Setting up a PDXO platform of pancreatic cancer with spatial -omics characterization

03:282 years ago

Pancreatic ductal adenocarcinoma (PDAC) is known for its aggressive biology and lethality. Due to a low success rate of current diagnostic and therapeutic approaches in clinic, there is an urgent need for
preclinical research studies to investigate the underlying biology of this malignancy. This knowledge is indispensable to facilitate the development and validation of potential new therapeutic compounds.
Superior to conventional biomedical research models, the focus of this study is on the development and use of a well-established patient-derived 3D in vivo model, mimicking the tumor as it is present in
a human body. The development and characterization of pancreatic cancer derived organoids. This model is extensively analysed using advanced histological methods omics technology to perform tumor
subtyping. 15 established PDAC organoid lines and their corresponding parental tumors are validated using immunostainings and DNA hotspot sequencing. This study is the first to show in situ detection of
important driver mutations of pancreatic cancer, like KrasG12D, both in parental tumor and organoids. Additionally, specific culture conditions are defined to develop subtype-specific organoids
which are validated using multiplex RNA in situ hybridization and transcriptomics. We are proud to collaborate in a fruitful international project, aiming to set-up a pre-clinical screening
platform for pancreatic cancer based on patient-derived organoids -and xenografts. Altogether, spatial-omics in depth analysis of both models will demonstrate (1) high resemblance to parental tissue
and (2) subtype-specific signatures associated with type of model. Ultimately, the screening platform can be used by pharmaceutical companies to facilitate oncological drug testing in a subtype specific
way.

Publications Ilse Rooman's lab:
https://pubmed.ncbi.nlm.nih.gov/34330784/
https://pubmed.ncbi.nlm.nih.gov/31161208/

Related

Cells4Thought: using iPSCs for neurodevelopmental health
Projects and initiatives
HealthToxicologyInnovationIn vitro

Cells4Thought: using iPSCs for neurodevelopmental health

The prevalence of neurodevelopmental disorders (NDDs), including cognitive impairments, is increasing worldwide with great impact on daily life quality. There is evidence that exposure to chemicals may contribute to the incidence of NDD. However, a causal link is lacking. Towards this goal, a human-relevant in vitro model system mimicking parts of brain development, such as neuronal network functioning, could be used for mechanistic research on how gene-environment interactions contribute to the development of NDD. This is going to be studied in the project Cells4Thought, using induced pluripotent stem cells form different individuals to study the effect of chemicals on neuronal differentiation.
02:3820 hours ago
We all want a safer world for humanity, animals and the environment: Transition Animal-free Innovation
Projects and initiatives
HealthInnovationPolicy

We all want a safer world for humanity, animals and the environment: Transition Animal-free Innovation

Why is the transition to animal-free research so important? What are animal-free models? How does TPI (Transition Animal-Free Innovation) encourage their development and use? And who are we working with to make this happen? We explain this in our animation. More and more animal-free tests and research methods are becoming available, but not all research questions or safety tests can be answered in this way yet. In addition, the validation, qualification and acceptance of non-animal innovations still lags behind. Therefore, the Dutch Ministry of Agriculture, Nature and Food Quality (LNV) stimulates the development and application of animal-free innovations. This is done with the partner programme Transition Animal-free Innovation (TPI).
02:4837 days ago
New approaches for cancer hazard assessment
Innovation examples

New approaches for cancer hazard assessment

Chemical substances are subjected to assessment of genotoxic and carcinogenic effects before being marketed to protect man and the environment from health risks. For cancer hazard assessment, the long-term rodent carcinogenicity study is the current mainstay for the detection of nongenotoxic carcinogens. However, carcinogenicity studies are shown to have prominent weaknesses and are subject to ethical and scientific debate. A transition toward a mechanism-based weight of evidence approach is considered a requirement to enhance the prediction of carcinogenic potential for chemicals. At RIVM, we are working on this alternative approach for cancer hazard assessment, which makes optimal use of innovative (computational) tools and be less animal demanding. For more information, click on the link in the video or read on here (https://doi.org/10.1080/10408444.2020.1841732) and here (https://doi.org/10.1080/10408444.2018.1458818). Contact the expert (https://nl.linkedin.com/in/mirjamluijten)
03:142 months ago
Helpathon #10 – Can you help Jolanda and Elza?
Meeting videos
HelpathonsEducation

Helpathon #10 – Can you help Jolanda and Elza?

Jolanda van der Velden, Chair of Physiology, and Elza van Deel, Educator, from Amsterdam University Medical Center want to support PhDs in preparing for the animal-free transition. They are both looking for an implementation strategy and course design. Do you have an interest in animal-free education and education about animal-free research? Read more and register here (https://www.helpathonhotel.org/coming-up).
00:552 months ago