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Palbociclib regulates the expression of dihydrofolate reductase and the cell cycle to inhibit t (11;14) multiple myeloma.

BackgroundMultiple myeloma (MM) with t (11;14) has a unique biology. New combinations of novel agents are needed to improve the prognosis of patients with t (11;14) MM. As a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), palbociclib (PAL) has been used to treat various malignancies, including breast cancer, ovarian cancer, and so on. However, the effects of PAL on MM remain unclear, and thus, further investigations are warranted.MethodsTwo t (11;14) MM cell lines, U266 and KMS27, were used in this study. The cell viability and cell cycle were detected to evaluate the anti-my

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… Organoids in cancer research. Nat Rev Cancer 2018;18:407-18. 10.1038/s41568-018-0007-6 27. Yin Y, Liu PY, Shi Y, et al. Single-Cell Sequencing and Organoids: A Powerful Combination for Modelling Organ Development and Diseases. …

Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells' Escape from the Bone Marrow Microenvironment.

Recent therapeutic advancements have markedly increased the survival rates of individuals with multiple myeloma (MM), doubling survival compared to pre-2000 estimates. This progress, driven by highly effective novel agents, suggests a growing population of MM survivors exceeding the 10-year mark post-diagnosis. However, contemporary clinical observations indicate potential trends toward more aggressive relapse phenotypes, characterized by extramedullary disease and dominant proliferative clones, despite these highly effective treatments. To build upon these advances, it is crucial to develop m

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… Does not model the perivascular niche. | [ 54 ] Spheroids + hydrogel | iPSC, MSCs, MM cells | Matrigel and Collagen Type I | 12 days | Bone marrow organoids support the engraftment, survival, and proliferation of MM cells. | Lacking natural occurring haematopoiesis. … Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies. Cancer Discov. 2023;13:364–385. doi: 10.1158/2159-8290.CD-22-0199. 56. …

Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization.

Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer cells and stromal components. This review consolidates current findings that position EVs as key architects of the bone-metastatic niche. We detail the biogenesis of EVs and their organotropic distribution, focusing on how integrin patterns and bone-specific ligands guide vesicle homi

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… In model systems, organoids are three-dimensional cell clusters grown from stem cells using specialized 3D culture techniques. These techniques allow the cells to self-organize and regenerate, mimicking the structure and function of the original tissue [ 228 ]. … EVs derived from organoids (OEVs) provide advantages such as increased yield of EVs, cargo consistency, and biocompatibility, which can be implemented for both diagnostic and therapeutic applications of EVs [ 229 ]. …

Nanomedicine for cancer patient-centered care.

Cancer is a leading cause of morbidity and mortality worldwide, and an increase in incidence is estimated in the next future, due to population aging, which requires the development of highly tolerable and low-toxicity cancer treatment strategies. The use of nanotechnology to tailor treatments according to the genetic and immunophenotypic characteristics of a patient's tumor, and to allow its targeted release, can meet this need, improving the efficacy of treatment and minimizing side effects. Nanomedicine-based approach for the diagnosis and treatment of cancer is a rapidly evolving field. Se

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… or spheroids, 177 , 178 can be assessed by LSC, flow cytometric analyses, and real‐time RT‐PCR or single cell sequencing. 179 High‐content screening measuring biological parameters and imaging platforms that are designed for single‐cell or whole organoids analysis and lightning‐fast time‐to‐data, perform … unbiased spontaneous phenotyping with live cells from the patient's tumor‐derived organoids. 180 Biodistribution and pharmacokinetics OOC technology allows to analyze the biodistribution of nanoparticles within the OOC compartments, tracking their movement and accumulation. …

Clinical Trials of Stem Cell Therapy in Japan: The Decade of Progress under the National Program.

Stem cell therapy is a current world-wide topic in medical science. Various therapies have been approved based on their effectiveness and put into practical use. In Japan, research and development-related stem cell therapy, generally referred to as regenerative medicine, has been led by the government. The national scheme started in 2002, and support for the transition to clinical trials has been accelerating since 2011. Of the initial 18 projects that were accepted in the budget for preclinical research, 15 projects have begun clinical trials so far. These include the transplantation of retin

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… The colonic stem cell-derived organoids showed the integration and repairment of an artificial ulcer in mouse colon, promising clinical application for inflammatory bowel diseases [ 15 ]. … Protocol for the generation and expansion of human iPS cell-derived ureteric bud organoids STAR Protoc. 2022 3 101484 10.1016/j.xpro.2022.101484 35769929 PMC9234152 64. Ikeo S. Yamamoto Y. Ikeda K. Sone N. Korogi Y. Tomiyama L. Matsumoto H. Hirai T. Hagiwara M. Gotoh S. …

CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment.

Cancer is a genetic disease stemming from genetic and epigenetic mutations and is the second most common cause of death across the globe. Clustered regularly interspaced short palindromic repeats (CRISPR) is an emerging gene-editing tool, acting as a defense system in bacteria and archaea. CRISPR/Cas9 technology holds immense potential in cancer diagnosis and treatment and has been utilized to develop cancer disease models such as medulloblastoma and glioblastoma mice models. In diagnostics, CRISPR can be used to quickly and efficiently detect genes involved in various cancer development, prol

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… In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis . Nat. Biotechnol . 2017 ; 35 ( 6 ): 569 ‐ 576 . 28459449 10.1038/nbt.3836 PMC5462879 80 Bakshi R Hassan MQ Pratap J , et al. … Modeling colorectal cancer using CRISPR-Cas9–mediated engineering of human intestinal organoids . Nat. Med . 2015 ; 21 ( 3 ): 256 ‐ 262 . 25706875 10.1038/nm.3802 …

From undruggable to degradable: A deep learning-enabled framework for precision orthopaedic protein degradation.

BACKGROUND/OBJECTIVE: A fundamental translational impasse in musculoskeletal disorders-from osteoarthritis to bone metastases-is the "undruggability" of critical pathological drivers sequestered within anatomically restricted and avascular skeletal niches. While Targeted Protein Degradation (TPD) offers a revolutionary event-driven modality to eradicate these refractory targets, its clinical translation to orthopaedics is severely hindered by the physicochemical incompatibility of large degraders with dense extracellular matrices and the scarcity of bone-specific E3 ligases. METHODS: In this

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… Experimental validation in microphysiological systems, organoids, and in vivo models, coupled with quantitative imaging endpoints, closes the loop by updating disease atlases and model parameters for iterative improvement. … Experimental validation in microphysiological systems, organoids, and in vivo models, coupled with quantitative imaging endpoints, closes the loop by updating disease atlases and model parameters for iterative improvement. …

ISEV2025 Резюме книги.

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… Results : We found that selective KRAS gene (G12D and G12V) inhibition and the synergistic anticancer effect of KRAS ASO and immRNA delivered by RBCEVs in mutant‐specific pancreatic cancer cell lines and patient‐derived organoids. …

Gene editing in cancer therapy: overcoming drug resistance and enhancing precision medicine.

The CRISPR system has revolutionized cancer gene therapy, offering unparalleled precision in genetic manipulation for targeted oncogene disruption, mutation correction, and immune system modulation. This breakthrough tool has demonstrated remarkable potential in overcoming drug resistance, enhancing chemotherapy sensitivity, and improving immunotherapy strategies such as CRISPR-engineered CAR-T cells. Additionally, oncolytic virus-mediated CRISPR delivery has emerged as a novel approach for tumor-specific gene editing, minimizing off-target effects. The rapid transition of CRISPR-based cancer

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… For instance, BEs have been successfully applied in patient-derived organoid (PDO) models targeting mutations in KRAS and TP53 . In PDOs of pancreatic ductal adenocarcinoma, efficient correction of the KRAS G12D was achieved, with an editing frequency of 30%. … These precise corrections led to a marked depletion of mutant cells and significant suppression of abnormal growth in cancer organoids. …

The Role of the CCR5 Receptor in Neuropathic Pain Modulation: Current Insights and Therapeutic Implications.

Neuropathic pain, a chronic condition arising from injury or dysfunction of the somatosensory nervous system, is characterized by persistent hypersensitivity and spontaneous pain. The chemokine receptor CCR5 (C-C motif chemokine receptor 5) has recently been identified as a critical mediator in neuroinflammation and neuropathic pain signaling pathways. Expressed on immune cells and neurons, CCR5 regulates immune cell recruitment and activation, thereby contributing to neuronal sensitization and maintenance of pain states. This review examines the currently characterized molecular mechanisms th

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… Humanized mouse models [ 243 ], patient-derived organoids [ 244 ], and high-throughput screening platforms [ 245 ] could provide insights into CCR5 biology in human tissues, helping to refine therapeutic strategies. …

ISEV2021 Abstract Book

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Precision in Action: The Role of Clustered Regularly Interspaced Short Palindromic Repeats/Cas in Gene Therapies.

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated enzyme-CAS holds great promise for treating many uncured human diseases and illnesses by precisely correcting harmful point mutations and disrupting disease-causing genes. The recent Food and Drug Association (FDA) approval of the first CRISPR-based gene therapy for sickle cell anemia marks the beginning of a new era in gene editing. However, delivering CRISPR specifically into diseased cells in vivo is a significant challenge and an area of intense research. The identification of new CRISPR/Cas variants, particularly

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… The CAS system has been used to generate robust and reproducible model systems such as transgenic animals, brain organoids, IPS-derived cells, and cancer models to study various diseases, which was challenging before. … The development of 3D microglia-containing brain organoids to study HIV pathogenesis and CRISPR application in HIV eradication has been developed [ 253 ]. …

The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities.

Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone modifications and their therapeutic targeting in endometriosis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The current manuscript represents the most comprehensive, up-to-date review of the literature focusing on the parti

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… Organoids: A New Chapter in Sarcoma Diagnosis and Treatment. Int. J. Mol. Sci. 2022;23:1271. doi: 10.3390/ijms231911271. 81. Psilopatis I., Pergaris A., Vrettou K., Theocharis S., Troungos C. Thymic Epithelial Neoplasms: Focusing on the Epigenetic Alterations. Int. J. Mol. … Patient-Derived Organoids: The Beginning of a New Era in Ovarian Cancer Disease Modeling and Drug Sensitivity Testing. Biomedicines. 2022;11:1. doi: 10.3390/biomedicines11010001. 85. Psilopatis I., Vrettou K., Fleckenstein F.N., Theocharis S. …

Unlocking hidden potential: advancements, approaches, and obstacles in repurposing drugs for cancer therapy.

High rates of failure, exorbitant costs, and the sluggish pace of new drug discovery and development have led to a growing interest in repurposing "old" drugs to treat both common and rare diseases, particularly cancer. Cancer, a complex and heterogeneous disease, often necessitates a combination of different treatment modalities to achieve optimal outcomes. The intrinsic polygenicity of cancer, intricate biological signalling networks, and feedback loops make the inhibition of a single target frequently insufficient for achieving the desired therapeutic impact. As a result, addressing these c

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… It is also worth noting the importance of pre-clinical models of cancer that are simple enough for screening, yet able to recapitulate the drug response in patients—such as emerging 3D tumour organoids [ 123 ]. … Weeber F Ooft SN Dijkstra KK Voest EE Tumor organoids as a pre-clinical cancer model for drug discovery Cell Chem Biol 2017 24 1092 100 28757181 10.1016/j.chembiol.2017.06.012 124. …

Microgel-Based 3D Bioprinting: A Convergent Strategy Integrating Material Design, Jamming Dynamics, and Biological Function.

Driven by rapid technological innovation and an increasing demand for personalized medicine, microgel-based bioprinting emerges as a versatile strategy for generating physiologically relevant tissue models and patient-specific constructs. By integrating microgel systems with 3D bioprinting, this approach enables the creation of complex, cell-laden architectures that closely recapitulate native tissue architecture and function. Pivotal to this potential are microgels that offer significant advantages over conventional hydrogel-based bioinks, including tunable rheological behavior, enhanced prin

Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy.

Chimeric antigen receptor (CAR) engineered cellular immunotherapy offers the potential for precise targeting and elimination of tumor cells, providing a tailored approach to cancer treatment. CAR-T cells demonstrate significant anti-tumor activity among these therapies. Nonetheless, these therapies may trigger adverse effects, including inflammatory and neurotoxic reactions during treatment. Recent efforts have been directed toward enhancing efficacy by optimizing CAR design or modulating its activity. Compared to CAR-T cells, CAR-engineered natural killer cells (CAR-NK) present notable advant

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… Using tumor organoids from one hundred patients, the second trial ( NCT05007379 ) observes how CAR-M cells combat tumors [ 124 , 125 ]. … Organoids derived from in vitro three-dimensional culture systems similar to tissues or organs also provide new materials and targets for CAR-T cell therapy [ 87 ]. …

Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies.

The improvement of human living conditions has led to an increase in average life expectancy, creating a new social and medical problem-aging, which diminishes the overall quality of human life. The aging process of the body begins with the activation of effector signaling pathways of aging in cells, resulting in the loss of their normal functions and deleterious effects on the microenvironment. This, in turn, leads to chronic inflammation and similar transformations in neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of

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… Furthermore, it has been demonstrated that p16INK4a-positive lung fibroblasts contribute to the growth of respiratory tract stem cell organoids, suggesting their potential role in supporting epithelial regeneration. … However, in the context of intestinal organoids as a model for tissue regeneration, it has been demonstrated that senescence-associated secretory phenotype (SASP) factors, particularly the secreted N-terminal domain of Ptk7, released by aging fibroblasts, dysregulate the activity and differentiation …

Redefining Chemoresistance: Natural Bioactives as Molecular Modulators at the Cancer-Tumor Microenvironment Interface.

Therapeutic resistance remains a critical barrier in effective cancer treatment, contributing to disease recurrence, progression, and reduced patient survival. In recent years, natural bioactive compounds have emerged as promising adjuncts in oncology due to their ability to modulate multiple biological processes involved in resistance. This review explores current evidence on the role of natural compounds in influencing cancer cell behavior and their interactions with the tumor microenvironment. By organizing these compounds into chemical families, we provide a structured overview of their po

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… Consequently, updated translational approaches, such as patient-derived xenografts, 3D tumor organoids, and early-phase pharmacokinetic profiling, are increasingly advocated to better simulate human biology and optimize dosing strategies [ 246 , 247 , 248 ]. …

Emerging roles for the IL-6 family of cytokines in pancreatic cancer.

Pancreatic cancer has one of the poorest prognoses of all malignancies, with little improvement in clinical outcome over the past 40 years. Pancreatic ductal adenocarcinoma is responsible for the vast majority of pancreatic cancer cases, and is characterised by the presence of a dense stroma that impacts therapeutic efficacy and drives pro-tumorigenic programs. More specifically, the inflammatory nature of the tumour microenvironment is thought to underlie the loss of anti-tumour immunity and development of resistance to current treatments. Inflammatory pathways are largely mediated by the exp

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… IL-11 may have a pro-tumorigenic role in PDAC Both IL-11 and IL-11R are expressed by pancreatic organoids and PSCs, with higher expression in cells isolated from the primary tumour, compared with those from metastatic sites [ 36 ]. … Moreover, it is the PSCs, especially those with an iCAF phenotype, rather than the tumour organoids, which are the prominent producers of IL-11 [ 36 ]. …

Научные достижения в отношении роли остеобластов и их производных в разработке, повторении и удалении метастаза злокачественных опухолей костей: обзор повествования.

Злоумышленные опухоли костей, включая первичные опухоли костей, такие, как остеосаркома (OS), саркома Евинга (ES) и множественная миелома, а также вторичные опухоли костей от рака простаты и груди, создают значительный риск смертности. Остеобласт (OBs) и их производные играют важнейшую роль в развитии, повторении и метастазе этих опухолей. ОБ пропагандируют события, связанные с метастазом, включая остеокластную дифференциацию и распространение. Их производные, включая внеклеточные везикли и цитокины, модулярируют реконструкцию костей и развитие опухоли по различным сигнальным путям. Недавние и