ABSTRACT
It has long been known that oncolytic viruses wield their therapeutic capability by priming an inflammatory state within the tumor and activating the tumor immune microenvironment, resulting in a multifaceted antitumor immune response. Vaccine-derived viruses, such as measles and mumps, have demonstrated promising potential for treating human cancer in animal models and clinical trials. However, the extensive cost of manufacturing current oncolytic viral products makes them far out of reach for most patients. Here by analyzing the impact of intratumoral (IT) administrations of the trivalent live attenuated measles, mumps, and rubella viruses (MMR) vaccine, we unveil the cellular and molecular basis of MMR-induced anti-cancer activity. Strikingly, we found that IT delivery of low doses of MMR correlates with tumor control and improved survival in murine hepatocellular cancer and colorectal cancer models via increased tumor infiltration of CD8+ granzyme B+ T-cells and decreased macrophages. Moreover, our data indicate that MMR activates key cellular effectors of the host's innate and adaptive antitumor immunity, culminating in an immunologically coordinated cancer cell death. These findings warrant further work on the potential for MMR to be repurposed as safe and cost-effective cancer immunotherapy to impact cancer patients globally.
ABSTRACT
Amla (Emblica officinalis Gaertn.) is a natural source of antioxidants and possesses valuable medicinal properties. However, the protective effect of amla in the kidney of two-kidneys-one-clip (2K1C) rats has not been explained sufficiently. This study was performed to evaluate the renoprotective effect of amla fruit powder (2.5% W/W) supplementation in kidneys of 2K1C rats. 2K1C rats increased the remnant kidney wet weight and also increased plasma creatinine and uric acid concentration compared to the control. Amla supplementation ameliorates elevated creatinine and uric acid concentration in plasma of 2K1C rats. Various oxidative stress indicators such as malondialdehyde, nitric oxide (NO), and advanced protein oxidation product (APOP) were also increased in plasma, heart, and kidney tissues in 2K1C rats that were also significantly brought down to normal level by amla supplementation. Moreover, the inflammatory cells entry and fibrosis in the 2K1C rat's tissues were prevented by amla supplementation. These research results suggest that amla may restore plasma antioxidant capacities and prevents oxidative stress, inflammation, and fibrosis in 2K1C rats. Taken these results as a base, clinical supplementation of dried amla powder in diet or juice to the CKD patients would be beneficial.
