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Current landscape and future directions of targeted-alpha-therapy for glioblastoma treatment.

Glioblastoma (GB) is the most aggressive malignancy of the central nervous system. Despite two decades of intensive research since the establishment of the standard of care, emerging strategies have yet to produce consistent satisfactory outcomes. Because of its specific localisation and intricate characteristics, GB is a uniquely regulated solid tumour with a strong resistance to therapy. Advances in targeted radionuclide therapy (TRT), particularly with the introduction of a-emitting radionuclides, have unveiled potential avenues for the management of GB. Recent preclinical and clinical stud

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… This process is accompanied by the release of cytokines and chemokines 214 , 215 , and the activation of the cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) signalling pathway, which drives type I interferon production necessary for dendritic cell maturation. … Abbreviations ataxia telangiectasia mutated ataxia telangiectasia and rad3-related gold nanoparticles fibroblast growth factor b blood-brain barrier brain-tumour barrier cancer-associated fibroblast chimeric antigen receptor chemokine CC ligand convection-enhanced delivery cyclic GMP-AMP synthase …

Immunotherapy for Colorectal Cancer: Mechanisms and Predictive Biomarkers.

Though early-stage colorectal cancer has a high 5 year survival rate of 65-92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells. Preclinical

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… Preliminary results from other initial clinical trials indicated that low or moderate doses of IFN-γ were more effective than high doses [ 150 ], suggesting that dose should be carefully considered when administering treatment and interpreting study results. 2.6.3. cGAS-STING The cyclic GMP-AMP synthase … bispecific antibodies | MDSCs | myeloid-derived suppressor cells bsTCEs | T cell-engaging bsAbs | miRNA | microRNA CAAs | cancer-associated antigens | MMR | mismatch repair CAR-T cell | chimeric antigen receptor T cell | MSI | microsatellite instable CEA | carcinoembryonic antigen | MSI-H | MSI-high cGAS | cyclic …

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers.

Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer's disease or myasthenia gravis will be discuss

Ageing, Cellular Senescence and Neurodegenerative Disease.

Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence mar

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… Another key feature of cellular senescence is the senescence-associated secretory phenotype (SASP), which is dependent on p38MAPK (p38 mitogen-activated protein kinases), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), cGAS(cyclic GMP-AMP synthase)/STING(stimulator of IFN genes … GMP-AMP synthase CIP/KIP | CDK interacting protein/kinase inhibitory protein CML | chronic myelogenous leukemia CNS | central nervous system CSF | cerebrospinal fluid DDR | DNA damage response Ecrg4 | esophageal cancer-related gene 4 EGF | epidermal growth factor ER | endoplasmic reticulum FGF-2 | fibroblast …

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding a

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… These diverse cellular effects have linked deficiencies in cyclic GMP production (primarily due to insufficient nitric oxide bioavailability) to the pathogenesis of various cardiovascular diseases. …

Advanced Technologies for Large Scale Supply of Marine Drugs.

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From a structural point of view and with few exceptions, MNPs of pharmaceutical importance derive from the so-called secondary metabolism of marine organisms. When production strategies rely on marine macroorganisms, harvesting or culturing coupled with extraction procedures frequently remain t

Epigenetic Dysregulation in Neurodegeneration: The Role of Histone Deacetylases and Emerging Inhibitor Strategies.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are characterized by complex pathologies with progressive neurodegeneration, protein misfolding, oxidative stress, and persistent inflammation. Recent findings indicate the pivotal involvement of epigenetic disruption, particularly aberrant histone deacetylase (HDAC) activity, in disease initiation and progression. In the current review, we systematically discuss the mechanistic function of HDACs across all classes (I, IIa, IIb, III, and IV) in neurodegenerative disease mechanis

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… PDEs regulate cyclic AMP (cAMP) and cyclic GMP (cGMP), which are crucial for memory, synaptic plasticity, and neuronal survival. Inhibiting specific PDEs restores cAMP/cGMP signaling, activates CREB, and increases neuroprotective factors like BDNF [ 100 ]. …

Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma.

Monoclonal antibodies (mAbs) directed against antigen-specific of multiple myeloma (MM) cells have Fc-dependent immune effector mechanisms, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but the choice of the antigen is crucial for the development of effective immuno-therapy in MM. Recently new immunotherapeutic options in MM patients have been developed against different myeloma-related antigens as drug conjugate-antibody, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CA

Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase

Invited Lectures : Overviews Purinergic signalling: past, present and future.

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Иммунитет Т-клеток, специфичный для EBV: значение для множественного склероза.

Генетические и экологические факторы совместно определяют подверженность развитию множественных склерозов (МС). Улучшения в разработке эпидемиологических исследований помогли выявить последовательные ассоциации экологического риска, такие, как повышенная подверженность НР после заражения вирусом Эпштейн-Барр (ЭБВ), в то время как биологические механизмы, влияющие на связь между ЕБВ и НР, по-прежнему недостаточно изучены. Увеличение и расширение репертуара антител и клеток иммунной реакции на антигены EBV, особенно на доминирующий антиген CD4+T-клеток EBV 1 (EBNA1) постоянно наблюдается у пацие

Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer.

The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-kn

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

The prince and the pauper. A tale of anticancer targeted agents.

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consiste

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… Thus, generation of cyclic GMP from GTP then engages various downstream targets including protein kinases, phosphodiesterases, and ion channels, giving rise to modifications in cell functions such as smooth muscle relaxation, platelet disaggregation, and synaptic plasticity. …

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

Clinical updates of B‑cell maturation antigen‑targeted therapy in multiple myeloma (MM) and relapsed/refractory MM (Review).

Despite significant progress in managing multiple myeloma (MM) in recent years, certain patients still have a short duration of therapeutic response, often relapsing within 18 months. These patients typically have high‑risk genetic mutations and may show little to no response to current treatments, highlighting the need for further exploration of optimal therapeutic targets for MM. B‑cell maturation antigen (BCMA), highly expressed in mature B lymphocytes and plasma cells and upregulated in MM, is a promising therapeutic target. Various BCMA‑targeted strategies, including antibody‑drug conjuga

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… MEDI2228 also activates the IFN-regulated innate immune response through the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK binding kinase 1-interferon regulatory factors (IRF)3 and signal transducer and activator of transcription 1-IRF1 pathways in MM cells, demonstrating efficacy against …

Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer.

Breast cancer is still one of the most prevalent cancers and a leading cause of cancer death worldwide. The key challenge with cancer treatment is the choice of the best therapeutic agents with the least possible toxicities on the patient. Recently, attention has been drawn to herbal compounds, in particular ginsenosides, extracted from the root of the Ginseng plant. In various studies, significant anti-cancer properties of ginsenosides have been reported in different cancers. The mode of action of ginsenoside Rg3 (Rg3) in in vitro and in vivo breast cancer models and its value as an anti-canc

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… Stimulation of aquaporin-mediated fluid transport by cyclic GMP in human retinal pigment epithelium in vitro Investig. Ophthalmol. Vis. Sci. 2012 53 2127 2132 10.1167/iovs.11-8471 22427546 PMC3995571 106. Qin F. Zhang H. Shao Y. Liu X. Yang L. Huang Y. Fu L. Gu F. Ma Y. …

The progression of HMGB1-induced autophagy in cancer biology.

Autophagy is an important process of cellular degradation and has been proven to contribute to tumorigenesis. High-mobility group box 1 (HMGB1) is an abundant nonhistone protein that has been widely reported to play a central role in the induction of autophagy. In nucleus, HMGB1 upregulates the expression of HSP27 to induce autophagy. In cytoplasm, the Beclin-1/PI3K-III complex can be activated by HMGB1 to promote autophagy. Extracellular HMGB1 binds to the receptor for advanced glycation end products to induce autophagy. Recent studies have shown that HMGB1-induced autophagy exerts multiple f

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… PDE5 inhibitors enhance the lethality of pemetrexed through inhibition of multiple chaperone proteins and via the actions of cyclic GMP and nitric oxide. Oncotarget. 2017;8(1):1449–1468. doi: 10.18632/oncotarget.13640. 80. Booth L, Roberts JL, Poklepovic A, Dent P. …

HMMR in human cancers: regulatory mechanism and biological function.

Hyaluronan-mediated motility receptor (HMMR), also referred to as RHAMM or CD168, has gained recognition as a multifunctional protein that mediates the transmission of extracellular matrix-derived hyaluronan (HA) signals to intracellular pathways regulating tumor growth, migration, and mitosis. Overexpression of HMMR is observed in various cancers, including head and neck squamous cell carcinoma, breast cancer, lung cancer, and prostate cancer, as well as several hematologic malignancies. This elevated expression correlates with poor prognosis, rendering it a valuable marker for survival predi

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… In the context of BRCA1 deficiency, overexpression of HMMR induces genomic instability and micronuclei formation, thereby activating the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. …

Резюме АОКНМБ и СНМИКС 2025

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