Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1924 - 1924

Published: Nov. 20, 2024

Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function contributes failure. However, acidic conditions TME disrupt interaction between cancer cells, driving tumor-infiltrating T cells NK into an inactivated, anergic state. Simultaneously, promotes recruitment activation of immunosuppressive such as myeloid-derived suppressor regulatory (Tregs). Notably, acidity enhances exosome release from Tregs, further amplifying immunosuppression. Tumor thus acts "protective shield," neutralizing anti-tumor responses transforming pro-tumor allies. Therefore, targeting lactate metabolism has emerged promising strategy overcome this barrier, with approaches including buffer agents neutralize pH inhibitors block production or transport, thereby restoring efficacy TME. Recent discoveries have identified genes involved (pHe) regulation, presenting new therapeutic targets. Moreover, ongoing research aims elucidate molecular mechanisms acidification develop treatments modulate levels enhance outcomes. Additionally, future studies are crucial validate safety pHe-targeted therapies patients. Thus, review explores regulation pHe its potential role improving immunotherapy.

Language: Английский

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Metabolic Atlas of Human Eyelid Infiltrative Basal Cell Carcinoma

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(1), P. 11 - 11

Published: Jan. 7, 2025

Purpose: Eyelid infiltrative basal cell carcinoma (iBCC) is the most common malignant tumor affecting ocular adnexa, but studies on metabolic changes within its microenvironment and heterogeneity at invasive area are limited. This study aims to analyze differences among iBCC types using single-cell spatial metabolomics analysis examine environment area. Methods: Single-cell transcriptomic data of human (BCC) were clustered visualized Uniform Manifold Approximation Projection. Metabolic reprogramming was analyzed with flux estimation analysis. Spatial obtained Timstof Flex MALDI 2 system, Bruker software used for region selection. Results: Eight identified microenvironment. Differences between inflammatory cancer-associated fibroblasts myofibroblastic analyzed. showed increased glycolysis, glutamine, heme, glutathione fluxes in revealed high levels taurine, deoxy-GMP, O-phosphoethanolamine, pyrithione. Both regions had significant upregulation fatty acid pathways, marked increases oleic arachidonic acids Specific UDP-glucuronic UDP-glucose 6-dehydrogenase (UGDH) expression suggest UXS1 as a potential therapeutic target iBCC. Conclusions: establishes atlas iBCC, revealing dominance lipid lysosome metabolism. Potential markers characteristic substances offer new insights immunotherapy exploration BCC's mechanisms.

Language: Английский

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MOX Nanosensors to Detect Colorectal Cancer Relapses from Patient’s Blood at Three Years Follow-Up, and Gender Correlation

Biosensors, Journal Year: 2025, Volume and Issue: 15(1), P. 56 - 56

Published: Jan. 16, 2025

Colorectal cancer represents 10% of all the annual tumors diagnosed worldwide, being often not timely diagnosed, because its symptoms are typically lacking or very mild. Therefore, it is crucial to develop and validate innovative low-invasive techniques detect before becoming intractable. To this aim, a device equipped with nanostructured gas sensors has been employed airborne molecules blood samples collected from healthy subjects, colorectal affected patients at different stages their pre- post-surgery therapeutic path. Data was scrutinized by using statistical standard highlight differences, through principal component analysis support vector machine classify them. The able readily distinguish between pre-surgery (i.e., taken when patient had cancer), ones up three years following tumor removal) subjects. Finally, correlation sensor responses patient/healthy subject’s gender investigated, resulting negligible. These results pave path toward clinical validation monitor patient’s health status detecting possible relapses, parallel follow-up protocols.

Language: Английский

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Glut-1 exerts anti-tumor activity in glioma by regulating AKT / mTOR signaling pathway

Technology and Health Care, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Objective Glioma is a common tumor in neurosurgery. Glut-1 the main carrier of glucose uptake by cells and can provide energy through glycolytic pathway. However, role related mechanisms glioma have not yet been elucidated. Methods Real time PCR Western blot were done to assess level tissues adjacent tissues. U87 separated into control group; negative (NC group); siRNA group followed analysis expression, cell proliferation MTT assay, invasion, apoptosis cycle flow cytometry AKT / mTOR signaling proteins blot. Results expression was significantly increased patients (P < 0.05) compared its size, pathological grade survival. Down-regulating inhibit increase induce G0 phase arrest, phosphorylation 0.05). Conclusions increased, which features. regulating

Language: Английский

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“Friends or foes”: a new perspective of tumour metabolic transcriptional modification

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 17, 2025

Abstract Energy metabolism plays a pivotal role in cancer clinical treatment and has become an important means of diagnosis tumour progression. However, current research mostly focuses on changes metabolic products neglects the deeper mechanisms transcriptional regulation. This paper proposes new perspective, establishing comprehensive network that reveals interaction between transcription, which explores how affects progression through modifications, provides novel approach for optimizing strategies. viewpoint is conducive to overcoming bottlenecks promoting development drug combinations personalized medicine.

Language: Английский

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Advancing Bladder Cancer Biomarker Discovery: Integrating Mass Spectrometry and Molecular Imaging

Onco, Journal Year: 2025, Volume and Issue: 5(2), P. 13 - 13

Published: March 24, 2025

Bladder cancer, a highly heterogeneous disease, necessitates precise diagnostic and therapeutic strategies to enhance patient outcomes. Metabolomics, through comprehensive small-molecule analysis, provides valuable insights into cancer-associated metabolic alterations at the cellular, tissue, systemic levels. Concurrently, molecular imaging modalities like PET, MRI, CT enable non-invasive, real-time visualization of tumor biology, facilitating spatial functional assessment biomarkers. Key findings highlight identification metabolomic profiles correlated with cancer progression, recurrence, treatment responses across serum, urine, tissue samples. Advanced analytical platforms, such as LC-MS NMR, uncover distinct signatures pathway in glycolysis, amino acid metabolism, lipid biosynthesis. Molecular further enhances staging accuracy monitoring by visualizing activity receptor expression. The integration these technologies addresses limitations invasive methods paves way for precision oncology. Future advancements should focus on multi-omics integration, AI-driven large-scale clinical validation ensure broad accessibility transformative impacts bladder management.

Language: Английский

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Caveolae: Metabolic Platforms at the Crossroads of Health and Disease

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2918 - 2918

Published: March 24, 2025

Caveolae are small flask-shaped invaginations of the plasma membrane enriched in cholesterol and sphingolipids. They play a critical role various cellular processes, including signal transduction, endocytosis, mechanotransduction. Caveolin proteins, specifically Cav-1, Cav-2, Cav-3, addition to their as structural components caveolae, have been found regulate activity signaling molecules. A growing body research has highlighted pivotal caveolae caveolins maintaining metabolic homeostasis. Indeed, studies demonstrated that interact with key insulin signaling, glucose uptake, lipid metabolism, thereby influencing energy production storage. The dysfunction or altered expression associated disorders, obesity, type 2 diabetes, ocular diseases. Remarkably, mutations caveolin genes can disrupt balance, promote oxidative stress, exacerbate dysregulation. This review examines current on molecular mechanisms through which explores involvement pathogenesis discusses potential therapeutic strategies targeting function stabilization restore

Language: Английский

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Beyond Genetics: Exploring Lifestyle, Microbiome, and Social Determinants in Oral Cancer Development

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1094 - 1094

Published: March 25, 2025

Oral cancer refers to cancers originating in the oral cavity and oropharyngeal regions. It is 16th most prevalent sixth leading cause of cancer-related deaths. However, mechanisms its progression are still being understood, interventions provide early diagnosis need be improved. More studies have recently been conducted on cancer, many reviews summarized findings this field, focusing individual factors. few review articles evaluated combinational impacts different factors cancer. This aimed an overview effects three extracellular factors, including lifestyle habits, microbiome, socioeconomic progression. differentially affected by habits; high-sugar diets, processed foods, alcohol, smoking, possibly sleep disorders benefit progression, whereas eating natural such as fruits, vegetables, fish, garlic, drinking tea or coffee, physical exercise can combat it. The microbiome could suppress promote Low status impact development. Furthermore, crosstalk among these affects has limitations not all cancer-affecting important publications. focus should placed multiple treatment. study update researchers landscape help formulate approaches prevention

Language: Английский

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LncRNA SPINT1-AS1 enhances the Warburg effect and promotes the progression of osteosarcoma via the miR-135b-5p/PGAM1 axis

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 1, 2025

Osteosarcoma (OS) is a malignant bone tumor that originates from interstitial tissues and affects the health of children adolescents. Long noncoding RNAs (lncRNAs) are an intriguing category widely distributed endogenous involved in OS progression, many which remain functionally uncharacterized. Herein, we observed increased expression lncRNA SPINT1-AS1 cell lines. Further analysis confirmed promotes proliferation metastasis cells. Moreover, miR-135b-5p was identified as downstream target SPINT1-AS1. Through bioinformatics analysis, PGAM1 mRNA validated via RIP luciferase reporter assays. could enhance by promoting aerobic glycolysis, acting ceRNA binding to miR-135b-5p, thereby increasing expression. Taken together, these results indicate functions promoter regulates progression through miR-135b-5p/PGAM1 axis.

Language: Английский

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WWOX attenuates the progression of gallbladder cancer by suppressing cellular glycolysis through the modulation of the P73/HIF-1α signaling pathway

Tissue and Cell, Journal Year: 2025, Volume and Issue: 95, P. 102885 - 102885

Published: April 4, 2025

Language: Английский

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