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The Potential and Prospects of Marine Drugs in Intervening Nerve-Tumor Crosstalk.

The bidirectional crosstalk between the nervous system and tumors has emerged as a transformative new frontier in both precision oncotherapy and mechanism-driven cancer pain management. Marine natural products with inherent neuroactive properties exhibit unparalleled intervention advantages for targeting this complex pathophysiological axis. Herein, we systematically and prospectively dissect the multi-layered bidirectional communication between the nervous system and malignancies, comprehensively summarize the pivotal contributions of marine-derived bioactive molecules to advances in neurosci

CAR T-клеточная терапия для неврологических расстройств: научное обоснование и механистические исследования.

Разработка и успешное клиническое применение инженерных Т-клеток, содержащих синтетические химериковые антигенные рецепторы (CARs), является важной вехой в лечении рака. Этот подход оптимизирует физиологическую активацию в виво Т-клеток в отношении конкретных целевых антигенов, выраженных на определенных поднаборах клеток, с целью их глубокого и устойчивого истощения. Значительный прогресс был достигнут в реорганизации зданий ЦАР-Т-клеток в целях повышения безопасности, терапевтической эффективности и доступности. Усилия также были сосредоточены на рационализации обрабатывающей промышленности

Abstracts of the Cell Therapy Transplant Canada 2024 Annual Conference.

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2024 Annual Conference. The conference was held on 1-3 May 2024 in beautiful Victoria, British Columbia, at the Victoria Conference Centre, and attracted 293 in-person delegates and five virtual attendees. Several plenary sessions were held on topics such as gene therapy for hemoglobin disorders, optimizing donor selection, graft-versus-host disease (GvHD) strategies, collaborative care, survivorship, graft failure, and CAR-T therapy. Poster authors presented their work during a lively and e

RESEARCH COMMUNICATIONS OF THE 34th ECVIM-CA CONGRESS.

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Ускоренная клеточная сенсация в прогрессивном многоразовом склерозе: гистопатологическое исследование.

ЦЕЛЬ: Неверодегенеративные процессы, приводящие к росту инвалидности при прогрессивном множественном склерозе (P-MS), не были в полной мере разъяснены. Последние данные увязывают клеточную сенсацию (CS) с нейродегенерацией. Мы расследовали доказательства CS в P-MS и пытались определить их структуру. Мы использовали 53BP1, p16 и липофускин в качестве маркеров CS при повреждениях белого материала (WML), обычном виде белого вещества (NAWM), обычном виде кортикального серого вещества (NAGM), контроле белого вещества (CWM) и контроле серого вещества (CGM) при вскрытии материала пациента с P-MS и зд

Infectious outcomes of a standardized subcutaneous immunoglobulin dose reduction strategy in primary immune deficiencies amid global shortage.

INTRODUCTION: Immunoglobulin replacement therapy (IgRT), either intravenous (IVIg) or subcutaneous (SCIg), is crucial for managing primary immune deficiencies (PIDs) with hypogammaglobulinemia by reducing infection rates and mortality. During the COVID-19 pandemic, a global shortage of SCIg prompted our unit to reduce SCIg doses or maintain the same dose intravenously. This study evaluates the impact of a standardized SCIg dose reduction on infection rates and clinical outcomes in patients with humoral PID and with a low burden of infections. METHODS: Adult PID patients on SCIg for at least 6

Combining Ixazomib With Subcutaneous Rituximab and Dexamethasone in Relapsed or Refractory Waldenström's Macroglobulinemia: Final Analysis of the Phase I/II HOVON124/ECWM-R2 Study.

PurposeProteasome inhibitors are effective in Waldenström's macroglobulinemia (WM) but require parenteral administration and are associated with polyneuropathy. We investigated efficacy and toxicity of the less neurotoxic oral proteasome inhibitor ixazomib combined with rituximab, in patients with relapsed WM.MethodsWe conducted a multicenter phase I/II trial with ixazomib, rituximab, and dexamethasone (IRD). Induction consisted of eight cycles IRD wherein rituximab was started in cycle 3, followed by rituximab maintenance. Phase I showed feasibility of 4 mg ixazomib. Primary end point for pha

Isotype-specific inhibition of the phosphatidylinositol-3-kinase pathway in hematologic malignancies.

In the last decade, the advent of biological targeted therapies has revolutionized the management of several types of cancer, especially in the realm of hematologic malignancies. One of these pathways, and the center of this review, is the phosphatidylinositol-3-kinase (PI3K) pathway. The PI3K pathway seems to play an important role in the pathogenesis and survival advantage in hematologic malignancies, such as leukemia, lymphoma, and myeloma. The objectives of the present review, hence, are to describe the current knowledge on the PI3K pathway and its isoforms, and to summarize preclinical an

Advances of DNA Damage Repair-Related Drugs and Combination With Immunotherapy in Tumor Treatment.

Cancer therapy has been an important and popular area in cancer research. With medical technology developing, the appearance of various targeted drugs and immunotherapy offer more choices to cancer treatment. With the increase in drug use, people have found more and more cases in which tumors are resistant to DNA damage repair (DDR)-based drugs. Recently, the concept of combination therapy has been brought up in cancer research. It takes advantages of combining two or more therapies with different mechanisms, aiming to benefit from the synergistic effects and finally rescue patients irresponsi

Advancing CAR T-Cell Therapy in Solid Tumors: Current Landscape and Future Directions.

BackgroundChimeric Antigen Receptor (CAR) T-cell therapy has transformed the treatment of hematological malignancies, yet its application in solid tumors remains constrained by unique biological and logistical barriers.ObjectiveThis review critically examines the evolving landscape of CAR T-cell therapy in solid malignancies, with a focus on antigen heterogeneity, the immunosuppressive tumor microenvironment, and risks of on-target, off-tumor toxicity.MethodsWe outline recent advances in CAR engineering, including co-stimulatory optimization, dual- and multi-antigen targeting, armored CARs, an

Совпадение в полном тексте источника
… Signaling Component | Native T-Cell Function | CAR T-Cell Equivalent | Purpose Signal 1 (Recognition) | TCR + CD3 complex sees peptide/MHC | scFv domain binds surface antigen | Target recognition and initial activation trigger Signal 2 (Costimulation) | CD28 binds B7 on an APC | Costimulatory Domain …

Immunosuppressants/Immunomodulators and Malignancy.

Individuals with immunosuppressive conditions are at a higher risk of developing malignancies than those in the general population. Immunosuppression weakens tumor immunity, hinders the detection of pro-oncogenic cells, and activates oncogenic viruses. Malignancies arising in immunosuppressed patients tend to be aggressive, have a high incidence of virus-associated cancers, and are reversible in some cases. Notably, immunosuppressive agents influence the frequency and type of malignancies, as well as their clinicopathological features. Organ transplant recipients receive long-term immunosuppre

RXR Agonists Enhance Lenalidomide Anti-Myeloma Activity and T Cell Functions while Retaining Glucose-Lowering Effect.

Retinoid X receptor (RXR) heterodimerizes with the PPAR nuclear hormone receptor and regulates its downstream events. We investigated the effects of RXR agonists (LG100754, bexarotene, AGN194204, and LG101506) on lenalidomide's anti-myeloma activity, T cell functions, and the level of glucose and lipids in vivo. Genetic overexpression and CRISPR/Cas9 knockout experiments were conducted in multiple myeloma (MM) cell lines and Jurkat T cell lines to determine the roles of CRBN in RXR-agonist mediated effects. A xenograft mouse model of MM was established to determine the combination effect of LG

Indication Expansion Dynamics and Trial Characteristics of Novel Multi-Indication Anti-Cancer Drugs in China (2000-2024): A Cross-Sectional Study.

PurposeTo perform a cross-sectional analysis of the indication expansion trends and pivotal trial features of novel multi-indication anti-cancer drugs approved in China from 2000 to 2024.MethodsWe conducted a cross‑sectional review of 74 novel multi-indication anti-cancer drugs approved by the National Medical Products Administration (NMPA) in China from 2000 to 2024, encompassing 265 total indications. Data were collected from multiple sources, including the NMPA, the Center for Drug Evaluation (CDE) of the NMPA, the National Healthcare Security Administration (NHSA), ClinicalTrials.gov, and

High-Dose Vitamin C for Cancer Therapy.

In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C could be effectively utilized in the management of various tumor types. Studies have shown that the pharmacological action of Vit-C can attack various processes that cancerous cells use for their growth and development. Here, we discuss the anti-cancer functions of Vit-C, but also the potenti

The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy.

The ubiquitin-proteasome system (UPS) plays a crucial role in modulating the proliferation, activation, and normal functioning of immune cells through the regulation of protein degradation and function. By influencing the expression of immune checkpoint-associated proteins, the UPS modulates T cell-mediated anti-tumor immune responses and can potentially facilitate the immune escape of tumor cells. Additionally, the UPS contributes to the remodeling of the tumor immunosuppressive microenvironment (TIME) by regulating B cells, dendritic cells (DCs), macrophages, and Treg cells. Targeting the UP

Совпадение в полном тексте источника
… GRAIL also regulates Treg function by degrading the TCR-CD3 complex, thereby reinforcing tumor immune escape. VHL: VHL, another E3 ubiquitin ligase, regulates thymus size and cell number by targeting HIF-1α for ubiquitination and proteasome-dependent degradation ( 63 ). …

Lipid metabolism in multiple myeloma: pathogenesis, therapeutic opportunities, and future directions.

BackgroundMultiple myeloma (MM) is a complex hematological malignancy characterized by the clonal expansion of plasma cells in the bone marrow. Emerging studies have emphasized the importance of lipid metabolism, which is closely associated with the survival, proliferation, and drug resistance of tumor cells. The hypoxic environment in the bone marrow (BM) contributes to metabolic reprogramming in MM cells, including alterations in metabolite levels, changes in metabolic enzyme activity, and metabolic shifts. Cancer cells possess the ability to adapt their metabolism in order to fulfill their

Immunosuppression in Glomerular Diseases: Implications for SARS-CoV-2 Vaccines and COVID-19.

BackgroundGlomerular diseases (GD) are chronic conditions that often involve immune dysfunction and require immunosuppressive therapy (IST) to control underlying pathogenesis. Unfortunately, such diseases appear to heighten risks of severe outcomes in COVID-19 and predispose to other infections that may be life-threatening. Thus, averting preventable infections is imperative in GD patients.SummaryThe advent of vaccines demonstrated to be safe and efficacious against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has favorably impacted the COVID-19 pandemic epidemiology. However,

Unveiling causal immune cell-gene associations in multiple myeloma: insights from systematic reviews and Mendelian randomization analyses.

BackgroundThe efficacy of novel chimeric antigen receptor T-cell (CAR-T) therapy is inconsistent, likely due to an incomplete understanding of the tumor microenvironment (TME). This study utilized meta-analysis to evaluate CAR-T-cell therapy efficacy and safety and employed two-sample Mendelian randomization (MR) analysis to investigate the causal links between immune cells and Multiple Myeloma (MM).MethodOur literature review, conducted from January 1, 2019, to August 30, 2024, across Medline/PubMed, Scopus, and Web of Science, identified 2,709 articles, 34 of which met our inclusion criteria

Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects.

The prognosis of patients with systemic lupus erythematosus has greatly improved since treatment regimens combining corticosteroids and immunosuppressive medications have been widely adopted in therapeutic strategies given to these patients. Immune suppression is evidently efficient but also leads to higher susceptibility to infectious and malignant diseases. Toxic effects and sometimes unexpectedly dramatic complications of current therapies have been progressively reported. Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. The aim of this rev

Cancer stem cells: advances in knowledge and implications for cancer therapy.

Cancer stem cells (CSCs), a small subset of cells in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, and maintain tumor heterogeneity. Cancer continues to be a significant global disease burden. In the past, surgery, radiotherapy, and chemotherapy were the main cancer treatments. The technology of cancer treatments continues to develop and advance, and the emergence of targeted therapy, and immunotherapy provides more options for patients to a certain extent. However, the limitations of efficacy and treatment resistance are still i