The range of diagnostic and therapeutic applications of needle arthroscopy (NA) continue to expand due to advances in image quality and resolution. Minimally invasive techniques can be augmented by the smaller camera size and reduced fluid use made possible by NA. Small-bore arthroscopy presents opportunities for use in smaller joints, such as the elbow, where applications of standard arthroscopic equipment may be limited by small anatomic spaces and fluid extravasation. In this Technical Note, we present our technique for NA-assisted treatment of terrible triad injuries, specifically in the setting of an intact radial head. The technique describes a stepwise approach to arthroscopically aided fixation of the coronoid process, followed by open reconstruction of the lateral collateral ligament complex.
The controlled division of cells requires a coordination of multiple cellular pathways. Hippo pathway controls the organ size and restricts cell proliferation in response to the signals from cell surface receptors, and genetic alterations in the components of this pathway are common in cancer. LATS1 and LATS2 are homologous protein kinases that relay the signals from the environment to the Hippo effector YAP by direct phosphorylation that promotes its degradation. The genes encoding these kinases undergo frequent genetic losses in human cancers, with particularly high rates in high grade serous ovarian carcinoma (HGSOC), a highly lethal cancer with poorly understood mechanisms of pathogenesis and progression. We hypothesized that loss of LATS kinases could be a driver in this cancer and investigated signaling pathways downstream of LATS that could influence the ovarian cancer tumorigenic phenotypes. Depletion of both LATS1 and LATS2 was required to increase cell proliferation and disrupt the assembly of the cell-cycle regulatory DREAM complex. LATS-depleted human ovarian cancer cells formed bigger tumors in the immunocompromised mice, consistent with their tumor suppressor role. DREAM assembly depends on the activity of DYRK1A protein kinase, which was decreased in the LATS1/2-depleted cells. Furthermore, loss of LATS kinases increased the inhibitory phosphorylation of the retinoblastoma (Rb) family proteins, further promoting the DREAM disassembly that was rescued by CDK4 inhibitor palbociclib. Our study describes a crosstalk between the Hippo pathway and the cell cycle regulatory machinery converging on cyclin D1, a major regulator of the Rb tumor suppressor family, and highlights cellular pathways that could contribute to ovarian cancer pathogenesis and progression.
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