Taxifolin Inhibits the Growth of Non-Small-Cell Lung Cancer via Downregulating Genes Displaying Novel and Robust Associations with Immune Evasion Factors DOI Open Access

Xiaozeng Lin,

Ying Dong, Yan Gu

и другие.

Cancers, Год журнала: 2023, Номер 15(19), С. 4818 - 4818

Опубликована: Сен. 30, 2023

Using an LL2 cell-based syngeneic mouse LC model, taxifolin suppressed allografts along with the appearance of 578 differentially expressed genes (DEGs). These DEGs were associated enhancement processes related to extracellular matrix and lymphocyte chemotaxis as well reduction in pathways relevant cell proliferation. From these DEGs, we formulated 12-gene (TxflSig) 7-gene (TxflSig1) panels; both predicted response ICB (immune checkpoint blockade) therapy more effectively non-small-cell lung cancer (NSCLC) than numerous well-established biomarkers, including PD-L1. In panels, counterparts ITGAL, ITGAX, TMEM119 downregulated by taxifolin. They strongly immune suppression LC, evidenced their robust correlations major immunosuppressive types (MDSC, Treg, macrophage) multiple checkpoints NSCLC across human types. IIT (ITGAL-ITGAX-TMEM119) NSCLC’s therapy; stratified mortality risk NSCLC. The stromal expressions ITGAL together tumor expression NSCLC, demonstrated. Collectively, report novel biomarkers—TxflSig, TxflSig1, IIT, ITGAX—and taxifolin-derived attenuation activities suggesting inclusion therapies for

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
The evolving landscape of PCSK9 inhibition in cancer DOI Creative Commons
Palak P. Oza, Khosrow Kashfi

European Journal of Pharmacology, Год журнала: 2023, Номер 949, С. 175721 - 175721

Опубликована: Апрель 12, 2023

Язык: Английский

Процитировано

18
Targeting PCSK9 to upregulate MHC-II on the surface of tumor cells in tumor immunotherapy DOI Creative Commons
Hanbing Wang, Xin Zhang, Yipeng Zhang

и другие.

BMC Cancer, Год журнала: 2024, Номер 24(1)

Опубликована: Апрель 10, 2024

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9), the last member of proprotein family, functions as a classic regulator low-density lipoprotein (LDL) by interacting with receptor (LDLR). Recent studies have shown that PCSK9 can affect occurrence and development tumors be used novel therapeutic target. However, comprehensive pan-cancer analysis has yet to conducted. Methods The potential oncogenic effects in 33 types were explored based on datasets Cancer Genome Atlas (TCGA) dataset. In addition, immune regulatory role inhibition was evaluated via vitro cell coculture tumor-bearing mouse model. Finally, antitumor efficacy targeted combined OVA-II vaccines verified. Results Our results indicated highly expressed most tumor significantly correlated late disease stage poor prognosis. Additionally, may regulate matrix score, infiltration, checkpoint expression, major histocompatibility complex expression. Notably, we first found dendritic (DC) infiltration complex-II (MHC-II) expression could upregulated improve CD8 + T activation microenvironment, thereby achieving potent control. Combining inhibitors enhance efficacies vaccine monotherapy. Conclusions Conclusively, our provided more understanding immunoregulatory roles demonstrated targeting increase long peptide upregulating DC MHC-II surface cells. Summary This study reveals critical various shows promise immunotherapy

Язык: Английский

Процитировано

6
Hyaluronic acid dissolving microneedle patch loaded with tranexamic acid for melasma treatment DOI
Cai Zhang, Xuejiao Song, Chuan Ma

и другие.

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 270, С. 132255 - 132255

Опубликована: Май 8, 2024

Язык: Английский

Процитировано

6
Integrative analysis of bulk and single-cell RNA-seq reveals the molecular characterization of the immune microenvironment and oxidative stress signature in melanoma DOI Creative Commons
Yaling Li, Bin Jiang,

Bancheng Chen

и другие.

Heliyon, Год журнала: 2024, Номер 10(6), С. e28244 - e28244

Опубликована: Март 1, 2024

BackgroundThe immune microenvironment and oxidative stress of melanoma show significant heterogeneity, which affects tumor growth, invasion treatment response. Single-cell bulk RNA-seq data were used to explore the heterogeneity melanoma.MethodsThe R package Seurat facilitated analysis single-cell dataset, while Harmony, another package, was employed for batch effect correction. Cell types classified using Uniform Manifold Approximation Projection (UMAP). The Secreted Signaling algorithm from CellChatDB.human applied elucidate cell-to-cell communication patterns within data. Consensus clustering skin cutaneous (SKCM) samples executed with ConsensusClusterPlus. To quantify infiltrating cells, we utilized CIBERSORT, ESTIMATE, TIMERxCell algorithms provided by Immuno-Oncology Biological Research (IOBR). Single nucleotide variant (SNV) conducted Maftools, an specifically designed this purpose. Subsequently, expression levels PXDN PAPSS2 genes assessed in tissues compared adjacent normal tissues. Furthermore, vitro experiments evaluate proliferation reactive oxygen species cells following transfection siRNA targeting PAPSS2.ResultsMalignant cell populations reclassified based on a comprehensive dataset analysis, yielded six distinct subsets. specific marker identified these subgroups then interrogate Cancer Genome Atlas Skin Cutaneous Melanoma (TCGA-SKCM) cohort, derived RNA sequencing data, resulting delineation two molecular subtypes. Notably, patients cluster2 (C2) subtype exhibited significantly more favorable prognosis those cluster1 (C1) subtype. An alignment characteristics observed between C2 unique functional Genes differentially expressed across subtypes subsequently leveraged construct predictive risk model. In investigations further revealed elevated tissue samples. Functional assays indicated that modulation could influence production (ROS) proliferative capacity cells.ConclusionThe constructed six-gene signature can be as response guide clinical diagnosis melanoma.

Язык: Английский

Процитировано

4
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

4
Pancreatic ductal adenocarcinoma cells reshape the immune microenvironment: Molecular mechanisms and therapeutic targets DOI Creative Commons
Yutong Zhao,

C.M. Qin,

Lin Chen

и другие.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1879(6), С. 189183 - 189183

Опубликована: Сен. 19, 2024

Язык: Английский

Процитировано

4
Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment DOI Creative Commons
Mengting Wan,

Shuaikang Pan,

Benjie Shan

и другие.

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Март 3, 2025

Aberrant lipid metabolism is a well-recognized hallmark of cancer. Notably, breast cancer (BC) arises from lipid-rich microenvironment and depends significantly on metabolic reprogramming to fulfill its developmental requirements. In this review, we revisit the pivotal role in BC, underscoring impact progression tumor microenvironment. Firstly, delineate overall landscape highlighting roles patient prognosis. Given that lipids can also act as signaling molecules, next describe exchanges between BC cells other cellular components Additionally, summarize therapeutic potential targeting aspects processes, lipid-related transcription factors immunotherapy BC. Finally, discuss possibilities problems associated with clinical applications lipid‑targeted therapy propose new research directions advances spatiotemporal multi-omics.

Язык: Английский

Процитировано

0
PCSK9 Promotes the Malignancy of Triple‐negative Breast Cancer Cells by Reducing Cholesterol Levels at the Plasma Membrane to Activate EGFR and HER3 DOI Creative Commons
Tianhong Li, Renfei Wu, Kathy Qian Luo

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Abstract Triple‐negative breast cancer (TNBC) is a highly heterogeneous and clinically aggressive disease with the highest mortality rate among all subtypes of cancer. To discover new driver genes for metastatic TNBC, this work compares transcription profiles MDA‐MB‐231‐GFP cells 231‐GFP‐derived lung (4–11). Results reveal that proprotein convertase subtilisin/kexin type 9 (PCSK9) upregulated in 4–11 cells. Knockdown PCSK9 greatly decreases tumorigenic potential cells, whereas overexpression significantly enhances tumor maliganancy. Mechanistically, binding to low‐density lipoprotein receptor (LDLR) results decreased LDLR at plasma membrane, which further cholesterol lipid raft membrane activates human epidermal growth factor 1 3 (EGFR HER3). Subsequently, phosphorylated EGFR HER3 activate Src/ERK/c‐Jun increase levels cyclin D3 vimentin thereby enhance cell metastasis. Metadata analyses also TNBC patients high expression exhibited worse clinical outcomes. Taken together, these findings not only novel mechanism by promotes malignant but indicate therapeutic target treating patients.

Язык: Английский

Процитировано

0
Tumor-intrinsic metabolic reprogramming and how it drives resistance to anti-PD-1/PD-L1 treatment DOI Open Access

Kyra Laubach,

Tolga Turan, Rebecca Mathew

и другие.

Cancer Drug Resistance, Год журнала: 2023, Номер 6(3), С. 611 - 41

Опубликована: Сен. 4, 2023

The development of immune checkpoint blockade (ICB) therapies has been instrumental in advancing the field immunotherapy. Despite prominence these treatments, many patients exhibit primary or acquired resistance, rendering them ineffective. For example, anti-PD-1/PD-L1 treatments are widely utilized across a range cancer indications, but response rate is only 10%-30%. As such, it necessary for researchers to identify targets and develop drugs that can be used combination with existing ICB overcome resistance. intersection cancer, metabolism, system gained considerable traction recent years as way comprehensively study mechanisms drive oncogenesis, evasion, immunotherapy result, new research continuously emerging support targeting metabolic pathways an adjuvant boost patient Due plethora studies highlighting this notion, review will integrate relevant articles demonstrate how tumor-derived alterations energy, amino acid, lipid metabolism dysregulate anti-tumor responses resistance therapy.

Язык: Английский

Процитировано

10