Rhabdoid tumors (RTs) are a well-defined entity in the kidney or central nervous system of infants or children. However, soft-tissue involvement is uncommon. It’s an exceptional neonatal tumor of soft tissue. The ima...Rhabdoid tumors (RTs) are a well-defined entity in the kidney or central nervous system of infants or children. However, soft-tissue involvement is uncommon. It’s an exceptional neonatal tumor of soft tissue. The imaging characteristics of this tumor are not specific. Biopsy allows diagnosis;the histomorphological characteristics of rhabdoid tumors, their immunoreactivity to epithelial markers and vimentin, and the INI-1 loss are important tools for diagnosis. RT tumors are aggressive and have a rapidly fatal clinical course in most cases. Despite multidisciplinary therapy, the survival rate is very low. We report a rare case occurring in a male neonate who presents at birth with a voluminous right axillary mass. A CT scan showed a well-limited tumor mass with lobulated contours. An ultrasound-guided biopsy was performed on day 8, showing the morphology and immunoprofile of RT. The mass showed rapid growth. The child was admitted for respiratory distress at 3 weeks. A thoraco-abdominal CT showed an increase in the size of the mass with the appearance of multiple lymph nodes and pleural, hepatic, and renal metastases. The child died two days later.展开更多
Atypical teratoid/rhabdoid tumor(ATRT)is a rare childhood malignancy that originates in the central nervous system.Over ninety-five percent of ATRT patients have biallelic inactivation of the tumor suppressor gene SMA...Atypical teratoid/rhabdoid tumor(ATRT)is a rare childhood malignancy that originates in the central nervous system.Over ninety-five percent of ATRT patients have biallelic inactivation of the tumor suppressor gene SMARCB1.ATRT has no standard treatment,and a major limiting factor in therapeutic development is the lack of reliable ATRT models.We employed CRISPR/Cas9 gene-editing technology to knock out SMARCB1 and TP53 genes in human episomal induced pluripotent stem cells(Epi-iPSCs),followed by brief neural induction,to generate an ATRT-like model.The dual knockout Epi-iPSCs retained their stemness with the capacity to differentiate into three germ layers.High expression of OCT4 and NANOG in neurally induced knockout spheroids was comparable to that in two ATRT cell lines.Beta-catenin protein expression was higher in SMARCB1-deficient cells and spheroids than in normal Epi-iPSC-derived spheroids.Nucleophosmin,Osteopontin,and Ki-67 proteins were also expressed by the SMARCB1-deficient spheroids.In summary,the tumor model resembled embryonal features of ATRT and expressed ATRT biomarkers at mRNA and protein levels.Ribociclib,PTC-209,and the combination of clofilium tosylate and pazopanib decreased the viability of the ATRT-like cells.This disease modeling scheme may enable the establishment of individualized tumor models with patient-specific mutations and facilitate high-throughput drug testing.展开更多
Natural killer(NK)cells are cytotoxic immune cells that can eliminate target cells without prior stimulation.Human induced pluripotent stem cells(iPSCs)provide a robust source of NK cells for safe and effective cell-b...Natural killer(NK)cells are cytotoxic immune cells that can eliminate target cells without prior stimulation.Human induced pluripotent stem cells(iPSCs)provide a robust source of NK cells for safe and effective cell-based immunotherapy against aggressive cancers.In this in vitro study,a feeder-free iPSC differentiation was performed to obtain iPSC-NK cells,and distinct maturational stages of iPSC-NK were characterized.Mature cells of CD56^(bright)CD16^(bright)phenotype showed upregulation of CD56,CD16,and NK cell activation markers NKG2D and NKp46 upon IL-15 exposure,while exposure to aggressive atypical teratoid/rhabdoid tumor(ATRT)cell lines enhanced NKG2D and NKp46 expression.Malignant cell exposure also increased CD107a degranulation markers and stimulated IFN-γsecretion in activated NK cells.CD56^(bright)CD16^(bright)iPSC-NK cells showed a ratio-dependent killing of ATRT cells,and the percentage lysis of CHLA-05-ATRT was higher than that of CHLA-02-ATRT.The iPSC-NK cells were also cytotoxic against other brain,kidney,and lung cancer cell lines.Further NK maturation yielded CD56^(-ve) CD16^(bright)cells,which lacked activation markers even after exposure to interleukins or ATRT cells-indicating diminished cytotoxicity.Generation and characterization of different NK phenotypes from iPSCs,coupled with their promising anti-tumor activity against ATRT in vitro,offer valuable insights into potential immunotherapeutic strategies for brain tumors.展开更多
Rhabdoid tumor of kidney （RTK） is a highly malignant tumor that occurs in infants and children, and approximately 80% of patients are diagnosed in the first two years of life. It was firstly described in 1978, and w...Rhabdoid tumor of kidney （RTK） is a highly malignant tumor that occurs in infants and children, and approximately 80% of patients are diagnosed in the first two years of life. It was firstly described in 1978, and was defined as an independent disease in 1981. In the reported literatures, there were less in adolescents and extremely rare in adults.展开更多
Teratoid</span></span></span><span><span><span><span style="font-family:""> </span></span></span></span><span><span><span...Teratoid</span></span></span><span><span><span><span style="font-family:""> </span></span></span></span><span><span><span><span style="font-family:""><span style="font-family:Verdana;">rhabdoid tumors are highly malignant, rare </span><span style="font-family:Verdana;">and</span><span style="font-family:Verdana;"> aggressive. The prognosis is very poor, with a pejorative and rapidly lethal evolution. The objective of this study was to show </span><span style="font-family:Verdana;">diagnostic</span><span style="font-family:Verdana;"> and therapeutic approach through the report of four observations of </span><span style="font-family:Verdana;">rhabdoid</span><span style="font-family:Verdana;"> tumor of the kidney in children, treated in the oncology unit at the pediatric department CHU Hassan II Fez Morocco, collected </span><span style="font-family:Verdana;">over a period of</span><span style="font-family:Verdana;"> 10 years. The ages of the patients varied from 8 months and 5 and a half, with 3 girls and a boy. All </span></span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">children</span></span></span></span><span><span><span><span style="font-family:""> </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">have </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">abdominal distention with the discovery of a mass on clinical examination. </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The </span></span></span></span><span><span><span><span style="font-family:""><span style="font-family:Verdana;">patients were treated </span><span style="font-family:Verdana;"展开更多
文摘Rhabdoid tumors (RTs) are a well-defined entity in the kidney or central nervous system of infants or children. However, soft-tissue involvement is uncommon. It’s an exceptional neonatal tumor of soft tissue. The imaging characteristics of this tumor are not specific. Biopsy allows diagnosis;the histomorphological characteristics of rhabdoid tumors, their immunoreactivity to epithelial markers and vimentin, and the INI-1 loss are important tools for diagnosis. RT tumors are aggressive and have a rapidly fatal clinical course in most cases. Despite multidisciplinary therapy, the survival rate is very low. We report a rare case occurring in a male neonate who presents at birth with a voluminous right axillary mass. A CT scan showed a well-limited tumor mass with lobulated contours. An ultrasound-guided biopsy was performed on day 8, showing the morphology and immunoprofile of RT. The mass showed rapid growth. The child was admitted for respiratory distress at 3 weeks. A thoraco-abdominal CT showed an increase in the size of the mass with the appearance of multiple lymph nodes and pleural, hepatic, and renal metastases. The child died two days later.
文摘Atypical teratoid/rhabdoid tumor(ATRT)is a rare childhood malignancy that originates in the central nervous system.Over ninety-five percent of ATRT patients have biallelic inactivation of the tumor suppressor gene SMARCB1.ATRT has no standard treatment,and a major limiting factor in therapeutic development is the lack of reliable ATRT models.We employed CRISPR/Cas9 gene-editing technology to knock out SMARCB1 and TP53 genes in human episomal induced pluripotent stem cells(Epi-iPSCs),followed by brief neural induction,to generate an ATRT-like model.The dual knockout Epi-iPSCs retained their stemness with the capacity to differentiate into three germ layers.High expression of OCT4 and NANOG in neurally induced knockout spheroids was comparable to that in two ATRT cell lines.Beta-catenin protein expression was higher in SMARCB1-deficient cells and spheroids than in normal Epi-iPSC-derived spheroids.Nucleophosmin,Osteopontin,and Ki-67 proteins were also expressed by the SMARCB1-deficient spheroids.In summary,the tumor model resembled embryonal features of ATRT and expressed ATRT biomarkers at mRNA and protein levels.Ribociclib,PTC-209,and the combination of clofilium tosylate and pazopanib decreased the viability of the ATRT-like cells.This disease modeling scheme may enable the establishment of individualized tumor models with patient-specific mutations and facilitate high-throughput drug testing.
基金supported by the National Science Foundation(CBET-1652992 and CBET-1917618 to Y.L.).
文摘Natural killer(NK)cells are cytotoxic immune cells that can eliminate target cells without prior stimulation.Human induced pluripotent stem cells(iPSCs)provide a robust source of NK cells for safe and effective cell-based immunotherapy against aggressive cancers.In this in vitro study,a feeder-free iPSC differentiation was performed to obtain iPSC-NK cells,and distinct maturational stages of iPSC-NK were characterized.Mature cells of CD56^(bright)CD16^(bright)phenotype showed upregulation of CD56,CD16,and NK cell activation markers NKG2D and NKp46 upon IL-15 exposure,while exposure to aggressive atypical teratoid/rhabdoid tumor(ATRT)cell lines enhanced NKG2D and NKp46 expression.Malignant cell exposure also increased CD107a degranulation markers and stimulated IFN-γsecretion in activated NK cells.CD56^(bright)CD16^(bright)iPSC-NK cells showed a ratio-dependent killing of ATRT cells,and the percentage lysis of CHLA-05-ATRT was higher than that of CHLA-02-ATRT.The iPSC-NK cells were also cytotoxic against other brain,kidney,and lung cancer cell lines.Further NK maturation yielded CD56^(-ve) CD16^(bright)cells,which lacked activation markers even after exposure to interleukins or ATRT cells-indicating diminished cytotoxicity.Generation and characterization of different NK phenotypes from iPSCs,coupled with their promising anti-tumor activity against ATRT in vitro,offer valuable insights into potential immunotherapeutic strategies for brain tumors.
文摘Rhabdoid tumor of kidney （RTK） is a highly malignant tumor that occurs in infants and children, and approximately 80% of patients are diagnosed in the first two years of life. It was firstly described in 1978, and was defined as an independent disease in 1981. In the reported literatures, there were less in adolescents and extremely rare in adults.
文摘Teratoid</span></span></span><span><span><span><span style="font-family:""> </span></span></span></span><span><span><span><span style="font-family:""><span style="font-family:Verdana;">rhabdoid tumors are highly malignant, rare </span><span style="font-family:Verdana;">and</span><span style="font-family:Verdana;"> aggressive. The prognosis is very poor, with a pejorative and rapidly lethal evolution. The objective of this study was to show </span><span style="font-family:Verdana;">diagnostic</span><span style="font-family:Verdana;"> and therapeutic approach through the report of four observations of </span><span style="font-family:Verdana;">rhabdoid</span><span style="font-family:Verdana;"> tumor of the kidney in children, treated in the oncology unit at the pediatric department CHU Hassan II Fez Morocco, collected </span><span style="font-family:Verdana;">over a period of</span><span style="font-family:Verdana;"> 10 years. The ages of the patients varied from 8 months and 5 and a half, with 3 girls and a boy. All </span></span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">children</span></span></span></span><span><span><span><span style="font-family:""> </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">have </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">abdominal distention with the discovery of a mass on clinical examination. </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The </span></span></span></span><span><span><span><span style="font-family:""><span style="font-family:Verdana;">patients were treated </span><span style="font-family:Verdana;"
