Development of an optimised contractile strategy to improve the muscle health of older surgical cancer patients


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  Dr B Phillips  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Following surgery for cancer, older patients lose significant muscle mass and function due to the physiological insult of surgery and physical inactivity in the postoperative period. These losses cause delayed recovery from surgery and return to normal activities and are associated with significant physical and psychological upset. Although exercise rehabilitation after surgery is recommended, and sometimes delivered, this does not begin until the surgical wound has healed- several weeks after surgery. Similarly, although exercise prehabilitation has shown great potential, many older adults are unable to complete this. Emerging evidence suggests that a single bout of resistance exercise (sRET) before surgery may have potential to reduce postoperative losses of muscle mass and function in older cancer patients. However, how this strategy may be optimised, including interactions with nutrition is not yet known. This PhD will use state-of-the-art mass-spectrometry and novel imaging techniques to: i) identify the best form of sRET to promote muscle anabolism during subsequent immobilisation; ii) determine the impact of adjuvant protein nutrition on sRET-induced anabolism; and iii) determine the impact of optimised sRET in older colorectal cancer patients. This project will provide the successful candidate with varied skills and experience across the translational research pathway (i.e., bench-to-bedside).

Biological Sciences (4) Medicine (26)

Funding Notes

This is a fully funded studentship provided by the Medical Research Council. If successful, you will receive a stipend (currently £18,622 per year for 2023/24) and tuition fee waiver for 4 years. Successful candidates will also receive an allowance for a laptop, a travel and conference allowance plus allowance for laboratory/PhD running costs.
Click on the institution website link which will redirect you to the MRC AIM website which contains full application information including application forms to complete. Please ensure you submit your application before the deadline of midday (GMT) Friday 12 January 2024 as late applications will not be considered.

References

1. Farhan, H., Moreno-Duarte, I., Latronico, N., Zafonte, R. & Eikermann, M. Acquired Muscle Weakness in the Surgical Intensive Care Unit. Anesthesiology 124, 207–234 (2016).
2. van Wijk, L. et al. Risk factors for surgery-related muscle quantity and muscle quality loss and their impact on outcome. Eur. J. Med. Res. 26, 36 (2021).
3. Aoyama, T. et al. Body composition analysis within 1 month after gastrectomy for gastric cancer. Gastric Cancer 19, 645–650 (2016).
4. Low, D. E. et al. Guidelines for Perioperative Care in Esophagectomy: Enhanced Recovery After Surgery (ERAS®) Society Recommendations. World J. Surg. 43, 299–330 (2019).
5. Dirks, M. L., Hansen, D., Van Assche, A., Dendale, P. & Van Loon, L. J. C. Neuromuscular electrical stimulation prevents muscle wasting in critically ill comatose patients. Clin. Sci. (Lond). 128, 357–65 (2015).
6. Strasser, E. M. et al. Neuromuscular electrical stimulation reduces skeletal muscle protein degradation and stimulates insulin-like growth factors in an age- and current-dependent manner: a randomized, controlled clinical trial in major abdominal surgical patients. Ann. Surg. 249, 738–43 (2009).
7. Hardy EJO, Inns TB, Hatt J, Doleman B, Bass JJ, Atherton PJ, Lund JN, Phillips BE. The time course of disuse muscle atrophy of the lower limb in health and disease. J Cachexia Sarcopenia Muscle. 2022 Sep 14.
8. Brook MS, Stokes T, Gorissen SHM, Bass JJ, McGlory C, Cegielski J, Wilkinson DJ, Phillips BE, Smith K, Phillips SM, Atherton PJ. Declines in muscle protein synthesis account for short-term muscle disuse atrophy in humans in the absence of increased muscle protein breakdown. J Cachexia Sarcopenia Muscle. 2022 Aug;13(4):2005-2016.
9. Brook MS, Wilkinson DJ, Tarum J, Mitchell KW, Lund JL, Phillips BE, Szewczyk NJ, Kadi F, Greenhaff PL, Smith K, Atherton PJ. Neither myonuclear accretion nor a myonuclear domain size ceiling is a feature of the attenuated hypertrophic potential of aged human skeletal muscle.Geroscience. 2022 Sep 9 (Epub ahead of print).
10. Hardy EJO, Inns TB, Hatt J, Bass JJ, Atherton PJ, Lund JN, Piasecki M, Phillips BE. Postoperative electrical muscle stimulation attenuates loss of muscle mass and function following major abdominal surgery in older adults: A split body randomised control trial. Age and Ageing. Accepted for publication.
11. Williams JP, Phillips BE, Smith K, Atherton PJ, Rankin D, Selby AL, Liptrot S, Lund J, Larvin M, Rennie MJ. Effect of tumor burden and subsequent surgical resection on skeletal muscle mass and protein turnover in colorectal cancer patients. Am J Clin Nutr. 2012 Nov;96(5):1064-70.
12. Narici M, McPhee J, Conte M, Franchi MV, Mitchell K, Tagliaferri S, Monti E, Marcolin G, Atherton PJ, Smith K, Phillips B, Lund J, Franceschi C, Maggio M, Butler-Browne GS. Age-related alterations in muscle architecture are a signature of sarcopenia: the ultrasound sarcopenia index. J Cachexia Sarcopenia Muscle. 2021 Aug;12(4):973-982.
13. Ely IA, Jones EJ, Inns TB, Dooley S, Miller SBJ, Stashuk DW, Atherton PJ, Phillips BE, Piasecki M. Training-induced improvements in knee extensor force accuracy are associated with reduced vastus lateralis motor unit firing variability. Exp Physiol. 2022 Sep;107(9):1061-1070.
14. Wilkinson DJ, Bukhari SSI, Phillips BE, Limb MC, Cegielski J, Brook MS, Rankin D, Mitchell WK, Kobayashi H, Williams JP, Lund J, Greenhaff PL, Smith K, Atherton PJ. Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women. Clin Nutr. 2018 Dec;37(6 Pt A):2011-2021.
15. Weimann A, Braga M, Carli F, Higashiguchi T, Hübner M, Klek S, Laviano A, Ljungqvist O, Lobo DN, Martindale R, Waitzberg DL, Bischoff SC, Singer P. ESPEN guideline: Clinical nutrition in surgery. Clin Nutr. 2017 Jun;36(3):623-650.

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