Selecting the Most Relevant Mouse Strains for Evaluating Radiation-Induced Multiple Tissue Injury after Leg-Shielded Partial-Body Gamma Irradiation.

Animal studies are needed that best simulate a large-scale, inhomogeneous body exposure after a radiological or nuclear incident and that provides a platform for future development of medical countermeasures. A partial-body irradiation (PBI) model using 137Cs gamma rays with hind limb (tibia) shielding was developed and assessed for the sequalae of radiation injuries to gastrointestinal tract, bone marrow (BM) and lung and among different genetic mouse strains (C57BL/6J, C57L/J, CBA/J and FVB/NJ). In this case, a marginal level of BM shielding (∼2%) provided adequate protection against lethality from infection and hemorrhage and enabled escalation of radiation doses with evaluation of both acute and delayed radiation syndromes.

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer.

Background: Genetically engineered mouse models (GEMMs) of cancer are powerful tools to study mechanisms of disease progression and therapy response, yet little is known about how these models respond to multimodality therapy used in patients. Radiation therapy (RT) is frequently used to treat localized cancers with curative intent, delay progression of oligometastases, and palliate symptoms of metastatic disease.

Methods: Here we report the development, testing, and validation of a platform to immobilize and target tumors in mice with stereotactic ablative RT (SART).

A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma.

The heterogeneity of cellular states in cancer has been linked to drug resistance, cancer progression and the presence of cancer cells with properties of normal tissue stem cells. Secreted Wnt signals maintain stem cells in various epithelial tissues, including in lung development and regeneration. Here we show that mouse and human lung adenocarcinomas display hierarchical features with two distinct subpopulations, one with high Wnt signalling activity and another forming a niche that provides the Wnt ligand.

Microdosimetric and Biological Effects of Photon Irradiation at Different Energies in Bone Marrow.

To ensure reliability and reproducibility of radiobiological data, it is necessary to standardize dosimetry practices across all research institutions. The photoelectric effect predominates over other interactions at low energy and in high atomic number materials such as bone, which can lead to increased dose deposition in soft tissue adjacent to mineral bone due to secondary radiation particles. This may produce radiation effects that deviate from higher energy photon irradiation that best model exposure from clinical radiotherapy or nuclear incidences.

A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength.

Diseases such as osteoporosis are associated with reduced bone mass. Therapies to prevent bone loss exist, but there are few that stimulate bone formation and restore bone mass. Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily, which act as pleiotropic regulators of skeletal organogenesis and bone homeostasis.

A novel therapeutic approach to treating obesity through modulation of TGFβ signaling.

Obesity results from disproportionately high energy intake relative to energy expenditure. Many therapeutic strategies have focused on the intake side of the equation, including pharmaceutical targeting of appetite and digestion. An alternative approach is to increase energy expenditure through physical activity or adaptive thermogenesis.

A soluble activin receptor type IIb prevents the effects of androgen deprivation on body composition and bone health.

Androgen deprivation, a consequence of hypogonadism, certain cancer treatments, or normal aging in men, leads to loss of muscle mass, increased adiposity, and osteoporosis. In the present study, using a soluble chimeric form of activin receptor type IIB (ActRIIB) we sought to offset the adverse effects of androgen deprivation on muscle, adipose tissue, and bone. Castrated (ORX) or sham-operated (SHAM) mice received either TBS [vehicle-treated (VEH)] or systemic administration of ActRIIB-mFc, a soluble fusion protein comprised of a form of the extracellular domain of ActRIIB fused to a murine IgG2aFc subunit.

A soluble activin type IIA receptor induces bone formation and improves skeletal integrity.

Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-beta superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-beta signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism.