Granulocyte colony-stimulating factor (G-CSF)-producing tumor is one of the rare types of cancer clinically characterized by an elevated fever and white blood cell (WBC) increment. Although G-CSF producing tumors have been reported in several types of cancer including those of the lungs, cervix and bladder, G-CSF producing hepatocellular carcinoma is extremely rare. Here, we report the case of a rapidly growing and poorly differentiated hepatocellular carcinoma producing G-CSF. The patient showed symptoms of continuous high fever, stomach pain and cough, and high serum WBC counts, C-reactive protein (CRP) and G-CSF levels were found in laboratory tests. After a radical hepatectomy, the patient completely recovered from the above symptoms and inflammatory state. The serum levels of G-CSF were reduced to normal levels after radical surgery. An immunohistochemical analysis revealed the overexpression of G-CSF in the cytoplasm of certain hepatocellular carcinoma (HCC) cell. The patient’s serum WBC, CRP and G-CSF levels remained within normal levels in the six months after surgery without recurrence. This is the 9th case report of G-CSF producing hepatocellular carcinoma in English literature. We review the clinical characteristics of the G-CSF producing HCC and discuss a possible treatment strategy.
Background Circular RNA is a novel endogenous non-coding RNA with a stable loop structure, and theories for its biogenesis and usefulness as a biomarker in various cancers have been proposed. The present study investigated the significance of circular FAT1 (circFAT1) as a novel biomarker in esophageal squamous cell carcinoma (ESCC). Method CircFAT1 expression levels were measured in ESCC cell lines and the effects of downregulating circFAT1 on cell migration and invasion were examined using a transwell assay. The functions of miR-548g, which will be sponged by circFAT1, were assessed. Furthermore, the expression of circFAT1 was evaluated in 51 radically resected ESCC tissue samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationships between circFAT1 expression, clinicopathological factors, and patient prognosis were analyzed. Results CircFAT1 expression levels were significantly lower in tumor tissue than in adjacent non-tumorous mucosal tissue (p = 0.01). The downregulation of circFAT1 expression promoted ESCC cell migration and invasive ability, but not proliferation. The expression of miR-548g was upregulated by the downregulation of circFAT1. The overexpression of miR-548g also promoted ESCC cell migration and invasion. Recurrence-free survival (p = 0.02) and cancer-specific survival (p = 0.04) rates were significantly higher in patients with elevated circFAT1 expression levels. Conclusion The expression level of circFAT1 is a novel prognostic marker in ESCC patients. New treatment strategies may be developed using the tumor suppressive functions of circFAT1.
Background: High-mobility group box-1 (HMGB1) is involved in the tumorigenesis and metastasis of various cancers. The present study investigated the roles of extracellular HMGB1 in the progression of gastric cancer (GC) and the therapeutic effects of recombinant human soluble thrombomodulin (rTM) targeting HMGB1. Methods: The effects of extracellular HMGB1 and rTM on GC cells were assessed using proliferation and Transwell assays. Their effects on local tumor growth and metastasis were evaluated using subcutaneous tumor and liver metastasis mouse models, respectively. Plasma HMGB1 concentrations in GC patients were measured using ELISA. The relationships between plasma HMGB1 concentrations and the prognosis and clinicopathological factors of patients were also investigated. Results: GC proliferation, migration, and invasion abilities were promoted by increases in extracellular HMGB1 concentrations and alleviated by rTM. In the subcutaneous tumor model, local tumor growth was promoted by the addition of rhHMGB1 and alleviated by rTM. Similar changes occurred in the liver metastasis model. Recurrence-free survival (p < 0.01) and overall survival (p = 0.01) were significantly worse in patients with high plasma HMGB1 concentrations. Conclusion: Plasma HMGB1 concentrations are a prognostic marker in GC patients. Extracellular HMGB1 promotes cancer progression and has potential as a novel treatment target in GC cells for rTM.
Anterior gradient 2 (AGR2) reportedly promotes tumor growth and has an unfavorable impact on survival in several cancers. However, no comprehensive functional analysis of AGR2 in esophageal squamous cell carcinoma (ESCC) has been performed. In the present study, the function and clinical significance of AGR2 were examined using ESCC cell lines and clinical samples. AGR2 was upregulated in EC tissue and ESCC cell lines. The downregulation of AGR2 suppressed cell proliferation and increased the proportion of G2/M-phase cells and phosphorylation of p53 in TP53-wild-type ESCC and osteosarcoma cells. However, these changes were not observed in TP53-mutant ESCC cells. In addition, immunohistochemistry results demonstrated that high AGR2 and low p53 expression levels in ESCC tissues were correlated with a worse prognosis. These results suggested that although AGR2 enhanced cell proliferation by inhibiting p53 phosphorylation in TP53-wild-type ESCC, the same mechanism did not regulate cell functions in TP53-mutant ESCC. Thus, AGR2 served an important role in ESCC progression and might be a useful prognostic marker in patients with TP53-wild-type ESCC.
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