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Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial.

BackgroundMoxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL).MethodsEligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and mi

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… IHC involved staining for the presence of phenotypical B-cell (CD20) and HCL (CD79a, annexin A1, DBA.44, and PAX-5) antigens. MRD negativity was defined as the absence of HCL phenotype cells in the bone marrow biopsy by IHC and in the bone marrow aspirate/blood by flow cytometry. …

Bibliometric analysis of bone metastases from lung cancer research from 2004 to 2023.

BackgroundBone metastases of lung cancer (BMLC) severely diminish patients' quality of life due to bone-related events, and the lack of clear guidelines globally regarding medical and surgical treatment significantly reduces patient survival. While knowledge about BMLC has grown exponentially over the past two decades, a comprehensive and objective bibliometric analysis remains absent.MethodsA comprehensive bibliometric analysis was conducted on relevant literature on BMLC extracted from the Web of Science database from 2004 to 2023 by Biblioshiny, VOSviewer, Scimago Graphica, CiteSpace, and M

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… Annexin A1 is a potential biomarker of bone metastasis in small cell lung cancer . Oncol Lett . ( 2021 ) 21 : 141 . doi: 10.3892/ol.2020.12402 33552260 PMC7798093 28 Tang Y Qu J Wu J Li S Zhou Y Xiao J . …

Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great heterogeneity among patients complicates therapeutic decision-making. In the past decades, development of new therapies and drugs have significantly improved survival of MM patients. However, resistance to drugs and relapse remain the most common causes of mortality and are the major challenges to overcome. The advent of high throughput omics technologies capable of analyzing big amount of clinical a

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… Several differentially expressed proteins were identified, including annexin A1. Subsequent functional studies showed that knockdown of annexin A1 potentiated dexamethasone effects insensitive and resistant HMCLs [ 265 ]. …

The Fifth International Meeting of ISEV, ISEV2016, Rotterdam, The Netherlands, 4 - 7 May, 2016.

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γδ T Cells: Game Changers in Immune Cell Therapy for Cancer.

Gamma delta (γδ) T cells are a unique subset of T lymphocytes with distinctive features that make them highly promising candidates for cancer therapy. Their MHC-independent recognition of tumor antigens, ability to mediate direct cytotoxicity, and role in modulating the tumor microenvironment position them as versatile agents in cancer immunotherapy. This review integrates and synthesizes the existing data on γδ T cells, with an emphasis on the development and optimization of in vitro expansion protocols. Critical aspects are detailed such as activation strategies, co-culture systems, cytokine

PI3K/AKT сигнализирующий путь: молекулярный перекресток в опухоли и терапевтические инновации.

PI3K/AKT сигнализирующий путь служит центральным регулирующим узлом, регулирующим основные клеточные процессы, включая рост, распространение, метаболизм, выживание и миграцию. В контексте развития опухоли и рака аберральная активация этого пути приводит к злокачественным преобразованиям, усиливает инвазивный и метастатический потенциал и оказывает сопротивление терапевтическому вмешательству, что в конечном счете приводит к прогрессированию опухоли и более низким клиническим результатам. В этом исследовании всесторонне изучается ИП3К/АКТ, сигнализирующий о его причастности к различным человече

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… PI3K phosphatidylinositol 3-kinase, AKT protein kinase B, EGFR epidermal growth factor receptor, PTEN phosphatase and tensin homolog, FAK focal adhesion kinase, ITGA10 integrin α10, ANXA1 annexin A1, ANXA3 annexin A3, HIF hypoxia-inducible factor, FTO fat mass and obesity-associated protein, NEDD4 neuronally …

Paeoniflorin непосредственно ставит ENO1 перед инхибитом M1 поляризацию микроглий/макропатических и смягчающих болезнь EAE.

В настоящее время хронические аутоиммунные заболевания, связанные с множественным склерозом (MS), остаются неизлечимыми. Паеонифлорин (PF), который представляет собой монотерпеновый глюкосид, полученный из Paeonia lactiflora Pall, признается за нейрозащитные и антивоспалительные свойства. Однако точный механизм, с помощью которого ПФ регулирует НР, является неясным. Эта работа направлена на разъяснение основополагающих механизмов PF в EAE, хорошо зарекомендовавшей себя животной модели MS, и на выявление целевых белков, которые PF действует непосредственно. Наши результаты показали, что управле

Meibomian Gland Dysfunction Is Associated with Low Levels of Immunoglobulin Chains and Cystatin-SN.

Meibomian gland dysfunction (MGD) is a highly prevalent condition and the most common cause of evaporative dry eye disease. Studying the proteome of MGD can result in important advances in the management of the condition. Here, we collected tear film samples from treatment naïve patients with MGD (n = 10) and age-matched controls (n = 11) with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography-tandem mass spectrometry. The proteins were considered differentially expressed if p < 0.05. A total of 88 proteins were significantly regulate

Aptamer Therapeutics in Cancer: Current and Future.

Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small-approximately one-tenth that of monoclonal antibodies-their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesize

Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours.

Individuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma. Here, we analysed CYLD mutant tumour genomes by array comparative genomic hybridisation and gene expression microarray analysis. CYLD mutant tumours were characterised by an absence of copy-number aberrations apart from LOH chromosome 16q, the genomic location of the CYLD gene. Gene expression profiling of CYLD mutant tumours showed dysregulated tropomyosin kinase (TRK) signalling, with overex

Emerging Target Discovery Strategies Drive the Decoding of Therapeutic Power of Natural Products and Further Drug Development: A Case Study of Celastrol.

Celastrol (CEL) is a natural pentacyclic triterpenoid demonstrating significant therapeutic properties against various diseases. However, the ambiguity of target information poses a significant challenge in transitioning CEL from a traditional remedy to a modern pharmaceutical agent. Recently, the emerging target discovery approaches of natural products have broadened extensive avenues for uncovering comprehensive target information of CEL and promoting its drug development. Herein, diverse target discovery strategies are overviewed for the pharmacological and toxicological studies of CEL, inc

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression.

Multiple myeloma (MM) is a hematological malignancy of plasma cells that proliferate and accumulate within the bone marrow (BM). Work from many groups has made evident that the complex microenvironment of the BM plays a crucial role in myeloma progression and response to therapeutic agents. Within the cellular components of the BM, we will specifically focus on mesenchymal stromal cells (MSCs), which are known to interact with myeloma cells and the other components of the BM through cell to cell, soluble factors and, as more recently evidenced, through extracellular vesicles. Multiple structur

Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer.

Cancer is one of the most dreadful diseases in the world with a mortality of 9.6 million annually. Despite the advances in diagnosis and treatment during the last couple of decades, it still remains a serious concern due to the limitations associated with currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. The importance of medicinal plants as primary healthcare has been well-known from time immemorial against various human diseases, including cancer. Commiphora wightii that belongs to Burseraceae family is one suc

The impact of the gut microbiome on tumor immunotherapy: from mechanism to application strategies.

Immunotherapy is one of the fastest developing areas in the field of oncology. Many immunological treatment strategies for refractory tumors have been approved and marketed. Nevertheless, much clinical and preclinical experimental evidence has shown that the efficacy of immunotherapy in tumor treatment varies markedly among individuals. The commensal microbiome mainly colonizes the intestinal lumen in humans, is affected by a variety of factors and exhibits individual variation. Moreover, the gut is considered the largest immune organ of the body due to its influence on the immune system. In t

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… Fusobacterium nucleatum adheres to colon tissues through its unique FadA adhesin, which binds to E-cadherin on the surface of colon cells and activates β-catenin signaling and Annexin A1, resulting in inflammatory and carcinogenic responses [ 29 , 30 ]. … Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/beta-catenin modulator Annexin A1. EMBO Rep. 2019;20(4):e47638. doi: 10.15252/embr.201847638. 31. Gur C, Ibrahim Y, Isaacson B, Yamin R, Abed J, Gamliel M, et al. …

Emerging Roles of Mesenchymal Stem/Stromal-Cell-Derived Extracellular Vesicles in Cancer Therapy.

Despite the tremendous efforts of many researchers and clinicians, cancer remains the second leading cause of mortality worldwide. Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in numerous human tissues and presenting unique biological properties, such as low immunogenicity, powerful immunomodulatory and immunosuppressive capabilities, and, in particular, homing abilities. Therapeutic functions of MSCs are mediated mostly by the paracrine effect of released functional molecules and other variable components, and among them the MSC-derived extracellular vesicles (MSC-EVs)

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… The membrane-linked protein Annexin A1 was proposed as a unique marker for microvesicles shed directly from the cell membrane. …

Poster Abstracts

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Simultaneous Inhibition of Mcl-1 and Bcl-2 Induces Synergistic Cell Death in Hepatocellular Carcinoma.

Despite the recent approval of new therapies, the prognosis for patients with hepatocellular carcinoma (HCC) remains poor. There is a clinical need for new highly effective therapeutic options. Here, we present a combined application of BH3-mimetics as a potential new treatment option for HCC. BH3-mimetics inhibit anti-apoptotic proteins of the BCL-2 family and, thus, trigger the intrinsic apoptosis pathway. Anti-apoptotic BCL-2 proteins such as Bcl-2 and Mcl-1 are frequently overexpressed in HCC. Therefore, we analyzed the efficacy of the two BH3-mimetics ABT-199 (Bcl-2 inhibitor) and MIK665

Epigenetic modification in diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microangiopathy in diabetic patients and the main cause of death in diabetic patients. The main manifestations of DKD are proteinuria and decreased renal filtration capacity. The glomerular filtration rate and urinary albumin level are two of the most important hallmarks of the progression of DKD. The classical treatment of DKD is controlling blood glucose and blood pressure. However, the commonly used clinical therapeutic strategies and the existing biomarkers only partially slow the progression of DKD and roughly predict disease progression. Therefor

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… The attenuation of diabetic nephropathy by annexin A1 Via regulation of lipid metabolism through the Ampk/Pparalpha/Cpt1b pathway. Diabetes (2021) 70(10):2192–203. doi: 10.2337/db21-0050 35. Alshehri AS. …

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

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Молекулярные биомаркеры, связанные с ATLL и HAM HTLV-1 Инфицирование: систематический обзор.

Тип вируса человека T-лимфотроп 1 (В тыс.HTLV-1) инфекционные вещества five в адрес 10 million по всему миру, хотя только у меньшинства возникают серьезные последствия, такие, как лейкемия/лимфома взрослых Т-клеток (ATLL) или HTLV-1-associated Миэлопатия (HAM). Несмотря на широкое использование доказательственной нагрузки (ПВН), она характеризуется ограниченной чувствительностью и специфичностью, что усиливает потребность в дополнительных биомаркерах. В качестве перспективных инструментов для совершенствования прогнозирования рисков стали использоваться подходы, основанные на использовании оми

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… Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP. 219BMC Infect Dis. 2021;21 doi: 10.1186/s12879-021-05917-y. 21. Guerrero CL, Yamashita Y, Miyara M, Imaizumi N, Kato M, Sakihama S, et al. …