The Experts below are selected from a list of 257208 Experts worldwide ranked by ideXlab platform
Kuanghung Cheng - One of the best experts on this subject based on the ideXlab platform.
-
stem Cell Marker nestin is critical for tgf β1 mediated tumor progression in pancreatic cancer
Molecular Cancer Research, 2013Co-Authors: Hueiting Su, Chingchieh Weng, Pijung Hsiao, Lihua Chen, Kuanghung ChengAbstract:The stem Cell Marker nestin is an intermediate filament protein that plays an important role in Cell integrity, migration, and differentiation. Nestin expression occurs in approximately one third of pancreatic ductal adenocarcinoma (PDAC), and its expression strongly correlates with tumor staging and metastasis. Little is known about the mechanisms by which nestin influences PDAC progression. Here, nestin overexpression in PDAC Cells increased Cell motility and drove phenotypic changes associated with the epithelial-mesenchymal transition (EMT) in vitro; conversely, knockdown of endogenous nestin expression reduced the migration rate and reverted Cells to a more epithelial phenotype. Mouse xenograft studies showed that knockdown of nestin significantly reduced tumor incidence and volume. Nestin protein expression was associated with Smad4 status in PDAC Cells; hence, nestin expression might be regulated by the TGF-b1/Smad4 pathway in PDAC. We examined nestin expression after TGF-b1 treatment in human pancreatic cancer PANC-1 and PANC-1 shSmad4 Cells. The TGF-b1/Smad4 pathway induced nestin protein expression in PDAC Cells in a Smad4dependent manner. Moreover, increased nestin expression caused a positive feedback regulator of the TGF-b1 signaling system. In addition, hypoxia was shown to induce nestin expression in PDAC Cells, and the hypoxiainduced expression of nestin is mediated by the TGF-b1/Smad4 pathway. Finally, the antimicrotubule inhibitors, cytochalasin D and withaferin A, exhibited anti-nestin activity; these inhibitors might be potential antimetastatic drugs. Our findings uncovered a novel role of nestin in regulating TGF-b1-induced EMT. Antinestin therapeutics may serve as a potential treatment for PDAC metastasis. Mol Cancer Res; 11(7); 768–79. � 2013 AACR.
-
stem Cell Marker nestin is critical for tgf β1 mediated tumor progression in pancreatic cancer
Molecular Cancer Research, 2013Co-Authors: Chingchieh Weng, Pijung Hsiao, Lihua Chen, Tzulei Kuo, Kungkai Kuo, Kuanghung ChengAbstract:The stem Cell Marker nestin is an intermediate filament protein that plays an important role in Cell integrity, migration, and differentiation. Nestin expression occurs in approximately one third of pancreatic ductal adenocarcinoma (PDAC), and its expression strongly correlates with tumor staging and metastasis. Little is known about the mechanisms by which nestin influences PDAC progression. Here, nestin overexpression in PDAC Cells increased Cell motility and drove phenotypic changes associated with the epithelial-mesenchymal transition (EMT) in vitro; conversely, knockdown of endogenous nestin expression reduced the migration rate and reverted Cells to a more epithelial phenotype. Mouse xenograft studies showed that knockdown of nestin significantly reduced tumor incidence and volume. Nestin protein expression was associated with Smad4 status in PDAC Cells; hence, nestin expression might be regulated by the TGF-β1/Smad4 pathway in PDAC. We examined nestin expression after TGF-β1 treatment in human pancreatic cancer PANC-1 and PANC-1 shSmad4 Cells. The TGF-β1/Smad4 pathway induced nestin protein expression in PDAC Cells in a Smad4-dependent manner. Moreover, increased nestin expression caused a positive feedback regulator of the TGF-β1 signaling system. In addition, hypoxia was shown to induce nestin expression in PDAC Cells, and the hypoxia-induced expression of nestin is mediated by the TGF-β1/Smad4 pathway. Finally, the antimicrotubule inhibitors, cytochalasin D and withaferin A, exhibited anti-nestin activity; these inhibitors might be potential antimetastatic drugs. Our findings uncovered a novel role of nestin in regulating TGF-β1-induced EMT. Anti-nestin therapeutics may serve as a potential treatment for PDAC metastasis.
Dieter Krahl - One of the best experts on this subject based on the ideXlab platform.
-
phlda1 tdag51 is a follicular stem Cell Marker and differentiates between morphoeic basal Cell carcinoma and desmoplastic trichoepithelioma
British Journal of Dermatology, 2011Co-Authors: Klaus Sellheyer, Dieter KrahlAbstract:Summary Background Morphoeic basal Cell carcinoma (BCC) and desmoplastic trichoepithelioma can often be difficult to differentiate on routine sections and few reliable immunohistochemical Markers are currently available. Recent cDNA microarray studies revealed the pleckstrin homology-like domain, family A, member 1 protein (PHLDA1) as a highly reliable Marker of the hair follicle stem Cells. Given the differentiation of trichoepithelioma along the follicular lineage and the proposed role of PHLDA1 as a follicular stem Cell Marker, we examined the staining pattern of PHLDA1 in the desmoplastic variant of trichoepithelioma and in its differential diagnostic conundrum, morphoeic BCC. Objectives To describe the expression pattern of PHLDA1 in morphoeic BCC and desmoplastic trichoepithelioma. Methods Evaluation of the staining pattern for PHLDA1 was performed using standard immunohistochemical techniques. For comparison reasons, we analysed staining for PHLDA1 in normal skin structures with particular reference to the hair follicle. Results With the exception of one case, all 16 desmoplastic trichoepitheliomas were immunoreactive with more than 80% of the Cells stained, whereas all 14 morphoeic BCCs were PHLDA1-negative with the exception of ulcerated tumours. In the latter, the tumour islands close to the ulcer were PHLDA1-positive whereas the deeper located tumour portions remained immunonegative. PHLDA 1 was prominently expressed in the hair follicle bulge of terminal and vellus hair follicles. Conclusions The hair follicle bulge Marker PHLDA1 differentiates between desmoplastic trichoepitheliomas and nonulcerated examples of morphoeic BCCs. We suggest incorporating PHLDA1 in the diagnostic work-up of difficult to differentiate basaloid tumours.
-
spatiotemporal expression pattern of neuroepithelial stem Cell Marker nestin suggests a role in dermal homeostasis neovasculogenesis and tumor stroma development a study on embryonic and adult human skin
Journal of The American Academy of Dermatology, 2010Co-Authors: Klaus Sellheyer, Dieter KrahlAbstract:Background Whereas keratinocytic bulge stem Cells are well characterized, comparably little is known about cutaneous mesenchymal stem Cells. The follicular connective tissue sheath is proposed as a niche for dermal stem Cells. Objective Because the neuroepithelial stem Cell Marker nestin represents a Marker for mesenchymal stem Cells in various tissues, our aim was to characterize its spatiotemporal expression pattern in the skin with special reference to the follicular mesenchyme. Methods We studied immunohistochemically nestin expression over the course of human cutaneous embryogenesis, in postnatal skin, in scalp wounds, and in the peritumoral stroma of basal Cell carcinomas and compared its expression with that of other known mesenchymal Markers. Results Nestin is expressed throughout the entire early embryonic dermis but confined later during development to the follicular connective tissue sheath, where it can also be found in postnatal human hair follicles. Its expression is up-regulated in scalp wounds and the nestin-positive Cells seem to originate from the follicular mesenchyme. Nestin is also expressed in a thin layer of fibroblasts in the immediate vicinity of basal Cell carcinomas. Limitations The examination for nestin expression of scalp wounds is considered preliminary, because we examined scalp wounds representing re-excisions of previously diagnosed neoplasms from which we had no exact time table available as to when the original excision took place. Conclusion We propose that nestin functions as a stem Cell Marker of the follicular mesenchyme and has a major regulatory role in dermal homeostasis, cutaneous neovasculogenesis, and tumor stroma development.
Klaus Sellheyer - One of the best experts on this subject based on the ideXlab platform.
-
follicular stem Cell Marker phlda1 tdag51 is superior to cytokeratin 20 in differentiating between trichoepithelioma and basal Cell carcinoma in small biopsy specimens
Journal of Cutaneous Pathology, 2011Co-Authors: Klaus Sellheyer, Paula NelsonAbstract:Background: Biopsies submitted to dermatopathologists are becoming increasingly smaller in size and thus the available diagnostic material is reduced. The distinction between trichoepithelioma and basal Cell carcinoma remains challenging, particularly if tissue is limited. Merkel Cells, which can be highlighted by means of cytokeratin-20 (CK20) immunostaining, are used as a surrogate Marker for the diagnosis of trichoepithelioma, as Merkel Cells commonly colonize trichoepithelioma but are generally lacking in basal Cell carcinomas. In the current study, we examined the expression of a recently characterized follicular stem Cell Marker, PHLDA1 (pleckstrin homology-like domain, family A, member 1), also known as TDAG51 (T-Cell death-associated gene 51). Methods: Using standard immunohistochemical techniques, we examined 19 trichoepitheliomas and 11 basal Cell carcinomas for the expression of PHLDA1 and compared it with CK20 expression. Results: All 19 trichoepitheliomas were immunoreactive for PHLDA1 and all 11 basal Cell carcinomas lacked PHLDA1 expression. Two of eleven basal Cell carcinomas harbored CK20-positive Merkel Cells. Three trichoepitheliomas lacked secondary CK20-positive Cells. Conclusions: Our results suggest that PHLDA1 represents a practical and easily used tool that can be applied to the differentiation of trichoepithelioma and basal Cell carcinoma in small biopsy specimens. Rather than searching for CK20-positive Merkel Cells, assessing PHLDA1 expression allows the differential diagnosis between trichoepithelioma and basal Cell carcinoma to be solved at scanning magnification. Sellheyer K, Nelson P. Follicular stem Cell Marker PHLDA1 (TDAG51) is superior to cytokeratin-20 in differentiating between trichoepithelioma and basal Cell carcinoma in small biopsy specimens.
-
phlda1 tdag51 is a follicular stem Cell Marker and differentiates between morphoeic basal Cell carcinoma and desmoplastic trichoepithelioma
British Journal of Dermatology, 2011Co-Authors: Klaus Sellheyer, Dieter KrahlAbstract:Summary Background Morphoeic basal Cell carcinoma (BCC) and desmoplastic trichoepithelioma can often be difficult to differentiate on routine sections and few reliable immunohistochemical Markers are currently available. Recent cDNA microarray studies revealed the pleckstrin homology-like domain, family A, member 1 protein (PHLDA1) as a highly reliable Marker of the hair follicle stem Cells. Given the differentiation of trichoepithelioma along the follicular lineage and the proposed role of PHLDA1 as a follicular stem Cell Marker, we examined the staining pattern of PHLDA1 in the desmoplastic variant of trichoepithelioma and in its differential diagnostic conundrum, morphoeic BCC. Objectives To describe the expression pattern of PHLDA1 in morphoeic BCC and desmoplastic trichoepithelioma. Methods Evaluation of the staining pattern for PHLDA1 was performed using standard immunohistochemical techniques. For comparison reasons, we analysed staining for PHLDA1 in normal skin structures with particular reference to the hair follicle. Results With the exception of one case, all 16 desmoplastic trichoepitheliomas were immunoreactive with more than 80% of the Cells stained, whereas all 14 morphoeic BCCs were PHLDA1-negative with the exception of ulcerated tumours. In the latter, the tumour islands close to the ulcer were PHLDA1-positive whereas the deeper located tumour portions remained immunonegative. PHLDA 1 was prominently expressed in the hair follicle bulge of terminal and vellus hair follicles. Conclusions The hair follicle bulge Marker PHLDA1 differentiates between desmoplastic trichoepitheliomas and nonulcerated examples of morphoeic BCCs. We suggest incorporating PHLDA1 in the diagnostic work-up of difficult to differentiate basaloid tumours.
-
spatiotemporal expression pattern of neuroepithelial stem Cell Marker nestin suggests a role in dermal homeostasis neovasculogenesis and tumor stroma development a study on embryonic and adult human skin
Journal of The American Academy of Dermatology, 2010Co-Authors: Klaus Sellheyer, Dieter KrahlAbstract:Background Whereas keratinocytic bulge stem Cells are well characterized, comparably little is known about cutaneous mesenchymal stem Cells. The follicular connective tissue sheath is proposed as a niche for dermal stem Cells. Objective Because the neuroepithelial stem Cell Marker nestin represents a Marker for mesenchymal stem Cells in various tissues, our aim was to characterize its spatiotemporal expression pattern in the skin with special reference to the follicular mesenchyme. Methods We studied immunohistochemically nestin expression over the course of human cutaneous embryogenesis, in postnatal skin, in scalp wounds, and in the peritumoral stroma of basal Cell carcinomas and compared its expression with that of other known mesenchymal Markers. Results Nestin is expressed throughout the entire early embryonic dermis but confined later during development to the follicular connective tissue sheath, where it can also be found in postnatal human hair follicles. Its expression is up-regulated in scalp wounds and the nestin-positive Cells seem to originate from the follicular mesenchyme. Nestin is also expressed in a thin layer of fibroblasts in the immediate vicinity of basal Cell carcinomas. Limitations The examination for nestin expression of scalp wounds is considered preliminary, because we examined scalp wounds representing re-excisions of previously diagnosed neoplasms from which we had no exact time table available as to when the original excision took place. Conclusion We propose that nestin functions as a stem Cell Marker of the follicular mesenchyme and has a major regulatory role in dermal homeostasis, cutaneous neovasculogenesis, and tumor stroma development.
B Hagen M D Huttner - One of the best experts on this subject based on the ideXlab platform.
-
the stem Cell Marker prominin 1 cd133 on membrane particles in human cerebrospinal fluid offers novel approaches for studying central nervous system disease
Stem Cells, 2008Co-Authors: B Hagen M D Huttner, Peggy Janich, Martin Kohrmann, Jozsef Jaszai, Florian A Siebzehnrubl, Ingmar Blumcke, Meinolf Suttorp, Manfred GahrAbstract:Cerebrospinal fluid (CSF) is routinely used for diagnosing and monitoring neurological diseases. The CSF proteins used so far for diagnostic purposes (except for those associated with whole Cells) are soluble. Here, we show that human CSF contains specific membrane particles that carry prominin-1/CD133, a neural stem Cell Marker implicated in brain tumors, notably glioblastoma. Differential and equilibrium centrifugation and detergent solubility analyses showed that these membrane particles were similar in physical properties and microdomain organization to small membrane vesicles previously shown to be released from neural stem Cells in the mouse embryo. The levels of membrane particle-associated prominin-1/CD133 declined during childhood and remained constant thereafter, with a remarkably narrow range in healthy adults. Glioblastoma patients showed elevated levels of membrane particle-associated prominin-1/CD133, which decreased dramatically in the final stage of the disease. Hence, analysis of CSF for membrane particles carrying the somatic stem Cell Marker prominin-1/CD133 offers a novel approach for studying human central nervous system disease.
Hideyuki Okano - One of the best experts on this subject based on the ideXlab platform.
-
the neural stem progenitor Cell Marker nestin is expressed in proliferative endothelial Cells but not in mature vasculature
Journal of Histochemistry and Cytochemistry, 2010Co-Authors: Sayuri Suzuki, Shinsuke Shibata, Yumi Mastuzaki, Jun Namiki, Hideyuki OkanoAbstract:Nestin is an intermediate filament protein that is known as a neural stem/progenitor Cell Marker. It is expressed in undifferentiated central nervous system (CNS) Cells during development, but also in normal adult CNS and in CNS tumor Cells. Additionally, nestin is expressed in endothelial Cells (ECs) of CNS tumor tissues and of adult tissues that replenish by angiogenesis. However, the regulation of nestin expression in vascular endothelium has not been analyzed in detail. This study showed that nestin expression was observed in proliferating endothelial progenitor Cells (EPCs), but not in mature ECs. In adherent cultured Cells derived from bone marrow Cells, EPCs that highly expressed nestin also expressed the endothelial Marker CD31 and the proliferation Marker Ki67. ECs cultured without growth factors showed attenuated nestin immunoreactivity as they matured. Trans-genic mice that carried the enhanced green fluorescent protein under the control of the CNS-specific second intronic enhancer of the nesti...
-
the neural stem progenitor Cell Marker nestin is expressed in proliferative endothelial Cells but not in mature vasculature
Journal of Histochemistry and Cytochemistry, 2010Co-Authors: Sayuri Suzuki, Shinsuke Shibata, Yumi Mastuzaki, Jun Namiki, Hideyuki OkanoAbstract:Nestin is an intermediate filament protein that is known as a neural stem/progenitor Cell Marker. It is expressed in undifferentiated central nervous system (CNS) Cells during development, but also in normal adult CNS and in CNS tumor Cells. Additionally, nestin is expressed in endothelial Cells (ECs) of CNS tumor tissues and of adult tissues that replenish by angiogenesis. However, the regulation of nestin expression in vascular endothelium has not been analyzed in detail. This study showed that nestin expression was observed in proliferating endothelial progenitor Cells (EPCs), but not in mature ECs. In adherent cultured Cells derived from bone marrow Cells, EPCs that highly expressed nestin also expressed the endothelial Marker CD31 and the proliferation Marker Ki67. ECs cultured without growth factors showed attenuated nestin immunoreactivity as they matured. Transgenic mice that carried the enhanced green fluorescent protein under the control of the CNS-specific second intronic enhancer of the nestin gene showed no reporter gene expression in EPCs. This indicated that the mechanisms of nestin gene expression were different in EPCs and CNS Cells. Immunohistochemistry showed nestin expression in neovascular Cells from two distinct murine models. Our results demonstrate that nestin can be used as a Marker protein for neovascularization.