Thrombospondin 1 and 2 along with PEDF inhibit angiogenesis and promote lymphangiogenesis in intrahepatic cholangiocarcinoma.

Background & Aims: The microenvironment of intrahepatic cholangiocarcinoma (iCCA) is hypovascularized, with an extensive lymphatic network. This leads to rapid cancer spread into regional lymph nodes and the liver parenchyma, precluding curative treatments. Herein, we investigated which factors released in the iCCA stroma drive the inhibition of angiogenesis and promote lymphangiogenesis.

Functional cooperation between ASK1 and p21 in the balance of cell-cycle arrest, cell death and tumorigenesis of stressed keratinocytes.

Both CDKN1A (p21 ) and Apoptosis signal-regulating kinase 1 (ASK1) play important roles in tumorigenesis. The role of p21 in attenuating ASK1-induced apoptosis by various stress conditions is well established. However, how ASK1 and p21 functionally interact during tumorigenesis is still unclear.

Hypotonic, Acidic Oxidizing Solution Containing Hypochlorous Acid (HClO) as a Potential Treatment of Hailey-Hailey Disease.

Hailey-Hailey disease (HHD) is a rare, chronic and recurrent blistering disorder, characterized by erosions occurring primarily in intertriginous regions and histologically by suprabasal acantholysis. Mutation of the Golgi Ca-ATPase has been identified as having a causative role in Hailey-Hailey disease. HHD-derived keratinocytes have increased oxidative-stress that is associated with impaired proliferation and differentiation.

PLK1 targets NOTCH1 during DNA damage and mitotic progression.

Notch signaling plays a complex role in carcinogenesis, and its signaling pathway has both tumor suppressor and oncogenic components. To identify regulators that might control this dual activity of NOTCH1, we screened a chemical library targeting kinases and identified Polo-like kinase 1 (PLK1) as one of the kinases involved in arsenite-induced NOTCH1 down-modulation. As PLK1 activity drives mitotic entry but also is inhibited after DNA damage, we investigated the PLK1-NOTCH1 interplay in the G phase of the cell cycle and in response to DNA damage.

DNA Damage Stress: Cui Prodest?

DNA is an entity shielded by mechanisms that maintain genomic stability and are essential for living cells; however, DNA is constantly subject to assaults from the environment throughout the cellular life span, making the genome susceptible to mutation and irreparable damage. Cells are prepared to mend such events through cell death as an extrema ratio to solve those threats from a multicellular perspective. However, in cells under various stress conditions, checkpoint mechanisms are activated to allow cells to have enough time to repair the damaged DNA.