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Proceedings of ICIS SGCR-WIRES 2024, held jointly with the 23rd International Cancer Imaging Society Annual Conference, collaborating with the Singapore Radiological Society and College of Radiologists Singapore.

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… Material(s) and Method(s): HGSOC cells, derived from the ascites of stage 3–4 HGSOC patients, were maintained as patient derived organoids (PDO) and implanted into mice subcutaneously. … Results: In patient-derived organoids and xenografts, the low OXPHOS subtypes (PDOs 1 and 5) showed increased lactate dehydrogenase activity, increased monocarboxylate transporter 4 expression and increased lactate labelling in 13C MRS measurements of hyperpolarized [1-13C]pyruvate metabolism. …

CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool.

Bacteriophages are pervasive viruses that infect bacteria, relying on their genetic machinery to replicate. In order to protect themselves from this kind of invader, bacteria developed an ingenious adaptive defence system, clustered regularly interspaced short palindromic repeats (CRISPR). Researchers soon realised that a specific type of CRISPR system, CRISPR-Cas9, could be modified into a simple and efficient genetic engineering technology, with several improvements over currently used systems. This discovery set in motion a revolution in genetics, with new and improved CRISPR systems being

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… Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat. Med. 2015;21:256–262. doi: 10.1038/nm.3802. 159. Chen S., Sanjana N.E., Zheng K., Shalem O., Shi X., Scott D.A., Song J., Pan J.Q., Weissleder R., Zhang F., et al. … Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell. 2013;13:653–658. doi: 10.1016/j.stem.2013.11.002. 168. Li C., Ding L., Sun C.W., Wu L.C., Zhou D., Pawlik K.M., Khodadadi-Jamayran A., Westin E., Goldman F.D., Townes T.M. …

Precision-Engineered CD3 T-Cell Engagers for Solid Tumours: Conditional Activation, Microenvironment Modulation, and Clinical Translation.

BackgroundT-cell-engaging bispecific antibodies (TCEs) have transformed haematological malignancy treatment (blinatumomab > 40% complete remission), yet solid tumour efficacy remains limited (MethodsReview of 55 phase I-III trials of CD3-based TCEs in solid tumours, including tarlatamab (DLL3-targeted, small-cell lung cancer) and xaluritamig (STEAP1-targeted, prostate cancer). Analysis of next-generation engineering strategies and resistance mechanisms via genomic and immunohistochemical data.ResultResponse rates now approach ~40% in selected settings, marking an inflection point. In extensive

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… In this context, three-dimensional colorectal cancer organoids have emerged as robust models for interrogating T-cell engagers such as CEA-TCB (cibisatamab), revealing how antigen density and microenvironment architecture shape therapeutic success [ 78 , 79 ]. …

Current concepts of the crosstalk between lncRNA and E2F1: shedding light on the cancer therapy.

Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context of cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These lncRNAs serve as competitive endogenous RNAs (ceRNAs) through sponging microRNAs and regulating the expression of targeted genes. Moreover, they also directly bind to RNA-binding proteins, which can be integrated into a complex mechanistic network. E2F1, an extensively studied

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… Additionally, advancements in human organoids, offer opportunities to boost clinical development in the realm of lncRNA research ( Diermeier and Spector, 2017 ). 3) An effective lncRNA delivery system is required for effective cancer treatment. … Antisense oligonucleotide-mediated knockdown in mammary tumor organoids. Bio Protoc. 7 (16), e2511. 10.21769/BioProtoc.2511 Dong W., Zhan C. (2022). Bioinformatic-based mechanism identification of E2F1-related ceRNA and E2F1 immunoassays in hepatocellular carcinoma. J. Gastrointest. …

Muscle and Bone Defects in Metastatic Disease.

PURPOSE OF REVIEW: The present review addresses most recently identified mechanisms implicated in metastasis-induced bone resorption and muscle-wasting syndrome, known as cachexia. RECENT FINDINGS: Metastatic disease in bone and soft tissues is often associated with skeletal muscle defects. Recent studies have identified a number of secreted molecules and extracellular vesicles that contribute to cancer cell growth and metastasis leading to bone destruction and muscle atrophy. In addition, alterations in muscle microenvironment including dysfunctions in hepatic and mitochondrial metabolism ha

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… There has been an increased interest in generating new three-dimensional (3D) in vitro models including patient-derived xenograft models, organoid, and scaffold models that can mimic native bone microenvironment [ 176 – 185 ]. … Novel dormancy mechanism of castration resistance in bone metastatic prostate cancer organoids. Int J Mol Sci [Internet]. MDPI; 2022;23:3203. Available from: https://pubmed.ncbi.nlm.nih.gov/35328625 179. Laranga R, Duchi S, Ibrahim T, Guerrieri AN, Donati DM, Lucarelli E. …

Gene regulation by non-Coding RNAs in infertility: a mechanistic review.

Infertility is a significant global health issue affecting millions of couples, with noncoding RNAs (ncRNAs) emerging as pivotal regulators in reproductive biology. This review explores the roles of various ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), PIWI-interacting RNAs (piRNAs), and circular RNAs (circRNAs) in male and female infertility. These ncRNAs modulate critical processes such as spermatogenesis, oogenesis, follicular development, and embryo implantation through mechanisms like post-transcriptional regulation, chromatin remode

Неврология Андрогенса и Андродогенных добавок.

ЦЕЛЬ ОБЗОРА: В этой статье рассматривается сложная взаимосвязь между индрогенами, индрогенными рецепторами и центральной нервной системой. Мы изучаем роль физиологически производных ирогенов и андрогенных добавок в нейроразвитии и нейропластике и вникаем в участие индрогенных путей в патогенезе различных неврологических расстройств. ПОСЛЕДНИЕ ВЫВОДЫ: В настоящем обзоре обращается внимание на растущее признание тестостеронного и индрогенного сигналов в различных неврологических условиях, при этом имеются свидетельства как защитного, так и вредного воздействия в зависимости от дозы и контекста.

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… Additionally, it has been shown to increase neurogenic output of excitatory progenitors in human brain organoids [ 10 – 12 ]. The ability of androgens to facilitate formation, growth, and modulation of neural networks may represent a target for neural recovery following an insult to the CNS. …

Neutralizing antibody against GDF15 for treatment of cancer-associated cachexia.

GDF15 (growth differentiation factor 15), also known as macrophage inhibitory cytokine 1 (MIC-1), is a circulating protein involved in the regulation of energy balance and weight control. Elevated levels of GDF15 have been associated with cachexia and reduced survival rates in cancer patients. Through the activation of the GFRAL (GDNF-family receptor α-like)-RET (Rearranged during Transfection) signaling pathway, GDF15 can induce weight loss, making it a potential target for treating cachexia. Currently, there are no approved antibody drugs specifically targeting GDF15 for cancer cachexia trea

Regenerative rehabilitation: a novel multidisciplinary field to maximize patient outcomes.

Regenerative rehabilitation is a novel and rapidly developing multidisciplinary field that converges regenerative medicine and rehabilitation science, aiming to maximize the functions of disabled patients and their independence. While regenerative medicine provides state-of-the-art technologies that shed light on difficult-to-treated diseases, regenerative rehabilitation offers rehabilitation interventions to improve the positive effects of regenerative medicine. However, regenerative scientists and rehabilitation professionals focus on their aspects without enough exposure to advances in each

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… Organoids generated from patient-derived iPSCs can be used to address the issues of organ shortages and immune rejection. … Fowler JL Ang LT Loh KM A critical look: challenges in differentiating human pluripotent stem cells into desired cell types and organoids Wiley Interdiscip Rev Dev Biol 2020 9 e368 10.1002/wdev.368 31746148 PMC7397816 60. …

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound tr

The Emerging Role of Interleukin-32 in HIV-Associated Cardiovascular Comorbidities: A Mini Review.

With the widespread use of antiretroviral therapy (ART), the life expectancy of people living with HIV (PLWH) has significantly improved. However, the incidence of cardiovascular disease (CVD) in this population has progressively increased. PLWH exhibit a significantly higher risk of cardiovascular diseases compared to the general population. Consequently, CVD has become one of the leading contributors to mortality not related to AIDS. The pathogenesis may involve several factors: HIV-related proteins exacerbating endothelial injury and inflammation; immune activation and chronic inflammation;

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… IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids . Cell Rep Med . 2024 ; 5 ( 1 ): 101352 . doi: 10.1016/j.xcrm.2023.101352 38232700 PMC10829727 40. Sun Y , Qian Y , Chen C , et al. …

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expre

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… Single-cell profiling of GP2-enriched pancreatic progenitors to simultaneously create acinar, ductal, and endocrine organoids. Theranostics. 2023;13(6):1949–1973. doi: 10.7150/thno.78323. Associated Data Supplementary Materials Additional file 1. …

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and inva

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… Indeed, myCAFs and iCAFs were first identified via PDAC organoids and murine stellate cells [ 149 ] followed by validation in pancreatic cancer patients [ 150 ]. …

Всемирный конгресс молекулярного воображения 2022.

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Targeted phytotherapy: essential oils, multi-target cancer action & nanodelivery.

Biochemical components of essential oils (EOs) are an innovative but largely underexplored type of precision phytotherapy (PT) in oncology owing to their anticancer activity against many types of tumors. This article discusses the important multitargeted molecular mechanisms of EOs (apoptosis, cell cycle arrest, angiogenesis, metastasis, tumor microenvironment) and their role as antitumor agents. In particular, an effort has been made to emphasize on the most notable volatile EOs such as thymol, eugenol, limonene, β-caryophyllene, and their interaction with oncogenic signaling pathways (NF-κB,

Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.

The thioredoxin (Trx) system, an integral component of cellular redox regulation, preserves protein dithiol-disulfide equilibrium through its conserved Cys-Gly-Pro-Cys active site and is involved in key cellular functions, including cell proliferation, apoptosis, and signal transduction. In cancer biology, the thioredoxin system plays dual roles: overexpression can suppress oxidative stress and promote tumor growth, whereas dysfunction can trigger programmed cell death (PCD). However, a critical area for future research is to delineate how Trx modulates the intricate networks of PCD, and to id

Advanced multifunctional thermo- and electro-stimulative hydrogels for bone regeneration.

Bone defects caused by trauma, infection, tumors, osteoporosis, and diabetes disrupt skeletal integrity and impair regeneration. The healing process involves inflammatory hematoma formation, callus development, and remodeling, coordinated by diverse cells and signaling pathways. Conventional grafts and inorganic implants are limited by donor scarcity, immune rejection, and low bioactivity, necessitating more effective repair strategies. Recently, multifunctional smart hydrogels have emerged as a frontier in bone regeneration due to their biocompatibility, tunable structure, and ability to inte

Late Breaking Orals.

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Applications of nanotechnologies for miRNA-based cancer therapeutics: current advances and future perspectives.

MicroRNAs (miRNAs) are short (18-25 nt), non-coding, widely conserved RNA molecules responsible for regulating gene expression via sequence-specific post-transcriptional mechanisms. Since the human miRNA transcriptome regulates the expression of a number of tumor suppressors and oncogenes, its dysregulation is associated with the clinical onset of different types of cancer. Despite the fact that numerous therapeutic approaches have been designed in recent years to treat cancer, the complexity of the disease manifested by each patient has prevented the development of a highly effective disease

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… To overcome these limitations, it is crucial to employ appropriate biological models that closely mimic the specific conditions of lung cancer in humans (e.g., patient-derived xenografts, lung cancer organoids, and 3D cell cultures). … Therefore, it is essential to develop advanced biological models that better capture the unique characteristics of glioblastoma, such as patient-derived xenografts or three-dimensional organoids, to improve the translatability of miRNA nanoformulations into clinical trials. …

Identification and verification of the key genes involved in gallbladder cancer.

BackgroundGallbladder cancer (GBC) is a highly aggressive malignancy of the biliary tract. It often lacks distinct symptoms in its early stages, and no specific biomarkers have yet been identified for its diagnosis.ObjectiveTo identify key genes involved in GBC pathogenesis using public databases and bioinformatics analysis and validate these findings experimentally, providing a foundation for developing potential GBC biomarkers.MethodsAnalysis of GBC-related data from the Gene Expression Omnibus database revealed that G protein-coupled receptor 64 (GPR64) was differentially expressed in GBC.

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… Cancer organoids 2.0: modelling the complexity of the tumour immune microenvironment . Nat Rev Cancer . ( 2024 ) 24 : 523–39 . doi: 10.1038/s41568-024-00706-6 , PMID: 38977835 40 Oliveira G Wu CJ . Dynamics and specificities of T cells in cancer immunotherapy . …