Результаты поиска

Darbepoetin alpha in the treatment of cancer chemotherapy-induced anemia.

Anemia is a common, but underestimated and undertreated, complication of patients with cancer receiving chemo- or radiotherapy, and negatively affects their quality of life (QoL). Erythropoietic proteins (EPS) offer an effective treatment of cancer anemia and ameliorate QoL, although their use requires the correct targeting of hemoglobin increase to avoid thromboembolic complications. Currently the effort is focused on offering patients this effective treatment with reduced frequency of administration. Higher weekly single doses of recombinant human Epo (rHuEpo) either alpha or beta, instead o

Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives.

Aberrant glycosylation is a hallmark of cancer and can lead to changes that influence tumor behavior. Glycans can serve as a source of novel clinical biomarker developments, providing a set of specific targets for therapeutic intervention. Different mechanisms of aberrant glycosylation lead to the formation of tumor-associated carbohydrate antigens (TACAs) suitable for selective cancer-targeting therapy. The best characterized TACAs are truncated O-glycans (Tn, TF, and sialyl-Tn antigens), gangliosides (GD2, GD3, GM2, GM3, fucosyl-GM1), globo-serie glycans (Globo-H, SSEA-3, SSEA-4), Lewis anti

Совпадение в полном тексте источника
… Moreover, addition of sialic acid to the Tn antigen, catalyzed by the ST6GalNAc-I, results in the sialyl-Tn antigen synthesis. The sialylation of the Tn antigen blocks further elongation of the saccharide chain. … Considering sialic acid residue involvement in tumor immune-evasion mechanisms, the laboratory of Carolyn Bertozzi developed a strategy to eliminate sialic acids of HER2+ breast cancer cells. …

Dysregulated expression of the Cd22 gene as a result of a short interspersed nucleotide element insertion in Cd22a lupus-prone mice.

The Cd22 gene encodes a B cell-specific adhesion molecule that modulates B cell Ag receptor-mediated signal transduction, and is allelic to a lupus-susceptibility locus in New Zealand White (NZW) mice. In this study, we show that, in addition to the wild-type transcripts, NZW (Cd22a) mice synthesize aberrant CD22 mRNAs that contain approximately 20-120 nucleotide insertions upstream of the coding region between exons 2 and 3, and/or approximately 100-190 nucleotide deletions of exon 4. Sequence analysis revealed that these aberrant mRNA species arose by alternative splicing due to the presence

Oncolytic Viruses for Cancer Therapy in Dogs.

Cancer remains the leading cause of death in domestic dogs. Conventional therapeutic approaches, including surgery, chemotherapy, and radiotherapy, frequently fail to achieve sustained remission or stabilization. Oncolytic virotherapy, a rapidly advancing therapeutic modality in human oncology, is emerging as a novel strategy in veterinary medicine. This systematic review summarizes current knowledge on the application of oncolytic viruses (OVs) in canine cancer treatment, focusing on their mechanisms of action, safety profiles, and clinical efficacy. We evaluate diverse OV platforms, includin

Совпадение в полном тексте источника
… Ubiquitous sialic acids serve as co-attachment factors, binding viral capsids to stabilize virus–cell interactions prior to receptor engagement [ 61 ]. … Sialic acid and its protein derivatives represent primary Sendai receptors; these are more abundantly expressed on tumor cells than non-transformed cells [ 92 ]. …

Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies.

Chimeric antigen receptor T (CAR-T) cell therapy has produced impressive results in clinical trials for B-cell malignancies. However, safety concerns related to the inability to control CAR-T cells once infused into the patient remain a significant challenge. Here we report the engineering of recombinant antibody-based bifunctional switches that consist of a tumor antigen-specific Fab molecule engrafted with a peptide neo-epitope, which is bound exclusively by a peptide-specific switchable CAR-T cell (sCAR-T). The switch redirects the activity of the bio-orthogonal sCAR-T cells through the sel

The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy.

Recently, the chimeric antigen receptor (CAR)-T approach represented a breakthrough in the treatment of B-cell malignancies, encouraging the application of the approach for other hematological diseases, such as acute myeloid leukemia (AML). Heterogeneity and antigen variation in the pathological cell population hinder the choice of molecular targets in the case of AML. In this review, the critical aspects were described that are usually considered when selecting molecular targets for the new CAR genetic constructs. The role of AML-associated antigens in AML progression was covered. In conclusi

Роль микроглии в синаптогенезе, синаптической и синаптической пластичности в физиологических условиях и в нарушениях центральной нервной системы.

Микроглии являются постоянными иммунными клетками мозга, которые были широко изучены для их иммунного наблюдения и фагоцитоза. В последние годы постепенно признается важная роль микроглии в синапсовом образовании, ликвидации и пластичности. Синапсы являются основным режимом связи между нейронами. Они постоянно меняются в количестве и пластичности на протяжении всего жизненного цикла, который является основой обучения и памяти. Микроглии являются сильно мотилированными, ветковыми формами, которые осуществляют мониторинг микроокружающей среды центральной нервной системы (КНС) и поощряют синапсов

Targeting hematologic malignancies by inhibiting E-selectin: A sweet spot for AML therapy?

E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewisx) on acute myeloid leukemia (AML) cells leads to chemotherapy resistance in vivo. Uproleselan (GMI-1271) is a carbohydrate analog of sialyl Lewisx that blocks E-selectin binding. A Phase 2 tri

Повышенное гликозилирование автоантител во время лечения истощения клеток B.

Для ряда хронических аутоиммунных заболеваний характерна повышенная аутоантибодиозная гликозилация Fab. Остается неясным, связаны ли Fab glycans со состоянием заболевания или развитием, но могут ли они служить его показателем. Многие аутоиммунные заболевания лечатся с помощью методов лечения истощения клеток В, что в первую очередь приводит к сокращению числа автоантител. Возникает вопрос, может ли терапия разрушения клеток B оказать воздействие на гликозилацию Fab. Здесь мы изучили продольное воздействие терапии истощения клеток B на гликозилацию Fab для общего ИгГ и IgG автоантифитов в ревма

The convergent evolution of influenza A virus: Implications, therapeutic strategies and what we need to know.

Influenza virus infection, more commonly known as the 'cold flu', is an etiological agent that gives rise to recurrent annual flu and many pandemics. Dated back to the 1918- Spanish Flu, the influenza infection has caused the loss of many human lives and significantly impacted the economy and daily lives. Influenza virus can be classified into four different genera: influenza A-D, with the former two, influenza A and B, relevant to humans. The capacity of antigenic drift and shift in Influenza A has given rise to many novel variants, rendering vaccines and antiviral therapies useless. In light

Совпадение в полном тексте источника
… release of sialic acids ( Palese et al., 1974 ; Mtambo et al., 2021 ). … The influenza HA protein is a glycoprotein found on the surface of influenza viruses, which interacts with the sialic acid (SA) receptors on the surface of erythrocytes ( Pedersen, 2014 ; Ravina et al., 2021 ). …

The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases.

PurposeIn 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121-167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper.MethodsA literature search mainly focusing on the role of the glycocalyx in the

Совпадение в полном тексте источника
… IAV binds to the host cell surface via its trimeric spike protein hemagglutinin, which recognizes sialic acids on the GCX of cellular membranes. … Despite the low binding affinity of individual hemagglutinin receptor binding sites to sialic acid, a stable adhesion originates from multiple ligand–receptor binding events between the virus and the sialic acid glycoconjugates on the cell surface. 105 Human Corona Viruses (HCoV-NL63) is an alpha coronavirus …

The Therapeutic Potential of Secreted Factors from Dental Pulp Stem Cells for Various Diseases.

An alternative source of mesenchymal stem cells has recently been discovered: dental pulp stem cells (DPSCs), including deciduous teeth, which can thus comprise potential tools for regenerative medicine. DPSCs derive from the neural crest and are normally implicated in dentin homeostasis. The clinical application of mesenchymal stem cells (MSCs) involving DPSCs contains various limitations, such as high cost, low safety, and cell handling issues, as well as invasive sample collection procedures. Although MSCs implantation offers favorable outcomes on specific diseases, implanted MSCs cannot su

Novel Therapies to Address Unmet Needs in ITP.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder that causes low platelet counts and subsequent bleeding risk. Although current corticosteroid-based ITP therapies are able to improve platelet counts, up to 70% of subjects with an ITP diagnosis do not achieve a sustained clinical response in the absence of treatment, thus requiring a second-line therapy option as well as additional care to prevent bleeding. Less than 40% of patients treated with thrombopoietin analogs, 60% of those treated with splenectomy, and 20% or fewer of those treated with rituximab or fostamatinib reach su

Совпадение в полном тексте источника
… Platelet Desialylation Inhibitors The sialic acids on complex glycan molecules prolong the life span of proteins and cells. Young platelet surfaces are rich in sialic acid. … Sialic acid is removed from platelets by sialidases, such as neuraminidase 1 and neuraminidase 3 [ 87 ], after which the platelets are cleared by the liver [ 88 ] via a mechanism led initially by hepatocytes, which recruit platelets through their Ashwell–Morell receptors, and finally by Kupffer cells …

GD2: hopes and challenges for the treatment of pediatric patients with tumors of the central nervous system.

Pediatric Central Nervous System (CNS) tumors are the leading cause of cancer-related death in children, yet effective treatment options remain limited. The tumor-associated antigen GD2 is a promising target for immunotherapeutic approaches aimed at treating pediatric CNS cancers; however, its heterogeneous expression within and between tumors can complicate the development of effective strategies. Here we review different aspects of GD2 biology, including its structure, synthesis pathway, and cellular and tissue expression, focusing on pediatric CNS tumors. We provide a detailed overview of t

Совпадение в полном тексте источника
… In particular, GD2 is a disialoganglioside containing 2 sialic acids and 5 monosaccharides linked to a ceramide. The cellular synthesis of GD2 is a complex and well-regulated 1 . … In addition, the Sialyl O-Acetyl transferases (SOAT) can add an O-acetyl group to the outer sialic acid residue, leading to the production of an O -acetylated derivative of GD2, the O-Ac-GD2, which significantly alters GD2 immunological properties 3 , 4 (Table 1 ). …

Новинка сывороточных биомаркеров с 7 кортикальными повреждениями Тесла МРТ, лептоминированием и глубоким объемом серого вещества в ранних множественных склерозах.

Повреждения серой материи, атрофии мозга и воспаления менингеев, гипотезы гипотезы имеют отношение к множественным склерозовым (MS) патогенезам, хотя их связь с иммунными изменениями в ранних склерозах не является достаточной. Цель этого исследования состоит в изучении корреляции между концентрацией 112 белков сыворотки и 7 показателями серьезности заболеваний у пациентов с ранним синдромом MS, определяемыми МРТ Тесла. В этот анализ были включены пациенты из СНГ или MS, имеющие МРТ мозга 7 Tesla и образцы крови в течение пяти лет с момента диагностирования MS (n = 57). Корреляционный анализ бы

The influence of neuro-tumor interactions on tumorigenesis and therapeutic response.

The intricate crosstalk between the nervous system and tumors has emerged as a pivotal determinant of tumorigenesis, progression, and therapeutic response. This review synthesizes current insights into neuro-tumor interactions, highlighting how neuronal networks within the tumor microenvironment (TME) modulate cancer cell proliferation, invasion, and angiogenesis by releasing neurotransmitters, growth factors, etc. The neuro-immune axis, a critical interface linking neural signaling to immune regulation, is explored in depth, elucidating how neuronal-derived molecules influence the phenotype a

Aptamers and Antisense Oligonucleotides for Diagnosis and Treatment of Hematological Diseases.

Aptamers or chemical antibodies are single-stranded DNA or RNA oligonucleotides that bind proteins and small molecules with high affinity and specificity by recognizing tertiary or quaternary structures as antibodies. Aptamers can be easily produced in vitro through a process known as systemic evolution of ligands by exponential enrichment (SELEX) or a cell-based SELEX procedure. Aptamers and modified aptamers, such as slow, off-rate, modified aptamers (SOMAmers), can bind to target molecules with less polar and more hydrophobic interactions showing slower dissociation rates, higher stability,

Совпадение в полном тексте источника
… CD33, also known as Siglec-3 as a member of the sialic acid-binding immunoglobulin-like lectins, is a 67 kDa transmembrane glycoprotein with an extracellular domain characterized by a sialic acid immunoglobulin(Ig)-like binding domain and a C2 Ig-like domain, and a cytoplasmic tail with an immunoreceptor … Sialic acids siglec interaction: A unique strategy to circumvent innate immune response by pathogens Indian J. Med. Res. 2013 138 648 662 24434319 PMC3928697 58. Laszlo G.S. Estey E.H. Walter R.B. …

Latest developments in MUC1 immunotherapy.

Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of appro

Nano-formulations in disease therapy: designs, advances, challenges, and future directions.

Nano-formulations, as an innovative drug delivery system, offer distinct advantages in enhancing drug administration methods, improving bioavailability, promoting biodegradability, and enabling targeted delivery. By exploiting the unique size advantages of nano-formulations, therapeutic agents, including drugs, genes, and proteins, can be precisely reorganized at the microscale level. This modification not only facilitates the precise release of these agents but also significantly enhances their efficacy while minimizing adverse effects, thereby creating novel opportunities for treatment of a

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ