Kidney transplantation at the time of a global viral pandemic has become challenging in many aspects.Firstly,we must reassess deceased donor safety(for the recipient)especially in communities with a relatively high in...Kidney transplantation at the time of a global viral pandemic has become challenging in many aspects.Firstly,we must reassess deceased donor safety(for the recipient)especially in communities with a relatively high incidence of coronavirus disease 19(COVID-19).With respect to elective live donors,if one decides to do them at all,similar considerations must be made that may impose undue hardship on the donor.Recipient selection is also problematic since there is clear evidence of a much higher morbidity and mortality from COVID-19 for patients older than 60 and those with comorbidities such as hypertension,diabetes,obesity and lung disease.Unfortunately,many,if not most of dialysis patients fit that mold.We may and indeed must reassess our allocation policies,but this must be done based on data rather than conjecture.Follow-up routines must be re-engineered to minimize patient travel and exposure.Reliance on technology and telemedicine is paramount.Making this technology available to patients is extremely important.Modifying or changing immunosuppression protocols is controversial and not based on clinical studies.Nevertheless,we should reassess the need for induction therapy across the board for ordinary patients and the more liberal use of mammalian target of rapamycin inhibitors in transplant patients with proven infection.展开更多
Tumor progression and metastasis are the major causes of death among cancer associated mortality.Metastatic cells acquire features of migration and invasion and usually undergo epithelia-mesenchymal transition(EMT).Ac...Tumor progression and metastasis are the major causes of death among cancer associated mortality.Metastatic cells acquire features of migration and invasion and usually undergo epithelia-mesenchymal transition(EMT).Acquirement of these various hallmarks rely on different cellular pathways,including TGF-βand Wnt signaling.Recently,we reported that WW domain-containing oxidoreductase(WWOX)acts as a tumor suppressor and has anti-metastatic activities involving regulation of several key microRNAs(miRNAs)in triple-negative breast cancer(TNBC).Here,we report that WWOX restoration in highly metastatic MDA-MB435S cancer cells alters mRNA expression profiles;further,WWOX interacts with various proteins to exert its tumor suppressor function.Careful alignment and analysis of gene and miRNA expression in these cells revealed profound changes in cellular pathways mediating adhesion,invasion and motility.We further demonstrate that WWOX,through regulation of miR-146a levels,regulates SMAD3,which is a member of the TGF-βsignaling pathway.Moreover,proteomic analysis of WWOX partners revealed regulation of the Wnt-signaling activation through physical interaction with Disheveled.Altogether,these findings underscore a significant role for WWOX in antagonizing metastasis,further highlighting its role and therapeutic potential in suppressing tumor progression.展开更多
文摘Kidney transplantation at the time of a global viral pandemic has become challenging in many aspects.Firstly,we must reassess deceased donor safety(for the recipient)especially in communities with a relatively high incidence of coronavirus disease 19(COVID-19).With respect to elective live donors,if one decides to do them at all,similar considerations must be made that may impose undue hardship on the donor.Recipient selection is also problematic since there is clear evidence of a much higher morbidity and mortality from COVID-19 for patients older than 60 and those with comorbidities such as hypertension,diabetes,obesity and lung disease.Unfortunately,many,if not most of dialysis patients fit that mold.We may and indeed must reassess our allocation policies,but this must be done based on data rather than conjecture.Follow-up routines must be re-engineered to minimize patient travel and exposure.Reliance on technology and telemedicine is paramount.Making this technology available to patients is extremely important.Modifying or changing immunosuppression protocols is controversial and not based on clinical studies.Nevertheless,we should reassess the need for induction therapy across the board for ordinary patients and the more liberal use of mammalian target of rapamycin inhibitors in transplant patients with proven infection.
基金supported by the Israel science foundation grant(ISF grant agreement No.15/1574)ICRF-City of Hope-Harvey L.Miller Family Foundation and European Research Council(ERC)-Consolidator Grant under the European Union’s Horizon 2020 research and innovation program(grant agreement No.682118).
文摘Tumor progression and metastasis are the major causes of death among cancer associated mortality.Metastatic cells acquire features of migration and invasion and usually undergo epithelia-mesenchymal transition(EMT).Acquirement of these various hallmarks rely on different cellular pathways,including TGF-βand Wnt signaling.Recently,we reported that WW domain-containing oxidoreductase(WWOX)acts as a tumor suppressor and has anti-metastatic activities involving regulation of several key microRNAs(miRNAs)in triple-negative breast cancer(TNBC).Here,we report that WWOX restoration in highly metastatic MDA-MB435S cancer cells alters mRNA expression profiles;further,WWOX interacts with various proteins to exert its tumor suppressor function.Careful alignment and analysis of gene and miRNA expression in these cells revealed profound changes in cellular pathways mediating adhesion,invasion and motility.We further demonstrate that WWOX,through regulation of miR-146a levels,regulates SMAD3,which is a member of the TGF-βsignaling pathway.Moreover,proteomic analysis of WWOX partners revealed regulation of the Wnt-signaling activation through physical interaction with Disheveled.Altogether,these findings underscore a significant role for WWOX in antagonizing metastasis,further highlighting its role and therapeutic potential in suppressing tumor progression.
