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Integrated clinico-molecular analysis of gastric cancer in European and Latin American populations: LEGACY project.

BACKGROUND: Gastric cancer (GC) is recognized for intrinsic heterogeneity, although it is similarly approached in Europe and Latin America (LATAM). The LEGACY project aimed to deepen GC molecular understanding through multi-omics analysis in Europe and LATAM GC samples. PATIENTS AND METHODS: Tumor samples were centrally reviewed for histology, human epidermal growth factor receptor 2 (HER2) expression, and mismatch repair-deficient (dMMR)/microsatellite instability (MSI) status. In addition, we assessed Epstein-Barr virus (EBV) status, programmed death-ligand 1 (PD-L1) combined positive score

A Review of the Potential Role of Human Cytomegalovirus (HCMV) Infections in Breast Cancer Carcinogenesis and Abnormal Immunity.

Previously recognized classical human onco-viruses can regulate complex neoplastic events, and are estimated to play a role during carcinoge … is known to exhibit a wide range of immunosuppressive effects, which can have radical impact on the tumor microenvironment. HCMV infected cells can avoid recognition and elimination by the immune system by orchestrating polarization of immunosuppressive type II macrophages, preventing antigen presentation, by expressing T cell inhibitory molecules, and possibly, by the …

Normalizing Tumor Vessels To Increase the Enzyme-Induced Retention and Targeting of Gold Nanoparticle for Breast Cancer Imaging and Treatment.

Abnormal tumor vessels impede the transport and distribution of chemotherapeutics, resulting in low drug concentration at tumor sites and compromised drug efficacy. Normalizing tumor vessels can modulate tumor vascular permeability, alleviate tumor hypoxia, increase blood perfusion, attenuate interstitial fluid pressure, and improve drug delivery. Herein, a novel strategy combining cediranib, a tumor vessel normalizing agent, with an enzyme responsive size-changeable gold nanoparticle (AuNPs-A&C) was developed. In vivo photoacoustic and fluorescence imaging showed that oral pretreatment with 6

The marrow stem cell niche in normal and malignant hematopoiesis.

The hematopoietic niche is composed of endothelial cells, mesenchymal stromal cells of several types, and megakaryocytes, and functions to support the survival, proliferation, and differentiation of normal hematopoietic stem cells (HSCs). An abundance of evidence from a range of hematological malignancies supports the concept that the niche also participates in the pathogenesis of malignant hematopoiesis, differentially supporting malignant stem or progenitor cells over that of normal blood cell development. In 2005, patients with myeloproliferative neoplasms were reported to harbor an acquire

Gallium-Containing Agents for Tumor Diagnosis and Therapy: Current Status and Future Prospects.

Ga-containing agents show great promise in tumor theranostics due to their unique physicochemical and biological features. Recent studies have extensively explored Ga-containing radiopharmaceuticals, therapeutic compounds, and multifunctional formulations, clarifying their interactions with the tumor microenvironment and antitumor mechanisms. Clinically, Ga imaging agents, especially 68Ga-labeled probes, have become standard tools for precise diagnosis of prostate cancer, neuroendocrine tumors, and other malignancies, while Ga therapeutic agents act by interfering with DNA metabolism, regulati…

Regulating Lipid Metabolism in Cancer: The Therapeutic Potential of Traditional Chinese Medicine.

Lipid metabolic reprogramming is a key feature of tumor cells to adapt to the microenvironment and plays an important role in tumor growth, invasion, and metastasis. This article provides a systematic review of the pathological mechanisms underlying lipid metabolism disorders in tumor cells, including abnormalities in fatty acid (FA) and cholesterol metabolism and their association with tumor progression. Furthermore, it summarizes the mechanisms by which traditional Chinese medicine (TCM) and its natural active compounds regulate lipid metabolism through multiple targets and pathways, such as

Single-cell sequencing in bladder cancer: new insights from tumor cell diversity to individualized treatment strategies.

Bladder cancer (BCa) is a prevalent malignancy and major cause of cancer-related mortality in men, with clinical outcomes still varying desp … reviews advancements in SCS technology and its applications in evaluating tumor heterogeneity, the tumor microenvironment, metastasis, and treatment resistance, offering new perspectives for future BCa research.

Carvedilol sensitizes chemotherapy by targeting STING to boost anti-tumor immunity.

The stimulator of interferon genes (STING)-mediated type I interferon (IFN) response is critical for mounting anti-tumor immunity and sensitizing chemotherapy by remodeling the tumor immune microenvironment. However, no clinically available drugs have been applied for STING activation. Based on high-throughput screening of small-molecule microarrays, we found that carvedilol, an adrenergic receptor blocker used to treat essential hypertension and symptomatic heart failure, is a STING activator. Mechanistically, carvedilol interacts with STING at threonine 263 and enhances its dimerization. Imp

What is the Relevance of Neuron-Tumor Interactions in Malignant CNS Tumors?

Crosstalk between neurons and tumor cells strongly affects tumor growth, invasion, metastasis, and resistance to treatment. In the CNS, connections between neurons and malignant tumor cells promote cell proliferation. Glutamatergic or GABAergic neurons promote glioblastoma growth through neuron-to-glioma synapses and through activity-dependentparacrine signals. Glioblastoma cells form an interconnected network for signal propagation and synaptically integrate into neural circuits. Brain metastasis, for example, from breast cancer, acquire neuronal-like features within the neural microenvironme

Colorectal cancer landscape from gut microbiota: Insights into mutations, epigenetic dysregulation, and immune microenvironment alterations.

This review explores how gut microbiota reshapes colorectal cancer (CRC) molecular landscape, driving initiation/progression via key mechanisms. Microbes/metabolites cause driver mutations (DNA damage, signaling interference) and alter epigenetics (DNA methylation, histone modifications, ncRNAs) to boost tumor cell proliferation/survival. Dysbiosis disrupts tumor immune microenvironment (TIME) by impairing immune cells and increasing immunosuppressive factors, fostering immune evasion.Integrating molecular biology, microbiology, and immunology, we show microbial changes are causal in oncogenes

Neurotransmitters in tumors: chemical cross-talk shaping tumor progression.

The role of innervation in the pathogenesis of malignancies has been documented in many investigations. Recent studies have revealed that neurotransmitters act as mediators in nerve-stimulated cancer progression by directly influencing tumor cells and modulating the tumor microenvironment, including immune cells, angiogenesis, and surrounding stromal cells. Notably, psychological stress has been identified as a contributing factor to oncogenesis, primarily mediated by neurotransmitters. However, the complex interplay between neurotransmitters and tumor cells remains only partially understood. …

[Research Progress of Treg/Th17 in the Treatment of Chronic Obstructive Pulmonary Disease with Lung Cancer].

Chronic obstructive pulmonary disease (COPD) and lung cancer are global high incidence and high mortality diseases, which seriously increase the socio-economic burden. Smoke exposure, genetic susceptibility and chronic inflammation are common susceptible factors. At present, abnormal inflammatory immune response plays an important role in the occurrence and development of the two diseases. In the process of immune response, tumor microenvironment (TME) is gradually produced, which is beneficial to angiogenesis and immunosuppression, and finally leads to immune escape of tumor cells, leading to…

Genome-wide CRISPR screens in primary human natural killer cells identify countermeasures against immunosuppressive environment.

Natural killer (NK) cells are promising effectors for cancer immunotherapy, but their efficacy is limited by immunosuppressive tumor microenvironments. To uncover strategies for enhancing NK cell function, we establish a CRISPR loss-of-function screening platform for primary human NK cells by combining BaEVRless-pseudotyped lentiviral transduction of sgRNA libraries with Cas9 protein electroporation. This platform enables genome-scale interrogation of gene function in non-transformed NK cells. Kinome-focused and genome-wide screens identify key regulators of NK cell proliferation, cytotoxicity…

Cellular crosstalk of fibroblast-myofibroblast transition in intestinal homeostasis and disease.

Fibroblasts are central components of the intestinal microenvironment and can acquire a myofibroblast phenotype through fibroblast-to-myofibroblast transition (FMT), a process linked to increased tissue mechanosensitivity and active extracellular matrix (ECM) remodeling. In this way, FMT participates in normal intestinal homeostasis and repair, but it can also contribute to fibrosis and tumor-associated stromal remodeling when sustained. More importantly, FMT is not a passive process but an active reprogramming event in response to physiological demands or pathological conditions. Its regulati

The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: "Crafting" a Microenvironment That Matters.

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of

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… Growing interest is focused on EVs and their potential impact on the regulation of normal and tumor microenvironment. Recent findings demonstrated EVs playing critical roles in cancer development (including blood cancers), progression and drug resistance. …

The influence of tumor blood flow and microenvironmental factors on the efficacy of radiation, drugs and localized hyperthermia.

It is generally accepted that tumor blood flow, microcirculation, oxygen and nutrient supply, tissue pH distribution, and the bioenergetic status-factors which are usually closely linked and which define the so-called metabolic microenvironment--can markedly influence the therapeutic response of malignant tumors to conventional irradiation, chemotherapy, other nonsurgical treatment modalities, and the cell proliferation activity within tumors. Currently available information on the parameters defining the metabolic micromilieu in human tumors is presented in this review. According to these dat

Natural extract-derived compounds for the treatment of hematological diseases through modulation of the bone marrow microenvironment.

The bone marrow microenvironment comprises a complex network of hematopoietic stem cells, immune cells, stromal cells, and non-cellular components such as the extracellular matrix and soluble factors, collectively maintaining the homeostasis of hematopoietic stem and progenitor cells. It is highly vulnerable to pathological perturbations induced by hematologic malignancies, solid tumors, inflammatory stress, and therapeutic exposure, which collectively destabilize microenvironmental homeostasis and promote hematopoietic failure, malignant progression, and immune dysregulation. Natural products

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… Visuals and labels depict origins as plants, minerals, microorganisms, nanomaterials; optimization through extraction process and targeted delivery; and chemical regulation involving ROS, metal ion chelation, and cellular components such as HSC, LSCs, NK cells, and TAMs, all centered around a tumor microenvironment … This ultimately impairs immune surveillance against abnormal hematopoietic clones or tumors in conditions like MDS, leukemia, or the tumor microenvironment ( Hua et al., 2017 ; Yao et al., 2023 ). Both in vitro and in vivo studies provide supportive evidence. …

Virus-inspired nanocages potentiate glioblastoma sonochemotherapy via structure-function mimicry.

Sonochemotherapy has emerged as a promising strategy for glioma treatment through synergistic therapeutic effects and reduced systemic toxicity. Nevertheless, clinical translation remains constrained by the hypoxic tumor microenvironment, antioxidant defense mechanism, inadequate tumor accumulation, and suboptimal cellular internalization. Inspired by the rabies virus, we engineered rabies virus glycopeptide-29 (RVG29)-anchored virus-like hollow mesoporous manganese oxide (vHMMn) nanocages co-encapsulating temozolomide (TMZ) and indocyanine green (ICG) (denoted as TI@vHMMnR) for amplified sono…

A CD36-Targeting Thermosensitive Berberine Nanogel Blocks Tumor Lipid Hijacking and Potentiates Anti-PD-L1 Immunotherapy in Triple-Negative Breast Cancer.

The limited efficacy of programmed death-ligand-1 (PD-L1) monoclonal antibodies (aPD-L1) in triple-negative breast cancer (TNBC) is largely attributable to the immunosuppressive tumor microenvironment (TME). Notably, the abundance of cancer-associated adipocytes (CAAs) constitutes a distinctive feature of the TNBC microenvironment, contributing significantly to its immunosuppressive nature. CAAs upregulate cluster of differentiation 36 (CD36), a fatty acid translocase on tumor cells, thereby promoting excessive fatty acids (FAs) uptake and lipid droplet (LD) accumulation, which starve immune c…

Shenling Baizhu Powder potentiates immunotherapy response: putative roles of gut microbial remodeling and fatty acid metabolism modulation.

BACKGROUND: Low response rates and immune-related adverse events (irAEs) are major factors affecting the efficacy of PD-1 monoclonal antibod … l 16S rDNA sequencing, untargeted/targeted plasma metabolomics, and immune profiling of splenic and tumor microenvironment (TME) lymphocytes. SLBZS/FMT interventions were applied to antibiotic-treated mice to assess microbiota-dependent effects. RESULTS: SLBZS synergized with PD-1 mAb to significantly inhibit tumor growth and reduce multi-organ irAEs. In the metastasis …