Regulation of growth, invasion and metabolism of breast ductal carcinoma through CCL2/CCR2 signaling interactions with MET receptor tyrosine kinases DOI Creative Commons

Diana S. Acevedo,

Wei Bin Fang, Vinamratha Rao

et al.

Neoplasia, Journal Year: 2022, Volume and Issue: 28, P. 100791 - 100791

Published: April 8, 2022

With over 60,000 cases diagnosed annually in the US, ductal carcinoma situ (DCIS) is most prevalent form of early-stage breast cancer. Because many DCIS never progress to invasive carcinomas (IDC), overtreatment remains a significant problem. Up 20% patients experience disease recurrence, indicating that standard treatments do not effectively treat for subset patients. By understanding mechanisms progression, we can develop new treatment strategies better tailored The chemokine CCL2 and its receptor CCR2 are known regulate macrophage recruitment during inflammation cancer progression. Recent studies indicate increased CCL2/CCR2 signaling epithelial cells enhance formation IDC. Here, characterized molecular important CCL2/CCR2-mediated Phospho-protein array profiling revealed stimulated phosphorylation MET tyrosine kinases cells. Co-immunoprecipitation proximity ligation assays demonstrated CCL2-induced activity depended on interactions with SRC. Extracellular flux analysis biochemical enhanced glycolytic enzyme expression activity. CRISPR knockout pharmacologic inhibition CCL2/CCR2-induced cell proliferation, survival, migration glycolysis through MET-dependent mechanisms. In animals, inhibitors blocked CCR2-mediated progression metabolism. were significantly co-expressed patient IDC tissues. summary, an mechanism metabolism cancer, clinical implications.

Language: Английский

Carrier-Free Immunotherapeutic Nano-Booster with Dual Synergistic Effects Based on Glutaminase Inhibition Combined with Photodynamic Therapy DOI

Ziyi Mai,

Jing Zhong, Jiasi Zhang

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(2), P. 1583 - 1596

Published: Jan. 3, 2023

The immunotherapeutic effect elicited by photodynamic therapy (PDT) is attenuated tumor defense mechanisms associated with glutamine metabolism, including the metabolic regulation of redox homeostasis and limitation immunosuppressive microenvironment (ITM). Herein, a carrier-free nanobooster C9SN dual synergistic effects was constructed self-assembly glutaminase (GLS) inhibitor compound 968 (C968) photosensitizer Chlorin e6. C968-mediated GSH deprivation through inhibiting metabolism prevented PDT-generated reactive oxygen species from being annihilated GSH, amplifying intracellular oxidative stress, which caused severe cell death also enhanced immunogenic (ICD) effect. In addition, genome-wide analysis carried out using RNA-sequencing to evaluate changes in transcriptome induced stress. Thereafter, neoantigens generated ICD promoted maturation dendritic cells, thereby recruiting activating cytotoxic T lymphocytes (CTLs). Meanwhile, remodeled ITM blocking polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, further recruited activated CTLs. Ultimately, this suppressed primary distant tumors. This "kill two birds one stone" strategy would shed light on enhancing immunogenicity alleviating immunosuppression improve PDT.

Language: Английский

Citations

71
Cancer metabolites: promising biomarkers for cancer liquid biopsy DOI Creative Commons
Wenxiang Wang, Zhiwei Rong, Guangxi Wang

et al.

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: June 30, 2023

Abstract Cancer exerts a multitude of effects on metabolism, including the reprogramming cellular metabolic pathways and alterations in metabolites that facilitate inappropriate proliferation cancer cells adaptation to tumor microenvironment. There is growing body evidence suggesting aberrant play pivotal roles tumorigenesis metastasis, have potential serve as biomarkers for personalized therapy. Importantly, high-throughput metabolomics detection techniques machine learning approaches offer tremendous clinical oncology by enabling identification cancer-specific metabolites. Emerging research indicates circulating great promise noninvasive detection. Therefore, this review summarizes reported abnormal cancer-related last decade highlights application liquid biopsy, specimens, technologies, methods, challenges. The provides insights into promising tool applications.

Language: Английский

Citations

46
Macrocycles and macrocyclization in anticancer drug discovery: Important pieces of the puzzle DOI
Chao Zhang,

Fenfen Liu,

You‐Ming Zhang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116234 - 116234

Published: Feb. 13, 2024

Language: Английский

Citations

20
Inside the genome: understanding genetic influences on oxidative stress DOI Creative Commons
Hari Krishnan Krishnamurthy,

Imbaasree Rajavelu,

Michelle Pereira

et al.

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: June 25, 2024

Genetics is a key factor that governs the susceptibility to oxidative stress. In body, burden regulated by balance between prooxidant genes orchestrate processes produce oxidant species, while antioxidant aid those involved in scavenging these species. Together, two components maintaining body. Genetic variations can influence expression and activity of encoded proteins which then affect their efficiency regulating redox processes, thereby increasing risk This review studies single nucleotide polymorphisms (SNPs) bear relevance stress exploring genes, such as XDH, CYBA, CYP1A1, PTGS2, NOS, MAO including SOD, CAT, GPX, GSS, GLUL, GSR, GSTM1, GSTM5, GSTP1, TXN HMOX1. Early identification individuals at increased possible from assessment sequence genes. Integrating genetic insights into management measures pave way for personalized medicine tailors’ healthcare approaches individual profiles. Effective along with routine quantification biological markers improve monitor treatment strategies, enhancing mitigation maintain cellular health promote longevity.

Language: Английский

Citations

16
The role of HIF-1α in hypoxic metabolic reprogramming in osteoarthritis DOI Creative Commons
Jie Zhang,

Peng Gao,

Weirong Chang

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107649 - 107649

Published: Feb. 1, 2025

The joint dysfunction caused by osteoarthritis (OA) is increasingly becoming a major challenge in global healthcare, and there currently no effective strategy to prevent the progression of OA. Therefore, better elucidating relevant mechanisms OA occurrence development will provide theoretical basis for formulating new prevention control strategies. Due long-term exposure cartilage tissue hypoxic microenvironment joints, metabolic reprogramming changes occur. Hypoxia-inducible factor-1alpha (HIF-1α), as core gene regulating hypoxia response vivo, plays an important regulatory role metabolism chondrocytes. HIF-1α adapts such glycolysis, oxidative phosphorylation (OXPHOS), amino acid metabolism, lipid In addition, also regulates macrophage polarization synovial inflammation, chondrocytes degeneration extracellular matrix (ECM) degradation, subchondral bone remodeling angiogenesis OA, affects pathophysiological Consequently, regulation has become therapeutic target this article reviews mechanism affecting chondrocyte reprogramming, focusing on summarizes potential ingredients or targets targeting order more beneficial treatment clinical drugs.

Language: Английский

Citations

2
Loss of CD4+ T cell-intrinsic arginase 1 accelerates Th1 response kinetics and reduces lung pathology during influenza infection DOI Creative Commons
Erin E. West,

Nicolas S. Merle,

Marcin M. Kamiński

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(9), P. 2036 - 2053.e12

Published: Aug. 11, 2023

Arginase 1 (Arg1), the enzyme catalyzing conversion of arginine to ornithine, is a hallmark IL-10-producing immunoregulatory M2 macrophages. However, its expression in T cells disputed. Here, we demonstrate that induction Arg1 key feature lung CD4+ during mouse vivo influenza infection. Conditional ablation accelerated both virus-specific helper (Th1) effector responses and resolution, resulting efficient viral clearance reduced pathology. Using unbiased transcriptomics metabolomics, found Arg1-deficiency was distinct from Arg2-deficiency caused altered glutamine metabolism. Rebalancing this perturbed flux normalized cellular Th1 response. rare ARG1-deficient patients or CRISPR-Cas9-mediated ARG1-deletion healthy donor phenocopied murine phenotype. Collectively, cell-intrinsic functions as an unexpected rheostat regulating kinetics mammalian lifecycle with implications for Th1-associated tissue pathologies.

Language: Английский

Citations

23
Emerging Chemodynamic Nanotherapeutics for Cancer Treatment DOI
Dongqi Sun, Xinxin Sun, Xuan Zhang

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(22)

Published: May 16, 2024

Abstract Chemodynamic therapy (CDT) has emerged as a transformative paradigm in the realm of reactive oxygen species ‐mediated cancer therapies, exhibiting its potential sophisticated strategy for precise and effective tumor treatment. CDT primarily relies on metal ions hydrogen peroxide to initiate Fenton or Fenton‐like reactions, generating cytotoxic hydroxyl radicals. Its notable advantages treatment are demonstrated, including specificity, autonomy from external triggers, favorable side‐effect profile. Recent advancements nanomedicine devoted enhancing CDT, promising comprehensive optimization efficacy. This review systematically elucidates cutting‐edge achievements chemodynamic nanotherapeutics, exploring strategies enhanced improved microenvironment modulation, regulation energy metabolism. Moreover, detailed analysis diverse CDT‐mediated combination therapies is provided. Finally, concludes with discussion prospects intrinsic challenges application nanotherapeutics domain

Language: Английский

Citations

15
Micropeptides: potential treatment strategies for cancer DOI Creative Commons

He Zhou,

Yan Wu,

Cai Ji

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 15, 2024

Abstract Some noncoding RNAs (ncRNAs) carry open reading frames (ORFs) that can be translated into micropeptides, although have been previously assumed to constitute a class of RNA transcripts without coding capacity. Furthermore, recent studies revealed ncRNA-derived micropeptides exhibit regulatory functions in the development many tumours. Although some these inhibit tumour growth, others promote it. Understanding role ncRNA-encoded cancer poses new challenges for research, but also offers promising prospects therapy. In this review, we summarize types ncRNAs encode highlighting technical developments made it easier research such as ribosome analysis, mass spectrometry, bioinformatics methods, and CRISPR/Cas9. based on distribution different subcellular locations, explain biological human cancers discuss their underestimated potential diagnostic biomarkers anticancer therapeutic targets clinical applications, information may contribute discovery micropeptide-based tools early diagnosis drug development.

Language: Английский

Citations

9
Nanomaterial-based regulation of redox metabolism for enhancing cancer therapy DOI

Xiaodan Jia,

Yue Wang, Yue Qiao

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

This review provides a comprehensive summary of the dysregulation redox metabolism in cancer cells and advantages latest advances nanomaterial-assisted metabolic regulation therapy.

Language: Английский

Citations

9
Glutamine Supplementation as an Anticancer Strategy: A Potential Therapeutic Alternative to the Convention DOI Open Access
Hayato Muranaka, Rasaq Akinsola, Sandrine Billet

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 1057 - 1057

Published: March 5, 2024

Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into intricate dynamics surrounding both glutamine antagonism strategies supplementation within context treatment, emphasizing critical role progression Glutamine antagonism, aiming disrupt tumor growth by targeting metabolic pathways, is challenged adaptive nature cells complex microenvironment, potentially compromising its therapeutic efficacy. In contrast, supports improves gut integrity, alleviates treatment-related toxicities, patient well-being. Moreover, recent studies highlighted contributions epigenetic regulation potential bolster anti-cancer functions. However, implementation necessitates careful consideration interactions with ongoing treatment regimens delicate equilibrium between supporting normal function promoting tumorigenesis. By critically assessing implications supplementation, this aims offer comprehensive insights for effective management.

Language: Английский

Citations

7