Medical Hypotheses, Год журнала: 2024, Номер 184, С. 111294 - 111294
Опубликована: Фев. 12, 2024
Язык: Английский
Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)
Опубликована: Янв. 30, 2025
HER2-targeted therapies have revolutionized the treatment of HER2-positive breast cancer patients, leading to significant improvements in tumor response rates and survival. However, resistance incomplete remain considerable challenges. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel therapeutic strategy for management dyslipidemia by enhancing clearance low-density lipoprotein cholesterol receptors, however recent evidence also shows links between PCSK9 cells. We present an innovative immunization approach combining capsid virus-like particle (cVLP)-based vaccines against HER2 PCSK9. The activity combined vaccine was evaluated female mice challenged with mammary carcinoma Controls included untreated treated cVLP-PCSK9 cVLP-HER2 as standalone therapies. Antibodies elicited vaccinations were detected through ELISA immunoassay. functional antibodies tested 3D-soft agar assay on human + trastuzumab sensitive resistant Mice vaccinated displayed regression from 40th day after cell challenge 100% remaining tumor-free even 4 months later. In contrast, 83% alone experienced initial regression, followed relapse 60% subjects. Untreated developed progressive tumors within 1–2 injection. strong anti-human antibody responses (reaching mg/ml range) comprising multiple immunoglobulins isotypes. anti-PCSK9 responses, resulting marked reduction serum levels. Although reduced when co-administered cVLP-HER2, it remained significant. Moreover, both induced anti-HER2 able inhibit 3D growth BT-474 trastuzumab-resistant C5 Strikingly, vaccination more effective than those results indicate that adjuvant vaccine, its efficacy holding promise overcoming challenges posed therapy.
Язык: Английский
Процитировано
0
Drug Discovery Today, Год журнала: 2025, Номер unknown, С. 104316 - 104316
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown, С. 108847 - 108847
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Metabolites, Год журнала: 2024, Номер 14(7), С. 388 - 388
Опубликована: Июль 17, 2024
Atherosclerotic cardiovascular disease poses a significant global health issue, with dyslipidemia standing out as major risk factor. In recent decades, lipid-lowering therapies have evolved significantly, statins emerging the cornerstone treatment. These interventions play crucial role in both primary and secondary prevention by effectively reducing through lipid profile enhancements. Beyond their effects, extensive research indicates that these exhibit pleiotropic actions, offering additional benefits. include anti-inflammatory properties, improvements vascular glucose metabolism, potential implications cancer management. While ezetimibe been extensively studied, newer agents also demonstrate similar even absence of direct This narrative review explores diverse properties lipid-modifying therapies, emphasizing non-lipid effects contribute to burden exploring benefits for non-cardiovascular conditions. Mechanistic insights into actions are discussed alongside therapeutic implications.
Язык: Английский
Процитировано
3
Pharmaceuticals, Год журнала: 2023, Номер 16(9), С. 1197 - 1197
Опубликована: Авг. 22, 2023
Atherosclerosis is the primary process that underlies cardiovascular disease. The connection between LDL cholesterol and formation of atherosclerotic plaques established by solid evidence. PCSK9 inhibitors have proven to be a valuable practical resource for lowering many patients in recent years. Their inhibitory effect on atherosclerosis progression seems driven not just lipid metabolism modification but also LDL-independent mechanisms. We review various mechanisms involving platelet activation, inflammation, endothelial dysfunction, resultant clot formation. main effectors activation platelets are CD36 receptors, lipoprotein(a), oxidised particles, tissue factor, factor VIII. Many more molecules under investigation, this area research growing rapidly.
Язык: Английский
Процитировано
4
BMC Cancer, Год журнала: 2024, Номер 24(1)
Опубликована: Май 31, 2024
Abstract Background The causal impact of lipid-lowering drugs on ovarian cancer (OC) and cervical (CC) has received considerable attention, but its relationship is still a subject debate. Hence, the objective this study to evaluate medications occurrence risk OC CC through Mendelian randomization (MR) analysis drug targets. Methods This investigation concentrated primary targets medications, specifically, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) proprotein convertase kexin 9 (PCSK9). Genetic variations associated with HMGCR PCSK9 were derived from published genome-wide association (GWAS) findings serve as substitutes for inhibitors. Employing MR approach, an was conducted scrutinize inhibitors targeting CC. Coronary heart disease (CHD) utilized positive control, outcomes encompassed Results suggest notable elevation in among patients treated (OR [95%CI] = 1.815 [1.316, 2.315], p 0.019). In contrast, no significant correlation observed between OC. Additionally, did not reveal any noteworthy connection inhibitors, Conclusion significantly elevate patients, their mechanism needs further investigation, influence been observed. There
Язык: Английский
Процитировано
1
PeerJ, Год журнала: 2024, Номер 12, С. e18018 - e18018
Опубликована: Сен. 10, 2024
Background Although CA19-9 is an essential blood biomarker of pancreatic cancer (PC), its sensitivity and specificity are limited for early detection. Methods We analyzed the serum proprotein convertase subtilisin/kexin type 9 (sPCSK9) in PC patients, benign disease groups (BDG), healthy controls (HC) by ELISA. Results Consistently, sPCSK9 was considerably lower patients than HC (Z = −2.546, P < 0.05), statistically significantly higher BDG −5.457, 0.001). linked to invasion lymph nodes (χ 2 6.846, 0.01). According ROC curves, combining with could potentially enhance diagnostic capability early-stage patients. Furthermore, low group ( n 41) exhibited prolonged overall survival compared high 15), median times 27 months (95% CI [17.59–36.41]) 11 [7.21–14.79]), respectively 0.022). Conclusion The performance be improved CA19-9. Moreover, has a shorter rate.
Язык: Английский
Процитировано
1
Medical Hypotheses, Год журнала: 2024, Номер 184, С. 111294 - 111294
Опубликована: Фев. 12, 2024
Язык: Английский
Процитировано
0