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1.
Tumour Biol ; 42(9): 1010428320962588, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32996421

RESUMO

A missense mutation of the guanine nucleotide binding protein alpha stimulating activity polypeptide 1 (GNAS) gene, typically Arg201Cys or Arg201His (R201H/R201C), leads to constitutive activation of the Gsα-cyclic AMP (cAMP) signaling pathway that causes several diseases. However, no germline mutations of GNAS have been identified to date, likely due to their lethality, and no robust human cell models have been generated. Therefore, the aim of this study was to generate GNAS-mutated disease-specific induced pluripotent stem cells as a model for these diseases. We then analyzed the functionality of this induced pluripotent stem cell model and differentiated epithelial cells. We generated disease-specific induced pluripotent stem cells by introducing a mutation in GNAS with the clustered regularly interspaced short palindromic repeats (CRISPR) nickase method, which has lower off-target effects than the conventional CRISPR/Cas9 method. We designed the target vector to contain the R201H mutation in GNAS, which was transfected into human control induced pluripotent stem cells (Nips-B2) by electroporation. We confirmed the establishment of GNASR201H-mutated (GNASR201H/+) induced pluripotent stem cells that exhibited a pluripotent stem cell phenotype. We analyzed the effect of the mutation on cAMP production, and further generated teratomas for immunohistochemical analysis of the luminal epithelial structure. GNAS-mutated induced pluripotent stem cells showed significantly higher levels of intracellular cAMP, which remained elevated state for a long time upon hormonal stimulation with parathyroid hormone or adrenocorticotropic hormone. Immunohistochemical analysis revealed that several mucins, including MUC1, 2, and MUC5AC, are expressed in cytokeratin 18 (CK18)-positive epithelial cells. However, we found few CK18-positive cells in mutated induced pluripotent stem cell-derived teratoma tissues, and reduced MUCINs expression in mutated epithelial cells. There was no difference in CDX2 expression; however, mutated epithelial cells were positive for CEA and CA19-9 expression. GNASR201H-mutated induced pluripotent stem cells and GNASR201H-mutated epithelial cells have distinct phenotypic and differentiation characteristics. We successfully established GNASR201H-mutated human induced pluripotent stem cells with increased cAMP production. Considering the differentiation potential of induced pluripotent stem cells, these cells will be useful as a model for elucidating the pathological mechanisms of GNAS-mutated diseases.


Assuntos
Cromograninas/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Células-Tronco Pluripotentes Induzidas/patologia , Modelos Biológicos , Mutação , Teratoma/patologia , Animais , Sistemas CRISPR-Cas , Células Cultivadas , Cromograninas/antagonistas & inibidores , Subunidades alfa Gs de Proteínas de Ligação ao GTP/antagonistas & inibidores , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Camundongos , Camundongos SCID , Teratoma/genética
2.
Medicine (Baltimore) ; 99(38): e22297, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957389

RESUMO

RATIONALE: Growing teratoma syndrome is defined as an increase in tumor size during or after systemic chemotherapy for germ cell tumors. These cases involve normal tumor maker levels and histological features of only mature teratoma. We report a rare case of an ovarian immature teratoma in a Japanese child that was diagnosed as growing teratoma syndrome. PATIENT CONCERNS: A 12-year-old girl presented a painful abdominal mass. She underwent left salpingo-oophorectomy for grade 1 immature teratoma in the left ovary. She did not undergo additional chemotherapy or radiotherapy. Four months later, she presented with grade 3 immature teratoma disseminated into the abdomen and pelvis. Chemotherapy resulted in the tumor maker levels returning to their normal ranges, although the tumors had grown slightly. DIAGNOSIS: The specimens resected by laparotomy after the chemotherapy consisted of mature tissue predominantly, although primitive neuroepithelium was observed in a small part of the specimen. The pathological diagnosis was grade 1 immature teratoma, notwithstanding the clinical diagnosis was growing teratoma syndrome based on the clinical features and pathogenesis. INTERVENTIONS: Laparotomy was performed at 7 months after the first operation, with resection of various tumors as well as the rectum, sigmoid colon, residual left fallopian duct, and a small part of the ileum and omentum. Some small tumors at the parietal peritoneum were ablated, although many tiny tumors around the uterus were left untreated. OUTCOMES: The patient has been free from recurrence for 5 years. LESSONS: Growing teratoma syndrome can develop in children, and their tumor size is comparable to that in adolescents and adults. Furthermore, development of growing teratoma syndrome from a primary germ cell tumor is presumably faster in children than in adolescents and adults. Complete resection of all growing teratoma tissue is recommended, although fertility-sparing surgery should be considered when possible.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/terapia , Salpingo-Ooforectomia/métodos , Teratoma/terapia , Bleomicina/uso terapêutico , Criança , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Gradação de Tumores , Recidiva Local de Neoplasia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Síndrome , Teratoma/diagnóstico por imagem , Teratoma/patologia
4.
Z Geburtshilfe Neonatol ; 224(4): 187-193, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32575128

RESUMO

Fetal intrapericardial teratomas are rare and benign cardiac tumors. By comprehensive literature retrieval of the pertinent articles published since 2000, 49 articles with 61 cases of intrapericadial teratomas were recruited into this study. The intrapericardial teratomas were found during pregnancy in 55 cases (fetal group), while the tumors were detected until neonatal period in 6 cases (neonatal group). In the fetal group, 15 cases were critical with fetal/neonatal respiratory distress or cardiac tamponade. Antenatal treatments including centesis, shunt placement, open fetal surgery and the ex utero intrapartum treatment were required in 24 (43.6%) fetal cases. Postnatal intubation was required in 19 cases with 18 of them having immediate intubation after birth. Postnatal tumor resection was performed in 41 (95.3%) cases. In neonatal group, 4 neonates had respiratory distress and/or cardiac tamponade. Neonatal intubation was required in 1 (16.7%) patient. Surgical tumor resection was performed in all 6 patients. A comparison between the fetal and neonatal groups revealed that the fetal group was associated with higher refractory effusions while the neonatal group had a higher incidence of respiratory distress. Although the all cause death rate was higher in the fetal group than in the neonatal (25.5 vs. 0%), but lack of a statistical significance. Antenatal treatments for fetal intrapericardial teratomas are feasible but carry higher risks in comparison to neonatal cases.


Assuntos
Tamponamento Cardíaco/etiologia , Neoplasias Cardíacas/cirurgia , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia , Teratoma/cirurgia , Feminino , Feto , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/patologia , Humanos , Recém-Nascido , Doenças do Recém-Nascido , Triagem Neonatal , Pericárdio , Gravidez , Cuidado Pré-Natal , Teratoma/diagnóstico por imagem , Teratoma/patologia , Ultrassonografia Pré-Natal
5.
Arch Gynecol Obstet ; 302(2): 315-320, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32556515

RESUMO

BACKGROUND: Anti-NMDA receptor antibody (anti-NMDAr) encephalitis, although still a rare condition, is well known to neurologists as it is the leading cause of non-infectious acute encephalitis in young women. However, this is less well known to gynecologists, who may have a decisive role in etiological management. Indeed, in 30-60% of cases in women of childbearing age, it is associated with the presence of an ovarian teratoma, whose removal is crucial in the resolution of symptomatology. OBJECTIVES: Primary objective of our work was to present a review in a very schematic and practical way for gynecologists, about the data on anti-NMDAr encephalitis in terms of epidemiology, clinical symptomatology, treatment and prognosis. The second objective was to propose a decision tree for gynecologists to guide them, in collaboration with neurologists and anesthesiologists, after the diagnosis of NMDAr encephalitis associated with an ovarian mass. METHOD: We conducted an exhaustive review of existing data using PubMed and The Cochrane Library. Then, we illustrated this topic by presenting two typical cases from our experience. RESULTS: Anti-NMDA antibody encephalitis association with an ovarian teratoma is common, especially in women of reproductive age. Complementary examinations in search of an ovarian teratoma must therefore be systematic to envisage a possible surgical excision that may improve patient prognosis. CONCLUSION: Anti-NMDA antibody encephalitis should not be ignored by gynecologists whose role in management is central.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Anticorpos/líquido cefalorraquidiano , Neoplasias Ovarianas/complicações , Receptores de N-Metil-D-Aspartato/imunologia , Teratoma/complicações , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/epidemiologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Exame Físico , Prognóstico , Reprodução , Teratoma/patologia , Teratoma/cirurgia , Adulto Jovem
6.
Medicine (Baltimore) ; 99(18): e20107, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358400

RESUMO

BACKGROUND: Intramedullary cervical spinal cord teratomas (ICTs) are extremely rare, and diagnosis and treatment are challenging. We conducted a systematic review of the literature on the diagnosis and treatment of ICT. METHOD: The presentation, imaging manifestations, diagnosis, management, surgery findings, prognosis and histology were reviewed following Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. English-language studies and case reports published from inception to 2018 were retrieved. Data on presentation, imaging characteristics, diagnosis, management, surgery findings, outcomes, and histopathology were extracted. RESULTS: Ten articles involving 10 patients were selected. The lesions were located in the upper cervical vertebrae in 4 cases, whereas in the lower cervical vertebrae in the remaining 6 cases. In 5 cases, the lesions were located on the dorsal side of the spinal cord, and in the center of the spinal cord in the remaining 5 cases. Quadriparesis (60%), paraplegia (30%), monoplegia (10%), and neck pain (50%) were the main presentations. The lesion appeared as a intramedullary heterogeneous signal during an MRI scan, and the lesion signal would be partially enhanced after the contrast medium was applied. All patients underwent surgical intervention through a posterior approach. Neurological function improved postoperatively in all patients. Two patients with pathology confirmed to be immature teratomas experienced recurrence. CONCLUSION: ICTs are extremely rare entities that are mainly located in the center or dorsal part of the spinal cord which mainly manifest as quadriplegia and neck pain. MRI is a useful modality that provides diagnostic clues. Surgery from a posterior approach is the primary treatment, and the effect of adjuvant therapy remains uncertain. The prognosis is mainly related to the pathological nature of the tumor and not the method of resection.


Assuntos
Vértebras Cervicais/patologia , Neoplasias da Medula Espinal/patologia , Teratoma/patologia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Humanos , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia
7.
Pediatr Blood Cancer ; 67(7): e28407, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32426927

RESUMO

Little is known about pseudoprogression in brain tumours other than gliomas. A 9-year-old male child with a pineal teratoma/germinoma underwent surgical resection followed by adjuvant chemo-radiotherapy. The magnetic resonance imaging scan 4 months post-radiotherapy showed a contrast-enhancing lesion within the surgical cavity suspicious of recurrence. These radiological findings subsequently resolved without any specific intervention. The child continues in remission 2 years post-treatment. This case illustrates the occurrence of pseudoprogression post-radiotherapy in intracranial GCT and highlights an unmet need for greater implementation of functional imaging techniques in paediatric neuro-oncology to avoid undue discontinuation of effective treatments or inappropriate enrolment in clinical trials.


Assuntos
Imagem por Ressonância Magnética/métodos , Imagem Molecular/métodos , Neoplasias Embrionárias de Células Germinativas/patologia , Pinealoma/patologia , Radioterapia Adjuvante/métodos , Teratoma/patologia , Criança , Progressão da Doença , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/radioterapia , Pinealoma/diagnóstico por imagem , Pinealoma/radioterapia , Prognóstico , Teratoma/diagnóstico por imagem , Teratoma/radioterapia
8.
J Pathol ; 251(3): 249-261, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32391583

RESUMO

Central nervous system (CNS) tumors are the most common solid tumor in pediatrics, accounting for approximately 25% of all childhood cancers, and the second most common pediatric malignancy after leukemia. CNS tumors can be associated with significant morbidity, even those classified as low grade. Mortality from CNS tumors is disproportionately high compared to other childhood malignancies, although surgery, radiation, and chemotherapy have improved outcomes in these patients over the last few decades. Current therapeutic strategies lead to a high risk of side effects, especially in young children. Pediatric brain tumor survivors have unique sequelae compared to age-matched patients who survived other malignancies. They are at greater risk of significant impairment in cognitive, neurological, endocrine, social, and emotional domains, depending on the location and type of the CNS tumor. Next-generation genomics have shed light on the broad molecular heterogeneity of pediatric brain tumors and have identified important genes and signaling pathways that serve to drive tumor proliferation. This insight has impacted the research field by providing potential therapeutic targets for these diseases. In this review, we highlight recent progress in understanding the molecular basis of common pediatric brain tumors, specifically low-grade glioma, high-grade glioma, ependymoma, embryonal tumors, and atypical teratoid/rhabdoid tumor (ATRT). © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Cerebelares/genética , Ependimoma/genética , Glioma/genética , Meduloblastoma/genética , Tumor Rabdoide/genética , Teratoma/genética , Idade de Início , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Cerebelares/classificação , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/patologia , Ependimoma/classificação , Ependimoma/mortalidade , Ependimoma/patologia , Predisposição Genética para Doença , Glioma/classificação , Glioma/mortalidade , Glioma/patologia , Humanos , Meduloblastoma/classificação , Meduloblastoma/mortalidade , Meduloblastoma/patologia , Gradação de Tumores , Fenótipo , Tumor Rabdoide/classificação , Tumor Rabdoide/mortalidade , Tumor Rabdoide/patologia , Teratoma/classificação , Teratoma/mortalidade , Teratoma/patologia
9.
J Ayub Med Coll Abbottabad ; 32(1): 132-135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468772

RESUMO

Paediatric thoracic tumours resection is one of the most difficult procedure for any anaesthetist. Paediatric population is different from adults in many aspects, as they have small thoracic volume and more compressible mass effect on their airway and vascular structures. we are reporting a case of a huge paediatric thoracic tumour resection occupying the left thoracic cavity. The possible mechanism, consequences, prevention and management discussed in this report.


Assuntos
Neoplasias do Mediastino , Teratoma , Criança , Humanos , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/cirurgia , Teratoma/diagnóstico , Teratoma/patologia , Teratoma/cirurgia , Tórax/diagnóstico por imagem , Tórax/patologia
10.
Nat Med ; 26(5): 712-719, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32341579

RESUMO

Atypical teratoid/rhabdoid tumors (ATRTs) typically arise in the central nervous system (CNS) of children under 3 years of age. Despite intensive multimodal therapy (surgery, chemotherapy and, if age permits, radiotherapy), median survival is 17 months1,2. We show that ATRTs robustly express B7-H3/CD276 that does not result from the inactivating mutations in SMARCB1 (refs. 3,4), which drive oncogenesis in ATRT, but requires residual SWItch/Sucrose Non-Fermentable (SWI/SNF) activity mediated by BRG1/SMARCA4. Consistent with the embryonic origin of ATRT5,6, B7-H3 is highly expressed on the prenatal, but not postnatal, brain. B7-H3.BB.z-chimeric antigen receptor (CAR) T cells administered intracerebroventricularly or intratumorally mediate potent antitumor effects against cerebral ATRT xenografts in mice, with faster kinetics, greater potency and reduced systemic levels of inflammatory cytokines compared to CAR T cells administered intravenously. CAR T cells administered ICV also traffic from the CNS into the periphery; following clearance of ATRT xenografts, B7-H3.BB.z-CAR T cells administered intracerebroventricularly or intravenously mediate antigen-specific protection from tumor rechallenge, both in the brain and periphery. These results identify B7-H3 as a compelling therapeutic target for this largely incurable pediatric tumor and demonstrate important advantages of locoregional compared to systemic delivery of CAR T cells for the treatment of CNS malignancies.


Assuntos
Antígenos B7/imunologia , Neoplasias Encefálicas/terapia , Vacinas Anticâncer/administração & dosagem , Imunoterapia Adotiva/métodos , Tumor Rabdoide/terapia , Teratoma/terapia , Adulto , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Células Cultivadas , Pré-Escolar , Feminino , Feto/patologia , Humanos , Lactente , Injeções Intraventriculares , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Receptores de Antígenos Quiméricos/administração & dosagem , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Tumor Rabdoide/imunologia , Tumor Rabdoide/patologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/transplante , Teratoma/imunologia , Teratoma/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Arch Gynecol Obstet ; 301(5): 1227-1233, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32253553

RESUMO

PURPOSE: To describe a case series of patients with malignant ovarian germ cell tumors (MOGCT) treated exclusively with fertility-sparing surgery (FSS) with or without adjuvant chemotherapy. METHODS: We retrospectively reviewed the records of 27 patients with MOGCT treated in the Department of Obstetrics and Gynecology, University Hospital Center Zagreb, Croatia, between January 2009 and July 2019. RESULTS: The median age at diagnosis was 22 years, and the main symptom was abdominal distension (57.0%). The most prevalent histological subtype was immature teratoma (n = 13, 48.1%). Twenty-three patients (85.2%) had laparotomy and 4 (14.8%) had laparoscopy, without conversions. Lymphadenectomy was performed in 16 (59.3%) patients, with 184 removed lymph nodes, and omentectomy was performed in 19 (70.4%) patients. The rate of chemotherapy administration was 81.5%. The follow-up length ranged between 6.30 and 115.1 months (median: 49.60 months). No patient experienced tumor recurrence. The rate of complete gross resection was 100%. At the time of analysis, all patients were alive and disease free. Fifty percent of patients who actively tried to conceive after FSS became pregnant, with 12 deliveries. CONCLUSION: This study suggests that FSS is a safe treatment option for MOGCT, regardless of tumor stage and histological type.


Assuntos
Preservação da Fertilidade , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Adolescente , Adulto , Quimioterapia Adjuvante/efeitos adversos , Croácia , Feminino , Fertilidade , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Omento/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovariectomia/métodos , Gravidez , Estudos Retrospectivos , Teratoma/patologia , Centros de Atenção Terciária , Adulto Jovem
12.
PLoS One ; 15(4): e0232047, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32339196

RESUMO

Spontaneous testicular teratomas (STTs) derived from primordial germ cells (PGCs) in the mouse embryonic testes predominantly develop in the 129 family inbred strain. Ter (spontaneous mutation) is a single nucleotide polymorphism that generates a premature stop codon of Dead end1 (Dnd1) and increases the incidence of STTs in the 129 genetic background. We previously found that DND1 interacts with NANOS2 or NANOS3 and that these complexes play a vital role in male embryonic germ cells and adult spermatogonia. However, the following are unclear: (a) whether DND1 works with NANOS2 or NANOS3 to regulate teratoma incidence, and (b) whether Ter simply causes Dnd1 loss or produces a short mutant DND1 protein. In the current study, we newly established a conventional Dnd1-knockout mouse line and found that these mice showed phenotypes similar to those of Ter mutant mice in spermatogenesis, oogenesis, and teratoma incidence, with a slight difference in spermiogenesis. In addition, we found that the amount of DND1 in Dnd1+/Ter embryos decreased to half of that in wild-type embryos, while the expression of the short mutant DND1 was not detected. We also found that double mutants for Dnd1 and Nanos2 or Nanos3 showed synergistic increase in the incidence of STTs. These data support the idea that Ter causes Dnd1 loss, leading to an increase in STT incidence, and that DND1 acts with NANOS2 and NANOS3 to regulate the development of teratoma from PGCs in the 129 genetic background. Thus, our results clarify the role of Dnd1 in the development of STTs and provide a novel insight into its pathogenic mechanism.


Assuntos
Células Germinativas Embrionárias/patologia , Proteínas de Neoplasias/fisiologia , Proteínas de Ligação a RNA/metabolismo , Teratoma/etiologia , Neoplasias Testiculares/etiologia , Testículo/patologia , Animais , Células Germinativas Embrionárias/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Oogênese , Proteínas de Ligação a RNA/genética , Espermatogênese , Teratoma/metabolismo , Teratoma/patologia , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Testículo/metabolismo
14.
Phytomedicine ; 69: 153198, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32151917

RESUMO

BACKGROUND: Induced pluripotent stem cells (iPSCs) are regarded as the best potential cell source for cell-based regenerative medicine. To develop a safe and efficient iPSC-based cell therapy, it is very important to avoid possible teratoma formation, which can arise from undifferentiated iPSCs (USCs) remaining among differentiated cell products. Dried bark of Magnolia officinalis (Magnolia cortex, MC) has long been used in traditional medicine to treat gastrointestinal ailments and allergic diseases, and has shown have various pharmacological activities, including anti-bacterial, anti-inflammatory, and anti-cancer effects. However, its effects on iPSCs have not yet been examined. PURPOSE: In this study, we investigated the selective cytotoxic effects of ethanol extract of MC (EEMC) on undifferentiated iPSCs and elucidated the underlying apoptotic mechanisms in detail. We also investigated the inhibitory effects of EEMC on teratoma formation via in ovo experiments. RESULTS: We found that EEMC greatly reduced cell growth and induced apoptotic cell death in USCs, but not in differentiated or normal cells. EEMC caused G2/M cell cycle arrest, mitochondrial damage, and caspase activation of USCs, accompanied by p53 accumulation. In p53KO human iPSCs, EEMC had no cytotoxicity, reinforcing that EEMC-mediated apoptosis of USCs is p53-dependent. EEMC did not cause DNA damage in iPSC-derived differentiated cells. In ovo teratoma formation assay revealed that EEMC treatment before injection efficiently eliminated USCs and prevented teratoma formation. CONCLUSIONS: These results collectively indicate that EEMC has potent anti-teratoma activity, and therefore can be used for the development of safe iPSC-based therapy.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Magnolia/química , Extratos Vegetais/farmacologia , Teratoma/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Etanol/química , Hepatócitos/citologia , Hepatócitos/fisiologia , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Extratos Vegetais/química , Teratoma/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
15.
Virchows Arch ; 477(1): 103-110, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32144540

RESUMO

INTRODUCTION: Two types of testicular teratomas are distinguished by the current WHO classification. Prepubertal-type teratomas are benign, while postpubertal-type teratomas are considered malignant with metastatic potential, and are associated with germ cell neoplasia in situ. Prepubertal-type cases have been reported in the adult testis potentially causing confusion and overtreatment. Demonstration of the absence of 12p abnormalities with fluorescence in situ hybridization may facilitate diagnosis. Recently, IMP3 has emerged as a potential marker of malignancy in this context. AIMS: The aim of this study was to assess histological characteristics, IMP3 expression and the presence of 12p abnormalities of pure testicular teratomas. RESULTS: Thirty-seven cases were studied, 7 patients were children and 30 were adults. Six out of 7 pediatric cases showed no 12p abnormality and were IMP3 positive. Seventy-four percent and 79% of adult cases showed 12p abnormalities and IMP3 expression, respectively. Negative cases were not associated with in situ neoplasia or metastasis, they were smaller (mean, 14 vs 39 mm), showed less histological diversity (2.4 vs 4.0 types of tissues on average) compared to positive cases. CONCLUSION: Our study provides further evidence that prepubertal-type (type I) teratomas may appear in adult testes, thus teratomas in adults may be either benign (type I) or malignant (type II). IMP3 expression may aid the distinction between type I and type II teratomas of the postpubertal testis even when GCNIS and 12p status cannot be assessed.


Assuntos
Neoplasias Embrionárias de Células Germinativas/patologia , Teratoma/patologia , Neoplasias Testiculares/patologia , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Criança , Cromossomos Humanos Par 12 , Feminino , Técnicas Histológicas/métodos , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/metabolismo
16.
Nat Commun ; 11(1): 1195, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139672

RESUMO

Here, we report that the functionality of vascular progenitors (VP) generated from normal and disease-primed conventional human induced pluripotent stem cells (hiPSC) can be significantly improved by reversion to a tankyrase inhibitor-regulated human naïve epiblast-like pluripotent state. Naïve diabetic vascular progenitors (N-DVP) differentiated from patient-specific naïve diabetic hiPSC (N-DhiPSC) possessed higher vascular functionality, maintained greater genomic stability, harbored decreased lineage-primed gene expression, and were more efficient in migrating to and re-vascularizing the deep neural layers of the ischemic retina than isogenic diabetic vascular progenitors (DVP). These findings suggest that reprogramming to a stable naïve human pluripotent stem cell state may effectively erase dysfunctional epigenetic donor cell memory or disease-associated aberrations in patient-specific hiPSC. More broadly, tankyrase inhibitor-regulated naïve hiPSC (N-hiPSC) represent a class of human stem cells with high epigenetic plasticity, improved multi-lineage functionality, and potentially high impact for regenerative medicine.


Assuntos
Vasos Sanguíneos/patologia , Diabetes Mellitus/patologia , Células-Tronco Pluripotentes Induzidas/patologia , Isquemia/terapia , Retina/patologia , Células-Tronco/patologia , Tanquirases/antagonistas & inibidores , Adulto , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Linhagem da Célula/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Dano ao DNA , Inibidores Enzimáticos/farmacologia , Epigênese Genética/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Código das Histonas , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Isquemia/patologia , Camundongos , Organoides/efeitos dos fármacos , Organoides/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Regiões Promotoras Genéticas/genética , Células-Tronco/efeitos dos fármacos , Células-Tronco/ultraestrutura , Tanquirases/metabolismo , Teratoma/patologia , Transcrição Genética/efeitos dos fármacos
17.
J Cardiothorac Surg ; 15(1): 35, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051013

RESUMO

BACKGROUND: Mediastinal mature teratomas are rare tumors with diverse surgical approaches. The aim of this study is to review our experience of thoracoscopic surgery management in patients with teratomas. METHODS: We retrospectively reviewed 28 consecutive patients with mediastinal mature teratomas who underwent thoracoscopic surgery at Viet Duc University Hospital from January 2008 to August2018. Patients were divided into 2 groups with 2 types of thoracoscopic surgery, closed thoracoscopic surgery (CTS) group and video-assisted thoracoscopic surgery (VATS) group. The selection of sugical approach was based on sizes, locations and characteristics of tumors. Post-operative outcomes were assessed and compared between these 2 groups. RESULTS: There were 14 female and 14 male patients with a median age of 41.2 ± 13.8 years. A total of 22 teratomas were located on the right side of the chest cavity and 6 on the left side. We performed CTS in 21 patients (75%) and VATS in 7 patients (25%) for tumor resection. There were 3 cases (10.7%) required conversion to minithoracotomy (5 cm in incision length). Skin appendages accounted for the highest rate (96.4%) in pathology. There was no record of mortality or tumor recurrence detected by computerized tomography. CONCLUSION: A thoracoscopic surgery for a mediastinal mature teratoma was a feasible choice. Challenging factors such as large tumors, intraoperative bleeding and strong tumor cell adhesion were considered handling by conversion to mini-thoracotomy that could ensure safety procedures and complete removal of tumors. Extraction of tumor contents might be performed for patients with large mature cystic teratomas to facilitate thoracoscopic surgery.


Assuntos
Neoplasias do Mediastino/cirurgia , Teratoma/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Adolescente , Adulto , Criança , Conversão para Cirurgia Aberta , Feminino , Humanos , Masculino , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Teratoma/patologia , Toracotomia , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
18.
J Cardiothorac Surg ; 15(1): 36, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066478

RESUMO

BACKGROUND: Mediastinal teratoma is a rare disease, many cases were reported before, but few articles focus on large case analyses. The objective of this article is to summarize the clinical characteristics of benign mediastinal teratoma and the experience of surgical treatment, especially thoracoscopic surgery for benign mediastinal teratoma. METHODS: The clinical data of 108 patients with benign mediastinal teratoma confirmed by operation and pathology from January 1992 to January 2018 were analyzed retrospectively. The clinical symptoms, imaging examination, surgical methods and prognosis of all patients were analyzed. We compared the difference of thoracoscopic surgery and thoracotomy surgery using 102 patients underwent only chest surgery. Normally distributed continuous variables were compared by independent sample t test. Categorical variables were analyzed by chi-square test. RESULTS: Imaging examination showed that all 108 cases of mediastinal teratoma were located in the anterior region of mediastinum. All cases underwent surgical resection, postoperative pathology confirmed that all cases were benign. 1 case was taken simple neck collar incision, 5 case was taken median thoracotomy combined with neck incision, other 102 cases were taken thoracoscopic surgery (22) or thoracotomy surgery (80). 4 cases were treated with partial pericardial resection due to adhesions, 12 cases underwent partial pericardial resection, 5 cases underwent lobectomy, 9 cases underwent wedge resection of lobe, and 2 patients underwent anonymous vein angioplasty. 1 case underwent second operation because of postoperative bleeding, 1 case of chylothorax, 1 case of recurrent laryngeal nerve injury, 2 cases of wound infection, 1 case of secondary pulmonary infection. 106 cases were followed up, period from 12 months to 10 years, no recurrence of tumor was found. Comparing to take thoracotomy surgery, patients underwent thoracoscopic surgery has strong advantage on intraoperative blood loss and hospital stay days after surgery (P < 0.05). tumor maximum diameter is larger for thoracotomy surgery group, as well as more patients suffer estimated adhesions from preoperative imaging. so we compared above parameters in patients with tumor diameter less than 10 cm with or without estimated adhesions from preoperative imaging, a strong advantage still can be found in thoracoscopic surgery group, inpatients with estimated adhesions from preoperative imaging, intraoperative blood loss (38.75 ± 15.53 vs 169.17 ± 208.82., P = 0.04) and hospital stay days after surgery (5.50 ± 0.93 vs 9.43 ± 6.54., P = 0.04) were better. In patients without estimated adhesions from preoperative imaging, intraoperative blood loss (46.67 ± 10.00 vs 110.53 ± 123.13., P = 0.06) and hospital stay days after surgery (4.70 ± 1.16 vs 7.53 ± 2.32., P = 0.01) were better. Especially, in thoracoscopic surgery group, hospital stay days after surgery was significantly shorter. CONCLUSION: The clinical manifestations and imaging performance of benign mediastinal teratoma were complicated, and the surgical treatment was effective. Compared with traditional thoracotomy surgery, thoracoscopic surgery can improve patients' quality of life, less intraoperative blood loss, and less hospital stay days after surgery, so if condition is permitted, thoracoscopic surgery should be a better choice.


Assuntos
Neoplasias do Mediastino/cirurgia , Teratoma/cirurgia , Toracoscopia , Toracotomia , Adulto , Perda Sanguínea Cirúrgica , Feminino , Humanos , Tempo de Internação , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Teratoma/diagnóstico por imagem , Teratoma/patologia , Toracoscopia/efeitos adversos , Toracotomia/efeitos adversos , Aderências Teciduais/complicações , Aderências Teciduais/cirurgia , Carga Tumoral
19.
Cancer Imaging ; 20(1): 15, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024553

RESUMO

BACKGROUND: Mature cystic teratoma (MCT) with meningioma of the ovary is a very rare benign tumor. There is only 3 reports of this disease until June 2019. The aim of the present study was to describe a ovarian mature cystic teratoma containing meningioma and nests of neuroblasts in a 15-year-old girl. METHODS: The method used in the present study consists of description of the clinical history, image lab features, and pathological result. RESULTS: The patient complained of a 2-month history of irregular vaginal bleeding. Abdominal computed tomography (CT) showed a large oval cystic-solid mass with septations and fat density shadow, in abdomen pelvic cavity. The cystic part was the main component in the mass. The tumoral solid parts and its internal division could be seen intensified from slight to moderate on contrast-enhanced CT images compared with those on precontrast images, and the solid parts showed heterogeneous enhancement. Neighbouring intestinal tract and the uterus displaced by compression. The pathological examination confirmed the diagnosis. CONCLUSIONS: The clinical feature of ovarian mature cystic teratoma with meningioma includes a lack of specificity. Only meticulous recording of the gross features, histopathological examination including immunohistochemistry and supportive clinical and radiological findings to arrive at a correct diagnosis in case of unconventional tumours. If necessary, preoperative puncture can be performed.


Assuntos
Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Teratoma/diagnóstico por imagem , Adolescente , Feminino , Humanos , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/patologia , Meningioma/complicações , Meningioma/patologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/patologia , Teratoma/complicações , Teratoma/patologia , Tomografia Computadorizada por Raios X
20.
J Urol ; 204(1): 96-103, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32003612

RESUMO

PURPOSE: We analyzed the oncologic outcomes of men undergoing primary retroperitoneal lymph node dissection and characterized the use of adjuvant chemotherapy and template dissections. MATERIALS AND METHODS: Retrospective review of the Indiana University testis cancer database identified patients who underwent primary retroperitoneal lymph node dissection between January 2007 and December 2017. Patients and providers were contacted to obtain information regarding adjuvant therapy, recurrence and survival. The primary outcome was recurrence-free survival. Kaplan-Meier curves assessed survival differences stratified by pathological stage, template of dissection and use of adjuvant chemotherapy. RESULTS: A total of 274 patients were included in the study. Most men presented with clinical stage I disease (214, 78%). A modified unilateral template was performed in 257 (94%) and bilateral template in 17 (6%). Overall 148 (54%) and 126 (46%) men had pathological stage (PS) I and PS-II disease, respectively. Thirteen patients (10%) with PS-II disease were treated with adjuvant chemotherapy. With a median followup of 55 months only 33 (12%) patients had recurrence. Of the 113 patients with PS-II disease who did not receive chemotherapy 21 (19%) had disease relapse and 81% were cured with surgery alone and never had recurrence. No difference in recurrence-free survival was noted between modified and bilateral template dissections. CONCLUSIONS: The use of adjuvant chemotherapy has been minimal during the last decade. The majority (81%) of men with PS-II disease were cured with retroperitoneal lymph node dissection alone and were able to avoid chemotherapy. Modified unilateral template dissection provided excellent oncologic control while minimizing morbidity.


Assuntos
Quimioterapia Adjuvante/estatística & dados numéricos , Excisão de Linfonodo , Espaço Retroperitoneal/cirurgia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Adulto , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Espaço Retroperitoneal/patologia , Estudos Retrospectivos , Seminoma/mortalidade , Seminoma/patologia , Seminoma/terapia , Teratoma/mortalidade , Teratoma/patologia , Teratoma/terapia , Neoplasias Testiculares/mortalidade
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