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New targets for the treatment of follicular lymphoma.

The last two decades have witnessed striking advances in our understanding of the biological factors underlying the development of Follicular lymphoma (FL). Development of newer treatment approaches have improved the outlook for many individuals with these disorders; however, with these advances come new questions. Given the long-term survival of patients with FL, drugs with favourable side-effect profile and minimal long-term risks are desired. FL is incurable with current treatment modalities. It often runs an indolent course with multiple relapses and progressively shorter intervals of remi

Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.

Conventional immunotherapy has emerged as a key option for cancer treatment. However, its efficacy has been limited in urological cancers, especially prostate cancer, because of the immunosuppressive tumor microenvironment (TME), difficulty in drug delivery, aberrant immune response, and damage to normal cells. Bispecific antibodies (BsAbs) are engineered proteins with two different antigen-binding domains, designed using different technologies and in various formats. BsAb-based tumor immunotherapy has yielded optimistic results in preclinical and clinical investigations of many tumor types, i

Septic Hyperinflammation-Is There a Role for Extracorporeal Blood Purification Techniques?

This manuscript investigates the role of extracorporeal blood purification techniques in managing septic hyperinflammation, a critical aspect of sepsis characterized by an uncontrolled immune response leading to multiorgan dysfunction. We provide an overview of sepsis, focusing on the dynamics of immune response, the involvement of neutrophils, and the role of the endothelium in the disease's progression. It evaluates the effectiveness of various blood purification methods, including high-cut-off membranes, high-volume hemofiltration, adsorption techniques, and albumin dialysis, in removing cy

Collateral Victim or Rescue Worker?-The Role of Histone Methyltransferases in DNA Damage Repair and Their Targeting for Therapeutic Opportunities in Cancer.

Disrupted DNA damage signaling greatly threatens cell integrity and plays significant roles in cancer. With recent advances in understanding the human genome and gene regulation in the context of DNA damage, chromatin biology, specifically biology of histone post-translational modifications (PTMs), has emerged as a popular field of study with great promise for cancer therapeutics. Here, we discuss how key histone methylation pathways contribute to DNA damage repair and impact tumorigenesis within this context, as well as the potential for their targeting as part of therapeutic strategies in ca

Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice.

Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main extra virgin olive oil secoiridoids, when used to supplement the diet of a murine pristane-induced SLE model. In the study, 12-week-old female BALB/c mice were injected with pristane and fed with an OLA-enriched diet (0.01 % (w/w)) for 24 weeks. The presence of immune complexes was evaluated by i

The Role of Platelet Dysfunctions in the Pathogenesis of the Hemostatic-Coagulant System Imbalances.

Platelet dysfunction plays a critical role in the pathogenesis of various disorders affecting the hemostatic-coagulant system. This review aims to explore the mechanisms by which platelet dysfunctions contribute to the disruption of hemostasis, leading to an increased risk of both thrombosis and bleeding. Platelets, traditionally known for their role in clot formation, can exhibit altered functionality under pathological conditions such as cardiovascular diseases, metabolic disorders, and autoimmune diseases, impacting their interaction with coagulation factors and vascular endothelium. The re

Recent advances in use of fresh frozen plasma, cryoprecipitate, immunoglobulins, and clotting factors for transfusion support in patients with hematologic disease.

Hematologic diseases include a broad range of acquired and congenital disorders, many of which affect plasma proteins that control hemostasis and immune responses. Therapeutic interventions for these disorders include transfusion of plasma, cryoprecipitate, immunoglobulins, or convalescent plasma-containing therapeutic antibodies from patients recovering from infectious diseases, as well as concentrated pro- or anticoagulant factors. This review will focus on recent advances in the uses of plasma and its derivatives for patients with acquired and congenital hematologic disorders.

Nonsteroidal Anti-Inflammatory Drugs as Modulators of Cation Channels: Fenamates Repurposing in Channelopathies.

Cationic ion channels are transmembrane proteins that regulate the flux of cations (potassium, sodium, and calcium) across cell membrane, playing a pivotal role in many cellular functions. Disruptions of their activity can lead to the so-called genetic or acquired channelopathies, a heterogeneous group of diseases that affect multiple human systems. Fenamates, a class of nonsteroidal anti-inflammatory drugs, has recently emerged as modulators of cationic ion channels highlighting the possibility of their repurposing for the treatment ion channel-related disorders, such as channelopathies, chro

Dynamic roles of inflammasomes in inflammatory tumor microenvironment.

The inflammatory tumor microenvironment has been known to be closely connected to all stages of cancer development, including initiation, promotion, and progression. Systemic inflammation in the tumor microenvironment is increasingly being recognized as an important prognostic marker in cancer patients. Inflammasomes are master regulators in the first line of host defense for the initiation of innate immune responses. Inflammasomes sense pathogen-associated molecular patterns and damage-associated molecular patterns, following recruitment of immune cells into infection sites. Therefore, dysreg

Cancer and Obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

BackgroundThis Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) provides an overview of cancer and increased body fat.MethodsThe scientific information for this CPS is based upon published scientific citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership.ResultsTopics include the increased risk of cancers among patients with obesity, cancer risk factor population-attributable fractions, genetic and epigenetic links between obesity and cancer, adiposopathic and mechanistic processes accounting for increased cancer risk

Immunotherapeutic approaches in EBV-associated nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) was the first tumor virus in humans. Nasopharyngeal carcinoma (NPC) accounts for approximately 60% of the 200,000 new tumor cases caused by EBV infection worldwide each year. NPC has an insidious onset and is highly malignant, with more than 70% of patients having intermediate to advanced disease at the time of initial diagnosis, and is strongly implicated in epithelial cancers as well as malignant lymphoid and natural killer/T cell lymphomas. Over 90% of patients with confirmed undifferentiated NPC are infected with EBV. In recent decades, much progress has been made

Совпадение в полном тексте источника
… These data showed that the application of the tetrameric gp350 1–470 and EBV protein multimerization, in general, may facilitate the development of a potent prophylactic EBV vaccine ( 76 ). …

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

The Ups and Downs of STAT Inhibition in Acute Myeloid Leukemia.

Aberrant Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is implicated in the pathogenesis of acute myeloid leukemia (AML), a highly heterogeneous hematopoietic malignancy. The management of AML is complex and despite impressive efforts into better understanding its underlying molecular mechanisms, survival rates in the elderly have not shown a substantial improvement over the past decades. This is particularly due to the heterogeneity of AML and the need for personalized approaches. Due to the crucial role of the deregulated JAK-STAT signaling in AML, select

Heyde Syndrome Unveiled: A Case Report with Current Literature Review and Molecular Insights.

Heyde syndrome, marked by aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome, is often underreported. Shear stress from a narrowed aortic valve degrades von Willebrand factor multimers, leading to angiodysplasia formation and von Willebrand factor deficiency. This case report aims to raise clinician awareness of Heyde syndrome, its complexity, and the need for a multidisciplinary approach. We present a 75-year-old man with aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome type 2A. The patient w

Modern radiopharmaceuticals for lung cancer imaging with positron emission tomography/computed tomography scan: A systematic review.

IntroductionIn this study, we evaluated the use and the contribution of radiopharmaceuticals to the field of lung neoplasms imaging using positron emission tomography/computed tomography.MethodsWe conducted review of the current literature at PubMed/MEDLINE until February 2020. The search language was English.ResultsThe most widely used radiopharmaceuticals are the following:Experimental/pre-clinical approaches: (18)F-Misonidazole (18F-MISO) under clinical development, D(18)F-Fluoro-Methyl-Tyrosine (18F-FMT), 18F-FAMT (L-[3-18F] (18)F-Fluorothymidine (18F-FLT)), (18)F-Fluoro-Azomycin-Arabinosi

Evaluation of Proteasome Inhibitors in the Treatment of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, and it has a worse prognosis than non-small cell lung cancer. The pathomechanism of IPF is not fully understood, but it has been suggested that repeated microinjuries of epithelial cells induce a wound healing response, during which fibroblasts differentiate into myofibroblasts. These activated myofibroblasts express α smooth muscle actin and release extracellular matrix to promote matrix deposition and tissue remodeling. Under physiological conditions, the remodeling process stops once wound heal

Endothelial dysfunction and hemostatic imbalance in CAR T-cell-associated toxicities: pathophysiological insights and the role of circulating biomarkers.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed or refractory hematologic malignancies. While its clinical efficacy is well established, CAR T-cell therapy is frequently associated with severe immune-mediated toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), coagulopathy, and hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Increasing evidence suggests that endothelial dysfunction, hemostatic imbalance, and complement activation are key contributors to the pathogenesis of

Экстренные ситуации в гематологии: Почему, когда и как я лечусь?

Гематологические чрезвычайные ситуации являются критическими медицинскими условиями, требующими неотложного внимания в силу их быстрого развития и опасного для жизни характера. В качестве примера можно привести гиперкальцемию, которая часто ассоциируется с раком, таким как множественная миелома, что может привести к серьезной неврологической и сердечной дисфункции. Гиперлейкоцитоз, распространенный в острой миэлоидной лейкемии, повышает риск лейкостаза и многоорганического отказа. Кислородный кризис, обычное осложнение серповидноклеточной болезни, является результатом вазооккуляции, приводящей

Ligand-based CAR-T cell: Different strategies to drive T cells in future new treatments.

Chimeric antigen receptor (CAR)-based therapies are presented as innovative treatments for multiple malignancies. Despite their clinical success, there is scientific evidence of the limitations of these therapies mainly due to immunogenicity issues, toxicities associated with the infusion of the product, and relapses of the tumor. As a result, novel approaches are appearing aiming to solve and/or mitigate the harmful effects of CAR-T therapies. These include strategies based on the use of ligands as binding moieties or ligand-based CAR-T cells. Several proposals are currently under development

Spliced or Unspliced, That Is the Question: The Biological Roles of XBP1 Isoforms in Pathophysiology.

X-box binding protein 1 (XBP1) is a member of the CREB/ATF basic region leucine zipper family transcribed as the unspliced isoform (XBP1-u), which, upon exposure to endoplasmic reticulum stress, is spliced into its spliced isoform (XBP1-s). XBP1-s interacts with the cAMP response element of major histocompatibility complex class II gene and plays critical role in unfolded protein response (UPR) by regulating the transcriptional activity of genes involved in UPR. XBP1-s is also involved in other physiological pathways, including lipid metabolism, insulin metabolism, and differentiation of immun