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Acute kidney injury: pathogenesis and therapeutic interventions.

Acute kidney injury (AKI) is a prevalent clinical condition that is associated with unacceptably high morbidity and mortality, as well as the development of chronic kidney disease (CKD). The pathogenesis of AKI is highly complex and heterogeneous, primarily attributed to metabolic disturbances arising from the disease itself and the administration of medications related to treatment. In recent years, AKI in cancer patients is highly concerned. The emergence of AKI caused injuries and dysfunction of remote organs but also enhanced the health-care costs. It's essential for early recognition of A

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… In rhabdomyolysis-induced AKI, necrotic muscle cells release substances that can activate platelets that could raise the production of macrophage extracellular traps (METs) by enhancing histone citrullination and intracellular ROS generation [ 217 ]. …

Освещение нанотерапевтики с точными глазами: от оптического к радионаностантике.

Рак по-прежнему относится к числу самых смертоносных заболеваний во всем мире, унося много жизней из-за высоких показателей смертности. Химиотерапия, являющаяся одной из основных форм лечения рака, приносит значительные выгоды, однако ей мешают недостатки, которые ставят под угрозу качество жизни пациентов. Таким образом, разработка альтернатив минимально инвазивному лечению по-прежнему представляет собой серьезную проблему. Среди них наноматериалы, легкая фототерапия, включая фотодинамическую терапию, фототермальную терапию и радиотерапию, являются перспективными вариантами, обеспечивающими т

Current Knowledge of Immune Checkpoint Inhibitor-Induced Thrombocytopenia: Epidemiology, Mechanisms, and Management.

Immune checkpoint inhibitors (ICIs) have been widely adopted in the treatment of malignant tumors, and their durable antitumor effects have revolutionized cancer therapy. Immune checkpoint inhibitor-induced thrombocytopenia (ICIIT) represents a rare but potentially severe or even fatal hematologic toxicity associated with immunotherapy. Therefore, it is imperative for healthcare professionals to recognize this potential adverse event and to understand its identification and management. However, the pathophysiological mechanisms underlying ICIIT remain incompletely understood, and both its diag

A study on a real-world data-based VTE risk prediction model for lymphoma patients.

BackgroundPatients diagnosed with malignant tumors exhibit a markedly elevated risk of venous thromboembolism (VTE), which has a negative impact on their prognosis. Currently, there is no reliable predictive model specifically for thrombosis risk in lymphoma patients. This study aims to develop and validate a machine learning model leveraging real-world data, offering a dependable risk assessment tool for the early identification of VTE in lymphoma patients.MethodsWe retrospectively analyzed 605 hospitalized patients with lymphoma between January 2019 and June 2024. Candidate predictors includ

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… In parallel, infection triggers innate immune pathways involving neutrophils and the formation of neutrophil extracellular traps (NETs), which help immobilize pathogens within the vasculature but also amplify thrombin generation and thrombosis ( Longstaff et al., 2013 ). …

CAR-T Cell Therapy-An Overview of Targets in Gastric Cancer.

Gastric cancer (GC) is one of the most commonly diagnosed malignancies and, unfortunately, still has a high mortality rate. Recent research points to CAR-T immunotherapy as a promising treatment for this disease. Using genetically engineered T cells designed to target a previously selected antigen, researchers are able to harness the natural anti-tumor activity of T cells. For therapy to be successful, however, it is essential to choose antigens that are present on tumor cells but not on healthy cells. In this review, we present an overview of the most important targets for CAR-T therapy in th

Invited Lectures : Overviews Purinergic signalling: past, present and future.

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Direct Endoplasmic Reticulum Targeting by the Selective Alkylphospholipid Analog and Antitumor Ether Lipid Edelfosine as a Therapeutic Approach in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, shows a dismal and grim overall prognosis and survival rate, which have remained virtually unchanged for over half a century. PDAC is the most lethal of all cancers, with the highest mortality-to-incidence ratio. PDAC responds poorly to current therapies and remains an incurable malignancy. Therefore, novel therapeutic targets and drugs are urgently needed for pancreatic cancer treatment. Selective induction of apoptosis in cancer cells is an appealing approach in cancer therapy. Apoptotic cell death is highly

Recombinant Oncolytic Viruses: Hexagonal Warriors in the Field of Solid Tumor Immunotherapy.

In the past decade, research on recombinant oncolytic viral agents in the treatment of solid tumors has evolved from the initial stage of simple genetic engineering to the current stage of multiple pipelines of parallel clinical application and combination therapy. Compared with T-VEC, the classical therapeutic agent that only expresses GM-CSF, which was approved in 2015, most new oncolytic virus designs include diverse gene constructs to reduce toxic effects, enhance multiple antitumor immunity, avoid immune clearance, or enhance tumor targeting. The single route of administration that activa

Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory.

Therapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. Many advances have been made in the characterization of immunoglobulins as a result of pharmaceutical companies investing in technologies that allow them to better understand MAbs during the development phase. Mass spectrometry is one of the new advancements utilized extensively by pharma to analyze MAbs and is now beginning to be applied in the clinical laboratory setting. The rise

Targeting Selectins and Their Ligands in Cancer.

Aberrant glycosylation is a hallmark of cancer cells with increased evidence pointing to a role in tumor progression. In particular, aberrant sialylation of glycoproteins and glycolipids has been linked to increased immune cell evasion, drug evasion, drug resistance, tumor invasiveness, and vascular dissemination, leading to metastases. Hypersialylation of cancer cells is largely the result of overexpression of sialyltransferases (STs). Differentially, humans express twenty different STs in a tissue-specific manner, each of which catalyzes the attachment of sialic acids via different glycosidi

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are unique hematopoietic stem cell disorders sharing mutations that constitutively activate the signal-transduction pathways involved in haematopoiesis. They are characterized by stem cell-derived clonal myeloproliferation. The key MPNs comprise chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is defined by the presence of the Philadelphia (Ph) chromosome and BCR-ABL1 fusion gene. Despite effective cytoreductive agents and targeted therapy, complete CML/MPN stem cell eradication is r

Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval.

The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data for approved COVID-19 vaccines and drugs, as well as developmental pipelines, using databases from the following organizations: United States Food and Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical

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… Fostamatinib inhibits signal transduction of B-cell receptor and Fc-activating receptors which bind to antibodies; the drug activates kinases,including SYK. 127 , 128 Activated SYK stimulates the the inflammatory pathway that promotes the release of neutrophil extracellular traps (NETs). …

Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy.

Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Hence, there is an urgent need for the development of next-generation treatments that, alone or in combination, stop the undesired autoimmune response and contribute to the restoration of homeostasis. This review analyzes current MS treatmen

Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resist

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.

Transforming growth factor-beta (TGF-β) signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically

Advanced Diagnostic Techniques

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Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.

Cytokines are essential components of the tumor microenvironment (TME) and play crucial roles in tumor initiation and progression. As key mediators of interactions between immune cells and tumor cells within the TME, many cytokines exhibit both protumor and antitumor properties. This complex duality, reminiscent of the balance philosophy pursued by "Onmyoji" in traditional Eastern philosophy, which involves observing and regulating opposing forces to achieve harmony, poses marked challenges in translating cytokine therapies from animal studies to clinical applications. More than 20 key cytokin

Prognostic Value of PSMB5 and Correlations with LC3II and Reactive Oxygen Species Levels in the Bone Marrow Mononuclear Cells of Bortezomib-Resistant Multiple Myeloma Patients.

Proteasome inhibitors (PIs) constitute the most common type of induction treatment for multiple myeloma. Interactions between the proteasome, autophagy, and reactive oxygen species (ROS) have been shown in the past, thus emphasizing the need for a better understanding of the underlying pathophysiology. For this study, bone marrow mononuclear cells from 110 myeloma patients were collected at different disease stages. PSMB5 and LC3I/II protein levels were determined using Western blot, proteasome proteolytic activity (PPA) with spectrofluorometry, and ROS with flow cytometry. PSMB5 accumulation

Application of Nanoparticles for Magnetic Hyperthermia for Cancer Treatment-The Current State of Knowledge.

Hyperthermia (HT) is an anti-cancer therapy commonly used with radio and chemotherapies based on applying heat (39-45 °C) to inhibit tumor growth. However, controlling heat towards tumors and not normal tissues is challenging. Therefore, nanoparticles (NPs) are used in HT to apply heat only to tumor tissues to induce DNA damage and the expression of heat shock proteins, which eventually result in apoptosis. The aim of this review article is to summarize recent advancements in HT with the use of magnetic NPs to locally increase temperature and promote cell death. In addition, the recent develop

Unmet Needs and Challenges in Cancer-Associated Venous Thromboembolism.

Cancer-associated venous thromboembolism (CA-VTE) is a significant complication in oncology, contributing to morbidity, mortality, and increased healthcare utilization. Due to multiple patient- and disease-related factors, patients with cancer are at a markedly elevated risk for VTE, particularly within the first 6 months of diagnosis. The aim of this review is to provide an overview of current challenges and unmet needs in CA-VTE prediction, prevention and management. While the Khorana score remains the most widely used risk stratification tool, its limited sensitivity has prompted the develo