This SuperSeries is composed of the SubSeries listed below.
Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma.
Specimen part
View Samplesgenome-wide methylation profile of 250 samples including 125 EAC, 19 Barretts, 64 normal adjacent squamous and 21 normal stomach. Transcriptome data was performed for 70 samples with methylation profile (48 EAC, 4 Barretts and 18 normal adjacent squamous). This is the first study to use methylome, transcriptome and ENCODE data to characterize the regulatory role of methylation in EAC.
Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy.
Specimen part
View SamplesThis study was designed to investigate tissue-specific transcriptional changes in spleen and liver CD4+ T cells from C57BL/6J mice infected with L. donovani.
No associated publication
Specimen part
View SamplesGenome-wide transcriptional profiling of purified telomerase deficient (Terc-/-) and WT LSCs was performed in order to gain insights into the mechanisms underlying the susceptibilities of Terc-/- LSCs in vivo.
Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy.
Specimen part
View SamplesTrial described in Lancet. 2006 Sep 2;368(9538):855-63. Rheumatoid arthritis patients were treated with chaperonin 10, with a dose of 10 mg rCpn10 i.v. twice weekly for 56 days. Blood samples were collected before and after treatment.
No associated publication
Sex, Specimen part, Disease, Treatment, Race, Subject, Time
View SamplesThe human EphA3 gene was discovered in a pre-B acute lymphoblastic leukemia (pre-B-ALL) using the EphA3-specific monoclonal antibody (mAb), IIIA4, which binds and activates both human and mouse EphA3. We use two models of human pre-B-ALL to examine EphA3 function, demonstrating effects on pre-B-cell receptor signaling. In therapeutic targeting studies, we demonstrated antitumor effects of the IIIA4 mAb in EphA3-expressing leukemic xenografts and no antitumor effect in the xenografts with no EphA3 expression providing evidence that EphA3 is a functional therapeutic target in pre-B-ALL. Here we show that the therapeutic effect of the anti-EphA3 antibody was greatly enhanced by adding an -particle-emitting 213Bismuth payload.
EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia.
Cell line
View SamplesSquamous cell carcinoma (SCC) is the second most common cancer worldwide and accounts for approximately 30% of all keratinocyte cancers. The vast majority of cutaneous SCCs of the head and neck (cSCCHN) are readily curable with surgery and/or radiotherapy unless high-risk features are present. Perineural invasion (PNI) is recognized as one of these high-risk features. The molecular changes during clinical PNI in cSCCHN have not been previously investigated. In this study, we assessed the global gene expression differences between cSCCHN with or without incidental or clinical PNI. The results of the analysis showed signatures of gene expression representative of activation of p53 in tumors with PNI compared to tumors without, amongst other alterations. Immunohistochemical staining of p53 showed cSCCHN with clinical PNI to be more likely to exhibit a diffuse over-expression pattern, with no tumors showing normal p53 staining. DNA sequencing of cSCCHN samples with clinical PNI showed no difference in mutation number or position with samples without PNI, however a significant difference was observed in regulators of p53 degradation, stability and activity. Our results therefore suggest that cSCCHN with clinical PNI may be more likely to contain alterations in the p53 pathway, compared to cSCCHN without PNI.
Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process.
Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Sex
View SamplesWe previously identified the induction of growth arrest with phenotypic characteristics of senescence in melanoma cell lines sensitive to diterpene esters, indicating a therapeutic potential. Here we compared the cytostatic effects of two diterpene esters namely TPA (12-O-tetradecanoylphorbol-13-acetate) and PEP008 (20-O-acetyl-ingenol-3-angelate) in sensitive and resistant cell lines derived from melanoma, breast cancer and colon cancer. We showed the diterpene esters to induce senescence-like growth arrest in the sensitive cells at 100-1000 ng/ml. Use of the pan-PKC inhibitor bisindolylmaleimide-l demonstrated that activation of PKC was required for growth arrest. Full genome expression profiling revealed that pivotal genes involved in DNA synthesis and cell cycle control were down-regulated by treatment in all three sensitive solid tumor models. At the protein level, prolonged down-regulation of E2F-1 and proliferating cell nuclear antigen (PCNA), sustained expression of p21WAF1/CIP1 and dephosphorylation of retinoblastoma (Rb) occurred in the sensitive cells. Although activation of extracellular signal-related kinase (ERK) 1/2 by the diterpene esters occurred in both sensitive and resistant cell lines, the HRASLS3 type II tumor suppressor, which appears to have a role in MAPK pathway suppression, was constitutively elevated in the resistant cell lines compared to their sensitive counterparts. Together, these results demonstrate the ability of the PKC activating drugs TPA and PEP008 to induce growth arrest with characteristics of senescence in solid tumor cell lines derived from a variety of tissue types through a similar mechanism. PKC-activating diterpene esters may therefore have therapeutic potential in a range of solid tumors.
Induction of senescence in diterpene ester-treated melanoma cells via protein kinase C-dependent hyperactivation of the mitogen-activated protein kinase pathway.
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