We report a case of an isolated hepatic neoplasia which originated in a site of the liver previously affected by radiation induced liver disease (RILD) in a patient resected for gastric cancer and referred to us for h...We report a case of an isolated hepatic neoplasia which originated in a site of the liver previously affected by radiation induced liver disease (RILD) in a patient resected for gastric cancer and referred to us for high serum alpha-fetoprotein (AFP) levels. This case challenged us in distiguishing, even histologically, between primary liver cancer and AFP producing gastric cancer metastasis. Only a panel of immunohis-tochemical markers allowed the definitive diagnosis of liver metastasis of endodermal stem cell-derived and AFP producing gastric cancer. We discuss the criteria for a differential diagnosis, as well as the possible link between RILD and emergence of liver neoplasia.展开更多
The Gsα/cAMP signaling pathway mediates the effect of a variety of hormones and factors that regulate the homeostasis of the post-natal skeleton.Hence,the dysregulated activity of Gsαdue to gain-of-function mutation...The Gsα/cAMP signaling pathway mediates the effect of a variety of hormones and factors that regulate the homeostasis of the post-natal skeleton.Hence,the dysregulated activity of Gsαdue to gain-of-function mutations (R201C/R201H)results in severe architectural and functional derangements of the entire bone/bone marrow organ.While the consequences of gain-of-function mutations of Gsαhave been extensively investigated in osteoblasts and in bone marrow osteoprogenitor cells at various differentiation stages,their effect in adipogenically-committed bone marrow stromal cells has remained unaddressed.We generated a mouse model with expression of Gsα^(R201C) driven by the Adiponectin(Adq)promoter.Adq-Gsα^(R201C) mice developed a complex combination of metaphyseal,diaphyseal and cortical bone changes.In the metaphysis,Gsα^(R201C) caused an early phase of bone resorption followed by bone deposition.Metaphyseal bone formation was sustained by cells that were traced by Adq-Cre and eventually resulted in a high trabecular bone mass phenotype.In the diaphysis,Gsα^(R201C),in combination with estrogen,triggered the osteogenic activity of Adq-Cre-targeted perivascular bone marrow stromal cells leading to intramedullary bone formation.Finally,consistent with the previously unnoticed presence of Adq-Cre-marked pericytes in intraosseous blood vessels,Gsα^(R201C) caused the development of a lytic phenotype that affected both cortical(increased porosity)and trabecular(tunneling resorption)bone.These results provide the first evidence that the Adq-cell network in the skeleton not only regulates bone resorption but also contributes to bone formation,and that the Gsα/cAMP pathway is a major modulator of both functions.展开更多
文摘We report a case of an isolated hepatic neoplasia which originated in a site of the liver previously affected by radiation induced liver disease (RILD) in a patient resected for gastric cancer and referred to us for high serum alpha-fetoprotein (AFP) levels. This case challenged us in distiguishing, even histologically, between primary liver cancer and AFP producing gastric cancer metastasis. Only a panel of immunohis-tochemical markers allowed the definitive diagnosis of liver metastasis of endodermal stem cell-derived and AFP producing gastric cancer. We discuss the criteria for a differential diagnosis, as well as the possible link between RILD and emergence of liver neoplasia.
基金supported by grants from Telethon GGP15198University of Pennsylvania Orphan Disease Center in partnership with the Fibrous Dysplasia Foundation MDBR16-114-FD, MDBR17-114-FD, MDBR18-114-FD/MAS+4 种基金Sapienza University RM11916B839074A8 to M.R.Fibrous Dysplasia Foundation MDBR-22101-FDMAS to B.P. and M.R.Sapienza University RM118164289636F0 to A.C.ZIA DE000380 to PGRAIRC IG-24614 to I.S。
文摘The Gsα/cAMP signaling pathway mediates the effect of a variety of hormones and factors that regulate the homeostasis of the post-natal skeleton.Hence,the dysregulated activity of Gsαdue to gain-of-function mutations (R201C/R201H)results in severe architectural and functional derangements of the entire bone/bone marrow organ.While the consequences of gain-of-function mutations of Gsαhave been extensively investigated in osteoblasts and in bone marrow osteoprogenitor cells at various differentiation stages,their effect in adipogenically-committed bone marrow stromal cells has remained unaddressed.We generated a mouse model with expression of Gsα^(R201C) driven by the Adiponectin(Adq)promoter.Adq-Gsα^(R201C) mice developed a complex combination of metaphyseal,diaphyseal and cortical bone changes.In the metaphysis,Gsα^(R201C) caused an early phase of bone resorption followed by bone deposition.Metaphyseal bone formation was sustained by cells that were traced by Adq-Cre and eventually resulted in a high trabecular bone mass phenotype.In the diaphysis,Gsα^(R201C),in combination with estrogen,triggered the osteogenic activity of Adq-Cre-targeted perivascular bone marrow stromal cells leading to intramedullary bone formation.Finally,consistent with the previously unnoticed presence of Adq-Cre-marked pericytes in intraosseous blood vessels,Gsα^(R201C) caused the development of a lytic phenotype that affected both cortical(increased porosity)and trabecular(tunneling resorption)bone.These results provide the first evidence that the Adq-cell network in the skeleton not only regulates bone resorption but also contributes to bone formation,and that the Gsα/cAMP pathway is a major modulator of both functions.
