Cancer is the 2nd most common cause of death among children after accidents.
Childhood cancer is an umbrella term for many other types of this disease. Every September, many charities, researchers and parents of children with cancer work hard to raise awareness of this cancer. You may learn more about kids with cancer, their loving families, the doctors and caregivers who look after them and treat them, the young survivors of cancer and those kids and teens who lost their battle, and the scientists who work hard to find a way to stop childhood cancer.
This year, our research team will run the Pub Quiz on September 18th, 2024, in honour of Childhood Cancer Awareness Month. All donations will go to the Conor Foley Neuroblastoma Research Foundation (CFNRF).
If you would like to get involved in this amazing challenge and help us raise vital funds for childhood cancers, you can contribute to our fundraising page:
HDAC inhibitors are drugs that target specific enzymes involved in gene regulation. This study tested broad-spectrum HDAC inhibitors as standalone treatments and combined them with doxorubicin, a well-known chemotherapy drug.
But why on Zebrafish? The zebrafish model provides a rapid and efficient means of testing these treatments, offering valuable insights into their potential use in combating neuroblastoma. This model allows for assessing drug efficacy and helps understand the associated toxicities quickly, making it a powerful tool for developing new anti-cancer therapies.
In the study, fish larvae were implanted with fluorescently labelled, well-established neuroblastoma cell line (SK-N-BE(2)-C) and patient samples (HD-N33, NB-S-124) to grow tumours. Non-cancerous cells (VH7 fibroblasts) were utilized to verify that tumour progression in zebrafish was specific to tumour cells. The engraftment of human cells into fish larvae was confirmed by immunohistochemistry (IHC) staining on zebrafish sections injected with neuroblastoma cells (SK-N-BE). This was achieved using a STEM121 antibody that reacts specifically with a human cytoplasmic protein. The findings showed that pediatric tumour cells survive and grow in the zebrafish model at rates like those observed in human tumours.
Before testing drug efficacy in zebrafish xenografts, optimal drug concentrations and maximal tolerated doses (MTD) were determined. Toxicity tests were conducted by treating fish larvae cells for three days without tumour cell injection to identify the maximum tolerated dose that did not cause observable morbidity, changes in morphology, or severe aberrations in larval behaviour. and lethal dose (LD) for each compound. To find optimal drug concentrations, larvae with xenografted tumour cells were incubated with increasing drug doses 24 hours post-implantation to the maximally tolerated dose (MTD). The relative IC50 values were then determined based on changes in tumour mass volume.
To evaluate the treatment, SK-N-BE(2)- cells were used to test the broad-spectrum HDAC inhibitors, including panobinostat, vorinostat, and tubastatin A, both alone and combined with doxorubicin. The partial response rate (PR) was measured to see how well different drug combinations work to shrink tumours in the zebrafish model. Here’s what they found: Doxorubicin combined with panobinostat resulted in a 23% PR, Doxorubicin combined with tubastatin A showed a 31% PR, and Doxorubicin combined with vorinostat achieved the best result with a 36% PR.
To test the effectiveness of the HDAC inhibitor treatment, they monitored the tumour growth using a confocal microscope before and 48 hours after giving the drug. The test revealed that a 48-hour treatment of SK-N-BE (2)-C zebrafish xenografts with vorinostat and doxorubicin alone, `and in combination, increased cell death. The combination of these two drugs was the most effective, causing a significant increase in cancer cell death (apoptosis) by decreasing cell proliferation, as indicated by reduced PPH3 marker and activating the number of Cleaved caspase-3 (Figure 1).
Figure 1: Treatment for 48 h with Vorinostat, doxorubicin, or a combination of both increased the amount of cleaved caspase-3 and reduced mitotic tumour cells. Adapted from Pharmaceuticals2020, 13(11), 345
In essence, this study validates the use of HDAC inhibitors in treating neuroblastoma and paves the way for broader applications of zebrafish models in cancer research. As we look to the future, these innovative models could significantly enhance our ability to develop effective cancer therapies, making strides towards better treatments and, ultimately, more effective cures.
This article by Krieger et al. discusses the most common form of brain cancer called glioblastoma. Due to its highly aggressive nature, research must be conducted consistently and rapidly to develop new treatments. This has proven challenging due to primary tumours being resected before further research can be done, as well as the lack of current technologies to fully explore relationships between GBM and surrounding brain tissues. This study aimed to study the aforementioned interactions in under 4 weeks, accounting for the rapid progression of the disease in real life.
GBM cells were first derived from four patients and treated with glutamine, heparin, epidermal and fibroblast growth factors, then underwent a sequence of manipulations, such as second-generation replication lentivirus infection of GBM cells, iPSC line 409b2 inoculation in Aggrewell plates and later manipulation with invasion assays, and scRNA sequencing, which, along with the Aggrewell cells, produced neural progenitor cell spheroids for analysis. Confocal microscopy and the developed image processing algorithm allowed for visualization of these cells following fluoroscopy and depicted consistent growth of tumour cells. There was also the growth of microtubules. Any dissociated organoids were then co-cultured with GBM cells again, promoting interaction between the two. Further analysis revealed the upregulation of 45 genes, including PAX6, GJA1, GPC3, and others involved in cell regulation.
In conclusion, this novel mechanism of analysis of GBM cells using Aggrewell plates provided fruitful results, indicating intricate relationships between GBM cells and organoids, providing crucial insight for treatments by elucidating specific gene expression, heterogeneity of cells, and offering new targets based on ligand-receptor interactions. The particular relevance of this study to my work is regarding the usage of Aggrewell plates, which I am currently studying to determine how best to keep cells growing successfully within the wells. This article proves the usability and efficiency of Aggrewell and establishes its crucial role in the realm of brain cancer treatment research.
Hi there, Federica here! In the fast-paced world of scientific research, staying informed about the latest studies and breakthroughs is crucial. It enables researchers to build upon existing knowledge, avoid redundant efforts, and discover new directions for their work. That’s why we’ve started a new series of blog posts highlighting recent papers and explaining their significance for our research.
The researchers investigated a combination of immune checkpoint blockade (ICB) and other drugs to turn “immune-cold” tumours (which evade the immune system) into “immune-hot” tumours (which the immune system can attack). They developed a special delivery system using nanoparticles called metal-organic frameworks (MOFs). These nanoparticles were loaded with two types of drugs—a TLR7/8 agonist and an epigenetic inhibitor (BRD4 inhibitor). To make the nanoparticles even more effective, they were coated with vesicles from the cancer cells themselves. This coating helps the nanoparticles specifically target cancer cells.
But how does it work?
The nanoparticles are designed to find and enter triple-negative breast cancer (TNBC) cells. Once inside, the drugs prompt the cancer cells to break apart and release signals that alert the immune system. These signals attract dendritic cells, which then activate CD8+ T cells—the body’s natural cancer fighters. The TLR7/8 agonist further enhances this immune response, making the treatment more powerful.
In both laboratory tests and animal models, this method showed significant promise. It not only slowed down tumour growth but also improved the body’s immune response to cancer. Importantly, the study found that this approach could remodel the tumour environment, making it more hostile to cancer cells. For example, they wanted to verify that their combined delivery system could really boost the body’s ability to fight tumours. They focused on a protein called calreticulin (CRT) that, when it shows up on the surface of tumour cells, helps the immune system spot and remove them. They found that when they used their special delivery system (CM@UN and MCM@UN), the levels of CRT on the surface of tumour cells went way up. This was especially true for the MCM@UN group, showing just how powerful their method was in getting the immune system to attack the tumours.
The original image was published in J Nanobiotechnology. 2024; 22: 296.
So, why is this study important for my work?
The principles of enhancing the immune system’s ability to fight cancer are central to both the research in the study and in my project. Like the nanoparticles in the study, mRNA vaccines can be designed to specifically target cancer cells, ensuring that the treatment reaches its intended destination. Another similarity is how the drugs activate the immune system, which parallels how mRNA vaccines work—by training the immune system to recognise and attack cancer cells.
I find this study really interesting as it sheds light on innovative strategies for cancer treatment and provides valuable insights that can inform and inspire our research on developing mRNA vaccines for childhood neuroblastoma!
A wonderful day of knitting – Knit-A-Thon-2023 raised 913 euros. A massive thank you to everyone who stopped by and donated on the day and beyond. Every cent counts! The money was split evenly between our four chosen charities: The Conor Foley Neuroblastoma Research Foundation (CFNRF), Neuroblastoma UK (NBUK), Oscars Kids and Childhood Cancer Ireland (CCI). These charities were established and are run by parents, some of whom lost their children to cancer. They continue their children’s legacy, doing an amazing job of advocating for children with cancer and better funding for research and aftercare.
Knit-A-Thon 2023
And a special thank you to Ciara’s mam Aggie for the amazing handmade raffle prizes (chromosomes, antibodies, cup holders and many more) and a Master class on the day! We thank Jenny Duffy (RCSI Events and Communications Coordinator) for her time crocheting with us and for us! Thanks to Anggie’s and Jenny’s skills, there were lots of mascots to win – and many of them collected already. We much appreciate the support from the RCSI Estates and Porters who looked after us on the day.
We are the Cancer Bioengineering Group, and September is a very special month for us as it is Childhood Cancer Awareness Month. Childhood cancer is the 2nd leading cause of death in children after accidents. Our group researches childhood cancer neuroblastoma, a cancer of immature nerve cells. Despite intensive multimodal treatment, as many as 1 in 5 children with aggressive neuroblastoma do not respond, and up to 50% of children that do respond experience disease recurrence with many metastatic tumours resistant to many drugs and more aggressive tumour behaviour that all too frequently results in death.
This is what we want to change! We believe that every child deserves a future, and our team of postgraduate researchers led by Dr Olga Piskareva is dedicated to strengthening our knowledge of this disease and identifying new potential ways to tackle it, as well as taking part in fundraising activities so our group and others can continue with this research.
On Tuesday, the 19th of September, we are running a Knit-A-Thon using gold and purple yarn to mark childhood cancer and neuroblastoma, respectively. Our patterns are inspired by Neuroblastoma UK and Mr Google, indeed.
This year, we honour 4 charities that are doing an amazing job of advocating for children with cancer and better funding for research and aftercare. Therefore, the donations we receive will be split equally among The Conor Foley Neuroblastoma Research Foundation (CFNRF), Neuroblastoma UK (NBUK), Oscars Kids and Childhood Cancer Ireland (CCI). If you would like to get involved in the Knit-A-Thon and help us raise vital funds for childhood cancers, come along on the day and make a donation to these wonderful charities.
On the day, RCSI 123 SSG will #GoGold in support of this cause. Please come by to see the RCSI building lit up and share your pictures on social media with the hashtag #ChildhoodCancerAwarenessMonth to raise awareness.
Ready, Steady, Go!
Every year we manage to raise an amazing 1500-2000 euros by organising a new challenge. We are eager to surpass that target this year. All donations no matter how small are appreciated at GoFundMe.
Hi there, Ciara here again, a final-year PhD student in our research group. I can’t believe September has rolled around again, meaning one thing: it’s Childhood Cancer Awareness Month (CCAM). In honour of this month, I would like to tell you a little bit about the childhood cancer we study in our lab and the research that I do to one day help save children from this disease.
Neuroblastoma is an aggressive childhood cancer, with sadly only 20% of late-stage patients surviving after 5 years. Progressive disease and cancer relapse are common in neuroblastoma. This is due to standard treatment regimens not being adequate for treating high-risk patients. Current treatment also may cause a series of adverse reactions in patients. Therefore, my research focuses on developing a 3D model of high-risk neuroblastoma that models the cancer more accurately in a laboratory setting. This will act as a beneficial platform to test whether new therapies effectively fight the patients’ cancer cells, leading to better treatment options for children with neuroblastoma.
Below is a picture of how we grow these cancerous cells on our 3D model and visualise them with fluorescent stains. When we can see them like this under a microscope, we can study how they move and grow to help us understand how to treat them.
Here, we can see the cells growing on our 3D cancer model. This image is magnified by 200 times to be able to see the individual cancer cells. The green stain is the outside of our cancer cells, or we use the term, the cell membrane. The blue is the inside, or as some of you may know the term, the nucleus of the cell. (It is amazing what we can see with the power of microscopes, right?)
As you may know, every year, we support amazing charities by raising vital funds to keep the fight against childhood cancer going. Keep your eyes peeled on our Twitter for updates on what crazy activity we have committed to this year!!
Every September, we celebrate Childhood Cancer Awareness Month. This is a great opportunity to raise awareness about childhood cancer. Unfortunately, kids get cancer, too. While much research has been done to understand how cancer develops in adults, we still know very little about what exactly leads to cancer in children.
We are the Cancer BioEngineering Group led by Dr Olga Piskareva at the RCSI University of Medicine and Health Sciences. Our research focuses on neuroblastoma, an aggressive childhood cancer of immature nerves. The group has 7 PhD students developing research projects around neuroblastoma biology. One postgraduate student successfully defended her work and was awarded a PhD last month.
We are a dynamic group proud to be engaged in research, science communication and patient involvement. We do that through different initiatives. Throughout September, we will share many of them and invite you to keep following us on social media.
Team 2023
Our projects address topics related to neuroblastoma microenvironment, cell interactions, tumour resistance and the development of new therapies. To do that, we use 3D in vitro models, identify immunotherapeutic targets and evaluate extracellular vesicles.
We are always happy to answer questions and interact with the public. Follow us on our social media channels and read our blog to learn more about us and our research.
We are running a fundraising event, “A knit-a-thon,” on the 19th of September. Stay tuned!
Thanks for reading, and we go ahead with neuroblastoma research!
Cancer is a disease which will have an impact on most people throughout their lifetimes, and there are few things that can bring people to agreement more than wanting a cure for this disease. But despite countless years of financial investments and researchers who dedicate their careers to cancer, we still don’t have a “cure”, and it can be difficult for non-scientists to fathom why.
One key concept to understand here is that cancer is not a single disease, does not have a single cause, and therefore cannot have a single cure. The differences between neuroblastoma and breast cancer are vast. And similarly, between patients with the same cancer type (e.g. two patients with breast cancer), the differences can be equally as big. Let’s for a minute, take an analogy of a large business company. (Disclaimer, I have never studied business in my life, so please humour me). The company is run by a CEO and board of directors and has many different departments with managers and teams of workers with specific roles. Suddenly, business is declining, and the company is not sure why. For one business, maybe this is down to someone in the Communications team spreading misinformation. For another, maybe a mistake has been made in the Finance team, which has had a knock-on effect on the other departments. Maybe Human Resources have not been properly reprimanding staff who have broken protocol. With hundreds of staff working in the company, it can be hard to pinpoint exactly where the problem has arisen, which has negatively impacted the company as a whole.
Standard business hierarchy, created with BioRender.com
Human cells aren’t so different to a company. They have a central “nucleus” tasked with controlling the functioning of the cell as a whole (Board of Directors/Management). They have proteins which relay messages inside the cell, as well as outside with other surrounding cells (Communications). They have proteins which are responsible for detecting when something goes wrong, to correct or destroy whatever is acting out of place (Human Resources). Issues within any of the “departments” in a human cell can potentially lead to cancer, and just like our business model, it can be hard to trace where the problem arose, and it is often different between two cancers.
Cell signalling networks, or the “business departments” within a cell, from Reactome.org
For decades cancer was treated with chemotherapy, famous for attacking the good healthy cells as well as the bad. The research focus has now shifted towards more targeted therapies. An example of this is Herceptin therapy for breast cancer. This therapy targets a specific protein called HER2. HER2 is a team within the Communications department in breast cells. It receives communications from outside the cell, which tells the cell it’s time to grow, and relays this message to the Nucleus, which instructs proteins involved in cell growth to start this process. However, in some breast cancers, there are too many members in the HER2 team, all relaying this message to the Nucleus, resulting in too much cell growth. Herceptin is a drug which specifically targets HER2 and prevents it from relaying this message, effectively preventing the cancer cells from growing. While this can be very efficient at preventing tumour growth in HER2+ breast cancer, HER2 is not the culprit in all breast cancers. It is estimated that only 1 in 5 breast cancers have too many members in the HER2 team (Irish Cancer Society), and so targeting this will be inefficient in treating 4 out of 5 breast cancers. Meanwhile, cells of other cancers, such as liver or thyroid cancer, may not even have a HER2 team.
Hopefully, it is becoming clear why one “cure” will likely never be a reality. All cancers are different, all have different causes, and different employees breaking protocol. So, a one-size-fits-all approach simply can’t work. Instead, we need to focus on finding common company malpractices for each cancer, such as HER2 in breast cancer, generate a repertoire of different targeted treatment options depending on the various causes of cancer, and treat each patient as an individual investigation to determine what employee/protein is acting out of line to cause their cancer, so we can specifically reprimand them.
