to be a crucial cause of cancer.As a member of PTPs,protein tyrosine phosphatase receptor type O(PTPRO)has been revealed to play tumor suppressive roles in several cancers,while its roles in colorectal cancer(CRC)remains to be elucidated.Hence,we aimed to explore the roles and mechanisms of PTPRO in CRC initiation and progression.Methods:The influences of PTPRO on the growth and liver metastasis of CRC cells and the expression patterns of different lipid metabolism enzymes were evaluated in vitro and in vivo.Molecular and biological experiments were conducted to uncover the underpinning mechanisms of dysregulated de novo lipogenesis and fatty acidβ-oxidation.Results:PTPRO expression was notably downregulated in CRC liver metastasis compared to the primary cancer,and such a downregulation was associated with poor prognosis of patients with CRC.PTPRO silencing significantly promoted cell growth and liver metastasis.Compared with PTPRO wild-type mice,PTPROknockout mice developed more tumors and harbored larger tumor loads under treatment with azoxymethane and dextran sulfate sodium.Gene set enrichment analysis revealed that PTPRO downregulation was significantly associated with the fatty acid metabolism pathways.Blockage of fatty acid synthesis abrogated the effects of PTPRO silencing on cell growth and liver metastasis.Further experiments indicated that PTPRO silencing induced the activation of the AKT serine/threonine kinase(AKT)/mammalian target of rapamycin(mTOR)signaling axis,thus promoting de novo lipogenesis by enhancing the expression of sterol regulatory element-binding protein 1(SREBP1)and its target lipogenic enzyme acetyl-CoA carboxylase alpha(ACC1)by activating the AKT/mTOR signaling pathway.Furthermore,PTPRO attenuation decreased the fatty acid oxidation rate by repressing the expression of peroxisome proliferator-activated receptor alpha(PPARα)and its downstream enzyme peroxisomal acyl-coenzyme A oxidase 1(ACOX1)via activating the p38/extracellular signal-regulated kinase(ERK)mitogen-activated protein kinase(MAPK)signaling pathway.Conclusions:PTPRO could suppress CRC development and metastasis via modulating the AKT/mTOR/SREBP1/ACC1 and MAPK/PPARα/ACOX1 pathways and reprogramming lipid metabolism.
基金supported by the Grant of National Natural Science Foundation of China(No.81871958 and No.81572351)Grant of Science and Technology Commission of Shanghai Municipality(No.16401970502 and No.17411951100 and No.19140902100).
文摘Cancer cells are usually characterized by hyperactive glucose metabolism,which can often lead to glucose scarcity;thus,alternative pathways to rewire cancer metabolism are required.Here,we demonstrated that GLUT3 was highly expressed in colorectal cancer(CRC)and negatively linked to CRC patient outcomes,whereas GLUT1 was not associated with CRC prognosis.Under glucoselimiting conditions,GLUT3 expedited CRC cell growth by accelerating glucose input and fuelling nucleotide synthesis.Notably,GLUT3 had a greater impact on cell growth than GLUT1 under glucose-limiting stress.Mechanistically,low-glucose stress dramatically upregulated GLUT3 via the AMPK/CREB1 pathway.Furthermore,high GLUT3 expression remarkably increased the sensitivity of CRC cells to treatment with vitamin C and vitamin C-containing regimens.Together,the results of this study highlight the importance of the AMPK/CREB1/GLUT3 pathway for CRC cells to withstand glucose-limiting stress and underscore the therapeutic potential of vitamin C in CRC with high GLUT3 expression.
