Proteomic and transcriptomic analyses identify apo-transcobalamin-II as a biomarker of overall survival in osteosarcoma.

Background: The large-scale proteomic platform known as the SomaScan® assay is capable of simultaneously measuring thousands of proteins in patient specimens through next-generation aptamer-based multiplexed technology. While previous studies have utilized patient peripheral blood to suggest serum biomarkers of prognostic or diagnostic value in osteosarcoma (OSA), the most common primary pediatric bone cancer, they have ultimately been limited in the robustness of their analyses. We propose utilizing this aptamer-based technology to describe the systemic proteomic milieu in patients diagnosed with this disease.

Spatial multiplexed immunofluorescence analysis reveals coordinated cellular networks associated with overall survival in metastatic osteosarcoma.

Patients diagnosed with advanced osteosarcoma, often in the form of lung metastases, have abysmal five-year overall survival rates. The complexity of the osteosarcoma immune tumor microenvironment has been implicated in clinical trial failures of various immunotherapies. The purpose of this exploratory study was to spatially characterize the immune tumor microenvironment of metastatic osteosarcoma lung specimens.

Spaceflight-associated pain.

Purpose Of Review: Consequences of the expanding commercial spaceflight industry include an increase in total number of spaceflight participants and an accompanying surge in the average number of medical comorbidities compared with government-based astronaut corps. A sequela of these developments is an anticipated rise in acute and chronic pain concerns associated with spaceflight. This review will summarize diagnostic and therapeutic areas of interest that can support the comfort of humans in spaceflight.

Nanosphere pharmacodynamics improves safety of immunostimulatory cytokine therapy.

Systemic administration of interleukin (IL)-12 induces potent anti-tumor immune responses in preclinical cancer models through the systemic activation of effector immune cells and release of proinflammatory cytokines. IL-12-loaded PLGA nanospheres (IL12ns) are hypothesized to improve therapeutic efficacy and thwart unwanted side effects observed in previous human clinical trials. Through the investigation of peripheral blood and local tissue immune responses in healthy BALB/c mice, the immune-protective pharmacodynamics of IL12ns were suggested.

Single-cell RNA-seq reveals intratumoral heterogeneity in osteosarcoma patients: A review.

While primary bone malignancies make up just 0.2% of all cancers, osteosarcoma (OS) is the third most common cancer in adolescents. Due to its highly complex and heterogeneous tumor microenvironment (TME), OS has proven difficult to treat.

Optimizing the synthesis of interleukin-12-loaded PLGA nanospheres (rmIL-12ns) via ultrasonication for treatment of metastatic osteosarcoma.

Clinical trials exploring bolus intravenous delivery of interleukin-12 (IL-12) for treatment of solid tumors ultimately failed due to lack of clinical response and severe dose-limiting toxicities. The present study was conducted to evaluate whether recombinant murine IL-12 (rmIL-12) could be successfully encapsulated within Poly (D, l-lactide-co-glycolide) (PLGA) nanospheres (rmIL-12ns) for safe and effective systemic delivery at pharmacologic scale. Optimal fabrication of rmIL-12ns occurs with dichloromethane as the organic solvent and emulsion formation via ultrasonication at 50% power (250 W sonicator) for 10 s (50W10s).

Synthesis, Characterization, and Cytokinome Profile of IL-12-Loaded PLGA Nanospheres.

We report the successful encapsulation and elution of recombinant murine IL-12 (rmIL-12) from poly(lactide-co-glycolic) acid (PLGA) nanospheres (IL-12-NS) synthesized using the double emulsion/solvent evaporation (DESE) technique with microsphere depletion through ultracentrifugation. Images obtained with scanning electron microscopy (SEM) showcased a characteristic spherical shape with a mean particle diameter of 138.1 ± 10.

Nanocapsule Delivery of IL-12.

Interleukin(IL)-12 is a protein that activates T cells and macrophages to kill tumor cells. However, despite this cytokine showing strong antitumor activity in preclinical settings, translation to patients has been slowed by toxic side effects, poor distribution to peripheral tissues, and improper dosing regimens. Osteosarcoma (OS) is an aggressive primary tumor of bone that has shown particular responsiveness to recombinant (r)IL-12 in preclinical models.