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Миэлоидно-подавительские клетки в карциноме ларингеальных клеток: недостаточно изученная иммунодепрессивная ось и стратегическая цель преодоления ингибиторного сопротивления на контрольно-пропускных пунктах.

Углубленные клеточные карциномы (LSCC) указывают на неизменно низкий коэффициент объективной реакции на ингибиторы на контрольно-пропускных пунктах (ИКИ) в отношении запрограммированных death-1 (В тыс.PD-1Путь. Его иммуновосприимчивая опухоль (TME), обогащенная макрофагами, связанными с опухолью, иммунодепрессивными опухолью, связанными с нейтрофилами (TANs), и регуляционными Т клетками, является основным фактором отказа ICI. Пока что one Миелоидное население, имеющее центральное значение для сопротивления ИКИ во многих случаях, не получает особого внимания в связи с этим заболеванием. Миелиои

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… Tier 3 (mechanistic causality) would employ the ex vivo functional suppression assays, patient-derived organoid/explant co-culture, and in vivo cytokine-neutralization models detailed above. Concordant causal evidence would justify Tier 4. … Reconstituting the head and neck tumor microenvironment with air-liquid interface organoids . Front Oncol . ( 2026 ) 15 : 1736505 . doi: 10.3389/fonc.2025.1736505 41551162 PMC12807938 43 Fang Q Li X Xu P Cao F Wu D Zhang X . …

Priorities in Cardio-Oncology Basic and Translational Science: GCOS 2023 Symposium Proceedings: JACC: CardioOncology State-of-the-Art Review.

Despite improvements in cancer survival, cancer therapy-related cardiovascular toxicity has risen to become a prominent clinical challenge. This has led to the growth of the burgeoning field of cardio-oncology, which aims to advance the cardiovascular health of cancer patients and survivors, through actionable and translatable science. In these Global Cardio-Oncology Symposium 2023 scientific symposium proceedings, we present a focused review on the mechanisms that contribute to common cardiovascular toxicities discussed at this meeting, the ongoing international collaborative efforts to impro

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… Although seminal work has shown the predictive capacity of human cardiomyocytes derived from iPSCs, 127 , 128 organoids 129 can generate small replicas of the tissue of choice and have been used to model the enhanced sensitivity of the human ischemic heart to AIC. 130 Recent technical advances, 131 including … Cellular and engineered organoids for cardiovascular models. Circ Res. 2022;130:1780–1802. doi: 10.1161/CIRCRESAHA.122.320305. 130. Richards D.J., Li Y., Kerr C.M., et al. Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity. …

Унификация одиссеи: искусственный интеллект для диагностирования и лечения редких заболеваний.

Подытожить текущие проблемы в диагностике и лечении редких заболеваний (РД), осветить последние достижения в области искусственного интеллекта (АИ) для РД и предложить модель будущего состояния лечения пациентов РД. Многодисциплинарный экспертный обзор с кратким изложением современных практических задач и мер по ограничению ставок в области РД-клиентов с учетом ключевых клинических и исследовательских соображений в отношении нормативных и экономических ограничений. 10,000 известные РД оказывают коллективное воздействие 1 В 10 Американцы, в целом 30 million Люди. Ежегодно на РД приходится свыше

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… Gate 2 tests concordance with human-derived biologic models such as induced cells, organoids, or engineered tissues using a battery that integrates molecular, morphological, and functional readouts. … Zhu Z , Cheng Y , Liu X , Advances in the development and application of human organoids: Techniques, applications, and future perspectives . Cell Transpl . 2025 ; 34 : 9636897241303272 . 71. …

mTOR pathway as a potential therapeutic target for cancer stem cells in canine mammary carcinoma.

Mammary adenocarcinoma, the most common cancer in female dogs, often exhibits the lymph node and lung metastases and has a higher mortality rate. However, mammary adenocarcinoma has no established treatment, except early surgical excision. Canine mammary carcinoma has many common features with human mammary carcinoma, including clinical characteristics, heterogeneity, and genetic aberrations, making it an excellent spontaneous tumor model for human breast cancer. Diverse cancers comprised heterogeneous cell populations originating from cancer stem cells (CSCs) with self-renewal ability. Theref

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… In further research, in addition to spheres, in vitro drug screening targeting cancer organoids will be essential for the development of new therapeutic strategies in veterinary medicine. … A living biobank of breast cancer organoids captures disease heterogeneity. Cell (2018) 172:373–386.e10. doi: 10.1016/j.cell.2017.11.010 85. Lee PJ, Ho CC, Ho H, Chen WJ, Lin CH, Lai YH, et al. …

Mucositis and Infection in Hematology Patients.

Survival in patients with hematological malignancies has improved over the years, both due to major developments in anticancer treatment, as well as in supportive care. Nevertheless, important and debilitating complications of intensive treatment regimens still frequently occur, including mucositis, fever and bloodstream infections. Exploring potential interacting mechanisms and directed therapies to counteract mucosal barrier injury is of the utmost importance if we are to continue to improve care for this increasingly growing patient population. In this perspective, I highlight recent advanc

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… Recently, organoid models for studying mucosal barrier injury have been developed [ 125 ]. Organoids are complex 3D culture systems, which represent in vitro miniaturized and simplified model systems of organs, such as the intestines. … Although becoming increasingly popular, their development is still in its infancy, and currently a number of limitations preclude its optimal use, such as a limited level of maturity and function, and heterogeneity in organoid systems [ 126 ]. …

Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise.

Aging is typified by a gradual loss of physiological fitness and accumulation of cellular damage, leading to deteriorated functions and enhanced vulnerability to diseases. Antiaging research has a long history throughout civilization, with many efforts put forth to understand and prevent the effects of aging. Multiple strategies aiming to promote healthy aging and extend the lifespan have been developed including lifestyle adjustments, medical treatments, and social programs. A multitude of antiaging medicines and remedies have also been explored. Here, we use data from the CAS Content Collect

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… of pluripotent stem cells into renal podocytes, hematopoietic progenitor cells, neurons, endothelial cells, cardiac muscle cells, retinal progenitor cells, pancreatic β islet cells, or ciliated epithelial cells infers no limits to human tissue modeling in vitro . 204 − 211 The reported progress in organoids … The most sophisticated current organoid models relate to the brain, intestine, kidney, heart, or retina. 212 − 221 With the emergence of cell 3D-printing technologies using pluripotent stem cells or differentiated cells as inks, impressive progress has been successful in the formation of heterogeneous …

Direct immunoactivation by chemotherapeutic drugs in cancer treatment.

The immune system plays a crucial role in recognizing and eliminating pathogenic substances and malignant cells in the body. For cancer treatment, immunotherapy is becoming the standard treatment for many types of cancer and is often combined with chemotherapy. Although chemotherapeutic agents are often reported to have adverse effects, including immunosuppression, they can also play a positive role in immunotherapy by directly stimulating the immune system. This has been demonstrated in preclinical and clinical studies in the past decades. Chemotherapeutics can activate immune cells through d

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… These T cells induced noticeably higher cell death in the organoids compared to untreated T cells ( Figure 6A ). To investigate whether the T cell killing was mediated by TCR, a lymphocyte kinase inhibitor (LCKi) was used to block TCR-mediated killing. … The LCKi didn't hinder docetaxel-induced T cell cytotoxicity in the KB1P organoids ( Figure 6B ). Interestingly, docetaxel-treated T cells contained a higher protein content compared to non-treated T cells. Notably, these proteins did not belong to known factors driving T cell-mediated killing. …

The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with limited therapeutic options. This review focuses on the role of retinoids, particularly all-trans retinoic acid (atRA), and hypoxia in the pathogenesis of IPF. Despite an established understanding of genetic and environmental factors in IPF, the interplay between retinoid signaling and the response to hypoxia remains poorly explored due to its complexity. Preclinical evidence suggests that atRA could help reduce pulmonary fibrosis by modulating TGF-β signaling pathways and epithelial-to-mesenchymal transition (EM

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… For instance, in both mouse and human organoids, direct treatment with atRA resulted in smaller organoids with reduced differentiation, while the inhibition of atRA led to organoid growth and differentiation through the activation of the YAP and FGF pathways [ 115 ]. … Using the lung organoid model, it has been discovered that AE2 cells may have intermediate transition states associated with aging, cellular senescence, TGF-β, and HIF1 [ 126 ]. …

Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study.

BackgroundPatients with refractory or relapsed haematological malignancies have few treatment options and short survival times. Identification of effective therapies with genomic-based precision medicine is hampered by intratumour heterogeneity and incomplete understanding of the contribution of various mutations within specific cancer phenotypes. Ex-vivo drug-response profiling in patient biopsies might aid effective treatment identification; however, proof of its clinical utility is limited.MethodsWe investigated the feasibility and clinical impact of multiparametric, single-cell, drug-respo

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… For example, ex-vivo chemosensitivity tests have been done in samples from patients with chronic or acute leukaemia and multiple myeloma, 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 in breast cancer-derived stable cell lines, 22 in patient-derived xenografts in mice, 23 , 24 and in gut stem-cell-derived organoids … cultures derived from patients with advanced prostate cancer Cell 159 2014 176 187 25201530 10.1016/j.cell.2014.08.016 PMC4237931 26 van de Wetering M Francies HE Francis JM Prospective derivation of a living organoid biobank of colorectal cancer patients Cell 161 2015 933 945 25957691 10.1016/j.cell …

Strategies to overcome the main challenges of the use of CRISPR/Cas9 as a replacement for cancer therapy.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) shows the opportunity to treat a diverse array of untreated various genetic and complicated disorders. Therapeutic genome editing processes that target disease-causing genes or mutant genes have been greatly accelerated in recent years as a consequence of improvements in sequence-specific nuclease technology. However, the therapeutic promise of genome editing has yet to be explored entirely, many challenges persist that increase the risk of further mutations. Here, we highlighted the main challenges fa

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… Modeling breast cancer using CRISPR-Cas9–mediated engineering of human breast organoids. J Natl Cancer Inst. 2020;112(5):540–4. doi: 10.1093/jnci/djz196. 48. … Gene correction of the CLN3 c.175G>A variant in patient-derived induced pluripotent stem cells prevents pathological changes in retinal organoids. Mol Genet Genomic Med. 2021;9(3):e1601. doi: 10.1002/mgg3.1601. 100. Xu L, Wang J, Liu Y, Xie L, Su B, Mou D, et al. …

Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening.

Molecular targeted therapy has revolutionized the landscape of cancer treatment due to better therapeutic responses and less systemic toxicity. However, therapeutic resistance is a major challenge in clinical settings that hinders continuous clinical benefits for cancer patients. In this regard, unraveling the mechanisms of drug resistance may identify new druggable genetic alterations for molecularly targeted therapies, thus contributing to improved therapeutic efficacies. The recent rapid development of novel methodologies including CRISPR-Cas9 screening technology and patient-derived models

How the mechanical microenvironment of stem cell growth affects their differentiation: a review.

Stem cell differentiation is of great interest in medical research; however, specifically and effectively regulating stem cell differentiation is still a challenge. In addition to chemical factors, physical signals are an important component of the stem cell ecotone. The mechanical microenvironment of stem cells has a huge role in stem cell differentiation. Herein, we describe the knowledge accumulated to date on the mechanical environment in which stem cells exist, which consists of various factors, including the extracellular matrix and topology, substrate stiffness, shear stress, hydrostati

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… Yoshihara E Immune-evasive human islet-like organoids ameliorate diabetes Nature 2020 586 7830 606 611 10.1038/s41586-020-2631-z 32814902 PMC7872080 133. … Wang D Long-term expansion of pancreatic islet organoids from resident procr(+) progenitors Cell 2020 180 6 1198 1211.e19 10.1016/j.cell.2020.02.048 32200801 134. …

Эволюционно сохраненная созвездие функциональных резинов программирует реагирующую на вирус судьбу человека (эпи)генома.

Здоровье человека зависит от запутанной защитной клеточной реакции на микробные патогены, такие как вирусы. Несмотря на предпринятые значительные усилия, (эпи)геномические механизмы, используемые клетками человека для адаптации программ защитного генного экспрессия к микробным атакам, по-прежнему недостаточно изучены, главным образом из-за значительного отсутствия регистрации в vivo функциональных модулей резного регулирования (КРМ) генома человека. Здесь мы представляем реагирующую на вирус судьбу человека (эпи)генома, описываемого в наивных и инфицированных клетках функциональными геномами,

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… Additional human and mouse cell systems of diverse origins, e.g. lung cells, fibroblasts, organoids, etc., were also investigated. … naïve or infected with SARS-CoV-2 (0 h, 2-day post infection); HPSCs-derived brain organoids naïve or infected with Zika Virus (ZIKV 0 h, 3-day post infection); and Primary Human macrophages isolated from healthy donors naïve or infected with West Nile Virus (WNV; 0 and 24 h). …

Enhancing the Safety of Nanoparticles in Medicine: Highlights of Progress and Critical Objectives.

Nanoparticles have transformed drug delivery, imaging, vaccination, and precision therapeutics, but their clinical translation remains constrained by safety profiles that are inseparable from material design, biological identity, host factors, and manufacturing. This review critically evaluates recent progress, persistent limitations, and priority objectives for safer nanomedicine. Unlike reviews organized primarily by material class or isolated toxicology endpoints, we integrate physicochemical determinants, protein corona formation, immune recognition, organ disposition, preclinical models,

Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer.

The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology that provided new tools for precise gene editing. It is possible to target any genomic locus virtually using only a complex nuclease protein with short RNA as a site-specific endonuclease. Since cancer is caused by genomic changes in tumor cells, CRISPR/Cas9 can be used in the field of cancer research to edit genomes for exploration of the mechanisms of t

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… Artegiani et al. found that after loss-of-function of BAP1 by CRISPR/Cas9 in normal human cholangiocyte organoids, the cells became more motile and fused with other organoids, features that resemble the metastatic invasion of cancer. … Artegiani B van Voorthuijsen L Lindeboom R Seinstra D Heo I Tapia P Probing the Tumor Suppressor Function of BAP1 in CRISPR-Engineered Human Liver Organoids Cell Stem Cell 2019 24 927 43.e6 10.1016/j.stem.2019.04.017 31130514 77. …

Challenges in Implementing Comprehensive Precision Medicine Screening for Ovarian Cancer.

Precision medicine has revolutionised targeted cancer treatments; however, its implementation in ovarian cancer remains challenging. Diverse tumour biology and extensive heterogeneity in ovarian cancer can limit the translatability of genetic profiling and contribute to a lack of biomarkers of treatment response. This review addresses the barriers in precision medicine for ovarian cancer, including obtaining adequate and representative tissue samples for analysis, developing functional and standardised screening methods, and navigating data infrastructure and management. Ethical concerns relat

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… Given the unique mode of ovarian cancer metastasis, high-throughput drug screening platforms that utilise 3D models such as tumour spheroids or organoids are required. … Patient-derived organoids and xenograft models may additionally serve as biologically relevant platforms for testing drug responses. …

Therapeutic siRNAs Targeting the JAK/STAT Signalling Pathway in Inflammatory Bowel Diseases.

Background and aimsInflammatory bowel diseases are highly debilitating conditions that require constant monitoring and life-long medication. Current treatments are focused on systemic administration of immunomodulatory drugs, but they have a broad range of undesirable side-effects. RNA interference is a highly specific endogenous mechanism that regulates the expression of the gene at the transcript level, which can be repurposed using exogenous short interfering RNA [siRNA] to repress expression of the target gene. While siRNA therapeutics can offer an alternative to existing therapies, with a

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… Future work should emphasize testing the in vivo stability of our JAK -targeting siRNAs, as well as their in vivo efficiency, either in human 3D organoids or in biopsies rather than animal models, as the sequence specificity of our siRNA-designed sequences restricted their use in human cellular models … Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens. Nucleic Acids Res 2018;46:e70. 50. Rajappa P, Cobb WS, Vartanian E, et al. Malignant astrocytic tumor progression potentiated by JAK-mediated recruitment of myeloid cells. …

Recent Advances in CAR-Based Solid Tumor Immunotherapy.

Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design-such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells-have shown promising results in

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… of breast cancer patients | Not yet recruiting | Breast cancer | Anti-HER2 CAR macrophages | HER2 | CAR-M efficacy testing against patient-derived organoids | | 1 September 2021 NCT05007379 determined the efficacy of new CAR macrophages against organoids derived from early and advanced breast cancer … Organoids from HER2-negative, low, and positive breast cancers were examined in this trial [ 40 ]. Moreover, the anti-tumor activity of non-modified macrophages was compared with that of new CAR macrophages [ 40 ]. 5. …

Пути к прогрессивной инвалидности при множественном склерозе: роль глиальных клеток в хроническом воспалении CNS.

Множественный склероз (MS) является наиболее распространенным неинфекционным воспалительным заболеванием CNS, характеризующимся прогрессивным нейродегенерацией и точечными демиелинированными повреждениями. Традиционно считается аутоиммунным заболеванием, MS движет атака иммунной системы на CNS Myelin, что приводит к кумулятивной инвалидности. Однако традиционные методы борьбы с воспламенением часто не позволяют предотвратить постепенное ухудшение состояния, особенно при отсутствии открытого воспаления, что подчеркивает необходимость более глубокого понимания его патогенеза. Недавние исследован

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… Additionally, the development of increasingly sophisticated 3D CNS organoid models offers a promising avenue for addressing unresolved questions in neuroscience. … Key studies now also demonstrate that the transplantation of human organoids into a mouse brain can lead to proper vascularization and integration within the host organism (Kelley et al.  2024 ). …

Targeting Death Receptor 5 (DR5) for the imaging and treatment of primary bone and soft tissue tumors: an update of the literature.

BackgroundDeath Receptor 5 (DR5) is expressed on the surface of primary bone and soft tissue sarcoma cells, and its activation induces cell death primarily through apoptosis. The combination of DR5 agonists and commonly used chemotherapeutic agents, such as doxorubicin, can promote cell death. Currently, clinical trials are investigating the effectiveness of DR5 activation using new biological agents, such as bi-specific or tetravalent antibodies, in improving the survival of patients with relapsed or refractory cancers. Furthermore, investigations continue into the use of novel combination th

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… There has been increasing use of spheroids, organoids, and 3D cell cultures, terms used interchangeably, to try to replicate malignant tissues and microtumors ( Bialkowska et al., 2020 ; Gunti et al., 2021 ). … Organoid and spheroid tumor models: techniques and applications. Cancers (Basel) 13, 874. 10.3390/cancers13040874 Hartung F., Kruwel T., Shi X., Pfizenmaier K., Kontermann R., Chames P., et al. (2020). …