PARP1 as a therapeutic target in acute myeloid leukemia and myelodysplastic syndrome.

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.

Corticotropin-releasing hormone receptor-1 and histidine decarboxylase expression in chronic urticaria.

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).

Bone microenvironment-related growth factors modulate differentially the anticancer actions of zoledronic acid and doxorubicin on PC-3 prostate cancer cells.

Objectives: We analyzed the actions of zoledronic acid (10-250 microM) and doxorubicin (10-250 nM) on PC-3 prostate cancer cells using both continuous (48-96 hr) and pulsatile exposures (15 min/day for up to three consecutive days).

Results: The proliferation of PC-3 cells was inhibited by either continuous or pulsatile exposures of zoledronic acid in a dose-dependent manner. In contrast, pulsatile exposures of doxorubicin failed to inhibit the growth of PC-3 cells.

Molecular evidence-based use of bone resorption-targeted therapy in prostate cancer patients at high risk for bone involvement.

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.