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Research Communications of the 26th ECVIM‐CA Congress

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… For feline organoids the β oxidation of excess FFA was studied using a carnitine palmitoyltransferase‐1 inhibitor (etomoxir) and supplementation of L‐carnitine. Organoids could be cultured successfully from all feline liver samples. … Feline liver organoids showed lipid accumulation when exposed to excess FFA and accumulated more lipids than human liver organoids. Lipid accumulation was enhanced when β oxidation was blocked with etomoxir and was attenuated when medium was supplemented with L‐carnitine. …

Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.

Adoptive T-cell transfer therapy (ACT) has significantly propelled the advancement of tumor immunotherapy. Among various strategies targeting solid tumors, the T-cell receptor (TCR)-engineered T-cell (TCR-T cell) therapy has emerged as a highly promising approach, exhibiting an expanded therapeutic window across diverse patient populations and superior tumoricidal activity in certain solid malignancies compared with chimeric antigen receptor T cell (CAR-T) and tumor-infiltrating T cells/lymphocyte (TIL) therapies. However, its clinical efficacy remains constrained. In this paper, we introduce

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… Xu Wang et al. integrated ultradeep single-cell TCR/RNA sequencing with autologous organoid technology to rapidly characterize neoantigen-reactive TCRs [ 81 ]. … Furthermore, the tumor organoids and autologous TILs co-culture systems have effectively amplified and isolated TCR-T cells, addressing challenges associated with imprecise antigen prediction and time-consuming synthesis [ 27 ]. …

Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk.

Cancer neuroscience is an emerging field that investigates the intricate relationship between the nervous system and cancer, gaining increasing recognition for its importance. The central nervous system governs the development of the nervous system and directly affects brain tumors, and the peripheral nervous system (PNS) shapes the tumor microenvironment (TME) of peripheral tumors. Both systems are crucial in cancer initiation and progression, with recent studies revealing a more intricate role of the PNS within the TME. Tumors not only invade nerves but also persuade them through remodeling

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… More advanced 3D organoid culture methods, which incorporate nerve cells, glial cells, immune cells, and cancer‐associated fibroblasts, offer a more accurate representation of the in vivo tumor environment. 354 , 355 , 356 Ongoing clinical trials with patient‐derived organoids may lead to personalized …

UEG Week 2017 Oral Presentations

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Utilization of Stem Cells in Medicine: A Narrative Review.

Regenerative medicine holds significant promise for addressing diseases and irreversible damage that are challenging to treat with conventional methods, making it a prominent research focus in modern medicine. Research on stem cells, a key area within regenerative medicine due to their self-renewal capabilities, is expanding, positioning them as a novel therapeutic option. Stem cells, utilized in various treatments, are categorized based on their differentiation potential and the source tissue. The term 'stem cell' encompasses a broad spectrum of cells, which can be derived from embryonic tiss

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… Newer approaches involving human-induced pluripotent stem cells (hiPSCs), derived from sources such as dermal fibroblasts or hair follicles, have shown potential to generate corneal epithelial cells and three-dimensional corneal organoids [ 171 ]. … Future directions include enhancing engraftment strategies, incorporating stem cell-derived organoids, and optimizing delivery platforms to bridge the gap between experimental models and clinical translation. 4. …

Коэффициенты транскрипции заболеваний экзокринной и эндокринной поджелудочной железы: эффекты, механизмы и клинические последствия.

Белки BTB и CNC (BACH) BACH1 и BACH2 являются высоко сберегаемыми транскрипционными репрессорами, которые оказывают свое воздействие, образуя гетеродимеры с маленькими мускулопоневрологическими фибросаркома (MAF). BACH1 повсеместно выражается и выполняет функции, конкурируя с эритроидом ядерного фактора 2-like 2 (NRF2) для привязки к MAF. Ограничивая транскрипцию гема кислородазы 1 (В тыс.HO-1/HMOX1), BACH1 препятствует выражению генов, участвующих в реакции клеточного окислительного стресса. Выражение BACH2 в основном ограничивается иммунными клетками как в врожденных, так и в адаптивных отсе

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… The studies on cell cultures should be extended to models closer to the patient, such as patient-derived organoids from resectates or punctates. At the animal model level, there is a need for studies on genetically engineered mouse models of PDAC, which currently best reflect human pathogenesis. …

Exploiting Nanomedicine for Cancer Polychemotherapy: Recent Advances and Clinical Applications.

The most important limitations of chemotherapeutic agents are severe side effects and the development of multi-drug resistance. Recently, the clinical successes achieved with immunotherapy have revolutionized the treatment of several advanced-stage malignancies, but most patients do not respond and many of them develop immune-related adverse events. Loading synergistic combinations of different anti-tumor drugs in nanocarriers may enhance their efficacy and reduce life-threatening toxicities. Thereafter, nanomedicines may synergize with pharmacological, immunological, and physical combined tre

Cell-to-cell communication in cancer: workshop report.

Recent advances in cancer biology and the development of new research tools have enabled interrogations of single cells and cell-cell interactions. Emerging technologies are capable of revealing data on the physical characteristics of cells, differences in the genome and proteome between cancerous and healthy cells, and variations in distinct cell subpopulations. Dynamic measurements enable studies that can reveal the evolution of cell characteristics. Cells can also be assembled in vitro or ex vivo into two- and three-dimensional cell environments, allowing for studies of cell-cell interactio

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… Although there was consensus that the complexity of the model depends on the experimental question(s), it was agreed that issues of vascularization and the viability of endothelial cells in mixed cultures and organoids, as well as how to retain viability of stromal cells, are inescapable. …

Tuning epigenetics to enhance cancer virotherapy.

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immu

Enhanced Antitumor Activity and Induction of Immunogenic Cell Death in NUT Carcinoma Cells by Combining Oncolytic Viruses with the Dual Inhibitor NEO2734.

NUT carcinoma (NC) is a rare exceptionally aggressive malignancy, defined by NUTM1 gene translocations, most commonly generating a BRD4::NUTM1 fusion that results in a poor prognosis and limited therapeutic options. Oncolytic virotherapy has emerged as a promising strategy for NC, and the dual bromodomain and extra-terminal domain (BET) and p300/CBP inhibitor NEO2734 has demonstrated potent antiproliferative activity. To investigate multimodal therapeutic approaches that combine epigenetic modulation with immunogenic and cytotoxic effects of oncolytic viruses (OVs), we evaluated two recombinan

Gene therapy of rare diseases as a milestone in medicine - overview of the field and report on initial experiences in Slovenia.

Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients' lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field s

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… The latter began developing gene therapy using an AAV9 vector on Urban’s cells and organoids, while Prof. Jerala’s group started exploring alternative treatment technologies and supporting preclinical drug testing in the Laboratory for in vivo experiments, led by Dr. Duško Lainšček at the NIC. … Once candidate drugs were identified through work on cells and cell organoids, they were tested on a mouse model of CTNNB1 syndrome created specifically for this purpose. …

Advancements in extensive-stage small cell lung cancer therapy: from molecular profiling to the advent of precision oncology.

Small cell lung cancer (SCLC) is challenging to manage due to its high malignancy and early metastatic spread. Although initial chemoradiotherapy responses are common, resistance rapidly develops, and long-term efficacy remains limited. Immune checkpoint inhibitors (ICIs) overcome previous survival barriers, extending overall survival (OS) and progression-free survival (PFS) in extensive-stage SCLC. Nevertheless, absolute clinical benefits remain modest. To address efficacy limitations, current research focuses on optimizing first-line strategies by exploring multimodal regimens (e.g., adding

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… Concurrently, preclinical models—encompassing murine cell lines, organoids ( 77 ), PDX, and genetically engineered mouse models (GEMMs)—have undergone significant refinement. … 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 …

Indian Ayurvedic medicine: Overview and application to brain cancer.

Ayurveda is the traditional medicine system of India, and has been in practice for millennia. It is a traditional approach that uses 1000's of different plant preparations in various combinations for treatment of human ailments, including cancer. Ethnopharmacological and phytochemical analyses are now elucidating the bioactive constituents of the different plant species and herbal formulations, including ashwagandha, curcumin, guduchi, triphala, and others. To provide an overview of: 1) the ethnopharmacology of Ayurveda and several of its most important plant species and formulations, includin

The osteoblast in regulation of tumor cell dormancy and bone metastasis.

Breast and prostate cancer are among the most common malignancies worldwide. After treatment of the primary tumor, distant metastases often occur after a long disease-free interval. Bone is a major site for breast and prostate cancer metastasis and approximately 70% of patients with advanced disese suffer from osteolytic or osteoblastic bone metastases, a stage at which the disease is incurable. In bone, the disseminated tumor cells (DTCs) can become quiescent or "dormant", a state where they are alive but not actively dividing. Alternatively, the cancer cells can proliferate, disturb the bone

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… Organoid 3D cell culture models have shown that the crosstalk between breast cancer cells (MCF-7, MDA-361, 4T1, 4TO7) and MSCs (mouse and human MSCs and FOB1.19 cells) accelerates tumor growth compared to organoids lacking MSCs [29] . …

The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.

Immunity to solid tumors is associated with the hallmarks of cancer-associated inflammation and the ability of immune mechanisms to limit tumor progression. Application of expanded tumor-infiltrating lymphocyte adoptive T cell therapy (TIL ACT) in clinical trials is now practiced at many sites around the world. Prior to immune checkpoint blockade (ICB), an approximate 50% objective response rate was consistently observed across multiple institutions for patients with melanoma. This now-approved strategy approaches 35% in recent studies from the USA and 49% with more highly selected patients in

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… Although sufficient TIL have been generated from lesions with aspirates or biopsies, conservative approaches would recommend resecting sufficient tumors to both allow generation of TIL but also paired autologous organoids, when possible. 10 The second step typically involves trimming the material of … WES of patient-derived tumor organoids can demonstrate false negatives from fresh tumor WES. …

Mechanisms, Diagnosis and Treatment of Bone Metastases.

Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. However, current therapeutic options for patients with bone metastatic disease are limited in efficacy and associated with increased morbidity. Therefore, most current therapies are mainly palliative in nature. A better understanding of the underlying molecular pathways of the bone metastatic process is warranted to develop novel, wel

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… More recently, bone explant [ 258 ] and scalable 3D in vitro models based on organoid and 3D bioprinting technologies have moved into the focus of pre-clinical research. … As an example, it was shown that organoids generated from human prostate cancer bone metastases retained the same resistance pattern to antiandrogen therapy as the patients’ metastases [ 259 ]. …

Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern.

Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute respiratory syndrome (SARS)-CoV-2 spreads across the world with impact on health and societies. Here, we report an image-based multicycle infection procedure with α-coronavirus hCoV-229E-eGFP in an arrayed chemical library screen of 5440 clinical and preclinical compounds. Toxicity counter selection and challenge with the β-coronaviruses OC43 and SARS-CoV-2 in tissue culture and human airway epithelial explant cultures (HAEEC) identified four FDA-approved compounds with ora

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… And MPA inhibits SARS-CoV-2 infection of humanized mice and human lung organoids ( Park, 2011 ). … Identification of SARS-CoV-2 inhibitors using lung and colonic organoids. Nature. 2021;589(7841):270–275. doi: 10.1038/s41586-020-2901-9. Hata K., Kimura J., Miki H., Toyosawa T., Nakamura T., Katsu K. …

Facing CAR T Cell Challenges on the Deadliest Paediatric Brain Tumours.

Central nervous system (CNS) tumours comprise 25% of the paediatric cancer diagnoses and are the leading cause of cancer-related death in children. Current treatments for paediatric CNS tumours are far from optimal and fail for those that relapsed or are refractory to treatment. Besides, long-term sequelae in the developing brain make it mandatory to find new innovative approaches. Chimeric antigen receptor T cell (CAR T) therapy has increased survival in patients with B-cell malignancies, but the intrinsic biological characteristics of CNS tumours hamper their success. The location, heterogen

2018 ACVIM Forum Research Report Program. Seattle, Washington, June 14 - 16, 2018.

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… Organoids were cryopreserved for the development of a canine ENT/COL bioarchive. Ten endoscopic biopsies per intestinal region were acquired from healthy or CE dogs. Minced samples were repeatedly washed. … Organoid yield was 5 enteroids/biopsy and 30 colonoids/biopsy on average. Optimized intestinal stem cell growth media for proliferation versus differentiation contained rho‐associated kinase ROCK inhibitor Y27632, glycogen synthase kinase 3β inhibitor CHIR99021, and wnt‐3a. …

C-X-C chemokine receptor type 4 (CXCR4) antagonism in precision oncology: Clinical applications and future directions.

Physiologically, the C-X-C chemokine receptor type 4 (CXCR4) signalling pathway regulates key aspects of tumor behavior (growth, metastasis, and immune evasion) and modulates immune system function. Anticancer researchers have identified peptide-based CXCR4 antagonists as promising candidates due to their high targeting specificity and favorable safety profiles. This review provides an analytical examination of CXCR4 antagonistic peptides,the selective Mavorixafor (X4P-001), an advanced, selective CXCR4 inhibitor. When Mavorixafor binds to the same location as C-X-C motif chemokine ligand 12 (

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… Extracellular vesicles secreted by 3D tumor organoids are enriched in stemness-associated markers and modulate tumor microenvironment Front Immunol 15 2024 1388769 10.3389/fimmu.2024.1388769 PMC11079215 38726003 26 Li J. Zhang Z. Sun Y. … Organoids in cancer therapies: a comprehensive review Front Bioeng Biotechnol 13 2025 1607488 10.3389/fbioe.2025.1607488 PMC12322668 40766972 27 Ramalingam K. Yadalam P.K. Ramani P. …