General Thoracic Surgery
- 1. New lung cancer treatments that target the cancer microenvironment
- 2. Analysis of tumor infiltrating lymphocytes from clincial samples
- 3. Lung regeneration using adipose-derived stem cells and iPS cells
- 4. New transplantation therapies for lung ischemia reperfusion injury
- 5. New lung cancer therapies targetting Arl4c
Research and medicine: from bench to bedside and beside to bench
Lung cancer therapies that target the cancer microenvironment
Fibroblasts in cancer and healthy lung tissue show different activation levels. Moreover, they have a role in regulating the cancer phenotype. Fibroblasts from cancer tissues secrete the cytokine IL-6, which along with TGF-β, supports the cancer microenvironment, including resistance to treatment. Research has shown that anti-cancer treatment increases the number of cancer fibroblasts, the risk of metastasis through an epithelial-mesenchymal transition, and development of the cancer stem cell-like phenotype, promoting resistance to the treatment. We are investigating the role of fibroblasts and cytokines to disrupt these changes and overcome the treatment resistance.
Analysis of tumor infiltrating lymphocytes from clinical samples
Among cancer therapies, including surgery, chemo and radiation, none dominates the news like immunotherapy. Indeed, cancer immunotherapy has especially gained attention for lung cancer. Researchers now understand that the immune response depends on immunocompetent cells including regulatory T cells, myeloid-derived suppressor cells and tumor associated macrophages. Furthermore, surface receptors such as PD-L1 are core to tumor immune evasion. To study this complex molecular mechanism, we are collecting and analyzing clinical cancer samples from the lung and thymus. Our data indicate that the therapies are most effect for type B3 and type C carcinomas.
Lung regenerative medicine using adipose-derived stem cells
Among the many patients with chronic respiratory diseases such as asthma, about half suffer from chronic obstructive pulmonary disease (COPD). Recently, anatomical and physiological studies have suggested that the lung parenchyma possesses regenerative properties. Using a COPD animal model, we have found hepatocyte growth factor (HGF) treatment has positive effects against chronic respiratory failure. Furthermore, the administration of adipose-derived stem cells (ADSC) caused the lung of an emphysema model to upregulate HGF. ADSC sheets engrafted to the lung secreted HGF, which caused regeneration of the alveoli. Consistently, ADSC can be differentiated into type II alveolar cells under proper culture conditions, suggesting their possible use in lung repair. The figure shows GFP-ADSC express alveoli markers in vitro and in vivo. We are now investigating new markers for growth factors and stem cells, which will be used for new gene therapies, cell therapies, and tissue engineering for the lungs.