Gut microbiota-mediated nucleotide synthesis attenuates the response to neoadjuvant chemoradiotherapy in rectal cancer

Cancer Cell, Год журнала: 2022, Номер 41(1), С. 124 - 138.e6

Опубликована: Дек. 22, 2022

Preoperative neoadjuvant chemoradiotherapy (nCRT) is a standard treatment for locally advanced rectal cancer (LARC) patients, yet little known about the mediators underlying heterogeneous patient response. In this longitudinal study, we performed 16S rRNA sequencing on 353 fecal specimens and find reduced microbial diversity after nCRT. Multi-omics data integration reveals that Bacteroides vulgatus-mediated nucleotide biosynthesis associates with nCRT resistance in LARC nonresponsive tumors are characterized by upregulation of genes related to DNA repair nucleoside transport. Nucleosides supplementation or B. vulgatus gavage protects cells from 5-fluorouracil irradiation treatment. An analysis 2,205 serum samples 735 patients suggests uric acid potential prognosis marker receiving Our unravel role intestinal microbiota-mediated response nCRT, highlight importance deciphering cross-talk between gut microorganisms during therapies.

Язык: Английский

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Dysbiosis of skin microbiome and gut microbiome in melanoma progression

BMC Microbiology, Год журнала: 2022, Номер 22(1)

Опубликована: Фев. 25, 2022

Abstract Background The microbiome alterations are associated with cancer growth and may influence the immune system response to therapy. Particularly, gut has been recently shown modulate melanoma immunotherapy. However, role of skin not well explored in tumour microenvironment link between investigated progression. Therefore, aim present study was examine associations dysbiosis using MeLiM porcine model progression spontaneous regression. Results Parallel analysis cutaneous microbiota faecal same individuals performed 8 12 weeks old piglets. bacterial composition samples analysed by high throughput sequencing V4-V5 region 16S rRNA gene. A significant difference diversity richness tissue healthy piglets control were observed. Both Principal Coordinate Analysis Non-metric multidimensional scaling revealed dissimilarities different communities. Linear discriminant effect size at genus level determined potential biomarkers multiple Lactobacillus, Clostridium sensu stricto 1 Corynebacterium most discriminately higher genera microbiome, while Fusobacterium, Trueperella, Staphylococcus, Streptococcus Bacteroides abundant microbiome. Bacteroides, Fusobacterium Escherichia-Shigella Potential functional pathways based on KEGG database indicated differences predicted profile metabolisms enriched genes related membrane transports allowing for increase intestinal permeability alteration mucosal barrier. Conclusion as identified. provide promising information further studies local involvement support development new therapeutic approaches.

Язык: Английский

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Defective Fe Metal–Organic Frameworks Enhance Metabolic Profiling for High‐Accuracy Diagnosis of Human Cancers

Advanced Materials, Год журнала: 2022, Номер 34(26)

Опубликована: Апрель 16, 2022

Cancers heavily threaten human life; therefore, a high-accuracy diagnosis is vital to protect beings from the suffering of cancers. While biopsies and imaging methods are widely used as current technologies for cancer diagnosis, new detection platform by metabolic analysis expected due significant advantages fast, simple, cost-effectiveness with high body tolerance. However, signal molecule biomarkers too weak acquire diagnosis. Herein, precisely engineered metal-organic frameworks laser desorption/ionization mass spectrometry, allowing favorable charge transfer within molecule-substrate interface mitigated thermal dissipation adjusting phonon scattering metal nodes, developed. Consequently, surprising enhancement ≈10 000-fold achieved, resulting in three major cancers (liver/lung/kidney cancer) area-under-the-curve 0.908-0.964 accuracy 83.2%-90.6%, which promises universal tool large-scale clinical

Язык: Английский

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A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma

Cancer Cell, Год журнала: 2022, Номер 40(9), С. 957 - 972.e10

Опубликована: Авг. 18, 2022

Язык: Английский

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Mass spectrometry‐based extracellular vesicle micromolecule detection in cancer biomarker discovery: An overview of metabolomics and lipidomics

View, Год журнала: 2023, Номер 4(5)

Опубликована: Май 1, 2023

Abstract Extracellular vesicles (EVs) become one of the most important sources cancer biomarkers during past decade due to their wide distribution in body fluids and physiological stability. Previous studies mainly focused on nucleic acids proteins, while lipids metabolites were largely neglected. Noticeably, many those micromolecules exhibited a high abundance EVs. Revealing metabolomics lipidomics EVs would provide more comprehensive information for biomarker discovery. With rapid development mass spectrometry (MS) facilities, MS‐based micromolecule detection has an emerging technique studies. Increasing evidence demonstrated presence EV‐associated different types samples (e.g., cell, urine, serum, stool), which promising performance diagnosis, prognosis, prediction treatment responses. This review aims summarize advances profiling discovery, with emphasis metabolomic lipidomic analytical techniques. Challenges this field, including minimum sample quantity, normalization methods, compound identifications, are also discussed along possible solutions.

Язык: Английский

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Metabolic reprogramming and interventions in endometrial carcinoma

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 161, С. 114526 - 114526

Опубликована: Март 16, 2023

Cancer cells are usually featured by metabolic adaptations that facilitate their growth, invasion, and metastasis. Thus, reprogramming of intracellular energy metabolism is currently one the hotspots in field cancer research. Whereas aerobic glycolysis (known as Warburg effect) has long been considered a dominant form cells, emerging evidence indicates other forms, especially oxidative phosphorylation (OXPHOS), may play critical role at least some types cancer. Of note, women with syndromes (MetS), including obesity, hyperglycemia, dyslipidemia, hypertension, have an increased risk developing endometrial carcinoma (EC), suggesting close link between EC. Interestingly, preferences vary among EC cell types, particularly stem chemotherapy-resistant cells. Currently, it commonly accepted main provider while OXPHOS reduced or impaired. Moreover, agents specifically targeting and/or pathways can inhibit tumor growth promote chemosensitization. For example, metformin weight control not only reduce incidence but also improve prognosis patients. In this review, we comprehensively overview current in-depth understanding relationship provide up-to-date insights into development novel therapies for auxiliary treatment combination chemotherapy EC, those resistant to conventional chemotherapy.

Язык: Английский

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Carbon-based catalysts: advances in synthesizing N-heterocyclic compounds using graphene family and graphite oxide

Research on Chemical Intermediates, Год журнала: 2024, Номер 50(2), С. 485 - 531

Опубликована: Янв. 5, 2024

Язык: Английский

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Identification of intratumoral bacteria that enhance breast tumor metastasis

mBio, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

ABSTRACT The central, mortality-associated hallmark of cancer is the process metastasis. It increasingly recognized that bacteria influence multiple facets progression, but extent to which tumor microenvironment-associated control metastasis in poorly understood. To identify tumor-associated and their role metastasis, we utilized established murine models non-metastatic metastatic breast tumors capable driving disease. We found several species Bacillus genus were unique tumors, cells cultured with a bacterium isolated from thermoamylovorans , produced nearly 3× burden as or tumors. then performed targeted metabolomics on different bacterial B. differentially regulated cell metabolite profiles compared Using these bacteria, de novo sequencing tested for presence genes patient population provide proof-of-concept identifying how specific functions are associated independent species. Together, our data directly demonstrate ability promote through interaction cells. IMPORTANCE Metastasis major barrier long-term survival patients, therapeutic options patients aggressive, forms remain limited. therefore critical understand differences between disease potential methods slowing even stopping In this work, present increasing capabilities sequenced well failed identified metastasis-promoting samples they more likely be mortality. also enrichment functions, providing insight into possible sources bacteria-driven increases types.

Язык: Английский

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Advances in targeting EGFR allosteric site as anti-NSCLC therapy to overcome the drug resistance

Pharmacological Reports, Год журнала: 2020, Номер 72(4), С. 799 - 813

Опубликована: Июль 14, 2020

Abstract Background The epidermal growth factor receptor (EGFR) inhibitors represent the first-line therapy regimen for non-small cell lung cancer (NSCLC). Most of these target ATP-site to stop aggressive development NSCLC. Stabilization ATP-binding on EGFR is difficult due autophosphorylation domain. This leads activation nonintrinsic influence tumor microenvironment and expression anti-apoptotic pathways drug resistance. Methods NSCLC related literature search was carried out using online databases such as Scopus, Web Sciences, PubMed, Protein Data Bank UniPort last ten years selected articles are referred discussion in this review. Results To overcome problem mutations NSCLC, allosteric site targeted, which shows significant therapeutic outcome without causing Compounds like EAI001, EAI045 JBJ-04-125-02, DDC4002 a series small molecules with an affinity towards reported under investigational stage. These compounds categorized fourth-generation anti-NSCLC agents. Conclusion Composition review highlights advantage inhibiting EGFRTK domains presents comparative analysis new agents

Язык: Английский

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Advances and Perspectives in Prostate Cancer Biomarker Discovery in the Last 5 Years through Tissue and Urine Metabolomics

Metabolites, Год журнала: 2021, Номер 11(3), С. 181 - 181

Опубликована: Март 19, 2021

Prostate cancer (PCa) is the second most diagnosed in men worldwide. For its screening, serum prostate specific antigen (PSA) test has been largely performed over past decade, despite lack of accuracy and inability to distinguish indolent from aggressive disease. Metabolomics widely applied biomarker discovery due well-known metabolic reprogramming characteristic cells. Most metabolomic studies have reported alterations urine PCa patients noninvasive collection, but analysis tissue metabolome an ideal approach disclose modifications development. This review aims summarize discuss recent findings discovery. Eighteen metabolites were found consistently altered among different studies, including alanine, arginine, uracil, glutamate, fumarate, citrate. Urine also showed consistency dysregulation 15 and, interestingly, levels valine, taurine, leucine citrate common between studies. These unveil that impact development human may offer a promising strategy find novel biomarkers for diagnosis.

Язык: Английский

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