MedWorm: Embryonal Carcinoma

What is the evidence for radical surgery in the management of localized embryonal bladder/prostate rhabdomyosarcoma?

Pediatric Blood and Cancer — Sun, 29 Jan 2012 12:58:06 +0100

AbstractAs survival outcomes for bladder/prostate rhabdomyosarcoma have improved over the last 40 years, the emphasis has shifted to minimizing treatment related morbidity. We undertook a critical review of the current literature to examine the role of radical pelvic surgery to achieve local control. We illustrate that there appears to be no difference in overall survival or event free survival when comparing differing modalities utilized in local disease control, microscopic disease clearance does not correlate with improved outcomes, and the morbidity associated with radical surgery for BP RMS is significantly greater than for a conservative method of local control. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

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Suppression of Cancer Stemness p21-regulating mRNA and microRNA Signatures in Recurrent Ovarian Cancer Patient Samples

Journal of Ovarian Research — Thu, 19 Jan 2012 05:00:00 +0100

Conclusion: We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p53-p21 mechanism in ovarian disease. Targeting CSCs within ovarian cancer represents a potential therapeutic avenue. (Source: Journal of Ovarian Research)

A new chitosan-thymine conjugate: Synthesis, characterization and biological activity.

International Journal of Biological Macromolecules — Wed, 18 Jan 2012 05:00:00 +0100

Authors: Kumar S, Koh J, Kim H, Gupta MK, Dutta PK Abstract Conjugation of chitosan with nucleobases is expected to expand its not only antimicrobial activity but also anti-cancer activity. Here, we report the synthesis of a novel chitosan-thymine conjugate by the reaction between chitosan and thymine-1-yl-acetic acid followed by acylation. The synthesized conjugate was characterized by FTIR, XRD, (1)H NMR, TGA and SEM. The microbiological screening results demonstrated the antimicrobial activity of the conjugate against bacteria viz., Escherichia coli, Staphylococcus aureus, and fungi viz., Aspergillus niger. The chitosan-thymine conjugate also inhibited (p<0.05) the proliferation of human liver cancer cells (HepG2) in a dose-dependent manner but had no cellular toxicity in non...

Regulation of neurogenesis and gliogenesis of retinoic acid-induced P19 embryonal carcinoma cells by P2X2 and P2X7 receptors studied by RNA interference.

International Journal of Developmental Neuroscience — Fri, 13 Jan 2012 05:00:00 +0100

Authors: Yuahasi KK, Demasi MA, Tamajusuku AS, Lenz G, Sogayar MC, Fornazari M, Lameu C, Nascimento IC, Glaser T, Schwindt TT, Negraes PD, Ulrich H Abstract Embryonic carcinoma cells are widely used models for studying the mechanisms of proliferation and differentiation occurring during early embryogenesis. We have now investigated how down-regulation of P2X2 and P2X7 receptors expression by RNA interference (RNAi) affects neural differentiation and phenotype specification of P19 embryonal carcinoma cells. Wild-type P19 embryonal carcinoma cells or cells stably expressing shRNAs targeting P2X2 or P2X7 receptor expression were induced to differentiate into neurons and glial cells in the presence of retinoic acid. Silencing of P2X2 receptor expression along differentiation promoted c...

18F‐FDG microPET imaging detects early transient response to an IGF1R inhibitor in genetically engineered rhabdomyosarcoma models

Pediatric Blood and Cancer — Wed, 11 Jan 2012 05:00:00 +0100

Conclusions18F‐FDG PET imaging is a potential imaging biomarker of molecular susceptibility to targeted agents early in treatment for this aggressive form of sarcoma, but may find best use serially for Phase I/II studies where chemotherapy and targeted agents are combined to cytoreduce tumors and abrogate Igf1r inhibitor resistance. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Differential effects of AdOx on gene expression in P19 embryonal carcinoma cells

BMC Neuroscience - Latest articles — Fri, 06 Jan 2012 05:00:00 +0100

Conclusions: Key pluripotency genes were controlled by different mechanisms, including the differential enrichment of repressive histone methylation marks. These data provided novel clues regarding the critical role of histone methylation in the maintenance of pluripotency and the determination of cell fate in P19 pluripotent cells. (Source: BMC Neuroscience - Latest articles)

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Malignant mesothelioma of the tunica vaginalis testis: diagnostic studies and differential diagnosis.

Archives of Pathology and Laboratory Medicine — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Chekol SS, Sun CC Abstract Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor representing 0.3% to 5% of all malignant mesotheliomas. Gross examination of testicular mesotheliomas typically reveals tumor nodules studding the thickened tunica vaginalis and, in some cases, infiltrating the testicular parenchyma, leading to diagnostic challenges. Microscopically, the tumor is characterized by epithelioid cells arising from the tunica vaginalis with papillary, tubulopapillary, or solid architectural patterns. The papillae are usually lined by a single layer of cells with relatively bland cytologic features. An epithelial cell phenotype admixed with a sarcomatoid pattern has also been described in a few cases. Immunohistochemically, the tumor is us...

Laparoscopic Retroperitoneal Lymph Node Dissection for Clinical Stage I Nonseminomatous Germ Cell Tumor: A Large Single Institution Experience

The Journal of Urology — Mon, 19 Dec 2011 05:00:00 +0100

Conclusions: Laparoscopic retroperitoneal lymph node dissection appears to be safe, viable and effective for stage I nonseminomatous germ cell tumors. The lack of retroperitoneal recurrence in pN0–N1 cases supports the oncological efficacy of this approach. Its low morbidity and rapid convalescence compare favorably with those in open series. (Source: The Journal of Urology)

DICER1 Mutations in embryonal rhabdomyosarcomas from children with and without familial PPB‐tumor predisposition syndrome

Pediatric Blood and Cancer — Fri, 16 Dec 2011 05:00:00 +0100

AbstractEmbryonal rhabdomyosarcoma (ERMS) is the most common childhood sarcoma and is a component of the familial pleuropulmonary blastoma (PPB)‐predisposition syndrome. Using the PPB model, we hypothesized that DICER1 mutations would be found in familial and sporadic forms of ERMS. Blood samples from four children with familial PPB and ERMS, and 52 sporadic ERMS tumors were tested for DICER1 mutations. Germline DICER1 mutations were found in all four patients with familial PPB and 2 of 52 (3.8%) sporadic ERMS had somatic mutations. Our findings confirm the pathogenetic relationship between ERMS and PPB suggesting that ERMS may result from abnormal miRNA regulation. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

LIM-domain proteins in transforming growth factor β-induced epithelial-to-mesenchymal transition and myofibroblast differentiation.

Cellular Signalling — Sun, 11 Dec 2011 05:00:00 +0100

Authors: Järvinen PM, Laiho M Abstract Epithelial to mesenchymal transition (EMT) is a process during which junctions of the cell-cell contacts are dissolved, actin cytoskeleton is deformed, apical-basolateral cell polarity is lost and cell motility is increased. EMT is needed during normal embryonal development and wound healing, but may also lead to pathogenic transformation and formation of myofibroblasts. Transforming growth factor β (TGFβ) is a multifunctional cytokine promoting EMT and myofibroblast differentiation, and its dysregulation is involved in pathological disorders like cancer and fibrosis. Lin11, Isl-1 and Mec-3 (LIM) domain proteins are associated with actin cytoskeleton and linked to regulation of cell growth, damage signaling, cell fate determination and sign...

Comparative epigenetic analysis of Oct4 regulatory region in RA-induced differentiated NT2 cells under adherent and non-adherent culture conditions.

Molecular and Cellular Biochemistry — Fri, 09 Dec 2011 05:00:00 +0100

In this study, we induced differentiation of a human embryonic carcinoma cell line, NT2, under two different adherent and non-adherent culture conditions, and compared histone modifications as the epigenetic marks on the regulatory region of Oct4 gene after 3 days of differentiation. Using chromatin immunoprecipitation coupled with real-time PCR technique, it was shown that the after induction of differentiation the repressive epigenetic marks of hypoacetylation and methylation on lysine-9 of histone H3 occurred very effectively on the upstream of Oct4, especially in PP region. Also, comparing the two culturing systems it was shown that methylation of lysine-9 of H3 histone was more drastic in PE region of adherent cells rather than suspension cells. This epigenetic profile was in agreeme...

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Isochromosome 17q, MYC amplification and large cell/anaplastic phenotype in a case of medullomyoblastoma with extracranial metastases

Pediatric Blood and Cancer — Wed, 07 Dec 2011 01:36:29 +0100

AbstractMedullomyoblastoma (MMB) is a rare variant of medulloblastoma, a member of the family of central nervous system (CNS) embryonal tumors. The outcome of standard therapy for CNS embryonal tumors is often unpredictable in the setting of MMB. Here, we present the clinical course and treatment of an almost 4‐year‐old girl with MMB that was characterized by MYC amplification, isochromosome 17q and large cell/anaplastic histopathology. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Antiangiogenic metronomic therapy for children with recurrent embryonal brain tumors

Pediatric Blood and Cancer — Tue, 06 Dec 2011 05:00:00 +0100

ConclusionOur results suggest that the chosen antiangiogenic drug combination is particularly beneficial for patients with MB and warrants further investigation. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways.

Clinical Cancer Research — Mon, 05 Dec 2011 05:00:00 +0100

CONCLUSIONS: In ERMS, ES, and NB, we identified novel occurrences of several oncogene mutations recognized as drivers in other cancers. Overall, NB and ERMS contain significant subsets of cases with non-overlapping mutated genes in growth signaling pathways. Tumor profiling can identify a subset of pediatric solid tumor patients as candidates for kinase inhibitors or RAS-targeted therapies. PMID: 22142829 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Expression of Wilms tumor 1 gene in a variety of pediatric tumors

Journal of Pediatric Surgery — Thu, 01 Dec 2011 05:00:00 +0100

Conclusion: The WT1 expression was broadly detected in various pediatric neoplasms. These results indicate that WT1 may therefore be a potentially useful therapeutic target in most of pediatric malignancies. (Source: Journal of Pediatric Surgery)

Expression of carbonic anhydrase IX in genitourinary and adrenal tumours

Histopathology — Thu, 01 Dec 2011 05:00:00 +0100

Conclusions: Carbonic anhydrase IX is a sensitive marker for clear cell RCC in core biopsies. However, other genitourinary or adrenal tumours that can have a clear cell appearance including urothelial, squamous cell, clear cell adeno and adrenal cortical carcinoma and Sertoli cell tumour express CAIX. Knowledge of expression overlap between these entities may prevent incorrect interpretation of immunohistochemical results, particularly if limited tissue is available. (Source: Histopathology)

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UTF1 deficiency promotes retinoic acid-induced neuronal differentiation in P19 embryonal carcinoma cells.

The International Journal of Biochemistry and Cell Biology — Thu, 17 Nov 2011 05:00:00 +0100

Authors: Lin CH, Yang CH, Chen YR Abstract UTF1 (undifferentiated embryonic cell transcription factor 1) is a marker for the pluripotency of embryonic stem cells. We found that UTF1-deficient clones, which were isolated from P19 embryonal carcinoma (EC) cells, showed higher neuron-differentiating potentials than the parental cell line. Consistent with this result, suppression of UTF1 expression in P19 cells by RNA interference enhanced retinoic acid (RA)-induced neuronal differentiation. Moreover, reconstitution of UTF1 expression in UTF1-deficient clones decreased their ability to undergo neuronal differentiation. Interestingly, the growth rates of UTF1-deficient P19 cells did not differ from that of parental cells in adherent cultures, but were increased in embryoid bodies during...

Increased cardiogenesis in P19-GFP teratocarcinoma cells expressing the propeptide IGF-1Ea.

Biochemical and Biophysical Research communications — Sat, 12 Nov 2011 05:00:00 +0100

Authors: Poudel B, Bilbao D, Sarathchandra P, Germack R, Rosenthal N, Santini MP Abstract The mechanism implicated in differentiation of endogenous cardiac stem cells into cardiomyocytes to regenerate the heart tissue upon an insult remains elusive, limiting the therapeutical goals to exogenous cell injection and/or gene therapy. We have shown previously that cardiac specific overexpression of the insulin-like growth factor 1 propeptide IGF-1Ea induces beneficial myocardial repair after infarct. Although the mechanism is still under investigation, the possibility that this propeptide may be involved in promoting stem cell differentiation into the cardiac lineage has yet to be explored. To investigate whether IGF-1Ea promote cardiogenesis, we initially modified P19 embryonal carcino...

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) with loss of morphological but retained genetic key features during progression

Acta Neuropathologica — Sat, 05 Nov 2011 17:08:03 +0100

Content Type Journal ArticleCategory CorrespondencePages 1-4DOI 10.1007/s00401-011-0903-2Authors Adelheid Woehrer, Institute of Neurology, Medical University of Vienna, Waehringer Guertel 18–20, 1097 Vienna, AustriaIrene Slavc, Department of Pediatrics, Medical University of Vienna, Vienna, AustriaAndreas Peyrl, Department of Pediatrics, Medical University of Vienna, Vienna, AustriaThomas Czech, Department of Neurosurgery, Medical University of Vienna, Vienna, AustriaChristian Dorfer, Department of Neurosurgery, Medical University of Vienna, Vienna, AustriaDaniela Prayer, Department of Radiology, Medical University of Vienna, Vienna, AustriaSusanne Stary, Department of Pathology, Medical University of Vienna, Vienna, AustriaBerthold Streubel, Department of Pathology, Medical Universi...

p63 Immunohistochemical Staining Is Limited in Soft Tissue Tumors.

American Journal of Clinical Pathology — Tue, 01 Nov 2011 04:00:00 +0100

Authors: Jo VY, Fletcher CD Abstract p63 is a p53 homolog that is expressed in various normal epithelial tissues and epithelial malignancies. Its expression in mesenchymal lesions has not been examined in depth; therefore, we studied p63 expression by immunohistochemical analysis in 650 soft tissue tumors. We found that p63 expression is limited in soft tissue tumors. The majority of tumors studied were p63-, including all cases of angiosarcoma, lipomatous neoplasms, dermatofibrosarcoma protuberans, solitary fibrous tumor, schwannoma, neurofibroma, gastrointestinal stromal tumor, and leiomyosarcoma. Nuclear p63 reactivity was found in a subset of soft tissue myoepithelioma and myoepithelial carcinoma of soft tissue, cellular neurothekeoma, soft tissue perineurioma, Ewing sarcoma/pe...

Reprogramming mediated by cell fusion technology.

International Review of Cell and Molecular Biology — Mon, 31 Oct 2011 22:55:03 +0100

Authors: Serov OL, Matveeva NM, Khabarova AA Abstract This review is focused on recent advances in fusion-based reprogramming of cells of different pluripotent statuses or lineage origins. Recent findings are discussed from standpoints of both the developmental potency of hybrid cells generated by fusion of pluripotent embryonic stem (ES) cells, embryonal carcinoma (EC) cells, and somatic cells and epigenetic mechanisms and other aspects involved in the reprogramming process. Complete reprogramming occurs at least 5-7 days after fusion and includes at least two steps. (i) initiation at the heterokaryon stage and choice of the direction of reprogramming using an "all-or-none principle" to establish the dominance of one parental genome and (ii) "fixation" of the newly acquired expres...

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2-Deoxyglucose Induces Noxa-Dependent Apoptosis in Alveolar Rhabdomyosarcoma

Cancer Research — Sun, 30 Oct 2011 04:00:00 +0100

Alveolar and embryonal rhabdomyosarcomas are childhood tumors that do not respond well to current chemotherapies. Here, we report that the glycolytic inhibitor 2-deoxyglucose (2-DG) can efficiently promote cell death in alveolar, but not embryonal, rhabdomyosarcoma cell lines. Notably, 2-DG also induced cell differentiation accompanied by downregulation of PAX3/FOXO1a, the chromosome translocation–encoded fusion protein that is a central oncogenic driver in this disease. Cell death triggered by 2-DG was associated with its ability to activate Bax and Bak. Overexpression of the antiapoptotic Bcl-2 homologues Bcl-xL and Mcl-1 prevented apoptosis, indicating that cell death proceeds through the mitochondrial pathway. Mechanistic investigations indicated that Mcl-1 downregulation and Noxa up...

Characterization of primary wilms tumor cultures as an in vitro model

Genes, Chromosomes and Cancer — Thu, 27 Oct 2011 04:00:00 +0100

We report the generation of a set of primary WT‐cell cultures using a simple cultivation protocol. Our cultures could be established after preoperative chemotherapy and irrespective of histological subtypes or genetic alterations. The presence of tumor‐specific genetic alterations validates these cultures as being tumor‐derived. Genetic characterization is of utmost importance as some cultures with similar morphological appearance lacked such alterations and either represent clonal variants or normal cells. By immunohistochemistry, the cells are either epithelial or more mesenchymal, and the latter exhibiting a longer life span with 30 or more passages before undergoing senescence. This may be related to WT being embryonal tumors with a strong differentiation potential that may preva...

Predictors of Positive Retroperitoneal Lymph Nodes in Patients With High Risk Testicular Cancer

The Journal of Urology — Wed, 19 Oct 2011 04:00:00 +0100

Conclusions: Embryonal carcinoma and lymphovascular invasion were significantly and independently associated with the risk of occult retroperitoneal metastatic disease. These results should be considered when counseling patients about appropriate treatment options. (Source: The Journal of Urology)

Detection of variable levels of RARα and RARγ proteins in pluripotent and differentiating mouse embryonal carcinoma and mouse embryonic stem cells

Cell and Tissue Research — Mon, 10 Oct 2011 15:05:58 +0100

Abstract Pluripotent mouse embryonal carcinoma (mEC) and mouse embryonic stem (mES) cells differentiate into several cell lineages upon retinoic acid (RA) addition. Differentiation is facilitated, in part, by RA activation of nuclear RA receptors (RARs) that bind to DNA response elements located in the promoters of target genes. The purpose of the studies reported here was to immunolocalize RARα and RARγ protein in mEC and mES cells and in their RA-induced differentiated progeny. Fixed cells were reacted with three different RARα antibodies and one RARγ antibody. Pluripotent and differentiated mEC and mES cells showed positive nuclear immunoreactivity with all antibodies tested. Two RARα antibodies also showed positive reactivity in the cytoplasm. Surprisingly, our re...

Novel amplifications in pediatric medulloblastoma identified by genome-wide copy number profiling

Journal of Neuro-Oncology — Fri, 07 Oct 2011 05:44:51 +0100

In this study, we profiled a series of 25 MB with a 32K BAC array covering 99% of the current assembly of the human genome for the identification of genetic copy number alterations possibly important in MB. Previously known aberrations as well as several novel focally amplified loci could be identified. As expected, the most frequently observed alteration was the combination of 17p loss and 17q gain, which was detected in both high- and standard-risk patients. We also defined minimal overlapping regions of aberrations, including 16 regions of gain and 18 regions of loss in various chromosomes. A few noteworthy narrow amplified loci were identified on autosomes 1 (38.89–41.97 and 84.89–90.76 Mb), 3 (27.64–28.20 and 35.80–43.50 Mb), and 8 (119.66–139.79 Mb...

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Identification of the estrogen receptor GPER in neoplastic and non-neoplastic human testes

Reproductive Biology and Endocrinology — Wed, 05 Oct 2011 04:00:00 +0100

Conclusions: These findings suggest that GPER could mediate estrogen signaling in both normal and transformed somatic cells of human testis, but they reveal a differential expression of the novel estrogen receptor in non neoplastic and neoplastic germ cells. (Source: Reproductive Biology and Endocrinology)

A new chitosan-thymine conjugate: Synthesis, characterization and biological activity.

International Journal of Biological Macromolecules — Sat, 01 Oct 2011 04:00:00 +0100

Authors: Kumar S, Kim H, Gupta MK, Dutta PK, Koh J Abstract Conjugation of chitosan with nucleobases is expected to expand its not only antimicrobial activity but also anti-cancer activity. Here, we report the synthesis of a novel chitosan-thymine conjugate by the reaction between chitosan and thymine-1-yl-acetic acid followed by acylation. The synthesized conjugate was characterized by FTIR, XRD, (1)H NMR, TGA and SEM. The microbiological screening results demonstrated the antimicrobial activity of the conjugate against bacteria viz., Escherichia coli, Staphylococcus aureus, Candida albicans, and fungi viz., Aspergillus niger. The chitosan-thymine conjugate also inhibited (p<0.05) the proliferation of human liver cancer cells (HepG2) in a dose-dependent manner but had no cellul...

Epidermoid Cysts in the Frontal Lobe – A Case Series

Journal of Pakistan Medical Students — Fri, 30 Sep 2011 04:00:00 +0100

Conclusion Intracranial epidermoid tumors are rarely found in the frontal lobes. Surgical resection appears the mainstay of treatment; however, the extent of resection is dictated by the adherence of the tumor capsule to surrounding vital structures. The advantages of aggressive neurosurgical intervention must be weighed against an acceptable risk of neurological outcomes. Due to indolent growth pattern, subtotal resection is also acceptable. REFERENCES 1. Bailey P. Cruveilhiers tumeur perlees. Surg Gynecol obstet. 1920;31:390-401. 2. Cushing H. A large epidermal cholesteatoma of the parieto-temporal region deforming the left hemisphere without cerebral symptoms. Surg Gynecol obstet. 1922;34:557-66. 3. Berger MS, Wilson CB. Epidermoid cysts o...

Very Late Relapse of Testicular Tumour in Combination with Renal Cancer and Their Retroperitoneoscopic Removal

Infectious Diseases in Obstetrics and Gynecology — Thu, 29 Sep 2011 16:29:26 +0100

We report a case of late relapse of a testicular tumour combined with a renal cancer and their successful removal with retroperitoneoscopy. The 36-year-old patient underwent left orchiectomy, retroperitoneal lymph node dissection, and chemotherapy, because of mixed tumor including teratoma and embryonal carcinoma. 18 years after the successful primary therapy elevated serum alpha-fetoprotein level had been confirmed, then MRI and PET-CT scans demonstrated a 30 mm left renal mass and 22 mm retroperitoneal lymph node above the bifurcation of the left common iliac artery. We performed retroperitoneoscopic lymph node dissection and left renal tumour resection in the same session. The histology revealed embryonal carcinoma for the retroperitoneal lymph node and renal cell carcinom...

Inhibition of the Notch-Hey1 Axis Blocks Embryonal Rhabdomyosarcoma Tumorigenesis.

Clinical Cancer Research — Fri, 23 Sep 2011 04:00:00 +0100

CONCLUSIONS: Aberrant Notch-Hey1 signaling contributes to eRMS by impeding differentiation and promoting proliferation. The efficacy of Notch pathway inhibition in vivo supports the development of Notch-Hey1 axis inhibitors in the treatment of eRMS. PMID: 21948088 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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Induction of a regenerative microenvironment in skeletal muscle is sufficient to induce embryonal rhabdomyosarcoma in p53‐deficient mice

The Journal of Pathology — Mon, 19 Sep 2011 08:21:43 +0100

AbstractWe have previously reported that mice with muscular dystrophy, including mdx mice, develop embryonal rhabdomyosarcoma (eRMS) with a low incidence after one year of age and that almost all such tumors contain cancer‐associated p53 mutations. To further demonstrate the relevance of p53 inactivation, we created p53‐deficient mdx mice. Here we demonstrate that loss of one or both p53 (Trp53) alleles accelerates eRMS incidence in the mdx background, such that almost all Trp53‐/‐mdx animals develop eRMS by five months of age. To ascertain if increased tumor incidence was due to the regenerative microenvironment found in dystrophic skeletal muscles, we induced muscle regeneration in Trp53+/+ and Trp53‐/‐ animals using cardiotoxin (Ctx). Wild type (Trp53+/+) animals treated wit...

RNA‐binding protein LIN28 is a sensitive marker of ovarian primitive germ cell tumours

Histopathology — Thu, 01 Sep 2011 04:00:00 +0100

Conclusions: LIN28 is a sensitive marker for gonadoblastomas, dysgerminomas, ECs, and YSTs. LIN28 can be used to distinguish them from non‐GCTs. (Source: Histopathology)

Vaccines targeting cancer stem cells: are they within reach?

Cancer Journal — Thu, 01 Sep 2011 04:00:00 +0100

Authors: Dhodapkar MV, Dhodapkar KM Abstract Increased appreciation of intraclonal heterogeneity of tumors in the past decade has led to the resurgence of the cancer stem cell hypothesis. This hypothesis also has potential implications for immunologic approaches targeting cancer, and it has been suggested that vaccines targeting cancer stem cells may be essential for durable antitumor immunity. Recent studies have provided novel insights into the nature of antigenic targets expressed on putative cancer stem cells and the capacity of both the innate and the adaptive immune system to target these cells, as well as the associated challenges. While the phenotypic properties of cancer stem cells may be plastic, their stemness and capacity for self-renewal may depend on a limited set of ...

Colonic adenocarcinoma as a secondary malignancy after treatment of embryonal rhabdomyosarcoma.

World Journal of Pediatrics : WJP — Fri, 26 Aug 2011 23:00:00 +0100

CONCLUSIONS: We report a rare case of colon cancer after treatment of rhabdomyosarcoma. Colorectal adenocarcinoma must be kept in mind as a secondary neoplasm following treatment for early childhood malignancies although it is extremely rare. PMID: 21874612 [PubMed - as supplied by publisher] (Source: World Journal of Pediatrics : WJP)

EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation

BMC Cancer — Thu, 25 Aug 2011 23:00:00 +0100

Conclusions: Biallelic EFS methylation is likely to be the result of a site-directed methylation mechanism. Based on partial methylation as observed in cultured melanocytes we hypothesize that there might be methylated and unmethylated precursor cells located in the uveal tract. The EFS methylation of a UM may depend on which type of precursor cell the tumor originated from. (Source: BMC Cancer)

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The seminoma cell line TCam‐2 is sensitive to HDAC inhibitor depsipeptide but tolerates various other chemotherapeutic drugs and loss of NANOG expression

Genes, Chromosomes and Cancer — Tue, 23 Aug 2011 23:00:00 +0100

AbstractSeminomas and embryonal carcinomas (EC) are both type II germ cell tumor (GCT) entities and develop from the same precursor lesion (carcinoma‐in situ, CIS). However, they show significant differences in growth behavior, differentiation potential, and gene expression. Although ECs are prone to differentiate into all three germ layers and give rise to the non‐seminomatous GCT entities teratoma, choriocarcinoma, and yolk‐sac tumor, differentiation of seminomas to these entities is only rarely observed. This might reflect the ability of seminomas to actively inhibit differentiation processes evoked by environmental cues. Also, it is not known why CIS gives rise to seminoma in some patients and to non‐seminoma in the others. Here, we treated the seminoma‐like cell line TCam‐...

HESRG: a novel biomarker for intracranial germinoma and embryonal carcinoma

Journal of Neuro-Oncology — Tue, 23 Aug 2011 05:54:48 +0100

In this study, we used RT-PCR to systematically investigate the expression of HESRG in various types of intracranial tumors and found that HESRG was expressed only in germinoma and embryonal carcinoma, but hardly at all in other types of brain tumors. Real-time PCR results further confirmed this expression pattern. Subsequently, we tested 134 intracranial non-germ cell tumors and 64 intracranial germ cell tumors by immunohistochemistry. Our results showed that HESRG was expressed strongly and diffusively in the nuclei of tumor cells in intracranial germinoma and embryonal carcinoma as well as in human embryonic stem cells. No positive staining signal was observed in any other type of intracranial tumors. In germinomas, 25 of 31 showed intensive (3+) expression, four cases showed mode...

Role of oxidative stress and the mitochondrial permeability transition in methylmercury cytotoxicity.

Neurotoxicology — Thu, 18 Aug 2011 23:00:00 +0100

Authors: Polunas M, Halladay A, Tjalkens RB, Philbert MA, Lowndes H, Reuhl K Abstract Oxidative stress has been implicated in the pathogenesis of methylmercury (MeHg) neurotoxicity. Studies of mature neurons suggest that the mitochondrion may be a major source of MeHg-induced reactive oxygen species and a critical mediator of MeHg-induced neuronal death, likely by activation of apoptotic pathways. It is unclear, however, whether the mitochondria of developing and mature neurons are equally susceptible to MeHg. Murine embryonal carcinoma (EC) cells, which differentiate into neurons following exposure to retinoic acid, were used to compare the differentiation-dependent effects of MeHg on ROS production and mitochondrial depolarization. EC cells and their neuronal derivatives were pre...

Concordance and Prediction Ability of Original and Reviewed Vascular Invasion and Other Prognostic Parameters of Clinical Stage I Nonseminomatous Germ Cell Testicular Tumors After Retroperitoneal Lymph Node Dissection

The Journal of Urology — Wed, 17 Aug 2011 04:00:00 +0100

Conclusions: In half of the patients no information was available on vascular invasion in the original reports. Concordance between original and reviewed reports was generally poor. Reviewed parameters better predicted nodal status at retroperitoneal lymph node dissection. These findings may have important implications in clinical practice. (Source: The Journal of Urology)

Mutation in the type IB bone morphogenetic protein receptor alk6b impairs germ-cell differentiation and causes germ-cell tumors in zebrafish [Developmental Biology]

Proceedings of the National Academy of Sciences — Mon, 08 Aug 2011 23:00:00 +0100

Germ-cell tumors (GCTs), which arise from pluripotent embryonic germ cells, exhibit a wide range of histologic differentiation states with varying clinical behaviors. Although testicular GCT is the most common cancer of young men, the genes controlling the development and differentiation of GCTs remain largely unknown. Through a forward genetic screen, we previously identified a zebrafish mutant line, tgct, which develops spontaneous GCTs consisting of undifferentiated germ cells [Neumann JC, et al. (2009) Zebrafish 6:319–327]. Using positional cloning we have identified an inactivating mutation in alk6b, a type IB bone morphogenetic protein (BMP) receptor, as the cause of the zebrafish GCT phenotype. Alk6b is expressed in spermatogonia and early oocytes, and alk6b mutant gonads display ...

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Methylation profile of DNA repetitive elements in human testicular germ cell tumor

Molecular Carcinogenesis — Sun, 31 Jul 2011 23:00:00 +0100

AbstractTesticular germ cell tumors (TGCTs) have a unique epigenetic profile distinct from that of other types of cancer. To further evaluate epigenetics of TGCTs, this study examines DNA methylation patterns of DNA repetitive elements in TGCTs. Bisulfite genomic sequencing and combined bisulfite restriction analysis (COBRA) were used to analyze the methylation patterns of DNA repetitive elements (LINE1 and Alu repeats) in embryonal carcinoma (EC) derived cell lines, primary TGCT tissues, noncancerous testicular tissues adjacent to TGCTs and cancer cells derived from somatic tissues (testicular malignant lymphoma tissues and renal cell carcinoma cell lines). Through both bisulfite genomic sequencing and COBRA, LINE1 was extensively hypomethylated in both seminomatous and nonseminomatous TG...

Identification of a novel recurrent 1q42.2‐1qter deletion in high risk MYCN single copy 11q deleted neuroblastomas

International Journal of Cancer — Tue, 26 Jul 2011 23:00:00 +0100

In this study, high resolution array comparative genome hybridization (CGH) was performed on 188 primary neuroblastoma tumors and 33 neuroblastoma cell lines in order to search for previously undetected recurrent DNA copy number gains and losses. A new recurrent distal chromosome 1q deletion (del(1)(q42.2qter)) was detected in seven cases. Further analysis of available array CGH datasets revealed 13 additional similar distal 1q deletions. The majority of all detected 1q deletions was found in high risk 11q deleted tumors without MYCN amplification (Fisher exact test p=5.61*10−5). Using ultra‐high resolution (∼115 bp resolution) custom arrays covering the breakpoints on 1q for 11 samples, clustering of nine breakpoints was observed within a 12.5 kb region, of which eight were found in...

Frequency, Risk‐Factors and Survival of Children With Atypical Teratoid Rhabdoid Tumors (AT/RT) of the CNS Diagnosed between 1988 and 2004, and Registered to the German HIT Database

Pediatric Blood and Cancer — Tue, 26 Jul 2011 23:00:00 +0100

ConclusionThe incidence of AT/RT in children below 1 year is higher than previously reported. A subset of patients with favorable clinical risk factors profits from intensive multimodal treatment. Prospective clinical and biological studies are needed to further define prognostic factors and optimize therapy. Pediatr Blood Cancer © 2011 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

Retinoic acid fails to induce cell cycle arrest with myogenic differentiation in rhabdomyosarcoma

Pediatric Blood and Cancer — Tue, 12 Jul 2011 23:00:00 +0100

ConclusionOur results indicate that ATRA could increase the expression of some genes associated with muscle differentiation in rhabdomyosarcoma cells, but there was no benefit of single‐agent therapy in an MRD model, likely because cell cycle arrest was uncoupled from the pro‐differentiation effects of retinoids. Pediatr Blood Cancer © 2011 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

Metastatic medulloblastoma at diagnosis

Journal of Cancer Research and Therapeutics — Mon, 11 Jul 2011 23:00:00 +0100

Seema Gupta, MC Pant, N Husain, S SundarJournal of Cancer Research and Therapeutics 2011 7(2):203-204Medulloblastoma is an aggressive tumor of the brain. It is the most common and the most malignant embryonal tumor of the pediatric central nervous system and a rare tumor of adults. We are reporting a rare presentation of adult classic subtype of medulloblastoma which was central in location with metastases in the suprasellar region at the time of diagnosis. (Source: Journal of Cancer Research and Therapeutics)

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High-Content Screening for Chemical Modulators of Embryonal Carcinoma Cell Differentiation and Survival

Journal of Biomolecular Screening — Wed, 06 Jul 2011 23:00:00 +0100

Disentangling the complex interactions that govern stem cell fate choices of self-renewal, differentiation, or death presents a formidable challenge. Image-based phenotype-driven screening meets this challenge by providing means for rapid testing of many small molecules simultaneously. Pluripotent embryonal carcinoma (EC) cells offer a convenient substitute for embryonic stem (ES) cells in such screens because they are simpler to maintain and control. The authors developed an image-based screening assay to identify compounds that affect survival or differentiation of the human EC stem cell line NTERA2 by measuring the effect on cell number and the proportion of cells expressing a pluripotency-associated marker SSEA3. A pilot screen of 80 kinase inhibitors identified several compounds that ...

Expression analysis of stem cell-related genes reveal OCT4 as a predictor of poor clinical outcome in medulloblastoma

Journal of Neuro-Oncology — Sat, 02 Jul 2011 05:43:16 +0100

Abstract Aberrant expression of stem cell-related genes in tumors may confer more primitive and aggressive traits affecting clinical outcome. Here, we investigated expression and prognostic value of the neural stem cell marker CD133, as well as of the pluripotency genes LIN28 and OCT4 in 37 samples of pediatric medulloblastoma, the most common and challenging type of embryonal tumor. While most medulloblastoma samples expressed CD133 and LIN28, OCT4 expression was found to be more sporadic, with detectable levels occurring in 48% of tumors. Expression levels of OCT4, but not CD133 or LIN28, were significantly correlated with shorter survival (P ≤ 0.0001). Median survival time of patients with tumors hyperexpressing OCT4 and tumors displaying low/undetectable OCT4 e...

Genomic aberrations in pediatric gliomas and embryonal tumors

Genes, Chromosomes and Cancer — Fri, 01 Jul 2011 15:10:38 +0100

This study indicates the existence of distinct cytogenetic patterns in pediatric gliomas and embryonal tumors; however, further studies of these rare tumors using a multimodal approach are required before their true genomic aberration pattern can be finally established. © 2011 Wiley‐Liss, Inc. (Source: Genes, Chromosomes and Cancer)

Antiproliferation and redifferentiation in thyroid cancer cell lines by polyphenol phytochemicals.

J Korean Med Sci — Thu, 30 Jun 2011 23:00:00 +0100

In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells...

CD56 expression is associated with neuroectodermal differentiation in ameloblastomas: an immunohistochemical evaluation in comparison with odontogenic cystic lesions

Medical Molecular Morphology — Thu, 30 Jun 2011 05:51:40 +0100

Abstract Ameloblastoma (AB), which is the most common odontogenic tumor, may originate from the dental lamina remnants. The expression of CD56, which is a transmembrane molecule, is associated with neuroectodermal differentiation of the embryonal cells. The aim of this study was to evaluate the expression of CD56 in AB, in comparison with other odontogenic cysts. We used formalin-fi xed, paraffi n-embedded specimens from 34 cases of AB, 10 cases of keratocystic odontogenic tumor (KCOT), and 7 cases of dentigerous cyst (DC). We immunohistochemically examined CD56, NeuroD1, and N-cadherin expression in these tumors as compared with the expression patterns of various epithelial markers. Seventy-four percent of AB showed immunopositivity for CD56, and both CD56 and N-cadherin ...

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Osteosarcoma Cells Differentiate into Phenotypes from all Three Dermal Layers.

Clinical Orthopaedics and Related Research — Wed, 15 Jun 2011 23:00:00 +0100

Authors: Russinoff S, Miran S, Gowda AL, Lucas PA BACKGROUND: Osteosarcomas are the most common solid malignant bone tumors, but little is known of their origin. The embryonal rest hypothesis views cancer cells as arising from committed progenitor stem cells in each tissue. Adult tissue contains primitive stem cells that retain the ability to differentiate across dermal lines, raising the possibility that the stem cell of origin of cancers may be from a more primitive stem cell than a progenitor. QUESTIONS/PURPOSES: Can osteosarcoma cells, when cultured under conditions used for multipotent stem cells, be induced to differentiate into multiple phenotypes, including those of the three different dermal lineages: mesodermal, ectodermal, and endodermal? METHODS: One rat and one human osteo...

Transcriptional regulation of the CADM1 gene by retinoic acid during the neural differentiation of murine embryonal carcinoma P19 cells

Genes to Cells — Tue, 14 Jun 2011 23:00:00 +0100

CADM1 is a multifunctional cell adhesion molecule expressed predominantly in the nerve system, testis and lung. The expression of the Cadm1 gene is induced during the neural differentiation of murine embryonal carcinoma P19 cells by treatment with retinoic acid (RA). Here, we show that the suppression of CADM1 expression using RNAi interfered with P19 cell aggregation and reduced cell populations expressing MAP2 after RA treatment. Nonaggregated P19 cells were not differentiated into neurons, suggesting that CADM1 participates in the aggregate formation and neuronal differentiation of P19 in vitro. A luciferase assay of a series of deletion mutants of the CADM1 promoter localized an RA‐responsive cis‐acting element to an approximately 90‐bp fragment upstream of the translational star...

Mapping the stem cell state: eight novel human embryonic stem and embryonal carcinoma cell antibodies

International Journal of Andrology — Wed, 08 Jun 2011 23:00:00 +0100

SummaryThe antigenic profile of human embryonic stem (ES) and embryonal carcinoma (EC) cells has served as a key element of their characterization, with a common panel of surface and intracellular markers now widely used. Such markers have been used to identify cells within the ‘undifferentiated state’, yet it appears that this categorization may be an oversimplification, because a number of sub‐states appear to exist within this state. To increase the resolution of the undifferentiated state, we have generated eight novel monoclonal antibodies, all capable of recognizing undifferentiated human ES and EC cells, and herein describe their characterization. The reactivity of these antibodies against a range of cell lines is reported, as well as their developmental regulation, basic bioc...

The testicular germ cell tumour transcriptome

International Journal of Andrology — Wed, 08 Jun 2011 23:00:00 +0100

SummaryTesticular germ cell tumours (TGCTs) are characterized by young age of onset and a complex pattern of histological subtypes. Transcriptomic studies have tried to uncover the gene expression patterns underlying this. Here, we present a systematic review of transcriptome studies of TGCTs of adolescents and young adults and identify genes common across the various studies, both for TGCTs in general as well as the histological subtypes, hence elucidating both transcriptional changes associated with malignant transformation and differentiation patterns. A meta‐analysis of this type adds power and significance to the genes thus found, where most studies have included only a limited number of samples. Both known (KRAS, MYCN and TPD52) and novel (CCT6A, IGFBP3 and SALL2) cancer genes are ...

Mapping the stem cell state: eight novel human embryonic stem and embryonal carcinoma cell antibodies.

International Journal of Andrology — Wed, 08 Jun 2011 23:00:00 +0100

Authors: Wright A, Andrews N, Bardsley K, Nielsen JE, Avery K, Pewsey E, Jones M, Harley D, Nielsen AR, Moore H, Gokhale P, Rajpert-De Meyts E, Andrews PW, Walsh J, Harrison NJ The antigenic profile of human embryonic stem (ES) and embryonal carcinoma (EC) cells has served as a key element of their characterization, with a common panel of surface and intracellular markers now widely used. Such markers have been used to identify cells within the 'undifferentiated state', yet it appears that this categorization may be an oversimplification, because a number of sub-states appear to exist within this state. To increase the resolution of the undifferentiated state, we have generated eight novel monoclonal antibodies, all capable of recognizing undifferentiated human ES and EC cells, and her...

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The testicular germ cell tumour transcriptome.

International Journal of Andrology — Wed, 08 Jun 2011 23:00:00 +0100

Authors: Alagaratnam S, Lind GE, Kraggerud SM, Lothe RA, Skotheim RI Testicular germ cell tumours (TGCTs) are characterized by young age of onset and a complex pattern of histological subtypes. Transcriptomic studies have tried to uncover the gene expression patterns underlying this. Here, we present a systematic review of transcriptome studies of TGCTs of adolescents and young adults and identify genes common across the various studies, both for TGCTs in general as well as the histological subtypes, hence elucidating both transcriptional changes associated with malignant transformation and differentiation patterns. A meta-analysis of this type adds power and significance to the genes thus found, where most studies have included only a limited number of samples. Both known (KRAS, MYCN ...

TGF‐β1, EGF and FGF4 synergistically induce differentiation of the seminoma cell line TCam‐2 into a cell type resembling mixed non‐seminoma

International Journal of Andrology — Tue, 07 Jun 2011 23:00:00 +0100

This study supports the model that seminomas indeed have an intrinsic ability to transform into a non‐seminoma. In addition, the data suggest that the transformation does not require an additional mutation, but can be triggered by changes in the tumour microenvironment. (Source: International Journal of Andrology)

TGF-β1, EGF and FGF4 synergistically induce differentiation of the seminoma cell line TCam-2 into a cell type resembling mixed non-seminoma.

International Journal of Andrology — Tue, 07 Jun 2011 23:00:00 +0100

This study supports the model that seminomas indeed have an intrinsic ability to transform into a non-seminoma. In addition, the data suggest that the transformation does not require an additional mutation, but can be triggered by changes in the tumour microenvironment. PMID: 21649665 [PubMed - as supplied by publisher] (Source: International Journal of Andrology)

Expression and interdependencies of pluripotency factors LIN28, OCT3/4, NANOG and SOX2 in human testicular germ cells and tumours of the testis

International Journal of Andrology — Wed, 01 Jun 2011 23:00:00 +0100

In conclusion, LIN28 regulates the differentiation status of seminoma and embryonal carcinoma and is likely to play a related role in normal human germ‐cell development. (Source: International Journal of Andrology)

Expression and interdependencies of pluripotency factors LIN28, OCT3/4, NANOG and SOX2 in human testicular germ cells and tumours of the testis.

International Journal of Andrology — Wed, 01 Jun 2011 23:00:00 +0100

In conclusion, LIN28 regulates the differentiation status of seminoma and embryonal carcinoma and is likely to play a related role in normal human germ-cell development. PMID: 21631526 [PubMed - as supplied by publisher] (Source: International Journal of Andrology)

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Impact of classification of mixed germ‐cell tumours on incidence trends of non‐seminoma

International Journal of Andrology — Tue, 31 May 2011 23:00:00 +0100

SummarySeminomas and non‐seminomas [embryonal carcinomas, yolk sac tumours, teratomas, choriocarcinomas, mixed germ‐cell tumours (MGCT)] are the major histological types of testicular germ‐cell tumours (TGCT). TGCTs composed of both seminomatous and non‐seminomatous elements have been coded as their non‐seminoma component in the World Health Organization classification. In the late 1980s, a provisional International Classification of Diseases for Oncology (ICD‐O) morphology code for MGCT was introduced. Using data from the Surveillance, Epidemiology and End Results Program and two population‐based German cancer registries, we examined the impact of MGCT classification on TGCT trends. Cases were identified using ICD‐O topography (ICD‐9: 186; ICD‐10: C62) and morphology c...

Intermediate‐term oncological efficacy of laparoscopic retroperitoneal lymph node dissection for non‐seminomatous germ cell testicular cancer

BJU International — Tue, 31 May 2011 23:00:00 +0100

CONCLUSIONS• Laparoscopic RPLND appears to be safe while providing the benefits of minimally invasive surgery.• Although the therapeutic benefit of L‐RPLND needs to be confirmed in additional patients and with longer follow‐up, our results suggest that L‐RPLND provides both diagnostic and therapeutic benefits. (Source: BJU International)

Impact of classification of mixed germ-cell tumours on incidence trends of non-seminoma.

International Journal of Andrology — Sun, 29 May 2011 23:00:00 +0100

Authors: Trabert B, Stang A, Cook MB, Rusner C, McGlynn KA Seminomas and non-seminomas [embryonal carcinomas, yolk sac tumours, teratomas, choriocarcinomas, mixed germ-cell tumours (MGCT)] are the major histological types of testicular germ-cell tumours (TGCT). TGCTs composed of both seminomatous and non-seminomatous elements have been coded as their non-seminoma component in the World Health Organization classification. In the late 1980s, a provisional International Classification of Diseases for Oncology (ICD-O) morphology code for MGCT was introduced. Using data from the Surveillance, Epidemiology and End Results Program and two population-based German cancer registries, we examined the impact of MGCT classification on TGCT trends. Cases were identified using ICD-O topography (ICD-9...

STK17A Is an Important p53 Target Gene [Cell Biology]

Journal of Biological Chemistry — Thu, 26 May 2011 23:00:00 +0100

In this study, we have discovered that a poorly characterized member of the death-associated protein family of serine/threonine kinases, STK17A (also called DRAK1), is a novel p53 target gene. Cisplatin-mediated induction of STK17A in the EC cell line NT2/D1 was prevented with p53 siRNA. Furthermore, STK17A was induced with cisplatin in HCT116 and MCF10A cells but to a much lesser extent in isogenic p53-suppressed cells. A functional p53 response element that binds endogenous p53 in a cisplatin-dependent manner was identified 5 kb upstream of the first coding exon of STK17A. STK17A is not present in the mouse genome, but the closely related gene STK17B is induced with cisplatin in mouse NIH3T3 cells, although this induction is p53-independent. Interestingly, in human cells containing both ...

Hedgehog pathway activity in pediatric embryonal rhabdomyosarcoma and undifferentiated sarcoma: A report from the Children's Oncology Group

Pediatric Blood and Cancer — Tue, 24 May 2011 23:00:00 +0100

ConclusionsOur findings support a role for Hh pathway activation in the genesis of a subset of ERMS and US tumors. Hh signaling may represent a novel therapeutic target in affected tumors. Pediatr Blood Cancer © 2011 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

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Lineage relationship of prostate cancer cell types based on gene expression

BMC Medical Genomics — Sun, 22 May 2011 23:00:00 +0100

Conclusions: Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types. (Source: BMC Medical Genomics)

A novel RING finger protein, Znf179, modulates cell cycle exit and neuronal differentiation of P19 embryonal carcinoma cells

Cell Death and Differentiation — Thu, 12 May 2011 23:00:00 +0100

Authors: P-C Pao, N-K Huang, Y-W Liu, S-H Yeh, S-T Lin, C-P Hsieh, A-M Huang, H-S Huang, J T Tseng, W-C Chang & Y-C Lee (Source: Cell Death and Differentiation)

Laryngeal embryonal rhabdomyosarcoma in an adult - a case presentation in the eyes of geneticists and clinicians

BMC Cancer — Wed, 11 May 2011 23:00:00 +0100

Conclusions: Considering the histological diagnosis and the highly aggressive nature of the lesion for optimal diagnosis positron electron tomography (PET) and computerized tomography (CT) of the neck and thorax should be performed. At this time surgical treatment with adjuvant radiotherapy seems to be the treatment of choice for this disease. Rhabdomyosarcoma of the larynx has a better prognosis than elsewhere in the body, probably because of its earlier recognition and accessibility to radical surgery. (Source: BMC Cancer)

AW551984: a novel regulator of cardiomyogenesis from pluripotent embryonic cells

BJ Disease — Mon, 09 May 2011 23:00:00 +0100

An understanding of the mechanism that regulates the cardiac differentiation of pluripotent stem cells is necessary for the effective generation and expansion of cardiomyocytes as cell therapy products. Here we have identified genes that modulate the cardiac differentiation of pluripotent embryonic cells. We isolated P19CL6 cell sublines that possess distinct properties in cardiomyogenesis and extracted 24 cardiomyogenesis-related candidate (CMR) genes correlated with cardiomyogenesis using a transcriptome analysis. Knockdown of the CMR genes by RNAi revealed that 18 CMR genes influence spontaneous contraction or transcript levels of cardiac marker genes in embryonal carcinoma (EC) cells. We also performed knockdown of the CMR genes in mouse embryonic stem (ES) cells and induced in vitro c...

Socioeconomic status and the incidence of non-central nervous system childhood embryonal tumours in Brazil

BMC Cancer — Wed, 04 May 2011 23:00:00 +0100

Conclusion: Regional variations of SES and the incidence of embryonal tumours were observed, particularly incidence rates for NB and RB. Further studies are necessary to investigate risk factors for embryonic tumours in Brazil. (Source: BMC Cancer)

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Mixed germ cell tumor with embryonal carcinoma, choriocarcinoma, and epithelioid trophoblastic tumor in the ovary of a cynomolgus monkey.

Toxicologic Pathology — Wed, 04 May 2011 20:45:02 +0100

Authors: Yokouchi Y, Imaoka M, Sayama A, Sanbuissho A A seven-year-old female cynomolgus monkey had a mass in the left ovary with metastasis to the lung and the right ovary. The mass of these organs showed three different characteristics, and its immunohistochemical profiles were consistent with embryonal carcinoma (EC), choriocarcinoma (CC), and epithelioid trophoblastic tumor (ETT). The EC was characterized with sheets and glandlike structures with large pleomorphic, single-nucleated epithelial cells that were immunohistochemically positive for α-fetoprotein, octamer-4, and CD30, and with multinucleated giant cells resembling syncytiotrophoblasts. The CC also represented biphasic proliferation of the cytotrophoblast positive for cytokeratin 7 (CK7), which showed negative immunoreact...

Adhesion, proliferation and differentiation of pluripotent stem cells on multi-walled carbon nanotubes

IET Nanobiotechnology — Sat, 30 Apr 2011 15:15:44 +0100

This article studies the adhesion, growth and differentiation of stem cells on carbon nanotube matrices. Glass coverslips were coated with multi-walled carbon nanotube (MWNT) thin films using layer-by-layer self-assembling techniques. Pluripotent P19 mouse embryonal carcinoma stem cells were seeded onto uncoated or MWNT-coated glass coverslips and either maintained in an undifferentiated state or induced to differentiate by the addition of retinoic acid. The authors found that cell adhesion was increased on the MWNT-coated glass surfaces, and that the expression patterns of some differentiation markers were altered in cells grown on MWNTs. The results suggest that MWNTs will be useful in directing pluripotent stem cell differentiation for tissue engineering purposes. (Source: IET Nanobiote...

Geminin escapes degradation in g1 of mouse pluripotent cells and mediates the expression of oct4, sox2, and nanog.

Current Biology — Mon, 25 Apr 2011 23:00:00 +0100

Authors: Yang VS, Carter SA, Hyland SJ, Tachibana-Konwalski K, Laskey RA, Gonzalez MA Geminin is an essential cell-cycle protein that is only present from S phase to early mitosis in metazoan somatic cells [1, 2]. Genetic ablation of geminin in the mouse results in preimplantation embryonic lethality because pluripotent cells fail to form and all cells differentiate to trophoblast [3, 4]. Here we show that geminin is present in G1 phase of mouse pluripotent cells in contrast to somatic cells, where anaphase-promoting complex/cyclosome (APC/C)-mediated proteasomal destruction removes geminin in G1 [1, 2, 5]. Silencing geminin directly or by depleting the APC/C inhibitor Emi1 causes loss of stem cell identity and trophoblast differentiation of mouse embryonal carcinoma and embryonic s...

Murine rhabdomyosarcoma is immunogenic and responsive to T‐cell‐based immunotherapy

Pediatric Blood and Cancer — Thu, 31 Mar 2011 23:00:00 +0100

ConclusionsM3‐9‐M derived murine ERMS is immunogenic and immunoresponsive; regulatory T cells contribute to immune evasion by murine rhabdomyosarcoma. Adoptive immunotherapy with DC vaccination can eradicate low tumor burdens. Future work will seek to identify the tumor‐associated antigens that mediate protective and therapeutic immunity in this model. Pediatr Blood Cancer © 2011 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

Extracellular Matrix Metalloproteinase Inducer is a Negative Prognostic Factor of Pediatric Medulloblastoma.

Pathology Oncology Research — Wed, 30 Mar 2011 23:00:00 +0100

Authors: Chu T, Chen X, Yu J, Xiao J, Fu Z Medulloblastoma (MB) is the most common embryonal CNS tumor of childhood. Its survival rates have significantly improved over the years due to developments in diagnostic techniques and therapeutic strategies. However, it is still an important cause of cancer-related deaths in children. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a member of the immunoglobulin family and a glycoprotein enriched on the surface of many types of tumor cells. Therefore, the aim of this study was to investigate whether the expression patterns of EMMPRIN may predict the clinical prognosis in MB. EMMPRIN expression in a series of 56 MB with various grades and pathological types was analyzed by immunohistochemical staining on paraffin-embedded sections...

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Embryonal tumor with abundant neuropil and true rosettes: a report of three cases of a rare tumor, with an unusual case showing rhabdomyoblastic and melanocytic differentiation

Neuropathology — Tue, 29 Mar 2011 18:11:56 +0100

Discussion of the clinicopathological findings is presented along with a recent literature review. Sixteen‐, 57‐ and 30‐month‐old children presented with tumors located in the pineal gland, the right fronto‐ parieto‐temporal region and the cerebellum, respectively. The findings of hypocellular neuropil as well as the characteristic ependymoblastic rosettes were seen. In addition the third case showed an abnormal combination of patterns including melanocytic and rhabdomyoblastic differentiation. The tumors stained positively for synaptophysin in the neuropil and small cell component, while the ependymoblastic rosettes stained for vimentin only. Epithelial membrane antigen and CD99 were negative in all components. One of the cases showed tetraploidy of chromosome 2. All cases exh...

Evaluation of risk factors in the development of stem cell therapy

Journal of Translational Medicine — Tue, 22 Mar 2011 00:00:00 +0100

Stem cell therapy holds the promise to treat degenerative diseases, cancer and repair of damaged tissues for which there are currently no or limited therapeutic options. The potential of stem cell therapies has long been recognised and the creation of induced pluripotent stem cells (iPSC) has boosted the stem cell field leading to increasing development and scientific knowledge. Despite the clinical potential of stem cell based medicinal products there are also potential and unanticipated risks. These risks deserve a thorough discussion within the perspective of current scientific knowledge and experience. Evaluation of potential risks should be a prerequisite step before clinical use of stem cell based medicinal products.The risk profile of stem cell based medicinal products depends on ma...

Continuing Medical Education: AFIP Archives: From the Archives of the AFIP: Pediatric Liver Masses: Radiologic-Pathologic Correlation Part 2. Malignant Tumors [Pediatric Imaging]

Radiographics recent issues — Thu, 17 Mar 2011 00:00:00 +0100

Malignant primary hepatic tumors in children include lesions unique to the pediatric age group and others that are more common in adults. Important considerations when evaluating a child with a liver tumor are the age of the patient, laboratory findings, and specific imaging features. The most common primary malignant hepatic tumor in the pediatric population, hepatoblastoma occurs almost exclusively in patients younger than 5 years with no history of liver disease. Hepatoblastoma is associated with elevated serum α-fetoprotein (AFP) level and appears predominantly solid. Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in older children, often with a history of liver disease. HCC is associated with elevated serum AFP level and also appears as a solid mass. Fib...

From the Archives of the AFIP: Pediatric Liver Masses: Radiologic-Pathologic Correlation Part 2. Malignant Tumors [AFIP Archives]

Radiographics recent issues — Thu, 17 Mar 2011 00:00:00 +0100

High‐resolution array CGH identifies common mechanisms that drive embryonal rhabdomyosarcoma pathogenesis

Genes, Chromosomes and Cancer — Tue, 15 Mar 2011 00:00:00 +0100

AbstractPediatric rhabdomyosarcoma occurs as two biologically distinct histological variants, embryonal (ERMS) and alveolar (ARMS). To identify genomic changes that drive ERMS pathogenesis, we used a new array comparative genomic hybridization (aCGH) platform to examine a specific subset of ERMS tumors, those occurring in children with clinically defined intermediate‐risk disease. The aCGH platform used has an average probe spacing ∼1 kb, and can identify genomic changes with single gene resolution. Our data suggest that these tumors share a common genomic program that includes inactivation of a master regulator of the p53 and Rb pathways, CDKN2A/B, and activation of FGFR4, Ras, and Hedgehog (Hh) signaling. The CDKN2A/B tumor suppressor is deleted in most patient samples. FGFR4, which ...

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Proton Radiotherapy for Parameningeal Rhabdomyosarcoma: Clinical Outcomes and Late Effects

International Journal of Radiation Oncology * Biology * Physics — Mon, 07 Mar 2011 05:00:00 +0100

Conclusions: Proton radiotherapy for patients with PM-RMS yields tumor control and survival comparable to that in historical controls with similar poor prognostic factors. Furthermore, rates of late effects from proton radiotherapy compare favorably to published reports of photon-treated cohorts. (Source: International Journal of Radiation Oncology * Biology * Physics)

US Army Makes 10 Year Old Cancer Patient An Honorary Soldier

About.com Cancer — Mon, 07 Mar 2011 00:00:00 +0100

I was so touched when I read about a young boy who was made an honorary soldier by the U.S. Army last week. 10 year old Brennan Daigle suffers from embryonal rhabdomyosarcoma, a rare type of cancer in which muscle tumors attach themselves to the bones. He has been fighting the disease since 2009 and was informed that all treatment methods have been exhausted. Brennan has only weeks to live....Read Full Post (Source: About.com Cancer)

MAGEC2 is a sensitive and novel marker for seminoma: a tissue microarray analysis of 325 testicular germ cell tumors

Modern Pathology AOP — Fri, 04 Mar 2011 00:00:00 +0100

Authors: Peter K Bode, André Barghorn, Florian R Fritzsche, Marc-Oliver Riener, Glen Kristiansen, Alexander Knuth & Holger Moch (Source: Modern Pathology AOP)

Potential role of heat shock proteins in neural differentiation of murine embryonal carcinoma stem cells (P19).

Cell Biology International — Mon, 28 Feb 2011 00:00:00 +0100

In conclusion our results raise the possibility that HSPs could regulate cell differentiation and proliferation under both physiological and pathological conditions. PMID: 21355853 [PubMed - as supplied by publisher] (Source: Cell Biology International)

The almighty MYC: Orchestrating the micro-RNA universe to generate aggressive liver cancer

Journal of Hepatology — Wed, 23 Feb 2011 00:00:00 +0100

COMMENTARY ON:: Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer. Cairo S, Wang Y, de Reyniès A, Duroure K, Dahan J, Redon MJ, Fabre M, McClelland M, Wang XW, Croce CM, Buendia MA. PNAS, 2010, November 23, 107(47), 20471–20476. Copyright (2010) by the National Academy of Sciences. Abstract reprinted with permission from the National Academy of Sciences.http://www.ncbi.nlm.nih.gov/pubmed/21059911Abstract: Myc activation has been implicated in the pathogenesis of hepatoblastoma (HB), a rare embryonal neoplasm derived from liver progenitor cells. Here, microRNA (miR) expression profiling of 65 HBs evidenced differential patterns related to developmental stage and Myc activity. Undifferentiated aggressive HBs overexpressed the miR-371–3 cluster with concomitant ...

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Accelerated biosynthesis of neolacto-series glycosphingolipids in differentiated mouse embryonal carcinoma F9 cells detected by using dodecyl N-acetylglucosaminide as a saccharide primer

Journal of Biochemistry — Tue, 22 Feb 2011 00:00:00 +0100

Using dodecyl N-acetylglucosaminide (GlcNAc-C12) as a saccharide primer, we investigated the biosynthetic changes of neolacto-series glycosphingolipids (GSLs) in mouse embryonal carcinoma F9 cells during differentiation induced by retinoic acid plus dibutyryl cyclic AMP (RA/dbcAMP). In the differentiated cells, the glycosylation of GlcNAc-C12 was greatly enhanced. The sugar compositions of glycosylated primers were assigned as Hex-GlcNAc, [Hex]2-GlcNAc, [Hex]2[HexNAc]-GlcNAc, and [NeuAc][Hex]-GlcNAc by liquid chromatography-tandem mass spectrometry. The detection of augmented biosynthesis of endogenous sialylparagloboside indicated that [NeuAc][Hex]-GlcNAc was predicted to be the non-reducing end trisaccharide of sialylparagloboside. The transcription of B3gnt5, B4galt1, Ggta1, Fut4 and St...

Rapid Differentiation of Human Embryonal Carcinoma Stem Cells (NT2) into Neurons for Neurite Outgrowth Analysis.

Cellular and Molecular Neurobiology — Fri, 18 Feb 2011 00:00:00 +0100

Authors: Tegenge MA, Roloff F, Bicker G Human neurons derived from stem cells can be employed as in vitro models to predict the potential of neurochemicals affecting neurodevelopmental cellular processes including proliferation, migration, and differentiation. Here, we developed a model of differentiating human neurons from well characterized human embryonal carcinoma stem cells (NT2). NT2 cells were induced to differentiate into neuronal phenotypes after 2 weeks of treatment with retinoic acid in aggregate culture. Nestin positive progenitor cells migrate out of NT2 aggregates and differentiate into βIII-tubulin expressing neuronal cells. Culturing the NT2 cells for an additional 7-14 days resulted in increased percentage of βIII-tubulin expressing cells, elaborating a long neurit...

GPR30 is over-expressed in post puberal testicular germ cell tumors.

Cancer Biology and Therapy — Wed, 16 Feb 2011 06:47:37 +0100

In this study, we have evaluated by immunohistochemical analysis GPR30 expression in post-puberal testicular germ cell tumours (30 seminomas, 5 teratomas, 12 embryonal carcinomas, and 20 intratubular germ cell tumors). The GPR30 protein expression was detected at high level in all intratubular germ cell tumours, seminomas, and embryonal carcinomas, whereas in teratomas the expression was low. The immunohistochemical data were further confirmed by Western blot analysis. GPR30 protein expression has also been analyzed in GC1 and TCam-2 cell lines, respectively derived from immortalized type B murine spermatogonia and human seminoma. Our results indicate that GPR30 could be a potential therapeutic target; the design of a specific GPR30 inhibitors could be a useful molecular target to block ne...

The regulatory role of histone deacetylase inhibitors in Fgf4 expression is dependent on the differentiation state of pluripotent stem cells

Journal of Cellular Physiology — Tue, 15 Feb 2011 15:03:35 +0100

This study uncovers an important role of HDAC1 and histone modifications in the repression of Fgf4 and perhaps other pluripotency genes during ESC differentiation. Our results also suggest that HDAC inhibitors may promote reprogramming partially through activating pluripotency genes at some intermediate stages. J. Cell. Physiol. © 2011 Wiley‐Liss, Inc. (Source: Journal of Cellular Physiology)

Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma

Cancer Cell — Tue, 15 Feb 2011 00:00:00 +0100

Brian P. Rubin, Koichi Nishijo, Hung-I Harry Chen, Xiaolan Yi, David P. Schuetze, Ranadip Pal, Suresh I. Prajapati, Jinu Abraham, Benjamin R. Arenkiel, Qing-Rong Chen, Sean Davis, Amanda T. McCleish, Mario R. Capecchi, Joel E. Michalek, Lee Ann Zarzabal, Javed Khan, Zhongxin Yu, David M. Parham, Frederic G. Barr, Paul S. Meltzer, Yidong Chen, Charles Keller. Embryonal rhabdomyosarcoma (eRMS) shows the most myodifferentiation among sarcomas, yet the precise cell of origin remains undefined. Using Ptch1, p53 and/or Rb1 conditional m.... (Source: Cancer Cell)

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RNA-binding protein LIN28 is a marker for testicular germ cell tumors

Human Pathology — Wed, 02 Feb 2011 00:00:00 +0100

Summary: LIN28 is an RNA-binding protein involved in maintaining the pluripotency of embryonic stem cells. Using formalin-fixed, paraffin-embedded tissue blocks, we performed immunohistochemical staining of LIN28 in 103 primary and 81 metastatic testicular germ cell tumors (54 intratubular germ cell neoplasias, unclassified type; 49 primary and 20 metastatic classic seminomas; 35 primary and 24 metastatic embryonal carcinomas; 35 primary and 15 metastatic yolk sac tumors; 23 primary and 12 metastatic teratomas; 6 primary and 10 metastatic choriocarcinomas; and 5 spermatocytic seminomas). The percentage of tumor cell stained was scored as 0 (0%), 1+ (≤30%), 2+ (31%-60%), 3+ (61%-90%), and 4+ (>90%). We stained LIN28 in 327 non–germ cell tumors to determine its specificity. We also compa...

Atypical teratoid/rhabdoid tumors may show morphological and immunohistochemical features seen in choroid plexus tumors

Neuropathology — Sun, 30 Jan 2011 00:00:00 +0100

Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal tumors having a poor prognosis and are associated with mutations in the tumor suppressor gene hSNF5/SMARCB1/INI1. Differential diagnosis includes choroid plexus carcinoma which has occasionally been attributed as showing an inactivation of INI1/SMARCB1 nuclear staining in immunohistochemistry. However, these findings have been challenged by others. We therefore examined eight AT/RTs from six patients by immunohistochemistry for membranous expression of the inward rectifier potassium channel Kir7.1, which was in the central nervous system so far considered specific for choroid plexus tumors and normal choroid plexus epithelium. Two AT/RT cases exhibited membranous staining of Kir7.1, indicating a plexus epithelial differenti...

Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma

Acta Neuropathologica — Fri, 28 Jan 2011 06:53:11 +0100

Abstract Missense mutations of the V600E type constitute the vast majority of tumor-associated somatic alterations in the v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene. Initially described in melanoma, colon and papillary thyroid carcinoma, these alterations have also been observed in primary nervous system tumors albeit at a low frequency. We analyzed exon 15 of BRAF spanning the V600 locus by direct sequencing in 1,320 adult and pediatric tumors of the nervous system including various types of glial, embryonal, neuronal and glioneuronal, meningeal, adenohypophyseal/sellar, and peripheral nervous system tumors. A total of 96 BRAF mutations were detected; 93 of the V600E type and 3 cases with a three base pair insertion between codons 599 and 600. The highest f...

A Spontaneous Teratocarcinoma in the Testis of a Swiss Albino Mouse.

Toxicologic Pathology — Wed, 26 Jan 2011 00:00:00 +0100

Authors: Jamadagni S, Jamadagni P, Upadhyay S, Gaidhani S, Hazra J A unilateral non-metastatic embryonal carcinoma and teratoma of the testis was observed in a 12-week-old Swiss Albino mouse at the end of a 28-day repeated dose toxicity study. The teratocarcinoma almost completely replaced the parenchyma of the left testis. The tumor was composed of sheets and rosettes of primitive embryonal cells, anaplastic cells, skeletal muscle tissue, sebaceous gland tissue, keratinized stratified squamous epithelium, and ciliated cuboidal epithelium. The histomorphological characteristics of the tumor were reviewed and presented in this report. To the best of the authors' knowledge, this is the first report of spontaneous teratocarcinoma of testis in the Swiss Albino strain of mice. PMID: 212...

Endometrial metaplasias and reactive changes: a spectrum of altered differentiation

Journal of Clinical Pathology — Mon, 24 Jan 2011 00:00:00 +0100

Endometrial metaplasias and changes (EMCs) are conditions frequently overlooked and misdiagnosed. The aim of this review is to update current issues and provide a classification with a practical clinicopathological approach. Hormonal or irritative stimuli are the main inducing factors of EMCs, although some metaplasias have a mutational origin. EMCs vary from reactive, degenerative lesions to those able to associate with malignancy or those having a preneoplastic potential. The most common types of EMCs are ciliated tubal metaplasia (CTM) and mucinous metaplasia (MM), which occur in simple and complex glands, and possibly these architectural changes hold the same prognostic significance as they do in hyperplastic endometrioid lesions. Immunohistochemically, CTM is positive for LhS28, bcl-2...

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Rhabdomyosarcoma in infants younger than 1 year

Cancer — Mon, 24 Jan 2011 00:00:00 +0100

CONCLUSIONS:Infants with RMS appeared to have worse outcomes than older patients, in part because of high rates of local failure. The authors concluded that concerns regarding morbidity in infants and reluctance to use aggressive local control measures may lead to higher rates of local failure. Cancer 2011. © 2011 American Cancer Society. (Source: Cancer)

MyoD Regulates Premyogenic Mesoderm Factors [Developmental Biology]

Journal of Biological Chemistry — Fri, 21 Jan 2011 00:00:00 +0100

Gain- and loss-of-function experiments have illustrated that the family of myogenic regulatory factors is necessary and sufficient for the formation of skeletal muscle. Furthermore, MyoD required cellular aggregation to induce myogenesis in P19 embryonal carcinoma stem cells. To determine the mechanism by which stem cells can be directed into skeletal muscle, a time course of P19 cell differentiation was examined in the presence and absence of exogenous MyoD. By quantitative PCR, the first MyoD up-regulated transcripts were the premyogenic mesoderm factors Meox1, Pax7, Six1, and Eya2 on day 4 of differentiation. Subsequently, the myoblast markers myogenin, MEF2C, and Myf5 were up-regulated, leading to skeletal myogenesis. These results were corroborated by Western blot analysis, showing up...

Persistent Müllerian duct syndrome with testicular malignancy and unilateral seminal vesicle agenesis

European Journal of Radiology Extra — Thu, 20 Jan 2011 00:00:00 +0100

Abstract: A 27-year-old male presented to our clinic for evaluation after operation which was made for a malignancy originated from undescended testis. Operation had revealed abdominal mass located right lateral to bladder originated from right testis. There were no additional findings at operation note. Pathology of specimen was mixed germ cell tumor consisting of embryonal carcinoma, yolk sac tumor and seminoma. Radiologic evaluation ultrasonography (US) showed a solid mass posterior to the bladder with a central cystic component and a hypoechoic oval shaped solid structure on the left side of this mass. Between these masses there was a hypoechoic band like structure. Magnetic resonance imaging (MRI) confirmed the presence of these masses. Four years after operation laboratory results re...

A polymeric nanoparticle formulation of curcumin inhibits growth, clonogenicity and stem-like fraction in malignant brain tumors.

Cancer Biology and Therapy — Sat, 15 Jan 2011 18:00:09 +0100

Authors: Lim KJ, Bisht S, Bar EE, Maitra A, Eberhart CG Curcumin is a polyphenolic compound derived from the Indian spice turmeric. We used nanoparticle-encapsulated curcumin to treat medulloblastoma and glioblastoma cells. This formulation caused a dose-dependent decrease in growth of multiple brain tumor cell cultures, including the embryonal tumor derived lines DAOY and D283Med, and the glioblastoma neurosphere lines HSR-GBM1 and JHH-GBM14. The reductions in viable cell mass observed were associated with a combination of G2/M arrest and apoptotic induction. Curcumin also significantly decreased anchorage-independent clonogenic growth and reduced the CD133-positive stem-like population. Down-regulation of the insulin-like growth factor pathway in DAOY medulloblastoma cells was observ...

Dual Roles of Oct4 in the Maintenance of Mouse P19 Embryonal Carcinoma Cells: As Negative Regulator of Wnt/β-Catenin Signaling and Competence Provider for Brachyury Induction

Stem Cells and Development — Sat, 08 Jan 2011 18:07:49 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

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Down‐regulation of estrogen receptor‐β associates with transcriptional coregulator PATZ1 delocalization in human testicular seminomas

The Journal of Pathology — Wed, 05 Jan 2011 00:00:00 +0100

AbstractEstrogen exposure has been linked to a risk for the development of testicular germ cell cancers. The effects of estrogen are now known to be mediated by estrogen receptor α (ERα) and ERβ subtypes, but only ERβ has been found in human germ cells of normal testis. However, its expression was markedly diminished in seminomas, embryonal cell carcinomas, and in mixed germ cell tumours but remains high in teratomas. PATZ1 is a recently discovered zinc finger protein that, due to the presence of the POZ domain, acts as a transcriptional repressor affecting the basal activity of different promoters. We have previously described that PATZ1 plays a crucial role in normal male gametogenesis and that its up‐regulation and mis‐localization could be associated to the development of testi...

Down‐regulation of oestrogen receptor‐β associates with transcriptional co‐regulator PATZ1 delocalization in human testicular seminomas

The Journal of Pathology — Wed, 05 Jan 2011 00:00:00 +0100

AbstractOestrogen exposure has been linked to a risk for the development of testicular germ cell cancers. The effects of oestrogen are now known to be mediated by oestrogen receptor‐α (ERα) and ERβ subtypes, but only ERβ has been found in human germ cells of normal testis. However, its expression was markedly diminished in seminomas, embryonal cell carcinomas and mixed germ cell tumours, but remains high in teratomas. PATZ1 is a recently discovered zinc finger protein that, due to the presence of the POZ domain, acts as a transcriptional repressor affecting the basal activity of different promoters. We have previously described that PATZ1 plays a crucial role in normal male gametogenesis and that its up‐regulation and mislocalization could be associated with the development of test...

Molecular and genetic basis of childhood cancer.

Cancer Biomarkers : Section A of Disease Markers — Sat, 01 Jan 2011 05:00:00 +0100

Authors: Rushton J, López-Terrada D Abstract Pediatric malignancies are a spectrum of biologically diverse cancers different from those seen in adults. Malignant solid tumors diagnosed in children are often, and at least partly the result of developmental pathways dysregulation, and may recapitulate stages of organogenesis. Significant insight into their pathogenesis came from studying normal embryonal and fetal organ development, as well as mechanisms responsible for developmental disorders and congenital syndromes associated with these tumors. Systematic integration of pathology, genetic and molecular analyses of pediatric solid tumors is allowing the recognition of distinct clinical tumor subtypes, as well as potential therapeutic targets for some of these neoplasms. From the d...

Central nervous system.

Cancer Biomarkers : Section A of Disease Markers — Sat, 01 Jan 2011 05:00:00 +0100

Authors: Adamson DC, Rasheed BA, McLendon RE, Bigner DD Abstract Several different types of tumors, benign and malignant, have been identified in the central nervous system (CNS). The prognoses for these tumors are related to several factors, such as the age of the patient and the location and histology of the tumor. In adults, about half of all CNS tumors are malignant, whereas in pediatric patients, more than 75% are malignant. For most benign CNS tumors that require treatment, neurosurgeons can offer curative resections or at least provide significant relief from mass effect. Unfortunately, we still lack effective treatments for most primary and secondary malignant CNS tumors. However, the past decade has witnessed an explosion in the understanding of the early molecular events ...

Stromal-epithelial interactions in early neoplasia.

Cancer Biomarkers : Section A of Disease Markers — Sat, 01 Jan 2011 05:00:00 +0100

Authors: Liu AY, Pascal LE, Vêncio RZ, Vêncio EF Abstract In prostate tumors, both the epithelial and stromal mesenchyme compartments show gene expression changes from their respective normal counterpart. In fact, there are more such changes in the stroma than the epithelium. These include down-regulated expression of genes involved in smooth muscle cell differentiation and those differentially expressed between prostate and bladder, i.e., organ-restricted. In development, the stromal cell type mediates tissue formation from differentiation of stem or progenitor cells. Diseases like cancer may arise as a result of defective stromal signaling. Stromal signaling can be demonstrated by co-culture of stromal cells and embryonal carcinoma NCCIT cells used as a stem cell substitute. In...

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Diagnosis of testicular carcinoma in situ‘(intratubular and microinvasive)’ seminoma and embryonal carcinoma using direct enzymatic alkaline phosphatase reactivity on frozen histological sections

Histopathology — Sat, 01 Jan 2011 00:00:00 +0100

Conclusions: The dAP test is an informative, reproducible and easy tool to diagnose CIS, (intratubular and microinvasive) seminoma and embryonal carcinoma on frozen tissue sections, being of great value in the context of sparing surgery. (Source: Histopathology)

Cancer and the evolution of stem cell fates

Bone — Tue, 28 Dec 2010 22:19:53 +0100

A key feature of pluripotent stem cells is that when they divide, they must choose between self renewal and commitment to differentiation. Further, if they commit to differentiate they must choose between different lineages. Some degree of spontaneous differentiation is common in cultures of human ES cells. This can confuse studies of human ES cell behavior if assays are based on assessment of the population as a whole, without taking account of the consequent heterogeneity of such cultures. Further, a propensity for differentiation provides a basis for selective pressures that may lead to the appearance of variant ES cells that exhibit an increased probability of self renewal over differentiation, or cell death through apoptosis. Indeed human ES cell lines do accumulate non-random genetic...

Treatment efficiency, outcome and surgical treatment problems in patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma: A report from the cooperative soft tissue sarcoma trial CWS‐96

Pediatric Blood and Cancer — Wed, 22 Dec 2010 00:00:00 +0100

ConclusionsLocal therapy is an important factor for prognosis of localized embryonal BPRMS. Inadequate primary or secondary surgery compromises the outcome and should be avoided. Radiotherapy alone, complete surgical tumor resection or combined preoperative radiotherapy with surgical resection lead to similar good local control rates and prognosis. Pediatr Blood Cancer © 2010 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

Notch pathway inhibition significantly reduces rhabdomyosarcoma invasiveness and mobility in vitro.

Clinical Cancer Research — Tue, 21 Dec 2010 00:00:00 +0100

CONCLUSIONS: Pharmacological or genetic blockage of the pathway significantly reduced invasiveness of RMS cell lines, thereby suggesting a possible role of the Notch pathway in the regulation of the metastatic process in RMS. PMID: 21177409 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Partial Orchiectomy for Presumed Malignancy in Patients With a Solitary Testis Due to a Prior Germ Cell Tumor: A Large North American Experience

The Journal of Urology — Fri, 17 Dec 2010 00:00:00 +0100

Conclusions: Partial orchiectomy is an option to decrease morbidity in men with a metachronous germ cell tumor. Clearly a definite benefit of partial orchiectomy is that a significant proportion of patients with suspicious testicular lesions did not have malignancy and were definitively treated with an organ sparing approach. However, partial orchiectomy is potentially associated with the need for adjuvant treatment and androgen substitution, which should be discussed with all patients. (Source: The Journal of Urology)

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Minimum regions of genomic imbalance in stage I testicular embryonal carcinoma and association of 22q loss with relapse

Genes, Chromosomes and Cancer — Thu, 16 Dec 2010 00:00:00 +0100

AbstractTesticular germ cell tumors (TGCT) are the most frequent solid tumor to affect young adult males and are histologically divided into seminomas and nonseminomas (NS). NS comprise undifferentiated embryonal carcinoma (EC) and differentiated tumors with embryonic (teratoma) or extra‐embryonic (choriocarcinoma, yolk sac tumor) features. In contrast to other subtypes, EC have uniform cellular morphology and lack normal cell infiltrates, ideal for nucleic acid profiling. EC are under‐represented in previous studies due to their relative rarity. To gain insights into NS tumorigenesis, metastatic dissemination and potential markers of relapse, a full tiling path BAC platform was used to obtain array comparative genomic hybridization (aCGH) profiles from 32 formalin fixed paraffin embed...

Tumor volume and patient weight as predictors of outcome in children with intermediate risk rhabdomyosarcoma

Cancer — Tue, 14 Dec 2010 00:00:00 +0100

CONCLUSIONS:The factors that had the strongest association with EFS were tumor volume, patient weight, and histology. On the basis of regression modeling, tumor volume and patient weight were superior predictors of outcome compared with greatest tumor dimension and patient age in children with intermediate‐risk RMS. The current results indicated that the prognostic performance of tumor volume and patient weight should be assessed in an independent prospective study. Cancer 2011. © 2010 American Cancer Society. (Source: Cancer)

miR‐492 is processed from the keratin 19 gene and upregulated in metastatic hepatoblastoma

Hepatology — Mon, 13 Dec 2010 00:00:00 +0100

Conclusion:A close functional relationship between KRT19 and miR‐492 was identified that may play an important role in the progression of malignant embryonal liver tumors. Additionally, miR‐492 and its associated targets might serve as new HB biomarkers of clinical utility and could assist to explore targeted therapies especially in metastatic HB with still poor prognosis. (HEPATOLOGY 2010.) (Source: Hepatology)

MicroRNA‐492 is processed from the keratin 19 gene and up‐regulated in metastatic hepatoblastoma

Hepatology — Mon, 13 Dec 2010 00:00:00 +0100

Conclusion: A close functional relationship between KRT19 and miR‐492 was identified that may play an important role in the progression of malignant embryonal liver tumors. Additionally, miR‐492 and its associated targets might serve as new HB biomarkers of clinical utility and could assist to explore targeted therapies, especially in metastatic HB with a poor prognosis. (HEPATOLOGY 2011) (Source: Hepatology)

Foxm1 transcription factor is required for maintenance of pluripotency of P19 embryonal carcinoma cells

Nucleic Acids Research — Sat, 11 Dec 2010 00:00:00 +0100

Transcription factor Foxm1 plays a critical role during embryonic development and its expression is repressed during retinoic acid (RA)-induced differentiation of pluripotent P19 embryonal carcinoma cells at the early stage, correlated with downregulation of expression of pluripotency markers. To study whether Foxm1 participates in the maintenance of pluripotency of stem cells, we knock down Foxm1 expression in P19 cells and identify that Oct4 are regulated directly by Foxm1. Knockdown of Foxm1 also results in spontaneous differentiation of P19 cells to mesodermal derivatives, such as muscle and adipose tissues. Maintaining Foxm1 expression prevents the downregulation of pluripotency-related transcription factors such as Oct4 and Nanog during P19 cell differentiation. Furthermore, overexpr...

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Caveolin 1 is a marker of poor differentiation in Rhabdomyosarcoma

European Journal of Cancer — Wed, 24 Nov 2010 00:00:00 +0100

Abstract: Caveolins consist of three different membrane scaffolding proteins that play a variety of processes in different tissues. In skeletal muscle caveolins are differentially distributed, with Caveolin 1 (Cav-1) being uniquely expressed in satellite cells and Caveolin 3 (Cav-3) in mature myofibers. Rhabdomyosarcoma (RMS) represents the most common childhood soft-tissue sarcoma arising from mesenchimal precursors which fail to undergo proper commitment to muscle lineage. Cav-3 has been proposed as a marker of RMS with a high degree of differentiation, while biological significance of Cav-1 expression in RMS is still a matter of debate. In the present study we show that Cav-1 is predominantly expressed in the embryonal RMS histotype, as further confirmed by transcript and protein analys...

Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer [Medical_Sciences]

Proceedings of the National Academy of Sciences — Tue, 23 Nov 2010 00:00:00 +0100

Myc activation has been implicated in the pathogenesis of hepatoblastoma (HB), a rare embryonal neoplasm derived from liver progenitor cells. Here, microRNA (miR) expression profiling of 65 HBs evidenced differential patterns related to developmental stage and Myc activity. Undifferentiated aggressive HBs overexpressed the miR-371–3 cluster with concomitant down-regulation of the miR-100/let-7a-2/miR-125b-1 cluster, evoking an ES cell expression profile. ChIP and Myc inhibition assays in hepatoma cells demonstrated that both miR clusters are regulated by Myc in an opposite manner. We show that the two miR clusters exert antagonistic effects on cell proliferation and tumorigenicity. Moreover, their combined deregulation cooperated in modulating the hepatic tumor phenotype, implicating...

Spontaneous and therapy-induced immunity to pluripotency genes in humans: clinical implications, opportunities and challenges

Cancer Immunology, Immunotherapy — Mon, 22 Nov 2010 16:43:55 +0100

Abstract Recent studies have suggested that the core pathways regulating pluripotency in embryonal stem cells bear considerable overlap with oncogenesis. Here, we discuss recent insights into the capacity of the human immune system to target some of the key pluripotency-associated genes. Immunity to these genes is also induced in humans in the context of chemotherapy-induced cell death in patients with germ cell tumors. Immunologic targeting of pathways associated with stemness has implications for both immune regulation of tumor growth as well as emerging regenerative therapies with embryonal stem cells. Content Type Journal ArticleDOI 10.1007/s00262-010-0944-8Authors Madhav V. Dhodapkar, Section of Hematology, Yale University, New Haven, CT 06510, USAKavita M. Dhoda...

Analysis of the adenomatous polyposis coli (APC) gene in childhood and adolescent germ cell tumors

Pediatric Blood and Cancer — Fri, 12 Nov 2010 00:00:00 +0100

ConclusionsMethylation of APC and LOH 5q21‐22 in YSTs and teratomas provide evidence for involvement of APC in the accumulation of β‐catenin and activation of the WNT pathway. Our additional analyses suggest that APC is unlikely to be solely responsible for the formation and progression of childhood GCTs. Pediatr Blood Cancer. © 2010 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

Embryonal rhabdomyosarcoma with metastases confined to the lungs: Report from the CWS study group

Pediatric Blood and Cancer — Mon, 08 Nov 2010 00:00:00 +0100

AbstractEmbryonal rhabdomyosarcoma (RME) is the most common pediatric soft tissue sarcoma. Whereas the prognosis of localized rhabdomyosarcoma has improved, it remains poor for metastatic disease. We analyzed RME‐patients with isolated pulmonary metastases treated in four consecutive CWS‐trials. Treatment included multiagent chemotherapy and local treatment of the primary tumor. Therapy of lung metastases after induction chemotherapy depended on response and individual decisions. Twenty‐nine patients <21 years had PRME. Their median age was 6 years, the median follow‐up 9 years. Twenty‐eight children had their primary tumor located in an unfavorable site and 22 of the primaries were >5 cm. In addition to conventional chemotherapy, seven patients received high‐dose...

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RNA-binding protein LIN28 is a marker for primary extragonadal germ cell tumors: an immunohistochemical study of 131 cases

Modern Pathology AOP — Fri, 05 Nov 2010 00:00:00 +0100

Authors: Dengfeng Cao, Aijun Liu, Fenghua Wang, Robert W Allan, Kaiyong Mei, Yan Peng, Jun Du, Shuangping Guo, Ty W Abel, Zhaoli Lane, Joe Ma, Maria Rodriguez, Shirin Akhi, Neha Dehiya & Jianping Li (Source: Modern Pathology AOP)

Evidence for a dynamic role of the linker histone variant H1x during retinoic acid-induced differentiation of NT2 cells

FEBS Letters — Mon, 25 Oct 2010 00:00:00 +0100

Abstract: The dynamics of chromatin structure are tightly regulated by multiple epigenetic mechanisms such as histone modifications and incorporation of histone variants. In the current work, differentiation of an embryonal carcinoma cell line, NT2, was induced by retinoic acid, and total histone proteins were compared throughout this process. The results showed a significant change in expression level of a variant of H1 histone named H1x. Chromatin immunoprecipitation coupled with real-time PCR analysis demonstrated a preferential incorporation of this protein in the regulatory region of Nanog, a marker gene of stemness that is significantly suppressed in differentiated cells. This finding reveals a dynamic role of H1x in differentiation, and implies a repressive role for this histone var...

A qPCR-based method (using TaqMan Protein Expression Assays) for detection of clinically relevant proteins in human testicular germ cell tumors

Cancer Genetics and Cytogenetics — Sat, 16 Oct 2010 14:33:22 +0100

Human testicular germ cell tumors (TGCTs) are the most frequent solid cancer in Caucasian males in the age between 15 and 45 years. In spite of the high success rate of current treatment strategies (surgery, irradiation, and chemotherapy), TGCTs account for the second cause of death in this age group. The initiating event, leading to carcinoma in situ (CIS), occurs during embryonal development, offering a window of opportunity for early detection and intervention, thereby preventing the need for intensive (systemic) treatment. CIS is the malignant counterpart of a primordial germ cell, and can be effectively diagnosed using immunohistochemistry for OCT3/4, NANOG, and c-KIT and its ligand (stem cell factor, SCF). SOX17 and SOX2 are informative for the diagnosis of the invasive components se...

Noonan syndrome, the SOS1 gene, and embryonal rhabdomyosarcoma

Cancer Genetics and Cytogenetics — Sat, 16 Oct 2010 14:33:13 +0100

In conclusion, we report a patient with a germline SOS1 mutation who developed ERMS. The homozygous nature of this SOS1 mutation in the tumor suggests that this mutation may underlie ERMS predisposition. (Source: Cancer Genetics and Cytogenetics)

Expression of chemokine receptor CXCR3, CXCR4, and CXCR7 and their respective ligands in rhabdomyosarcoma

Cancer Genetics and Cytogenetics — Sat, 16 Oct 2010 14:33:12 +0100

Rhabdomyosarcomas (RMS) are the most common malignant soft-tissue tumors of childhood, and nearly 15% of cases develop metastatic disease. They are histologically divided into two main subtypes: embryonal rhabdomyosarcomas (eRMS), which usually gain extra copies of whole chromosomes, and alveolar rhabdomyosarcomas (aRMS), more aggressive, with characteristic reciprocal translocations in about 80% of the tumors. The resulting chimeric fusion genes involve PAX3 or PAX7 and FKHR, and encode fusion proteins with enhanced transcriptional activity. Chemokines are a type of cytokine that bind to G-protein coupled receptors and mediate in cell trafficking, survival, and growth processes. Some reports have described the expression of chemokine receptors CXCR4 and CXCR7 by rhabdomyosarcoma cells. Th...

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Gobal DNA methylation in fetal human germ cells and germ cell tumors: correlation with differentiation and cisplatin resistance

Cancer Genetics and Cytogenetics — Sat, 16 Oct 2010 14:33:06 +0100

Differences in the global methylation pattern, i.e., hyper- as well as hypo-methylation, are observed in cancer, including germ cell tumors (GCTs). Related to their precursor cells, the GCT methylation status differs according to histology. We investigated the methylation pattern of normal fetal, infantile, and adult germ cells (n = 103) and GCTs (n = 251) by immunohistochemical staining for 5-mCytidine. We found that the global methylation pattern of male germ cells changes from hypomethylation to hypermethylation, while female germ cells remain unmethylated at all stages. Undifferentiated GCTs (seminomas, intratubular germ cell neoplasia unclassified, and gonadoblastomas) were hypomethylated, whereas more differentiated GCTs (teratomas, yolk sac tumors, choriocarcinomas) showed a higher ...

Constitutional submicroscopic genome imbalances in children with both cancer and a congenital anomaly

Cancer Genetics and Cytogenetics — Sat, 16 Oct 2010 14:32:59 +0100

The objective of our study was to find new cancer-predisposing genes by identifying submicroscopic copy number variations in individuals with both childhood cancer and morphological abnormalities, using a whole-genome approach. To this end, twenty-seven patients with a pediatric malignancy and congenital anomalies were analyzed for copy number changes using SNP array. In two of these patients a submicroscopic genome imbalance was found. The first patient is a girl with acute lymphoblastic leukemia (ALL) and polysyndactyly of the toes harboring a germline intragenic deletion in the THADA gene. Somatic deletions in THADA have been reported in paediatric ALL at a low frequency, and this gene has a presumable role in apoptosis. In the second patient, a girl with embryonal rhabdomyosarcoma and ...

An embryo-specific expressing TGF-beta family protein, growth-differentiation factor 3 (GDF3), augments progression of B16 melanoma

Journal of Experimental and Clinical Cancer Research — Thu, 14 Oct 2010 23:00:00 +0100

We examined the expression of ES cell-specific genes in the mouse B16 melanoma cell line to identify the factors promoting tumorigenesis. We found that endogenous growth-differentiation factor 3 (GDF3) expression was induced in implant B16 tumor during tumor progression in syngenic C57BL/6 mice. B16 F10, a subline with a high metastatic potential, continuously expressed GDF3 while low metastatic B16 F1 expressed comparatively decreased levels of GDF3. Overexpression of GDF3 promoted growth of implanted melanoma B16 F1 and F10 in syngenic mice. Ectopic expression of GDF3 was accompanied by an increased level of production of CD24/CD44. Such a profile was reported to be characteristic of melanoma stem cell-like cells. GDF3 expression was observed in embryonal carcinomas, primary testicular g...

Induction of murine embryonic stem cell differentiation by medicinal plant extracts.

Experimental Cell Research — Thu, 14 Oct 2010 23:00:00 +0100

Authors: Reynertson KA, Charlson ME, Gudas LJ Epidemiological evidence indicates that diets high in fruits and vegetables provide a measure of cancer chemoprevention due to phytochemical constituents. Natural products are a rich source of cancer chemotherapy drugs, and primarily target rapidly-cycling tumor cells. Increasing evidence indicates that many cancers contain small populations of resistant, stem-like cells that have the capacity to regenerate tumors following chemotherapy and radiation, and have been linked to the initiation of metastases. Our goal is to discover natural product-based clinical or dietary interventions that selectively target cancer stem cells, inducing differentiation. We adapted an alkaline phosphatase (AP) stain to assay plant extracts for the capacity to i...

[Mixed germ cell tumor of the ovary with rhabdomyosarcomatous component. A case report.]

Annales de Pathologie — Fri, 01 Oct 2010 00:00:00 +0100

We present a case of a 15-year old girl admitted for a voluminous left ovarian mass revealed by pelvic pain. Pathological examination of the dissected material revealed the tumor to be a mixed germ cell tumor (immature teratoma and yolk sac tumor) with rhabdomyosarcomatous component of embryonal type. Clinico-pathological characteristics of such ovarian tumors will be discussed with emphasis on diagnostic difficulties. PMID: 21055529 [PubMed - as supplied by publisher] (Source: Annales de Pathologie)

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Molecular diagnostics of CNS embryonal tumors

Acta Neuropathologica — Thu, 30 Sep 2010 08:16:44 +0100

Abstract Tremendous progress has recently been made in both molecular subgrouping, and the establishment of prognostic biomarkers for embryonal brain tumors, particularly medulloblastoma. Several prognostic biomarkers that were initially identified in retrospective cohorts of medulloblastoma, including MYC and MYCN amplification, nuclear β-catenin accumulation, and chromosome 17 aberrations have now been validated in clinical trials. Moreover, molecular subgroups based on distinct transcriptome profiles have been consistently reported from various groups on different platforms demonstrating that the concept of distinct medulloblastoma subgroups is very robust. Well-described subgroups of medulloblastomas include tumors showing wingless signaling pathway (Wnt) activation, a...

αvβ3 imaging can accurately distinguish between mature teratoma and necrosis in 18F-FDG-negative residual masses after treatment of non-seminomatous testicular cancer: a preclinical study

European Journal of Nuclear Medicine and Molecular Imaging — Thu, 30 Sep 2010 08:16:08 +0100

Conclusion Imaging αvβ3 integrin accurately distinguished mature teratoma from necrosis following cisplatin-based treatment in human NSGCT xenografts. Content Type Journal ArticleDOI 10.1007/s00259-010-1624-9Authors Nicolas Aide, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, François Baclesse Cancer Centre and Caen University, Caen, FranceMélanie Briand, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, François Baclesse Cancer Centre and Caen University, Caen, FrancePierre Bohn, Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital and QuantIF- LITIS (EA4108), Rouen, FranceSoizic Dutoit, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, François Baclesse Cancer Centre and Caen University, Caen, FranceCharline Lasnon, PET Unit, Caen...

Malignant Mixed Ovarian Germ Cell Tumor with Embryonal Component

Journal of Pediatric and Adolescent Gynecology — Tue, 28 Sep 2010 00:00:00 +0100

Conclusions: Malignant germ cell tumors frequently affect adolescent women of reproductive age. Management of these tumors requires consideration of fertility sparing surgical techniques and chemotherapy management. Using these techniques, the vast majority of patients will maintain their ovarian function and the ability to bear children after their recovery. (Source: Journal of Pediatric and Adolescent Gynecology)

Expression of glypican 3 in placental site trophoblastic tumor

BioMed Central — Fri, 24 Sep 2010 23:00:00 +0100

Conclusions: Identification of GPC3 in PSTT and PSN is consistent with the derivation of these lesions from intermediate trophoblasts, which have been described to express GPC3. GPC3 may be a useful adjunct immunohistochemical marker in differentiating PSTT from non-trophoblastic tumors. (Source: BioMed Central)

Expression of UTF1 in Primary and Metastatic Testicular Germ Cell Tumors.

American Journal of Clinical Pathology — Thu, 23 Sep 2010 21:42:22 +0100

Authors: Wang P, Li J, Allan RW, Guo CC, Peng Y, Cao D We immunohistochemically evaluated UTF1 in 104 primary and 68 metastatic testicular germ cell tumors and 339 non-germ cell tumors. The percentage of tumor cells stained was semiquantitatively scored (0, no tumor cell staining; 1+, â¤30% of cells; 2+, 31%-60% of cells; 3+, 61%-90% of cells; 4+, >90% of cells). Staining intensity (nuclear) was scored as weak, moderate, or strong. UTF1 staining was seen in all 56 intratubular germ cell neoplasias, unclassified type (2+, 1; 3+, 2; 4+, 53; weak, 4; moderate, 49; strong, 3), all 72 seminomas (1+, 2; 2+, 4; 3+, 8; 4+, 58; weak, 10; moderate, 33; strong, 29), and 59 embryonal carcinomas (3+, 2; 4+, 57; moderate, 1; strong, 58). Weak UTF1 staining was seen in 15 of 37 yolk sac tumors...

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A 5α-reductase inhibitor, finasteride, increases differentiation and proliferation of embryonal carcinoma cell-derived-neural cells

Medical Hypotheses — Mon, 20 Sep 2010 00:00:00 +0100

Summary: Recent advances in stem cell biology have resulted in identifying new agents to differentiate stem cell-derived-neural cells. Different stem cell types have been shown to differentiate into neural cells. It has been shown that P19 line of embryonal carcinoma cells develops into neurons and astroglia after exposure to some hormones such as dehydroepiandrosterone (DHEA). Steroid 5α-reductase is a key enzyme in the conversion of several Δ4-3 keto steroids, such as testosterone into their respective 5α-reductase derivatives. Finasteride is a 5α-reductase inhibitor that inhibits conversion of testosterone to the more potent androgen dihydrotestosterone (DHT). Reduction in DHT and sustaining testosterone levels has an important impact on differentiation and proliferation of embryona...

KIT expression and methylation in medulloblastoma and PNET cell lines and tumors

Journal of Neuro-Oncology — Sat, 18 Sep 2010 16:59:34 +0100

Abstract The stem cell factor/kit tyrosine kinase receptor pathway is related to tumor growth and progression in several cancers including Ewing sarcoma, a peripheral PNET (pPNET). Identifying additional groups of tumors that may use the pathway is important as they might be responsive to imatinib mesylate treatment. MB and central PNET (cPNET) are embryonal tumors of the CNS that share similar undifferentiated morphology with Ewing sarcomas and display aggressive clinical behavior. cPNET outcome is significantly lower than MB outcome, even for localized tumors treated with high-risk MB therapy. The elucidation of signaling pathways involved in MB and cPNET pathogenesis, and the discovery of new therapeutic targets is necessary to improve the treatment of these neoplasms. ...

Podoplanin, a novel marker for seminoma: A comparison study evaluating immunohistochemical expression of podoplanin and OCT3/4

Annals of Diagnostic Pathology — Sat, 18 Sep 2010 07:34:40 +0100

In this study we investigate the utility of podoplanin expression in the diagnosis of testicular germ cell tumors. Sixty-eight cases of testicular mixed germ cell tumors were analyzed using a polyclonal antibody and compared to the results for OCT3/4. Stained sections were graded semiquantitatively as follows: negative (no expression), 1+ (mild intensity), 2+ (moderate intensity), 3+ (intense staining). Diffuse cytoplasmic expression of podoplanin with membrane accentuation was seen in the seminoma component of all cases. Lymphocytes and interstitial cells were negative. In mixed germ cell tumors, podoplanin identified small clusters of seminoma cells lying adjacent to nonseminomatous components. Focal staining was present in one third of cases of choriocarcinoma. There was no significant ...

Childhood Rhabdomyosarcoma: New Insight on Biology and Treatment

Current Oncology Reports — Tue, 07 Sep 2010 17:25:47 +0100

Abstract Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. The two most common histologic variants are the embryonal and alveolar subtypes. Although successive collaborative group clinical trials have improved survival rates for many RMS patients, the outcome for those patients with metastatic or recurrent disease remains poor. Recent studies have pointed to a possible mesenchymal stem cell as the progenitor for alveolar RMS. Other studies have implicated several cellular mechanisms and pathways being involved in RMS pathogenesis and survival, such as the cyclin-dependent kinase inhibitors, insulin-like growth factor pathway, and the mammalian target of rapamycin pathway, thus providing potential avenues for targeted therapy. Recent clinical trial...

Increased Levels of FoxA1 Transcription Factor in Pluripotent P19 Embryonal Carcinoma Cells Stimulate Neural Differentiation

Stem Cells and Development — Fri, 03 Sep 2010 23:02:27 +0100

Stem Cells and Development Sep 2010, Vol. 19, No. 9: 1365-1374. (Source: Stem Cells and Development)

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Cytoplasmic p21 expression levels determine cisplatin resistance in human testicular cancer

Journal of Clinical Investigation — Fri, 03 Sep 2010 09:00:27 +0100

Platinum-based chemotherapies such as cisplatin are used as first-line treatment for many cancers. Although there is often a high initial responsiveness, the majority of patients eventually relapse with platinum-resistant disease. For example, a subset of testicular cancer patients still die even though testicular cancer is considered a paradigm of cisplatin-sensitive solid tumors, but the mechanisms of chemoresistance remain elusive. Here, we have shown that one key determinant of cisplatin-resistance in testicular embryonal carcinoma (EC) is high cytoplasmic expression of the cyclin-dependent kinase (CDK) inhibitor p21. The EC component of the majority of refractory testicular cancer patients exhibited high cytoplasmic p21 expression, which protected EC cell lines against cisplatin-induc...

Recurrent seminomas: Clinical features and biologic implications.

Urologic Oncology — Thu, 02 Sep 2010 23:00:00 +0100

CONCLUSIONS: Although these atypical seminomas tend to be resistant to chemotherapy, they may still respond to certain chemotherapeutic regimens. Our pilot immunohistochemical study also suggested that the unique phenotypes associated with these atypical seminomas do not result from any relationship with embryonal carcinomas. More study is needed to confirm these initial findings. PMID: 20822932 [PubMed - as supplied by publisher] (Source: Urologic Oncology)

Comparative proteomics of human embryonic stem cells and embryonal carcinoma cells

Proteomics. Clinical Applications — Tue, 31 Aug 2010 23:00:00 +0100

This article was originally published in Proteomics (Source: Proteomics. Clinical Applications)

Non-seminomatous germ cell tumour of a testis in an 80-year-old man: A rare case

British Journal of Medical and Surgical Urology — Sat, 28 Aug 2010 08:13:49 +0100

An 80-year-old man referred to the urology clinic for lower urinary tract symptoms also complained of a painless left testicular swelling which he had noticed for the last 3–4 months. Physical examination revealed a firm non-tender smooth left scrotal swelling. The initial clinical impression was that of a tense hydrocoele. A scrotal ultrasound showed a 7.5cm×3.5cm×3.5cm mixed reflectivity area entirely replacing the left testes with large cystic areas within it. The appearances were suggestive of a seminoma (). Alpha fetoprotein (AFP), beta human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) were elevated at 770kU/L (normal range 0–10kU/L), 553IU/L (normal range 0–10IU/L), and 337U/L (normal range 0–215U/L), respectively. The patient underwent left radical orchide...

Non-canonical ubiquitylation of the proneural protein Ngn2 occurs in both Xenopus embryos and mammalian cells.

Biochemical and Biophysical Research communications — Fri, 27 Aug 2010 23:00:00 +0100

Authors: McDowell GS, Kucerova R, Philpott A Polyubiquitin chains targeting proteins for 26S proteasomal degradation are classically anchored on internal lysines of substrates via isopeptide linkages. However recently, linkage of ubiquitin moieties to non-canonical nucleophilic residues, such as cysteines, serines and threonines, has been demonstrated in a small number of cases. Non-canonical ubiquitylation of the proneural protein Ngn2 has previously been seen in Xenopus egg extract, but it was not clear whether such highly unusual modes of ubiquitylation were restricted to the environment of egg cytoplasm. Here we show that Ngn2 is, indeed, ubiquitylated on non-canonical sites in extracts from neurula stage Xenopus embryos, when Ngn2 is usually active. Moreover, in the P19 mammalian ...

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Alternative splicing of genes during neuronal differentiation of NT2 pluripotential human embryonal carcinoma cells

FEBS Letters — Thu, 19 Aug 2010 23:00:00 +0100

Abstract: We analyzed the mRNA diversity of genes after inducing neuronal differentiation in human NT2 teratocarcinoma cells using all-trans retinoic acid (RA). DNA microarray analyses of cells treated with RA identified 358 RA-responsive genes. mRNA diversity analysis revealed that 274 genes produced multiple protein-coding transcripts by alternative splicing. Among these 274 genes, we chose 26 genes that showed AS in their C-terminus and 12 transcription factor genes for further analysis. By using transcript-specific primers, we performed quantitative real-time PCR analysis to examine the expression profiles of all the protein-coding transcripts. Consequently, we identified genes which showed different RA-induced changes in the expression of their protein-coding transcripts. (Source: FEB...

Lovastatin induces neuronal differentiation and apoptosis of embryonal carcinoma and neuroblastoma cells: enhanced differentiation and apoptosis in combination with dbcAMP.

Molecular and Cellular Biochemistry — Sun, 08 Aug 2010 23:00:00 +0100

This study suggests the potential of combining these therapeutic approaches in EC and NB patients. PMID: 20694854 [PubMed - as supplied by publisher] (Source: Molecular and Cellular Biochemistry)

Clinical relevance of HER-2/neu overexpression in patients with testicular nonseminomatous germ cell tumor.

Urology Journal — Sat, 07 Aug 2010 15:39:03 +0100

CONCLUSION: We observed overexpression of HER-2/neu receptor in teratocarcinoma subtype of germ cell tumor. We suggest further studies to evaluate the clinical importance of this finding. PMID: 20209452 [PubMed - indexed for MEDLINE] (Source: Urology Journal)

Heterochromatin marks HP1γ, HP1α and H3K9me3, and DNA damage response activation in human testis development and germ cell tumours

International Journal of Andrology — Sun, 01 Aug 2010 23:00:00 +0100

Heterochromatinization has been implicated in fundamental biological and pathological processes including differentiation, senescence, ageing and tumourigenesis; however, little is known about its regulation and roles in human cells and tissues in vivo. Here, we show distinct cell-type- and cancer-stage-associated patterns of key heterochromatin marks: histone H3 trimethylated at lysine 9 (H3K9me3) and heterochromatic adaptor proteins HP1[alpha] and HP1[gamma], compared with the [gamma]H2AX marker of endogenously activated DNA damage response (DDR) and proliferation markers in normal human foetal (n = 4) and adult (n = 29) testes, pre-invasive carcinoma in situ (CIS; n = 26) lesions and a series of overt germ cell tumours, including seminomas (n = 26), embryonal carcinomas (n = 18) and ter...