Pharmaceuticals (Basel)
Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
Published: November 2023
Aim: Angiotensin II (AngII) is known to play a significant part in the development of breast cancer by triggering cell propagation of breast cancer, tumor angiogenesis, and regulating tumor invasion and cell migration. AngII arbitrates its action via two G-protein-coupled receptors, AngII type 1 receptor (AT1) and AngII type 2 receptor (AT2). Overexpression of the AT1 receptor in breast cancer cells seems to promote tumor growth and angiogenesis, thus targeting the AT1 receptor using AngII peptide would facilitate the detection of breast carcinoma. We developed an AngII peptide intending to assess whether the peptide of the renin-angiotensin system holds the ability to target AT1 receptor-overexpressing breast cancer in vivo.
Methods: DOTA-coupled AngII peptide was synthesized by conventional solid-phase peptide synthesis according to Fmoc/HATU chemistry. Ga/Lu labeled AngII peptide was evaluated for its binding with TNBC MDA-MB-231 and ER+ MCF7 cell lines. Pharmacokinetics was studied in healthy balb/c mice and in vivo tumor targeting in nude mice with MDA-MB-231 tumors xenografts.
Results: DOTA-AngII peptide was labeled efficiently with Ga/Lu with high labeling efficiency (≥90%). The stability of the radiopeptide in human plasma was found to be high. The AngII peptide analog showed nanomolar (<40 nM) AT1 receptor-specific binding affinity. The radioactivity internalized into MDA-MBA-231 and MCF7 cells were 14.97% and 11.75%, respectively. In vivo, biodistribution in balb/c mice exhibited efficient clearance of Ga/Lu-DOTA-AngII peptide from the blood and elimination predominantly by the renal system due to its hydrophilic nature. A low amount of radioactivity was seen in the major organs including lungs, liver, stomach, spleen, and intestines (<3% ID/g) except the kidneys. A high renal-urinary excretion was observed for the radiotracer. In the TNBC MDA-MB-231 xenografts model, radiolabeled AngII peptide exhibited specific and effective AT1-based targeting in vivo. A rapid and efficient tumor targeting (2.18% ID/g at 45 min p.i.) together with fast renal excretion (~67% ID) highlights the tumor-targeting potential of the radiotracer. The AT1 receptor specificity of the radiotracer was validated by blocking assays. Furthermore, PET imaging provided sufficient visualization of MDA-MB-231 tumors in nude mice.
Conclusion: Our findings suggest that Ga/Lu-DOTA-AngII peptide can be useful for the theranostic application of breast carcinomas. This study suggests the potential of this innovative class of peptides for rapid and efficient targeting of tumors and warrants further evaluation.
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http://dx.doi.org/10.3390/ph16111550 | DOI Listing |
EClinicalMedicine
February 2025
Department of Breast and Gynaecological Surgery, Institut Curie, Paris, France.
Background: Randomized clinical trials (RCTs) are fundamental to evidence-based medicine, but their real-world impact on clinical practice often remains unmonitored. Leveraging large-scale real-world data can enable systematic monitoring of RCT effects. We aimed to develop a reproducible framework using real-world data to assess how major RCTs influence medical practice, using two pivotal surgical RCTs in gynaecologic oncology as an example-the LACC (Laparoscopic Approach to Cervical Cancer) and LION (Lymphadenectomy in Ovarian Neoplasms) trials.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Breast and Thyroid Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, characterized by frequent recurrence, metastasis, and poor survival outcomes despite chemotherapy-based treatments. This study aims to investigate the mechanisms by which Traditional Chinese Medicine (TCM) modulates the tumor immune microenvironment in TNBC, utilizing CiteSpace and bioinformatics analysis.
Methods: We employed CiteSpace to analyze treatment hotspots and key TCM formulations, followed by bioinformatics analysis to identify the main active components, targets, associated pathways, and their clinical implications in TNBC treatment.
Front Immunol
January 2025
Key Lab of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Introduction: Breast cancer (BC) is the most prevalent malignant tumor in women, with triple-negative breast cancer (TNBC) showing the poorest prognosis among all subtypes. Glycosylation is increasingly recognized as a critical biomarker in the tumor microenvironment, particularly in BC. However, the glycosylation-related genes associated with TNBC have not yet been defined.
View Article and Find Full Text PDFJ Exp Pharmacol
January 2025
University Center of Excellence for Nutraceuticals, Bioscience and Biotechnology Research Center, Bandung Institute of Technology, Bandung, West Java, Indonesia.
Purpose: A promising feature of marine sponges is the potential anticancer efficacy of their secondary metabolites. The objective of this study was to explore the anticancer activities of compounds from the fungal symbiont of on breast cancer cells.
Methods: In the present research, , an endophytic fungal strain derived from the marine sponge was successfully isolated and characterized.
Breast Cancer (Dove Med Press)
January 2025
Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21859, Saudi Arabia.
Nanoparticle technology has revolutionized breast cancer treatment by offering innovative solutions addressing the gaps in traditional treatment methods. This paper aimed to comprehensively explore the historical journey and advancements of nanoparticles in breast cancer treatment, highlighting their transformative impact on modern medicine. The discussion traces the evolution of nanoparticle-based therapies from their early conceptualization to their current applications and future potential.
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