NUS Centre for Cancer Research (N2CR)’s Post

New paper out! Patient-derived tumor organoids (PDTOs) are regarded as a promising tool for predicting patient responses to anticancer therapies. However, mitochondrial metabolism is rarely investigated in this 3D model. In this important research project, I contributed to the initial steps in investigating the status of complex II in ccRCC PDTOs. These findings are the product of a collaborative effort, underscoring the fundamental role of teamwork in advancing scientific discovery. #Organoids #PDOs #PDTOs #mitochondria #Metabolism #ComplexII

✨ Did you know that the combination of extracorporeal membrane oxygenation (ECMO) and hematopoietic stem cell transplant (HSCT) is an emerging, yet rarely documented therapeutic strategy for managing life-threatening complications in rare genetic disorders? 🧒🏻In this extraordinary case, a 3-month-old patient with Hunter Syndrome developed recurrent diffuse alveolar hemorrhage (DAH) following HSCT. ECMO was employed as a lifesaving measure, along with unconventional techniques like endotracheal tube clamping, to address this severe complication. 🔬 While the initial response to ECMO was promising, recurrent episodes of DAH ultimately led to the patient’s decline, underscoring the complexity of balancing innovative therapies with the unpredictable course of rare diseases. 💡 What sets this case apart? It’s the first documented instance of DAH requiring ECMO in a Hunter Syndrome patient post-HSCT, offering valuable insights into the challenges and potential of these advanced therapies. 👉 Can ECMO and HSCT pave the way for new treatment paradigms in Hunter Syndrome, or do the risks outweigh the benefits? 🔗 [Read the full case report and its implications: https://lnkd.in/dVu92vtr] #HunterSyndrome #DiffuseAlveolarHemorrhage #ECMO #HSCT #RareDiseases #CriticalCareMedicine #ArchiveOfClinicalCases #MedicalBreakthroughs #CaseReport

Citrullination modulation stabilizes HIF-1α to promote tumour progression Post-translational modifications on HIF-1α can regulate its stability and activity in tumoral processes. Here, the authors show that PADI4-mediated citrullination avoids HIF-1α degradation to promote hepatocellular carcinoma progression and this can be prevented by a PADI4 antagonist https://lnkd.in/gz_c84ir

Check out our recently published paper on clinical characteristics of Malignant Histiocytosis (includes Histiocytic Sarcoma, Langerhans Cell Sarcoma, Interdigitating Dendritic Cell Sarcoma); the key is triaging tissue for NGS to identify therapeutic targets! #raredisease

#STINGpathway #LipidNanoparticles #AntitumorImmunity | 𝗖𝗮𝗻 𝗧𝗮𝗶𝗹𝗼𝗿𝗶𝗻𝗴 𝗡𝗮𝗻𝗼𝗽𝗮𝗿𝘁𝗶𝗰𝗹𝗲𝘀 𝗥𝗲𝘃𝗼𝗹𝘂𝘁𝗶𝗼𝗻𝗶𝘇𝗲 𝗖𝗮𝗻𝗰𝗲𝗿 𝗜𝗺𝗺𝘂𝗻𝗼𝘁𝗵𝗲𝗿𝗮𝗽𝘆? 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰 𝗺𝗮𝗻𝗶𝗽𝘂𝗹𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝘁𝗵𝗲 𝗦𝗧𝗜𝗡𝗚 𝗽𝗮𝘁𝗵𝘄𝗮𝘆 𝗵𝗼𝗹𝗱𝘀 𝗴𝗿𝗲𝗮𝘁 𝗽𝗿𝗼𝗺𝗶𝘀𝗲 𝗳𝗼𝗿 𝗲𝗻𝗵𝗮𝗻𝗰𝗶𝗻𝗴 𝗮𝗻𝘁𝗶𝘁𝘂𝗺𝗼𝗿 𝗶𝗺𝗺𝘂𝗻𝗶𝘁𝘆. 𝗦𝗧𝗜𝗡𝗚 𝗮𝗴𝗼𝗻𝗶𝘀𝘁𝘀, 𝗰𝘂𝗿𝗿𝗲𝗻𝘁𝗹𝘆 𝗶𝗻 𝗰𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝘁𝗿𝗶𝗮𝗹𝘀, 𝗵𝗮𝘃𝗲 𝘀𝗵𝗼𝘄𝗻 𝗶𝗻𝗰𝗿𝗲𝗮𝘀𝗲𝗱 𝘀𝗮𝗳𝗲𝘁𝘆 𝗮𝗻𝗱 𝗲𝗳𝗳𝗶𝗰𝗮𝗰𝘆 𝘄𝗵𝗲𝗻 𝗹𝗼𝗮𝗱𝗲𝗱 𝗶𝗻𝘁𝗼 𝗹𝗶𝗽𝗶𝗱 𝗻𝗮𝗻𝗼𝗽𝗮𝗿𝘁𝗶𝗰𝗹𝗲𝘀 (𝗟𝗡𝗣𝘀). This recent study published in Journal of Controlled Release, developed STING agonist-loaded LNPs using the ionizable lipid YSK12-C4 (YSK12-LNPs), demonstrating significant antitumor effects. How do different LNP compositions affect antitumor immune responses? They compared YSK12-LNPs with DLin-MC3-DMA (MC3-LNPs) LNPs. 𝗙𝗶𝗻𝗱𝗶𝗻𝗴𝘀 𝗿𝗲𝘃𝗲𝗮𝗹𝗲𝗱 𝘁𝗵𝗮𝘁 𝗠𝗖𝟯-𝗟𝗡𝗣𝘀 𝗱𝗲𝗹𝗶𝘃𝗲𝗿𝗲𝗱 𝗺𝗼𝗿𝗲 𝗦𝗧𝗜𝗡𝗚 𝗮𝗴𝗼𝗻𝗶𝘀𝘁𝘀 𝘁𝗼 𝘁𝗵𝗲 𝗹𝗶𝘃𝗲𝗿 𝗮𝗻𝗱 𝘄𝗲𝗿𝗲 𝗶𝗻𝘁𝗲𝗿𝗻𝗮𝗹𝗶𝘇𝗲𝗱 𝗯𝘆 𝗺𝗼𝗿𝗲 𝗹𝗶𝘃𝗲𝗿 𝗹𝗲𝘂𝗸𝗼𝗰𝘆𝘁𝗲𝘀, 𝘄𝗵𝗶𝗹𝗲 𝗬𝗦𝗞𝟭𝟮-𝗟𝗡𝗣𝘀 𝗱𝗲𝗹𝗶𝘃𝗲𝗿𝗲𝗱 𝗵𝗶𝗴𝗵𝗲𝗿 𝗮𝗺𝗼𝘂𝗻𝘁𝘀 𝗱𝗶𝗿𝗲𝗰𝘁𝗹𝘆 𝘁𝗼 𝗹𝗶𝘃𝗲𝗿 𝗹𝗲𝘂𝗸𝗼𝗰𝘆𝘁𝗲𝘀, 𝗶𝗻𝗱𝘂𝗰𝗶𝗻𝗴 𝘀𝘁𝗿𝗼𝗻𝗴𝗲𝗿 𝗶𝗻𝗻𝗮𝘁𝗲 𝗶𝗺𝗺𝘂𝗻𝗶𝘁𝘆 𝗮𝗻𝗱 𝘁𝘂𝗺𝗼𝗿 𝗶𝗻𝗳𝗹𝗮𝗺𝗺𝗮𝘁𝗶𝗼𝗻. Interestingly, both LNP types showed similar antitumor effects in lung metastasis and tumor models. Yet, YSK12-LNPs were more likely to activate natural killer cells and M1 macrophages, while MC3-LNPs activated CD8+ T cells. 𝗧𝗵𝗶𝘀 𝘀𝘁𝘂𝗱𝘆 𝘂𝗻𝗱𝗲𝗿𝘀𝗰𝗼𝗿𝗲𝘀 𝘁𝗵𝗲 𝗻𝗲𝗲𝗱 𝘁𝗼 𝘂𝗻𝗱𝗲𝗿𝘀𝘁𝗮𝗻𝗱 𝗻𝗮𝗻𝗼𝗽𝗮𝗿𝘁𝗶𝗰𝗹𝗲 𝗯𝗲𝗵𝗮𝘃𝗶𝗼𝗿 𝗶𝗻 𝘃𝗶𝘃𝗼 𝘁𝗼 𝗼𝗽𝘁𝗶𝗺𝗶𝘇𝗲 𝗮𝗻𝘁𝗶𝘁𝘂𝗺𝗼𝗿 𝘁𝗿𝗲𝗮𝘁𝗺𝗲𝗻𝘁𝘀. Kudos to authors: Rikito Endo, Tomoki Ueda, @Takumi Nagaoki, @Natsumi Shima, @Yusuke Sato, Hideyoshi Harashima, @Takashi Nakamura Check here for more: https://lnkd.in/gNXuWQ6h

Glioblastoma is the most aggressive malignant primary brain tumour with an average survival time of around 15-20 months. Research in Nature Communications identifies a molecular signature of network connectivity in glioblastoma, with the potential to inform novel biomarker and therapeutic development. Read the original article: https://lnkd.in/ezCWvnnt #cancerresearch #glioblastoma #biomarkerdiscovery

This may support the mechanisms of action regarding Curucmin and omega 3 having an anti-inflammatory effect in Alzheimer’s via reduced TNF-A and IL-6 activation. In essence if beta amyloid plaques are a form of cytokine then this could exemplify why curcumin and omega 3 have a positive impact in Alzheimer’s patients. Further research is needed to validate the AB plaque-cytokine connection but very interesting and warranting further research.

https://lnkd.in/dt3bnXPW PRECAME Study: Preventing cardiovascular effects with metformin in obese patients ( Corpori Sano Biotechnology & Walter LAB, Brasil 🇧🇷 2002 ): " Creating a scientific basis for an infinite possibility of future studies and research " " Specific therapy, to live healthily " " A new therapeutic approach in cardiovascular, metabolic and oncological prevention " " Creating a scientific basis for an infinite possibility of future studies and research " " The era of insulin resistance modulators, ability to alter the cellular regulatory circuit " " Scientific research that studies the basis of the iceberg of cardiovascular disease " " Through innovative medicines for public health and committed to bringing better health and a better future for patients, translating science and regenerative medicine into medicines that change human lives, as the main objective " " PRECAME Study and Walter's Metabolic Theory, improving the perspective and quality of life of patients " #science #ciencia #cardiovascular #cancer #oncology

β-Amyloid (Aβ) is ubiquitous in ALZHEIMER’S DISEASE (AD) pathology, central to AD’s neuropathological diagnosis, and contentiously argued to be pivotal to disease pathogenesis. Recent data however suggest that AD is also an immunopathic disorder – and thus an obvious question emerges: does Aβ play a role in the immunopathy of AD? Or even more specifically, is Aβ an immunopeptide, and if so, what type of immunopeptide, and why does it go rogue to contribute to AD? I am pleased that our thoughts on answering these questions have now been published in ACS Chemical Neuroscience (link below). We conclude that Aβ is a kinocidin, where kinocidins are cytokines with antimicrobial properties: i.e. kinocidins are immunopeptides with the combined properties of both cytokines and antimicrobial peptides, thereby enabling Aβ to be not only antibacterial/antiviral but also to interact extensively with other inflammatory cytokines and molecular elements of the innate immunity network. The implications are significant: For example, does this mean that Aβ-targeting biologics (lecanemab, donanemab) are analogous to other biologics such as infliximab (TNF-α) or tocilizumab (IL-6) that inhibit cytokine-mediated inflammation? Also, might this concept open new venues for drug design and development for AD?   Read here: https://lnkd.in/gP63ZCVz   #alzheimerdisease, #dementia, #neurodegeneration, #drug design, #immunology, #neuroimmunology

We are beyond excited to share our latest work on the role of peroxiredoxin 6 (PRDX6) in #ferroptosis out today in Molecular Cell and spearheaded by two exceptional postdocs in our lab Helmholtz Munich: Eikan Mishima and Junya Ito. This study proposes PRDX6 as a novel ferroptosis regulator by acting as an intracellular selenium transport protein. Its role is crucial for effectively utilizing selenium, a vital component for synthesizing selenoproteins, including GPX4, thereby regulating the propensity to undergo #ferroptosis. Our findings furthermore suggest that PRDX6 could be a promising therapeutic target for cancer treatment via ferroptosis modulation. It may also offer valuable clues to better understand the underlying mechanisms driving #neurodegenerative disease. My heartfelt appreciation goes out to all collaborators and funding agencies, including Deutsche Forschungsgemeinschaft (DFG) - German Research Foundation, and the European Research Council (ERC), having made this achievement possible! The full article can be found here: https://lnkd.in/dWQhhtNW