Canine rapamycin
Pro Research Analysisby 
Searched over 200M research papers for "canine rapamycin"
Canine Rapamycin: Therapeutic Applications and Effects
Rapamycin in Canine Mammary Tumors
Anti-Tumoral Effects on Mammary Tumor Cells
Rapamycin, an mTOR inhibitor, has shown significant antitumor activity in canine mammary tumors. Studies have demonstrated that rapamycin can inhibit cell growth in both primary and metastatic mammary tumor cells in vitro. The IC50 values for rapamycin ranged between 2 and 10 µM across different tumor cell lines. Proteomic analysis revealed that rapamycin treatment led to a decrease in proteins associated with enhanced tumor malignancy and an increase in proteins related to apoptosis.
Rapamycin in Canine Brain Injury
mTOR Inhibition and Cerebral Vasospasm
In canine models of subarachnoid hemorrhage (SAH), rapamycin has been effective in reducing cerebral vasospasm. The mTOR pathway, which is crucial for cell growth and survival, was found to be significantly involved in the activation of cerebral vasospasm post-SAH. Rapamycin treatment attenuated vasospasm and improved clinical outcomes by reducing the expression of mTOR and its downstream targets, such as P70S6K1 and 4E-BP1.
Rapamycin in Glycogen Storage Disease
Therapeutic Potential in GSD III
Rapamycin has shown promise as a treatment for glycogen storage disease type III (GSD III) in canines. It significantly reduced glycogen accumulation in muscle cells and prevented the progression of liver fibrosis. Early treatment was more effective in reducing liver glycogen content compared to late treatment, highlighting the importance of timely intervention.
Rapamycin in Canine Osteosarcoma
Inhibition of mTOR Pathway
In canine osteosarcoma cells, rapamycin effectively inhibited the mTOR pathway, leading to a decrease in phosphorylated mTOR and p70S6 kinase levels. This inhibition resulted in a dose-dependent reduction in the surviving fraction of osteosarcoma cells, suggesting that rapamycin could be a viable antineoplastic treatment for this type of cancer.
Rapamycin in Canine Malignant Melanoma
Effects on AKT and mTOR Pathways
Rapamycin has also been studied in canine malignant melanoma, where it inhibited the mTOR pathway and reduced the expression of phosphorylated mTOR and p70S6K. This led to a significant decrease in the surviving fraction of melanoma cells, supporting the potential use of mTOR inhibitors in treating canine melanoma.
Rapamycin in Renal Allograft Survival
Enhancing Allograft Survival
Rapamycin, when used in combination with antilymphocyte serum, donor bone marrow cells, and cyclosporine, significantly improved renal allograft survival in canines. This combination therapy reduced early rejections and was associated with long-term graft survival without significant toxicity.
Pharmacokinetics of Rapamycin in Healthy Dogs
Oral Administration and Blood Concentrations
The pharmacokinetics of orally administered rapamycin in healthy dogs showed that low doses achieved measurable blood concentrations. The study indicated that the optimal dosing regimen for therapeutic effects in tumor-bearing dogs needs further investigation.
Rapamycin in Canine Skin Tumors
Expression of p-mTOR
In canine skin tumors, high or moderate expression of phosphorylated mTOR (p-mTOR) was observed in a significant proportion of cases. This suggests that mTOR activation plays a role in the development of these tumors and that mTOR inhibitors like rapamycin could be explored as therapeutic options.
Rapamycin in Aging and Cardiac Function
Effects on Heart Function in Middle-Aged Dogs
A study on middle-aged companion dogs treated with rapamycin showed improvements in age-related heart function measures without clinical side effects. This suggests that rapamycin could potentially improve healthspan and reduce mortality in aging dogs.
Metabolic Impact of Rapamycin in Islet Graft Recipients
Effects on Glucose Metabolism
In canine models of pancreatic islet transplantation, rapamycin treatment was associated with improved glucose clearance and increased insulin release. These findings indicate that rapamycin does not adversely affect islet function or glucose metabolism, making it a viable option for managing islet graft recipients.
Conclusion
Rapamycin exhibits a wide range of therapeutic effects in canines, from treating various cancers and genetic disorders to improving organ transplant outcomes and potentially extending healthspan. Its ability to inhibit the mTOR pathway makes it a versatile drug with significant clinical implications for veterinary medicine. Further research is warranted to optimize dosing regimens and fully understand its long-term effects.
Sources and full results
Most relevant research papers on this topic