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Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in genome-editing technologies and promising clinical trial data, significant challenges remain, including graft-

A recommended practical approach to the management of target therapy and angiogenesis inhibitors cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity and cardioprotection, Italian Society of Cardiology.

The US National Cancer Institute estimates that cardiotoxicity (CTX) from target therapy refers mostly to four groups of drugs: epidermal growth factor receptor 2 inhibitors, angiogenic inhibitors, directed Abelson murine leukemia viral oncogene homolog inhibitors, and proteasome inhibitors. The main cardiotoxic side-effects related to antiepidermal growth factor receptor 2 therapy are left ventricular systolic dysfunction and heart failure. Angiogenesis inhibitors are associated with hypertension, left ventricular dysfunction/heart failure, myocardial ischemia, QT prolongation, and thrombosis

От диагностики к лечению: изучение механизмов, лежащих в основе оптического неврата в множестве склерозов.

Множественный склероз (MS) — хроническое аутоиммунное заболевание, воздействующее на центральную нервную систему, которое, как правило, вызывает сенсорные расстройства, моторную слабость, слабую походку, несогласованность и оптический неуриит (ON). Согласно статистическим данным, до 50% пациентов, страдающих синдромом MS, испытывают проблемы со зрением в период болезни, страдающие от нечеткого зрения, боли, недостатка зрения и даже слепоты. Лечение перешло от кортикостероидов к лечению, ориентированному на клетки В/Т. В рамках этого обзора проводится всеобъемлющая и систематическая оценка диаг

Mechanisms of Resistance to Chemotherapy in Breast Cancer and Possible Targets in Drug Delivery Systems.

Breast cancer (BC) is one of the most important cancers worldwide, and usually, chemotherapy can be used in an integrative approach. Usually, chemotherapy treatment is performed in association with surgery, radiation or hormone therapy, providing an increased outcome to patients. However, tumors can develop resistance to different drugs, progressing for a more aggressive phenotype. In this scenario, the use of nanocarriers could help to defeat tumor cell resistance, providing a new therapeutic perspective for patients. Thus, this systematic review aims to bring the molecular mechanisms involve

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies.

In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new know

CXCL12 in astrocytes contributes to bone cancer pain through CXCR4-mediated neuronal sensitization and glial activation in rat spinal cord.

BackgroundPrevious studies have demonstrated that chemokine CXCL12 and its receptor CXCR4 are critical for pain sensitization, but the mechanisms involved are not clear. In this study, we investigated the specific cellular mechanisms of CXCL12/CXCR4 chemokine signaling in the development and maintenance of bone cancer pain after tumor cell implantation (TCI).MethodsTCI in the tibial cavity of rats was used to establish a bone cancer pain model. Mechanical allodynia and thermal hyperalgesia were determined by measuring the paw withdrawal threshold and latency, respectively. The protein expressi

Global first-in-class drugs approved in 2023-2024: Breakthroughs and insights.

First-in-class (FIC) drugs are considered the main drivers of new drug discovery and have novel targets and mechanisms. The proportion of FIC drugs among new drugs provides fundamental guidance for both academic and pharmaceutical research. From a global perspective, 81 FIC drugs were approved in 2023 and 2024. Among them, small-molecule drugs account for a greater percentage (51.9%), illustrating the discovery of new chemical entities. Macromolecule drugs (48.1%), which mainly consist of antibody analogs, represent a growing trend as new biotechnology techniques have emerged. In terms of FIC

Interventional Cardio-Oncology: Adding a New Dimension to the Cardio-Oncology Field.

The management of cardiovascular disease in patients with active cancer presents a unique challenge in interventional cardiology. Cancer patients often suffer from significant comorbidities such as thrombocytopenia and coagulopathic and/or hypercoagulable states, which complicates invasive evaluation and can specifically be associated with an increased risk for vascular access complications. Furthermore, anticancer therapies cause injury to the vascular endothelium as well as the myocardium. Meanwhile, improvements in diagnosis and treatment of various cancers have contributed to an increase i

Precision immunotherapy with CAR-T cells in pediatric B-cell acute lymphoblastic leukemia: advances and unanswered challenges.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a groundbreaking treatment for pediatric B-cell acute lymphoblastic leukemia (B-ALL), especially for patients with relapsed or refractory disease. CD19-targeted CAR T cells, such as tisagenlecleucel, have demonstrated high rates of complete remission and long-lasting responses in clinical trials. However, challenges such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), antigen escape, and T-cell exhaustion hinder its broader clinical application. Recent advances aim to overcome thes

Waldenström macroglobulinemia: clinical and immunological aspects, natural history, cell of origin, and emerging mouse models.

Waldenström macroglobulinemia (WM) is a rare and currently incurable neoplasm of IgM-expressing B-lymphocytes that is characterized by the occurrence of a monoclonal IgM (mIgM) paraprotein in blood serum and the infiltration of the hematopoietic bone marrow with malignant lymphoplasmacytic cells. The symptoms of patients with WM can be attributed to the extent and tissue sites of tumor cell infiltration and the magnitude and immunological specificity of the paraprotein. WM presents fascinating clues on neoplastic B-cell development, including the recent discovery of a specific gain-of-function

Совпадение в полном тексте источника
… Additional characteristics include the presentation, on the cell surface, of the memory marker, CD27, and costimulatory and activation markers, including CD80 and CD86 (tandem ligands for CD28 and CD152 on T cells, resp.), as well as CD95 (FAS receptor). …

Allogeneic and other innovative chimeric antigen receptor platforms.

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Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer.

Bone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rat

Advances and Prospects of Prolamine Corn Protein Zein as Promising Multifunctional Drug Delivery System for Cancer Treatment.

Zein is a type of prolamine protein that is derived from corn, and it has been recognized by the US FDA as one of the safest biological materials available. Zein possesses valuable characteristics that have made it a popular choice for the preparation of drug carriers, which can be administered through various routes to improve the therapeutic effect of antitumor drugs. Additionally, zein contains free hydroxyl and amino groups that offer numerous modification sites, enabling it to be hybridized with other materials to create functionalized drug delivery systems. However, despite its potential

Семья гистона деацетилазы в здравии и болезни.

Классические деацетилазы, включая классы I, II и IV, в зависимости от цинка, повсеместно присутствуют у млекопитающих и играют жизненно важную роль в многочисленных биологических процессах. На сегодняшний день eleven Были выявлены члены < < хисттон деацетилаза > > , а именно < < хиттон деацетилаза > > . 1 через гистонную деацетилазу 11. Растущий объем данных подчеркивает важнейшую роль этих гистоновых деацетилазов как в физиологических, так и патологических условиях. В частности, эти гистонные деацетилазы участвуют в различных клеточных процессах, включая воспаление, ме

Indocyanine Green (ICG) and Colorectal Surgery: A Literature Review on Qualitative and Quantitative Methods of Usage.

Background: Due to its many benefits, indocyanine green (ICG) has gained progressive popularity in operating rooms (ORs) globally. This literature review examines its qualitative and quantitative usage in surgical treatment. Method: Relevant terms were searched in five international databases (1. Pubmed, 2. Sciencedirect, 3. Scopus, 4. Oxfordjournals, 5. Reaxys) for a comprehensive literature review. The main benefits of using ICG in colorectal surgery are: intraoperative fluorescence angiography; fluorescence-guided lymph node involvement detection and the sentinel technique; the fluorescent

Disease-Modifying Therapies for Multiple System Atrophy: Where Are We in 2022?

Multiple system atrophy is a rapidly progressive and fatal neurodegenerative disorder. While numerous preclinical studies suggested efficacy of potentially disease modifying agents, none of those were proven to be effective in large-scale clinical trials. Three major strategies are currently pursued in preclinical and clinical studies attempting to slow down disease progression. These target α-synuclein, neuroinflammation, and restoration of neurotrophic support. This review provides a comprehensive overview on ongoing preclinical and clinical developments of disease modifying therapies. Furth

Zoledronic acid enhances lipopolysaccharide-stimulated proinflammatory reactions through controlled expression of SOCS1 in macrophages.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of nitrogen-containing bisphosphonate (NBP) use. Many studies have shown that BRONJ is limited to the jawbone and does not occur in the other bones. We hypothesized that BRONJ is related to local bacterial iections and involves the innate immune system. To examine the relationship between BRONJ and innate immunity, we examined the effects of NBPs on macrophages, one of the important cell types in innate immunity. The expression of toll-like receptor-4 (TLR4) in cells after pretreatment with zoledronic acid (ZOL) d

Epoetin-beta treatment in patients with cancer chemotherapy-induced anaemia: the impact of initial haemoglobin and target haemoglobin levels on survival, tumour progression and thromboembolic events.

BackgroundEpoetin-beta is used to treat patients with cancer undergoing chemotherapy to alleviate the symptoms of anaemia, reduce the risk of blood transfusions and improve quality of life (QoL).MethodsThis meta-analysis of all 12 randomised, controlled studies of epoetin-beta evaluated the impact of therapy at different Hb-initiation levels and to different target Hb levels on overall survival, tumour progression and thromboembolic events (TEE). An analysis of risk factors pre-disposing patients to TEEs under epoetin-beta therapy was also performed. A total of 2297 patients are included in th

Esid 2014 oral presentations.

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IgG replacement in multiple myeloma.

T cell engagers (TCE) such as chimeric antigen receptor (CAR) T cell therapy and bispecific antibodies (BiAbs) for the treatment of multiple myeloma (MM) have significantly improved clinical outcomes, but have also raised awareness for ensuing post-treatment secondary immunodeficiency and hypogammaglobulinemia (HG). As patients with MM live longer, recurrent infections become a significant component of therapy-associated morbidity and mortality. Treatment of HG with immunoglobulin G replacement therapy (IgG-RT) has been a mainstay of the primary immunodeficiency (PI) world, and extrapolation t