The Value of CXCL1, CXCL2, CXCL3, and CXCL8 as Potential Prognosis Markers in Cervical Cancer: Evidence of E6/E7 from HPV16 and 18 in Chemokines Regulation

Biomedicines, Journal Year: 2023, Volume and Issue: 11(10), P. 2655 - 2655

Published: Sept. 28, 2023

Cervical cancer (CC) is a serious global health issue, and it well-known that HPV infection the main etiological factor triggers carcinogenesis. In cancer, chemokine ligands receptors are involved in tumor cell growth, metastasis, leukocyte infiltration, angiogenesis; however, information on role played by E6/E7 of HPV16/18 modulation chemokines very limited. Therefore, this study aimed to determine whether differentially expressed CC-derived lines; if oncoproteins from HPV16 18 capable mediating expression, what expression profile tissues derived CC their impact overall survival patients with pathology? For purpose, RNA sequencing real-time PCR were performed SiHa, HeLa, C33A tumorigenic lines, non-tumorigenic HaCaT cells, HPV-transduced models. Furthermore, analysis executed 304 22 normal tissue samples The Cancer Genome Atlas (TCGA) repository. results demonstrate CXCL1, CXCL2, CXCL3, CXCL8 regulated 18, overexpressed biopsies, higher related worse prognostic survival.

Language: Английский

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Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content

Frontiers in Pain Research, Journal Year: 2024, Volume and Issue: 5

Published: Jan. 18, 2024

Objectives This explorative study analyses interrelationships between peripheral compounds in saliva, plasma, and muscles together with body composition variables healthy subjects fibromyalgia patients (FM). There is a need to better understand the extent cytokines chemokines are associated which differentiate FM from controls. Methods Here, 32 female 30 age-matched controls underwent clinical examination that included blood sample, saliva samples, pain threshold tests. In addition, completed health questionnaire. From these panel of 68 mainly were determined. Microdialysis trapezius erector spinae muscles, phosphorus-31 magnetic resonance spectroscopy muscle, whole-body imaging for determination (BC)—i.e., muscle volume, fat content infiltration—were also performed. Results After standardizing BC measurements remove confounding effect Body Mass Index, infiltration generally increased, fat-free volume decreased FM. Mainly proteins differentiated When including all investigated variables, most important, followed by plasma. Various plasma correlated positively intensity negatively thresholds taken together. A mix increased an index covering different tissues. analysis, several identified as important regressors, although many remained significant. Discussion Peripheral factors group differentiation (but not plasma), significantly membership The importance when included. Plasma sensitivity. Cytokines index. Conclusion Our findings associations tissues confirm inflammation immune secreted adipose tissue. clearly characterized complex interactions central nervous systems, nociceptive, immune, neuroendocrine processes.

Language: Английский

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Altered gut microbiome drives heightened pain sensitivity in a murine model of metastatic triple-negative breast cancer

American Journal of Cancer Research, Journal Year: 2024, Volume and Issue: 14(1), P. 274 - 299

Published: Jan. 1, 2024

The microbiota residing in the gut environment is essential for host homeostasis.Increasing evidence suggests that microbial perturbation (dysbiosis) regulates cancer initiation and progression at local distant sites.Here, we have identified dysbiosis with depletion of commensal bacteria as a host-intrinsic factor associated metastatic dissemination to bone.Using mouse model triple-negative mammary cancer, demonstrate pre-established disruption homeostasis using an antibiotic cocktail increases tumor growth, enhanced circulating cells, subsequent bone.We found presence pathogenic loss antibiotic-induced sustained inflammation.Increased secretion G-CSF MMP-9 intestinal tissues, followed by increased neutrophil infiltration severe systemic inflammation tumor-bearing mice, indicates direct consequence dysbiotic microbiome.Increased bone niche facilitates extravasation transendothelial migration cells.It provides novel, pre-established, favorable form immunosuppressive pre-metastatic niche.The cells disrupts balance between osteoblasts osteoclasts, promotes osteoclast differentiation, remodels structure.Excessive resorption osteoclasts causes degradation ultimately extreme pain model.In clinical settings, metastasis intractable severely compromises quality life these patients.

Language: Английский

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CXCL5 as a biomarker for early diagnosis and prognosis of sepsis: A comprehensive clinical evaluation

Clinical Biochemistry, Journal Year: 2025, Volume and Issue: 136, P. 110878 - 110878

Published: Jan. 7, 2025

Language: Английский

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Inflammatory biomarkers and therapeutic potential of milk exosome-mediated CCL7 siRNA in murine intestinal ischemia-reperfusion injury

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 20, 2025

Background Intestinal ischemia-reperfusion injury (IIRI) is a severe clinical condition associated with high morbidity and mortality. Despite advances in understanding the pathophysiology of IIRI, effective diagnostic therapeutic strategies remain limited. Methods Using transcriptome sequencing mouse model we identified potential biomarkers that were significantly upregulated IIRI group compared to sham group. Based on these findings, developed evaluated strategy using milk-derived exosomes loaded siRNA targeting CCL7 (M-Exo/siCCL7). Results Focusing Ccl7 as hub gene, explored efficacy (M-Exo/siCCL7) model. M-Exo/siCCL7 treatment effectively attenuated intestinal inflammation injury, evidenced by reduced histological damage, decreased serum markers barrier dysfunction, systemic inflammation. Conclusion Our findings provide new insights into molecular mechanisms underlying identify biomarkers, highlight promise exosome-based delivery novel approach for IIRI.

Language: Английский

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CCL20 in the tumor microenvironment: implications for cancer progression and therapeutic approaches

Clinical & Translational Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Abstract Increasing knowledge of the immunosuppressive tumor microenvironment in cancer-related processes has led to developing novel immune-based therapies that have changed cancer treatment paradigm. In microenvironment, plethora soluble factors secreted by cells interacts with immune and non-immune components deliver signals necessary for progression. Accordingly, targeting tumor-derived inducing this become an appealing therapeutic potential advancing treatment. CCL20, a chemokine best known induce leucocyte migration response pathological inflammatory conditions, been implicated proliferation, angiogenesis, metastasis, immunosuppression, resistance. Notably, CCL20 its receptor CCR6 are important interactions. This review discusses interaction between CCL20–CCR6 axis how these interactions promote Also, outline studies utilizing combination other standard treatments shed.

Language: Английский

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Pan-cancer characterization of C–C motif chemokine ligand 5 (CCL5) identifies its role as biomarker and therapeutic target

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

Published: March 4, 2025

C–C Motif Chemokine Ligand 5 (CCL5) is known for its role in immune regulation and has been implicated cancer progression. However, expression prognostic significance pan-cancer require comprehensive evaluation. This study was initiated to decipher the of CCL5 genes. In silico analyses involving various online databases molecular experiments knockdown KIRC cell lines evaluated proliferation, colony formation, migration. significantly up-regulated several cancers. High correlated with poorer overall survival kidney renal carcinoma (KIRC) esophageal (ESCA) patients. Promoter hypomethylation elevated prognosis. mutations were rare; indicating driven by overexpression rather than genetic alterations. Positive correlations inhibitory MHC genes suggested CCL5's fostering an immunosuppressive tumor microenvironment. increased infiltration, particularly CD8 T cells macrophages. did not influence drug sensitivity. resulted reduced migration, underscoring critical dynamics. Our highlights progression prognosis, ESCA. modulating microenvironment potential as a therapeutic target warrant further investigation.

Language: Английский

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Macrophages in graft-versus-host disease (GVHD): dual roles as therapeutic tools and targets

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 6, 2025

Graft-versus-host disease remains one of the most formidable barriers to complete success hematopoietic stem cell transplantation that has emerged as curative approach for many malignancies because it affects quality life and overall survival. Macrophages are among important members immune system, which perform dual roles in GVHD both therapeutic tools targets. This review epitomizes multifunctional role macrophages pathophysiology acute chronic GVHD. play an early phase their recruitment infiltration into target organs. Furthermore, they polarize two functionally different phenotypes, including M1 M2. In case GVHD, express phenotype characterized by production pro-inflammatory cytokines contribute tissue damage. contrast, tend toward M2 associated with repair tissues fibrosis. A critical balance these phenotypes is central course severity Further interactions other lymphocytes such T cells, B fibroblast further determine Macrophage interaction alloreactive cells promotes inflammation. therefore inducing injuries during Interaction macrophages, cell, fibroblast, CD4+ fibrosis and, hence, subsequent dysfunction These some insights, while several challenges remain. First, impact dominant on polarization incompletely sometimes controversial. Second, development targeted therapies able modulate macrophage function without systemic side effects area ongoing investigation. Future directions involve exploration macrophage-targeted therapies, small molecules, antibodies, nanotechnology, behavior improve patient outcomes. underlines fact a profound understanding essential developing new more effective strategies. Targeting might represent avenue decreasing incidence improving safety HSCT.

Language: Английский

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Combined mitoxantrone and anti-TGFβ treatment with PD-1 blockade enhances antitumor immunity by remodelling the tumor immune landscape in neuroblastoma

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Nov. 17, 2022

Abstract Background Poor infiltration of functioning T cells renders tumors unresponsive to checkpoint-blocking immunotherapies. Here, we identified a combinatorial in situ immunomodulation strategy based on the administration selected immunogenic drugs and immunotherapy sensitize poorly T-cell-infiltrated neuroblastoma (NB) host antitumor immune response. Methods 975A2 9464D NB cell lines derived from spontaneous TH-MYCN transgenic mice were employed study drug combinations able enhancing response using vivo ex approaches. Migration towards drug-treated murine-derived organotypic tumor spheroids (MDOTS) assessed by microfluidic devices. Activation status co-cultured with MDOTS was evaluated flow cytometry analysis. The effect treatment content subcutaneous or orthotopic comprehensively analyzed flow-cytometry, immunohistochemistry multiplex immunofluorescence. chemokine array assay used detect soluble factors released into microenvironment. Patient-derived (PDOTS) generated human specimens. activation autologous PDOTS performed. Results We found that low-doses mitoxantrone (MTX) recalled promoted CD8 + NK when combined TGFβ PD-1 blockade. This curbed growth resulting enrichment variety both lymphoid myeloid cells, especially intratumoral dendritic (DC) IFNγ- granzyme B-expressing cells. A concomitant production inflammatory chemokines involved remodelling landscape also detected. Interestingly, this induced recruitment against Conclusions Combined low-dose MTX anti-TGFβ blockade improves immunity overcoming immunosuppressive microenvironment aggressive NB.

Language: Английский

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The roles of cancer stem cell-derived secretory factors in shaping the immunosuppressive tumor microenvironment in hepatocellular carcinoma

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

Published: May 29, 2024

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide and has a poor prognosis. Although immune checkpoint inhibitors have entered new era HCC treatment, their response rates are modest, which can be attributed to immunosuppressive tumor microenvironment within tumors. Accumulating evidence shown that growth fueled by cancer stem cells (CSCs), contribute therapeutic resistance above treatments. Given CSCs regulate cellular physical factors niche secreting various soluble in paracrine manner, there been increasing efforts toward understanding roles CSC-derived secretory creating an microenvironment. In this review, we provide update on how these factors, including cytokines, chemokines, exosomes, TME, leads resistance. addition, present current strategies targeting describe future perspectives. summary, better CSC biology TME provides rational basis for combination therapy with ICIs effective treatment.

Language: Английский

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