InnoSer ’s Post

In response to the issue previously raised by Robert Gillies and Michal Tomaszewski, PhD on the biological meaning of radiomics features, we have developed a pipeline centered around tumor cell glycolysis using quantitative immune histochemistry as starting point and [18F]FDG-PET radiomics as non-invasive imaging biomarker. Key findings: 👉 Radiomic features can reveal hidden patterns in the tumor, but usually lack an underlying biological explanation  👉 To assess patterns of glycolysis in pancreatic ductal adenocarcinoma, expression patterns of monocarboxylate transporter-4 (MCT4) were used to identify a corresponding set of radiomics features derived from [18F]FDG PET images  🆕 The histology-based [18F]FDG PET radiomics score allowed to non-invasively capture tissue heterogeneity and identified a subset of pancreatic cancer patients with a distinct metabolic phenotype and poor prognosis #pancreas #tumormetabolism #glycolysis #imaging #molecularimaging #radiomics #computationalpathology #pathomics #PET #heterogeneity #Radboudumc This was a truly interdisciplinary effort, with great contributions of Esther Markus-Smeets Daan Geijs Monica van Zanten Lodewijk Brosens Martin Gotthardt Francesco Ciompi, our collaborators in University Hospital Essen @Marija Trajkovic, @Sinan Karakaya Prof. Dr. Jens Siveke and Technical University Munich Rickmer Braren @Benedikt Feuerecker https://lnkd.in/e7hvq4HQ

Join us at the American Association for Cancer Research Annual Meeting 2024 in San Diego, where we'll unveil two posters showcasing advancements in our oncology models.   Cell line-derived xenograft models are widely used preclinically but are often criticized for lacking translational value. A model with higher clinical relevance is the patient-derived xenografts (PDX) model established by implanting patients’ tumor tissue onto immunodeficient mice. Our Scientist Sigrid Cold will present how we established a PDX-derived cell line (PDXc) and characterized it extensively in a head-to-head comparison to the parental PDX model. Cells were isolated from a subcutaneous glioblastoma (GBM) PDX tumor (ST146), processed into single cells and cultivated in vitro. Tumor-take and growth rate were evaluated against the parental PDX model and common characteristics of the model such as EFGR and Vimentin expression were determined by IHC. We furthermore generated a stable Luciferase expressing PDXc. Tumor growth for subcutaneous and intracranial implanted cells was evaluated using Bioluminescence Imaging, caliper, and MRI.   Learn more about the model during the poster session on April 10, 2024, 9:00 AM - 12:30 PM, Section 10, or drop by our booth #4450 if you want to explore how molecular imaging can enhance your translational cancer research programs.   Click here to learn more about the posters or if you are interested scheduling a meeting with us at the AACR:  https://lnkd.in/eZkWz-WE #AACR24 #oncology #radiopharmaceuticals #PDX #molecularimaging #diagnostics #theranostics

A good read! An article published by #ErasmusMC on radiotheranostic imaging in prostate cancer. It explores the therapy and imaging capabilities of the 177Lu labeled compounds. #ProstateCancer #Radiotheranostic #MedicalImaging #HealthcareInnovation #CancerResearch #MILabs #VECTorCT

Our understanding of the molecular mechanisms set in motion before tumor initiation and that later culminate in advanced carcinogenesis is still very limited. A previous study from our laboratory reported the identification by single-cell transcriptomics of an intestinal tumor cell population expressing gastric and fetal features, termed tumor fetal metaplastic cells, that accumulates in the most aggressive form of colorectal cancer and predicts poor survival in patients [https://lnkd.in/dheTJ4bN]. In a new paper published today in Developmental Cell [https://lnkd.in/dbscc2Uk], Hiroto Kinoshita and Anxo Martinez-Ordoñez, as part of an international collaborative team effort led by our lab (https://lnkd.in/g5SJQPF), report recent work in which we discover the signaling mechanisms responsible for driving the accumulation of that malignant cell population even before tumorigenesis starts. The pathways, driven by deficiency of the two atypical Protein Kinase Cs (PKCiota and PKCzeta) in the intestinal epithelium, also unexpectedly trigger the loss of intestinal stem cells by apoptosis, which fosters a vicious cycle of intestinal damage and regeneration underlying tumor initiation even before oncogenic mutations occur. We propose that this newly identified mechanism is common to the start of all forms of colorectal tumors. Interrogation of pre-malignant human colon specimens demonstrates that the signaling pathways discovered in our mouse and organoid systems, funneled by a JNK/AP1/YAP cascade, are of pathophysiological relevance, highlighting its great potential significance in the clinic. These findings provide a new paradigm for understanding the initial steps in colorectal carcinogenesis, which is key for designing preventive therapeutic strategies that eventually stop tumors before they even start.  #cancer #colorectal #cancertreatment #cancerprevention #cancerresearch #pkc #metaplasia #stemcells #yap #JNK #AP1 #adenoma #premalignant #tumorinitiation

🚀 Portrai Inc.'s Largest Clinical Study with the MERSCOPE® Platform! We are thrilled to share a groundbreaking preprint article from Portrai Inc. -"Spatial Transcriptomics Reveals Spatially Diverse Cancer-Associated Fibroblasts in Lung Squamous Cell Carcinoma Linked to Tumor Progression." 📝 Abstract: This study delves into the spatial organization of cancer-associated fibroblasts (CAFs) in lung squamous cell carcinoma (LUSC), a highly aggressive form of lung cancer. Portrai Inc.'s research underscores the critical role of spatial dynamics within the tumor microenvironment and its implications for patient prognosis in #LUSC. 🔬 Key Findings: 🔄Spatial Interactions: Significant associations between the spatial interactions of tumor epithelium and CAFs with tumor size and metabolic activity. ↗️Recurrence-Free Survival: Proximity of fibroblasts to tumor epithelial cells linked to recurrence-free survival in LUSC patients. ✳️Molecular Signatures: Identification of distinct molecular signatures related to spatially distinct fibroblast subpopulations. ↔️Metabolic Pathways: Overlapping fibroblast regions characterized by upregulated glycolysis pathways. 📖 Read the full article here: https://hubs.ly/Q02zDynk0

Thrilled to announce you the release of my last postdoc research preprint paper!!!! In this study, we investigate the role of Cyclin-Dependent Kinase 4 (CDK4) far beyond its known canonical role in cell cycle. Indeed, we demonstrate for the first time that this CDK is able to regulate small subcellular structures, called Mitochondria-Endoplasmic Reticulum Contacts (MERCs). This regulation modulates cell death sensitivity but also mitochondrial bioenergetics impacting cell fate of triple-negative breast cancer (TNBC) cells. This could partly explained some of the therapeutic resistance effects observed using CDK4/6inhibitors in TNBC settings. Fortunately, we found that CDK4 inactivation, through MERCs modulation, not only hinders cell death mechanism but also makes TNBC cells more vulnerable and sensitive to metabolic challenges, opening interesting therapeutic avenues. If you want to know more, please check it out: https://lnkd.in/eCNdsuxk Thanks to all co-authors and collaborators for their great contribution: Lucía Leal-Esteban, PhD Kanishka Parashar Jaime López-Alcalá Katharina Haushofer Wilson Castro Nadège Zanou Xavier Berney Maria M Malagon Catherine Roger Marie-Agnès Berger Giulia Paone Hector Gallart-Ayala Julijana Ivanisevic Jennifer Rieusset Melita Irving Lluis Fajas.

Interesting new paper on alveolar transitional cells in lung cancer from the Kim lab!

Novel anti-TIP1 human antibody sets the stage for noninvasive PET imaging breakthrough. In a recent study published in Clinical Cancer Research (American Association for Cancer Research), Abhay Singh, Calvin Lewis, Cristian A. Wieczorek Villas Boas, Ph.D., Philipp J. Diebolder, Prashant Jethva, Ph.D., Aaron Rhee, Jong Hee Song, Young Ah Goo, Shunqian Li, Mike Nickels, Yongjian Liu, Buck Rogers, Vaishali Kapoor, and Dennis Hallahan presented a novel approach for noninvasive PET imaging in cancer patients. Focused on Tax-interacting protein 1 (TIP1), a cancer-specific radiation-inducible cell surface antigen implicated in cancer progression and therapy resistance, the study aimed to develop a human antibody for PET imaging. Through a meticulous process involving phage-displayed scFv library creation, antibody selection, and engineering, the team developed the lead antibody, L111. Characterization assays confirmed L111's purity, intact mass, and optimal conjugation with the positron emitter [89Zr]. PET studies in lung cancer tumor models demonstrated the specificity and potential of [89Zr]Zr-DFO-L111 for imaging, paving the way for its evaluation in human safety and PET imaging studies. https://lnkd.in/gy6WZJMN #cancerresearch #cancertreatment #massspectrometry

🌐 Diagnostics, Volume 13, Issue 5 (March-1 2023) 🔬 Can Imaging Using Radiomics and Fat Fraction Analysis Detect Early Tissue Changes on Historical CT Scans in the Regions of the Pancreas Gland That Subsequently Develop Adenocarcinoma? 🔍 Genomic analyses of #pancreas tissue revealed that it may take years for pancreatic cancer to develop. Using contrast-enhanced CT scans, imaging features of the normal pancreas that may portend the development of cancer were identified from 22 patients with historical scans 4–14 years before diagnosis. 💡 In this IRB-exempt, retrospective, single institution study, radiomic analysis on seven regions of interest around the pancreas revealed that fat fraction in the pancreas tail and skewness of pancreas tissue were the most important imaging signatures for subsequent cancer development, confirming the utility of radiomics-based imaging to screen patients for pancreatic cancer. Such techniques could help detect pancreas cancer at an early stage, thereby improving survival. 📖 Discover more: https://lnkd.in/dB8eKiAY #PancreasCancer #PancreaticTumors #Radiomics #MedicalImaging #Radiology #CancerScreening #EarlyDetection #Diagnostics

Biology Lesson of the day: Differences between cancer organoids and spheroids. Both spheroids and tumoroids offer valuable insights into tumor biology and drug responses, but their applications and limitations must be carefully considered. Read the article below to learn more.