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Targeting the RANKL/RANK/OPG Axis for Cancer Therapy.

RANKL and RANK are expressed in different cell types and tissues throughout the body. They were originally described for their essential roles in bone remodeling and the immune system but have subsequently been shown to provide essential signals from regulating mammary gland homeostasis during pregnancy to modulating tumorigenesis. The success of RANKL/RANK research serves as a paragon for translational research from the laboratory to the bedside. The case in point has been the development of Denosumab, a RANKL-blocking monoclonal antibody which has already helped millions of patients sufferin

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… RANKL inhibition also significantly suppressed the proliferation of tumor organoids derived from BRCA1 mutant human breast biopsy specimens, and RANKL/RANK pathway blockade strongly reduced tumorigenesis in patient-derived xenograft (PDX) breast tumor mouse model ( 91 ). …

Stem cells for luminal, fistulizing, and perianal inflammatory bowel disease: a comprehensive updated review of the literature.

Much research has been performed over the last decade on stem cell therapy as treatment for patients with inflammatory bowel disease. Hematopoietic and mesenchymal stem cells, both allogeneic (from someone else) and autologous (from own patient), have been studied with safe and efficacious results in the majority of patients treated for luminal, perianal, and/or fistulizing disease. Here in this review, we highlight all human trials that have been conducted utilizing stem cell therapy treatment in patients with inflammatory bowel disease.

Using an integrated omics approach to uncover the mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN).

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect with limited treatment options. The primary challenge in developing therapies is the lack of identified neurotoxic mechanisms. To address this, an integrated omics approach, combining transcriptomics, proteomics, and metabolomics, is essential to map the biological changes underlying the condition. Here, we show how data from these complementary approaches converge on key mechanisms involved in CIPN through a critical summary of animal and human studies. Current research highlights several key drivers of CIPN, such

Механизм поглощения и токсичности антителного препарата BCMA в сочетании с полезной нагрузкой MMAF неантигенными функционирующими элементами.

Belantamab mafodotin, антитело-наркомания (ADC), продемонстрировал высокую эффективность в множестве миеломы. Он состоит из гуманизированного антиклектового антигена (BCMA) IgG1 моноклонального антитела, смешанного с монометил-ауристатином F (MMAF) с помощью манимидокапроилового связующего устройства. С помощью неизвестных механизмов поступили сообщения о связанных с окультизмом неблагоприятных явлениях, в частности о роговицах, в которых содержится АКЦ, в том числе белантамб мафодотин. В ходе этого исследования изучался механизм поглощения и цитотоксичности белантамбом мафодотином, содержащим

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… Therefore, more human-representative models of ADC ocular effects (e.g., three-dimensional corneal organoids) are necessary for understanding the pathophysiology of ocular adverse events and developing mitigation strategies. …

Pharmacological Strategies for Mitigating Cytarabine-Induced Multi-Organ Toxicity: A Scoping Review on Mechanisms, Efficacy and Clinical Implications.

BACKGROUND: Cytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available. OBJECTIVES: This scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-org

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… . | Purely in vitro preparations (cell lines, organoids, tissue explants). Studies using Ara-C solely as an antineoplastic without dedicated host-tissue toxicity endpoints. …

Mechanistic and Clinical Perspectives on Traditional Chinese Medicine in Thyroid Cancer Management.

Thyroid cancer is one of the most prevalent malignancies of the endocrine system, comprising various subtypes such as papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC), and the aggressive anaplastic thyroid carcinoma (ATC). Despite a generally favorable prognosis for PTC, recurrence, metastasis, and resistance to conventional therapies continue to pose significant challenges. The pathogenesis of thyroid cancer involves genetic mutations in BRAF, RAS, and RET, as well as dysregulated molecular pathways such as MAPK, PI3K/Akt/mTOR, and NF-κB

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… Wang L. 2025 Transforming cancer treatment: integrating patient-derived organoids and CRISPR screening for precision medicine Front. Pharmacol. 16 1563198 10.3389/fphar.2025.1563198 40201690 PMC11975957 …

Single-cell sequencing in molecular diagnostics: Transformative yet untapped potential.

Single-cell sequencing (SCS) techniques have the potential to offer precise insights into cellular diversity by revealing unique genetic and transcriptomic profiles at the single-cell level. This advanced technology has been used extensively in research, but it has still not translated to clinical diagnostics, despite its potential. SCS provides more accurate granular information about heterogeneous cell populations and the creation of personalized treatment strategies. However, the integration of SCS into clinical practice is challenging. This review discusses the potential of SCS technologie

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… Previously unidentified subtypes of hepatocytes, Kupffer cells, and endothelial cells with distinct gene expression profiles were identified, together with a rare subset of bile duct cells with the ability to develop into organoids. …

SLAMF7 regulates goblet cell mucus production and negatively impacts gut homeostasis and commensalism.

Crosstalk between the intestinal mucosal barrier and the gut microbiota contributes to maintaining intestinal homeostasis. Accumulating evidence suggests that diverse mechanisms are involved in maintaining intestinal homeostasis. Any disturbance in these pathways can compromise gut homeostasis and trigger chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, how host factors regulate the intestinal mucosal barrier and change the gut microbiome has not been well defined. Here, we discovered that disruption of SLAMF7 protects against intestinal inflammation. SLAMF7 def

Anticancer potential of decursin, decursinol angelate, and decursinol from Angelica gigas Nakai: A comprehensive review and future therapeutic prospects.

Many naturally derived compounds are currently used in oncotherapy. Besides official medicine, complementary and alternative medicine practices, including old herbal remedies, are widely used and accepted as additional tools in cancer treatment. Angelica gigas Nakai (AGN), a medicinal herb in Asia, has roots historically used in medicine. This review focuses on key bioactive compounds from AGN roots - decursin, decursinol angelate (DA), and decursinol (DOH). Exploring their source, biosynthesis, and therapeutic mechanisms, the review highlights their role in cancer treatment. Biotechnological

Полнотрансформатная ретиноидальная кислота в гематологическое расстройство: не только острая промиелоцитическая лейкемия.

Всетранс-ретиноиновая кислота (ATRA) играет определенную роль в развитии тканей, нейронной функции, воспроизводстве, зрение, росте и дифференциации клеток, иммунитете от опухоли и апоптозе. АТРА может действовать, вызывая автофагическую сигнализацию, ангиогенез, клеточную дифференциацию, апоптоз и иммунную функцию. В крови ATRA впервые с большим успехом использовалась в острой промиелоцитической лейкемии (APL), где ATRA дифференцировала клетки лейкемии на зрелые гранулоциты. АТРА может играть определенную роль не только в ППН, но и в других гематоологических заболеваниях, таких, как иммунная т

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… All-trans retinoic acid modulates pigmentation, neuroretinal maturation, and corneal transparency in human multiocular organoids. Stem Cell Res. Ther. 13 (1), 376. 10.1186/s13287-022-03053-1 Itzykson R., Ayari S., Vassilief D., Berger E., Slama B., Vey N., et al. (2009). …

Biology of stem cell paradox: a double-edged sword-implications for cancer therapy.

This comprehensive review investigates the complex interactions between oncogenesis and stem cells, underscoring the crucial importance of cancer stem cells (CSCs) in the mechanisms of tumorigenesis, metastatic dissemination, and resistance to therapeutic interventions. CSCs constitute a distinct subset within neoplasms, defined by unique characteristics such as the ability to self-renew, the potential to differentiate into various cellular phenotypes, and an inherent resistance to conventional treatment strategies. It is hypothesized that these properties are regulated by a multitude of signa

Conditioned Media-Derived Tumor Extracellular Vesicles: Bridging Molecular Insights and Therapeutic Applications in Oncology.

Tumor-derived extracellular vesicles (EVs) are major mediators of oncogenic intercellular communication. However, many studies using conditioned media (CM) recover operationally defined EV- or small EV-enriched fractions rather than biogenesis-proven exosomes. This review synthesizes evidence from CM-derived tumor EV studies and aligns their biological interpretation with current EV nomenclature, characterization, and reporting principles. We first discuss exosome biogenesis as a defined endosomal pathway and then examine how CM collection, serum handling, culture format, oxygen tension, condi

Musculoskeletal Organs-on-Chips: An Emerging Platform for Studying the Nanotechnology-Biology Interface.

Nanotechnology-based approaches are promising for the treatment of musculoskeletal (MSK) disorders, which present significant clinical burdens and challenges, but their clinical translation requires a deep understanding of the complex interplay between nanotechnology and MSK biology. Organ-on-a-chip (OoC) systems have emerged as an innovative and versatile microphysiological platform to replicate the dynamics of tissue microenvironment for studying nanotechnology-biology interactions. This review first covers recent advances and applications of MSK OoCs and their ability to mimic the biophysic

Последствия злоупотребления наркотиками для путей ферроптоза: потенциальные терапевтические цели для расстройств, связанных с потреблением психоактивных веществ.

Серьезными проблемами в области здравоохранения во всем мире, особенно в развитых странах, по-прежнему являются расстройства, связанные с потреблением психоактивных веществ. Для ОСВ характерна устойчивая нейроинфламмация и синаптическая дисфункция мозга. Несмотря на десятилетия интенсивного расследования, детальные механизмы, лежащие в основе ВСГ, по-прежнему остаются иллюзорными. Ферроптоз — это высокорегулируемый процесс смерти клеток, на который сильно влияют метаболизм железа, пероксидация липидов, производство реактивных видов кислорода (РОС) и антиоксидантные системы. Он был связан с мно

Combination Cancer Therapy and Reference Models for Assessing Drug Synergy in Glioblastoma.

Glioblastoma is currently an incurable disease despite the development of a wide variety of therapeutic approaches, from surgical methods to immunotherapy. In current clinical practice, treatment typically involves a combination of existing methods, often comprising three stages: tumor resection, radiotherapy, and chemotherapy. Modern research offers improved chemotherapy strategies, as well as combinations of chemotherapy with immunotherapy. However, the efficacy of these therapies is profoundly influenced by factors such as tumor and peritumoral heterogeneity, alongside complex molecular sig

Research progress on N6-methyladenosine and non-coding RNA in multiple myeloma.

N6-methyladenosine (m6A) and non-coding RNA (ncRNA) play important roles in the occurrence, development, and prognosis of multiple myeloma (MM). They not only affect stemness, growth, and apoptosis of MM cells but also intervene in MM proliferation, migration, invasion, and even drug resistance. It is also a prognostic factor for poor MM survival. Therefore, in-depth research on the mechanisms of m6A and ncRNA in MM significant for diagnosis, treatment, and prognosis of MM.

Why do patients with cancer die?

Cancer is a major cause of global mortality, both in affluent countries and increasingly in developing nations. Many patients with cancer experience reduced life expectancy and have metastatic disease at the time of death. However, the more precise causes of mortality and patient deterioration before death remain poorly understood. This scarcity of information, particularly the lack of mechanistic insights, presents a challenge for the development of novel treatment strategies to improve the quality of, and potentially extend, life for patients with late-stage cancer. In addition, earlier depl

MicroRNA-Based Risk Score for Predicting Tumor Progression Following Radioactive Iodine Ablation in Well-Differentiated Thyroid Cancer Patients: A Propensity-Score Matched Analysis.

To identify molecular markers that can accurately predict aggressive tumor behavior at the time of surgery, a propensity-matching score analysis of archived specimens yielded two similar datasets of DTC patients (with and without RAI). Bioinformatically selected microRNAs were quantified by qRT-PCR. The risk score was generated using Cox regression and assessed using ROC, C-statistic, and Brier-score. A predictive Bayesian nomogram was established. External validation was performed, and causal network analysis was generated. Within the eight-year follow-up period, progression was reported in 5

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… Patient-Derived Papillary Thyroid Cancer Organoids for Radioactive Iodine Refractory Screening Cancers 2020 12 3212 10.3390/cancers12113212 PMC7692469 33142750 7. Lechner M. Praw S.S. Angell T.E. Treatment of Differentiated Thyroid Carcinomas Surg. Pathol. …

Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.

Endoplasmic reticulum (ER) stress is a key cellular mechanism that is important in the development of many diseases, including cancer. Since the discovery of the unfolded protein response (UPR), research has greatly improved our understanding of how ER stress affects cellular functions, especially protein folding and adaptation to stress. The UPR consists of three main branches: IRE1, ATF6, and PERK, each of which is crucial for regulating stress responses, protein homeostasis, and apoptosis. These pathways normally help cells handle stress effectively; however, excessive or prolonged activati

Anti-Cancer Research Progress of Triptolide: Mechanisms of Action, Structural Modifications, Nanodelivery Systems and Clinical Challenges.

Triptolide is a bioactive diterpenoid lactone from traditional Chinese medicine with notable anti-tumor, immunosuppressive, and anti-inflammatory properties. However, its clinical utility is hampered by poor solubility, a narrow therapeutic index, and multi-organ toxicity. In response, extensive efforts have been made to improve its efficacy and safety profile. This review critically examines recent progress in Triptolide research, covering its mechanisms of action, derivative design, drug delivery systems, and cancer-specific applications. It also evaluates its clinical potential against panc

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… CK21 retained potent anticancer activity comparable to Triptolide in human pancreatic cancer cells (AsPC-1, Panc-1) and in four types of patient derived pancreatic tumor organoids, while exhibiting minimal toxicity toward normal human fibroblasts, with effects only observed at concentrations ≥ 296 …