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Targeting Notch-1 positive acute leukemia cells by novel fucose-bound liposomes carrying daunorubicin.

Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes

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… L-fucose is a monosaccharide that is a common component of many N- and O-linked glycans and glycolipids produced by mammalian cells [ 10 ]. …

Chimeric antigen receptor modified T-cells for cancer treatment.

T cells engineered with the chimeric antigen receptor (CAR) are rapidly emerging as an important immunotherapy for hematologic malignancies. The anti-cluster of differentiation (CD)19 CAR-T cell therapy has been remarkably successful against refractory/relapsed acute lymphoblastic leukemia (ALL), and a complete remission rate as high as 90% was observed, in both children and adults. Although the achievement of clinical efficacy using CAR-T cell therapy for solid tumors has encountered several obstacles that were associated with the multiple mechanisms contributing to an immunosuppressive micro

Устроенная ЦАР клеточная терапия: текущее понимание и перспективы на будущее.

Инженерная клеточная терапия химерического антигенного рецептора (CAR) представляет собой значительный прорыв в иммунотерапии, первоначально в раке и в настоящее время распространяется на различные клинические области. Хотя изначально эти платформы разрабатывались для онкологии, они все чаще адаптируются к таким ненасытным условиям, как аутоиммунные расстройства, инфекционные заболевания, фиброз, проблемы старения и трансплантация органов. В настоящем обзоре содержится подробная информация об эволюции и диверсификации методов ЦАР, включая CAR-T, CAR-NK, CA-Macrophages и CAR-NKT, а также о новы

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… CARs can identify antigens independently of MHC, enabling them to target various tumour-associated structures such as glycoproteins and glycolipids [ 37 ]. … Derived from donors or NK cell lines like NK-92, less risk of GvHD, more consistent product | Monocytes isolated from blood can potentially be reprogrammed into macrophages | Neutrophils isolated from blood are often not genetically modified Target Antigens | Specific TAAs (e.g., CD19, BCMA) | Lipid and glycolipid …

Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses.

High mobility group box 1 (HMGB1), a protein with important functions, has been recognized as a potential therapeutic target for the treatment of sepsis. One possible mechanism for this is that inhibiting HMGB1 secretion can exert antiseptic effects, which can restore the integrity of the vascular barrier. (7S)-(+)-cyclopentyl carbamic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (CGK012) is a newly synthesized pyranocoumarin compound that could function as a novel small-molecule inhibitor of the Wnt/β-catenin signaling pathway. However, no studies have yet determi

Oncofetal Chondroitin Sulfate Is a Highly Expressed Therapeutic Target in Non-Small Cell Lung Cancer.

Broad-spectrum therapeutics in non-small cell lung cancer (NSCLC) are in demand. Most human solid tumors express proteoglycans modified with distinct oncofetal chondroitin sulfate (CS) chains that can be detected and targeted with recombinant VAR2CSA (rVAR2) proteins and rVAR2-derived therapeutics. Here, we investigated expression and targetability of oncofetal CS expression in human NSCLC. High oncofetal CS expression is associated with shorter disease-free survival and poor overall survival of clinically annotated stage I and II NSCLC patients (n = 493). Oncofetal CS qualifies as an independ

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… Glycolipids of hamster fibroblasts and derived malignant-transformed cell lines Proc. Natl. Acad. Sci. USA 1968 59 254 261 10.1073/pnas.59.1.254 4298334 PMC286029 11. Khazamipour N. Al-Nakouzi N. Oo H.Z. Orum-Madsen M. Steino A. Sorensen P.H. Daugaard M. …

Mycobiota и Antifungal Antibodies как новые целевые показатели для диагностики и прогнозирования болезней человека.

Человеческое тело колонизируется различными микроорганизмами, при этом наиболее активно изучаются бактерии. Однако грибы, которые в совокупности известны как «микобиота», все чаще признаются в качестве составных компонентов микробиоты, населяющей почти все мукосальные поверхности. Комменсальные грибы оказывают влияние на иммунитет хост-приемника, как и бактерии, и способствуют выполнению других важных функций, включая метаболизм. В этом новом понимании грибы рассматриваются как потенциальные биомаркеры для диагностики и прогнозирования различных заболеваний. В этом обзоре мы изучаем двойную ро

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… Adaptive Humoral Immunity Against Fungal Infections Antibodies generated against the fungal pathogen responsible for the infection are typically directed at peptides, glycoproteins, glycolipids, and polysaccharides, many of which are integral components of the fungal cell wall. …

Small-Fiber Neuropathy: An Etiology-Oriented Review.

BackgroundSmall-fiber neuropathy (SFN), affecting Aδ or C nerve fibers, is characterized by alterations of pain and temperature sensation, as well as autonomic dysfunction. Its diagnosis may still remain challenging as methods specifically assessing small nerve fibers are not always readily available, and standard techniques for large-fiber neuropathies, such as electroneuromyography, yield negative results. Still, skin biopsy for epidermal innervation and quantitative sensory testing allow for diagnosis in the presence of a congruent clinical picture.ObjectivesMany different etiologies may un

Gene Expression Profiling and Pathway Network Analysis Predicts a Novel Antitumor Function for a Botanical-Derived Drug, PG2.

PG2 is a botanical drug that is mostly composed of Astragalus polysaccharides (APS). Its role in hematopoiesis and relieving cancer-related fatigue has recently been clinically investigated in cancer patients. However, systematic analyses of its functions are still limited. The aim of this study was to use microarray-based expression profiling to evaluate the quality and consistency of PG2 from three different product batches and to study biological mechanisms of PG2. An integrative molecular analysis approach has been designed to examine significant PG2-induced signatures in HL-60 leukemia ce

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… Potent immune-modulating and anticancer effects of NKT cell stimulatory glycolipids Proceedings of the National Academy of Sciences of the United States of America 2007 104 25 10299 10304 10.1073/pnas.0703824104 2-s2.0-34547512326 17566107 PMC1965507 26 Tabakman R. Lecht S. Sephanova S. …

Biological response modifiers and infectious diseases: actual and potential therapeutic agents.

Biological response modifiers (BRMs) are agents which can modify the immune response to cancer or invasion of the organism by infectious agents. An explosive appearance of new BRMs has resulted from the development of recombinant gene technology and the availability of monoclonal antibodies. Colony-stimulating factors first became available for the prevention of neutropenia but may also have a role in the treatment of infections. Interleukin-1 is being tested as a modular of hematopoiesis and may be useful as a helper factor for T- and B-cell function. Immunoglobulins are being used against vi

Uncommon Factors Leading to Nephrotic Syndrome.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransfe

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… The glycocalyx, which is made of polysaccharides bound to proteins located on the outer surface of the cell membrane, builds glycoproteins and glycolipids, passes the filtration clefts, covers the endothelial cells and restricts the passage of macromolecules, and therefore ensures that plasma albumin … Congenital Disorders of Glycosylation: Pathophysiology and Histopathological Changes Linked to Nephrotic Syndrome Rare multisystem hereditary metabolic diseases resulting from impaired synthesis, transport and processing of glycoproteins and glycolipids are classified in the group of congenital glycosylation …

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.

Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue with poor outcome and little survivability of patients. The staging system has also been improved to better fit patient needs and to administer therapies in a more focused manner in consideration of pathology features. New and improved therapies have been developed; nevertheless, low efficacy and high

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… Gangliosides are sialic acid-containing glycolipids [ 119 ] that are able to stimulate the immune response, and their use in immunotherapy was demonstrated to improve the outcome in a patient with HR-NB [ 114 , 120 , 121 , 122 ]. … Monoclonal Antibodies to a Glycolipid Antigen on Human Neuroblastoma Cells. Cancer Res. 1985;45:2642–2649. 121. Yu A.L., Gilman A.L., Ozkaynak M.F., London W.B., Kreissman S.G., Chen H.X., Smith M., Anderson B., Villablanca J.G., Matthay K.K., et al. …

Стратегия FACS-Proteomics, направленная на экстраклелектальную эмоциональную характеристику однофенотипов в биологических жидкостях: изучение роли лейкоцитных ЭМ в множественном склерозе.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Изоляция и протеомика внеклеточной везиклетки (ЭМ) от жидкостей организма сопряжены с трудностями из-за их большой неоднородности. Недавно мы продемонстрировали, что срабатывание ячеек (FACS) с флюоресцентной активацией эффективно изолирует весь ЭМ-диапазон непосредственно от нетронутых жидкостей тела, что позволяет провести всеобъемлющий протеомикальный анализ ЭМ. Здесь мы впервые описали однофенотипный ЭВ, сортируя лейкоцитные ЭВ (Leuko EVs) из периферической крови и слез здоровых добровольцев.Используя оптимизированный и запатентованный протокол пятна всего ЭМ-отсека,

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… Moreover, isolated EVs could be “coated” with proteins, glycoproteins or glycolipids likely to cause aggregation, fusion and co-sedimentation of similar vesicles, negatively affecting the recovery, purity, and further molecular analyses. …

Immunotherapy Strategies Against Multiple Myeloma

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Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy.

The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP). Pure motor (multifocal motor neuropathy), sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy), exclusively distal sensory (distal acquired demyelinating sensory neuropathy) and very proximal sensory (chronic immune sensory polyradiculopathy) constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. T

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… reported variations in the incidence of GM1 antibodies are probably related to the different enzyme-linked immunosorbent assays used in the different studies as well as heterogeneous control populations.[ 27 ] Besides GM1 antibodies, immunoreactivity against other axon or myelin components such as the glycolipids …

Новые границы для лечения множественных склерозов: от целесообразных молекулов до биконкретных антител.

Множественный склероз (MS) — аутоиммунное демиелинирующее заболевание центральной нервной системы. С 1990-х годов был достигнут значительный прогресс в развитии терапевтического ландшафта MS, в результате чего было разработано более 20 различных методов лечения заболеваний (ДМТ). Эта терапия эффективно решает проблемы рецидивов и воспаления, но большинство из них не смогли реально предотвратить прогрессирование заболеваний. В то время как классически понимается как состояние с Т-камерой, наиболее эффективные DMT в замедлении движения также нацелены на клетки B. Новые классы методов лечения MS

Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature.

Commonly used chemotherapeutic agents in oncology/hematology practice, causing toxic peripheral neuropathy, include taxanes, platinum compounds, vinca alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents. This review paper intends to put together and discuss the spectrum of chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to highlight areas of future research to pursue on the topic. Current knowledge shows that the pathogenesis of CIPN still remains elusive, mostly because there are several sites of involvement in the peripheral nervous system. In

Ocular complications of antineoplastic therapies.

Ocular complications of antineoplastic agents can have a profound effect on the quality of life of cancer patients. New oncologic treatments like monoclonal antibodies, immunotherapies, antibody-drug conjugates, checkpoint inhibitors and growth factor receptors have resulted in increased ocular complications. These ocular complications differs in respect to distinct mechanisms of actions and lead to significant challenges in the management of cancer patients. In this review, we reviewed literature, clinical studies and cases detailing ocular complications due to administration of antineoplasti

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… This gives CAR a wide flexibility to recognize and target other surface antigens including proteins, carbohydrates, and glycolipids. This therapy is commonly used for B-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma [ 88 ]. …

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues.

Compared with conventional optical microscopy techniques, mass spectrometry imaging (MSI) or imaging mass spectrometry (IMS) is a powerful, label-free analytical technique, which can sensitively and simultaneously detect, quantify, and map hundreds of biomolecules, such as peptides, proteins, lipid, and other organic compounds in cells and tissues. So far, although several soft ionization techniques, such as desorption electrospray ionization (DESI) and secondary ion mass spectrometry (SIMS) have been used for imaging biomolecules, matrix-assisted laser desorption/ionization (MALDI) is still t

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… /CCA) | Proteins, peptides, N-glycans, lipids Sinapinic acid (SA) | Proteins and peptides 4-Chloro-α-cyanocinnamic acid (CICCA) | Proteins and peptides 2,5-Dihydroxyacetophenone (2,5-DHAP) | Phospholipids, proteins 9-Aminoacridine (9-AA) | Free fatty acids, lipids 1,5-Diaminonaphthalene (1,5-DAN) | Glycolipids … An On-Tissue Paterno-Buchi Reaction for Localization of Carbon-Carbon Double Bonds in Phospholipids and Glycolipids by Matrix-Assisted Laser-Desorption-Ionization Mass-Spectrometry Imaging. Angew. Chemie-International Edition 57, 12092–12096. Bergmann S., Lawler S. E., Qu Y., Fadzen C. …

Ось Гут-Брэйна в нейродегенерации: механистические связи между дисбиозом и нейроатологией.

& ЦЕЛЬ: Ось кишечника по сути представляет собой two- система связи, которая физически соединяет мозг с кишечным трактом. Связь поддерживается через ряд путей, включая нейронные, эндокринные и иммунные пути. Гут дисбиоз, который объясняется как дисбаланс в микробном сообществе, связан с причинно-следственной связью различных нейродегенеративных расстройств, таких, как болезнь Альцгеймера, болезнь Паркинсона и множественный склероз. Однако патологические механизмы в мозге известны лишь частично. В настоящем обзоре описывается процесс кишечного дисбиоза и нейродегенерации с подробным описанием ф

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… Lipopolysaccharides (LPS) are complex glycolipids that make up the outer membrane of Gram-negative bacteria. Normally, only small amounts of LPS can pass through the intestinal barrier and are efficiently eliminated by hepatic Kupffer cells( 52 , 53 ). …

Targeting endoplasmic reticulum stress-induced lymphatic dysfunction for mitigating bisphosphonate-related osteonecrosis.

BACKGROUND: Bisphosphonates (BPs) are the first-line treatment to stop bone resorption in diseases, including osteoporosis, Paget's disease, multiple myeloma and bone metastases of cancer. However, BPs-related osteonecrosis of the jaw (BRONJ), characterized by local inflammation and jawbone necrosis, is a severe intractable complication. The cumulative inflammatory burden often accompanies impaired lymphatic drainage, but its specific impact on BRONJ and the underlying mechanisms remain unclear. METHODS: The mouse BRONJ model was established to assess the integrity and drainage function of ly