Although the consequences of genotoxic injury include cell cycle arrest and apoptosis, cell survival responses after genotoxic injury can produce intrinsic death-resistance and contribute to the development of a transformed phenotype. Protein tyrosine phosphatases (PTPs) are integral components of key survival pathways, and are responsible for their inactivation, while PTP inhibition is are often associated with enhanced cell proliferation. Our aim was to elucidate signaling events that modulate cell survival after genotoxin exposure. Diploid human lung fibroblasts (HLF) were treated with Cr(VI) (as Na2CrO4), a well known human respiratory carcinogen that induces a wide spectrum of DNA damage, in the presence and absence of a broad-range PTP inhibitor, sodium orthovanadate. Notably, PTP inhibition abrogated Cr(VI)-induced clonogenic lethality. The enhanced survival of Cr(VI)-exposed cells after PTP inhibition was predominantly due to a bypass of cell cycle arrest and was not due to decreased Cr uptake as evidenced by unchanged Cr-DNA adduct burden. Additionally, the bypass of Cr-induced growth arrest by PTP inhibition, was accompanied by a decrease in Cr(VI)-induced expression of cell cycle inhibiting genes, and an increase in the Cr(VI)-induced expression of cell cycle promoting genes. Importantly, PTP inhibition resulted in an increase in forward mutations at the HPRT locus, supporting the hypothesis that PTP inhibition in the presence of DNA damage may lead to genomic instability, via bypass of cell cycle checkpoints.
Bypass of hexavalent chromium-induced growth arrest by a protein tyrosine phosphatase inhibitor: enhanced survival and mutagenesis.
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View SamplesDermal papilla cells isolated from the human hair follicle are capable of inducing hair growth in recipient epithelia. However, demonstrating disparity from rodent dermal papilla, human cells lose this inductive competance immediately upon growth in culture under normal growth conditions. We grew dermal papilla cells in hanging drop cultures that are morphologically akin to intact dermal papilla, and found that by enhancing the environment for aggregation, we could restore the inductive capacity of human dermal papilla cells in culture. The underlying genes that regulate the inductive potential of dermal papilla cells is not well understood, and we sought to use global profiling to identify key genes and pathways related to inductive competance within dermal papilla cells.
Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth.
Sex, Specimen part, Subject
View SamplesGene expression profiling of scalp skin biopsies from patients with alopecia areata or normal healthy controls
Molecular signatures define alopecia areata subtypes and transcriptional biomarkers.
Sex, Age, Disease, Subject
View SamplesThis goal of these studies were to examine gene expression profiles of skin from patients with alopecia areata undergoing treatment with oral ruxoltinib.
Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata.
Sex, Race, Subject
View SamplesOur goal was to demonstrate the similarity between the original keratinocytes and iPSC-derived keratinocytes from the same individual
Induced pluripotent stem cells from human revertant keratinocytes for the treatment of epidermolysis bullosa.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Specimen part, Treatment, Time
View SamplesThe C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease.
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Specimen part, Treatment, Time
View SamplesThe C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease.
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Specimen part, Treatment, Time
View SamplesThe C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease.
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Specimen part, Treatment, Time
View SamplesThe samples include RNA from scalp biopsies before treatment and at 8 weeks of treatment with Tofacitinib Citrate 5 mg BID in patients with Alopecia Areata. 32% had a SALT score of 50% or higher and 47% had clinically significant response. Overall design: Open label trial of patients with Alopecia Areata of more than 6 months in duration refractory to standard therapy. Each patient took tofacitinib citrate 5mg BID for 3 months and then stopped. Biopsies were taken pretreatment and then at 8 weeks from the scalp and submitted for RNA sequencing.
Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata.
Specimen part, Disease stage, Subject, Time
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