Facts and Hopes on Neutralization of Protumor Inflammatory Mediators in Cancer Immunotherapy

Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 29(23), P. 4711 - 4727

Published: July 31, 2023

Abstract In cancer pathogenesis, soluble mediators are responsible for a type of inflammation that favors the progression tumors. The mechanisms chiefly involve changes in cellular composition tumor tissue stroma and functional modulation myeloid lymphoid leukocytes. Active immunosuppression, proangiogenesis, leukocyte traffic, extracellular matrix remodeling, alterations tumor-antigen presentation main linked to fosters growth metastasis. Soluble inflammatory their receptors amenable various types inhibitors can be combined with other immunotherapy approaches. proinflammatory targets which interfered at present under preclinical clinical development IL1β, IL6, CXCR1/2 chemokine axis, TNFα, VEGF, leukemia inhibitory factor, CCL2, IL35, prostaglandins. many instances, corresponding neutralizing agents already clinically available repurposed as result use areas medicine such autoimmune diseases chronic conditions.

Language: Английский

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Prostaglandin analogs signal detection by data mining in the FDA Adverse Event Reporting System database.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 23, 2024

Background: Adverse Events (AEs) which are not mentioned in the safety information label any drug, considered “unexpected” and must be regarded analyzed as a signal. Prostaglandins cause effects on different cell types around body, triggering diverse actions, due to analogy of an endogenous prostamida prostaglandin’s analogs, it is essential identify possible association that could use these drugs ophthalmologic practice. This study aims signals ophthalmic prostaglandin analogs (PGAs) through data mining Food Drug Administration Event Reporting System (FAERS) database. Methods: A search by proportional reporting ratio, odds Bayesian confidence propagation neural network, component 0.25, Chi-squared for detection was conducted FAERS database following medications: latanoprost, travoprost, tafluprost, bimatoprost identification AE with statistical associations. Results: Twelve preferred terms were statistically associated: diabetes mellitus, n=2; hypoacusis, malignant mediastinal neoplasm, n=1; blood immunoglobulin E increased, cataract, blepharospasm, full count abnormal, skin exfoliation, chest discomfort, dry mouth, n=1. Conclusions: Of twelve PTs analyzed, eight them found relationship biological plausibility derived from previous research; this reason, relevant continue investigating drug-event association, whether refute signal or new risk its consequent minimization.

Language: Английский

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Mechanism of isoflurane‑mediated breast cancer growth in vivo

Oncology Letters, Journal Year: 2024, Volume and Issue: 27(6)

Published: April 30, 2024

Use of volatile anesthetics is associated with worse outcome following tumor resection surgery compared the use intravenous anesthetics. However, underlying mechanism has not been clearly delineated yet in vivo. The EO771 cell‑based congenic breast cancer model was used in present study. Isoflurane directly binds to and inhibits two adhesion molecules, leukocyte function‑associated antigen‑1 (LFA‑1) macrophage‑1 antigen (Mac‑1). Similarly, exposure sevoflurane, another anesthetic LFA‑1 inhibitor, an increase size non‑exposure. Thus, study first examined role Mac‑1 model. Both deficiency inhibition enhanced growth, which supported by cytokine eicosanoid data profiles. By contrast, did affect growth. isoflurane sevoflurane These suggested that growth interacting LFA‑1. LFA‑1‑deficient mice. In summary, showed facilitated isoflurane, also increased

Language: Английский

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Identification of promising cancer target proteins of major sesquiterpene lactones from Vernonia spp

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 12

Published: Dec. 27, 2024

The potential sesquiterpene lactone groups from the Vernonia genus; namely vernolide-A, vernolide-B, and vernodalin, have been reported for anticancer effects by downregulating cancer promoter proteins. Nevertheless, prior investigations failed to identify target proteins that are associated with compounds' actions. Subsequently, present investigation attempts cancer. number of candidate predicted our molecular docking study vernodalin were one, five, seven, respectively. Vernolide-A, most selective attractive interactions proteins; such as p38α, PGEP2R, HSP90α, In addition, MD simulation revealed on residual flexibility not substantial. This suggested their relative binding-free energy was similar well-established ligands; including PD169316, dinoprostone, Pu-H54. We also addressed mechanisms may be compounds in this report. potentially inhibit proliferation, survival, angiogenesis, migration cells through strong affinity a variety cancer-related molecules. Additional laboratory experimental designs; vitro vivo studies, further computational findings.

Language: Английский

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Interferon-gamma is Quintessential for NOS2 and COX2 Expression in ER^-Breast Tumors that Lead to Poor Outcome

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 6, 2023

A strong correlation between NOS2 and COX2 tumor expression poor clinical outcomes in ER-breast cancer has been established. However, mechanisms of induction these enzymes are unclear. Analysis The Cancer Genome Atlas (TCGA) revealed correlations Th1 cytokines. Herein, single cell RNAseq analysis TNBC cells shows potent by IFNγ combined with IL1β or TNFα. Given that is secreted cytolytic lymphocytes, which improve outcomes, this role IFNγpresents a dichotomy. To explore conundrum, NOS2, COX2, CD8 + T were spatially analyzed aggressive ER-, TNBC, HER2+ breast tumors. High clustering NOS2-expressing occurred at the tumor/stroma interface presence stroma-restricted cells. COX2-expressing extended into immune desert regions core where penetration was limited absent. Moreover, high proximal to areas increased satellitosis suggestive clusters higher metastatic potential. Further vitro experiments IFNγ+IL1β/TNFα elongation migration treated This spatial microenvironment provides important insight distinct neighborhoods exist niches could have

Language: Английский

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