Androgen receptor function and targeted therapeutics across breast cancer subtypes.

Despite significant progress in breast cancer (BC) therapy, it is globally the most commonly diagnosed cancer and leads to the death of over 650,000 women annually. Androgen receptor (AR) is emerging as a potential new therapeutic target in BC. While the role of AR is well established in prostate cancer (PCa), its function in BC remains incompletely understood.

Protein Synthesis Inhibition Activity of Mesothelin Targeting Immunotoxin LMB-100 Decreases Concentrations of Oncogenic Signaling Molecules and Secreted Growth Factors.

LMB-100 is a mesothelin-targeted recombinant immunotoxin (iTox) that carries a modified exotoxin A (PE) payload. PE kills cells by inhibiting synthesis of new proteins. We found that treatment of pancreatic cancer cells with LMB-100 for 24⁻48 h did not change total protein level despite inducing protein synthesis inhibition (PSI).

The impact of mechanically stimulated muscle-derived stromal cells on aged skeletal muscle.

Perivascular stromal cells, including mesenchymal stem/stromal cells (MSCs), secrete paracrine factor in response to exercise training that can facilitate improvements in muscle remodeling. This study was designed to test the capacity for muscle-resident MSCs (mMSCs) isolated from young mice to release regenerative proteins in response to mechanical strain in vitro, and subsequently determine the extent to which strain-stimulated mMSCs can enhance skeletal muscle and cognitive performance in a mouse model of uncomplicated aging. Protein arrays confirmed a robust increase in protein release at 24h following an acute bout of mechanical strain in vitro (10%, 1Hz, 5h) compared to non-strain controls.

Mesothelin-targeted immunotoxin RG7787 has synergistic anti-tumor activity when combined with taxanes.

Recombinant immunotoxins (RITs) are antibody-based therapeutics that carry a toxin payload. The RG7787 RIT targets the cancer antigen mesothelin to deliver a recombinantly-engineered, reduced immunogenicity variant of Pseudomonas exotoxin A (PE) to the cytosol where it inhibits protein synthesis. Here we demonstrate that maximal doses of RG7787 temporarily halt growth of pancreatic cancer tumor xenografts, similar to the approved drugs gemcitabine and nab-paclitaxel, however, combination of the RIT with nab-paclitaxel produces durable complete regressions in most mice.

Protection of the Furin Cleavage Site in Low-Toxicity Immunotoxins Based on Pseudomonas Exotoxin A.

Recombinant immunotoxins (RITs) are fusions of an Fv-based targeting moiety and a toxin. Pseudomonas exotoxin A (PE) has been used to make several immunotoxins that have been evaluated in clinical trials. Immunogenicity of the bacterial toxin and off-target toxicity have limited the efficacy of these immunotoxins.

Oral antibiotic therapy of skeletal infections in children.

Oral and intravenous (IV) antibiotic regimens were compared in 15 children with etiologically defined osteomyelitis and/or septic arthritis. On admission all children were started on standard IV therapy; seven were changed to oral antibiotics within 72 hours and the remaining eight continued on IV therapy for four weeks. Oral antibiotic doses were adjusted to achieve a peak serum bactericidal titer of greater than or equal to 1:8 against the patient's own pathogen.

Serial 67Ga-citrate imaging during treatment of acute osteomyelitis in childhood.

To test the hypothesis that abnormalities on 67Ga-citrate scans parallel the clinical course of acute osteomyelitis and revert to normal with successful antibiotic therapy, serial scans were performed in ten children. Scans improved markedly within the first two to four weeks of treatment, but abnormalities persisted at six or more weeks in over 50% of the cases, despite complete clinical resolutions of disease.