CARD9 deficiency promotes pancreatic cancer growth by blocking dendritic cell maturation via SLC6A8-mediated creatine transport DOI Creative Commons
Cheng Tian, Huimin Yuan,

Yi Lu

и другие.

OncoImmunology, Год журнала: 2023, Номер 12(1)

Опубликована: Апрель 19, 2023

Pancreatic cancer (PC) is featured with low survival rate and poor outcomes. Herein, we found that the expression of caspase-recruitment domain-containing protein 9 (CARD9), predominantly expressed in innate immune cells, was positively related to prognosis PC patients. CARD9-deficient mice exhibited rapider progression poorer rate. CARD9 knockout decreased dendritic cell (DC) maturation impaired DC ability activate T cells vivo vitro. Adoptive transfer confirmed role deficiency relied on DCs. Creatine identified as most significant differential metabolite between WT DCs CARD9−/− wherein it played an essential maintaining function. led creatine levels by inhibiting transcription creatine-specific transporter, solute carrier family 6 member 8 (SLC6A8). Furtherly, deletion blocked p65 activation abolishing formation CARD9-BCL10-MALT1 complex, which prevented binding SLC6A8 promoter. These events transport into DCs, immaturity impairment antitumor immunity, consequently promoting progression.

Язык: Английский

Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway DOI Creative Commons
Mengyang Ding,

Jingyu Liu,

Honghui Lv

и другие.

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Фев. 28, 2023

Pancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is a highly lethal malignancy with poor prognosis. Polypeptide N-acetylgalactosaminyltransferase-6 (GALNT6) frequently overexpressed in PDAC. However, role GALNT6 PDAC remains unclear.The expression cancer and normal tissues were analyzed by bioinformatic analyses immunohistochemistry. CCK8 colony formation used to detect cell proliferation. Flow cytometry was applied cycle.The pyroptosis detected scanning electron microscopy. The mRNA qRT-PCR. protein localization western blot immunofluorescence assay. ELISA levels inflammatory factors.The associated advanced tumor stage, had an area under curve (AUC) value 0.919 based on genome atlas (TCGA) dataset. Knockdown inhibited proliferation, migration, invasion cycle arrest cells. Meanwhile, knockdown increased interleukin-1β (IL-1β), interleukin-6 (IL-6), necrosis factor-α (TNF-α) interleukin-18 (IL-18), release inflammasome increasing Gasdermin D (GSDMD), N-terminal GSDMD (GSDMD-N), E (GSDME) GSDME (GSDME-N) suppressed NOD-like receptor thermal domain 3 (NLRP3) glycosylation NF-κB inhibiting nucleus NF-κB. Additionally, promotes degradation O-glycosylation.We found that expressed plays carcinogenic role. results suggested regulates cells through NF-κB/NLRP3/GSDMD signaling. Our study might provides novel insights into roles progression.

Язык: Английский

Процитировано

10
Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges DOI

Zhichen Jiang,

Xiaohao Zheng,

Min Li

и другие.

Frontiers of Medicine, Год журнала: 2023, Номер 17(6), С. 1135 - 1169

Опубликована: Дек. 1, 2023

Язык: Английский

Процитировано

10
Ensemble machine learning and tree-structured Parzen estimator to predict early-stage pancreatic cancer DOI
Kah Keng Wong

Biomedical Signal Processing and Control, Год журнала: 2025, Номер 108, С. 107867 - 107867

Опубликована: Апрель 16, 2025

Язык: Английский

Процитировано

0
Stromal and tumor immune microenvironment reprogramming through multifunctional cisplatin-based liposomes boosts the efficacy of anti-PD-1 immunotherapy in pancreatic cancer DOI
Hang Yu, Wenting Zhu,

Caiyan Lin

и другие.

Biomaterials Science, Год журнала: 2023, Номер 12(1), С. 116 - 133

Опубликована: Ноя. 3, 2023

Application of ATF decorated cisplatin liposomes and anti PD-1 antibodies to mice with pancreatic cancer showed improved efficacy by enhancing drug penetration remodeling the immunosuppressive microenvironment.

Язык: Английский

Процитировано

9
A stratified two-stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer DOI Creative Commons
Saskia Hussung, Dilara Akhoundova, Clelia Pistoni

и другие.

ESMO Gastrointestinal Oncology, Год журнала: 2025, Номер 7, С. 100134 - 100134

Опубликована: Фев. 10, 2025

Язык: Английский

Процитировано

0
An Analysis of the mRNA Expression of Peripheral-Blood Stem and Progenitor Cell Markers in Pancreatic Neoplastic Disorders DOI Creative Commons
Krzysztof Dąbkowski, Maciej Tarnowski, Krzysztof Safranow

и другие.

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(4), С. 236 - 236

Опубликована: Март 28, 2025

Background: Our aim was to assess the expression profiles of messenger RNA (mRNA) stem-cell genes (POU5F1, NANOG) and pancreatic progenitor (CK19, HES1, INS, PDX1) in peripheral-blood mononuclear cells (PBMCs) selected neoplastic diseases, such as cancer neuroendocrine tumors, identify disease markers pancreas. Methods: In this study, 49 patients diagnosed with diseases (37 12 tumors) 34 control patients, all whom were hospitalized at a tertiary center, enrolled. Venous blood samples collected from participants, extracted PBMCs. The mRNA levels six markers— POU5F1 (POU class 5 homeobox 1), NANOG, CK19 (keratin 19), HES1 (HES family bHLH transcription factor INS (insulin), PDX1 (pancreatic duodenal 1)—were quantified via real-time quantitative PCR. data statistically analyzed explore associations between gene-expression various clinical, biochemical, morphological parameters (including full count, Ca 19-9, weight, height, BMI) Kruskal–Wallis test, Mann–Whitney U Spearman rank correlation coefficient. Results: results revealed that gene associated early stem cells, NANOG (median= 0.002, p = 0.03), well encoding insulin (median 0.004, 0.02) 0.0003, 0.005), significantly elevated cancer. However, tumors did not exhibit significant differences compared those observed group. Additionally, no among different stages Furthermore, overexpression found be positively correlated inflammatory markers, specifically C-reactive protein (CRP) WBC, Conclusions: An specific (NANOG, CK19) PBMCs may serve potential for cancer, reflecting disease’s interplay systemic inflammation.

Язык: Английский

Процитировано

0
Oligodendroglioma: Advances in Molecular Mechanisms and Immunotherapeutic Strategies DOI Creative Commons
Yongxin Zhao, Yan Yu, Weizhi Chen

и другие.

Biomedicines, Год журнала: 2025, Номер 13(5), С. 1133 - 1133

Опубликована: Май 7, 2025

Oligodendroglioma is a central nervous system tumor defined by IDH1/2 mutations and 1p/19q co-deletion. Current management involves maximal resection followed radiotherapy/chemotherapy, yielding 20-year survival rate of 37% for grade 3 tumors according to the WHO 2021 classification. As these primarily affect young middle-aged patients, novel therapies are urgently needed improve outcomes. Immunotherapy has revolutionized treatment modulating immune responses. However, its application in oligodendrogliomas faces two major hurdles, including immunosuppressive microenvironment (TME) blood–brain barrier’s restrictive properties. This review first examines oligodendroglioma’s molecular alterations refine diagnosis guide targeted therapies. Next, we focus on oligodendroglioma TME evaluate emerging immunotherapies, oncolytic viruses, checkpoint blockade, chimeric antigen receptor (CAR) T-cell therapy, cancer vaccines. Finally, discuss current challenges future directions overcome therapeutic limitations advance strategies.

Язык: Английский

Процитировано

0
Complete Response in Recurrent End-Stage Pancreatic Cancer After Combined Immune Cell Therapy of α-Galactosylceramide Dendritic Cell Vaccine Therapy, Wilms’ Tumor 1 Dendritic Cell Vaccine and Natural Killer Cell Therapy DOI Open Access
Keibun Liu,

Hisashi Nagai,

Nobuo Kanai

и другие.

Cureus, Год журнала: 2025, Номер unknown

Опубликована: Май 6, 2025

Язык: Английский

Процитировано

0
Breaking the immune desert: Strategies for overcoming the immunological challenges of pancreatic cancer DOI
Tianming Wang, Wenjing Song, Yuan Tang

и другие.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер 1880(4), С. 189353 - 189353

Опубликована: Май 22, 2025

Язык: Английский

Процитировано

0
The deubiquitinating enzyme MINDY2 promotes pancreatic cancer proliferation and metastasis by stabilizing ACTN4 expression and activating the PI3K/AKT/mTOR signaling pathway DOI Creative Commons
Peng Liu, Songbai Liu, Changhao Zhu

и другие.

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Май 3, 2023

The pathogenic mechanisms of pancreatic cancer (PC) are still not fully understood. Ubiquitination modifications have a crucial role in tumorigenesis and progression. Yet, the MINDY2, member motif interacting with Ub-containing novel DUB family (MINDY), as newly identified deubiquitinating enzyme, PC is unclear. In this study, we found that MINDY2 expression elevated tissue (clinical samples) was associated poor prognosis. We also pro-carcinogenic factors such epithelial-mesenchymal transition (EMT), inflammatory response, angiogenesis; ROC curve suggested has high diagnostic value PC. Immunological correlation analysis deeply involved immune cell infiltration checkpoint-related genes. vivo vitro experiments further promotes proliferation, invasive metastasis, EMT. Meanwhile, actinin alpha 4 (ACTN4) MINDY2-interacting protein by mass spectrometry other experiments, ACTN4 levels were significantly correlated expression. ubiquitination assay confirmed stabilizes level deubiquitination. pro-oncogenic effect inhibited silencing ACTN4. Bioinformatics Analysis Western blot through deubiquitination thus activates PI3K/AKT/mTOR signaling pathway. conclusion, oncogenic mechanism PC, suggesting viable candidate gene for may be therapeutic target critical prognostic indicator.

Язык: Английский

Процитировано

7