Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cells

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: Feb. 4, 2025

At all stages of gastric cancer (GC), cisplatin is the first-line chemotherapeutic agent, but its efficacy remains limited, with a response rate less than 20%, largely because resistance to drug. It aims determine whether macrophage-derived exosomes are involved in mechanism resistance, order identify potential methods for reversing and improving patient outcomes. Macrophages induced by IL-13 IL-4 were characterized using flow cytometry, then co-cultured GC cells cisplatin. Cell viability apoptosis subsequently evaluated through CCK-8 assays cytometry. Exosome miR-194, derived from M2 macrophages, was assess cell survival. Furthermore, mouse model established, miR-194 injected observe tumor growth. Results indicate that macrophages enhance mainly as demonstrated assays. Cellular uptake experiments can transfer exert functional effects. Western blotting PCR analysis further confirmed inhibits enhances downregulating PTEN. Macrophage-derived promotes inhibiting PTEN downregulation. These findings provide new insights theoretical backing clinical treatment strategies GC.

Language: Английский

---

The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 19, 2025

Abstract Renal cell carcinoma (RCC), a therapeutically recalcitrant genitourinary malignancy, exemplifies the profound interplay between oncogenic signaling and metabolic adaptation. Emerging evidence positions reprogramming as central axis of RCC pathogenesis, characterized by dynamic shifts in nutrient utilization that transcend canonical Warburg physiology to encompass lipid anabolism, glutamine auxotrophy, microenvironment-driven plasticity. This orchestrated rewiring cellular energetics sustains tumor proliferation under hypoxia while fostering immunosuppression through metabolite-mediated T exhaustion myeloid-derived suppressor activation. Crucially, exhibits heterogeneity across histological subtypes intratumoral regions—a feature increasingly recognized determinant therapeutic resistance. Our review systematically deciphers molecular architecture metabolism, elucidating how VHL/HIF mutations, mTOR pathway dysregulation, epigenetic modifiers converge reshape glucose flux, droplet biogenesis, amino acid catabolism. We present novel insights into spatial zonation within tumors, where pseudohypoxic niches engage lactate shuttling cholesterol efflux adjacent vasculature, creating pro-angiogenic immunosuppressive microdomains. Therapeutically, we evaluate first-in-class inhibitors targeting rate-limiting enzymes de novo lipogenesis proposing biomarker-driven strategies overcome compensatory highlight synergy glutaminase PD-1 blockade reinvigorating CD8 + function, role lipid-loaded cancer-associated fibroblasts shielding tumors from ferroptosis. Finally, outline translational roadmap integrating multi-omics profiling, functional metabolomics, biology match vulnerabilities with precision therapies.

Language: Английский

---

Single-cell RNA-seq reveals heterogeneity in metastatic renal cell carcinoma and effect of anti-angiogenesis therapy in the pancreas metastatic lesion

Cancer Letters, Journal Year: 2024, Volume and Issue: 601, P. 217193 - 217193

Published: Aug. 17, 2024

Language: Английский

---

Proteoglycan-degrading enzymes engineered for enhanced tumor microenvironment interaction in renal cell carcinoma

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140440 - 140440

Published: Jan. 1, 2025

Language: Английский

---

New mouse models for exploring renal tumor extension into the inferior vena cava

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 5, 2025

Renal tumors with inferior vena cava tumor thrombus (IVCTT) remain a challenge in urology. However, vivo models unavailable, which hampers the elucidation of its pathogenesis, identification therapeutic targets, and screening for effective drugs. In this study, we initially develop two IVCTT BALB/c BALB/c-nu/nu mice using mouse Renca cell line. The pathological features immune microenvironment immunocompetent closely resembles those observed humans. Single-cell transcriptome sequencing, immunohistochemistry multiplex reveal predominance monocytes, macrophages, neutrophils within IVCTT, mirroring cellular composition human IVCTT; however, fewer lymphocytes are observed. immunodeficient progresses much faster than mice. More importantly, successfully use line on nu/nu to create an model. proposed mimic progression renal clarify that system can inhibit progression, provide tools subsequent mechanistic research translational preclinical studies.

Language: Английский

---

Translational Advances in Oncogene and Tumor-Suppressor Gene Research

Cancers, Journal Year: 2025, Volume and Issue: 17(6), P. 1008 - 1008

Published: March 17, 2025

Cancer, characterized by the uncontrolled proliferation of cells, is one leading causes death globally, with approximately in five people developing disease their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology progression, there still a significant gap knowledge about genetic aberrations nuclear DNA damage. The study two critical groups genes—tumor suppressors, which inhibit promote apoptosis, oncogenes, regulate survival—can help to understand genomic behind tumorigenesis, more personalized approaches diagnosis treatment. Aberration tumor undergo two-hit loss-of-function mutations, activated forms proto-oncogenes that experience one-hit gain-of-function are responsible for dysregulation key signaling pathways cell division, such as p53, Rb, Ras/Raf/ERK/MAPK, PI3K/AKT, Wnt/β-catenin. Modern breakthroughs genomics research, like next-generation sequencing, have provided efficient strategies mapping unique changes contribute heterogeneity. Novel therapeutic enabled medicine, helping address variability suppressors oncogenes. This comprehensive review examines molecular mechanisms tumor-suppressor they regulate, epigenetic modifications, heterogeneity, drug resistance drive carcinogenesis. Moreover, explores clinical application sequencing techniques, multiomics, diagnostic procedures, pharmacogenomics, treatment prevention options, discussing future directions emerging technologies.

Language: Английский

---

Platelet Count as an Independent Prognostic Marker in Clear Cell Renal Cell Carcinoma: Insights from Multi-source Data Analysis

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Background: Clear Cell Renal Carcinoma (ccRCC) is one of the most common and aggressive forms kidney cancer, identifying reliable prognostic indicators remains a critical challenge. While various biomarkers have been explored, platelet count has not comprehensively evaluated as an independent factor in ccRCC. Given its clinical accessibility, could be valuable tool for predicting patient outcomes. Objective: This study aims to evaluate potential marker ccRCC patients using multi-source data analysis. Methods: We collected summary from four large-scale genome-wide association studies (GWAS), constructed bidirectional Mendelian randomization (MR) framework, used statistical methods such inverse variance weighted (IVW), MR Egger regression, median, analyzed relationship between risk prognosis clear cell renal carcinoma by propensity score matching reduce selection bias. Then, we retrospectively 231 who underwent partial or radical nephrectomy at First Affiliated Hospital Anhui Medical University 2014 2020 verify accuracy results. Results: found through analysis that increase positively correlated with cancer (OR=1.001, 95% CI: 1.000-1.001, P=0.035). In patients, high was significantly later tumor staging (T, N, AJCC) higher Fuhrman grade (P<0.05). addition, TCGA cohort, overall survival rate (OS) disease-free (DFS) counts were lower than those low Patients burden mutations, especially key genes VHL PBRM1. GO enrichment revealed gene expression changes related proliferation extracellular matrix. Conclusions: Platelet simple, non-invasive, This supports utility stratification, offering integrating it into personalized treatment strategies. By outcomes, can improve decision-making guide therapeutic interventions patients.

Language: Английский

---

6-Phosphogluconate dehydrogenase promotes glycolysis and fatty acid synthesis by inhibiting the AMPK pathway in lung adenocarcinoma cells

Cancer Letters, Journal Year: 2024, Volume and Issue: 601, P. 217177 - 217177

Published: Aug. 23, 2024

Abnormal metabolism has emerged as a prominent hallmark of cancer and plays pivotal role in carcinogenesis progression lung adenocarcinoma (LUAD). In this study, single-cell sequencing revealed that the metabolic enzyme 6-phosphogluconate dehydrogenase (PGD), which is critical regulator pentose phosphate pathway (PPP), significantly upregulated malignant epithelial cell subpopulation during progression. However, precise functional significance PGD LUAD its underlying mechanisms remain elusive. Through integration TCGA database analysis tissue microarray data, it was found expression closely correlated with poor prognosis patients. Moreover, vitro vivo analyses demonstrated knockout inhibition activity mitigated proliferation, migration, invasion cells. Mechanistically, immunoprecipitation-mass spectrometry (IP-MS) for first time IQGAP1 robust novel interacting protein PGD. decreased p-AMPK levels by competitively IQ domain known AMPKα binding partner IQGAP1, promoted glycolysis fatty acid synthesis Furthermore, we combination Physcion (a PGD-specific inhibitor) metformin (an AMPK agonist) could inhibit tumor growth more effectively both vitro. Collectively, these findings suggest potential prognostic biomarker therapeutic target LUAD.

Language: Английский

---

Spatial transcriptomic revealed intratumor heterogeneity and cancer stem cell enrichment in colorectal cancer metastasis

Cancer Letters, Journal Year: 2024, Volume and Issue: 602, P. 217181 - 217181

Published: Aug. 17, 2024

Language: Английский

---

Development and Validation of a Comprehensive Predictive Model for Surgical Planning in Patients with Renal Cell Carcinoma and Inferior Vena Cava Tumor Thrombus

European Journal of Surgical Oncology, Journal Year: 2024, Volume and Issue: 51(1), P. 109381 - 109381

Published: Nov. 12, 2024

Language: Английский

---