Renal transplantation is the definitive treatment for the end-stage renal failure. Despite concerted efforts to increase the number of available organs there remains a wide gap. Kidneys with small renal cell carcinoma have been used for transplantation after ex vivo resection of tumours with excellent results. Concerns regarding the behaviour of tumour under standard immunosuppression prevent this source from being popularised. We studied tumour behaviour with standard immunosuppression and immunosuppressives with anti-proliferative properties and the effect of MHC matching on tumour behaviour. Luciferase labelled Wistar rat kidney tumour cells were injected subcutaneously into Wistar or Lewis rats to mimic well and poorly matched groups. These were divided into groups receiving Cyclosporine, Sirolimus high and Sirolimus low dose and Leflunomide. Effects of matching on tumour rejection were studied by immunosuppression withdrawal in half of the animals within each group. Tumour progression was monitored with IVIS spectrum imaging system. When the immunosuppression was continued for the length of the study period with Cyclosporine immunosuppression, the tumour continued to grow in both strains. With high dose Sirolimus, the tumour was eradicated within 2 weeks in both Wistar and Lewis rats (p < 0.05). Both strains receiving low dose Sirolimus also eradicated the tumour within four weeks of treatment (p < 0.05). In Leflunomide group, 4/7 animals rejected the tumour within the 4 weeks of study period (p < 0.05). To study the effects of rejection and matching on the tumour behaviour, the immunosuppression was stopped after 2 weeks of treatment and the animals followed for another two weeks to study these effects. After treatment withdrawal, the tumour rejection was noted which was significantly stronger in poorly matched animals than in well-matched animals (p < 0.05) in cyclosporine treated animals. These results appeared to be in line with our hypothesis, that newer immunosuppressive medications with anti-neoplastic effects may be better options after transplanting kidneys after small tumour ex-vivo resection. Acute rejection showed significant ability to lead to tumour eradication, more effectively in less well-matched animals than well-matched combinations. Thus perhaps clinically, recipients of such restored kidneys should be less well matched and immunosuppressed with agents with anti-proliferative properties. These results will need to be replicated with further studies including closely monitored clinical studies before it can be popularised at a significant new source of precious organs.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:730817 |
| Date | January 2017 |
| Creators | Khurram, Muhammad Arslan |
| Publisher | University of Sunderland |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://sure.sunderland.ac.uk/8559/ |
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