Targeting YAP Activity and Glutamine Metabolism Cooperatively Suppresses Tumor Progression by Preventing Extracellular Matrix Accumulation.

Cancer cells use multiple mechanisms to evade the effects of glutamine metabolism inhibitors. The pathways that govern responses to alterations in glutamine availability within the tumor may represent therapeutic targets for combinatorial strategies with these inhibitors. Here, we showed that targeting glutamine utilization stimulated Yes-associated protein (YAP) signaling in cancer cells by reducing cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-dependent phosphorylation of large tumor suppressor (LATS). Elevated YAP activation induced extracellular matrix (ECM) deposition by increasing secretion of connective tissue growth factor (CTGF) that promoted production of fibronectin and collagen by surrounding fibroblasts. Consequently, inhibiting YAP synergized with inhibition of glutamine utilization to effectively suppress tumor growth in vivo, along with a concurrent decrease in ECM deposition. Blocking ECM remodeling also augmented the tumor suppressive effects of the glutamine utilization inhibitor. Collectively, these data reveal mechanisms by which targeting glutamine utilization increases ECM accumulation and identify potential strategies to reduce ECM levels and increase the efficacy of glutamine metabolism inhibitors.

A Severe Cervical Spondylotic Myelopathy Patient Treated with Integrative Korean Medicine Including Acupuncture, Bee Venom Pharmacopuncture and Herbal Medicine: a case report.

Cervical spondylotic myelopathy (CSM) is common in elderly people and severe CSM patients are recommended to receive surgery. However, in some cases, surgery may fail to improve the patients' symptoms. An 80-year-old man diagnosed with CSM complained of right hemiplegia and right arm and leg pain with the presence of a Foley catheter, despite treatment with laminectomy and laminoplasty. Acupuncture, bee venom pharmacopuncture, and herbal medicine were administered for 129 days. As a result, manual muscle testing (MMT) and the Modified Barthel Index (MBI) improved, the pain in his right arm and leg decreased, and he was able to urinate by himself. This case report implies that integrative Korean medicine (IKM) can be an option for patients suffering from muscular weakness resulting from myelopathy.