[original title] LMP-420: a novel purine nucleoside analogue with potent cytotoxic effects for chronic lymphocytic leukemia cells and minimal toxicity for normal hematopoietic cells.
LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells.
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View SamplesPuberty unmasks or accelerates nephropathies, including the nephropathy of diabetes mellitus (DM). A number of cellular systems implicated in the kidney disease of DM interweave, forming an interdependent functional web. We performed focused microarray analysis to test the hypothesis that one or more genes in the transforming growth factor beta (TGF-) signaling system would be differentially regulated in male rats depending on the age of onset of DM.
Prepubertal onset of diabetes prevents expression of renal cortical connective tissue growth factor.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Autophagy maintains the metabolism and function of young and old stem cells.
Specimen part
View SamplesMicroarray-based gene expression data were generated from RNA from Ls174T colorectal carcinoma cell lines in which Wnt-dependent transcriptional activity can be abrogated by inducible overexpression of a dominant-negative form of Tcf4 or siRNA against -catenin.
Integrated genome-wide analysis of transcription factor occupancy, RNA polymerase II binding and steady-state RNA levels identify differentially regulated functional gene classes.
Specimen part, Cell line, Time
View SamplesCirculating microvesicles (MVs) have been described as important players in cell-to-cell communication carrying biological information both in normal and pathologic condition. MVs released by cancer cells may incorporate biomolecules such as active lipids, proteins and RNA, which can be delivered and internalized by recipient cells potentially altering gene expression of receiving cells eventually impacting disease progression. In this study, we took advantage of a leukemia in vitro model to investigate MVs as vehicles of protein coding messages. Leukemic cell lines (K562, REH and SHI-1) carrying recurrent translocations were analyzed. In the leukemic cells these translocations are transcribed into oncogenic fusion transcripts. Here, using gene expression microarrays we monitored leukemic fusion transcripts as hallmarks of leukemic cells transcriptome to track mRNA transfer from parental cells to MVs. Transcriptome analysis of K562 cells and released MVs disclosed MVs as not just small scale cells. In fact, a number of transcripts related to membrane activity, cell surface receptors and extracellular communication were enriched in the MVs pool. On the other hand, sets of transcripts related to the basal cellular functions and transcripts of the BCR-ABL oncogenic pathway downstream of the fusion protein were detected in MVs as well as in parental K562 cells. Moreover, through co-culture analyses uptake of leukemic MVs in receiving cells was confirmed and an MV-dosage dependent increase of target cell proliferation was demonstrated.
Expression Profiling of Circulating Microvesicles Reveals Intercellular Transmission of Oncogenic Pathways.
Cell line
View SamplesAutophagy is critical for protecting HSCs from metabolic stress. Here, we used a genetic approach to inactivate autophagy in adult HSCs by deleting the Atg12 gene. We show that loss of autophagy causes accumulation of mitochondria and an oxidative phosphorylation (OXPHOS)-activated metabolic state, which drives accelerated myeloid differentiation likely through epigenetic deregulations rather than transcriptional changes, and impairs HSC self-renewal activity and regenerative potential.
Autophagy maintains the metabolism and function of young and old stem cells.
Specimen part
View SamplesParathyroid hormone (PTH) and PTH-related protein (PTHrP) are involved in cachexia associated with chronic kidney disease and cancer respectively. Tumor-derived PTHrP triggers adipose tissue browning and thereby leads to wasting of fat tissue in tumor-bearing mice. Similarly, elevated in 5/6 nephrectomized mice, PTH stimulates adipose tissue browning and wasting. Mice lacking the PTH/PTHrP receptor in their fat tissue are resistant to wasting of both adipose tissue and skeletal muscle. Therefore, the PTH/PTHrP signaling in adipocytes should activate various pathways that contribute to hypermetabolism and muscle wasting.
PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.
Sex, Specimen part
View SamplesPulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy.
Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression.
No sample metadata fields
View SamplesPulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy.
Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression.
Specimen part, Disease, Disease stage, Cell line
View SamplesPulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy.
Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression.
Specimen part, Disease, Disease stage
View Samples