ABSTRACT
Estrogen biosynthesis is catalyzed by aromatase cytochrome P-450 (the product of the CYP19 gene). Adipose tissue is the major site of estrogen biosynthesis in postmenopausal women, with the local production of estrogen in breast adipose tissue implicated in the development of breast cancer. In human adipose tissue, aromatase is primarily expressed in the mesenchymal stromal cells and is a marker of the undifferentiated preadipocyte phenotype. Aromatase expression in adipose tissue is regulated via the distal promoter I.4, under the control of glucocorticoids and class I cytokines such as oncostatin M, interleukin 6, and interleukin 11, as well as tumor necrosis factor alpha. These cytokines, which are expressed in adipose, also inhibit adipocyte differentiation. Therefore, we hypothesized that factors which stimulate adipocyte differentiation should inhibit aromatase expression. These factors include synthetic peroxisome proliferator-activated receptor gamma (PPARgamma) ligands such as thiazolidinediones, e.g., troglitazone and rosiglitazone (BRL49653) and the endogenous PPARgamma ligand 15-deoxy-delta12,14-prostaglandin J2. We have demonstrated by measurement of aromatase activity and by reverse transcription-PCR/Southern blotting that these PPARgamma ligands inhibit aromatase expression in cultured breast adipose stromal cells stimulated with oncostatin M or tumor necrosis factor alpha plus dexamethasone in a concentration-dependent manner, whereas a metabolite of troglitazone that does not activate PPARgamma has no effect. We have also shown that troglitazone inhibits luciferase activity of reporter constructs containing various lengths of the upstream region of promoter I.4 transfected into mouse 3T3-L1 preadipocyte mesenchymal cells, whereas the troglitazone metabolite does not. Because local estrogen production in breast fat is implicated in breast cancer development in postmenopausal women, the actions of PPARgamma ligands suggest that they may have potential therapeutic benefit in the treatment and management of breast cancer.
Subject(s)
Adipose Tissue/metabolism , Breast/metabolism , Estrogens/biosynthesis , Receptors, Cytoplasmic and Nuclear/metabolism , Thiazolidinediones , Transcription Factors/metabolism , Adipose Tissue/cytology , Adipose Tissue/drug effects , Animals , Aromatase/genetics , Aromatase/metabolism , Aromatase Inhibitors , Binding, Competitive , Breast/cytology , Breast/drug effects , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Cell Line , Cells, Cultured , Chromans/metabolism , Chromans/pharmacology , Dose-Response Relationship, Drug , Female , Gene Expression Regulation, Enzymologic/drug effects , Humans , Ligands , Promoter Regions, Genetic/genetics , Prostaglandin D2/analogs & derivatives , Prostaglandin D2/pharmacology , Recombinant Fusion Proteins/antagonists & inhibitors , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Rosiglitazone , Stromal Cells/cytology , Stromal Cells/drug effects , Stromal Cells/enzymology , Thiazoles/metabolism , Thiazoles/pharmacology , Transcription, Genetic , TroglitazoneABSTRACT
One hundred children with glass injuries to the hand were studied with an average follow-up of twenty-two months. Fifty-two had involvement of deep structures. The treatment and results are discussed.
Subject(s)
Glass , Hand Injuries/etiology , Child , Child, Preschool , Female , Hand Injuries/surgery , Humans , Infant , Male , Scotland , Tendon Injuries/etiology , Tendon Injuries/surgeryABSTRACT
Aluminium foil has been found to be an extremely useful and painless way of dressing wounds prior to delayed skin grafting. However, it is not recommended for use on skin-graft donor sites as it delays epithelial healing.
Subject(s)
Aluminum , Bandages , Aluminum/adverse effects , Humans , Skin Transplantation , Transplantation, Homologous , Wound HealingABSTRACT
Conventional pulse echo ultrasound equipment was modified to provide resolution capable of distinguishing the interfaces in burnt skin. The identification of these interfaces allowed a quantitative assessment of the depth of a burn. Ultrasound is non-invasive and accurate, and so is highly acceptable for clinical use.
