Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighty-one patients with testicular tumours received para-aortic and iliac lymph node irradiation using 16 MV X-rays through a single anterior field. Eleven of 62 patients with seminoma (18%) and 11 of 19 with teratoma (58%) developed dose-related gastro-duodenal complications. There were no long-term sequelae. The average follow-up is 4.3 years (range 9 months to 8 years). With this method of treatment the structures anterior to the nodes receive a higher dose than the nodes themselves, and it is not suitable when the patient's antero-posterior separation necessitates an applied dose greater than 4000 cGy in 20 daily fractions over 28 days (1351 RET).
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PMID:Gastro-duodenal morbidity of para-aortic and iliac lymph node irradiation using a single anterior 16 MV X-ray field. 314 Nov 2

The authors describe an extremely rare case of a teratoma of the placenta. The course of pregnancy was complicated by an EPH-gestosis pattern of signs and symptoms, and the foetus had hydrocephalus and a maxillary cleft combined with generalised hydrops foetalis and hydramnion. The morphological criteria of a placental teratoma are described and the requisite differential diagnostic delineations are drawn.
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PMID:[Teratoma of the placenta]. 341 97

Between 1954 and 1984 41 primary testicular tumours were treated in 40 children at the age of 0 to 9 years as well as 9 secondary testicular tumours in malignant systemic diseases or metastases. The histological reclassification of the number of cases revealed 15 yolk-sac-tumours, 10 differentiated teratomas of immature subtype, 1 intermediary malignant teratoma, 3 undifferentiated malignant teratomas, 2 Sertoli-cell-tumours (1 double-sided) and 5 rhabdomyosarcomas. 2 children each with undifferentiated malignant teratomas and rhabdomyosarcomas died, all before 1970. 5 children with yolk-sac-tumours and 2 with rhabdomyosarcomas who since 1974 have been treated with Ablatio testis and combination chemotherapy live without tumour. Histological classification and division into stages are proved and form the basis of a therapy conception which in all testicular tumours apart from the Ablatio testis contains the chemotherapy of different intensity (HTK-84), taking into consideration form of tumour, stage and age of the children. The retroperitoneal lymphadenectomy is recommended only in the proof of metastases.
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PMID:[Therapy of testicular tumors in childhood]. 403 83

IGF-II is abundant in the nascent mesoderm of the gastrulating mouse embryo. Its function at this developmental stage is unknown. We investigated it by following the in vitro and in vivo differentiation of several androgenetic, biparental, parthenogenetic, and androgenetic Igf2 -/- murine ES cell lines; these cells differed in endogenous IGF-II levels because Igf2 is paternally expressed in the mouse embryo in most tissues. The expression of mesoderm markers and the subsequent formation of muscle structures were correlated with endogenous IGF-II level during teratoma formation and during in vitro differentiation. In addition, the absence of Igf2 in androgenetic Igf2 -/- ES cells led to a severe impairment of mesoderm development, demonstrating the dependence of the preferential mesoderm development of androgenetic ES cells upon Igf2 activity, among the numerous known imprinted genes. The addition of exogenous IGF-II to in vitro differentiation culture medium led to a specific increase in the expression of mesoderm markers. Thus, we propose a novel model in which the binding of IGF-II to its principal signaling receptor, IGF1R, at the surface of mesoderm precursor cells increases the formation of mesoderm cells.
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PMID:IGF-II promotes mesoderm formation. 1107 82

Nonseminomatous components within testicular germ cell tumors affect patient prognosis to varying degrees. These components are well known to mimic early embryonic totipotential tissues. Prompted by the recent observation that fibroblast growth factor (FGF) 8, FGF4, and FGF receptor (FGFR) 1 are required for the growth of early postimplantational embryonic tissues, we investigated the expressions of FGF8, FGF4, and FGFRI in surgically resected specimens of primary testicular germ cell tumors using an immunohistochemical method. All cases of embryonal carcinoma (14 cases), yolk sac tumor (3 cases), and choriocarcinoma (3 cases) showed positive immunostaining for FGF8, FGF4, and FGFR1. In contrast, out of 13 cases of seminoma, immunostaining was negative for FGF8, FGF4, and FGFR1 in 8 cases (61.5%), 6 cases (46.1%), and 7 cases (53.8%), respectively. In 7 cases of mature and immature teratoma, most areas showed negative immunostaining. In addition, the Ki-67 labeling index showed extremely high mitogenic activity in embryonal carcinoma, yolk sac tumor, and choriocarcinoma, which are precisely the carcinomas with the highest expressions of FGF8, FGF4, and FGFR1. It is in keeping with the immunohistochemical result that murine teratocarcinoma P19 cells were shown to express FGF8, FGF4, and FGFRI only under undifferentiated growth conditions. Taken together, these findings confirm the involvement of FGF8, FGF4, and FGFR1 in highly proliferative conditions of nonseminomatous germ cell tumors.
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PMID:Predominant expression of fibroblast growth factor (FGF) 8, FGF4, and FGF receptor 1 in nonseminomatous and highly proliferative components of testicular germ cell tumors. 1176 80

Embryonic stem (ES) cells have been regarded as a powerful resource for cell replacement therapy. In recent reports mouse ES cells have been successfully applied in the treatment of spinal cord injury, hereditary myelin disorder of the central nervous system, and diabetes mellitus. Another type of disease that could benefit from the availability of stem cell therapy is liver disease. However, for this potential to be realized, it is necessary to demonstrate the differentiation of ES cells into hepatocytes. To demonstrate the in vivo differentiation potential of mouse ES cells, we injected ES cells into the spleen of immunosuppressed nude mice. Histological analysis of teratomas derived from injected ES cells revealed that some areas contained typical hepatocytes arranged in a sinusoidal structure. The hepatic nature of these cells was further confirmed by showing that transcripts of liver-specific genes were present in the differentiated teratoma using reverse transcriptase-polymerase chain reaction and immunohistochemistry using several liver-specific antibodies including HEP-PAR, phenylalanine hydroxylase, and mouse N-system aminotransferase to identify the respective proteins in the differentiated hepatocytes. This is the first demonstration that mouse ES cells can differentiate in vivo into a mixed population of hepatocytes of varying maturity. This finding extends the potential use of ES cells in the cell replacement therapy by including its possible application for treating liver diseases.
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PMID:In vivo differentiation of mouse embryonic stem cells into hepatocytes. 1216 76

This article has reviewed recent advances in understanding the molecular mechanisms of germ cell transformation, germ cell tumor differentiation, and germ cell tumor chemotherapy sensitivity and resistance. Future developments should include the following: The use of high-throughput techniques to assess tumor biology and evaluate new markers will allow more sophisticated assessment of prognosis. Future therapy will use oligonucleotide chips, perhaps specific to germ cell tumors or gene products associated with drug resistance, to assign treatment (radiation, RPLND, chemotherapy). The pathways associated with metastases and resistance will either replace or amplify the current risk algorithms and the clinician's ability to select therapy. The same high-throughput techniques will identify critical molecules and pathways, providing new specific treatment targets. Cell cycle-specific targets are an ideal focus of study, because genes abrogating normal cell cycle control and promoting germ cell tumorigenesis are increasingly identified. In germ cell tumors, CCND2 and KIT are open to study. Molecular and genetic markers of differentiation are additional resistance markers and should be a focus of study. In this context, the treatment of malignant transformation and the prediction of teratoma at metastatic sites will take on a greater importance. Over the past 2 decades, the treatment of germ cell tumors has become well-defined. Further improvement requires that investigators find new markers corresponding to tumor phenotype. This achievement will prevent unnecessary treatment in patients destined to have a favorable outcome, and will target biologically unfavorable or resistant disease for new therapy developed specifically to target the molecular or genetic defects that disrupt normal cell cycle control.
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PMID:The future of therapy for nonseminomatous germ cell tumors. 1247 77

The objective of the present study was to determine the level of EGFR expression in patients having benign ovarian tumors and in morphologically normal ovarian tissue by quantitative ligand binding assays. In a prospective study 42 patients with benign ovarian tumors and 30 with normal ovaries were included. In the group of patients expressing EGFR, those having benign tumors were 23 (64%) and the ones with normal ovaries--13 (36%). The average level of EGFR expression was the highest in the cases of teratoma adultum (110 fmol/mg), followed by mucinous (97 fmol/mg) and serous (30 fmol/mg) cystadenomas. The differences between the average levels of EGFR expression in mucinous and serous benign ovarian tumors were significant (p = 0.032), as for the remaining histological variants--statistically insignificant (p = 0.086). Mucinous cystadenomas possessed higher proliferative potential compared to serous cystadenomas.
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PMID:[Expression of epidermal growth factor receptors in benign ovarian tumors]. 1531 36

Metastatic germ cell tumors (GCT) are curable, however GCTs refractory to cisplatin-based chemotherapy have a poor prognosis. This study explores D-type cyclins as molecular targets in GCTs because all-trans-retinoic acid (RA)-mediated differentiation of the human embryonal carcinoma (EC) cell line NT2/D1 is associated with G1 cell cycle arrest and proteasomal degradation of cyclin D1. RA effects on D-type cyclins are compared in human EC cells that are RA sensitive or dually RA and cisplatin resistant (NT2/D1-R1) and in clinical GCTs that have both EC and mature teratoma components. Notably, GCT differentiation was associated with reduced cyclin D1 but increased cyclin D3 expression. RA was shown here to repress cyclin D1 through a transcriptional mechanism in addition to causing its degradation. The siRNA-mediated repression of individual cyclin D species resulted in growth inhibition in both RA sensitive and resistant EC cells. Only repression of cyclin D1 occurred in vitro and when clinical GCTs mature, implicating cyclin D1 as a molecular therapeutic target. To confirm this, the EGFR-tyrosine kinase inhibitor, Erlotinib, was used to repress cyclin D1. This inhibited proliferation in RA and cisplatin sensitive and resistant EC cells. Taken together, these findings implicate cyclin D1 targeting agents for the treatment of GCTs.
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PMID:Repression of cyclin D1 as a target for germ cell tumors. 1720 14

The distinction between seminoma and embryonal carcinoma based on morphology alone can sometimes be problematic, requiring the use of immunohistochemistry to facilitate diagnosis. D2-40 is a monoclonal antibody that reacts with an oncofetal antigen expressed by fetal germ cells and testicular germ cell tumors. The diagnostic value of D2-40 immunohistochemistry in distinguishing seminoma from embryonal carcinoma has not been determined. D2-40 immunoreactivity was evaluated in a series of testicular germ cell tumors and compared with that of KIT (CD117) and CD30, to assess the relative utility of this marker in discriminating between seminoma and embryonal carcinoma. Forty testicular germ cell neoplasms were examined, which included 19 seminomas, three embryonal carcinomas, three teratomas, one yolk sac tumor, and 14 mixed germ cell tumors. The 14 cases of mixed germ cell tumors contained components of seminoma (n=7), embryonal carcinoma (n=11), teratoma (n=10), yolk sac tumor (n=2), and choriocarcinoma (n=1). All cases of pure seminoma and the seminomatous components of mixed germ cell tumors exhibited positive immunoreactivity for D2-40. Focal positivity for D2-40 was also observed in 29% of the embryonal carcinoma samples. D2-40 immunoreactivity in seminomas was characterized by diffuse membrane staining, whereas for embryonal carcinomas, staining was focal and distributed along the apical surfaces of the neoplastic cells. Immunohistochemical staining for KIT was observed in 92% of the seminoma samples and in none of the embryonal carcinomas. Conversely, CD30 expression was identified in 93% of the embryonal carcinoma samples and in none of the seminomas. Other germ cell components showed no immunoreactivity for D2-40, KIT, or CD30. KIT and CD30 are effective immunohistochemical markers in separating seminoma from embryonal carcinoma. Although a highly sensitive marker for seminomas, D2-40 positivity was also observed in a subset of embryonal carcinomas, thus limiting the utility of this antibody for discriminating between these two malignancies.
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PMID:D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30. 1727 61


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