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Platform
GSE108524
Homo sapiens
29 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Neurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth cause progressive hearing loss, and the standard treatment including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allows hearing test. Here we developed a cerebellopontine angle (CPA) schwannomas model that faithfully recapitulates the tumor-induced hearing loss. Using this model we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation. CRZ treatment had no adverse effect on hearing; however, it did not affect tumor-induced hearing loss, presumably because cMET blockade did not change tumor HGF levels. cMET gene knockdown study independently confirmed the role of cMET pathway in mediating the effect of CRZ. Furthermore, we evaluated the translational potential of cMET blockade in human schwannomas. We found that human NF2-associated and sporadic VSs showed significantly elevated HGF expression and cMET activation compared to normal nerves, which correlated with tumor growth and cyst formation. Using organoid brain slice culture, cMET blockade inhibited the growth of patient-derived schwannomas. Our findings provide the rationale and necessary data for the clinical translation of combined cMET blockade with radiation therapy in NF2 patients.
Publication Title
Targeting the cMET pathway augments radiation response without adverse effect on hearing in NF2 schwannoma models.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 50 Downloadable Samples
Illumina HiSeq 2000
Description
To delineate comprehensive transcriptomic profiling in the malignant progression of human gliomas
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Conversion of Human Gastric Epithelial Cells to Multipotent Endodermal Progenitors using Defined Small Molecules.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Endodermal stem/progenitor cells have diverse potential applications in research and regenerative medicine, so a readily available source could have widespread uses. Here we describe derivation of human induced endodermal progenitor cells (hiEndoPCs) from gastrointestinal epithelial cells using a cocktail of defined small molecules along with support from tissue-specific mesenchymal feeders. The hiEndoPCs show clonal expansion in culture and give rise to hepatocytes, pancreatic endocrine cells, and intestinal epithelial cells when treated with defined soluble molecules directing differentiation. The hiEndoPC-derived hepatocytes are able to rescue liver failure in Fah-/-Rag2-/- mice after transplantation, and, unlike hESCs, transplanted hiEndoPCs do not give rise to teratomas. Since human gastric epithelial cells are readily available from donors of many ages, this conversion strategy can generate clonally expandable cell populations with a variety of potential applications, including personalized drug screening and therapeutic strategies for liver failure and diabetes.
Publication Title
Conversion of Human Gastric Epithelial Cells to Multipotent Endodermal Progenitors using Defined Small Molecules.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MEFs were stimulated for 6 h with IFNa or IFNg after pretreatment with AMN107 or DMSO for at least 18 h.
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Allergen exposure was thought to play a critical role in the etiology of AR. And allergen avoidance, the practice of avoiding exposure to allergens, has been generally advised as the management of AR. However, the effect is uncertain and the underlying mechanism is far from known.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
HPSE plays important roles in gastric cancer cell proliferation, apoptosis and metastasis.The aim of this study is to explore molecular mechanism underling roles of HPSE in gastric cancer cell proliferation, survival, migration and metastasis.
Publication Title
No associated publication
Sample Metadata Fields
Disease, Disease stage, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aortic aneurysm is a life-threatening cardiovascular disorder due to the predisposition for dissection and rupture. Genetic studies have proved the involvement of the transforming growth factor- (TGF-) pathway in aortic aneurysm. Smad4 is the central mediator of canonical TGF- signaling. However, the exact role of Smad4 confined to the smooth muscle cells (SMCs) in the pathogenesis of aortic aneurysm is largely unknown. Furthermore, whether TGF- signaling disruption in SMCs could directly trigger aortic wall inflammation remains poorly investigated. Recently, we revealed a pivotal role of smooth muscle Smad4 signaling in maintaining aortic wall homeostasis and protecting against the development of aortic aneurysm and dissection. To evaluate the underlying mechanism by which Smad4 regulate VSMC functions and affects aneurysm formation and development, Smooth muscle specific Smad4 Knockout mice and the control littermate were sacrificed at 6 weeks old, and their aortic ateries were collected.We combined 3-5 vessels for one sample, and 2 samples for each phenotype. Subsequently, a total of 400ng RNA was used following Affymetrix instruction and 2 ug of cRNA were hybridized for 16 hr at 45. GeneChips were scanned using the Scanner 7G and the data was analyzed with Expression Console using Affymetrix default analysis settings and global scaling as normalization method. RMA analysis was employed to evaluate the gene expression.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
KLF3, a member of the Krppel-like factor (KLF) family, is expressed in a wide range of cell types. It is involved in hematopoiesis of several blood cell lineages including erythrocyte and B lymphocyte. However, the research of regulatory roles on hematopoiesis of KLF3 in K562 cells has been still largely limited. To comprehensively assess the regulatory roles of KLF3 on hematopoiesis in K562 cells, a microarray analysis was performed in KLF3-deficient K562 cells. The differentially expressed genes were applied to IPA analysis to observe the perturbed hematopoiesis-associated functions, networks, and molecular pathways. This study will extensively assess the regulatory roles of KLF3 on hematopoiesis in K562 cells.
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
TGF-beta/Smads signaling plays important roles in vascular integrity. To identify potential Smad4 target genes in brain endothelial cells that control cerebrovascular integrity, the microarray assay was performed to compare the gene expression profiles of bEnd3 transfected with Smad4-siRNA and control-siRNA.
Publication Title
Endothelial Smad4 maintains cerebrovascular integrity by activating N-cadherin through cooperation with Notch.
Sample Metadata Fields
Specimen part, Cell line
View Samples