Although the role of copper (Cu) in promoting KRas- or BRaf-mutation driven cancers via activating MEK1/2 kinases is known, the mechanism by which the copper transporter SLC31A1 (CTR1) is upregulated in pancreatic can...Although the role of copper (Cu) in promoting KRas- or BRaf-mutation driven cancers via activating MEK1/2 kinases is known, the mechanism by which the copper transporter SLC31A1 (CTR1) is upregulated in pancreatic cancer (PDAC, KRas mutation) is not defined. In this study, we provide evidence that MEK signal maintains a high level of SLC31A1 through silencing the expression of miR-124-3P (miR-124) via a novel MEK-DNMT1-miR-124 feedback loop in PDAC cells. Further, we reveal that miR-124 directly targets suppression of SLC31A1, and miR-124 introduction together with tetrathiomolybdate (TM) treatment hampered pancreatic cancer growth in vitro and in vivo. Our results demonstrate that a SLC31A1-MEK-DNMT1-miR-124 feedback loop is an important pathway to maintain copper absorption and promote pancreatic cancer progression, and we hope to provide a Cu-chelation as an adjuvant treatment strategy, to block the progression in Kras mutant PDAC patients.展开更多
Background:Surgical treatment of tumors near the center of the liver is challenging.Right hemihepatic or triple resection is considered the preferred approach,but it is associated with a high mortality rate due to pos...Background:Surgical treatment of tumors near the center of the liver is challenging.Right hemihepatic or triple resection is considered the preferred approach,but it is associated with a high mortality rate due to postoperative liver failure.Therefore,attempts should be made to preserve liver parenchyma to the maximum extent possible.Segment VI of the liver is often excised“innocently”.This article aims to discuss the experience of the right hemihepatectomy with the segment VI preserved.Case presentation:The clinical medical records of 7 patients with right lobe liver cancer who underwent right hemihepatectomy with segment VI preservation during 2015–2021 were collected to selectively reconstruct the right hepatic vein to ensure liver blood return at segment VI.Conclusions:Right hemihepatectomy with segment VI preservation can preserve more liver parenchyma and is a safe and reliable surgical method for patients who need to preserve more liver parenchyma.展开更多
基金supported by The National Natural Science Foundation of China(No.32072801)Fundamental Research Funds for the Central Universities of China(No.2572020DY12).
文摘Although the role of copper (Cu) in promoting KRas- or BRaf-mutation driven cancers via activating MEK1/2 kinases is known, the mechanism by which the copper transporter SLC31A1 (CTR1) is upregulated in pancreatic cancer (PDAC, KRas mutation) is not defined. In this study, we provide evidence that MEK signal maintains a high level of SLC31A1 through silencing the expression of miR-124-3P (miR-124) via a novel MEK-DNMT1-miR-124 feedback loop in PDAC cells. Further, we reveal that miR-124 directly targets suppression of SLC31A1, and miR-124 introduction together with tetrathiomolybdate (TM) treatment hampered pancreatic cancer growth in vitro and in vivo. Our results demonstrate that a SLC31A1-MEK-DNMT1-miR-124 feedback loop is an important pathway to maintain copper absorption and promote pancreatic cancer progression, and we hope to provide a Cu-chelation as an adjuvant treatment strategy, to block the progression in Kras mutant PDAC patients.
基金funded by National Natural Science Foundation of China(No.81972724)。
文摘Background:Surgical treatment of tumors near the center of the liver is challenging.Right hemihepatic or triple resection is considered the preferred approach,but it is associated with a high mortality rate due to postoperative liver failure.Therefore,attempts should be made to preserve liver parenchyma to the maximum extent possible.Segment VI of the liver is often excised“innocently”.This article aims to discuss the experience of the right hemihepatectomy with the segment VI preserved.Case presentation:The clinical medical records of 7 patients with right lobe liver cancer who underwent right hemihepatectomy with segment VI preservation during 2015–2021 were collected to selectively reconstruct the right hepatic vein to ensure liver blood return at segment VI.Conclusions:Right hemihepatectomy with segment VI preservation can preserve more liver parenchyma and is a safe and reliable surgical method for patients who need to preserve more liver parenchyma.
