the-efficacy-underlying-pathway-mechanisms-shidugao-treatment-for

The Efficacy and Underlying Pathway Mechanisms of ShiDuGao Treatment for Anus Eczema Based on GEO Datasets and Network Pharmacology

Anus eczema is a chronic and recurrent inflammatory skin disease affecting the area around the anus. While the lesions primarily occur in the anal and ...

a-rat-model-pouchitis-following-proctocolectomy-ileal-pouch-anal

A Rat Model of Pouchitis Following Proctocolectomy and Ileal Pouch-Anal Anastomosis Using Dextran Sulfate Sodium

Ulcerative colitis (UC) is a chronic immune-mediated disease that affects the entire colon and rectum with a relapsing and remitting course, causing ...

Tianjin Medical University General Hospital

Tianjin General Surgery Institute

Esophageal squamous cell carcinoma (ESCC) has a dismal prognosis, and hypoxia plays a key role in metastasis and proliferation of ESCC. Thus, we aimed to develop a hypoxia-based gene signature to assist in the treatment decisions and prognosis.

Establishment of a risk model by integrating hypoxia genes in predicting prognosis of esophageal squamous cell carcinoma.

To date, a few studies indicated that probiotics are beneficial to pouchitis, but no meta-analyses summarized the outcomes of probiotics in pouchitis in detail.

The efficacy of probiotics on the prevention of pouchitis for patients after ileal pouch-anal anastomosis: A meta-analysis.

Heterogeneous mismatch repair (MMR) status in metastatic colorectal cancer (mCRC) may associate with refractoriness to immunotherapy. We aimed here to study the concordance in MMR status between primary and paired metastasis in mCRC. Our study included 84 patients diagnosed with mCRC with primary and matched metastatic cancers. Immunohistochemistry was used to determine the MMR status of primary lesions and matched metastases. Pooled analysis of 913 cases was used to evaluate the prevalence and organ specificity of MMR status heterogeneity. The correlations between MMR pattern heterogeneity and clinical outcomes were analyzed. MMR status heterogeneity between primary and corresponding metastatic sites was exhibited by 10 (11.9%) patients. The prevalence of the heterogeneous MMR phenotype was significantly higher in primary tumors with deficient MMR (dMMR) than with proficient MMR (pMMR), which was verified in the pooled analysis ( P <0.001). Among patients with a dMMR primary tumor, the discrepancy was detected in liver, lung, ovary, peritoneum, and distant lymph node metastases. However, the discrepancy was confined to liver (26/440) or peritoneum (7/112) ( P =0.02) in patients with a pMMR primary tumor. Patients with or without MMR status heterogeneity experienced comparable overall survival ( P =0.452). Heterogeneous MMR patterns generally existed in a subset of patients with mCRC, particularly those with dMMR primary tumors. Testing the metastatic site may be valuable because the discordance of MMR status may potentially affect immune surveillance and immunotherapy.

Intraindividual Tumor Heterogeneity of Mismatch Repair Status in Metastatic Colorectal Cancer.

PTPRF interacting protein alpha 1 (PPFIA1) is reportedly related to the occurrence and progression of several kinds of malignancies. However, its role in esophageal squamous cell carcinoma (ESCC) is unclear. This current study investigated the prognostic significance and biological functions of PPFIA1 in ESCC.

High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis.

Ubiquitin-specific protease 4 (USP4) represents a potential oncogene involved in various human cancers. Nevertheless, the biological roles and precise mechanism of USP4 in esophageal squamous cell carcinoma (ESCC) progression are not understood. Here, USP4 expression was found to be markedly upregulated in ESCC tumor tissues and cells. Loss- and gain-of-function assays suggested that USP4 silencing inhibited ESCC cell proliferation, migration, and invasion, while USP4 overexpression promoted these behaviors. Consistently, USP4 silencing repressed tumor growth and metastasis in an ESCC nude mouse model in vivo. As a target molecule of USP4, transforming growth factor-β-activated kinase 1 (TAK1) also showed high expression in ESCC. Moreover, we observed that USP4 specifically interacted with TAK1 and stabilized TAK1 protein levels via deubiquitination in ESCC cells. Importantly, USP4 promotes ESCC proliferation, migration, and invasion via the MEK/ERK signaling pathway and can be inhibited by U0126. Neutral red (NR), an inhibitor of USP4 can suppress ESCC progression in vitro and in vivo. Overall, this study revealed that USP4/TAK1 plays crucial roles in ESCC progression by modulating proliferation, migration, and invasion, and USP4 might be a potential therapeutic target in ESCC.

USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1.

Through transcriptome sequencing, we previously identified a new osteosarcoma-specific, frequent fusion gene, LRP1-SNRNP25, and found that it played an important role in tumor cell invasion and migration. However, the specific mechanism remains unclear. In this article, whole-genome sequencing further confirmed that the LRP1-SNRNP25 fusion gene is formed by fusion of LRP1 exon 8 and SNRNP25 exon 2. In vitro, scratch and Transwell assays demonstrated that the migration and invasion abilities of LRP1-SNRNP25-overexpressing osteosarcoma cells were significantly increased. To explore the molecular mechanism of the LRP1-SNRNP25 fusion in affecting osteosarcoma cell migration and invasion, we evaluated the migration and invasion-related molecular signaling pathways by western blotting. Some migration- and invasion-related genes, including pJNK and MMP2, were upregulated. Coimmunoprecipitation-mass spectrometry showed that 37LRP can interact with pJNK. Western blotting confirmed that LRP1-SNRNP25 overexpression upregulates 37LRP protein expression. Immunofluorescence staining showed the intracellular colocalization of LRP1-SNRNP25 with pJNK and 37LRP proteins and that LRP1-SNRNP25 expression increased the pJNK and 37LRP levels. Coimmunoprecipitation (co-IP) confirmed that LRP1-SNRNP25 interacted with pJNK and 37LRP proteins. The pJNK inhibitor SP600125 dose-dependently decreased the pJNK/37LRP/MMP2 levels. After siRNA-mediated 37LRP knockdown, the MMP2 protein level decreased. These two experiments proved the upstream/downstream relationship among pJNK, 37LRP, and MMP2, with pJNK the farthest upstream and MMP2 the farthest downstream. These results proved that the LRP1-SNRNP25 fusion gene exerts biological effects through the pJNK/37LRP/MMP2 signaling pathway. In vivo, LRP1-SNRNP25 promoted osteosarcoma cell growth. Tumor growth was significantly inhibited after SP600125 treatment. Immunohistochemical analysis showed that the pJNK, MMP2, and Ki-67 protein levels were significantly increased in tumor tissues of LRP1-SNRNP25-overexpressing cell-injected nude mice. Furthermore, lung and liver metastasis were more prevalent in these mice. In a word, LRP1-SNRNP25 promotes invasion, migration, and metastasis via pJNK/37LRP/MMP2 pathway. LRP1-SNRNP25 is a potential therapeutic target for LRP1-SNRNP25-positive osteosarcoma.

ArticleTotal : 2	Year
Publication title	2024
Publication title	2024

Article	Year
Establishment of a risk model by integrating hypoxia genes in predicting prognosis of esophageal squamous cell carcinoma. Cancer medicine\| PubMed ID: 35789548	2023
The efficacy of probiotics on the prevention of pouchitis for patients after ileal pouch-anal anastomosis: A meta-analysis. Technology and health care : official journal of the European Society for Engineering and Medicine\| PubMed ID: 36278367	2023
Intraindividual Tumor Heterogeneity of Mismatch Repair Status in Metastatic Colorectal Cancer. Applied immunohistochemistry & molecular morphology : AIMM\| PubMed ID: 36409630	2023
High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis. BMC cancer\| PubMed ID: 37158817	2023
USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1. Cell death & disease\| PubMed ID: 37949874	2023
The fusion gene LRP1-SNRNP25 drives invasion and migration by activating the pJNK/37LRP/MMP2 signaling pathway in osteosarcoma. Cell death discovery\| PubMed ID: 38678020	2024

Wanyi Xiao

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