This SuperSeries is composed of the SubSeries listed below.
Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150.
No sample metadata fields
View SamplesGene expression of Double Positive, and Single Positive CD4+ human thymocytes
Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150.
No sample metadata fields
View SamplesTo determine the IFN-alpha signature in non-side population of ovarian cancer
No associated publication
No sample metadata fields
View SamplesThe side population (SP), recently identified in several normal tissues and in a variety of tumors, may comprise cells endowed with stem cell features. In this study, we investigated the presence of SP in epithelial ovarian cancer (EOC) and found it in 4 out of 6 primary cultures from xenotransplants, as well as in 9 out of 25 clinical samples analyzed. SP cells from one xenograft bearing a large SP fraction were characterized in detail and they were capable of recreate the full repertoire of cancer cell populations observed in the parent tumor. Moreover, SP cells had higher proliferation rates, were much less apoptotic compared to non-SP cells, and generated tumors more rapidly than non-SP cells.
The side population of ovarian cancer cells is a primary target of IFN-alpha antitumor effects.
No sample metadata fields
View SamplesCategorisation of LGGs related to their lesion site (infratentorial vs. supratentorial)
Molecular fingerprinting reflects different histotypes and brain region in low grade gliomas.
No sample metadata fields
View SamplesRNF10 is a synapse-to-nucleus protein messsenger regulating NMDAR-dependent gene trascription. We have charaterized the impact of the absence of RNF10 on structural synaptic plasticity.
No associated publication
Specimen part
View SamplesSREBF-1c is a transcription factor regulating fatty acid biosynthesis. We have charaterized the impact of the abcence of SREBF-1c on the development of peripheral neuropathy
Lack of sterol regulatory element binding factor-1c imposes glial Fatty Acid utilization leading to peripheral neuropathy.
Age
View SamplesMyeloma bone disease is characterized by tremendous bone destruction with suppressed bone formation. IL-3 is a multifunctional cytokine that increases myeloma cell growth and osteoclast proliferation while inhibiting osteoblast differentiation. While IL-3 appears to be an attractive therapeutic target for myeloma, attempts at targeting IL-3 have been unsuccessful due to IL-3s effects on normal hematopoiesis. Thus identification of IL-3s downstream effects in MMBD is important for effective targeting of this cytokine in MM. Here we demonstrated that treatment of myeloma patient CD14+ bone marrow monocyte / macrophages with IL-3 induces high levels of Activin A (ActA), a pluripotent TGF- superfamily member that, like IL-3, modulates MMBD by enhancing osteoclastogenesis and inhibiting osteoblasts. We show that IL-3 induced osteoclastogenesis is mediated by ActA and is RANKL independent. Additionally, IL-3 induced ActA secretion is greatest early in osteoclastogenesis and ActA acts early in osteoclastogenesis. Therefore we suggest that therapies targeting ActA production should block IL-3s effects in myeloma bone disease.
Bone marrow monocyte-/macrophage-derived activin A mediates the osteoclastogenic effect of IL-3 in multiple myeloma.
Specimen part, Disease, Disease stage, Treatment
View SamplesAlthough intensification of chemotherapy approaches considerably increased the outcome of pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) patients, a subgroup of them still experience treatment failure and relapse. In this context, we hypothesized that the Nrf2 signalling and its downstream effectors could be involved in sustain therapy resistance in T-ALL, as previously reported in other cancers. Indeed, in this study we identified the Aldo-Keto Reductase (AKR) enzymes AKR1C1-3, as over-expressed in T-ALL samples from therapy-resistant patients, demonstrating their fundamental role in the control of the response to vincristine (VCR) treatment. In particular, we evidence that the modulation of AKR1C1-3 gene expression and activity is sufficient to strongly affect the sensitivity of T-ALL cell lines and primary cells to VCR treatment, but not to daunorubicin, cytarabine or L-asparaginase. Moreover, we found a correlation between the degree of VCR response and the amount of AKR1Cs expression in patient-derived T-ALL xenografts. Interestingly, we show that daunorubicin and cytarabine are able to induce the over-activation of AKR1C enzymes, thus establishing a potential resistance loop generated by the combination of these drugs during T-ALL treatment.
AKR1C enzymes sustain therapy resistance in paediatric T-ALL.
Specimen part, Disease stage
View SamplesJuvenile myelomonocytic leukemia (JMML) is a very rare and aggressive stem cell disease that mainly occurs in young children. RAS activation constitutes the core component of oncogenic signaling. In addition, the leukemic blasts of a quarter of JMML patients present with monosomy 7 (-7), whereas more than half of the patients show enhanced age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care. This results in an event-free survival of 50 - 60%, indicating that novel molecular driven therapeutic options are urgently needed. Using gene expression profiling in an extensive series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression.
LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia.
Disease
View Samples