The Role of Chronic Inflammation in Pediatric Cancer DOI Open Access

Christine Mella,

Panogiotis Tsarouhas,

Maximillian Brockwell

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(1), P. 154 - 154

Published: Jan. 6, 2025

Inflammation plays a crucial role in wound healing and the host immune response following pathogenic invasion. However, unresolved chronic inflammation can result tissue fibrosis genetic alterations that contribute to pathogenesis of human diseases such as cancer. Recent scientific advancements exploring underlying mechanisms malignant cellular transformations cancer progression have exposed significant disparities between pediatric adult-onset cancers. For instance, cancers tend lower mutational burdens arise actively developing tissues, where cell-cycle dysregulation leads gene, chromosomal, fusion gene development not seen counterparts. As such, findings adult cannot be directly applied cancers, unique mutations inherent etiologies remain poorly understood. Here, we review processes chromosomal instability, tumor microenvironment, tumorigenesis transformation explore current therapeutic interventions maintain and/or restore inflammatory homeostasis.

Language: Английский

Association of Intratumoral Microbiota With Prognosis in Patients With Nasopharyngeal Carcinoma From 2 Hospitals in China DOI Creative Commons
Han Qiao,

Xi-Rong Tan,

Hui Li

et al.

JAMA Oncology, Journal Year: 2022, Volume and Issue: 8(9), P. 1301 - 1301

Published: July 14, 2022

Microbiota-tumor interactions have qualified microbiota as a promising prognostic biomarker in various types of cancers. Although the nasopharynx acts crucial niche upper respiratory tract microbiome, whether intratumoral exists and its clinical significance nasopharyngeal carcinoma (NPC) remain uncertain.To evaluate for individual prognostication patients with NPC.This retrospective cohort study included NPC biopsy samples from 2 hospitals: Sun Yat-sen University Cancer Center (Guangzhou, China) Zhejiang Hospital (Hangzhou, between January 2004 November 2016, follow-up through 2020. A total 802 were according to following criteria: histologically proven NPC, without distant metastasis at initial diagnosis, had not received antitumor treatment before sampling, aged 18 70 years, complete medical records regular follow-up, history cancer, successfully extracted enough DNA experiments.The primary end point was disease-free survival, secondary points metastasis-free survival overall survival. To assess existence load 96 or tumor relapse, 16S rRNA sequencing quantitative polymerase chain reaction used. The associations bacterial outcome evaluated 241 fresh-frozen (training cohort) validated paraffin-embedded internal (n = 233) external 232) validation cohorts. Metagenomic transcriptome analyses performed ascertain origin underlying mechanism bacteria.A (mean [SD] age, 46.2 [10.6] years; 594 [74.1%] male) enrolled. Microbiota presented within tissues, among which Corynebacterium Staphylococcus predominated. Patients high training inferior rates (hazard ratio [HR], 2.90; 95% CI, 1.72-4.90; P < .001), (HR, 3.18; 1.58-6.39; 3.41; 1.90-6.11, .001) than those low load, finding that by Single-nucleotide variant analysis revealed main bacteria. Transcriptome digital pathology demonstrated higher negatively associated T-lymphocyte infiltration.Intratumoral robust tool this study, indicating potential guidance decisions different levels risk malignant progression.

Language: Английский

Citations

98
Acetyltransferase fromAkkermansia muciniphilablunts colorectal tumourigenesis by reprogramming tumour microenvironment DOI
Yi Jiang, Yuejie Xu, Chang Zheng

et al.

Gut, Journal Year: 2023, Volume and Issue: 72(7), P. 1308 - 1318

Published: Feb. 8, 2023

The protein post-translational modification (PTM) in host cells can be rewritten by bacterial enzymes and represents an unprecedented mechanism the communication between intestinal flora host. Although Akkermansia muciniphila has been widely investigated as a probiotic blunts colitis-associated tumourigenesis mice, there is little understanding regarding whether A. involved PTM of colorectal cancer (CRC). This study investigates how engages CRC.The secreting extracellular vesicles from purified Amuc_2172 were used for different mice models. Amuc_2172-induced immune activity CD8+ cytotoxic T lymphocytes (CTLs) evaluated vitro vivo. acetyltransferase downstream target genes investigated.Amuc_2172, general control non-derepressible 5-related muciniphila, was accessible to macropinocytosis functioned Lys14 on histone H3 (H3K14ac). Elevated H3K14ac Hspa1a loci promoted transcription secretion heat-shock 70 (HSP70) cells. High level HSP70 CTLs Moreover, bioengineered nanoparticles provided safe reliable drug delivery strategy CRC treatment allograft model.Amuc_2172 reprogrammed tumour microenvironment inducing promoting CTL-related response process tumourigenesis.

Language: Английский

Citations

81
Ferroptosis in colorectal cancer: Potential mechanisms and effective therapeutic targets DOI Open Access

Yunhan Wang,

Zongying Zhang,

Weichen Sun

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 153, P. 113524 - 113524

Published: Aug. 13, 2022

Colorectal cancer (CRC) is a common malignant tumor characterized by unchecked division and survival of abnormal cells in the colon or rectum with high morbidity mortality. Despite rapid development early screening methods improved therapies, prognosis CRC not satisfactory. Identification new biomarkers for detection more effective therapies are still urgent tasks current studies to achieve ideal treatment CRC. Ferroptosis recently emerged novel regulated form cell death massive accumulation iron-dependent lipid peroxidates, making it morphologically molecularly distinct from apoptosis, death, autophagy. Accumulating have shown that induction ferroptosis successfully eliminates resistant other modes death. Thus, may become direction design therapy. Although many research articles investigated possible roles CRC, study summarizes main findings, including regulators mechanisms action, available. Herein, recent literature regarding on progression were summarized, mainly focusing molecular biological vitro vivo. In particular, numerous regulators, such as SLC7A11, reactive oxygen species (ROS), glutathione (GSH), iron, discussed application ferroptosis-associated genes diagnosis was explored. addition, an outlook future barriers corresponding solutions discussed.

Language: Английский

Citations

77
Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy DOI Creative Commons
Dominic Denk,

Valentina Petrocelli,

Claire Conche

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(11), P. 2059 - 2073.e8

Published: Oct. 19, 2022

T memory stem cells (TSCM) display increased self-renewal and prolonged survival capabilities, thus preventing cell exhaustion promoting effective anti-tumor responses. TSCM can be expanded by Urolithin A (UA), which is produced the commensal gut microbiome from foods rich in ellagitannins known to improve mitochondrial health. Oral UA administration tumor-bearing mice conferred strong CD8+ immunity, whereas ex vivo pre-treated displayed improved function upon adoptive transfer. UA-induced formation depended on Pink1-mediated mitophagy triggering cytosolic release of phosphatase Pgam5. Cytosolic Pgam5 dephosphorylated β-catenin, drove Wnt signaling compensatory biogenesis. Collectively, we unravel a critical pathway linking suggest that well-tolerated metabolic compound represents an attractive option immune therapy.

Language: Английский

Citations

75
Association between C-reactive protein-albumin-lymphocyte (CALLY) index and overall survival in patients with colorectal cancer: From the investigation on nutrition status and clinical outcome of common cancers study DOI Creative Commons
Ming Yang, Shiqi Lin, Xiaoyue Liu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 30, 2023

Background Colorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development influenced by inflammation, nutrition, immune status. Therefore, we combined C-reactive protein (CRP), albumin, lymphocyte, which could reflect above status, to be CRP-albumin-lymphocyte (CALLY) index, evaluated association with overall survival (OS) in patients CRC. Methods The clinicopathological laboratory characteristics of 1260 CRC were collected from Investigation on Nutrition Status Clinical Outcome Common Cancers (INSCOC) study. Cox regression analysis was performed assess between CALLY index OS. A nomogram including sex, age, TNM stage constructed. Concordance Index (C-index) utilized evaluate prognostic value classical factors, such as modified Glasgow score (mGPS), neutrocyte lymphocyte ratio (NLR), systemic inflammation (SII), platelet (PLR), well stage. Results Multivariate analyses demonstrated that independently associated OS [Hazard (HR) = 0.91, 95% confidence interval (CI) 0.87-0.95, P &lt;0.001]. showed highest (C-index 0.666, CI 0.638-0.694, &lt;0.001), followed mGPS, NLR, SII, PLR. higher 0.784, 0.762-0.807, &lt;0.001) than Conclusion factors. provide more accurate prediction

Language: Английский

Citations

67
Methods and biomarkers for early detection, prediction, and diagnosis of colorectal cancer DOI Open Access
Yue Zhang, Yin Wang, Bingqiang Zhang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114786 - 114786

Published: April 27, 2023

Colorectal cancer (CRC) is one of the most common digestive diseases worldwide. It has steadily ascended to top three cancers in terms incidence and mortality. The primary cause inability diagnose it at an early stage. Therefore, detection diagnosis are essential for colorectal prevention. Although there now various methods CRC detection, addition recent developments surgical multimodal therapy, poor prognosis late still remain significant. Thus, important investigate novel technologies biomarkers improve sensitization specification diagnosis. Here, we present some CRC, hope this review will encourage adoption screening programs clinical use these potential molecules as prognosis.

Language: Английский

Citations

67
The microbial landscape of colorectal cancer DOI
Maxwell T. White, Cynthia L. Sears

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 22(4), P. 240 - 254

Published: Oct. 4, 2023

Language: Английский

Citations

65
Role of Epithelial to Mesenchymal Transition in Colorectal Cancer DOI Open Access
Jian Lu, Marko Kornmann, Benno Traub

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14815 - 14815

Published: Oct. 1, 2023

The epithelial–mesenchymal transition (EMT) is a cellular reprogramming process that occurs during embryonic development and adult tissue homeostasis. This involves epithelial cells acquiring mesenchymal phenotype. Through EMT, cancer acquire properties associated with more aggressive EMT its opposite, mesenchymal–epithelial (MET), have been described in tumors over the past ten years, including colorectal (CRC). When activated, expression of marker E-cadherin decreased vimentin raised. As result, temporarily take on phenotype, becoming motile promoting spread tumor cells. Epithelial–mesenchymal plasticity (EMP) has become hot issue CRC because strong inducers (such as transforming growth factor β, TGF-β) can initiate regulate metastasis, microenvironment, immune system resistance CRC. In this review, we into account significance EMT-MET impact cells’ prognosis analysis connection between stem (CCSCs) will help to further clarify current meager understandings EMT. Recent advances affecting important transcription factors CCSCs are highlighted. We come conclusion regulatory network for complicated, great deal crosstalk alternate paths. More thorough research required effectively connect clinical management biomarkers targeted treatments

Language: Английский

Citations

61
The Role of Fusobacterium nucleatum in Oral and Colorectal Carcinogenesis DOI Creative Commons
Pamela Pignatelli,

Federica Nuccio,

Adriano Piattelli

et al.

Microorganisms, Journal Year: 2023, Volume and Issue: 11(9), P. 2358 - 2358

Published: Sept. 20, 2023

In recent years, several studies have suggested a strong association of microorganisms with human cancers. Two periodontopathogenic species in particular been mentioned frequently: Fusobacterium nucleatum (F. nucleatum) and Porphyromonas gingivalis. Chronic periodontal disease has reported to be risk factor for oral squamous cell carcinoma (OSCC), colorectal cancer (CRC) pancreatic cancer. F. is Gram-negative anaerobic bacterium that lives the cavity, urogenital, intestinal upper digestive tract. It plays significant role as co-aggregation factor, almost all bacterial participate plaque formation acting bridge between early late colonizers. nucleatum, gives an important inflammatory contribution tumorigenesis progression associated epithelial-derived malignancies, such OSCC CRC. produces adhesion protein, FadA, which binds VE-cadherin on endothelial cells E-cadherins epithelial cells. The last binding activates oncogenic pathways, Wnt/βcatenin, carcinogenesis. also affects immune response because its Fap2 protein interacts receptor named TIGIT present some T natural killer inhibiting activities. Morover, release outer membrane vesicles (OMVs), induce production proinflammatory cytokines initiating inflammation. migrates from cavity reaches colon hematogenously but it not known if bloodstream CRC free, erythrocyte-bound bacteria or OMV. abundance tissue inversely correlated overall survival (OS). prevention treatment through improvement hygiene should included protocols. FadA virulence factors may serve novel targets therapeutic intervention

Language: Английский

Citations

60
Colorectal Cancer Organoid–Stroma Biobank Allows Subtype-Specific Assessment of Individualized Therapy Responses DOI Creative Commons
Henner F. Farin, Mohammed H. Mosa, Benardina Ndreshkjana

et al.

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(10), P. 2192 - 2211

Published: July 25, 2023

In colorectal cancers, the tumor microenvironment plays a key role in prognosis and therapy efficacy. Patient-derived organoids (PDTO) show enormous potential for preclinical testing; however, cultured cells lose important characteristics, including consensus molecular subtypes (CMS). To better reflect cellular heterogeneity, we established cancer organoid-stroma biobank of matched PDTOs cancer-associated fibroblasts (CAF) from 30 patients. Context-specific phenotyping showed that xenotransplantation or coculture with CAFs improves transcriptomic fidelity instructs subtype-specific stromal gene expression. Furthermore, functional profiling exposed CMS4-specific therapeutic resistance to gefitinib SN-38 prognostic expression signatures. Chemogenomic library screening identified patient- therapy-dependent mechanisms MET as common target. Our results demonstrate phenotypes are encrypted epithelium plastic fashion strongly depends on context. Consequently, essential faithful representation responses ex vivo. Systematic characterization provides resource context dependency cancer. We subtype memory is independent specific driver mutations. data underscore importance cocultures improved testing identification mechanisms. This article featured Selected Articles Issue, p. 2109.

Language: Английский

Citations

58