#NCRC – Page 2 – Blog about neuroblastoma research

Remote Research Projects

Regardless COVID19 pandemic, we continue to host undergraduate students from various Universities for their research projects. Two students, Carla and Chris, from the Technical University of Dublin, carried out BSc projects remotely. Having in-house datasets and many more published in open access, their projects were focused on bioinformatics, re-analysing them and giving a second look. Both Carla’s and Chris’ research received the highest score in their classes. Many congratulations – well deserved!! We wish to thank both for their kind words and willingness to share their story.

*Chris Sheridan, the final year student in Biomolecular Science at the Technical University of Dublin, 2021*

“My project concerned analysing the exosomal miRNA expression of neuroblastoma cells in response to chemotherapy. Though the project was not too large, it certainly was the largest project I have ever taken part in. The work Dr. Piskareva and her team are conducting is so interesting and novel that I felt very fortunate to be participating in such an exciting field. Despite the novel and complex nature of the topic, the project was extremely engaging, allowing for an opportunity to learn new valuable research and data analysis skills. I was able to get very useful and helpful feedback regularly from everyone on the research team, where there was a very welcoming and positive attitude. This made the topic seem less daunting and my goals more achievable. I was really happy with my results, and I am excited to see where they may lead in the future. Some of the miRNAs identified in the analysis may represent potential biomarkers or therapeutic targets for high-risk neuroblastoma patients. As I have yet to experience any lab-based research, it was cool to see the team’s approaches and applications of lab techniques and analysis strategies to see how research is conducted in the “Real World” after seeing these topics before only in lecture notes. Overall, the project was challenging but very rewarding and enjoyable. Throughout the project, the overall experience, the excitement of the results coming together, and the realisation that I may have something to contribute to this field of research cemented the idea in me that this is certainly the path I wish to pursue in science and for that, I would like to thank Dr. Piskareva and her team for such a positive and educational experience during my time with them.“

*Carla Tejeda Monné, the final year Technological University of Dublin Biomolecular Science Student, specialising in Biotechnology, Therapeutics, and Drug Development*, 2021

“During my final year project, I had the unique and amazing opportunity to work under the supervision of Dr. Olga Piskareva. The purpose of my thesis was to assess the clinical significance of Tumour Necrosis Factor Receptor Superfamily Member 1B and Member 4 (TNFRSF1B and TNFRSF4) in neuroblastoma patients. I accomplished this by analysing the gene profiles of several tumours using bioinformatic tools. In addition, I investigated the potential of microRNAs as therapeutic agents for neuroblastoma treatment. I thoroughly enjoyed carrying out this research project, and I hope the findings from my thesis can aid future research into the pathogenesis of neuroblastoma and the development of effective treatments for these children.“

Best of luck to Chris and Carla in their next endeavour!

Sparkles of A Researcher Day

Once I mentioned the importance of the publication track record for a career in science. My team has been productive despite the COVID pandemic. Two review articles were published.

The first was a review written by Tom and published in Cancers focusing on the small extracellular vesicles produced by cancer cells that can transfer various growth signals to the tumour microenvironment aka neighbourhood and promote tumour expansion. The signal in focus was a protein called epidermal growth factor receptor (EGFR). It contributes to the healthy fitness of many different cells in the body. However, many cancer cells produce an excess of this protein giving them an advantage of growth over normal cells. Increased EGFR can be seen in breast, lung, glioblastoma and head and neck cancers.

*Cancers* **2020**, 12(11), 3200; https://doi.org/10.3390/cancers12113200

The second review has been published in Journal of Personalized Medicine on March, 16th. Originally, it was a small review project for Nadiya, a medicine student, last summer. However, it became a big one with all data systematically collected, analysed and condensed. The focus of this review was on Retinoic Acid (RA), widely known as Vitamin A and its role in neuroblastoma. RA plays a vital role in human development. The main feature of RA is to push neuroblastoma cells to become neuron-like cell stopping their aggressiveness and cancer fate. So, we wanted to know more about the ongoing research both in the labs and the clinic. We reviewed primary research articles reporting basic and translational findings as well as clinical trials. Hopefully, it would help other researchers to get a full picture of this topic and a structured resource of experimental models and drugs tested.

*J. Pers. Med.* **2021**, 11(3), 211; https://doi.org/10.3390/jpm11030211

Annual NCRC Symposia 2020

As the year comes to an end, you are looking back and seeing all achievements in a different light, a light of the COVID glaze. Lab research was at bay for a while, challenges to return and re-start experiments, no scientific meetings in the traditional format where you build your new collaborative net at coffee breaks. Despite all, the team has expanded and we welcomed Ellen and Erin in October.

The NCRC Winter Symposia is a lovely way to wrap the year putting together all hard work and look at the progress done so far. We have an exciting project that has two arms: a blue-sky science and a translational. Working together John and Tom were able to generate promising results on understanding how small membrane-bound vesicles or exosomes can send signals from neuroblastoma cells to cells responsible for new blood vessels formation. They developed a protocol to scale up the production of exosomes, isolate them and characterise. We have a dataset on what these exosomes carry on and now can test how they promote new blood vessels formation. Indeed, more left to do but knowing the direction makes this journey meaningful.

Hallmarks of Research

Research is a fascinating journey no doubt. Inquisitive minds try to solve burning puzzles. It takes time. Some puzzles are more complected than the others. One of the hallmarks is the conversion of the resolved puzzle into a scientific story to tell to your peers.

We write and publish these stories. The publishing is another caveat that often makes your story sharper and neater. However, while you are in the process you feel that the mission is impossible.

Delighted to see that one of the missions is completed – a great hallmark for John which coincided with his new research adventure starting in a few days. This is his first first author paper! It is not tautology! It is his first original research paper where he is the first author. This position is a success measure in a research career. His teamwork skills secured him another few original papers. Well done John! Well deserved!

This study is an excellent example of the many roles that small RNA molecules such as miR-124-3p can play in neuroblastoma pathogenesis. The ability of this miRNA to work together with standard chemo drugs can be exploited further in the development of new anticancer therapeutics targeting relapse and drug-resistant tumours.

Hot Chocolate Morning In Aid of ICCD2019

Across countries and continents, we are celebrating International Childhood Cancer Day (ICCD).We do it to raise awareness tto raise awareness of childhood cancer, its consequences for children and their parents and make it as a priority for Governments and research.

My team research is focused on neuroblastoma biology. This is a solid tumour of undeveloped nerves. Some forms of neuroblastoma spread quickly and become very aggressive and challenging to treat. We are searching for the weaknesses that can be targeted with drugs.

Today, we team up with Amorino to run the Hot Chocolate Morning to raise funds for Childhood cancer research charities – Children’s Medical Research Foundation/National Children’s Research Centre and the Conor Foley Neuroblastoma Cancer Research Foundation. Research advances our knowledge and helps to develop new treatments.

A guessing game was a part of the event. Everyone had a chance to guess how many marshmallows fitted in the cell culture flask T75. The guesses ranged from as low as 95 to as high as 500. Fortunately, one of the participants gave an absolutely correct answer. Micheal Flood put on 173 and won. Her fantastic ability to guess is incredible! Congratulations!!! Well done to all!

We raised 698.91 Euros for childhood cancer research! We thank everyone who came along and supported the Hot Chocolate Morning & the International Childhood Cancer Day 2019!

Many special thanks go to Amorino for delicious Italian hot chocolate & tasty bites contributors!

September is Childhood Cancer Awareness Month!

Today marks the start of Childhood Cancer Awareness Month.

The cause of childhood cancers is believed to be due to faulty genes in stem cells that give rise to nerves, skin, blood and other body tissues. For some unknown reasons, the faulty genes can sit quiet and show their ‘bad’ character after birth and programme the cells into cancer cells.
So, there is no evidence that links lifestyle or environmental risk factors to the development of childhood cancer, which is opposite to many adult’s cancers.

Every 100th cancer patient is a child. Cancer is the 2nd most common cause of death among children after accidents.

Children are not little adults and so their cancer. Some childhood cancers have a good outlook and successful protocol of treatments. However, some of the cancers do not respond to the known drugs, or if respond cancer cells find the way to develop resistance and come back being more aggressive. Among theme are some forms of 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). Less than50% of children with the aggressive form of neuroblastoma will live beyond 5 years with current treatment strategies.

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.

The most common types of childhood cancer are:

Leukaemia and lymphoma (blood cancers)
Brain and other central nervous system tumours
Muscle cancer (rhabdomyosarcoma)
Kidney cancer (Wilms tumour)
Neuroblastoma (tumour of the non-central nervous system)
Bone cancer (osteosarcoma)
Testicular and ovarian tumours (gonadal germ cell tumours)

Please see a short video The Childhood Cancer Ripple Effect created by St. Baldrick’s Foundation.

A new, three-dimensional approach to cancer research

Appeared in today’s Irish Times. Lovely crafted by Dr. Vanesa Martinez

Although the discovery could be applicable in principle to any a solid tumour, Dr Piskareva’s target is neuroblastoma, a relatively common child cancer which affects a specific type of nerve cells in unborn children. “It’s quite aggressive and unfortunately there are many children who have metastasis when they are diagnosed, and this is the most challenging group to treat.”

https://www.irishtimes.com/news/science/a-new-three-dimensional-approach-to-cancer-research-1.3505347

How current IT advances help in research?

Here is the perfect example of the teamwork troubleshooting protein extractions. My Dream Team 2018 in action. The current information and communication technologies allow to stay connected and respond quickly.

Five minutes later in the lab: troubleshooting is the exchange of experiences!

A new 3D strategy to study neuroblastoma

Our body has 3 dimensions: height, width and depth. Every single part of our body grows in the same 3 dimensions. This is true for cancer cells. Researchers use different ways to study cancer cells behaviour, how they grow and spread. We grow cells in the flasks, where they change their structure and shape and become flat losing one dimension. This is a very popular approach. We also grow cells in mice, where cells keep their 3D shape and mimic their behaviour to one observed in humans.

It is well known that we need to give a different amount of drug to kill cancer cells grown in flasks and in mice. This, in turn, delays the development of new drugs. Why does it happen this way? So, the drug works only on one side of the cell when they grow on the flat surface. In contrast, in mice, drug surrounds the cancer cell habitat and attacks cells at the edge first and then getting to those at the core. So we need more drug to kill cancer cells in mice.

We decided to design a new way to grow cancer cells that recreate their growth in 3 dimensions as in the human or mice body. We used special cotton wool like sponges as a new home for cancer cells and populated them with cancer cells. At the next step, we gave cells the drug at the different amount and checked what happened.

To understand cell fitness we stained them with red and blue dyes. On the left bottom side of the image, we see an equal amount of red and blue dyes telling us that cells were healthy and fit. Cells did not get any drug. When we gave a little amount of the drug but enough to kill cells in the flask, the balance of red and blue dyes was the same telling us that nothing really happened (the image in the middle). Cells were feeling well and healthy. The right bottom image has only blue dye. In this case, cells were given the amount of drug enough to destroy cancer cells in mice or humans. The lack of red dye tells us that this time the drug worked and killed the cancer cells.

We found that the drug killed cells on sponges only at doses enough to do the same in mice.

So, we concluded the new tactic to grow cancer cells in 3D on cotton-like sponges can bridge the gap between traditional way and animal models. This new strategy to grow cells on sponges should help to understand cancer cell behaviour better and accelerate the discovery and development of new effective drugs for neuroblastoma and other cancers. This, in turn, will make the outlook for little patients better and improve their quality of life.

This work has been published in Acta Biomaterialia and presented recently at the Oral Posters Session at the 54th Irish Association for Cancer Research Conference 2018.

This study was supported by Neuroblastoma UK and National Children’s Research Centre.

You can find more at

A physiologically relevant 3D collagen-based scaffold–neuroblastoma cell system exhibits chemosensitivity similar to orthotopic xenograft models.

IACR Meeting 2018 Programme

Goodbye 2017! Hello 2018!

When I look back on my journey in 2017, there were many junctions, traffic lights and stops as well as ups and downs. Junctions were to make decisions, while traffic lights and stops – to be patient. Ups and downs were my feelings of satisfaction. The good mix of both kept me to stay human. It is not the number of grants received that matters it is who around you. I have met genuinely curiosity-driven students who made this journey fascinating and very special.

My most memorable Ups were the successful examination and graduation of my PhD student John Nolan, organisation and chairing the IACR Meeting session: Challenges in Childhood Cancers, the Mad Hatter’s Tea Party and the Gala Dinner with the CFNCRF, the launch of my very own research team thanks to the funding by the NCRC and the Neuroblastoma UK, the successful completion of two final year undergraduate and two MSc projects, and welcoming the new PhD student Tom Frawley.

My team is growing and I am looking forward to 2018!

Tag: #NCRC