​Liver and Pancreatic Cancer Research and Development charity (LAPR&D) is delighted to announce a new funding partnership with a research team based in Southampton University Hospital.  The project, led by Dr William Tapper, has attracted £35,000 of LAPR&D funding.  The project will undertake studies to produce a risk score which will assist in the prediction of pancreatic cancer.  The risk score should help identify population at risk of developing pancreatic cancer for secondary screening.  
 
Dr. Tapper comments “pancreatic cancer remains a stubbornly difficult cancer to treat and as with many cancers early detection is crucial to improving patient outcomes.  Often detection comes too late and survival rates remain low compared to other forms of cancer.  We are in the fortunate position of having access to the UK BioBank which retains samples that we can utilise to speed the research”.
 
The diagnosis of pancreatic cancer is challenging at early stages because of its hidden anatomical position and relatively low occurrence in population.  A change of pancreatic function is mainly translated to vague abdominal symptoms and deranged blood sugar.  Therefore, further innovative technologies to predict people at risk of pancreatic cancer is particularly important for early detection.  The aim is that this research programme will identify a group of people who will benefit from screening without major financial impact on the public health system.
 
Professor Andrew Collins & Dr. Zaed Hamady will support the project and regular updates will be provided here as progress is made.
 
The funds will be used, along with other secured funds, to employ a full-time PhD student to undertake the research.  Recruitment is underway to identify a suitable appointee.  
 
Kelvin Davis, LAPR&D Patron and former Southampton Football Club goalkeeper and captain stated “The Charity is delighted to be involved in this research.  The past 18 months have been very difficult for the charity sector generally to run events and raise funds and we are no exception.  It is therefore particularly pleasing to get underway again with our first major new funding initiative on such an important cause.”
 
LAPR&D strongly believe that raising awareness of pancreatic cancer and its signs and symptoms can save lives.  More than 50% of patients have never heard of pancreatic cancer before their own diagnosis and half the population cannot name a single symptom of pancreatic cancer – that’s why raising awareness is so vital!  Unlike many other forms of cancer, detection and cure rates have not improved in the last 40 years.
 
LAPR&D, via its world leading research programme based at the Southampton University Hospital, is trying to improve the life chances of those who contract this disease. 
 
You can find out more about the signs and symptoms of pancreatic cancer at: https://pancreaticcanceraction.org/about-pancreatic-cancer/symptoms.
The pancreas has two main functions – to aid digestion and regulate blood sugar levels.
 
The Liver and Pancreatic Research and Development cancer charity (registered Charity Number 1051543 and affiliated to the Southampton University Hospital Trust) was set up by surgeon Prof. Mo Abu Hilal in 2012 and several patients with liver and pancreatic diseases.  The charity, based at Southampton Hospital, aims to deliver improvements in the prevention, diagnosis and treatment of cancers of the liver and pancreas.  Further ways to support the charity can be found at: http://www.lapcancercharity.com
 
Press enquiries to: Paul Over tel: 07775706082 
email: Liverandpancreaticrd@gmail.com  
 
Picture credit: shows the position of the pancreas and its relation to adjoining organs and symptoms

LAPR&D are delighted to announce on World Cancer Day that £35,000 of Charity funds have been allocated to a team based at Southampton University Hospital @UoS_Medicine to lead research into identifying early signs of pancreatic cancer.  The project will be managed by @zaedhamady.   Look out for a full press release shortly!

​Created in 2000 World Cancer Day is a global initiative led by the Union for International Cancer Control (UICC) to face one of our greatest challenges.

Stay well, look after each other and a heartfelt thanks for staying with us during this difficult period.  Look out for a new research project in the New Year!

LAPR&D joined family and friends to celebrate charity supporter and cancer survivor Katrina Tottman’s 60th birthday. Florence Gimonet and Paul Over represented the charity at this special occasion held at the Old Thorns Hotel, near Liphook. We wish Katrina many more happy, healthy years ahead. Read more about Katrina's story.

Following the departure of our founder Professor Hilal to pastures new in Italy we are delighted to announce his sucessor Dr Nadeem Tehami BSc, MRCP (UK), MRCP Gastroenterology, FEBGH, FRCP (Glasgow).

Dr Tehami provides the expert medical input into the charity when considering research grant requests.  Dr Tehami is a consultant Hepatologist & HPB (Pancreas) physician.  He joined University Hospital Southampton UHS in August 2018.  He previously worked as a consultant Hepatologist & HPB (Pancreas) physician at Shrewsbury and Telford Hospitals NHS Trust. 

Dr Tehami's main clinical interests and specialisms are HPB medicine and endoscopy, endoscopy teaching and training, and improving patient care through education of other health professionals and service development.

He is an endoscopy training lead at UHS; Royal College of Physician MRCP PACES examiner; JAG accredited endoscopy trainer; member of BSG pancreas section and reviewer for Journal of Medical Sciences KMC.  Dr Tehami is interested in HPB endoscopy research and is regularly published, the latest example of which is: Attitudes to radiation safety and cholangiogram interpretation in endoscopic retrograde cholangio pancreatography (ERCP): a UK survey published in Frontline Gastroenterology (Dec 2020).

We look forward to working closely with Dr. Tehami over the coming months and are grateful for his expert input into our work.

​                                        ‘Isolation and expansion of human liver stem cells’

Principal investigators    Prof. Abu Hilal & Prof. Salim Khakoo    University of Southampton

Researcher                            Mogibelrahman Khedr    University of Southampton    

Collaborators                       Prof. Martyn Hill & Dr Peter Glynne-Jones    University of Southampton
                                                      Faculty of Engineering and the Environment

                                                      Dr Jonathan Dawson    University of Southampton    
​                                                      Bone and Joint Research Group, Faculty of Medicine
 
 Acknowledgments:

The research team wish to express their grateful thanks to the ‘Liver & Pancreatic R&D Cancer Charity’ for their funding and great support of the ‘Isolation and expansion of human liver stem cells’ project in University of Southampton.  We are also intensely thankful for the charity committee, charity members and all funders who worked hard to make this work possible. 
​
Introduction:

This project started initially with work on laboratory animals and involved isolation and growing of mouse liver cells.  This initial work, reported on elsewhere on the news section of the LAPR&D website, progressed to using human tissues which provide cells in cultures that resemble those that we have in our bodies.  Collectively, we have recruited patients and used collected tissues in 179 experiments.  In addition, we conducted 81 experiments involving cell lines and liver stem cells.
​
Objectives:
​
        1.    To grow and maintain functioning liver cells outside of the body and to identify a way to grow the cells as three dimensions model.
        2.    To allow for earlier drug experimentation on functioning cultured liver tissues with reduced risks to patients.
        3.    To isolate liver stem cells, grow them in the lab and evolve liver stem cells to mature liver cells with full liver functions.
        4.    In depth characterisation of newly formed cells at the functional and the genetic levels.
        5.    To apply for grants from further funding sources to continue and expand our work.

Ultimately the aim is to be able to grow a human cell outside of the body from the dna of the patient.  Once proven this will enable surgeons to remove the whole of the liver thereby increasing the change of leaving no cancer cells in the patient before replacing the “grown” liver into the patient.

Outcomes:

        1.    Succeeded in making liver cells grow.

We had studied the growth of liver cells in our laboratory and factors which help maintenance and growth of those cells. We made great progress in this area by unveiling the role of Vasoactive-Intestinal Peptide (VIP) the small protein that is normally found in our livers and which support liver cells to grow and proliferate.  These novel results were published in Wiley’s Journal of Cell Proliferation in 2018.  The full medical research article can be found here: https://doi.org/10.1111/cpr.12482
​
       2.    Identify a way to grow the cells in three dimensions. 

The second theme involved methods by which we can involve earlier experimentation of new drugs and reduce risk for patients.  Generation of liver tissue in the laboratory which closely resembles the function of our livers was the aim.  We had established a collaboration with the Faculty of Bioengineering at Southampton University to develop an ultrasound device which might enable us to grow liver cells in an environment resembling normal conditions and hence use it for drug screening.  We established a three dimensional (3D) hepatic cancer cell line culture.  The research successfully tested anti-cancer drugs in this model.  This model will provide an easy and safe way for drug toxicity screening and estimation of anti-cancer drug effect.  The results were published in The Journal of Acoustical Society of America in 2019.  The full medical research paper can be found here: https://doi.org/10.1063/1.5082603

In addition, clay could improve the generation of mature liver cells from stem cells.  Several experiments have been performed to explore some of the essential characteristics of the clay nanoparticle culture.  The team have had good success in modifying the clay matrix, as a composite, to permit culture of various cell type including cancer cell lines.  A new clay composite was successfully used as a 3D matrix for hepatocellular carcinoma cell line. The results confirmed the beneficial use of this material in growing liver cells.  This new technique has successfully led to the formation of sphere like cells in less than one week. These spheroids could be used in screening anti-cancer drugs and could mimic the response of cancer tissue present in the human body.  These results will be published soon.

      3.    Successfully isolated stem cells and evolve these stem cells to mature liver cells with full liver functions.
​
We were successfully able to isolate progenitor/stem cells (HPCs) in our laboratory.  We were able to characterize these rare cells, grow and maintain them.  In collaboration with Dr J Dawson from the Human Development & Health department at Soiuthampton University, a novel clay gel matrix has been tested.  The results show that material was able to push stem cells to form mature and functioning liver cells which is a promising step forward towards the fabrication of liver tissue in this gel.  The results of this interesting technique were presented to the national conference ‘The British Association for the Study of the Liver (BASL) Annual Meeting, York 2018’.

4.    In depth characterisation of newly formed cells at the functional and the genetic levels.
 
We have initially tested the functions of formed liver cells in clay material.  Although we have approval for an additional fund to perform a detailed analysis of cell functions and genetic characterisation, we are not able to conduct these experiments due to the Covid pandemic.

5.    Applications for grants.
 
Proposals for research grants have been submitted but have not been successful at present.

We have initiated a new collaboration with the ‘Centre of Regenerative Medicine, Edinburgh’, which is a world class centre in the field aiming to use the novel clay material on a wider scale for the cultivation of liver cells.  We have benefited from the experience and reputation of this centre to draft a proposal for a substantial Engineering and Physical Sciences Research Council (ESPRC) research fund.

Experimental summary:

Growth of liver cells in culture is a challenge.  Cells outside our bodies lack support from their neighbouring cells and separate them from chemical messengers which help their viability and growth.  We have therefore tested the addition of growth factors EGF and VIP to our cells in the culture dish.  This addition has a substantial impact on cell viability, growth and functionality.  Cells produced more albumin, metabolised proteins and urea with these factors added.  A beneficial effect has been demonstrated on liver cell genomic machinery which favours their functions and improves their growth. 

However, the culture of liver cells as a flat layer in laboratory flask is far removed from their organisation in our liver.  Therefore, the assembly of cells in a 3D structure is more physiological.  We had studied an ultrasound wave driven device to create a 3D liver cell culture.  Human liver carcinoma cell lines were used as a model for this technology.  The results show that cells in this device were viable and their functions were better than those grown conventionally.  Moreover, these micro-tissues may mimic the shape of tumour mass in patients which is critical for drug treatment.  The model was successful in showing the effect of anti-cancer drugs.  This is promising as a model for drug toxicity screening. 

In addition to ultrasound device, we have tested a clay gel material to grow cells in a 3D environment.  Interestingly, encapsulating cells in clay gel was found to be helpful in maintaining mature liver cells for longer time than conventional methods.  Moreover, liver cells were able to synthesise more albumin and metabolise urea better than when grown as a flat layer of cells.
Isolation and maintenance of human liver stem cell was challenging.  We have tried several methods including speed isolation and magnetic beads sorting, and we were successfully able to isolate a certain population with stem cell marker.  We have tried several forms of culture medium to maintain cells and fully characterise liver stem cells using their genetic signature such as Thy1, CK19 and Claudin 3.  Growing liver stem cells in clay gel was successful in generation of mature liver cells which was able to produce more albumin.  We have found that VIP treatment improves maintenance of our stem cells in culture.

Summary:

In summary, in our laboratory we have established research in the University of Southampton on liver mature and stem cells which will open the gates for further development, progress and research.  LAPR&D hope to be able to be involved in this promising future research when viable to do so.

Chief investigator:    Prof Mohammed Abu Hilal
Study Coordinator:  Christoph Kummerli
 
Without a spleen we run the risk of developing overwhelming (life-threatening) infections. Often the spleen is removed following pancreatic surgery and as a result lifelong antibiotics and vaccines are prescribed for patients. 

The aim of this study is to perform re-implant part of the spleen (26% of the original volume) in patients who lose their spleen during pancreas surgery and to investigate the performance of the re-implanted spleen with the antibody response to a Salmonella Typhi vaccine. Antibodies are measured before and after vaccination and a difference in antibodies will tell us how well the implanted spleen is performing.  In the long-term, the aim is to preserve the splenic function.

Patients are divided into three groups: spleen-preservation surgery (control group), splenectomy with splenic implantation (intervention group) and without (control group).

Since commencing the project the following centres have been recruiting appropriate patients:

• University Hospital Southampton, UK 
• Virginia Mason, Seattle, USA
• Poliambulanza, Brescia, Italy
• Birmingham University Hospital, UK
• Morriston Hospital, Swansea, UK

A further centre is in the process of setting up at the Miami Cancer Institute at Baptist Health, Miami, USA.

At the time of writing this report 28 patients have been recruited.  Progress in reaching the target of 45 by October 2020 might be impacted by the Covid-19 pandemic.  However, patients with low malignant cancer can now also be included. 
 
A further update report will be provided in 6 months time.  LAPR&D has committed to maintain its funding of this project despite the challenges presented by Covid-19.
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Picture: Christoph Kummerli (Study Coordinator) being presented with the research grant by Charity Chairman Kelvin Davis

LAPR&D pledge to continue to support vital research during the Covid-19 Pandemic  – LAPR&D has three important research projects underway at the present time (please see the Research section of this website for details).  However, they have all been impacted to differing degrees by the worldwide Covid-19 pandemic.  In some cases this is as a result of an inability to recruit patients due to non-critical operations being postponed or as a result of our researchers being utilised to support the fight against Coronavirus.  However, LAPR&D Chairman Kelvin Davis committed charity funds to the future of these projects and said “these projects remain vital to improve the life chances of those facing the challenges presented by liver and pancreatic cancer.  I have agreed that funding already promised towards these projects remains in place and project timescales will be extended where projects have been impacted by the Covid-19 pandemic. 

We wish all our researchers and charity supporters well over these difficult months ahead.  Our fundraising events will be postponed but we hope to be back with our exciting events once it is safe to do so.  In the meantime if you wish to donate please use the “donate” buttons on either our Facebook page or website.”