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Paraneoplastic Neuropathies: What's New Since the 2004 Recommended Diagnostic Criteria.

The diagnostic criteria published by the PNS (Paraneoplastic Neurological Syndromes) Euronetwork in 2004 provided a useful classification of PNS, including paraneoplastic neuropathies. Subacute sensory neuronopathy (SSN) was the most frequently observed peripheral PNS, whereas other forms of neuropathy, as sensory polyneuropathy, sensorimotor polyneuropathy, demyelinating neuropathies, autonomic neuropathies, and focal nerve or plexus lesions, were less frequent. At the time of publication, the main focus was on onconeural antibodies, but knowledge regarding the mechanisms has since expanded.

LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.

Lysosomal-associated protein transmembrane (LAPTM) family members-LAPTM4A, LAPTM4B, and LAPTM5-regulate lysosomal integrity, autophagy-lysosome flux, lipid homeostasis, and immune signaling, pathways increasingly implicated in neurological disease. This review synthesizes structure-function evidence for LAPTM proteins and examines how their dysregulation contributes to Alzheimer's and Parkinson's disease, ischemia-reperfusion injury, and gliomas. Based on a targeted narrative analysis of primary and translational studies, we highlight that LAPTM proteins influence lysosomal acidification and m

Storage diseases with hypertrophic cardiomyopathy phenotype.

Never judge a book by its cover, nor assume hypertrophic cardiomyopathy (HCM) as sarcomeric, as appearances can deceive. HCM phenocopies account for a 5-10% of the cases, mainly represented by storage diseases, flagged by the increasing prevalence of senile cardiac amyloid in developing countries. Multisystemic and heterogeneous presentation of these entities is a challenge for clinicians, and time delay in diagnosis is a major concern. Promising drugs and gene-specific tailored therapies are under development, therefore, more than ever, appropriate understanding of these conditions is mandato

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… coronary artery narrowing or pulmonary and systemic hypertension. 2.2 Anderson–Fabry disease 2.2.1 Introduction Fabry disease (Anderson–Fabry Disease (AFD) or angiokeratoma corporis diffusum ) is a rare disorder of the metabolism of the α -galactosidase A, a lysosomal enzyme that degrades neutral glycosphingolipids …

Immunotherapy targets in pediatric cancer.

Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made b

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… Gangliosides and allied glycosphingolipids in human peripheral nerve and spinal cord . Biochim. Biophys. Acta 1214 , 115 – 123 7918590 10.1016/0005-2760(94)90034-5 Takenouchi M. Hirai S. Sakuragi N. Yagita H. Hamada H. Kato K. ( 2011 ). …

The Black Hole: CAR T Cell Therapy in AML.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed/refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen-targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything. One must consider the fact that only around 30% of

Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.

Cancer immunotherapy has redefined cancer treatment. However, the molecular and cellular basis of immune evasion and therapeutic resistance remains incompletely understood. Early immune checkpoint inhibitors have delivered significant clinical benefit, but their efficacy and durability remain limited in many patients. These limitations have driven the exploration of next-generation immune checkpoints and additional regulatory pathways that shape tumor-immune interactions. Recent advances have broadened the immune checkpoint landscape and revealed new targets. These targets operate within inter

Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.

Acute myeloid leukemia (AML) is a high-risk hematologic malignancy with poor long-term survival and frequent relapse, sustained by leukemic stem cells, antigenic heterogeneity, and an immunosuppressive bone marrow niche. Although chimeric antigen receptor (CAR) T-cell therapy achieves durable responses in B-cell malignancies, its application in AML is restricted by on-target myelotoxicity from antigen overlap with normal progenitors, heterogeneous and dynamic antigen expression, rapid T-cell exhaustion in suppressive microenvironments, limited manufacturing windows with compromised T-cell qual

Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities.

New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. This review provides an overview of protein-based adjuvants (PBAs) obtained from different organisms, including bacteria, mollusks, plants, and humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- a

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… The B5 pentameric ring is essential to pathogenesis because it binds to glycosphingolipids on target cells, such as the ganglioside GM1, allowing CT endocytosis. …

Экстраклектные везикли для клинической диагностики: от массовых измерений до одновидового анализа.

Экстраклектные везикулы (ЭМ) играют ключевую роль в межклеточном общении, сигнальных путях и патогенезе заболеваний, перевозя биомолекулы, такие, как ДНК, РНК, белки и липиды, полученные из клеток их происхождения, и они продемонстрировали значительный потенциал в области клинического применения. Их клиническое значение подчеркивает необходимость применения чувствительных методов для полной реализации их диагностического потенциала. В рамках этого всеобъемлющего обзора мы изучаем гетерогенность ЭМ, связанную с биогенезом, структурой, содержанием, происхождением, типом выборки и функциональными

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… EV membranes are enriched in various lipids, such as cholesterol, sphingomyelin (SM), PS, phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylethanolamine (PE), glycosphingolipids, ceramides, and the membrane lipid composition plays a critical role in EV structure, stability, and function … Glycosphingolipids, such as gangliosides (GM), are commonly present in EVs and contribute to membrane stability and cellular interactions. …

Необычные хранители мозга: MAIT клетки как новые игроки в иммунитете от глиобластомы.

Глиобластома (GBM) является агрессивной формой рака мозга без лечения. Несмотря на то, что T-клеточная терапия продемонстрировала значительный успех в борьбе с раком крови, их применение для лечения твердых опухолей, включая GBM, затрудняется иммуновосприимчивой микроопухолью и нехваткой целевых показателей по борьбе с опухолью. Существует настоятельная необходимость более глубокого понимания иммунной реакции на ГБМ, с тем чтобы можно было разработать новые терапевтические подходы. Недавно было описано постоянное население мукосальных инвариантов Т (MAIT) в мозгу, которые могут выполнять крити

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… A CAR-NKT cell therapy developed by Xu et al. in 2019 ( 99 ), showed limited success in phase I clinical trials, with injection of autologous NKT cells targeted to GD2 ganglioside – a molecule composed of glycosphingolipids linked with sialic acid chains, which is expressed by neuroblastoma cells – reducing …

The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.

Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potent

Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.

Cancer stem cells (CSCs) drive tumor progression, therapy resistance, and metastasis through unique membrane biology, glycosylation patterns, and metabolic adaptations. CSCs exhibit a distinct glycocalyx profile enriched in hyaluronan, heparan sulfate, and sialylated glycans, facilitating immune evasion, adhesion, and survival. Key signaling pathways-Wnt/β-catenin, Hedgehog, Notch, JAK/STAT, TGF/SMAD, and PI3K/AKT/mTOR-regulate CSC stemness and therapeutic resistance. Emerging biomarkers (CD44, CD133, ALDH1, EpCAM) and targeted therapies (CAR-T cells, miRNA modulation, lipid metabolism inhibit

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… Glycan-based biomarkers hold great promise for CSC detection and therapeutic targeting, which include CD44 variants (CD44v) with unique glycosylation, CD133 (Prominin-1) glycosylation, podocalyxin (PODXL), integrins with altered glycosylation, and glycosphingolipids (GSLs) ( Hu et al., 2019 ). …

The Confluence of Nanotechnology and Heat Shock Protein 70 in Pioneering Glioblastoma Multiforme Therapy: Forging Pathways Towards Precision Targeting and Transformation.

Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70's dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal-organic framework

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… This specificity arises from the interaction between HSP70 and tumour-specific glycosphingolipids like globotriaosylceramide (Gb3), found in lipid rafts of tumour cells but lacking in normal cells. …

Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response.

Radiotherapy and surgery are curative treatment options for localized prostate cancer (PCa) with a 5-year survival rate of nearly 100%. Once PCa cells spread into distant organs, such as bone, the overall survival rate of patients drops dramatically. The metastatic cascade and organotropism of PCa cells are regulated by different cellular subtypes, organ microenvironment, and their interactions. This cross-talk leads to pre-metastatic niche formation that releases chemo-attractive factors enforcing the formation of distant metastasis. Biological characteristics of PCa metastasis impacting on m

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… Upon stabilization of CTC-endothelium interaction, CTCs induce extravasation through binding of sialofucosylated proteins, such as podocalyxin or glycosphingolipids with C-type lectin binding, e.g., E-selectin (CD62E), on endothelial cells ( 194 ). …

Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predic

Bispecific Antibody-Based Immune-Cell Engagers and Their Emerging Therapeutic Targets in Cancer Immunotherapy.

Cancer is the second leading cause of death worldwide after cardiovascular diseases. Harnessing the power of immune cells is a promising strategy to improve the antitumor effect of cancer immunotherapy. Recent progress in recombinant DNA technology and antibody engineering has ushered in a new era of bispecific antibody (bsAb)-based immune-cell engagers (ICEs), including T- and natural-killer-cell engagers. Since the first approval of blinatumomab by the United States Food and Drug Administration (US FDA), various bsAb-based ICEs have been developed for the effective treatment of patients with

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… Sphingolipid as ICE Targets in Solid Cancers GD2 GD2 is a 1.6-kDa glycosylated lipid molecule that belongs to the class of glycosphingolipids [ 126 , 127 , 128 , 129 ]. It plays a key role in the attachment of tumor cells to extracellular matrix proteins. …

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

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… The use of an engineered endoglycoceramidase II (EGCase) from Rhodococcus sp. which has been modified to catalyze the synthesis of glycosphingolipids rather than their degradation facilitated the coupling of oligosaccharides with various sphingosines allowing for the creation of structurally diverse …

Monoclonal Antibodies Approved for Cancer Therapy

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Lung cancer immunotherapy: progress, pitfalls, and promises.

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are

Myelin Displacement and Revention in the Central Nervous System: Молекулярные механизмы, болезни и перспективные терапевтические цели.

Майлин пластичность имеет основополагающее значение для формирования нейронных сетей и оптимизации нейронных функций, формирования схем, регулирующих эмоции, сознание, сенсацию и управление двигателем. Подкомбинированный олигодендроцитами, миелин подвергается пожизненной реконструкции, которая требует высокой метаболической активности; это делает миелин-олигодендроцитную единицу весьма восприимчивой к метаболическому стрессу, старению и патологическим оскорблениям. Хотя обезвоживание является основной характеристикой различных хронических неврологических расстройств, в настоящем обзоре особо п

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… Myelin sheath comprises a diverse array of lipid components, primarily including cholesterol, glycosphingolipids (GSLs), and phospholipids [ 20 ]. This composition contrasts with most biological membranes, which typically exhibit a higher protein‐to‐lipid ratio. …