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Keyword Index for Volume 88

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Targeting the RANKL/RANK/OPG Axis for Cancer Therapy.

RANKL and RANK are expressed in different cell types and tissues throughout the body. They were originally described for their essential roles in bone remodeling and the immune system but have subsequently been shown to provide essential signals from regulating mammary gland homeostasis during pregnancy to modulating tumorigenesis. The success of RANKL/RANK research serves as a paragon for translational research from the laboratory to the bedside. The case in point has been the development of Denosumab, a RANKL-blocking monoclonal antibody which has already helped millions of patients sufferin

Extracellular Vesicles in Multiple Myeloma-Cracking the Code to a Better Understanding of the Disease.

Multiple myeloma (MM) is a plasma cell-derived malignancy that stands for around 1.5% of newly discovered cancer cases. Despite constantly improving treatment methods, the disease is incurable with over 13,000 deaths in the US and over 30,000 in Europe. Recent studies suggest that extracellular vesicles (EVs) might play a significant role in the pathogenesis and evolution of MM. Further investigation of their role could prove to be beneficial in establishing new therapies and hence, improve the prognosis of MM patients. What is more, EVs might serve as novel markers in diagnosing and monitorin

Bench-to-bedside review: Angiopoietin signalling in critical illness - a future target?

Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and - despite many unanswered questions - therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting mu

Роль микробиомы в множестве миелом: новые знания и терапевтические возможности.

Множественная миелома — гематологический рак, описываемый распространением плазменных клеток в костном мозге, что вызывает иммунную дисфункцию и другие аномалии. Микробиом кишечника, микробное сообщество в желудочно-кишечном тракте, было обнаружено, что он модифицирует системный иммунитет, воспаление и метаболизм. Хотя взаимосвязь между кишечным микробиомом и множеством миелома была обнаружена в недавних исследованиях, существует пробел в знаниях, связывающий воздействие микробиома на патогенез и лечение множественной миеломы. Несбалансированность в кишечном микробиоме, дисбиозе, может влиять

Появляющаяся роль BTK Inhibitors в многоразовом склерозе: от иммунобиологии к клиническому переводу.

Множественный склероз (MS), аутоиммунное заболевание, предполагает периферическую иммунную активацию, за которой следует воспаление CNS в разрозненной форме. Несмотря на то, что высокоэффективные методы коррекции заболеваний (HO-DMT) оказались эффективными в борьбе с рецидивами у пациентов с синдромом MS, они не позволяют эффективно ориентироваться на хроническую микрогильевую активацию и удушающие повреждения у пациентов с синдромом MS. Тейросиновые ингибиторы киназы Брютона (BTKis), которые являются перорально активными и способными пересечь мозговой барьер, были признаны эффективными для мо

Cytokine-induced killer cells: new insights for therapy of hematologic malignancies.

BackgroundCytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC-unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment-related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies.Main bodyCIK cells consist of CD3+/CD56+ natural killer (NK) T cells, CD3-/CD56+ NK cells, and CD3+/CD56- cytotoxic T cells. In this regard, the CD3+/CD56+ NK T cells are the primary

Совпадение в полном тексте источника
… Increase of proliferation rate and enhancement of antitumor cytotoxicity of expanded human CD3+ CD56+ immunologic effector cells by receptor-mediated transfection with the interleukin-7 gene. Gene Ther. 1998;5(1):31–9. 98. Pfirrmann V, Oelsner S, Rettinger E, Huenecke S, Bonig H, Merker M, et al. …

Цель METTL3/m6A/SOCS3 перепрограммирует макрофажную поляризацию, связанную с опухолью, с тем чтобы повысить эффективность анти-PD-1-терапии в множестве миеломы.

ИССЛЕДОВАНИЯ: В ходе этого исследования были изучены функции иммуномодулятора подавителя цитокина, сигнализирующего 3 (SOCS3) в макрофаге поляризации и активации цитотоксичных Т-клеток в микроопухоли (TME) множественной миэломы (MM). МЕТОДЫ: Выражение SOCS3 оценивалось в клинических образцах MM и здоровом контроле. Для разъяснения воздействия SOCS3 на злокачественное развитие клеток MM и поляризацию макрофага были разработаны анализы эффективности и потери функций, а также система кокультуры MM-камер. В рамках механистических исследований основное внимание было уделено модуляции SOCS3 при помо

The role of procalcitonin in identifying high-risk cancer patients with febrile neutropenia: A useful alternative to the multinational association for supportive care in cancer score.

BackgroundThe Multinational Association for Supportive Care in Cancer (MASCC) risk index has been utilized to determine the risk for poor clinical outcomes in patients with febrile neutropenia (FN) in an emergency center (EC). However, this index comprises subjective elements and elaborated metrics limiting its use in ECs. We sought to determine whether procalcitonin (PCT) level (biomarker of bacterial infection) with or without lactate level (marker of inadequate tissue perfusion) offers a potential alternative to MASSC score in predicting the outcomes of patients with FN presenting to an EC.

Engineering enhanced CAR T-cells for improved cancer therapy.

Chimeric antigen receptor (CAR) T-cell therapies have evolved from a research tool to a paradigm-shifting therapy with impressive responses in B cell malignancies. This review summarizes the current state of the CAR T-cell field, focusing on CD19- and B cell maturation antigen-directed CAR T-cells, the most developed of the CAR T-cell therapies. We discuss the many challenges to CAR-T therapeutic success and innovations in CAR design and T-cell engineering aimed at extending this therapeutic platform beyond hematologic malignancies.

Breaking Boundaries: Immunotherapy for Myeloid Malignancies.

Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment options available to patients. Immunotherapy in myeloid malignancies, however, faces numerous challenges due to the dynamic nature of the disease, immune dysregulation, and the development of immune evasion mechanisms. This review outlines the progress made in the field of im

Ageing, autoimmunity and arthritis: senescence of the B cell compartment - implications for humoral immunity.

Immunosenescence is associated with a decline in both T and B lymphocyte function. Although aged individuals have normal numbers of B cells in the periphery and are capable of mounting robust humoral responses, the antibodies produced are generally of lower affinity and are less protective than those produced by young animals. Here we review multiple studies that address the mechanisms that contribute to this decline. Taken together, these studies suggest that age-associated loss of the ability to generate protective humoral immunity results in part from reduced B lymphopoiesis. As the output

Биологическая роль мономеров традиционной китайской медицины в нейронных расстройствах.

Традиционная китайская медицина (TCM) является биоактивным соединением, извлекаемым из китайских травяных лекарственных препаратов, обладающих определенной биологической активностью и фармакологическими последствиями, и привлекла большое внимание к лечению нейронных заболеваний. Однако применение мономеров ТХМ ограничено их низкой растворимостью и низкой способностью пересекать барьер кровеносного мозга (ББД). Экзосомы представляют собой небольшие внеклеточные везикли (ЭМ) диаметром от 30 до 150 нм и могут использоваться в качестве носителей наркотиков, которые непосредственно предназначены дл

Potential Associations between Vascular Biology and Hodgkin's Lymphoma: An Overview.

Hodgkin's lymphoma (HL) is a lymphatic neoplasm typically found in the cervical lymph nodes. The disease is multifactorial, and in recent years, the relationships between various vascular molecules have been explored in the field of vascular biology. The connection between vascular biology and HL is intricate and the roles of several pathways remain unclear. This review summarizes the cellular and molecular relationships between vascular biology and HL. Proteins associated with various functions in vascular biology, including cytokines (TNF-α, IL-1, IL-13, and IL-21), chemokines (CXCL10, CXCL1

Синергическое регенеративное, иммунодуляционное и антивоспалительное воздействие ваниллина и адипозы производных стволовых клеток в животной модели купризонного склероза.

ЦЕЛИ: Ваниллин как потенциальный терапевтический агент наряду с трансплантацией нейротрофических факторов, отделяющих клетки, считается перспективным средством лечения неврологических расстройств. В этом исследовании последствия ваниллина в сочетании с трансплантацией стволовых клеток, полученных человеком, были оценены с точки зрения дифференциации олигодендроцитов, повторного сглаживания и улучшения моторных функций. МАТЕРИАЛЫ И МЕТОДЫ: Женский C57BL/6 Мышей кормили кухонной зоной.400 мг/кг/сут.) 5 неделями, чтобы вызвать MS. Демилинированные мыши были разделены на группы MS, MS/vanillin, MS

Circulating biosignatures in multiple myeloma and their role in multidrug resistance.

A major obstacle to chemotherapeutic success in cancer treatment is the development of drug resistance. This occurs when a tumour fails to reduce in size after treatment or when there is clinical relapse after an initial positive response to treatment. A unique and serious type of resistance is multidrug resistance (MDR). MDR causes the simultaneous cross resistance to unrelated drugs used in chemotherapy. MDR can be acquired through genetic alterations following drug exposure, or as discovered by us, through alternative pathways mediated by the transfer of functional MDR proteins and nucleic

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial.

(1) Background: Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a dose reduction and/or the interruption of chemotherapy treatment, limiting its effectiveness. Potential pathophysiological mechanisms involved in the pathogenesis of CIPN include chronic oxidative stress and subsequent increase in free radicals and proinflammatory cytokines. Approaches for the treatment of CIPN are highly limited in their number and efficacy, although several antioxidant-based therapies have been tried. On the other hand, ozone therapy can induce an ada

Update on preclinical models of cancer therapy-related cardiac dysfunction: Challenges and perspectives. A scientific statement of the Heart Failure Association (HFA) of the ESC, the ESC Council of Cardio-Oncology, and the ESC Working Group on Cellular Biology of the Heart.

New anticancer therapies with potential cardiovascular side effects are continuously being introduced into clinical practice, with new and often unexpected toxicities becoming apparent only after clinical introduction. These unknown toxicities should be identified and understood beforehand to better prepare patients and physicians, enabling the implementation of effective treatments. Therefore, there is a crucial need for appropriate preclinical models to understand the biological basis of their cardiotoxicity. This scientific statement summarizes the preclinical models hitherto used, from in

Utility of blood procalcitonin concentration in the management of cancer patients with infections.

Diagnosis of infections in cancer patients is usually problematic since differentiating between infection and fever of unknown origin is often a considerable clinical challenge. In general, increase concentration of blood procalcitonin (PCT) is associated with severe bacterial infection. PCT with an optimal cutoff level of 0.5 ng/mL seems to be the most helpful biochemical parameter in detecting severe infections, mainly bloodstream infection, in patients with hematological cancers. In all clinical situations, the elevated level of PCT should be carefully analyzed, always with a thorough physi

The pathogenesis, diagnosis, prevention, and treatment of CAR-T cell therapy-related adverse reactions.

Chimeric antigen receptor (CAR)-T cell therapy is effective in the treatment of refractory/relapsed (r/r) hematological malignancies (r/r B-cell lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma). In addition, it is being explored as a treatment option for solid tumors. As of 31 March 2022, seven CAR-T therapies for hematological malignancies have been approved worldwide. Although CAR-T therapy is an effective treatment for many malignancies, it also causes adverse effects. The incidence of cytokine release syndrome (CRS), the most common adverse reaction after infusion of CAR-T ce