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Cancer: Evaluating ultrasound guided tumour resection using gadolinium-conjugated nanoparticles in colorectal and brain cancer

PGR-P-398

Key facts

Type of research degree
4 year PhD
Application deadline
Ongoing deadline
Country eligibility
International (outside UK)
Funding
Non-funded
Additional supervisors
Ryan Mathew, Aaron Quyn, David Jayne
<h2 class="heading hide-accessible">Summary</h2>

Surgical margins are a key predictor of oncological outcomes. Recurrent pelvic malignancy and primary brain malignancy both rely on accurate MRI based imaging to predict margins and determine surgical plains. Intra operatively, there are few accepted techniques to determine this accuracy and residual malignant cells residing in the margins of these cavities, according to the cancer cell hypothesis, these residual cells have been proposed to be responsible for resistance to treatment and subsequent recurrence. <br />

<h2 class="heading hide-accessible">Full description</h2>

<p paraeid="{cc785095-b778-4447-b9fb-0fe4256e60bc}{203}" paraid="850526725">Identifying malignant margins and specifically these residual cells is a surgical challenge as they are intermingled with normal tissue, and usually beyond the realms of current intra-operative imaging technology. This subsequently limits extent of resection (linked to outcomes such as progression free and overall survival). Such cancers (including residual cells) can usually be readily visualised on post-operative gadolinium-enhanced magnetic resonance imaging (MRI). We propose that an established gadolinium-conjugated nanoparticle, AGuIX (TherAGuIX, Lyon) may be used in conjunction with ultrasound (USS) in real-time analysis of these tumours. This approach utilises the combined advantages of the nanoparticle &ndash; selective due to the gadolinium and echogenic due to the particle itself.&nbsp;</p> <p paraeid="{cc785095-b778-4447-b9fb-0fe4256e60bc}{203}" paraid="850526725">After securing ethical approval and local new interventional procedures group (NIPG) approval at Leeds Teaching Hospitals NHS Trust (already in progress due to another project using these nanoparticles), the project would deliver 4 workstreams.&nbsp;</p> <ol role="list" start="1"> <li aria-setsize="-1" data-aria-level="1" data-aria-posinset="1" data-font="Arial" data-leveltext="%1." data-listid="20" role="listitem"> <p paraeid="{cc785095-b778-4447-b9fb-0fe4256e60bc}{209}" paraid="1912882232">Determine&nbsp;AGuIX&nbsp;nanoparticle uptake variability within brain and recurrent pelvic tumours&nbsp;</p> </li> </ol> <ol role="list" start="2"> <li aria-setsize="-1" data-aria-level="1" data-aria-posinset="2" data-font="Arial" data-leveltext="%1." data-listid="20" role="listitem"> <p paraeid="{cc785095-b778-4447-b9fb-0fe4256e60bc}{220}" paraid="683278425">Determine sensitivity of&nbsp;AGuIX&nbsp;detection within residual tumour following resection&nbsp;</p> </li> </ol> <ol role="list" start="3"> <li aria-setsize="-1" data-aria-level="1" data-aria-posinset="3" data-font="Arial" data-leveltext="%1." data-listid="20" role="listitem"> <p paraeid="{cc785095-b778-4447-b9fb-0fe4256e60bc}{231}" paraid="44830287">Determine sensitivity of USS at detecting&nbsp;AGuIX&nbsp;intraoperatively&nbsp;</p> </li> <li aria-setsize="-1" data-aria-level="1" data-aria-posinset="4" data-font="Arial" data-leveltext="%1." data-listid="20" role="listitem"> <p paraeid="{cc785095-b778-4447-b9fb-0fe4256e60bc}{246}" paraid="655877336">Development of imaging techniques to identify residual tumour margins/cells.&nbsp;</p> </li> </ol> <p paraeid="{06c95b3a-75c2-48fe-b322-8e629da4a321}{2}" paraid="2062621734">If the clinical workstreams of the project progress well, the student will have opportunities to perform mechanistic studies in established brain and colorectal cancer in vivo models.&nbsp;</p> <p paraeid="{06c95b3a-75c2-48fe-b322-8e629da4a321}{2}" paraid="2062621734">Techniques associated with the project</p> <p paraeid="{06c95b3a-75c2-48fe-b322-8e629da4a321}{2}" paraid="2062621734">Ultrasound, immunohistochemistry,&nbsp;electron microscopy, cell culture,&nbsp;biological functional validation,&nbsp;qRT-PCR&nbsp;ethics, MRI imaging,&nbsp;</p> <p paraeid="{06c95b3a-75c2-48fe-b322-8e629da4a321}{2}" paraid="2062621734">References</p> <ol role="list" start="1"> <li aria-setsize="-1" data-aria-level="1" data-aria-posinset="1" data-font="Calibri" data-leveltext="%1." data-listid="21" role="listitem"> <p paraeid="{06c95b3a-75c2-48fe-b322-8e629da4a321}{56}" paraid="1982204868">Lux F, Tran VL, Thomas E, et al&nbsp;AGuIX((R)) from bench to bedside-Transfer of an&nbsp;ultrasmall&nbsp;theranostic&nbsp;gadolinium-based nanoparticle to clinical medicine. Br J Radiol.2018 20180365.&nbsp;</p> </li> </ol> <ol role="list" start="2"> <li aria-setsize="-1" data-aria-level="1" data-aria-posinset="2" data-font="Calibri" data-leveltext="%1." data-listid="21" role="listitem"> <p paraeid="{06c95b3a-75c2-48fe-b322-8e629da4a321}{75}" paraid="1703955999">Sanai N and Berger M. Operative Techniques for Gliomas and the Value of Extent of Resection.&nbsp;Neurotherapeutics&nbsp;2009;6:478-486&nbsp;</p> </li> </ol> <ol role="list" start="3"> <li aria-setsize="-1" data-aria-level="1" data-aria-posinset="3" data-font="Calibri" data-leveltext="%1." data-listid="21" role="listitem"> <p paraeid="{06c95b3a-75c2-48fe-b322-8e629da4a321}{86}" paraid="1961785123">PelvEx&nbsp;Collaborative.&nbsp;<a href="https://www.ncbi.nlm.nih.gov/pubmed/28938268" rel="noreferrer" target="_blank">Surgical and Survival Outcomes Following Pelvic Exenteration for Locally Advanced Primary Rectal Cancer: Results&nbsp;From&nbsp;an International Collaboration.</a>&nbsp;Ann Surg. 2019 Feb;269(2):315-321.&nbsp;</p> </li> </ol> <p paraeid="{06c95b3a-75c2-48fe-b322-8e629da4a321}{86}" paraid="1961785123">This project is part of the&nbsp;<a href="https://medicinehealth.leeds.ac.uk/leeds-institute-research-st-james/doc/international-phd-academy-medical-research">International PhD Academy: Medical Research</a></p> <p paraeid="{06c95b3a-75c2-48fe-b322-8e629da4a321}{86}" paraid="1961785123"><strong>In line with the bespoke nature of our International PhD Academy a modified PhD project can be proposed dependent on students interests and background.</strong></p>

<h2 class="heading">How to apply</h2>

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. To apply for this project applicants should complete an <a href="http://www.leeds.ac.uk/info/130206/applying/91/applying_for_research_degrees">online application form</a> and submit this&nbsp;alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates. Please make it clear in the research information section that you are applying for the International PhD Academy: Medical Research, as well as the title of the project you wish to be considered for.</p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="https://medicinehealth.leeds.ac.uk/downloads/download/130/faculty_graduate_school_-_scholarship_reference_form">references</a> on your behalf, directly to <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p>

<h2 class="heading heading--sm">Entry requirements</h2>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

<h2 class="heading heading--sm">English language requirements</h2>

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD are: &bull; British Council IELTS - score of 7.0 overall, with no element less than 6.5 &bull; TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.

<h2 class="heading">Contact details</h2>

<p>Informal enquires about regarding the bespoke taught first year of the PhD programme and research projects can be made by contacting LIMRPhD@leeds.ac.uk.</p> <p>Enquiries regarding the application process should be directed to the Faculty of Medicine and Health Graduate School Office e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>, t: +44 (0)113 343 8221.</p>


<h3 class="heading heading--sm">Linked research areas</h3>