Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 6, 2025

Abstract Hypoxia-inducible factors (HIFs) are essential transcription that orchestrate cellular responses to oxygen deprivation. HIF-1α, as an unstable subunit of HIF-1, is usually hydroxylated by prolyl hydroxylase domain enzymes under normoxic conditions, leading ubiquitination and proteasomal degradation, thereby keeping low levels. Instead hypoxia, sometimes even in normoxia, HIF-1α translocates into the nucleus, dimerizes with HIF-1β generate then activates genes involved adaptive such angiogenesis, metabolic reprogramming, survival, which presents new challenges insights its role processes. Thus, review delves mechanisms HIF-1 maintains stability normoxia including but not limited giving transcriptional, translational, well posttranslational regulation underscore pivotal adaptation malignancy. Moreover, extensively cancer cardiovascular diseases potentially serves a bridge between them. An overview HIF-1-related drugs approved or clinical trials summarized, highlighting their potential capacity for targeting toxicity related treatment. The provides comprehensive insight HIF-1’s regulatory mechanism paves way future research therapeutic development.

Language: Английский

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Emerging Nanoparticle-Based Diagnostics and Therapeutics for Cancer: Innovations and Challenges

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 70 - 70

Published: Jan. 7, 2025

Malignant growth is expected to surpass other significant causes of death as one the top reasons for dismalness and mortality worldwide. According a World Health Organization (WHO) study, this illness approximately between 9 10 million instances deaths annually. Chemotherapy, radiation, surgery are three main methods treating cancer. These seek completely eradicate all cancer cells while having fewest possible unintended impacts on healthy cell types. Owing lack target selectivity, majority medications have substantial side effects. On hand, nanomaterials transformed identification, diagnosis, management Nanostructures with biomimetic properties been grown late, fully intent observing sickness. nanostructures be consumed by in areas profound disease. Furthermore, because their extraordinary physicochemical properties, which incorporate nanoscale aspects, more prominent surface region, explicit geometrical features, ability embody different substances within or outside surfaces, remarkable nano-vehicles conveying restorative specialists designated regions. This review discusses recent developments nanostructured materials such graphene, dendrimers, cell-penetrating peptide nanoparticles, nanoliposomes, lipid magnetic nano-omics diagnosis

Language: Английский

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Transcriptomic and proteo-metabolic determinants of the grading system in clear cell renal cell carcinoma

Urologic Oncology Seminars and Original Investigations, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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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

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A pilot metabolomics study on clear cell renal cell carcinoma

BMC Urology, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 9, 2025

Clear cell renal carcinoma (ccRCC) is fundamentally a metabolic disease. To investigate the underlying metabolite changes in occurrence of ccRCC, we analyzed untargeted metabolomics 15 ccRCC samples and paired adjacent non-malignant tissues by UHPLC-MS/MS analyses. In this study, 511 differential metabolites were screened, which top ten up-regulated histamine, 1-methylnicotinamide, L-kynurenine, cortisol, tetrahydrocorticosterone, calcitriol, D-erythrose 4-phosphate, citric acid, sedoheptulose 1,7-bisphosphate, UDP-alpha-D-galactose, down-regulated D-cysteine, acetylcholine, pantothenic cytosine, UMP, biocytin, dUMP, 5-phosphoribosyl 1-pyrophosphate, cytidine-5'-monophosphate, 16α-hydroxyestrone. KEGG pathways enrichment analysis further demonstrated several highlighted pathways: steroid hormone biosynthesis, pyrimidine metabolism, vitamin digestion absorption. Our study reveals patterns provides insight into potential biomarker panel to diagnose ccRCC.

Language: Английский

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Effect of microenvironmental viscosity on the emergence of colon cancer cell resistance to doxorubicin

Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Microenvironmental viscosity enhanced doxorubicin resistance of colon cancer cells.

Language: Английский

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Bioinformatics analysis of mitochondrial metabolism-related genes demonstrates their importance in renal cell carcinoma

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 9, 2025

Clear cell renal carcinoma (ccRCC) is resistant to radiotherapy and chemotherapy. Thus, it necessary find new diagnostic markers therapeutic targets increase the overall outcomes of ccRCC. Recent studies have shown that methods interfere with energy transfer system can also positively affect treatment process. The present study focused on finding associated mitochondrial metabolic pathways outcome For this purpose, we investigated various aspects relationship between metabolism ccRCC based analysis gene network connections differentially expressed genes, through assessment protein–protein interaction, mutations, promoter methylation related genes. We interaction miRNAs immune infiltration analysis. Through these steps, provided a list possible for current further proved importance in pathogenesis from be used

Language: Английский

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The evolving landscape of renal surgery for complex renal masses (CRM): implications for oncologic and functional outcomes

Mini-invasive Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Partial nephrectomy (PN) has become the standard of treatment for most T1 renal masses and is suitable selected T2 cortical masses. In this setting, management complex (CRM) requires a thorough understanding potential risks benefits both PN radical (RN). Indeed, thanks to advent robotic surgery, indications have expanded include larger tumors CRM, despite associated surgical complexity oncologic risks. The decision-making process CRM with or RN complex. Thus, current review aims explore essentials patients identify research gaps, address clinical challenge determining approach. Current evidence suggests that while offers clear advantage in tissue preservation, it may carry higher perioperative compared RN. However, these should be balanced long-term function preservation. conclusion, further high-quality, prospective studies are needed better define comparative effectiveness vs . guide CRM.

Language: Английский

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The application value of preoperative F-FDG PET/CT in preoperative localized clear cell renal cell carcinoma

Journal of Cancer Metastasis and Treatment, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Aim: In cancer tissues, glycolysis metabolism is often heightened, making 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) useful for assessing glucose metabolism. However, the kidneys' high makes it difficult to distinguish between normal renal tissue and cancer. This study aims evaluate maximum standardized uptake value (SUVmax) in using PET/CT determine its relationship prognosis. Methods: We also aim examine correlation SUVmax clinical parameters potential link enrolled 105 patients who underwent FDG-PET/CT March 2012 October 2017. These patients, diagnosed with localized cell carcinoma (RCC), surgery were pathologically confirmed have clear RCC (ccRCC). investigated impact of other on recurrence. Results: C-reactive protein (CRP) associated tumor progression, alongside stage, nuclear grade, microvascular invasion [v(+)], tumor-infiltrating lymphocytes (TILs). Multivariate analysis recurrence-free survival (RFS) as endpoint indicated significant results (SUVmax ≥ 3.7: relative risk 8.98, P < 0.01; CRP 0.11 mg/dL: 6.03, 0.01, n = 89). curve RFS, or elevated predicted poor prognosis, further worsening when v(+) was added. Conclusion: a strong prognostic factor outcomes. factor, though should be interpreted cautiously, reflects overall systemic conditions may not exclusively represent activity. Further research into pre-treatment prognosis prediction anticipated.

Language: Английский

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CECT-Based Radiomic Nomogram of Different Machine Learning Models for Differentiating Malignant and Benign Solid-Containing Renal Masses

Journal of Multidisciplinary Healthcare, Journal Year: 2025, Volume and Issue: Volume 18, P. 421 - 433

Published: Jan. 1, 2025

This study aimed to explore the value of a radiomic nomogram based on contrast-enhanced computed tomography (CECT) for differentiating benign and malignant solid-containing renal masses. A total 122 patients with pathologically confirmed (n=47) or (n=75) masses were enrolled in this study. Radiomic features extracted from arterial, venous delayed phases further analysed by dimensionality reduction selection. Four mainstream machine learning algorithm training models, namely, support vector (SVM), k-nearest neighbour (kNN), light gradient boosting (LightGBM) logistic regression (LR), constructed determine best classifier model. Univariate multivariate analyses used clinical characteristics constructing The signatures integrated construct combined Receiver operating characteristic (ROC) curves area under curve (AUC) evaluate performance nomogram, signature, Thirteen selected development signature. Among various LR model demonstrated superior predictive efficiency robustness, yielding an AUC 0.952 cohort 0.887 test cohort. was 0.854 0.747 Furthermore, which incorporated sex, age, alcohol consumption history, exhibited excellent discriminative performance, 0.973 0.900 CECT offers promising noninvasive approach distinguishing solid tool can be guide treatment strategies effectively provide valuable insights clinicians.

Language: Английский

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