Macrophages play a critical role in the initiation and progression in various human solid tumors; however, their role and transformation in pancreatic ductal adenocarcinoma (PDAC) were still illusive. Here, immunohistochemistry was used to determine CD206 (specific marker of M2 macrophage) and PKM2 expression in PDAC tissues. Statistical analysis, such as Pearson χ test, Spearman's rank test, Kaplan-Meier and COX regression assay were used to evaluate their roles on PDAC prognosis. Data showed that both CD206 and PKM2 were elevated and responsible for a poor prognosis for PDAC. In addition, we showed that the two factors were positively correlated; co-overexpression of the two factors conferred the worst prognosis and functioned as an independent prognostic factor for the disease. Our data showed that M2 macrophage infiltration was correlated with PKM2 expression in PDAC cells. The two markers exerted synergistic effect on PDAC progression. Our results suggested dual-target inhibition M2 macrophage polarization and PKM2 expression of cancer cells might be novel approaches to treat PDAC.
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http://dx.doi.org/10.7150/jca.38981 | DOI Listing |
JCI Insight
January 2025
Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Chronic wounds have emerged as a tough clinical challenge. An improved understanding of wound healing mechanisms is paramount. Collagen XVII (COL17), a pivotal constituent of hemidesmosomes, holds considerable promise for regulating epidermal cell adhesion to the basement membrane, as well as for epidermal cell motility and self-renewal of epidermal stem cells.
View Article and Find Full Text PDFBlood
January 2025
St Jude Children's Research Hospital, Memphis, Tennessee, United States.
Recurrent IDH mutations catalyze NADPH-dependent production of oncometabolite R-2HG for tumorigenesis. IDH inhibition provides clinical response in a subset of acute myeloid leukemia (AML) cases; however, most patients develop resistance, highlighting the need for more effective IDH-targeting therapies. By comparing transcriptomic alterations in isogenic leukemia cells harboring CRISPR base-edited IDH mutations, we identify the activation of adhesion molecules including CD44, a transmembrane glycoprotein, as a shared feature of IDH-mutant leukemia, consistent with elevated CD44 expression in IDH-mutant AML patients.
View Article and Find Full Text PDFJ Diabetes Investig
January 2025
Faculty of Medicine, Internal Medicine, Shimane University, Izumo, Shimane, Japan.
Aim/introduction: Senescence is a key driver of age-related kidney dysfunction, including diabetic kidney disease. Oxidative stress activates cellular senescence, induces abnormal glycolysis, and is associated with pyruvate kinase muscle isoform 2 (PKM2) dysfunction; however, the mechanisms linking PK activation to cellular senescence have not been elucidated. We hypothesized that PKM2 activation by TEPP-46 could suppress oxidative stress-induced renal tubular cell injury and cellular senescence.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
January 2025
Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Background: Triggering receptor expressed on myeloid cells 2 (TREM2), a surface receptor predominantly expressed on myeloid cells, is a major hub gene in pathology-induced immune signaling. However, its function in hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the role of TREM2 in the tumor microenvironment in the context of HCC progression.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
3-Hydroxyacyl-CoA dehydratase 2 (HACD2), an obesity-related gene involved in the elongation of long-chain fatty acids, is highly expressed in pancreatic cancer (PC) and is associated with patient prognosis. Interestingly, the study reveals that HACD2 mediated the proliferation of PC cells in a dehydratase-independent manner, affecting the downstream glycolytic pathway. Mechanistically, HACD2 promotes PC cells proliferation by binding to E3 ubiquitin-protein ligase parkin (PRKN) and enhancing pyruvate kinase PKM (PKM2) dissociation from PRKN, resulting in reduced ubiquitination of PKM2 and increased dimerization of PKM2, which subsequently promote c-Myc expression and tumor growth.
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