On November 20th, the Irish neuroblastoma researchers have met for the first time to set up a collaborative research hub. The aim is to consolidate their expertise and skills in order to crack the neuroblastoma code together.
They all have different science background spanning from molecular and cellular biologists, immunologists, tissue-engineering, bioinformatics, mathematical modelling and clinicians representing RCSI, UCD, TCD, OLCHC and NCRC. During this meeting, researchers talked about their challenges and progress finding out that we are complementing each other projects. Clinicians from different OLCHC departments exposed basic researchers to realities of the disease. None would find this information in academic papers: it is what you see in the clinic and how it works in practice.
Big thank you to Dr Cormac Owens for the invitation and linking us together and Prof Jacinta Kelly for mapping the support available from the NCRC and CMRF.
Our next meeting will be held in RCSI in January 2018.
Happy Birthday the Irish Neuroblastoma Research Consortium!
As a part of Science Week, our Department hosted Lab Safari for the secondary school students aiming to give a sense of what scientists do in the lab. The focus of my research is the identification of novel biomarkers for neuroblastoma response to chemotherapy. So, we decided to explain the concept of biomarkers and the importance of discovering novel biomarkers for neuroblastoma. Between me and John we covered biomarker’s basics and carried out the detection of MYCN in neuroblastoma cell lines. Here, I am summing up our activities in the form of Qs & As:
1. What are biomarkers?
Biomarkers are signposts of the body condition. Biomarkers – bio is for biological and markers – for molecules indicating that something is going wrong or differently in the body. They can help doctors to read these changes and identify a condition or disease. There are biomarkers for heart disease, cancer, diabetes and many others.
2. What type of molecules can serve as biomarkers?
Various types of molecules can do the job as long as they can differentiate the normal and abnormal process in the body. It can be DNA, RNA, proteins and hormones. These molecules can be detected in the blood, urine, stool, tumour tissue or any other bodily tissues or fluids.
3. How can we discover novel biomarkers?
Research, research and again research. We have to learn more basic facts about DNA, RNA and proteins. We need to be able to link this knowledge with health conditions including cancer. We need to identify how these molecules speak about the unhealthy conditions. We need to explore whether biomarkers exist within the disease that can predict the response to treatment and outlook.
4. What biomarkers are known in neuroblastoma?
There are various biomarkers that are specific for neuroblastoma. Catecholamines in urine are chemicals produced by neuroblastoma cells. Chromogranin A – is a protein that can be detected in the blood. It is unspecific biomarker because it can be secreted by neuroblastomas and some other tumours (e.g. pancreas and prostate cancer). Various chromosomal aberrations can be biomarkers of neuroblastoma aggressiveness. One of the strongest predictors of rapid neuroblastoma progression is MYCN status.
5. What is MYCN?
The MYCN is a proto-oncogene protein and a member of the MYC family of transcription factors. MYCN was identified in 1983 and very soon became a routine biomarker for neuroblastoma aggressiveness. This protein is very important for the normal embryo development. The amplification of this gene leads to the excess of MYCN protein in cells prompting cells to grow and divide faster transforming normal cells into tumour cells.
6. How did we detect MYCN in neuroblastoma cell lines?
A day before the demonstration, we carried out some preparation steps. We selected several neuroblastoma cell lines with known MYCN status. Some cell lines had MYCN amplification, other didn’t. Among those that did have the amplification, the expression of MYCN protein was different giving us a good illustration of biomarker’s quantity. So, we run SDS-PAGE, a technique that helps to separate the cellular protein mix based on their size.
Then the separated proteins were transferred onto a membrane and exposed to a buffer containing an antibody for MYCN (primary antibody). This antibody recognises only MYCN. At the next step, we added another antibody that has a dual role – it can attach to the primary antibody and produce a signal that can be visualised. The next step would have been the visualisation itself and the one for Lab Safari. So, we were ready.
Once we finished the basics of biomarkers, we moved to the biomarker MYCN detection step. The buffer for visualisation was added and the membrane was imaged.
If you like this idea and want to have this demonstration for your science classes at school, please contact me and we would be happy to do it for you.
The focus of the scientific program was on “Translating Science into Survival”. Talks covered the challenging areas in cancer immunology and immunotherapy. The full list of topics can be found in the meeting program.
At the moment cancer immunology and immunotherapy is a hot topic in the next generation of anti-cancer therapies. Lots of attention is given to checkpoint immunodrugs as it was proven by the prevalence of talks on this subject in the program. Indeed, this drug has great potential, but at the same time, it is not universal. About 50% of patients do not benefit from it.
What lessons have been learned from the talks:
Checkpoint immunotherapies are the main stream
Not all cancer patients would respond to immunodrug
Genetic landscape of a tumour and/or the patient may contribute to this, thus making beneficial to check genetics for this type of treatment
Immunodrugs work better in combination with conventional therapies such as chemotherapy.
The immune system can be tuned by a drug, but it will switch on compensatory mechanisms to balance the intervention.
On Saturday – April 9th, the Conor Foley Neuroblastoma Cancer Research Foundation had their annual fundraising Dinner. This year the theme of the Dinner was Jungle Jazz in memory of the favourite movie of Conor – Madagascar at Trim Castle Hotel.
So many people came to support this fantastic family. The family, who lost their beloved son to neuroblastoma, but has found unacceptable to stop their fight against neuroblastoma. They do know that a cure won’t be found tomorrow. Instead, it may take time, money and efforts to crack the code of this disease so other kids can do better. Thier deal with the situation is priceless and infectious – none can stand still around.
If you asked me after completion of my PhD, would I have ever thought of further education? I would have said – unlikely. Maybe short-term courses to advance my skills, but definitely no to a different field and a 2 years commitment.
Never say never. About four years ago, I started to feel uncomfortable with where I was – a piece of my life jigsaw was missing… I looked up different courses for further education in my field and for anything just relevant to my day job, like project management or teaching. I was even looking around for another job. But nothing…Nothing could be compared with my long life affair – science. This is the only thing that fuels me regardless the career or grant success trajectory.
Ten years after PhD I decided to do Masters in Science Communication, but part-time. The full-time job, family and research challenges did not leave me a choice. This was the same missing piece of the jigsaw. There were a lot to learn exploring another dimension – social sciences. All concepts and ideas of social sciences were studied through lenses of my current interests: cancer research, gender issues, science for public to name the least.
The experience was priceless. It is also inspired me to look outside the ‘box’, see research everywhere and communicate it, and last but not least to start my own blog.
This is the first time in the history of the IACR meetings when an entire plenary session is solely dedicated to challenges and advancements in childhood cancer.
This session will unite Internationally recognised leaders in childhood cancer research. They will speak about what we know about origin and evolution of childhood cancers (Prof. Tariq Enver), how blood biomarkers can help in stratification and treatment of children (Prof. Sue Burchill), what impact Down syndrome has in the white blood cell cancer development and progression (Prof. Irene Roberts), how epigenetic changes affect tumour pathogenesis and future of therapeutics targeting theses changes (Prof Raymond Stallings).
Childhood cancer is an umbrella term for a great variety of malignancies which vary by site of disease origin, tissue type, race, sex, and age.
The cause of childhood cancers is believed to be due to faulty genes in embryonic cells that happen before birth and develop later. In contrast to many adult’s cancers, there is no evidence that links lifestyle or environmental risk factors to the development of childhood cancer.
Every 100th patient diagnosed with cancer is a child.
In the last 40 years the survival of children with most types of cancer has radically improved owing to the advances in diagnosis, treatment, and supportive care. Now, more than 80% of children with cancer in the same age gap survive at least 5 years when compared to 50% of children with cancer survived in 1970s-80s.
Childhood cancer is the second most common cause of death among children between the ages of 1 and 14 years after accidents.
Unfortunately, no progress has been made in survival of children with tumours that have the worst prognosis (brain tumours, neuroblastoma and sarcomas, cancers developing in certain age groups and/or located within certain sites in the body), along with acute myeloid leukaemia (blood cancer). Children with a rare brain cancer – diffuse intrinsic pontine glioma survive less than 1 year from diagnosis. Children with soft tissue tumours have 5-year survival rates ranging from 64% (rhabdomyosarcoma) to 72% (Ewing sarcoma).
For majority of children who do survive cancer, the battle is never over. Over 60% of long‐term childhood cancer survivors have a chronic illness as a consequence of the treatment; over 25% have a severe or life‐ threatening illness.
This week can be rated for sure as feeling good, excited and accomplished. A UK based charity – Neuroblastoma UK has awarded a small grant to characterise a pre-clinical model of neuroblastoma which is a collaborative project between our lab and Tissue Engineering Research Group at RCSI. This project will study features of neuroblastoma cells growing on collagen-based scaffolds. The NBUK grant will contribute to one of the most expensive parts of the study – characterisation of cell secreting proteins using antibody-based profiling platforms.
Another research was accomplished yesterday – John Nolan had his Voice Viva examination and successfully defended his PhD Thesis. This 3 year PhD project was funded by the National Children’s Research Centre. As his supervisor, I am delighted for him and wish him best of luck in his research career.