ABSTRACT
Pseudoarthrosis is a severe complication of spinal fusion surgery with occurrence rates as high as 35%-40%. Current options of revision surgery to correct pseudoarthrosis frequently carry high failure rates and risk of developing junctional kyphosis. Pedicled vascularized bone grafts (VBGs) are an innovative approach to boost spinal fusion rates via improving structural integrity and increasing the delivery of blood to the donor site. This versatile technique can be performed at different spinal levels without additional skin incisions and with minimal added operative time. Here we present the first bilateral rib and iliac crest VBG spinoplastic surgery performed to augment spinal fusion in a 68-year-old woman with distal junctional kyphosis and severe positive sagittal balance with low back and neck pain and significant difficulty standing upright. The patient had history of multiple spinal operations with preoperative CT imaging demonstrating loosening and pull out of L3 and fracture of L2 screws. She underwent two-stage surgical treatment involving anterior lumbar interbody fusion L3-S1 followed by removal of hardware, T4 to pelvis fusion with L2-3 prone lateral interbody fusion, and T11-S1 posterior column osteotomies. The surgery was augmented by bilateral rib and iliac crest VBGs performed by plastic surgery. At three-month follow-up the patient demonstrated functional improvement, being able to maintain upright posture and walk; was satisfied with the result of the surgery; and demonstrated no graft-related complications. In conclusion, utilization of pedicled VBGs is a novel, promising approach to augment spinal surgery in high risk patients.
ABSTRACT
Endosomes and lysosomes are membrane-bound organelles crucial for the normal functioning of the eukaryotic cell. The primary function of endosomes relates to the transportation of extracellular material into the intracellular domain. Lysosomes, on the other hand, are primarily involved in the degradation of macromolecules. Endosomes and lysosomes interact through two distinct pathways: kiss-and-run and direct fusion. In addition to the internalization of particles, endosomes also play an important role in cell signaling and autophagy. Disruptions in either of these processes may contribute to cancer development. Lysosomal proteins, such as cathepsins, can play a role in both tumorigenesis and cancer cell apoptosis. Since endosomal and lysosomal biogenesis and signaling are important components of normal cellular growth and proliferation, proteins involved in these processes are attractive targets for cancer research and, potentially, therapeutics. This literature review provides an overview of the endocytic pathway, endolysosome formation, and the interplay between endosomal/lysosomal biogenesis and carcinogenesis.
Subject(s)
Carcinogenesis/metabolism , Endosomes/metabolism , Lysosomes/metabolism , Neoplasms/metabolism , Animals , Apoptosis , Cathepsins/metabolism , HumansABSTRACT
Basement membranes (BMs) are supramolecular matrices built on laminin and type IV collagen networks that provide structural and signaling support to tissues. BM complexity, however, has hindered an understanding of its formation, dynamics, and regulation. Using genome editing, we tagged 29 BM matrix components and receptors in C. elegans with mNeonGreen. Here, we report a common template that initiates BM formation, which rapidly diversifies during tissue differentiation. Through photobleaching studies, we show that BMs are not static-surprisingly, many matrix proteins move within the laminin and collagen scaffoldings. Finally, quantitative imaging, conditional knockdown, and optical highlighting indicate that papilin, a poorly studied glycoprotein, is the most abundant component in the gonadal BM, where it facilitates type IV collagen removal during BM expansion and tissue growth. Together, this work introduces methods for holistic investigation of BM regulation and reveals that BMs are highly dynamic and capable of rapid change to support tissues.
