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PubMed1997

Transcriptional regulation in endoderm development: characterization of an enhancer controlling Hnf3g expression by transgenesis and targeted mutagenesis.

The hepatic nuclear factor 3gamma (Hnf3g) is a member of the winged helix gene family of transcription factors and is thought to be involved in anterior-posterior regionalization of the primitive gut. In this study, cis-regulatory elements essential for the expression of Hnf3g in vivo have been characterized. To this end, a 170 kb yeast artificial chromosome (YAC) carrying the entire Hnf3g locus was isolated and modified with a lacZ reporter gene. The two mouse lines carrying the unfragmented Hnf3g-lacZ YAC showed tissue-specific, copy number-dependent and position-independent expression, proving that 170 kb of the Hnf3g locus contain all elements important in the regulation of Hnf3g. Cis-regulatory elements necessary for expression of Hnf3g were identified in a three-step procedure. First, DNase I hypersensitive site mapping was used to delineate important chromatin regions around the gene required for tissue-specific activation of Hnf3g. Second, plasmid-derived transgenes and gene targeting of the endogenous Hnf3g gene locus were used to demonstrate that the 3'-flanking region of the gene is necessary and sufficient to direct reporter gene expression in liver, pancreas, stomach and small intestine. Third, a binding site for HNF-1alpha and beta, factors expressed in organs derived from the endoderm such as liver, gut and pancreas, was identified in this 3'-enhancer and shown to be crucial for enhancer function in vitro. Based on its expression pattern we inferred that HNF-1beta is a likely candidate for directly activating Hnf3g gene expression during development.

Animals↗
PubMed1985

Abnormal laminin secretion from parietal endoderm-like F9 cells in the presence of monensin.

We studied the effects of monensin on post-translational modification and intracellular transport of precursors of laminin subunits in parietal endoderm-like F9 cells. At concentrations higher than 0.1 microM, monensin inhibited the processing of high-mannose type precursors for all three subunits and caused their cytoplasmic accumulation. Furthermore, the secretion of mature subunits of laminin was inhibited. Instead, polypeptides with similar molecular weights to those of intracellular precursors were secreted. These polypeptides were immunologically related to laminin subunits and were sensitive to digestion with beta-N-acetylglucosaminidase H (Endo H). This indicated that Golgi complexes of the cells can transport the precursors of laminin subunits even with their terminal glycosylation inactivated by monensin. Tunicamycin induced the accumulation of unglycosylated precursors and strongly reduced their secretion into the medium.

Animals↗
PubMed1991

The influence of extracellular matrix components on the proliferation and migration of inner cell mass-derived parietal endodermal cells.

Reichert's membrane is a basement membrane deposited on the inner surfaces of rat and mouse trophectodermal (TE) cells beginning at the blastocyst stage of embryonic development that may play a role in the migration of the parietal endodermal (PE) cells to form an inner lining to the TE. The abilities of various glycoproteins present in Reichert's membrane to support PE cell migration and replication in vitro were examined by isolating inner cell masses (ICMs) from Day 5 rat blastocysts (Day 1 = day of vaginal plug) and culturing them (24-72 h) either on surfaces that had been precoated with collagen IV, fibronectin, or laminin or on thin (1-2-mm) gels of Matrigel (a tumor cell-derived basement membrane preparation) or type I collagen. Time-dependent changes in the area occupied by each ICM on the culture surface and the number of migrating cells per ICM were quantified by morphometric analysis. Type IV collagen, the basement membrane-specific collagen, supported ICM attachment and the outward migration (overall increase of approx. 60-fold in mean ICM area occupied on the culture surface) and proliferation (cell doublings following every 24 h of culture) of laminin-containing PE-like cells. These effects were not altered by the inclusion of exogenous fibronectin or laminin in the culture medium. Collagen IV coating concentrations as low as 0.16 micrograms/ml supported PE cell attachment and migration, and maximal responses were seen with a coating concentration of 0.63 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Primary prostatic endodermal sinus tumor (yolk sac tumor) combined with a small focal seminoma.

We report on a primary endodermal sinus tumor (EST) (yolk sac tumor) combined with a focal seminoma of the prostate occurring in a 24-year-old man. The prostate was widely infiltrated with neoplasms that penetrated the capsule and invaded into the bladder wall and urethra. Most areas of the tumor were composed of papillary and glandular epithelium in the fibrous or myxoid stroma. Schiller-Duval bodies and periodic acid-Schiff-positive hyaline bodies were focally present. In addition to yolk sac tumor, solid nests of seminoma were found in some areas. Immunohistochemistry using specific antibodies for alpha-fetoprotein and cytokeratin showed positive reaction on the EST portion, and placental alkaline phosphatase revealed positive staining in the seminoma portion and a part of EST. Tumor cells exhibited negative staining for prostate-specific antigen, prostatic acid phosphatase, carcinoembryonic antigen, vimentin, chromogranin A, and human chorionic gonadotropin. Despite radical surgery and ordinary cisplatin-based chemotherapy, the patient died 8 months after operation. At autopsy, only EST elements had metastasized to the lungs, liver, and brain, and no tumors were found in either testis. To our knowledge, this is the first reported case of a primary EST combined with a focal seminoma in the prostate.

Adult↗
PubMedDate not supplied

Genetic analysis of childhood endodermal sinus tumors by comparative genomic hybridization.

Childhood endodermal sinus tumors (CEST) are a distinct category of germ cell tumors that involve the testis and extragonadal sites of young children. Recurrent deletions of 1p and 6q have been reported by classic cytogenetic analysis of a small number of cases. Comparative genomic hybridization, a technique that screens the entire genome for genetic abnormalities, is applied to additionally define the genetic changes present in CESTs. Sixteen frozen CESTs (10 testicular, 6 extragonadal) obtained from Pediatric Oncology Group-affiliated institutions or from the Cooperative Human Tissue Network were analyzed. The most common changes were gain of 20q (10 tumors), 1q (6 tumors), 11q and 22 (4 tumors each), and loss of 6q (8 tumors with common deleted region of 6q24-qter), 16q (4 tumors), and 1p (4 tumors). Localized regions of gain were identified at 8q24 (2 tumors both showing c-myc amplification by fluorescence in situ hybridization). Gain of 12p, characteristic of adolescent germ cell tumor, was present in one testicular tumor. Comparative genomic hybridization was useful in defining genetic differences between adult and childhood tumors, in determining the common regions deleted on chromosome 6, and in identifying other involved loci to be correlated with clinical parameters in future studies.

Child, Preschool↗
PubMedDate not supplied

Successful chemotherapeutic decompression of primary endodermal sinus tumor presenting with severe spinal cord compression.

Management of spinal cord compression from a primary paraspinal endodermal sinus tumor (EST) is described. A 17-month-old child presented for treatment with near-complete paraplegia secondary to spinal cord compression from a primary paraspinal EST. The child was treated with cisplatin-based chemotherapy without laminectomy or radiation therapy. Rapid resolution of symptoms was observed. The child had an excellent tumor response and complete neurologic recovery with no sequelae. Chemotherapy alone is an alternative to laminectomy or radiation therapy in the management of epidural cord compression from EST, even when the cord compression is severe.

Endodermal Sinus Tumor↗
PubMed2004

Hemolytic uremic syndrome presenting after treatment of endodermal sinus tumor.

BACKGROUND: Hemolytic uremic syndrome is a rare multisystem disorder that is caused by infections, preeclampsia, autoimmune disorders, or oral contraceptive agents, and rarely in association with different cancers and chemotherapeutic agents. CASE: A 34-year-old woman who presented for evaluation of a pelvic mass received a diagnosis of International Federation of Gynecology and Obstetrics (FIGO) stage 1c endodermal sinus tumor at laparotomy. Three months after receiving 3 courses of bleomycin, etoposide, and cisplatinum, she presented with renal failure, thrombocytopenia, anemia, and severe hypertension. Cancer-associated hemolytic uremic syndrome was diagnosed, and the patient was treated with plasmaphoresis, blood transfusion, and hemodialysis. CONCLUSION: Cancer-associated hemolytic uremic syndrome has a high mortality rate; thus, prompt diagnosis is critical to survival.

Abdominal Pain↗
PubMed2006

Endodermal sinus tumor of the infant vagina treated exclusively with chemotherapy.

Endodermal sinus tumor (EST) of the vagina is a rare malignancy usually diagnosed before 3 years of age. Historically, the approach to therapy has included radical surgical resection, with adjuvant irradiation, and chemotherapy. An infant presented with vaginal bleeding, imaging evidence of a vaginal mass and an elevated alpha-fetoprotein level. Examination under anesthesia with vaginal biopsies confirmed the diagnosis of an EST (yolk sac) tumor of the vagina. After 5 cycles of chemotherapy, the alpha-fetoprotein had normalized and repeat vaginal biopsies for suspected residual disease was negative for malignancy. To allow preservation of sexual and reproductive function, chemotherapy as a sole modality of treatment for EST should be considered.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Mucinous carcinoid as an unusual manifestation of endodermal differentiation in ovarian yolk sac tumors.

We present, for the first time, two yolk sac tumors (YST) in women 37 and 18 years of age, one with a typical parietovisceral pattern and the other with a glandular pattern, which were associated with extensive areas of mucinous carcinoid (MC). The tumor in the first case had numerous nodules of tubulopapillary YST that merged with well-differentiated MC. This patient responded well to chemotherapy. The tumor in the second case consisted of an AFP-positive glandular YST, with a glandulopapillary pattern closely resembling fetal lung type adenocarcinoma, coexisting with an AFP-negative, cytokeratin 20-positive, atypical MC; transitional areas between the two components were also seen. In the material from the recurrences and metastases; however, no YST was present, the atypical MC having become the predominant component including areas that had become carcinomatous. There was a poor response to various chemotherapeutic regimens. AFP levels became negative during the course of disease paralleling the disappearance of the YST component and the overgrowth of an increasingly anaplastic MC. The patient died 1 year after diagnosis. We think that, in these cases, MC represented an unusual form of endodermal differentiation of the YST. It is important to differentiate the yolk sac and carcinoid components due to their different responses to chemotherapy and to evaluate the possibility of mucinous carcinoid developing into a highly aggressive carcinoma.

Adolescent↗
PubMed2006

Characteristics of the endoderm: embryonic and extraembryonic in mouse.

In mouse, four endodermal lineages are generated during the period from the late blastocyst to the end of gastrulation. The characteristics of each lineage and the proposed genetic cascades involved in their formation are reviewed. In addition, a list of the current markers used to identify these lineages in vivo and in vitro is presented.

Animals↗
PubMed1998

Functional intertwining of Dpp and EGFR signaling during Drosophila endoderm induction.

Endoderm induction in Drosophila is mediated by the extracellular signals Decapentaplegic (Dpp) and Wingless (Wg). We discovered a secondary signal with a permissive role in this process, namely Vein, a neuregulin-like ligand that stimulates the epidermal growth factor receptor (EGFR) and Ras signaling. Dpp and Wg up-regulate vein expression in the midgut mesoderm in two regions overlapping the Dpp sources. Experiments based on lack of function and ectopic stimulation of Dpp and EGFR signaling show that these two pathways are functionally interdependent and that they synergize with each other, revealing functional intertwining. The transcriptional response elements for the Dpp signal in midgut enhancers from homeotic target genes are bipartite, comprising CRE sites as well as binding sites for the Dpp signal-transducing protein Mad. Of these sites, the CRE seems to function primarily in the response to Ras, the secondary signal of Dpp. We discuss the potential significance of why an inductive process might use a secondary signal whose function is intertwined with that of the primary signal.

Animals↗
PubMed2004

BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo.

Deletion of various bone morphogenetic proteins (BMPs) and their downstream Smads in mice have clearly shown that BMP signaling is essential for the formation of primordial germ cells (PGCs). However, the molecular mechanism through which this takes place is still unclear. Here, we demonstrate that BMP4 produced in the extraembryonic ectoderm signals through ALK2, a type I BMP receptor, in the visceral endoderm (VE) to induce formation of PGCs from the epiblast. Firstly, embryonic day 5.5-6.0 (E5.5-E6.0) embryos cultured on fibronectin formed PGCs in the presence of VE, but not in its absence. Secondly, Alk2-deficient embryos completely lacked PGCs and the heterozygotes had reduced numbers, resembling Bmp4-deficient phenotypes. Thirdly, expression of constitutively active ALK2 in the VE, but not in the epiblast, was sufficient to rescue the PGC phenotype in Bmp4-deficient embryos. In addition, we show that the requirement for the VE at E5.5-E6.0 can be replaced by culturing embryos stripped of VE on STO cells, indicating that STO cells provide or transduce signals necessary for PGC formation that are normally transmitted by the VE. We propose a model in which direct signaling to proximal epiblast is supplemented by an obligatory indirect BMP-dependent signal via the VE.

Activin Receptors, Type I↗
PubMedDate not supplied

Endodermal sinus tumor of the vulva: successfully treated with high-dose chemotherapy.

Endodermal sinus tumors (EST) of the lower female genital tract are uncommon malignancies. Most of these tumors are found in the vagina or in the cervix. Only seven cases of EST involving the vulva are reported. We report an eighth case of vulvar EST. The patient recurred and was successfully treated with high-dose chemotherapy and peripheral blood cell transplantation. Because of their location, an early diagnosis of vulvar EST should be possible. Resection of the lesion by using a modified radical vulvectomy followed by cisplatin-based chemotherapy seems the best treatment for these tumors today. Our patient was initially treated with the help of local surgery and adjuvant chemotherapy consisting of three courses of etoposide and cisplatin. Sixteen months after the first diagnosis, pleural and lung metastases were diagnosed. Second-line chemotherapy followed by high-dose chemotherapy with autologous peripheral blood stem cell support was administered after resection of the lung metastases and biopsy of the pleural metastases. There is no evidence of disease 40 months after the diagnosis of the lung and pleural metastases, and 56 months after the primary diagnosis.

Adult↗
PubMed1993

A cytoplasmic actin gene from the silkworm Bombyx mori is expressed in tissues of endodermal origin and previtellogenic germ cells of transgenic Drosophila.

A cytoplasmic actin gene from Bombyx mori introduced into Drosophila melanogaster by P-element mediated transformation, is efficiently transcribed in larvae, pupae and adults of the host. The exogenous mRNA has the same size as the one observed in the Bombyx cells and the intron located within the coding region is properly excised, indicating a correct recognition of the exogenous sequences by the Drosophila transcriptional and splicing machineries. The expression of the Bombyx gene in Drosophila tissues was determined by transforming flies with a hybrid gene in which a large part of the Bombyx actin coding sequences was replaced by those of the bacterial lac Z gene. This chimaeric gene is specifically and highly expressed, from the embryo to the adult of the transgenic lines, in tissues of endodermal origin, the midgut and its derivatives, i.e. gastric caeca, the outer layer of the proventriculus, and in the Malpighian tubules. This gene is also expressed, at a lower level, in germ cells but restricted to the sixteen cell cysts during previtellogenesis. The expression of the Bombyx gene during development of transgenic flies was compared to that of the two Drosophila endogenous cytoplasmic actin genes and the results are discussed.

Actins↗
PubMed1987

Immortalization of precursors of endodermal, neuroectodermal and mesodermal lineages, following the introduction of the simian virus (SV40) early region into F9 cells.

F9 embryonal carcinoma cells were transfected with a hybrid plasmid containing the early genes of the simian virus SV40 under the control of the adenovirus type 5 E1A promoter [21]. These cells were induced to differentiate in aggregates in the presence of retinoic acid (RA). Unlike the derivatives of F9 that are usually obtained in this manner, the plasmid-containing cells were both programmed and immortalized; in addition, expression of the SV40 T antigen was now triggered. These immortalized cells could be separated into three classes: (1) extraembryonic derivatives, (2) embryonic differentiated tissues, (3) immature cells surrounding the differentiated cells. When injected into mice, the mixture of these cells gave rise to multipotential tumors. From the immature cells, committed precursors of the neuroectodermal, endodermal, and mesodermal pathways could be isolated by cloning and selection according to: (a) their specific pattern of differentiation in the tumors and (b) the occurrence of specific markers in the differentiated progeny. The isolation of stable immortalized cell lines corresponding to precursors of the three primitive germ layers and capable of differentiating reproducibly along a particular restricted pathway should facilitate molecular studies on early embryonic development in mouse.

Animals↗
PubMed1981

Studies on the biosynthesis of laminin by murine parietal endoderm cells.

The biosynthesis and processing of the polypeptides A (Mr = 450 x 10(3)), B1 (Mr = 240 x 10(3)), B2 (Mr = 230 x 10(3)) and C (Mr = 150 x 10(3)) of the extracellular matrix protein, laminin, were studied in murine parietal endoderm cells labelled with [35S]methionine. Various lines of evidence suggest that the A chains are not precursors to the smaller B chains. Firstly, the pulse-chase experiments, radioactivity in cytoplasmic A and (B1 + B2) chains declines with the same half-life of about 70 min. Secondly, peptide maps generated by digestion of A and B (B1 + B2) chains with Staphylococcus aureus V8 protease are different. Finally, rabbit antibodies to isolated, denatured (B1 + B2) chains do not cross-react with reduced and alkylated A chains. A, B1, B2 and C polypeptides are all glycosylated by an intracellular process involving the addition of tunicamycin and endo-beta-N-acetylglucosaminidase-H-sensitive N-linked oligosaccharide side chains. Further glycosylation probably occurs around the time of secretion. Disulphide bonding of some A and B chains can be observed in the cytoplasm within 10 min of adding [35S]methionine. However, it appears that some free A and B2 chains are present in the cytoplasm and that free A chains exist in the medium. The relationship between the 150 x 10(3)-Mr C glycoprotein and the A and B components is discussed. Although B and C chains generate different peptide maps after digestion with S. aureus V8 protease, antibodies raised against isolated, denatured C chains cross-react with reduced and alkylated B (but not A) chains. This suggests that B and C chains may share some antigenic determinant(s).

Animals↗
PubMed2006

Hindgut specification and cell-adhesion functions of Sphox11/13b in the endoderm of the sea urchin embryo.

Sphox11/13b is one of the two hox genes of Strongylocentrotus purpuratus expressed in the embryo. Its dynamic pattern of expression begins during gastrulation, when the transcripts are transiently located in a ring of cells at the edge of the blastopore. After gastrulation, expression is restricted to the anus-hindgut region at the boundary between the ectoderm and the endoderm. The phenotype that results when translation of Sphox11/13b mRNA is knocked down by treatment with morpholino antisense oligonucleotides (MASO) suggests that this gene may be indirectly involved in cell adhesion functions as well as in the proper differentiation of the midgut-hindgut and midgut-foregut sphincters. The MASO experiments also reveal that Sphox11/13b negatively regulates several downstream endomesoderm genes. For some of these genes, Sphox11/13b function is required to restrict expression to the midgut by preventing ectopic expression in the hindgut. The evolutionary conservation of these functions indicates the general roles of posterior Hox genes in regulating cell-adhesion, as well as in spatial control of gene regulatory network subcircuits in the regionalizing gut.

Animals↗
PubMed1998

Ovarian mixed germ cell tumor composed of dysgerminoma, endodermal sinus tumor, choriocarcinoma and mature teratoma in a 44-year-old woman: case report and literature review.

A case of ovarian mixed germ cell tumor in a 44-year-old woman was examined. The tumor was well circumscribed, measured 15 x 11 x 10 cm and appeared solid and partly cystic on the cut surface. Light microscopic examinations revealed that the tumor was composed of four different neoplastic germ cell elements, intermingled with each other. They are: (i) choriocarcinoma, immunohistochemically positive for human placental lactogen (hPL) and human chorionic gonadotropin (hCG); (ii) dysgerminoma, positive for placental alkaline phosphatase; (iii) endodermal sinus tumor positive for alpha-fetoprotein (AFP); and (iv) mature teratoma. Among these histological types, dysgerminoma occupied more than 50% of the neoplasm. The patient was diagnosed as a stage la ovarian mixed germ cell tumor and was subsequently treated with chemotherapy. A second-look laparotomy after completion of chemotherapy revealed no residual tumors in the abdomen and the patient is alive and well 15 months after operation. This is the fourth reported case of ovarian mixed germ cell tumor arising in patients over 40 years old.

Adult↗