MRS and Optical Imaging Studies of Therapeutic Response to Combination Therapy Targeting BRAF/MEK in Murine Melanomas

Academic Radiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Impact of lactate on immune cell function in the tumor microenvironment: mechanisms and therapeutic perspectives

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Lactate has emerged as a key regulator in the tumor microenvironment (TME), influencing both progression and immune dynamics. As byproduct of aerobic glycolysis, lactate satisfies metabolic needs proliferating cells while reshaping TME to facilitate evasion. Elevated levels inhibit effector such CD8 + T natural killer cells, supporting immunosuppressive regulatory myeloid-derived suppressor thus fostering an environment. promotes epigenetic reprogramming, stabilizes hypoxia-inducible factor-1α, activates nuclear factor kappa B, leading further immunological dysfunction. In this review, we examined role suppression, treatment resistance. We also discuss promising therapeutic strategies targeting metabolism, including dehydrogenase inhibitors, monocarboxylate transporter neutralization methods, all which can restore function enhance immunotherapy outcomes. By highlighting recent advances, review provides theoretical foundation for integrating lactate-targeted therapies into clinical practice. highlight potential synergy between these current immunotherapeutic strategies, providing new avenues addressing TME-related challenges improving outcomes patients with cancer.

Language: Английский

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Tumor Microenvironment Lactate: Is It a Cancer Progression Marker, Immunosuppressant, and Therapeutic Target?

Molecules, Journal Year: 2025, Volume and Issue: 30(8), P. 1763 - 1763

Published: April 15, 2025

The “Warburg effect” is a term coined century ago for the preferential use of glycolysis over aerobic respiration in tumor cells energy production, even under conditions. Although this less efficient mechanism generating from glucose, glycolysis, addition to canonical anaerobic an effective means lactate production. abundant waste product, lactate, yielded by dual tumor, has been discovered be major biomolecule that drives cancer progression. Lactate metabolic source that, via cell membrane transporters, shuttles and out as well cell-associated stromal immune within microenvironment (TME). Additionally, serves pH tuner, signaling ligand transducer, epigenetic gene transcription regulator, TME modifier, suppressor, chemoresistance modulator, prognostic marker. With such broad functionalities, production–consumption–reproduction fuels growth dissemination. Here, we elaborate on sources contribute pool TME, functions influence function local tissue immunity, anticancer therapeutic approaches adopting manipulations their efficacies. By scrutinizing these properties others have addressed field, it expected better weighing development, progression, prognosis, efficacy can achieved.

Language: Английский

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Navigating the tumor landscape: VEGF, MicroRNAs, and the future of cancer treatment

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Journal Year: 2025, Volume and Issue: 1868(2), P. 195091 - 195091

Published: May 3, 2025

Language: Английский

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Protonophore activity of short‐chain fatty acids induces their intracellular accumulation and acidification

FEBS Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

Short‐chain fatty acids (SCFAs), produced by dietary fiber fermentation in the colon, play essential roles cellular metabolism, with butyrate notably modulating immune responses and epigenetic regulation. Their production contributes to an acidic colonic environment where protonated SCFAs permeate membranes, leading intracellular acidification SCFA accumulation. Using our method measure pH, we investigated how extracellular pH influences butyrate‐induced immunomodulatory effects human macrophages. Our data show that accumulates acidifies cells at due permeability of its form. While inflammatory cytokine was mildly influenced histone acetylation exhibited a dependence, underscoring importance considering when assessing SCFA's functions.

Language: Английский

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Physiological Oxygen Levels in the Microenvironment Program Ex Vivo-Generated Conventional Dendritic Cells Toward a Tolerogenic Phenotype

Cells, Journal Year: 2025, Volume and Issue: 14(10), P. 736 - 736

Published: May 18, 2025

Dendritic cells (DCs) are critical regulators of immune homeostasis, balancing tolerance and immunity through antigen presentation T cell modulation. While the influence hypoxia (<2% O2) on DC function in pathological settings is well-documented, impact physiological O2 levels remains underexplored. This study investigates role physioxia (4% programming mature DCs toward a tolerogenic phenotype compared to atmospheric conditions (21% typically present vitro assays. cultures generated under 4% exhibited reduced monocyte-to-DC transformation rate, increased lactate production, semi-mature surface marker profile, expression tolerance-associated ILT4. priming was altered only when were co-cultured physioxia, suggesting an O2-dependent threshold for immunostimulatory capacity. These findings highlight complexity mechanisms DC-T interactions, revealing delicate balance between immunogenicity. Our results underscore need physiologically relevant research better reflect vivo behavior inform immunotherapy design. Overall, this advances understanding how microenvironmental cues shape biology, with implications tolerance, autoimmunity, cancer immunotherapy.

Language: Английский

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Harnessing Metal Nanoparticles: Revolutionizing Cancer Therapy Through Targeted Drug Delivery and Tumor Microenvironment Modulation

NANO, Journal Year: 2024, Volume and Issue: 19(10)

Published: May 4, 2024

Cancer remains a significant global health burden, claiming countless lives annually and incurring substantial direct indirect economic costs. Despite advancements in therapeutic modalities, conventional cancer treatments, including chemotherapy, radiotherapy surgery, are often hampered by limitations such as insufficient efficacy, dose-dependent side effects, high costs patient tolerability. This has spurred extensive research into novel approaches for this life-threatening disease. Metal nanoparticles (MNPs) have emerged promising tools therapy due to their unique physicochemical properties spanning the past two decades. Owing size similarity biological molecules, MNPs possess inherent ability penetrate cellular barriers, making them ideal carriers targeted drug delivery. These multifunctional nanoplatforms offer distinct advantages over therapeutics enabling delivery of anticancer agents specific tumor sites, thereby enhancing efficacy minimizing systemic effects. Photodynamic sonodynamic represent particularly strategies that leverage treatment. review delves potential applications modulating microenvironment, paving way exploration vast rapidly evolving field nanomedicine.

Language: Английский

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Targeting Macrophages as a Novel Therapy to Treat Triple-Negative Breast Cancer: A Literature Review

Undergraduate Research in Natural and Clinical Science and Technology (URNCST) Journal, Journal Year: 2024, Volume and Issue: 8(4), P. 1 - 9

Published: April 19, 2024

Triple-negative breast cancer (TNBC) is a highly aggressive form of which lacks the traditional cellular targets other types cancer. As such, it increasingly important to find alternative treat this deadly disease. Recently, tumour-associated macrophages (TAMs) have become an exciting area focus for research and may provide source treatment options TNBC. Macrophages are part innate immune response also play crucial role in tumour progression, inflammation, metastasis. TAMs fall along spectrum generally presented as either M1 type or M2 type. considered anti-tumorigenic whereas pro-tumorigenic, promoting growth inhibiting T-cell response. A search University Alberta's online library database was carried out with specific emphasis on clinical research. Search efforts focused effects progression Further searches were performed determine efficacy targeting Increasing relative ratio depletion lead better prognosis be repolarized phenotype using metformin, inhibition SerpinE2, YAP/STAT3, MED1/PPARy. Macrophage recruitment microenvironment inhibited by chemokines such CCL2. Current methods could not efficiently deplete at high abundance. The abundance their phagocytic properties instead exploited increase cell phagocytosis CD47-SIRPɑ axis. Exciting opportunities been revealed regarding macrophage recruitment, repolarization type, through exploitation macrophages. However, conflicting results can found all these emerging strategies. Worsening matters lack knowledge functions confusing landscape current naming conventions. further required target treatment.

Language: Английский

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How Does Cancer Occur? How Should It Be Treated? Treatment from the Perspective of Alkalization Therapy Based on Science-Based Medicine

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2197 - 2197

Published: Sept. 26, 2024

This review article investigates the relationship between mitochondrial dysfunction and cancer progression, emphasizing metabolic shifts that promote tumor growth. Mitochondria are crucial for cellular energy production, but they also play a significant role in progression by promoting glycolysis even under oxygen-rich conditions, phenomenon known as Warburg effect. reprogramming enables cells to maintain an alkaline internal pH acidic external environment, which critical their proliferation survival hypoxic conditions. The explores microenvironment (TME), consequence of intensive glycolytic activity proton production cells. milieu enhances invasiveness metastatic potential contributes increased resistance chemotherapy. Alkalization therapy, involves neutralizing this acidity through dietary modifications administration alkalizing agents such sodium bicarbonate, is highlighted effective strategy counteract these adverse conditions impede progression. Integrating insights from science-based medicine, evaluates effectiveness alkalization therapy across various types clinical assessments. Science-based utilizes inductive reasoning observed outcomes, lends support hypothesis treatment. By addressing both environmental disruptions, suggests considering primarily disorder could lead more targeted treatment strategies, potentially improving outcomes patients with advanced-stage cancers.

Language: Английский

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In Vivo HOXB7 Gene Silencing and Cotreatment with Tamoxifen for Luminal A Breast Cancer Therapy

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(10), P. 1325 - 1325

Published: Oct. 4, 2024

Acquired resistance and adverse effects are some of the challenges faced by thousands Luminal A breast cancer patients under tamoxifen (TMX) treatment. Some authors associate overexpression HOXB7 with TMX in this molecular subtype, knockdown gene could be an effective strategy to regain sensitivity. Therefore, we used calcium phosphate hybrid nanoparticles (HNP) for delivery short interfering RNA molecule (siRNA) complementary evaluated interference (RNAi) associated treatment vivo.

Language: Английский

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