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Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy.

During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular p

Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase

Exploring the impact of m6A modification on immune diseases: mechanisms and therapeutic implication.

N6-methyladenosine (m6A) is a chemical modification of RNA and has become a widely discussed topic among scientific researchers in recent years. It is distributed in various organisms, including eukaryotes and bacteria. It has been found that m6A is composed of writers, erasers and readers and is involved in biological functions such as splicing, transport and translation of RNA. The balance of the human immune microenvironment is important for human health abnormalities. Increasing studies have found that m6A affects the development of immune diseases such as inflammatory enteritis and system

Aptamers and Antisense Oligonucleotides for Diagnosis and Treatment of Hematological Diseases.

Aptamers or chemical antibodies are single-stranded DNA or RNA oligonucleotides that bind proteins and small molecules with high affinity and specificity by recognizing tertiary or quaternary structures as antibodies. Aptamers can be easily produced in vitro through a process known as systemic evolution of ligands by exponential enrichment (SELEX) or a cell-based SELEX procedure. Aptamers and modified aptamers, such as slow, off-rate, modified aptamers (SOMAmers), can bind to target molecules with less polar and more hydrophobic interactions showing slower dissociation rates, higher stability,

Роль микробиотики в гематологических заболеваниях: описательный обзор механизмов и терапевтического потенциала.

Микробиота человека, в частности кишечный микробиом, играет центральную роль в поддержании иммунного гомеостаза, регулировании гематопоисиса и модуляции хост-метаболизма с помощью биоактивных метаболитов, таких, как короткоцепные жирные кислоты (СКФА), желчные кислоты и соединения триптофана. Разрушение этой микробной экосистемы (дисбиоз) стало одним из ключевых факторов развития и развития гематологических магнатов (ГМ), включая острые и хронические лейкемии, лимфомы и множественные миеломы. В настоящем обзоре описательной части обобщаются последние данные (см.2022-2025) о сложных двухнаправл

2020 ACVIM Forum On Demand Research Abstract Program.

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BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.

The BCL-2 family of proteins plays a central role in the regulation of apoptosis, with BCL-2 and BCL-xL representing two of its most prominent antiapoptotic members. This review explores the molecular regulation of BCL-2 and BCL-xL genes, emphasizing the structural domains that define the functions of the broader BCL-2 family. Beyond their canonical roles in preventing mitochondrial outer membrane permeabilization, both proteins contribute significantly to cancer development. Their overexpression enhances invasiveness and tumor progression, supports angiogenesis, and critically modulates cellu

Deciphering and targeting oncogenic pathways through integrated approaches and amino acid metabolism in hematologic malignancies.

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, represent a diverse group of blood cancers driven by complex oncogenic pathways and genetic aberrations. Despite advances in treatment, resistance and relapse remain significant clinical challenges. This review presents an integrative approach to blood cancer therapy, highlighting the convergence of precision medicine, CRISPR-based gene editing, immunotherapy (including CAR-T cells and immune checkpoint inhibitors), and targeted modulation of amino acid metabolism. We investigate the molecular pathways driving tumour

Dermatologic conditions in women receiving systemic cancer therapy.

As advances in cancer therapies have improved cancer-related survival, novel therapeutics have also introduced a variety of dermatologic toxicities, and an increased number of patients are living with these sequalae. Women with cancer in particular experience a spectrum of dermatologic conditions that affect their skin, hair, nail, and mucosal surfaces. Studies have shown that these toxic effects can significantly affect quality of life and alter a woman's self-image, cultural identity, femininity, sexuality, and mental health. In severe instances, dermatologic toxicities may even disrupt canc

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Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.

Adoptive T-cell transfer therapy (ACT) has significantly propelled the advancement of tumor immunotherapy. Among various strategies targeting solid tumors, the T-cell receptor (TCR)-engineered T-cell (TCR-T cell) therapy has emerged as a highly promising approach, exhibiting an expanded therapeutic window across diverse patient populations and superior tumoricidal activity in certain solid malignancies compared with chimeric antigen receptor T cell (CAR-T) and tumor-infiltrating T cells/lymphocyte (TIL) therapies. However, its clinical efficacy remains constrained. In this paper, we introduce

Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia.

Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as chemopreventive when adequately integrated into nutritional interventions. With a renovated interest in natural remedies as a commodity and their essential role in cancer drug discovery, Malaysia is looking towards capitalizing on its mega biodiversity, which includes the oldest rainforest in the world and an estim

Protein kinase CK2: a potential therapeutic target for diverse human diseases.

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (ei

A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach.

Gaucher disease (GD), a rare hereditary lysosomal storage disorder, occurs due to a deficiency in the enzyme β-glucocerebrosidase (GCase). This deficiency leads to the buildup of substrate glucosylceramide (GlcCer) in macrophages, eventually resulting in various complications. Among its three types, GD2 is particularly severe with neurological involvements. Current treatments, such as enzyme replacement therapy (ERT), are not effective for GD2 and GD3 due to their inability to cross the blood-brain barrier (BBB). Other treatment approaches, such as gene or chaperone therapies are still in expe

Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration.

The dynamic changes in chromatin conformation alter the organization and structure of the genome and further regulate gene transcription. Basically, the chromatin structure is controlled by reversible, enzyme-catalyzed covalent modifications to chromatin components and by noncovalent ATP-dependent modifications via chromatin remodeling complexes, including switch/sucrose nonfermentable (SWI/SNF), inositol-requiring 80 (INO80), imitation switch (ISWI) and chromodomain-helicase DNA-binding protein (CHD) complexes. Recent studies have shown that chromatin remodeling is essential in different stag

The multiple roles of interferon regulatory factor family in health and disease.

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores the diverse functions of nine mammalian IRF members, each featuring conserved domains essential for interactions with other transcription factors and cofactors. These interactions allow IRFs to modulate a broad spectrum of physiological processes, encompassing host defense, immune response, and cell development. Conversely, their pivotal role in immune regulation implicates them in the pathophysiology of v

Recent Progress of CircRNAs in Hematological Malignancies.

Circular RNAs (circRNAs) are now recognized as key regulators in the epigenetic control of genetic expression, being involved in a wide range of cellular activities such as proliferation, differentiation, and apoptosis. Their unique closed-loop structure endows them with stability and resistance to exonuclease degradation, making them not only key regulatory molecules within the cell but also promising biomarkers for disease diagnosis and prognosis, particularly in hematological malignancies. This review comprehensively explores the role of circRNAs in the pathogenesis, progression, and therap

Therapeutic Targeting of DNA Damage Repair in the Era of Precision Oncology and Immune Checkpoint Inhibitors.

Cancer manifestation is a multistep process involving accumulation of various genetic and epigenetic changes that results in oncogenic "hallmarks of cancer" processes including genomic instability. Exploitation of aberrant DNA-damage response (DDR) mechanisms in cancer is in part a goal of many therapeutic strategies, and recent evidence supports the role of targeting DDR in modulating the tumor immune microenvironment to enhance immunotherapeutic response. Improved cancer profiling, including next-generation and whole-genome mutational sequencing of tumor tissue, as well as circulating nuclei

Combination Therapies in Chronic Myeloid Leukemia for Potential Treatment-Free Remission: Focus on Leukemia Stem Cells and Immune Modulation.

Although tyrosine Kinase Inhibitors (TKI) has revolutionized the treatment of chronic myeloid leukemia (CML), patients are not cured with the current therapy modalities. Also, the more recent goal of CML treatment is to induce successful treatment-free remission (TFR) among patients achieving durable deep molecular response (DMR). Together, it is necessary to develop novel, curative treatment strategies. With advancements in understanding the biology of CML, such as dormant Leukemic Stem Cells (LSCs) and impaired immune modulation, a number of agents are now under investigation. This review up

The Application of CAR-T Cells in Haematological Malignancies.

Chimeric antigen receptor (CAR)-T cells (CART) remain one of the most advanced and promising forms of adoptive T-cell immunotherapy. CART represent autologous, genetically engineered T lymphocytes expressing CAR, i.e. fusion proteins that combine components and features of T cells as well as antibodies providing their more effective and direct anti-tumour effect. The technology of CART construction is highly advanced in vitro and every element of their structure influence their mechanism of action in vivo. Patients with haematological malignancies are faced with the possibility of disease rela

Natural anti-cancer products: insights from herbal medicine.

Herbal medicine exhibits a broad spectrum of potent anti-cancer properties, including the enhancement of tumor immune responses, reversal of multidrug resistance, regulation of autophagy and ferroptosis, as well as anti-proliferative, pro-apoptotic, and anti-metastatic effects. This review systematically explores recent advances (primarily documented since 2019) in research on key anti-cancer compounds derived from herbal medicine, such as apigenin, artemisinin, berberine, curcumin, emodin, epigallocatechin gallate (EGCG), ginsenosides, icariin, resveratrol, silibinin, triptolide, and ursolic