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Biomedical subjects

A Dahler

Publications and source records attributed to A Dahler.

7 recordsLinked to original sources
PubMed1999

Histone deacetylase inhibitors as potential anti-skin cancer agents.

The regulation of squamous differentiation is a tightly regulated process involving transcriptional repression and activation. Previous studies have established that squamous carcinoma cell lines inappropriately regulate the transcription of genes important to the control of squamous differentiation. Histone deactylase inhibitors such as trichostatin A (TSA) and butyrate disrupt normal chromatin structure and cause alterations in gene expression/regulation. For these reasons, we examined the effects of both butyrate and TSA on the growth and differentiation of human keratinocytes or squamous carcinoma cells in tissue culture. We found that treatment of keratinocytes or squamous carcinoma cells with butyrate induced a reversible growth arrest. TSA, on the other hand, induced an irreversible growth arrest in both keratinocytes and squamous carcinoma cells. The growth arrest of keratinocytes induced by TSA or butyrate was accompanied by a reduction in the mRNA levels for proliferation gene cdk1 and an induction of the mRNA for the differentiation-specific transglutaminase type I gene (TG1). In contrast, the squamous carcinoma cells had decreased cdk1 and TG1 mRNA in response to TSA or butyrate. Both of these agents produced transient increases in the acetylation of histone H4 in keratinocytes and squamous carcinoma cells. These data indicated that TSA may have potential as a topical treatment for epidermal malignancies.

Antineoplastic Agents↗
PubMed1996

Interferon-gamma as a regulator of squamous differentiation.

Interferon-gamma (IFN-gamma) is a potent immunomodulatory molecule. Recent studies demonstrate that IFN-gamma can induce growth arrest and differentiation in epithelial cells. The signalling pathways controlling growth and differentiation in epithelial cells appears to be different to those regulating immune functions in non-epithelial cells and appear to impact on key cell cycle regulatory genes such as cdk1 and E2F1. In addition, studies with IFN-gamma have highlighted the complexity of the signalling pathways regulating the expression of differentiation markers in squamous differentiating epithelia. Given the actions of IFN-gamma upon epithelial cell growth and differentiation it should be considered a potential regulator of both immune and epithelial cell targets in various inflammatory pathologies such as psoriasis.

Adjuvants, Immunologic↗
PubMed1994

Expression vectors encoding human growth hormone (hGH) controlled by human muscle-specific promoters: prospects for regulated production of hGH delivered by myoblast transfer or intravenous injection.

We report here the construction of vectors that produce and secrete human growth hormone (hGH) in a muscle-specific manner. The promoter regions of the genes encoding human skeletal alpha-actin (HSA) and troponin I slow (HTnIs) were linked to the hGH-encoding gene. These vectors were designated pHSA2000GH and pHTnIs4200GH, respectively. The HSA and HTnIs promoters linked to the cat gene have previously been shown to be necessary and sufficient for developmentally regulated muscle-specific expression. Furthermore, these promoters function in a fibre-type-specific manner in transgenic animals. Transient and stable transfection analyses with pHSA2000GH and pHTnIs4200GH indicated that: (i) these vectors efficiently synthesized hGH in a muscle-specific manner; (ii) the myogenic master regulatory gene, myoD, a determinant of cell fate, trans-activated expression of hGH in pluripotential non-muscle cells; and (iii) these hGH expression vectors were developmentally regulated during myogenic differentiation. These regulated tissue/fibre-type-specific hGH-containing plasmids are suitable vectors for the delivery and stable production of GH in livestock and GH-deficient hosts by either transgenesis, myoblast transfer or liposome-mediated intravenous injection.

Actins↗