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Immunotherapy for prostate cancer: lessons from responses to tumor-associated antigens.

Prostate cancer (PCa) is the most common cancer in men and the second most common cause of cancer-related death in men. In recent years, novel therapeutic options for PCa have been developed and studied extensively in clinical trials. Sipuleucel-T is the first cell-based immunotherapeutic vaccine for treatment of cancer. This vaccine consists of autologous mononuclear cells stimulated and loaded with an immunostimulatory fusion protein containing the prostate tumor antigen prostate acid posphatase. The choice of antigen might be key for the efficiency of cell-based immunotherapy. Depending on

Nonlinear Association Between Calculated Globulin Levels and 28-Day Mortality in Patients with Sepsis: A Retrospective Cohort Study.

BackgroundSepsis remains a significant global health challenge, causing approximately 11 million deaths annually. The calculated globulin (CG) level, which is derived from total protein and albumin levels, plays crucial roles in the immune response and inflammation. However, the relationship between the CG level and sepsis mortality remains unexplored.MethodsThis retrospective cohort study analyzed sepsis patients from the eICU Collaborative Research Database. The primary outcome was 28-day ICU mortality. The relationship between the CG level and mortality was examined via generalized additive

Anti-BCMA/CD19 CAR T cell therapy in patients with refractory generalized myasthenia gravis: a single-arm, phase 1 trial.

BACKGROUND: Treating refractory generalized myasthenia gravis is still a big challenge, so new treatments are needed. Several studies have shown the potential of chimeric antigen receptor (CAR) T cell therapy in the treatment of autoimmune diseases. However, no clinical trial of bispecific CAR T cells targeting refractory myasthenia gravis has been done. We developed autologous anti-B-cell maturation antigen (BCMA) and CD19 bispecific CAR T cells to evaluate the safety and efficacy in refractory myasthenia gravis. METHODS: This single-arm, phase 1 trial (ChiCTR2200061267) was conducted at the

Advances in cancer immunotherapy: Strategies and innovations strategies for adoptive immunotherapy of cancer.

Cancer immunotherapy has emerged as a transformative approach in oncology, offering alternatives beyond traditional treatments. This narrative review focuses on major innovations, including adoptive cell therapy (ACT), chimeric antigen receptor T-cells (CAR-T), T-cell receptor (TCR) engineering, monoclonal antibodies (mAbs), bispecific antibodies (BsAbs), and immune checkpoint inhibitors (ICIs). The central aim of this article is to analyze how these technologies improve antitumor responses and help overcome resistance in hematologic and solid tumors. This narrative review combines the latest

Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision.

Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and

From Cellular Stress to Systemic Adaptation: The Circadian Clock and Stress Response at Cellular and Systemic Levels.

The stress response is essential for cellular and organismal survival as it acts as a protective and adaptive mechanism to maintain homeostasis. At the organismal level, physical stressors induce responses in mammals that are mediated primarily by the hypothalamic-pituitary-adrenal (HPA) axis, which regulates glucocorticoid secretion. The HPA axis functions as a circadian-regulated, multi-oscillator system, in which the paraventricular nucleus, the pituitary, and the adrenal gland exhibit intrinsic rhythmicity while remaining coordinated by the output from the suprachiasmatic nucleus. Glucocor

Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter Generations of Chimeric Antigen Receptor T Cells.

T cells equipped with chimeric antigen receptors (CAR T cells) have recently provided promising advances as a novel immunotherapeutic approach for cancer treatment. CAR T cell therapy has shown stunning results especially in B-cell malignancies; however, it has shown less success against solid tumors, which is more supposed to be related to the specific characteristics of the tumor microenvironment. In this review, we discuss the structure of the CAR, current clinical advantages from finished and ongoing trials, adverse effects, challenges and controversies, new engineering methods of CAR, and

Role of Bruton's tyrosine kinase in B cells and malignancies.

Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor a

α2-3-sialylated Гликосфинголипиды при нейроинфламмации, иммунитете и запрограммированной смерти клеток: механистические доказательства и регулирование в зависимости от контекста: всеобъемлющий обзор.

α2-3-sialylated glycosphingolids (α2)3-GSLs) являются основными составляющими нейронных мембран и липидных плотов, где они формируют сепарацию рецепторов, комплекс сигналов и связь с клетками. Однако их биологическое воздействие варьируется в зависимости от молекулярного подтипа, типа клеток, стадии заболевания, концентрации и местной микроокружающей среды. В настоящем обзоре обобщены данные о перепончатых изменениях в α2-3-GSL профили и их связи с нейроинфламмацией, иммунной реакцией, протеостазом и запрограммированной клеточной смертностью через болезнь Паркинсона, болезнь Альцгеймера, болез

Сигналы лимфоцита соответствуют клиническим фенотипам аутоиммунного лимфатического энцефалита.

Аутоиммунный лимфатический энцефалит - это воспалительное состояние, ограниченное лимбической системой мозга, которая считается результатом дисрегулируемой иммунной реакции. Вместе с тем конкретные патофизиологические механизмы по-прежнему остаются труднодостижимыми. Диагноз аутоиммунного лимбового энцефалита в настоящее время основывается на критериях клинического консенсуса. Однако диагностический анализ может быть непростым, что может задержать начало лечения, связанного с плохими клиническими результатами. Мы ретроспективно идентифицировали 640 пациентов (81 аутоиммунный лимфатический энце

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… In this scenario, they exert both inflammatory and anti-inflammatory functions depending on the subset and polarization. 25 A regulated Tc response is crucial to protect the CNS from infections e.g. herpes simplex viruses, varicella zoster virus and JC virus. 26 However, a dysregulated Tc response …

Catchment area and cancer population health research through a novel population-based statewide database: a scoping review.

BackgroundPopulation-based linked datasets are vital to generate catchment area and population health research. The novel Cancer Information and Population Health Resource (CIPHR) links statewide cancer registry data, public and private insurance claims, and provider- and area-level data, representing more than 80% of North Carolina's large, diverse population of individuals diagnosed with cancer. This scoping review of articles that used CIPHR data characterizes the breadth of research generated and identifies further opportunities for population-based health research.MethodsArticles publishe

Interventions to reduce infections in patients with hematological malignancies: a systematic review and meta-analysis.

Acquired hypogammaglobulinemia is common in chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). No previous systematic reviews (SRs) have compared different approaches to infection prevention. We sought to assess the efficacy and safety of prophylactic immunoglobulin, antibiotics, and vaccination in these patients. We performed an SR and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of prophylactic immunoglobulin, antibiotics, and vaccination in adult patients with hematological malignancies commonly associated wi

Canine Cancer: Strategies in Experimental Therapeutics.

Cancer is the most common cause of death in adult dogs. Many features of spontaneously developing tumors in pet dogs contribute to their potential utility as a human disease model. These include similar environmental exposures, similar clonal evolution as it applies to important factors such as immune avoidance, a favorable body size for imaging and serial biopsy, and a relatively contracted time course of disease progression, which makes evaluation of temporal endpoints such as progression free or overall survival feasible in a comparatively short time frame. These criteria have been leverage

miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1.

MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified S

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that govern the expression of genes responsible for energy metabolism, cellular development, and differentiation. Their crucial biological roles dictate the significance of PPAR-targeting synthetic ligands in medical research and drug discovery. Clinical implications of PPAR agonists span across a wide range of health conditions, including metabolic diseases, chronic inflammatory diseases, infections, autoimmune diseases, neurological and psychiatric disorders, and malignancies. In this review we aim to consolidate exist

Serving Vietnam Veterans Hospitalized Outside the VA System: A Scoping Review of Presumptive Service-Related Illnesses and Presentations.

BackgroundRecent legislation, the MISSION Act and the PACT Act, expanded access to and utilization of non-Department of Veterans Affairs (VA) health care; more Veterans now receive care from non-VA healthcare providers. Hospitalists outside the VA may be less familiar with Veterans' service-related exposures and presumptive service-related conditions. We aimed to summarize research findings on service-related exposures and conditions among Vietnam War Veterans.MethodsUsing Arksey and O'Malley's methodological framework for scoping reviews, we searched PubMed, EMBASE, and Web of Science databas

Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.

Pathways that govern cellular bioenergetics are deregulated in tumor cells and represent a hallmark of cancer. Tumor cells have the capacity to reprogram pathways that control nutrient acquisition, anabolism and catabolism to enhance their growth and survival. Tumorigenesis requires the autonomous reprogramming of key metabolic pathways that obtain, generate and produce metabolites from a nutrient-deprived tumor microenvironment to meet the increased bioenergetic demands of cancer cells. Intra- and extracellular factors also have a profound effect on gene expression to drive metabolic pathway

Activated Ras as a Therapeutic Target: Constraints on Directly Targeting Ras Isoforms and Wild-Type versus Mutated Proteins.

The ability to selectively and directly target activated Ras would provide immense utility for treatment of the numerous cancers that are driven by oncogenic Ras mutations. Patients with disorders driven by overactivated wild-type Ras proteins, such as type 1 neurofibromatosis, might also benefit from progress made in that context. Activated Ras is an extremely challenging direct drug target due to the inherent difficulties in disrupting the protein:protein interactions that underlie its activation and function. Major investments have been made to target Ras through indirect routes. Inhibition

Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy.

Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin w

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a