Результаты поиска

Research advances of lactylation modification in breast cancer.

Breast cancer (BC), a leading cause of cancer mortality in women, involves complex molecular mechanisms including post-translational modifications (PTMs). While common PTMs are well-studied, lactylation-a novel PTM linking metabolism to epigenetics-has emerged as a critical regulator in BC pathogenesis. The high concentration of lactate caused by the Warburg effect makes lactylation in tumor tissue possible. Machine learning enhances the discovery and analysis of lactylation sites by processing large datasets, revealing patterns that influence tumor behavior and patient outcomes. This review o

Revisiting potential value of antitumor drugs in the treatment of COVID-19.

Since an outbreak started in China in 2019, coronavirus disease 2019 (COVID-19) has rapidly become a worldwide epidemic with high contagiousness and caused mass mortalities of infected cases around the world. Currently, available treatments for COVID-19, including supportive care, respiratory support and antiviral therapy, have shown limited efficacy. Thus, more effective therapeutic modalities are highly warranted. Drug repurposing, as an efficient strategy to explore a potential broader scope of the application of approved drugs beyond their original indications, accelerates the process of d

The role of CD8+ T cells in the immunoregulation of osteoporosis.

INTRODUCTION: Osteoporosis weakens the skeleton by lowering bone mass and damaging bone microarchitecture. A growing body of evidence points to disruptions in osteoimmune homeostasis as a key driver of this disease. In particular, apoptosis of bone cells and immune cells appears to be a critical contributing mechanism. Within the bone marrow, CD8+ T cells display a surprising functional duality: whether they protect bone or promote its loss depends heavily on local signals. Under healthy conditions or after mechanical loading, activated CD8+ T cells help maintain bone mass. They do so mainly b

Reporting of surrogate endpoints in randomised controlled trial protocols (SPIRIT-Surrogate): extension checklist with explanation and elaboration.

Randomised controlled trials often use surrogate endpoints to substitute for a target outcome (an outcome of direct interest and relevance to trial participants, clinicians, and other stakeholders—eg, all cause mortality) to improve efficiency (through shortened duration of follow-up, reduced sample size, and lower research costs), and for ethical or practical reasons. However, their use has a fundamental limitation in terms of uncertainty of the intervention effect on the target outcome and limited information on potential intervention harms. There have been increasing calls for improved repo

Post-Transplant Maintenance Treatment Options in Multiple Myeloma.

Maintenance therapy post autologous stem cell transplant (ASCT) is commonly employed in myeloma patients to prolong remission, as relapse invariably occurs after ASCT. After initial diagnosis and risk stratification, patients receive initial therapy with a combination of drugs, typically a proteasome inhibitor and an immunomodulatory imide drug (IMiD), and in those considered eligible, high-dose chemotherapy followed by autologous stem cell transplant. The aim of our study was to review the literature and consolidate evidence regarding different maintenance therapies post stem cell transplant

Shaping the Innate Immune Response by Dietary Glucans: Any Role in the Control of Cancer?

β-glucans represent a heterogeneous group of naturally occurring and biologically active polysaccharides found in many kinds of edible mushrooms, baker's yeast, cereals and seaweeds, whose health-promoting effects have been known since ancient times. These compounds can be taken orally as food supplements or as part of daily diets, and are safe to use, nonimmunogenic and well tolerated. A main feature of β-glucans is their capacity to function as biological response modifiers, exerting regulatory effects on inflammation and shaping the effector functions of different innate and adaptive immuni

Killing me softly--future challenges in apoptosis research.

The induction of apoptosis, a highly regulated and clearly defined mode of cell dying, is a vital tenet of modern cancer therapy. In this review we focus on three aspects of apoptosis research which we believe are the most crucial and most exciting areas currently investigated and that will need to be better understood in order to enhance the efficacy of therapeutic measures. First, we discuss which target to select for cancer therapy and argue that not the cancer cell as such, but its interaction with the microenvironment is a more promising and genetically stable site of attack. Second, the

Tumour-associated macrophages: versatile players in the tumour microenvironment.

Tumour-Associated Macrophages (TAMs) are one of the pivotal components of the tumour microenvironment. Their roles in the cancer immunity are complicated, both pro-tumour and anti-cancer activities are reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis and tumour regression. Interestingly, TAMs are highly dynamic and versatile in solid tumours. They show anti-cancer or pro-tumour activities, and interplay between the tumour microenvironment and cancer stem cells and under specific conditions. In addition to the c

Совпадение в полном тексте источника
… Allogeneic CAR invariant natural killer T cells exert potent antitumor effects through host CD8 T-cell cross-priming. Clin. Cancer Res. 27 (21), 6054–6064. 10.1158/1078-0432.CCR-21-1329 Siu L. L., Wang D., Hilton J., Geva R., Rasco D., Perets R., et al. (2022). …

Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.

Recent studies highlight the multifaceted roles of neurotransmitters in tumor immunomodulation, offering novel avenues for increasing therapeutic efficacy. These signaling molecules are classified into cholinergic agents, monoamines, amino acids, and peptides and regulate tumorigenesis, metastasis, and immune evasion via autocrine/paracrine pathways and receptor-mediated interactions. Notably, neurotransmitters influence tumor cell proliferation, apoptosis, and immune cell activity by modulating intracellular signaling cascades through posttranslational modifications (serotonylation and dopami

RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.

RNA interference (RNAi) provides researchers with a versatile means to modulate target gene expression. The major forms of RNAi molecules, genome-derived microRNAs (miRNAs) and exogenous small interfering RNAs (siRNAs), converge into RNA-induced silencing complexes to achieve posttranscriptional gene regulation. RNAi has proven to be an adaptable and powerful therapeutic strategy where advancements in chemistry and pharmaceutics continue to bring RNAi-based drugs into the clinic. With four siRNA medications already approved by the US Food and Drug Administration (FDA), several RNAi-based thera

Targeting signaling pathways in lymphoma: From molecular mechanisms to clinical breakthroughs.

AbstractThe treatment paradigm for lymphoma, a highly heterogeneous group of hematologic malignancies, has been revolutionized by the development of therapies targeting oncogenic signaling pathways. This shift from conventional chemotherapy to precision medicine is driven by a deep molecular understanding of the pathways that govern lymphoma cell survival and proliferation. This review comprehensively surveys the landscape of these targeted therapies, from fundamental molecular mechanisms to clinical breakthroughs. We first dissect the molecular architecture of key oncogenic drivers, covering

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

The role of autophagy in cancer: from molecular mechanism to therapeutic window.

Autophagy is a cellular degradation process that plays a crucial role in maintaining metabolic homeostasis under conditions of stress or nutrient deprivation. This process involves sequestering, breaking down, and recycling intracellular components such as proteins, organelles, and cytoplasmic materials. Autophagy also serves as a mechanism for eliminating pathogens and engulfing apoptotic cells. In the absence of stress, baseline autophagy activity is essential for degrading damaged cellular components and recycling nutrients to maintain cellular vitality. The relationship between autophagy a

Prospects and Advances in Adoptive Natural Killer Cell Therapy for Unmet Therapeutic Needs in Pediatric Bone Sarcomas.

Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune

Drugging the efferocytosis process: concepts and opportunities.

The daily removal of billions of apoptotic cells in the human body via the process of efferocytosis is essential for homeostasis. To allow for this continuous efferocytosis, rapid phenotypic changes occur in the phagocytes enabling them to engulf and digest the apoptotic cargo. In addition, efferocytosis is actively anti-inflammatory and promotes resolution. Owing to its ubiquitous nature and the sheer volume of cell turnover, efferocytosis is a point of vulnerability. Aberrations in efferocytosis are associated with numerous inflammatory pathologies, including atherosclerosis, cancer and infe

Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic.

Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung an

Novel insight and perspectives of nanoparticle-mediated gene delivery and immune-modulating therapies for pancreatic cancer.

Current standard-of-care therapies have failed to improve the survival of patients with metastatic pancreatic cancer (PCA). Therefore, exploring novel therapeutic approaches for cancer targeting is of utmost need. During the past few years, many efforts have been made to develop conventional treatment strategies to reduce chemotherapy resistance. However, critical challenges have impeded current cancer management outcomes, and limited clinical responses have been achieved due to unfavorable off-target effects. Advances in nanotechnology-based gene and immune-modulator delivery systems have exc

Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.

This review introduces a paradigm-shifting concept of Dual Distinct Immunotherapy (DDI), which strategically integrates two distinct immunotherapeutic modalities to overcome the limitations of current monotherapies and dual immune checkpoint inhibitor (ICI) combinations. The concept of DDI extends beyond traditional ICI combinations to encompass various innovative pairings: ICIs with oncolytic viruses (OVs), adoptive cell therapies (CAR-T/TIL), cancer vaccines, or cytokine therapies. These combinations demonstrate unique synergistic mechanisms and enhanced therapeutic potential through multi-f

Enhancing the Safety of Nanoparticles in Medicine: Highlights of Progress and Critical Objectives.

Nanoparticles have transformed drug delivery, imaging, vaccination, and precision therapeutics, but their clinical translation remains constrained by safety profiles that are inseparable from material design, biological identity, host factors, and manufacturing. This review critically evaluates recent progress, persistent limitations, and priority objectives for safer nanomedicine. Unlike reviews organized primarily by material class or isolated toxicology endpoints, we integrate physicochemical determinants, protein corona formation, immune recognition, organ disposition, preclinical models,

Neutrophils unveiled in chronic lymphocytic leukemia.

This review explores neutrophils' roles in chronic lymphocytic leukemia (CLL), highlighting their functions within the immune system. While neutrophils are known for fighting infections, their altered behavior in CLL significantly impacts disease progression. This review notes the reduced phagocytic abilities of neutrophils and the increased formation of neutrophil extracellular traps (NETs) in patients with CLL. It also examines the effects of CLL treatments, including chemotherapy, immunotherapy and targeted therapies, on neutrophils' count and function, stressing the need for improved strat