Aims: Our study investigates the significance of the expression of Wnt pathway proteins including beta-catenin, Axin, beta-transducin-repeat-containing protein (beta-TrCP), and adenomatous polyposis coli (APC) in squamous cell carcinoma of the esophagus (ESCC).
Methods: Immunohistochemical analysis was performed on paraffin-embedded tissue specimens from 128 resected ESCC tumors to detect the expression of beta-catenin, Axin, beta-TrCP, and APC. Correlation between immunoexpression, clinicopathological parameters, and patient survival was analyzed.
Results: Increased beta-catenin expression was noted in 22 (18.2%) of 121 tumor specimens. Reduced expression of Axin, beta-TrCP, and APC was observed in 57 (46.0%) of 124, 29 (24.4%) of 119, and 54 (48.2%) of 119 specimens, respectively. No correlation was found among these protein expressions. Axin protein expression was inversely correlated with tumor invasion depth (P = 0.033). Reduced Axin protein expression, lymph node involvement, and distant metastasis were significant negative predictors for overall survival and disease-free survival on univariate analysis. In multivariate analysis, reduced Axin expression remained a significant prognostic factor for patients with ESCC (P = 0.005).
Conclusions: Reduced Axin expression was observed in 46% of ESCC tumor specimens and was associated with poor prognosis in patients with ESCC. Further study is mandatory to elucidate the underlying mechanism responsible for loss of Axin expression and the role of Axin in ESCC tumorigenesis.
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http://dx.doi.org/10.1245/s10434-009-0593-3 | DOI Listing |
Nat Commun
November 2024
Department of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Embryonic axis formation is essential for patterning and morphogenesis in vertebrates and is tightly regulated by the dorsal organizer. Previously, we demonstrated that maternally derived Huluwa (Hwa) acts as a dorsal determinant, dictating axis formation by activating β-catenin signaling in zebrafish and Xenopus. However, the mechanism of activation and fine regulation of the Hwa protein remains unclear.
View Article and Find Full Text PDFPhytomedicine
December 2024
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China. Electronic address:
Background And Purpose: Targeting Wnt/β-catenin signaling emerges as one of the promising strategies for colorectal cancer (CRC) treatment, as this signaling is highly activated in CRC progression. Despite reports on the cytotoxic effects of hirsutine (HT), an indole alkaloid found in herbal medicines from the genus Uncaria, its therapeutic potential for CRC and the involved mechanisms are poorly understood. This study investigates the anticancer efficacy and the probable mechanisms of HT against CRC.
View Article and Find Full Text PDFSignal Transduct Target Ther
October 2024
Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
Front Endocrinol (Lausanne)
August 2024
Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sepsis, a life-threatening condition, involves complex interactions among metabolic alterations, inflammatory mediators, and host responses. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationships between 1400 metabolites and sepsis, and the mediating role of inflammatory factors. We identified 36 metabolites significantly associated with sepsis (p < 0.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
November 2024
Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit, Amsterdam, The Netherlands.
The inhibition of intracellular protein-protein interactions is challenging, in particular, when involved interfaces lack pronounced cavities. The transcriptional co-activator protein and oncogene β-catenin is a prime example of such a challenging target. Despite extensive targeting efforts, available high-affinity binders comprise only large molecular weight inhibitors.
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