Validation of a PD-1/CD28 chimeric switch receptor to augment CAR-T function in dogs with spontaneous B cell lymphoma.

Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented clinical outcomes in patients with relapsed/refractory B cell leukemias; however, response rates in patients with large B cell lymphoma (LBCL) are less impressive. Expression of PD-1 on activated T cells and PD-L1 on malignant, stromal, and immune cells within the tumor microenvironment (TME) contribute to CAR-T exhaustion, hypofunction, and treatment failures. Here, a comparative approach is taken to develop a chimeric switch receptor (CSR) with potential to augment CAR-T persistence, function, and clinical efficacy in immune competent, pet dogs with spontaneous B cell lymphoma (BCL).

Exercise training affects hemodynamics and exercise capacity in cases of heart failure with preserved ejection fraction: a non-randomized controlled trial in individuals aged 65-80 years.

Introduction: Exercise training is an established intervention method for improving exercise capacity and survival rates in patients with heart failure with preserved ejection fraction (HFpEF). However, most reports have focused on European and American patients, with limited data regarding the effects of exercise training on cardiac function, hemodynamics, and exercise capacity in East Asian patients. This study investigated the effects of exercise training on cardiac function, hemodynamics, and exercise capacity in Japanese patients aged 65-80 years with HFpEF.

Negative Influence of Aging on Differentiation and Proliferation of CD8 T-Cells in Dogs.

Immunosenescence is an age-related change in the immune system characterized by a reduction in naïve T-cells and an impaired proliferative capacity of CD8 T-cells in older individuals. Recent research revealed the crucial impact of immunosenescence on the development and control of cancer, and aging is one of the causes that diminish the therapeutic efficacy of cancer immunotherapies targeting CD8 T-cell activation. Despite dog cancer being defined as an age-related disease, there are few fundamental understandings regarding the relationship between aging and the canine immune system.

Evaluation of the influence of the C-X-C motif chemokine ligand 12 / C-X-C chemokine receptor 4 axis on canine mammary gland tumor cell migration.

C-X-C motif chemokine ligand 12 (CXCL12) is one of the chemokines that binds to C-X-C chemokine receptor 4 (CXCR4) on tumor cell membranes and induces chemotaxis and/or migration. Mammary gland tumors (MGT) are the most common neoplasms in intact female dogs, with local invasion and distant metastasis regarded as problems. However, the influence of the CXCL12/CXCR4 axis on canine MGT cell migration has not been elucidated.

Thoracic Wall Reconstruction with Dorsal Diaphragmatic Traction and Preservation of Diaphragmatic Attachments in a Dog with Resection of the 11-13th Ribs.

A 9-year-old, 4.7 kg, spayed female Chihuahua presented with a 3.5 cm soft tissue sarcoma on the dorsal right thoracic wall.

Biological features of canine cancer-associated fibroblasts and their influence on cancer cell invasion.

Cancer-associated fibroblasts (CAFs) play an essential role in tumor invasion and metastasis. In dogs, the biological features of CAFs have not been well characterized. The purpose of this study was to investigate differences in the biological activities of canine CAFs and normal fibroblasts (NFs), and their influence on the migration and invasion of cancer cells.

Adhesion and Disintegration Phenomena on Fractal Agar Gel Surfaces.

In the present study, mechanical phenomena on fractal agar gel were analyzed to understand the interfacial properties of hydrophilic biosurfaces. The evaluation of adhesion strength between the fractal agar gel surfaces showed that the fractal structure inhibits the adhesion between the agar gel surfaces. In addition, when the disintegration behavior of an agar gel block was observed between fractal agar gel substrates, the rough structure prevented the sliding of an agar gel block.