Breast cancer stroma frequently recruits fetal derived cells during pregnancy

Breast carcinomas associated with pregnancy display a high frequency of inflammatory types, multifocal lesions and lymph node metastasis. Because pregnancy results in transfer to mothers of foetal stem cells that can migrate and differentiate into various tissues, we addressed the issue of whether such cells are present in breast carcinoma associated with pregnancy

Sickle cell disease induces resistance to cutaneous carcinogenesis

International audienceBACKGROUND: While skin carcinomas are reported in chronic ulcers and in patients treated with hydroxyurea (HU) for myeloproliferative neoplasms, no skin carcinoma has been reported in patients with sickle cell disease (SCD), presenting chronic skin ulcers or treated with HU. The objective was to estimate the risk of cutaneous malignant transformation in SCD patients with prolonged leg ulcers or under HU therapy.RESULTS: In this cross-sectional study, the cohort consisted of 1543 patients. In the first series, 29 patients presented a total of 53 ulcers lasting more than two years. The median age was 35 ± 8.4 years old. The median duration for a single ulcer was 9.2 ± 7 years. None of the examined ulcers showed any suspicious area of malignant transformation. In the second series, 187 patients treated with HU for more than two years were identified. The median age was 31.3 ± 9.9 years old. The median duration of treatment with HU was 6 ± 3.2 years. No skin carcinoma or actinic keratosis was recorded.CONCLUSIONS: This study showed that skin carcinogenesis did not occur in our series of SCD patients exposed to transforming events such as long term HU treatment or prolonged leg ulcers

Mineralocorticoid receptor blockade improves glucocorticoid-induced skin atrophy but partially ameliorates anti-inflammatory actions in an irritative model in human skin explants

3 páginas, 2 figuras. 1 tabla y 1 figura en material suplementario y material suplementario de Material y MétodoWe recently demonstrated that blockade of the mineralocorticoid receptor (MR) effectively ameliorated GC-induced skin atrophy in healthy human skin explants and epidermal MR knockout mice. However, whether MR blockade improves the therapeutic index of glucocorticoids (GCs) in skin pathology was not investigated. We assessed the effects of GCs, MR antagonists (MRA) or both, in SDS-treated human skin explants. All treatments restored SDS-augmented epidermal thickness but only GC plus MRA restored the expression of COL1A1. However, MRA alone or in combination with GCs may exert a dual role in regulating inflammatory cytokines. Thus, although combined treatment may be beneficial to improve irritative skin, extensive in vivo testing is required to establish whether the anti-inflammatory effects of GCs are maintained in the presence of MRA.This work was supported by the Spanish Ministerio de Ciencia e Innovación (grant SAF2014-59474-R) and by the ADMIRE COST Action BM-1301Peer reviewe

Dermatological manifestations associated with pregnancy

Various types of cutaneous lesions may develop during the course of pregnancy. These may be classified into four main categories: physiological changes, which are very diverse, specific conditions; dermatoses, that are linked to pregnancy; cutaneous infections that may influence the course of gestation; and finally, miscellaneous skin diseases, which may be affected by pregnancy or affect the fetus. All of these categories contain disorders that are important to recognize, since some may require specific management while in others unnecessary investigations should be avoided. This review will examine physiological changes and dermatoses

Delayed Healing of Sickle Cell Ulcers Is due to Impaired Angiogenesis and CXCL12 Secretion in Skin Wounds

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Re-epithelialization of pathological cutaneous wounds is improved by local mineralocorticoid receptor antagonism

International audienceImpaired cutaneous wound healing is a social burden. It occurs as a consequence of glucocorticoid treatment and in several pathologies. Glucocorticoids (GC) bind not only to the glucocorticoid receptor (GR), but also to the mineralocorticoid receptor (MR), both expressed by keratinocytes. In addition to its beneficial effects through the GR, GC exposure may lead to inappropriate MR occupancy. We hypothesized that dermatological use of MR antagonists (MRA) may be beneficial by overcoming the negative impact of GC treatment on pathological wounds. The potent GC clobetasol, applied as an ointment to mouse skin, or added to cultured human skin explants, induced delayed wound closure and outgrowth of epidermis with reduced proliferation of keratinocytes. Delayed wound re-epithelialization was rescued by local MRA application. Normal skin was unaffected by MRA. The benefit of MR blockade is explained by the increased expression of MR in clobetasol-treated mouse skin. Blockade of the epithelial sodium channel by phenamil also rescued cultured human skin explants from GC- impaired growth of the epidermis. MRA application over post-biopsy wounds of clobetasol-treated skin zones of healthy volunteers (from the SPIREPI clinical trial) also accelerated wound closure. In conclusion, we propose repositioning MRA for cutaneous application to improve delayed wound closure occurring in pathology

Cutaneous Wound Healing in Diabetic Mice Is Improved by Topical Mineralocorticoid Receptor Blockade

Producción CientíficaSkin ulcers resulting from impaired wound healing are a serious complication of diabetes. Unresolved inflammation, associated with the dysregulation of both the phenotype and function of macrophages, is involved in the poor healing of diabetic wounds. Here, we report that topical pharmacological inhibition of the mineralocorticoid receptor (MR) by canrenoate or MR small interfering RNA can resolve inflammation to improve delayed skin wound healing in diabetic mouse models; importantly, wounds from normal mice are unaffected. The beneficial effect of canrenoate is associated with an increased ratio of anti-inflammatory M2 macrophages to proinflammatory M1 macrophages in diabetic wounds. Furthermore, we show that MR blockade leads to downregulation of the MR target, LCN2, which may facilitate macrophage polarization toward the M2 phenotype and improve impaired angiogenesis in diabetic wounds. Indeed, diabetic LCN2-deficient mice showed improved wound healing associated with macrophage M2 polarization and angiogenesis. In addition, recombinant LCN2 protein prevented IL-4-induced macrophage switch from M1 to M2 phenotype. In conclusion, topical MR blockade accelerates skin wound healing in diabetic mice via LCN2 reduction, M2 macrophage polarization, prevention of inflammation, and induction of angiogenesis