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Polypoid pulmonary endodermal tumor resembling fetal lung: report of a case.

Pulmonary blastoma is a rare malignant neoplasm that histologically resembles airway structures and mesenchymal supporting tissues seen in the early phases of fetal lung development. The tumor either is biphasic with immature epithelial and stromal components or consists solely of an epithelial component. The preferred terminology for the latter is pulmonary endodermal tumor resembling fetal lung. Pulmonary blastoma is usually peripheral in location, and rarely does this tumor present intrabronchially. We report a case of pulmonary endodermal tumor resembling fetal lung presenting as a polypoid intrabronchial mass.

Adenocarcinoma↗

[Polycystic endodermal heterotopy of the atrioventricular node].

We present the two first Spanish cases about the endodermic heterotopia of the atrioventricular node. This is an infrequent and probably congenital lesion, with a not well known histogenesis and associated with heart blocks and sudden death, which affects women in most cases. The first observation attaches a 55 years-old woman with an acute leukemia who died during the first chemotherapy treatment. The second observation affects a 25 years-old woman, with previous heart blocks, who died suddenly. A complete post-mortem study was done in both cases (including cardiac conduction system) with conventional histopathological study and extensive immunohistochemical panel. Ultrastructural study of first case was done. In both cases a multicystic and tubular lesion was found in the atrioventricular node region. It was lined by two or more cubic and polyhedral cell layers. In the cystic lumina an eosinophilic material, which corresponded to acid and neutral mucosubstances was found. The maximal lesion's diameter were: 0.9 and 1.3 cm, respectively. Immunohistochemically it was detected in both cases strong positivity for cytoqueratines, EMA, CEA and focally for chromogranin A and calcitonin. The immunohistochemical results in both cases express and endodermic differentiation (with neuroendocrine fenotipe).

Adult↗

[A case of endodermal sinus tumor in the basal ganglia associated with Down's syndrome].

A case of Down's syndrome accompanied by endodermal sinus tumor of the left basal ganglia is reported. She was referred to us because of right hemiparesis. A CT scan showed a calcified mass in the left basal ganglia, which was well enhanced on contrast CT. Emergency removal of the tumor was performed because of its rapid growth, intratumoral hemorrhage, and acute hydrocephalus. The histological diagnosis established after surgery was endodermal sinus tumor. Alphafetoprotein-positive cells were seen in the resected tumor by light microscopy. Postoperative irradiation was very effective, and the high level of serum alphafetoprotein decreased during the course of irradiation. The residual tumor, enhanced on contrast CT, was treated by administration of cisplatin and etoposide after irradiation. Cases of malignant tumors other than leukemia, which are associated with Down's syndrome, are extremely rate. To our knowledge, including three cases of germ cell tumor, there have been only nine cases of brain tumors associated with Down's syndrome reported previously.

Adolescent↗

Transcription factor GATA-6 is expressed in malignant endoderm of pediatric yolk sac tumors and in teratomas.

Transcription factors GATA-4 and GATA-6 play critical roles in mammalian yolk sac differentiation and function. Previously, we showed that GATA-4 is a potential marker for malignant yolk sac endoderm in pediatric germ cell tumors. This highly malignant tissue can cause diagnostic problems because yolk sac components may be difficult to differentiate from other, especially immature, tissue types in teratomas. In the search for new molecular markers for germ cell tumors, we have surveyed GATA-6 expression in benign and malignant pediatric germ cell tumors using mRNA in situ hybridization and immunohistochemistry. GATA-6 was expressed in most yolk sac tumors examined and also in nonmalignant tissues including gut/respiratory epithelium, sebocytes, and neuroepithelium in mature and immature teratomas. Given that GATA-6 has not been discovered in sebocytes before, this finding was confirmed by immunohistochemistry of normal mouse samples, indicating a function for this transcription factor in the mammalian skin. Taken together, GATA-6 can be used to identify yolk sac components in pediatric germ cell tumors. Furthermore, it is also expressed in specific tissues in teratomas. GATA-6, together with GATA-4, can thus be used as a novel molecular marker in characterizing of pediatric germ cell tumors.

Adolescent↗

Metalloproteinases regulate parietal endoderm differentiating and migrating in cultured mouse embryos.

Extracellular matrix (ECM) adhesion and proteolysis play important roles in embryonic development. In previous work (Behrendtsen et al. [1992] Development 114:447-456) we showed that gelatinase B activity is rate-limiting for trophoblast-mediated invasion and degradation of ECM in culture. In the present study, we show that metalloproteinases (MMPs) have distinct roles in migration along ECM as opposed to invasion through ECM. We investigated the role of ECM proteolysis in the differentiation and migration of parietal endoderm (PE), the first embryonic migratory cell type, adhering to ECM surfaces. Gelatinase B was the major MMP of PE; mRNA and protein were detected in PE of 7.5- and 8.5-day embryos. Using cultures of inner cell masses (ICMs) isolated from mouse blastocysts, we found that inhibitors of metalloproteinases, specifically, tissue inhibitor of metalloproteinases (TIMP)-1 and a peptide hydroxamic acid stimulated outgrowth and differentiation of PE from ICMs cultured on fibronectin, but inhibitors of plasminogen activators did not. TIMP-1 increased the number of PE cells and mean distance migrated and increased expression of the PE differentiation marker vimentin; the increase in cell number was not at the expense of other cell types. The stimulatory effect of TIMP-1 was most marked on low concentrations of substrate fibronectin, decreasing as concentrations of fibronectin increased. TIMP-1 also stimulated the outgrowth of PE in blastocyst cultures and in ICM/trophectoderm co-cultures; in ICM/trophectoderm co-cultures TIMP-1 stimulated PE differentiation on higher concentrations of fibronectin than was permissive for ICMs cultured alone. These data indicate that metalloproteinase inhibitors preserved the migration-inducing status of the ECM. We conclude that metalloproteinases have distinct roles in invasive activity through ECM barriers and migratory activity along ECM surfaces.

Animals↗

Deletion of 1p36 in childhood endodermal sinus tumors by two-color fluorescence in situ hybridization: a pediatric oncology group study.

Childhood endodermal sinus tumors (CESTs) are a unique category of germ cell tumors involving the testis and extragonadal region in children less than 4 years of age. Recent studies of CEST have shown recurrent cytogenetic abnormalities involving the short arm of chromosome 1, most commonly, a deletion of distal 1p. Experience with neuroblastomas has shown that cytogenetic analyses may underestimate the frequency of 1p deletion. To determine the frequency of deletion of Ip in CEST and to verify that 1p is, in fact, deleted and not translocated, we analyzed ten tumors by two-color fluorescence in situ hybridization on single-cell suspensions of interphase nuclei by using a cosmid probe from the PITSLRE kinase (p58) locus (previously mapped to 1p36) cohybridized with plasmid probe pUC1.77 (which recognizes the 1q heterochromatic region) to determine the copy number of chromosome 1. Eight of the ten tumors examined showed evidence of deletion of 1p36. Five of the eight tumors exhibited multiple subdones, and all subdones showed deletion of at least one copy of 1p36, indicating that the deletion probably occurred before the development of chromosome 1 aneusomy. We conclude that deletions of the short arm of chromosome 1, specifically 1p36, do occur in CEST and probably occur at a, higher incidence than that found in neuroblastoma Further studies are needed to determine the degree of overlap of the common area of deletion in CEST with that of neuroblastoma and to determine whether 1p deletion in CEST has prognostic significance.

Child, Preschool↗

The endodermal origin of the endocrine cells of an adenocarcinoma of the colon of the rat.

A transplantable adenocarcinoma of the colon of the rat, which contained mucous, columnar, endocrine, and undifferentiated carcinoma cells, were cloned to see if each of the differentiated cell lineages had a common cell or origin. Four clonal lines were produced by the transplantation of single cells using micropipettes. Each tumor contained all four cell lineages but in markedly differing proportions. A confirmatory experiment was performed using a lung colony cloning assay. Seven tumors were obtained; each had mucous, columnar, endocrine, and undifferentiated cells. It is concluded that the endocrine cells of the colon are derived by differentiation from endoderm. They are not of neural crest origin.

Adenocarcinoma↗

Effects of cytochalasin B on the fine structure of organized endodermal cells of the early chick embryo.

Fresh pullet eggs (White Leghorn) were incubated for 36 to 48 hours. The blastoderms were exposed to cytochalasin B (CB), 10 or 40 microgram/ml, for 2, 5, and 15 minutes prior to fixation by immersion in buffered chick Ringers solution containing CB, previously dissolved in dimethysulfoxide (DMSO), or by sub-blastodermic injection. Controls fixed in ovo possess relatively flat surfaces with bulges due to uptake of yolk. Numerous microappendages (blebs, microvilli and ruffles) are present, especially at cell margins. DMSO-controls present a similar cell surface except that small blebs are more prominent. The plasmalemmas of CB-treated endodermal cells possess numerous large blebs (2-10 micron in diameter), smaller blebs (0.2 micron) and microvilli. Cell dissociation occurs in selected areas resulting in rounded cells, devoid of microappendages, with peripheral processes. Transmission electron microscopic preparations of tissues similar to those used for scanning electron microscopy reveal that large blebs are filled with membranous material. Microfilaments are present but lack their normal subplasmalemmal arrangement. Microtubules and other cell organelles are apparently unaffected by CB. Evidence in this study supports the concept that cytochalasin B exerts its influence through alteration of the plasmalemma.

Animals↗

Monoclonal antibodies identifying subsets of ectodermal, mesodermal, and endodermal cells in gastrulating and neurulating avian embryos.

The goal of our laboratory research is to elucidate the mechanisms underlying gastrulation and neurulation, using the avian embryo as a model system. In previous studies, we used two approaches to map the morphogenetic movements involved in these processes: (1) we constructed quail/chick transplantation chimeras in which grafted quail cells could be identified within chick host embryos by the presence of nucleolar-associated heterochromatin, and (2) we microinjected exogenous cell markers. However, it would be advantageous to be able to detect endogenous markers to demarcate various subsets of cells within the unmanipulated embryo. To elucidate such a series of natural markers, we have used monoclonal antibodies to identify epitopes found on subsets of ectodermal, mesodermal, and endodermal cells. Antibodies were made by immunizing mice against either homogenized ectoderm (i.e., prospective neural plate and surface ectoderm) or primitive streak, which had been microdissected from stage 3 chick embryos. Additionally, we screened a panel of antibodies made against soluble protein obtained from isolates of cell nuclei from late embryonic chick brain. Here, we describe the labeling patterns of three monoclonal antibodies, called MAb-GL1, GL2, and GL3 (GL, germ layer), during avian gastrulation and neurulation. Our results show that labeling early avian embryos with monoclonal antibodies can reveal previously undetected distributions of cells bearing shared epitopes, providing new labels for subsets of cells in each of the three primary germ layers.

Animals↗

Expression of a novel homeobox gene Ehox in trophoblast stem cells and pharyngeal pouch endoderm.

Ehox is an X-linked paired like homeobox gene identified from a differentiating embryonic stem (ES) cell cDNA library and is expressed at low levels in the preimplantation blastocyst and in ES cells in vitro. In embryos at 6.5 days post coitum (dpc), Ehox expression was restricted to the extraembryonic ectoderm which correlates with high-level expression in cultures of trophoblast stem cells. Extraembryonic expression becomes further restricted to the chorion and by 15.5 dpc Ehox is expressed in chorionic trophoblast of the labyrinth and spongiotrophoblast layers of the placenta. Ehox expression in the embryo proper first appears at 8.5 dpc in the anterior foregut endoderm and by 9.5 dpc is visible in pharyngeal pouches 2-4. By 10.5 dpc, Ehox expression becomes restricted to the ventral end of pouches 2 and 3. The data presented here is the first description of Ehox expression during embryogenesis and suggests a dual role for Ehox: (1) in trophoblast stem cells and compartments of the developing placenta, and (2) during development of the pharyngeal pouches, possibly delineating the area to become thymus.

Animals↗

The anterior visceral endoderm-turning heads.

The Anterior Visceral Endoderm is an extraembryonic tissue that plays a pivotal role during embryogenesis, being responsible for the proper orientation of the anterior-posterior axis of the embryo and for appropriate pattering of adjacent embryonic tissue. In this review I discuss the formation and migration of the AVE, and attempt to place some recent findings in the context of a working model.

Animals↗

A monoclonal antibody marker of human primitive endoderm.

Monoclonal antibodies were raised against the human germ-cell tumor line, LICR LON HT39/7. The cells of this human embryonal carcinoma cell line were first fixed in formol saline and then dehydrated prior to immunization so that antibodies were produced which reacted with antigens surviving conventional histological processing. Eleven hybrid clones secreted antibody that reacted with both formol saline-fixed and living cells of the immunogen. One of these antibodies, LICR LON FC 10.2, has been found to react with a membrane glycoprotein of molecular weight 200,000 restricted in distribution to the surfaces of undifferentiated teratoma-derived cell lines, the luminal surface of human fetal intestine and bronchus and areas of putative endodermal differentiation within germ-cell neoplasms.

Antibodies, Monoclonal↗

Evidence from molecular cloning that SPARC, a major product of mouse embryo parietal endoderm, is related to an endothelial cell 'culture shock' glycoprotein of Mr 43,000.

We describe the molecular cloning and characterization of a secreted, acidic, cysteine-rich glycoprotein (SPARC) of apparent Mr 43,000 which is a major product of mouse embryo parietal endoderm. These cells are specialized for the synthesis of a rapidly expanding basement membrane, but SPARC is not itself an integral matrix component. We show that SPARC is related structurally and antigenically to an Mr 43,000 glycoprotein secreted in large amounts by bovine aortic endothelial cells as part of a 'culture shock' response to in vitro conditions promoting their proliferation and migration.

Amino Acid Sequence↗

Villin expression in the visceral endoderm and in the gut anlage during early mouse embryogenesis.

Villin is an evolutionarily well conserved, Ca2+ regulated actin-binding protein, and a major structural component of the brush border of specialized absorptive cells. Using paraffin sections and an affinity purified polyclonal anti-villin antibody, we have investigated the early expression of villin during mouse embryogenesis. Villin is first detectable at the early post-implantation stage in visceral endodermal cells at the periphery of the egg cylinder. In this extra embryonic layer, the expression of villin increases and then persists until full term gestation. In the embryo, villin first appears in gut anlage during the axial rotation. Using the same methodology, villin expression is also demonstrated in differentiating embryoid bodies from a teratocarcinoma. Both in extra embryonic and embryonic extracts, villin expression is confirmed by immunoblot and Northern blot analysis which reveal, respectively, a single polypeptide of 93 kd and an mRNA of 3.4 kb in length, two well defined parameters for adult mouse villin gene expression. The results presented here show that paraffin sections allow very sensitive and highly resolutive detection of antigens in early embryogenesis. They provide a detailed developmental profile of villin expression and demonstrate the usefulness of villin as a marker for epithelial cells involved in absorptive processes.

Animals↗

Migration of F9 parietal endoderm cells is regulated by the ERK pathway.

Cell migration is regulated by the action of many signaling pathways that are activated in specific regions of migrating cells. Extracellular regulated kinase 1/2 (ERK) signaling can modulate the migration of cells by controlling the turnover of focal adhesions and the dynamics of actin polymerization. Focal adhesion turnover is necessary for cell migration, and the formation of strong actin stress fibers and mature focal adhesions puts the brakes on cell migration. We used F9 wild-type and vinculin null (vin-/-) parietal endoderm (PE) outgrowth to study the role of the ERK signaling pathway in cell migration. Upon plating of F9 embryoid bodies (EBs) onto laminin-coated dishes, PE cells migrate away from the EBs, providing an in vitro model for studying directed migration of this embryonic cell type. Our results suggest that the ERK pathway regulates PE cell migration by affecting the formation of focal adhesions and lamellipodia through the action of myosin light chain kinase (MLCK).

Animals↗

A factor necessary for normal morphogenetic function of anuran endoderm.

Cytoplasmic preparations obtained from late blastulae and early gastrulae of normal R. pipiens eggs contain factors which induce delayed lethal effects when injected into normal eggs at the beginning of cleavage. The same preparations can rescue some defective eggs which occur spontaneously (NS eggs), or are produced experimentally (ES eggs), by relieving the specific developmental syndrome displayed by either type of egg. The syndrome involves abnormal endoderm in which cytolysis is time-programmed. The lethal factors as well as the rescue factors are absent in the normal egg cytoplasm prior to the late blastula stage.

Animals↗

Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis.

Bone marrow stromal stem cells (MSCs) normally differentiate into mesenchymal derivatives but recently have also been converted into neurons, classical ectodermal cells. To begin defining underlying mechanisms, we extended our characterization of MSCs and the differentiated neurons. In addition to expected mesodermal mRNAs, populations and clonal lines of MSCs expressed germinal, endodermal, and ectodermal genes. Thus, the MSCs are apparently "multidifferentiated" in addition to being multipotent. Conversely, the differentiating neurons derived from populations and clonal lines of MSCs expressed the specific markers beta-III tubulin, tau, neurofilament-M, TOAD-64, and synaptophysin de novo. The transmitter enzymes tyrosine hydroxylase and choline acetyltransferase were localized to neuronal subpopulations. Our observations suggest that MSCs are already multidifferentiated and that neural differentiation comprises quantitative modulation of gene expression rather than simple on-off switching of neural-specific genes.

Age Factors↗