Obesity-induced thymic involution and cancer risk

Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 93, P. 3 - 19

Published: April 23, 2023

Declining thymic functions associated either with old age (i.e., age-related involution), or acute involution as a result of stress, infectious disease, cytoreductive therapies (e.g., chemotherapy/radiotherapy), have been cancer development. A key mechanism underlying such increased risk is the thymus-dependent debilitation adaptive immunity, which responsible for orchestrating immunoediting mechanisms and tumor immune surveillance. In past few years, blooming set evidence has intriguingly linked obesity development progression. The majority studies focused on obesity-driven chronic inflammation, steroid/sex hormone adipokine production, hyperinsulinemia, principal factors affecting microenvironment driving primary malignancy. However, experimental observations about negative impact T cell maturation existed more than half century. Here, we critically discuss molecular cellular previously underrepresented intermediary pathology leading to This knowledge could be especially relevant in context childhood obesity, because impaired function young individuals leads system abnormalities, predisposes various pediatric cancers. thorough understanding behind circuitries governing obesity-induced therefore help towards rationalized targeted regeneration strategies obese at high

Language: Английский

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Tobacco exposure primes the secretion of CCL21 positively associated with tertiary lymphoid structure and response to immunotherapy

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(6), P. e006939 - e006939

Published: June 1, 2023

Background It has been reported that smoking history as a predictor of immunotherapy efficacy in patients with advanced lung cancer, however, the underlying mechanisms this phenomenon remain largely unknown. Methods The adenocarcinoma’s (LUAD) cohort and orthotopical transplanted mouse model were used to explore correlation between status tertiary lymphoid structure (TLS) chemokine CCL21, respectively. Cell adhesion co-immunoprecipitation assays performed interaction CD4+T cells CD20+B under tobacco exposure. Chromatin immunoprecipitation-PCR was dissect mechanism upregulated CCL21 secretion treatment. Serum level recorded LUAD treated immunotherapy. Results Here we observed individuals exhibit an increased quantity maturation TLS compared non-smokers, along higher levels secretion. Tobacco exposure promoted expression epithelial cell-intrinsic manner, which BaP, main component tobacco, facilitated nuclear retention aryl hydrocarbon receptor occupied promoter CCL21. Additionally, activated CCL21/CCR7 axis CD11a cells, boosting dependent on ICAM1, potentially induced TLSs formation. Patients elevated serum benefited more from Conclusions exhibited via CCL21-dependent mechanism, identified reliable biomarker for predicting

Language: Английский

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Beyond Small Molecules: Antibodies and Peptides for Fibroblast Activation Protein Targeting Radiopharmaceuticals

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(3), P. 345 - 345

Published: Feb. 29, 2024

Fibroblast activation protein (FAP) is a serine protease characterized by its high expression in cancer-associated fibroblasts (CAFs) and near absence adult normal tissues benign lesions. This unique pattern positions FAP as prospective biomarker for targeted tumor radiodiagnosis therapy. The advent of FAP-based radiotheranostics anticipated to revolutionize cancer management. Among various types ligands, peptides antibodies have shown advantages over small molecules, exemplifying prolonged retention human volunteers. Within scope, this review summarizes the recent research progress radiopharmaceuticals based on imaging Additionally, it incorporates insights from studies, providing valuable perspectives clinical utility FAP-targeted radiopharmaceuticals.

Language: Английский

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Advances in immunotherapy for breast cancer and feline mammary carcinoma: From molecular basis to novel therapeutic targets

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(5), P. 189144 - 189144

Published: June 22, 2024

The role of inflammation in cancer is a topic that has been investigated for many years. As established, emerges as defining characteristic cancer, presenting itself compelling target therapeutic interventions the realm oncology. Controlling tumor microenvironment (TME) gained paramount significance, modifying not only effectiveness immunotherapy but also modulating outcomes and prognoses standard chemotherapy other anticancer treatments. Immunotherapy surfaced central focus within domain treatments, using immune checkpoint inhibitors therapy. Immune checkpoints their influence on dynamic are presently under investigation, aiming to ascertain viability across several types. Cancer presents significant challenge humans cats, where female breast ranks most prevalent malignancy feline mammary carcinoma stands third frequent. This review seeks summarize data about cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), programmed cell death protein-1 (PD-1), V-domain Ig suppressor T (VISTA), T-cell immunoglobulin mucin 3 (TIM-3) respective ongoing investigations prospective targets therapy human while outlining findings from studies reported (FMC), strengthening rationale employing FMC representative model exploration cancer.

Language: Английский

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Novel Siglec-15-Sia axis inhibitor leads to colorectal cancer cell death by targeting miR-6715b-3p and oncogenes

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

Published: Oct. 6, 2023

Siglecs are well known immunotherapeutic targets in cancer. Current checkpoint inhibitors have exhibited limited efficacy, prompting a need for novel therapeutics such as Siglec-15. Presently, small molecule targeting Siglec-15 not explored alongside characterised regulatory mechanisms involving microRNAs CRC progression. Therefore, inhibitor to target was elucidated vitro and microRNA mediated effects were investigated. Our research findings demonstrated that the SHG-8 exerted significant cytotoxicity on cell viability, migration, colony formation, with an IC 50 value of approximately 20µM. exposure induced late apoptosis SW480 cells. Notably, miR-6715b-3p most upregulated miRNA high-throughput sequencing, which also validated via RT-qPCR. MiR-6715b-3p may regulate PTTG1IP , potential oncogene RT-qPCR silico analysis. Additionally, molecular docking studies revealed interactions binding pocket affinity -5.4 kcal/mol, highlighting its role inhibitor. Importantly, PD-L1 expressed mutually exclusive cancer populations, suggesting combination therapies antagonists.

Language: Английский

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Post-operative C-reactive protein as a strong independent predictor of long-term colorectal cancer outcomes: consistent findings from two large patient cohorts

ESMO Open, Journal Year: 2024, Volume and Issue: 9(4), P. 102982 - 102982

Published: April 1, 2024

•Patients were treated with surgery for CRC.•Post-operative CRP (poCRP) was measured from blood collected ≥1 month after surgery.•Associations of poCRP long-term survival assessed using Cox regression.•Elevated independently associated poorer survival.•poCRP may be valuable CRC surveillance. BackgroundPost-surgery blood-based biomarkers useful guiding treatment and surveillance decisions among colorectal cancer (CRC) patients. However, most candidate provide little if any predictive value beyond stage at diagnosis. We aimed to investigate the independent prognostic post-operative serum C-reactive protein (CRP), a highly sensitive biomarker inflammation, outcomes in two large patient cohorts.Materials methodsCRP levels samples patients post-surgery German DACHS (n = 1416) UK Biobank 1149) cohorts. Associations overall (OS) CRC-specific (CSS) regression presented as hazard ratios (HRs) 95% confidence intervals (CIs), adjusted key sociodemographic clinical covariates.ResultsIn both cohorts, consistent strong dose–response relationships between OS CSS observed. Adjusted HRs (95% CI) >10 versus <3 mg/l 1.93 (1.58-2.35) 2.70 (2.03-3.59) cohort, (1.96-3.71) 2.61 (1.83-3.72) respectively. particularly younger (<65 years diagnosis; P interaction by age <0.01).ConclusionsSerum determined or more therapeutic course disease patients, those <65 Post-surgery covariates. In <0.01). Serum

Language: Английский

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Prediction of the Binding to the Nuclear Factor NF-Kappa-B by Constituents from Teucrium polium L. Essential Oil

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(1), P. 48 - 48

Published: Jan. 14, 2025

Teucrium polium L. is a plant with various claims of ethnobotanical use, primarily for inflammatory diseases. Chemical studies have already isolated different types terpenes from the species, and established its pharmacological potential. The present study evaluates components T. essential oil cultivated in Algerian Saharan Atlas. GC-MS identified major as fenchone (31.25%), 3-carene (15.77%), cis-limonene oxide (9.77%), myrcene (9.15%). In silico prediction, molecules more than 1% abundance were selected. Regarding Lipinski’s rule, all followed rule. All found to be toxic at least one model, some being non-genotoxic (6, 8, 10, 11, 12, 13) others non-mutagenic (5, 7, 9, 14). Three selected that showed best results pharmacokinetic toxicity studies: did not carcinogenic potential (7—myrtenal; 9—myrtenol; 14—verbenol). molecular target was established, it seems three bound nuclear factor NF-kappa-B. Based on docking dynamics results, these anti-inflammatory antitumor therapies, further vitro vivo needed evaluate their activity toxicity.

Language: Английский

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The role of functional foods in inflammation management

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 175 - 198

Published: Jan. 1, 2025

Language: Английский

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A Longitudinal Study Examining the Impact of Chronic Rhinosinusitis on the Risk of Cancer Development: A National Population-Based Cohort Study

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 546 - 546

Published: Feb. 6, 2025

Background/Objectives: We investigated the association between chronic rhinosinusitis (CRS) and cancer risk in an adult Korean population. Methods: This retrospective cohort study used data from National Health Insurance Service database. To ensure comparability groups, adjustments were made for potential confounding factors, including sex, age, residence, household income, diabetes, hypertension, kidney disease. The primary endpoint was presence of newly diagnosed cancer. Results: Among 1,337,120 individuals nationally representative database, 10,567 patients with CRS identified matched 42,268 control subjects without CRS. Patients had a significantly higher overall events than controls. adjusted hazard ratio (HR) group 1.16 (95% confidence interval [CI]: 1.05–1.28). Notably, female elevated incident events. Furthermore, nasal polyps exhibited increased cancer, whereas those did not show similar association. Conclusions: These findings underscore need physicians to carefully monitor progression develop appropriate therapeutic strategies mitigate impact this condition.

Language: Английский

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Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition

Open Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 1, 2025

Abstract Background and objective Early nutritional support holds paramount importance for postoperative gastric cancer (GC) patients. Peptidase M20 domain containing 1 (PM20D1) is a secretory enzyme associated with glucose lipid metabolism. However, there dearth of clinical studies delving into the connection between PM20D1, metabolism, inflammatory factors in GC patients who have received enteral nutrition (EN). This research aimed to investigate serum levels PM20D1 following early EN their potential associations markers, factors. Methods prospective observational study enrolled 180 May 2020 July 2022. On first day, all support, which was maintained duration 5 days. Serum interleukin (IL)-6, IL-1β, C-reactive protein were measured on sixth day after surgery using an enzyme-linked immunosorbent assay. Data demographics, statistics, parameters, prognostic index (PNI) collected. Patients followed up 12 months, both overall survival disease-free recorded. Results In low PNI group, albumin (ALB), blood lymphocytes (BL) showed significant reductions. Pearson analysis revealed negative correlation IL-6 levels, whereas positive emerged ALB BL levels. Furthermore, demonstrated as biomarker diagnosing poor status (PNI < 43) risk factor Conclusion remarkably declined status.

Language: Английский

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