Pediatric Long Bone Fractures After Dog Bites: A Case Series and Systematic Review.

This study presents a case series and systematic review of pediatric patients who sustained long bone fractures following dog bites. A systematic review of the studies on "pediatric fracture dog bite" based on a search of PubMed and OVID Medline databases was performed by adhering to PRISMA guidelines. Articles in English describing pediatric long bone fractures due to dog bites were included. Studies not differentiating pediatric from adult patients and not describing long bone fractures due to dog bites were excluded. Study characteristics, fracture epidemiology, management decisions, and follow-up data were extracted. Additionally, a seven-year retrospective chart review of cases treated at our level one pediatric trauma center was performed. Data on fracture characteristics, surgical management, choice of antibiotic therapy, and follow-up were collected. Five studies that met our criteria were analyzed. Pediatric long bone fractures from dog bites were identified in 0.35% (11/3,156) of patients. Such fractures most commonly involved the upper extremity (9/11, 82%). None of the studies described the choice of antibiotics, surgical decision-making, or wound closure preference for an underlying fracture. Our chart review elicited three cases of long bone fractures due to dog bites. Pediatric long bone fractures after dog bites are a rare injury pattern in the United States. These injuries should be treated as contaminated open fractures, and urgent immunization, intravenous antibiotic administration, wound care, and fracture stabilization should be provided. We recommend meticulous surgical debridement in the operating room, as wounds often probe deep into the bone. Nevertheless, there is much that remains unclear about these injuries. Hence, further research with greater power is needed to improve treatment decisions.

A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy.

Cancer cells disseminate and seed in distant organs, where they can remain dormant for many years before forming clinically detectable metastases. Here we studied how disseminated tumor cells sense and remodel the extracellular matrix (ECM) to sustain dormancy. ECM proteomics revealed that dormant cancer cells assemble a type III collagen-enriched ECM niche. Tumor-derived type III collagen is required to sustain tumor dormancy, as its disruption restores tumor cell proliferation through DDR1-mediated STAT1 signaling. Second-harmonic generation two-photon microscopy further revealed that the dormancy-to-reactivation transition is accompanied by changes in type III collagen architecture and abundance. Analysis of clinical samples revealed that type III collagen levels were increased in tumors from patients with lymph node-negative head and neck squamous cell carcinoma compared to patients who were positive for lymph node colonization. Our data support the idea that the manipulation of these mechanisms could serve as a barrier to metastasis through disseminated tumor cell dormancy induction.

Multi-modal Profiling of the Extracellular Matrix of Human Fallopian Tubes and Serous Tubal Intraepithelial Carcinomas.

Recent evidence supports the fimbriae of the fallopian tube as one origin site for high-grade serous ovarian cancer (HGSOC). The progression of many solid tumors is accompanied by changes in the microenvironment, including alterations of the extracellular matrix (ECM). Therefore, we sought to determine the ECM composition of the benign fallopian tube and changes associated with serous tubal intraepithelial carcinomas (STICs), precursors of HGSOC. The ECM composition of benign human fallopian tube was first defined from a meta-analysis of published proteomic datasets that identified 190 ECM proteins. We then conducted de novo proteomics using ECM enrichment and identified 88 proteins, 7 of which were not identified in prior studies (COL2A1, COL4A5, COL16A1, elastin, LAMA5, annexin A2, and PAI1). To enable future in vitro studies, we investigated the levels and localization of ECM components included in tissue-engineered models (type I, III, and IV collagens, fibronectin, laminin, versican, perlecan, and hyaluronic acid) using multispectral immunohistochemical staining of fimbriae from patients with benign conditions or STICs. Quantification revealed an increase in stromal fibronectin and a decrease in epithelial versican in STICs. Our results provide an in-depth picture of the ECM in the benign fallopian tube and identified ECM changes that accompany STIC formation. (J Histochem Cytochem XX: XXX-XXX, XXXX).

MatrisomeDB: the ECM-protein knowledge database.

The extracellular matrix (ECM) is a complex and dynamic meshwork of cross-linked proteins that supports cell polarization and functions and tissue organization and homeostasis. Over the past few decades, mass-spectrometry-based proteomics has emerged as the method of choice to characterize the composition of the ECM of normal and diseased tissues. Here, we present a new release of MatrisomeDB, a searchable collection of curated proteomic data from 17 studies on the ECM of 15 different normal tissue types, six cancer types (different grades of breast cancers, colorectal cancer, melanoma, and insulinoma) and other diseases including vascular defects and lung and liver fibroses. MatrisomeDB (http://www.pepchem.org/matrisomedb) was built by retrieving raw mass spectrometry data files and reprocessing them using the same search parameters and criteria to allow for a more direct comparison between the different studies. The present release of MatrisomeDB includes 847 human and 791 mouse ECM proteoforms and over 350 000 human and 600 000 mouse ECM-derived peptide-to-spectrum matches. For each query, a hierarchically-clustered tissue distribution map, a peptide coverage map, and a list of post-translational modifications identified, are generated. MatrisomeDB is the most complete collection of ECM proteomic data to date and allows the building of a comprehensive ECM atlas.

Exploring the extracellular matrix in health and disease using proteomics.

The extracellular matrix (ECM) is a complex assembly of hundreds of proteins that constitutes the scaffold of multicellular organisms. In addition to providing architectural and mechanical support to the surrounding cells, it conveys biochemical signals that regulate cellular processes including proliferation and survival, fate determination, and cell migration. Defects in ECM protein assembly, decreased ECM protein production or, on the contrary, excessive ECM accumulation, have been linked to many pathologies including cardiovascular and skeletal diseases, cancers, and fibrosis. The ECM thus represents a potential reservoir of prognostic biomarkers and therapeutic targets. However, our understanding of the global protein composition of the ECM and how it changes during pathological processes has remained limited until recently.In this mini-review, we provide an overview of the latest methodological advances in sample preparation and mass spectrometry-based proteomics that have permitted the profiling of the ECM of now dozens of normal and diseased tissues, including tumors and fibrotic lesions.