This summer I worked under Dr Piskareva supervision in the remote research program. My original plans for a lab experience were put down by COVID. My ultimate goal was to write the review article on the potential uses of retinoic acid in neuroblastoma research.
Nadiya Bayeva
Before starting the project, I didn’t have any specific expectations. While I always had fun picking the primary articles apart and summarising the gathered data during my undergrad and med school, I didn’t believe that this experience would be the special one. And I kept thinking so as I was collecting the information from the numerous data on cell cultures. And as I was looking at the mice models studies. And clinical trials.
Then I started to write my introduction, and so researched the information on the neuroblastoma prognosis, contemporary treatment protocol and outcomes. And suddenly I saw my project in the new light. I was used to regarding the clinical trials outcomes as simple statistics, but this time no desensitization could shield me. Yes, 60% of the patients in the high-risk group die in 5 years after diagnosis, and yes, 90% of those patients are children less than 5 years old. And there is nothing that we could currently do to save those children.
On the other hand, this realisation brought meaning to my work. This time, I was not doing a PubMed search to get a good mark or CV reference. Instead, I was looking for the possible treatment of the disease. My review on the current knowledge about retinoic acid will let the other primary researchers target the most promising drug for future experiments and, eventually, create a novel and effective therapy to help those children.
And isn’t it what we are all striving for in medical research?
Today marks the start of Childhood Cancer Awareness Month.
Three girls fountain in Mainz Germany
I like this photo of a lovely fountain capturing 3 girls under umbrellas (Drei-Mädchen-Brunnen) in Ballplatz Mainz. It is about a happy childhood; every child deserves a happy childhood. So, I select it again to support #ChildhoodCancerAwarnessMonth.
Childhood cancer is an umbrella term for many other types of this disease. This month is a big channel to support and learn more about kids with cancer, their loving families, the doctors and caregivers who looking after them and treating them, the young survivors of cancer and those kids and teens who lost their battle, and the scientists who working hard to find a way to stop childhood cancer.
When it comes to a disease, we have to acknowledge that children are not little adults. They are constantly developing. So their diseases have a different way to progress and respond to treatment. This is very true for childhood cancers. For example, children diagnosed with neuroblastoma before a 1.5 years old mark will do better than older children.
Every 100th cancer patient is a child. Cancer is the 2nd most common cause of death among children after accidents. 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)
Here, we are – the Irish neuroblastoma research team landed at the 5th Neuroblastoma Research Symposium in Cambridge. Four poster presentations by four enthusiastic scientists. The two days crash course in neuroblastoma – vibrant, intense, informative.
I had one of the most enjoyable poster sessions in the last few years! A genuine interest in our 3D in vitro cancer models by both academics and Industry. Hope, to keep the ball rolling and strengthen these new links.
The Symposium programme was an excellent balance of the new transnational outcomes with hardcore developmental cellular programmes. From ‘How neuronal precursors select their fate and how they can escape the developmental constraints? How this knowledge can help to advance our understanding of neuroblastoma aetiology?’ to ‘New drugs that demonstrated great potency in pre-clinical studies’ via ‘how we can work together more efficiently to progress quicker’
Indeed, the success of the research meeting became possible thanks to the strategic vision and leadership of organisers!
13:00 – 13:10 Introduction – Neuroblastoma UK & CRUK Cambridge Centre
Session 1: Neuroblastoma biology & prognosis
Cancer Research UK Cambridge Centre Neuro-oncology Programme Session
Chair: Kate Wheeler (Oxford Children’s Hospital)
13:10 – 13:40 Sandra Ackermann (Cologne): The genetic basis of favourable outcome and fatal tumour progression in neuroblastoma
13:40 – 14:10 Rogier Versteeg (Amsterdam): The dark side of neuroblastoma
14:10 – 14:40 Katleen de Preter (Ghent): Improved diagnosis and risk stratification of paediatric cancers using liquid biopsies
14:40 – 14:55 Sue Burchill (Leeds): Self-renewing neuroblastoma cells isolated from bone marrow aspirates of children with stage M disease share a mesenchymal expression signature: an NCRI CCL CSG Neuroblastoma Group Study
14:55 – 15:15 Combined discussion
15:15 – 15:45 Tea with Posters
Session 2: Targeted & combination therapy I
Cancer Research UK Cambridge Centre Neuro-oncology Programme Session
Chair: Marie Arsenian Henriksson (Karolinska)
15:45 – 16:15 Frank Westermann (Heidelberg): Novel metabolic dependencies of MYCN-driven neuroblastoma
16:15 – 16:45 Gerard Evan (Cambridge): Is Myc really master of the universe?
16:45 – 17:00 Melinda Halasz (University College Dublin): Anti-Cancer Effects of Diphenyleneiodonium Chloride (DPI) In MYCN-Amplified Neuroblastoma
17:00 – 17:15 Evon Poon (ICR, Sutton): Pharmacological blockade of high-risk MYCN driven neuroblastoma using an orally-bioavailable CDK2/9 inhibitor
17:15 – 17:35 Combined discussion
Downing College – Main Hall.jpg
17:35 – 19:15 Poster viewing & Drinks
19:30 Symposium Dinner at Downing College (map for dinner)
FRIDAY 12TH APRIL 08:30 – 08:50 Coffee & pastries
Session 3: Neural crest & differentiation therapy I
Chair: Margareta Wilhelm (Karolinska)
08:50 – 09:20 Igor Adameyko (Karolinska): Normal development of sympathoadrenal system resolved with lineage tracing and single cell transcriptomics
09:20 – 09:50 Quenten Schwarz (Adelaide): Guiding sympathoadrenal neural crest cells to the adrenal primordia
09:50 – 10:05 Claudia Linker (King’s College London): Notch coordinates cell cycle progression and migratory behaviour leading to collective cell migration
10:05 – 10:20 Combined discussion
10:20 – 10:50 Coffee with Posters
Session 4: Neural crest & differentiation therapy II
Chair: Gareth Evans (York)
10:50 – 11:20 Karen Liu (King’s College London): ALK and GSK3 – shared features of neuroblastoma and neural crest
11:20 – 11:35 Anestis Tsakiridis (Sheffield): Efficient generation of trunk neural crest and sympathetic neurons from human pluripotent stem cells via a neuromesodermal progenitor intermediate
11:35 – 12:05 Anna Philpott (Cambridge): Using developmental mechanisms to drive differentiation of neuroblastoma
12:05 – 12:20 Combined discussion
12:20 – 13:20 Lunch with Posters
Session 5: Targeted & combination therapy II
Chair: Bengt Hallberg (Gothenburg)
Cancer Research UK Cambridge Centre Paediatrics Programme Lecture:
13:20 – 13:50 Sharon Diskin (Philadelphia): A multi-omic surfaceome study identifies DLK1 as a candidate oncoprotein and immunotherapeutic target in neuroblastoma
13:50 – 14:05 Donne Nile (Glasgow): Manipulation of cancer cell metabolism for neuroblastoma combination therapy with targeted radiotherapy
14:05 – 14:35 Suzanne Turner (Cambridge): CRISPR-dCas9 screens to identify resistance mechanisms to ALK in neuroblastoma
14:35 – 14:50 Combined discussion
14:50 – 15:20 Tea with Posters
15:20 – 15:30 Poster prizes
Session 6: Targeted & combination therapy III
Chair: John Lunec (Newcastle)
15:30 – 16:00 Per Kogner (Karolinska): The PPM1D encoded WIP1 phosphatase is an oncogene significant for cancer development and tumour progression and a druggable therapy target in neuroblastoma and medulloblastoma. A hint as to how aggressive childhood cancer manages with wild-type p53
16:00 – 16:15 Deb Tweddle (Newcastle): Preclinical assessment of MDM2/p53, ALK and MEK inhibitor combinations in neuroblastoma
16:15 – 16:30 Sally George (ICR, Sutton): A CRISPR-Cas9 genomic editing and compound screening approach identifies therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma
16:30 – 16:45 Miriam Rosenberg (Jerusalem): Expression- and immune-profiling of neuroblastoma-associated Opsoclonus Myoclonus Ataxia Syndrome (OMAS) to identify features of auto- and tumour-immunity
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.
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!
International Childhood Cancer Day (ICCD) was founded in 2002 by Childhood Cancer International (CCI). Each year on February 15th we unite together to recognise childhood cancer as a national and global child health priority & to raise support, funding and awareness of this devastating desiease.
This year we team up with Amorino to run Hot Chocolate Morning. Please come along! All proceeds go to CMRF/NCRC and CFNCRF.
Reading my posts, it looks like I am more enjoying the cultural part and almost forgot the main reason I crossed the Atlantic with the Fulbright wings.
The first month in the lab was more a warming up. Where is my desk? Where is the cell culture rooms? How do they run it? How different is it? So, many microscopes – am I capable of imaging? And so on and so forth…
My typical day starts at 8-8.30 am and finishes once all is done. It may be 6pm or 10pm. Once the experiment is set up, I have to monitor cells every 24 hours for 5-7 days with no weekends or days off. The monitoring includes imaging. Lots of imaging. Every condition has 20-30 single cells to follow up. Each cell gets its own GPS tag manually to be able to image exactly the same cell as it grows and becomes a group of hundreds by multiplication. For example, I am running 8 different cell lines in 3 experimental conditions. So, 20-30 cells per all 24 combinations give us 480-720 individual cells to follow up. The imaging takes ~5 hours every day. After 5 days, I will have 2400 – 3600 pics of cells to analyse. It will be fun! I may need lots of Guinness to fly through that numbers.
Tagging cells. The left arrow points to a group of neuroblastoma cells. The arrow in the middle point to the same cells, but this image allows you to see the actual number of the cells. This group has 8 cells. The right arrow points to individual GPS tags for each cell
At the next step, I will select some of the conditions for video recording to trace cell fate from a single neuroblastoma cell to a metastatic niche consisting of hundreds of them. This video will show me how it all happens minute after minute.
Last year I have selected this photo of a lovely fountain capturing 3 girls under umbrellas (Drei-Mädchen-Brunnen) in Ballplatz Mainz in support of #ChildhoodCancerAwarnessMonth. This fountain was built between two Catholic girl’s schools symbolising the separate education and a happy childhood. It is charming on its own. And I’ve select it again.
Every child deserves a happy childhood. Raising awareness about childhood cancer we help to make the dreams of children with cancer come true. Dreams for a happy childhood, better treatment, better quality of life full of love ahead through better funding of childhood cancer research and access to innovative treatments.
Today marks the start of Childhood Cancer Awareness Month.
Three girls fountain in Mainz Germany
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)
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.”
Though the official announcement is scheduled for the first week of June, the groundwork is on. Lots of reading and planning for the trip to Johns Hopkins later this year. One of the first is the book by Rebecca Skloot ‘The Immortal Life Of Henrietta Lacks”. The famous HeLa cells were generated by researchers at JH. The story is a fascinating journey for biomedical scientists and a tragedy for the Lacks family.
