Patient-derived tumoroids from CIC::DUX4 rearranged sarcoma identify MCL1 as a therapeutic target.

High-risk sarcomas, such as metastatic and relapsed Ewing and CIC-rearranged sarcoma, still have a poor prognosis despite intensive therapeutic regimens. Precision medicine approaches offer hope, and ex vivo drug response profiling of patient-derived tumor cells emerges as a promising tool to identify effective therapies for individual patients. Here, we establish ex vivo culture conditions to propagate Ewing sarcoma and CIC::DUX4 sarcoma as tumoroids.

Development of a Cellular Assay as a Personalized Model for Testing Chronic Wound Therapeutics.

Exudates of nonhealing wounds contain drivers of pathogenicity. We utilized >800 exudates from nonhealing and healing wounds of diverse etiologies, collected by 3 different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to (i) differentiate between healing and nonhealing wounds, (ii) follow the healing process of individual patients, and (iii) assess the effects of therapeutics for chronic wounds ex vivo.

In vitro and in vivo investigation of antibacterial silver nanoparticles functionalized bone grafting substitutes.

Infection is a major concern in surgery involving grafting and should be considered thoroughly when designing biomaterials. There is considerable renewed interest in silver nanoparticles (AgNPs) owing to their ability to potentiate antibacterial properties against multiple bacterial strains. This study aimed to develop two antibacterial bone regenerative scaffolds by integrating AgNPs in bovine bone particles (BBX) (Product 1), and a light cross-linked hydrogel GelMA (Product 2).

In vivo healing of low temperature deproteinized bovine bone xenograft in a rabbit cranial model.

The physicochemical properties of grafting materials affect the quality of the osteointegration, resorption rate, and the new bone (NB) formation. This study assessed the physicochemical properties and integration of a low temperature deproteinized bovine bone xenograft (BBX), referred to as optimized MoaBone® (OMB). This novel BBX was physiochemically characterized both pre and post chemical bleaching and sterilization by gamma irradiation.

Neuro-Urology and Biobanking: An Integrated Approach for Advancing Research and Improving Patient Care.

Understanding the molecular mechanisms underlying neuro-urological disorders is crucial for the development of targeted therapeutic interventions. Through the establishment of comprehensive biobanks, researchers can collect and store various biological specimens, including urine, blood, tissue, and DNA samples, to study these mechanisms. In the context of neuro-urology, biobanking facilitates the identification of genetic variations, epigenetic modifications, and gene expression patterns associated with neurogenic lower urinary tract dysfunction.

Intra-articular injection of triamcinolone acetonide sustains macrophage levels and aggravates osteophytosis during degenerative joint disease in mice.

Background And Purpose: Corticosteroids such as triamcinolone acetonide (TAA) are potent drugs administered intra-articularly as an anti-inflammatory therapy to relieve pain associated with osteoarthritis (OA). However, the ability of early TAA intervention to mitigate OA progression and modulate immune cell subsets remains unclear. Here, we sought to understand the effect of early intra-articular injection of TAA on OA progression, local macrophages, and peripheral blood monocytes.

TASCI-transcutaneous tibial nerve stimulation in patients with acute spinal cord injury to prevent neurogenic detrusor overactivity: protocol for a nationwide, randomised, sham-controlled, double-blind clinical trial.

Introduction: Neurogenic lower urinary tract dysfunction (NLUTD), including neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia, is one of the most frequent and devastating sequelae of spinal cord injury (SCI), as it can lead to urinary incontinence and secondary damage such as renal failure. Transcutaneous tibial nerve stimulation (TTNS) is a promising, non-invasive neuromodulatory intervention that may prevent the emergence of the C-fibre evoked bladder reflexes that are thought to cause NDO. This paper presents the protocol for TTNS in acute SCI (TASCI), which will evaluate the efficacy of TTNS in preventing NDO.

Short postsurgical antibiotic therapy for spinal infections: protocol of prospective, randomized, unblinded, noninferiority trials (SASI trials).

Background: There are several open scientific questions regarding the optimal antibiotic treatment of spinal infections (SIs) with or without an implant. The duration of postsurgical antibiotic therapy is debated.

Methods: We will perform two unblinded randomized controlled trials (RCTs).

The miR-143/145 Cluster, a Novel Diagnostic Biomarker in Chondrosarcoma, Acts as a Tumor Suppressor and Directly Inhibits Fascin-1.

Chondrosarcoma is the second most frequent bone sarcoma. Due to the inherent chemotherapy and radiotherapy resistance and absence of known therapeutic targets, clinical management is limited to surgical resection. Consequently, patients with advanced disease face a poor prognosis.

Optimization of the antibiotic management of diabetic foot infections: protocol for two randomized controlled trials.

Background: Few studies have addressed the appropriate duration of antibiotic therapy for diabetic foot infections (DFI) with or without amputation. We will perform two randomized clinical trials (RCTs) to reduce the antibiotic use and associated adverse events in DFI.

Methods: We hypothesize that shorter durations of postdebridement systemic antibiotic therapy are noninferior (10% margin, 80% power, alpha 5%) to existing (long) durations and we will perform two unblinded RCTs with a total of 400 DFI episodes (randomization 1:1) from 2019 to 2022.

Remineralization of Artificial Dentin Caries Using Dentin and Enamel Matrix Proteins.

To assess the remineralizing potential of dentin matrix proteins and enamel matrix derivatives (DMPs and EMDs) after application on artificially induced dentin lesions, given the hypothesis that these materials increase the mineral uptake, binding, and mineralization. Forty-eight caries-free human premolars were used. Teeth were cut, polished, and embedded, leaving an open window on the root surface, of which one-third was covered with a flowable composite to preserve the healthy untreated dentin.

Evaluation of F8-TNF-α in Models of Early and Progressive Metastatic Osteosarcoma.

The targeted delivery of tumor necrosis factor-α (TNF-α) with antibodies specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra-domain A (EDA) domain of fibronectin] has already shown efficacy against experimental sarcomas but has not yet been investigated in orthotopic sarcomas.

Foscan and foslip based photodynamic therapy in osteosarcoma in vitro and in intratibial mouse models.

Current osteosarcoma therapies cause severe treatment-related side effects and chemoresistance, and have low success rates. Consequently, alternative treatment options are urgently needed. Photodynamic therapy (PDT) is a minimally invasive, local therapy with proven clinical efficacy for a variety of tumor types.

Evaluation of intraarterial and intravenous cisplatin chemotherapy in the treatment of metastatic osteosarcoma using an orthotopic xenograft mouse model.

Background: Osteosarcoma is the most common primary malignancy of bone. Its treatment relies on the administration of neoadjuvant and adjuvant chemotherapy combined with surgery. Alternative to common intravenous (i.

Altered CXCL12 expression reveals a dual role of CXCR4 in osteosarcoma primary tumor growth and metastasis.

Purpose: Better understanding of the molecular mechanisms of metastasis-the major cause of death in osteosarcoma (OS)-is a key for the development of more effective metastasis-suppressive therapy. Here, we investigated the biological relevance of the CXCL12/CXCR4 axis in OS.

Methods: We interfered with CXCL12/CXCR4 signaling in CXCR4-expressing human 143-B OS cells through stable expression of CXCL12, of its competitive antagonist P2G, or of CXCL12-KDEL, designed to retain CXCR4 within the cell.

Explant culture of sarcoma patients' tissue.

Human sarcomas comprise a heterogeneous group of rare tumors that affect soft tissues and bone. Due to the scarcity and heterogeneity of these diseases, patient-derived cells that can be used for preclinical research are limited. In this study, we investigated whether the tissue explant technique can be used to obtain sarcoma cell lines from fresh as well as viable frozen tissue obtained from 8 out of 12 soft tissue and 9 out of 13 bone tumor entities as defined by the World Health Organization.

Preclinical mouse models of osteosarcoma.

Osteosarcoma is the most common form of primary bone tumors with high prevalence in children. Survival rates of osteosarcoma are low, especially in the case of metastases. Mouse models of this disease have been very valuable in investigation of mechanisms of tumorigenesis, metastasis, as well as testing possible therapeutic options.

Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy.

Background: Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy.

Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency.

As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg-/- mouse model which -in a C57BL6/FVB F1 hybrid genetic background- displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4-5 months.

Cytotoxic efficacy of photodynamic therapy in osteosarcoma cells in vitro.

In recent years, there has been the difficulty in finding more effective therapies against cancer with less systemic side effects. Therefore Photodynamic Therapy is a novel approach for a more tumor selective treatment. Photodynamic Therapy (PDT) that makes use of a nontoxic photosensitizer (PS), which, upon activation with light of a specific wavelength in the presence of oxygen, generates oxygen radicals that elicit a cytotoxic response(1).

Recent advances in osteosarcoma.

Although osteosarcoma (OS) is a rare malignancy, it is ranked among the leading causes of cancer-related death in the pediatric age group. The cancer's low prevalence and its large tumor heterogeneity make it difficult to obtain meaningful progress in patient survival. In this review we present an overview of current clinical trials which largely focus on stimulation of the immune system or rely on the inhibition of kinases such as Src and mTOR.

Genes regulated in metastatic osteosarcoma: evaluation by microarray analysis in four human and two mouse cell line systems.

Osteosarcoma (OS) is a rare bone neoplasm that affects mainly adolescents. It is associated with poor prognosis in case of metastases formation. The search for metastasis predicting markers is therefore imperative to optimize treatment strategies for patients at risk and important for the search of new drugs for the treatment of this devastating disease.

Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice.

Trichothiodystrophy (TTD) is a rare, autosomal recessive nucleotide excision repair (NER) disorder caused by mutations in components of the dual functional NER/basal transcription factor TFIIH. TTD mice, carrying a patient-based point mutation in the Xpd gene, strikingly resemble many features of the human syndrome and exhibit signs of premature aging. To examine to which extent TTD mice resemble the normal process of aging, we thoroughly investigated the bone phenotype.

Osteoarthritis induction leads to early and temporal subchondral plate porosity in the tibial plateau of mice: an in vivo microfocal computed tomography study.

Objective: In osteoarthritis (OA), changes occur in both cartilage and subchondral bone. The subchondral bone plate facilitates normal cross-talk between articular cartilage and trabecular subchondral bone, and adaptive changes in the plate due to OA may therefore disturb cross-talk homeostasis. To investigate these changes over time, we examined the cartilage-subchondral bone interface using a combined approach of histologic analysis and in vivo microfocal computed tomography.

Analysis of osteoarthritis in a mouse model of the progeroid human DNA repair syndrome trichothiodystrophy.

The increasing average age in developed societies is paralleled by an increase in the prevalence of many age-related diseases such as osteoarthritis (OA), which is characterized by deformation of the joint due to cartilage damage and increased turnover of subchondral bone. Consequently, deficiency in DNA repair, often associated with premature aging, may lead to increased pathology of these two tissues. To examine this possibility, we analyzed the bone and cartilage phenotype of male and female knee joints derived from 52- to 104-week-old WT C57Bl/6 and trichothiodystrophy (TTD) mice, who carry a defect in the nucleotide excision repair pathway and display many features of premature aging.