Exocrine pancreatic neoplasms represent up to 95%of pancreatic cancers(PCs)and are widely recognized among the most lethal solid cancers,with a very poor 5-year survival rate of 5%-10%.The remaining<5%of PCs are ne...Exocrine pancreatic neoplasms represent up to 95%of pancreatic cancers(PCs)and are widely recognized among the most lethal solid cancers,with a very poor 5-year survival rate of 5%-10%.The remaining<5%of PCs are neuroendocrine tumors that are usually characterized by a better prognosis,with a median overall survival of 3.6 years.The most common type of PC is pancreatic ductal adenocarcinoma(PDAC),which accounts for roughly 85%of all exocrine PCs.However up to 10%of exocrine PCs have rare histotypes,which are still poorly understood.These subtypes can be distinguished from PDAC in terms of pathology,imaging,clinical presentation and prognosis.Additionally,due to their rarity,any knowledge regarding these specific histotypes is mostly based on case reports and a small series of retrospective analyses.Therefore,treatment strategies are generally deduced from those used for PDAC,even if these patients are often excluded or not clearly represented in clinical trials for PDAC.For these reasons,it is essential to collect as much information as possible on the management of PC,as assimilating it with PDAC may lead to the potential mistreatment of these patients.Here,we report the most significant literature regarding the epidemiology,typical presentation,possible treatment strategies,and prognosis of the most relevant histotypes among rare PCs.展开更多
Peritoneal metastases (PM) from colorectal cancer (CRC) are associated with poor survival. The extracellular matrix (ECM) plays a fundamental role in modulating the homing of CRC metastases to the peritoneum. The mech...Peritoneal metastases (PM) from colorectal cancer (CRC) are associated with poor survival. The extracellular matrix (ECM) plays a fundamental role in modulating the homing of CRC metastases to the peritoneum. The mechanisms underlying the interactions between metastatic cells and the ECM, however, remain poorly understood, and the number of in vitro models available for the study of the peritoneal metastatic process is limited. Here, we show that decellularized ECM of the peritoneal cavity allows the growth of organoids obtained from PM, favoring the development of three-dimensional (3D) nodules that maintain the characteristics of in vivo PM. Organoids preferentially grow on scaffolds obtained from neoplastic peritoneum, which are characterized by greater stiffness than normal scaffolds. A gene expression analysis of organoids grown on different substrates reflected faithfully the clinical and biological characteristics of the organoids. An impact of the ECM on the response to standard chemotherapy treatment for PM was also observed. The ex vivo 3D model, obtained by combining patient-derived decellularized ECM with organoids to mimic the metastatic niche, could be an innovative tool to develop new therapeutic strategies in a biologically relevant context to personalize treatments.展开更多
文摘Exocrine pancreatic neoplasms represent up to 95%of pancreatic cancers(PCs)and are widely recognized among the most lethal solid cancers,with a very poor 5-year survival rate of 5%-10%.The remaining<5%of PCs are neuroendocrine tumors that are usually characterized by a better prognosis,with a median overall survival of 3.6 years.The most common type of PC is pancreatic ductal adenocarcinoma(PDAC),which accounts for roughly 85%of all exocrine PCs.However up to 10%of exocrine PCs have rare histotypes,which are still poorly understood.These subtypes can be distinguished from PDAC in terms of pathology,imaging,clinical presentation and prognosis.Additionally,due to their rarity,any knowledge regarding these specific histotypes is mostly based on case reports and a small series of retrospective analyses.Therefore,treatment strategies are generally deduced from those used for PDAC,even if these patients are often excluded or not clearly represented in clinical trials for PDAC.For these reasons,it is essential to collect as much information as possible on the management of PC,as assimilating it with PDAC may lead to the potential mistreatment of these patients.Here,we report the most significant literature regarding the epidemiology,typical presentation,possible treatment strategies,and prognosis of the most relevant histotypes among rare PCs.
基金supported by an Italian law that allows taxpayers to allocate 0.5%of their tax to a research institution of their choice,by EU Horizon 2020 Marie Skłodowska-Curie programme 812772(project Phys2BioMed)by FET Open 801126(project EDIT).
文摘Peritoneal metastases (PM) from colorectal cancer (CRC) are associated with poor survival. The extracellular matrix (ECM) plays a fundamental role in modulating the homing of CRC metastases to the peritoneum. The mechanisms underlying the interactions between metastatic cells and the ECM, however, remain poorly understood, and the number of in vitro models available for the study of the peritoneal metastatic process is limited. Here, we show that decellularized ECM of the peritoneal cavity allows the growth of organoids obtained from PM, favoring the development of three-dimensional (3D) nodules that maintain the characteristics of in vivo PM. Organoids preferentially grow on scaffolds obtained from neoplastic peritoneum, which are characterized by greater stiffness than normal scaffolds. A gene expression analysis of organoids grown on different substrates reflected faithfully the clinical and biological characteristics of the organoids. An impact of the ECM on the response to standard chemotherapy treatment for PM was also observed. The ex vivo 3D model, obtained by combining patient-derived decellularized ECM with organoids to mimic the metastatic niche, could be an innovative tool to develop new therapeutic strategies in a biologically relevant context to personalize treatments.
