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Cytokine-Induced Killer Cells: A Unique Platform for Adoptive Cell Immunotherapy after Allogeneic Hematopoietic Stem Cell Transplantation.

BackgroundImmunotherapies in general, and cellular immunotherapies, in particular are becoming increasingly integrated into current personalized cancer treatment, though still facing some obstacles in the allogeneic hematopoietic stem cell transplantation (HSCT) setting.SummaryThe concept of isolating immune effector cells, expanding their numbers, enhancing their anticancer capabilities by modifying them without increasing their alloreactive potential is the mainstay of adoptive cellular immunotherapy after allogeneic HSCT. In this context, cytokine-induced killer (CIK) cells, a polyfunctiona

Взаимоотношения между Т-помощником 1 Воспаление биомаркеров и гематологический индекс реакции пациентов с множественным склерозом.

Множественный склероз - это хроническая, прогрессивная, нетрудоспособная болезнь, связанная с высоким уровнем инфицирования, свидетельствами хронического воспаления и высоким коэффициентом смертности. Ненормальные свойства сыворотки цитокины и изменения в активности провокационных клеток были связаны с повторным излучением множественных склерозов (MS-RR). Цель этого исследования состоит в том, чтобы ввести новые подстрекательские коэффициенты, полученные на основе гематологических и липидных индексов в качестве дискриминаторов Т-помощи (Th)-1/Th-2 - деятельность в ОР-МС. Методы, используемые п

Functional variant of IL33 is associated with survival of osteosarcoma patients.

ObjectivesPrevious genome-wide association study showed that GLDC/IL33 loci were associated with overall survival in patients with osteosarcoma (OS). We performed a replication study to explore whether variants of GLDC/IL33 are associated with the survival of OS patients and to further verify their functional role in the gene expression.MethodsA total of 216 patients with OS were enrolled. The overall survival time was calculated from the date of diagnosis till the date of last follow-up or mortality. Two SNPs were genotyped, including rs55933544 and rs74438701. OS specimens were obtained from

Development of an Active Chimeric IL13Rα2 ADC for Diffuse Intrinsic Pontine Glioma.

IntroductionDiffuse intrinsic pontine glioma (DIPG) is a rare pediatric brain tumor with a critical unmet need due to the lack of approved, curative interventions available. The interweaving of malignant cells with normal tissue makes surgical extraction essentially impossible, and radiation provides only transient benefit. The recent ONC201 FDA approval, however, suggests DIPG therapy is tractable. Having identified overexpression of IL13Rα2 in DIPG tumor tissue versus normal brain tissue, we investigated binding of commercially available IL13Rα2 monoclonal antibodies. The top candidate antib

Role of B-Cell in the Pathogenesis of Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare multisystem autoimmune disease, characterized by fibrosis, vasculopathy, and autoimmunity. Recent advances have highlighted the significant implications of B-cells in SSc. B-cells are present in affected organs, their subpopulations are disrupted, and they display an activated phenotype, and the regulatory capacities of B-cells are impaired, as illustrated by the decrease in the IL-10+ producing B-cell subpopulation or the inhibitory membrane co-receptor density. Recent multi-omics evidence highlights the role of B-cells mainly in the early stage of SSc and p

The Key Role of Hepcidin-25 in Anemia in Multiple Myeloma Patients with Renal Impairment.

Background and objectives: Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron turnover: serum soluble transferrin receptor (sTfR) and hepcidin-25 in patients at various stages of MM in relation with markers of anemia, iron status, inflammation, renal impairment and burden of the disease and as predictors of mortality. Materials and methods: Seventy-three MM patients (six with smoldering and 67 with symptomatic disease) were recruited and observed for up to 27 months. Control gro

Antibody-based therapies in multiple myeloma.

The unmet need for improved multiple myeloma (MM) therapy has stimulated clinical development of monoclonal antibodies (mAbs) targeting either MM cells or cells of the bone marrow (BM) microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic r

Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogeno

Regulatory Effect and Mechanism of Erythroblastic Island Macrophages on Anemia in Patients with Newly Diagnosed Multiple Myeloma.

ObjectiveTo examine the clinical characteristics and anemia-related factors in patients with newly diagnosed multiple myeloma (NDMM), as well as the effect and mechanism of erythroblastic islands (EBIs) and EBI macrophages in NDMM patients with anemia.MethodsWe collected and analyzed clinical data to find anemia-related factors. Using flow cytometry, the numbers and ratios of erythroblasts and EBI macrophages were determined. RNA sequencing (RNA-seq) was used to determine the differences of EBI macrophages in NDMM patients with or without anemia.ResultsBased on the clinical characteristics of

Role of IL-5 in eosinophil-associated diseases and prospects for multi-target therapy.

Eosinophil-associated diseases are a group of inflammatory disorders characterized by abnormal eosinophil infiltration, which significantly impacts patients' quality of life. Interleukin-5 (IL-5), a critical cytokine that regulates eosinophil development, activation, chemotaxis, and survival, plays a central role in the pathogenesis of these diseases. This review systematically examines the molecular structure and signaling pathways of IL-5, its mechanisms of action in asthma and chronic obstructive pulmonary disease (COPD), and the development and clinical applications of monoclonal antibodie

Перекресток между диабетом и болезнью Альцгеймера: Молекулярная перспектива.

Общемировая распространенность видов 2 Заболевание сахарным диабетом (T2DM) и болезнью Альцгеймера (AD) значительно возрастает в зависимости от возраста. Растущие данные подтверждают концептуализацию АД как типа 3 диабет, термин, предлагаемый для описания метаболического заболевания, вызванного главным образом поврежденной инсулиновой сигнализацией и инсулиновой резистентностью в мозге. В рамках этого обзора изучаются общие молекулярные механизмы, лежащие в основе как T2DM, так и AD, включая хроническую нейроинфламму, окислительный стресс, митохондриальную дисфункцию и поврежденный метаболизм

Modulation of Angiogenic Processes by the Human Gammaherpesviruses, Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus.

Angiogenesis is the biological process by which new blood vessels are formed from pre-existing vessels. It is considered one of the classic hallmarks of cancer, as pathological angiogenesis provides oxygen and essential nutrients to growing tumors. Two of the seven known human oncoviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), belong to the Gammaherpesvirinae subfamily. Both viruses are associated with several malignancies including lymphomas, nasopharyngeal carcinomas, and Kaposi's sarcoma. The viral genomes code for a plethora of viral factors, includin

Pathogenesis of bone disease in multiple myeloma: from bench to bedside.

Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. Several intracellular and intercellular signaling cascades, including RANK/RANKL/OPG, Notch, Wnt, and numerous chemokines and interleu

Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies.

Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells

Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.

Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable fo

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… Interleukin-7: from bench to clinic Blood 2002 99 11 3892 3904 10.1182/blood.v99.11.3892 2-s2.0-0036624721 12010786 40 Condomines M. Veyrune J.-L. Larroque M. …

Pathogenesis and treatment of Sjogren's syndrome: Review and update.

Sjogren's syndrome (SS) is a chronic autoimmune disease accompanied by multiple lesions. The main manifestations include dryness of the mouth and eyes, along with systemic complications (e.g., pulmonary disease, kidney injury, and lymphoma). In this review, we highlight that IFNs, Th17 cell-related cytokines (IL-17 and IL-23), and B cell-related cytokines (TNF and BAFF) are crucial for the pathogenesis of SS. We also summarize the advances in experimental treatment strategies, including targeting Treg/Th17, mesenchymal stem cell treatment, targeting BAFF, inhibiting JAK pathway, et al. Similar

Treatment-induced mucositis: an old problem with new remedies.

Mucositis may be a painful, debilitating, dose-limiting side-effect of both chemotherapy and radiotherapy for which there is no widely accepted prophylaxis or effective treatment. The basis of management is pain relief, prevention of dehydration and adequate nutrition. When tested vigorously, most antiseptic mouthwashes and anti-ulcer agents are ineffective. Simple mechanical cleansing by saline is the most effective traditional measure. A variety of new agents are effective. Granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) act outwith

Inflammation in cancer: therapeutic opportunities from new insights.

As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors

Targeting NETosis: nature's alarm system in cancer progression.

Neutrophils are recognized active participants in inflammatory responses and are intricately linked to cancer progression. In response to inflammatory stimuli, neutrophils become activated, releasing neutrophils extracellular traps (NETs) for the capture and eradication of pathogens, a phenomenon termed NETosis. With a deeper understanding of NETs, there is growing evidence supporting their role in cancer progression and their involvement in conferring resistance to various cancer therapies, especially concerning tumor reactions to chemotherapy, radiation therapy (RT), and immunotherapy. This

Use of Nutraceuticals in Elderly to Fight Inflammation and Immuno-Senescence: A Randomized Case-Control Study.

Elderly people are at high risk of suffering from infection and being affected by severe forms of disease because their immunosystem suffers from aging. The alteration of normal immune functions causes the increase of pro-inflammatory cytokines which can expose these people to increased risk of developing pathologies as cancer, diabetes, and/or arthritis. Some supplements could be helpful for restoring normal immune functions. We conducted a case-control study to evaluate the efficacy of a supplement containing Sambucus nigra, zinc, tyndallized Lactobacillus acidophilus (HA122), arabinogalacta