Patient-derived xenograft models in musculoskeletal malignancies.

Successful oncological drug development for bone and soft tissue sarcoma is grossly stagnating. A major obstacle in this process is the lack of appropriate animal models recapitulating the complexity and heterogeneity of musculoskeletal malignancies, resulting in poor efficiency in translating the findings of basic research to clinical applications. In recent years, patient-derived xenograft (PDX) models generated by directly engrafting patient-derived tumor fragments into immunocompromised mice have recaptured the attention of many researchers due to their properties of retaining the principle histopathology, biological behaviors, and molecular and genetic characteristics of the original tumor, showing promising future in both basic and clinical studies of bone and soft tissue sarcoma. Despite several limitations including low take rate and long take time in PDX generation, deficient immune system and heterologous tumor microenvironment of the host, PDXs offer a more advantageous platform for preclinical drug screening, biomarker identification and clinical therapeutic decision guiding. Here, we provide a timely review of the establishment and applications of PDX models for musculoskeletal malignancies and discuss current challenges and future directions of this approach.

Elemental carbon - An efficient method to measure occupational exposure from materials in the graphene family.

Graphene is a 2D-material with many useful properties such as flexibility, elasticity, and conductivity among others. Graphene could therefore become a material used in many occupational fields in the future, which can give rise to occupational exposure. Today, exposure is unknown, due to the lack of efficient measuring techniques for occupational exposure to graphene. Readily available screening techniques for air sampling and -analysis are either nonspecific or nonquantitative. Quantifying materials from the broad graphene family by an easy-to-use method is important for the large-scale industrial application of graphene, especially when for the safety of working environment. Graphene consists primarily of elemental carbon, and the present study evaluates the organic carbon/elemental carbon (OC/EC)-technique for exposure assessment. The purpose of this work is to evaluate the OC/EC analysis technique as an efficient and easy-to-use method for quantification of occupational exposure to graphene. Methods that can identify graphene would be preferable for screening, but they are time consuming and semi-quantitative and therefore not suited for quantitative work environment assessments. The OC/EC-technique is a thermal optical analysis (TOA), that quantitively determines the amount of and distinguishes between two different types of carbon, organic and elemental. The technique is standardised, well-established and among other things used for diesel exposure measurements (ref standard). OC/EC could therefore be a feasible measuring technique to quantitively determine occupational exposure to graphene. The present evaluation of the technique provides an analytical method that works quantitatively for graphene, graphene oxide and reduced graphene oxide. Interestingly, the TOA technique makes it possible to distinguish between the three graphene forms used in this study. The technique was tested in an industrial setting and the outcome suggests that the technique is an efficient monitoring technique to be used in combination with characterisation techniques like for example Raman spectroscopy, scanning electron microscopy and atomic force microscopy.

Neuroprotective potential of GDF11 in experimental intracerebral hemorrhage in elderly rats.

The occurrence of intracerebral hemorrhage (ICH) costs long-standing neurologic deficits in ICH survivors, elderly ones in particular. Recent researches have proved rejuvenating effect of Growth Differentiation Factor 11 (GDF11) in improving multiple systemic diseases on old individuals. Thus, we designed this study to explore the neuroprotective effect and mechanisms of GDF11 in elderly ICH. 45 aged male Sprague-Dawley (SD) rats were randomly divided into sham + vehicle, ICH + vehicle and ICH + rGDF11 groups. ICH models were induced via injection of autologous whole blood into right basal ganglia of rats. ICH rats were given a daily injection of either recombinant (r) GDF11 at 0.1 mg/kg or vehicle for 28 days prior to operation and continued till the experiment completed. Neurological deficits, brain edema, cell apoptosis, microglial activation and heme oxygenase-1 (HO-1) positive cells were compared among each group. In addition, cytochrome c release, mitochondrial calcium buffering capacity and ATP level were monitored to explore the level of mitochondrial injury. Seen in the result, behavior disorders, severe perihematomal edema, inflammation, apoptosis, oxidative stress and mitochondria damage indicated a significant increase in ICH + vehicle group. While in ICH + rGDF11 group, administration of rGDF11 successfully reduced neurological deficits and alleviated ICH-induced edema, inflammation, apoptosis, oxidative stress, and mitochondria damage in perihematomal tissues. Collectively, our study showed that GDF11 ameliorated ICH-induced neurological deficits in elderly individuals via reducing perihematomal edema, apoptosis, inflammatory reaction, oxidative stress and improving mitochondrial dysfunction, indicating neuroprotective effect of GDF11 in elderly ICH.