Prognostic Value of PCSK9 Levels in Premenopausal Women at Risk of Breast Cancer—Evidence from a 17-Year Follow-Up Study DOI Open Access
Massimiliano Ruscica, Chiara Macchi, Sara Gandini

и другие.

Cancers, Год журнала: 2024, Номер 16(7), С. 1411 - 1411

Опубликована: Апрель 4, 2024

Background and aim: The involvement of cholesterol in cancer development remains a topic debate, its association with breast has yet to be consistently demonstrated. Considering that circulating levels depend on several concomitant processes, we tested the liability plasma proprotein convertase subtilisin/kexin type 9 (PCSK9), one key regulators levels, as prognostic biomarker context neoplastic events. Methods: Within prospective randomized prevention trial measured baseline PCSK9. A total 235 at-risk premenopausal women were followed up for 17 years. Participants enrolled this placebo-controlled, phase II, double-blind randomly assigned receive either tamoxifen 5 mg/d or fenretinide 200 mg/d, both agents, placebo 2 associations events evaluated through competing risk Cox regression survival models, adjusted randomization strata (5-year Gail ≥ 1.3% vs. intraepithelial neoplasia small invasive favorable prognosis), age, treatment allocation. PCSK9 biomarkers linked assessed blood samples collected at baseline. Results: plasmatic median interquartile range 207 ng/mL 170–252 ng/mL, respectively. Over follow-up period years 89 events, disease-free curves showed hazard ratio 1.002 (95% CI: 0.999–1.005, p = 0.22) compared below ng/mL. No differences between observed. We found negative correlation estradiol (r −0.305), maintained even after partial adjustment BMI age −0.287). Cholesterol 0.266), LDL-C 0.207), non-HDL-C 0.246), remnant 0.233), triglycerides 0.233) also correlated Conclusions: In early-stage cancer, did not appear have role Larger studies are warranted investigating patients different settings.

Язык: Английский

Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside DOI Creative Commons

Xuhui Bao,

Yongjun Liang,

Hanman Chang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Янв. 8, 2024

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has evolved as a pivotal enzyme in lipid metabolism and revolutionary therapeutic target for hypercholesterolemia its related cardiovascular diseases (CVD). This comprehensive review delineates the intricate roles wide-ranging implications of PCSK9, extending beyond CVD to emphasize significance diverse physiological pathological states, including liver diseases, infectious autoimmune disorders, notably, cancer. Our exploration offers insights into interaction between PCSK9 low-density lipoprotein receptors (LDLRs), elucidating substantial impact on cholesterol homeostasis health. It also details evolution PCSK9-targeted therapies, translating foundational bench discoveries bedside applications optimized patient care. The advent clinical approval innovative inhibitory therapies (PCSK9-iTs), three monoclonal antibodies (Evolocumab, Alirocumab, Tafolecimab) one small interfering RNA (siRNA, Inclisiran), have marked significant breakthrough medicine. These demonstrated unparalleled efficacy mitigating hypercholesterolemia, reducing risks, showcased profound value applications, offering novel avenues promising future personalized medicine disorders. Furthermore, emerging research, inclusive our findings, unveils PCSK9's potential role indicator cancer prognosis prospective application transformative treatment. highlights aberrant expression various forms, association with prognosis, crucial carcinogenesis immunity. In conclusion, this synthesized integrates existing knowledge providing holistic perspective reshaping paradigms across emphasizes effect PCSK9-iT, underscoring advancing landscape biomedical research capabilities heralding new eras

Язык: Английский

Процитировано

50
Potential use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and prevention method in viral infection DOI Creative Commons
Khursheed Muzammil, Mohammad Hosseini Hooshiar,

Shirin Varmazyar

и другие.

Microbial Cell Factories, Год журнала: 2024, Номер 23(1)

Опубликована: Март 25, 2024

Cellular lipid membranes serve as the primary barrier preventing viral infection of host cell and provide viruses with a critical initial point contact. Occasionally, can utilize lipids receptors. Viruses depend significantly on rafts for at virtually every stage their life cycle. The pivotal role that proprotein convertase subtilisin/kexin Type 9 (PCSK9) plays in cholesterol homeostasis atherosclerosis, primarily by post-transcriptionally regulating hepatic low-density lipoprotein receptor (LDLR) promoting its lysosomal degradation, has garnered increasing interest. Conversely, using therapeutic, fully humanized antibodies to block PCSK9 leads significant reduction high LDL (LDL-C) levels. Food Drug Administration (FDA) approved inhibitors, including inclisiran (Leqvio®), alirocumab (Praluent), evolocumab (Repatha). At present, active immunization strategies targeting present compelling substitute passive through administration antibodies. In addition current inquiry into potential therapeutic application inhibition human immunodeficiency virus (HIV)-infected patients hyperlipidemia associated HIV antiretroviral therapy (ART), preclinical research suggests may also play inhibiting hepatitis C (HCV) replication. Furthermore, been suggested protect against dengue (DENV) potentially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses. Recent evidence regarding impact variety infections, HCV, HIV, DENV, SARS-CoV-2, is examined this article. As result, inhibitors vaccines viable therapies our indicates involved pathogenesis infections.

Язык: Английский

Процитировано

14
The role of lipids and lipids lowering drugs in human papillomavirus (HPV) and HPV-associated cancers DOI Creative Commons

Ehsan Shabani,

Aida Hasanzadi, Omer Qutaiba B. Allela

и другие.

Infectious Agents and Cancer, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 28, 2025

Both women and men are now confronted with the grave threat of cancers caused by human papillomavirus (HPV). It is estimated that 80% may encounter HPV over their lives. In preponderance cases involving anal, head neck, oral, oropharyngeal, penile, vaginal, vulvar, cervical malignancies, high-risk (HR-HPV) causative agent. 2019, believed to have been cause 620,000 new cancer in 70,000 worldwide. The bulk 530,000 (~ 270,000 fatalities) infection (86% cases, 88% deaths) happen poor nations each year. Lipid metabolism crucial development related HPV. One most noticeable metabolic abnormalities lipid reprogramming, which cells dysregulate obtain sufficient energy, building blocks for cell membranes, signaling molecules necessary invasion, metastasis, proliferation, survival. Moreover, proteins' stimulation production infected will probably a significant effect on oncogenesis. addition, lipids critical producing cellular epithelial-mesenchymal transition (EMT) process, therapy resistance HPV-related (HRCs). Therefore, essential HRC also be an important target approaches associated treatments during or development. This review study looked at role lipid-lowering drugs cancers.

Язык: Английский

Процитировано

0
Glycolysis-cholesterol metabolic axis in immuno-oncology microenvironment: emerging role in immune cells and immunosuppressive signaling DOI Creative Commons
Jing Jin, Qijie Zhao,

Zhigong Wei

и другие.

Cell & Bioscience, Год журнала: 2023, Номер 13(1)

Опубликована: Окт. 13, 2023

Abstract Cell proliferation and function require nutrients, energy, biosynthesis activity to duplicate repertoires for each daughter. It is therefore not surprising that tumor microenvironment (TME) metabolic reprogramming primarily orchestrates the interaction between immune cells. Tumor affords bioenergetic, signaling intermediates, requirements both malignant Different cell subsets are recruited into TME, these manifestations have distinct effects on progression therapeutic outcomes, especially mutual contribution of glycolysis cholesterol metabolism. In particularly, glycolysis-cholesterol axis interconnection plays a critical role in TME modulation, their changes metabolism appear be double-edged sword regulating various responses immunotherapy efficacy. Hence, we discussed signature manifestation its pivotal regulation. We also highlight how hypothetical combinations glycolysis/cholesterol-related interventions unleash potential anti-tumor immunotherapies, as well developing more effective personalized treatment strategies.

Язык: Английский

Процитировано

11
Targeting PCSK9, through an innovative cVLP-based vaccine, enhanced the therapeutic activity of a cVLP-HER2 vaccine in a preclinical model of HER2-positive mammary carcinoma DOI Creative Commons

Laura Scalambra,

Francesca Ruzzi,

Olga Maria Pittino

и другие.

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
Prognostic implications of PCSK9 expression in HER2-positive breast cancer DOI Creative Commons

Zongwen Wu,

D. Wu,

Chengsheng Huang

и другие.

ONCOLOGIE, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Язык: Английский

Процитировано

0
Effects of PCSK9 inhibitors on cancer, diabetes, and cardiovascular diseases DOI
Mojgan Nejabat, Farzin Hadizadeh, Wael Almahmeed

и другие.

Drug Discovery Today, Год журнала: 2025, Номер unknown, С. 104316 - 104316

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Targeting cholesterol metabolism: a promising therapy strategy for cancer DOI

Chun-Lan Dai,

Zhixin Qiu, Anqi Wang

и другие.

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

Язык: Английский

Процитировано

0
The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy DOI
Chou‐Yi Hsu,

Mustafa Nasrat Abdulrahim,

Mohammed Ahmed Mustafa

и другие.

Medical Oncology, Год журнала: 2024, Номер 41(8)

Опубликована: Июль 15, 2024

Язык: Английский

Процитировано

3
Serum PCSK9 is a novel serological biomarker for the diagnosis and prognosis of pancreatic cancer DOI Creative Commons
Ying Xu, Yongfeng Xu, Yang Yang

и другие.

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