Certain skin disorders, such as contact dermatitis and chronic urticaria, are characterized by inflammation involving mast cells and worsen by stress. The underlying mechanism of this effect, however, is not known. The skin appears to have the equivalent of a hypothalamic-pituitary-adrenal (HPA) axis, including local expression of corticotropin-releasing hormone (CRH) and its receptors (CRH-R). We have reported that acute stress and intradermal administration of CRH stimulate skin mast cells and increase vascular permeability through CRH-R1 activation. In this study, we investigated the expression of CRH-R1, the main CRH-R subtype in human skin, and the mast cell related gene histidine decarboxylase (HDC), which regulates the production of histamine, in normal and pathological skin biopsies. Quantitative real time PCR revealed that chronic urticaria expresses high levels of CRH-R1 and HDC as compared to normal foreskin, breast skin and cultured human keratinocytes. The lichen simplex samples had high expression of CRH-R1, but low HDC. These results implicate CRH-R in chronic urticaria, which is often exacerbated by stress.

These data suggest that (i) repetitive and pulsatile (15 min/day) exposure to zoledronic acid inhibited the growth of PC-3 cells, (ii) this anticancer action of zoledronic acid was partially mediated by the attenuation of GGPP production, and (iii) bone microenvironment-related growth factors do not alter the anticancer actions of zoledronic acid on PC-3 cells.

Background: To improve median survival of patients with prostate cancer that has metastasized to bone, we need to better understand the early events of the metastatic process in skeleton and develop molecular tools capable of detecting the early tumor cell dissemination into bones (micrometastasis stage). However, the initial phase of tumor cell dissemination into the bone marrow is promptly followed by the migration of tumor cells into bone matrix, which is a crucial step that signals the transformation of micrometastasis to macrometastasis stage and clinically evident metastasis. The migration of cancer cells into bone matrix requires the activation of local bone resorption. Such an event contributes to tumor cell hiding/ escaping from high immunologic surveillance of bone marrow cells. Within bone matrix, tumor cells are establishing plethoric cell-cell interactions with bone marrow-residing

Poly (ADP-ribose) polymerase-1 (PARP1) is a key mediator of various forms of DNA damage repair and plays an important role in the progression of several cancer types. The enzyme is activated by binding to DNA single-strand and double-strand breaks. Its contribution to chromatin remodeling makes PARP1 crucial for gene expression regulation. Inhibition of its activity with small molecules, leads to the synthetic lethal effect by impeding DNA repair in the treatment of cancer cells. At first PARP1 inhibitors (PARPi) were developed to target BRCA mutated cancer cells. Currently, PARPi are being studied to be used in a broader variety of patients either as single agents or in combination with chemotherapy, antiangiogenic agents, ionizing radiation, and immune checkpoint inhibitors. Ongoing clinical trials on olaparib, rucaparib, niraparib, veliparib and the most recent talazoparib show the advantage of these agents in overcoming PARPi resistance and underline their efficacy in targeted treatment of several hematologic malignancies. In this review, focusing on the crucial role of PARP1 in physiological and pathological effects in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), we give an outline of the enzyme's mechanisms of action and its role in the pathophysiology and prognosis of MDS/AML and we analyze the available data on the use of PARPi, highlighting their promising advances in clinical application.