Hong Tang

Characterization of Tumor-Suppressive Function of SOX6 in Human Esophageal Squamous Cell Carcinoma

Purpose: By using cDNA microarray analysis, we identified a transcriptional factor, SOX6, was frequently downregulated in esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the role of SOX6 in human esophageal cancer development, and to examine the prevalence and clinical significance of SOX6 downregulation in ESCC. Experimental Design: Expressions of SOX6 mRNA in 50 ESCCs and SOX6 protein in 300 ESCCs were investigated by semiquantitative RT-PCR and immunohistochemistry, respectively. The tumor-suppressive function of SOX6 was characterized by cell growth, foci formation, wound-healing and cell invasive assays, and tumor xenograft experiment. Western blot analysis was applied to detect protein expression levels. Results: SOX6 was frequently downregulated in primary ESCCs in both mRNA level (29/50, 58%) and protein level (149/219, 68.0%), which was significantly associated with the poor differentiation (P = 0.029), lymph node metastases (P = 0.014), advanced TNM stage (P = 0.000), and disease-specific survival (P < 0.001). Multivariate analysis indicated that the downregulation of SOX6 (P = 0.000) was a significant independent prognostic factors for ESCC. Functional studies showed that SOX6 was able to suppress both in vitro and in vivo tumorigenic ability of ESCC cells. The tumor-suppressive mechanism of SOX6 was associated with its role in G1/S cell-cycle arrest by upregulating expressions of p53 and p21WAF1/CIP1 and downregulating expressions of cyclin D1/CDK4, cyclin A, and β-catenin. Conclusions: We provided the first evidence that SOX6 is a novel tumor-suppressor gene in ESCC development and is a potential prognostic marker in ESCC. Clin Cancer Res; 17(1); 46–55. ©2010 AACR.

Overexpression of GPR39 contributes to malignant development of human esophageal squamous cell carcinoma

BackgroundBy using cDNA microarray analysis, we identified a G protein-coupled receptor, GPR39, that is significantly up-regulated in ESCC. The aim of this study is to investigate the role of GPR39 in human esophageal cancer development, and to examine the prevalence and clinical significance of GPR39 overexpression in ESCC.MethodsThe mRNA expression level of GPR39 was analyzed in 9 ESCC cell lines and 50 primary ESCC tumors using semi-quantitative RT-PCR. Immunohistochemistry was used to assess GPR39 protein expression in tissue arrays containing 300 primary ESCC cases. In vitro and in vivo studies were done to elucidate the tumorigenic role of GPR39 in ESCC cells.ResultsWe found that GPR39 was frequently overexpressed in primary ESCCs in both mRNA level (27/50, 54%) and protein level (121/207, 58.5%), which was significantly associated with the lymph node metastasis and advanced TNM stage (P < 0.01). Functional studies showed that GPR39 has a strong tumorigenic ability. Introduction of GPR39 gene into ESCC cell line KYSE30 could promote cell proliferation, increase foci formation, colony formation in soft agar, and tumor formation in nude mice. The mechanism by which amplified GPR39 induces tumorigenesis was associated with its role in promoting G1/S transition via up-regulation of cyclin D1 and CDK6. Further study found GPR39 could enhance cell motility and invasiveness by inducing EMT and remodeling cytoskeleton. Moreover, depletion of endogenous GPR39 by siRNA could effectively decrease the oncogenicity of ESCC cells.ConclusionsThe present study suggests that GPR39 plays an important tumorigenic role in the development and progression of ESCC.

Pathological complete response to gefitinib in a 10-year-old boy with EGFR-negative pulmonary mucoepidermoid carcinoma: a case report and literature review.

Pulmonary Mucoepidermoid carcinoma (MEC) accounts for 0.1‐0.2% of all lung cancer. It occurred in the 3‐78 years old, and 50% patients younger than 30. MEC has no standard treatment, but recently reports indicated MEC without epidermal growth factor receptor (EGFR) mutations sensitive to gefitinib.

Predictive significance of HMGCS2 for prognosis in resected Chinese esophageal squamous cell carcinoma patients

Despite a series of attempts during the last decades, the prognosis of esophageal squamous cell carcinoma (ESCC) remains poor. Different responses of individual tumors encouraged us to look for valuable prognostic markers. As a key regulator controlling the anabolic ketogenic pathway, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) has been reported to play a crucial role in colorectal cancer and prostate cancer. However, its importance to ESCC has not been verified. Therefore, a large cohort retrospective study was planned, to investigate the relationship between HMGCS2 expression and ESCC prognosis. By adopting real-time polymerase chain reaction (PCR) and immunohistochemical (IHC) staining, HMGCS2 expression was examined in tissues of 300 ESCC patients with complete resection. Besides, the association between HMGCS2 protein expression and survival time was evaluated through chi-square test and Kaplan–Meier analysis. With the use of Cox-proportional hazards model, the prognostic impact of clinicopathologic variables and biomarker expression was evaluated. Compared with their non-tumor counterparts, HMGCS2 downregulation occurred in 65.5% and 37.6% of primary ESCCs on the mRNA and protein levels (P<0.001), respectively. On the protein level, HMGCS2 expression was associated with tumor cell differentiation (P=0.003), pT status (P=0.006), and TNM stage (P=0.010). In the down-HMGCS2 expression group, the 5-year overall survival (OS) and relapse-free survival (RFS) are poorer than those in the normal expression group (19 months vs 24 months, P=0.002; 13 months vs 17 months, P=0.007, respectively). According to the TNM stage, stratified analysis revealed that its discernibility on RFS was only pronounced in patients with advanced clinical stage (P=0.001). In addition, multivariate Cox regression analysis showed that HMGCS2 expression was an independent risk factor for RFS (P=0.032) instead of OS (P=0.099). The findings of this study provided the evidence that HMGSC2 represented a potential novel prognostic biomarker for ESCC patients.

PET-CT evaluation of the curative effect of crizotinib on malignant myofibroblastoma with rare mutation of ALK R401: a case report and literature review

Objective The purpose of this article is to explore the targeted treatment of malignant myofibroblastoma and evaluate the role of neoplasm metabolite markers in the evaluation of efficacy after targeted therapy. Method This report described a case of myofibroblastic sarcoma with rare mutation of ALK R401 in a 58-year-old man prescribed with crizotinib, to evaluate its curative effect by positron emission tomography coupled with computed tomography (PET-CT). After the progressive disease in the brain, bevacizumab combined with crizotinib was administered. The Response Evaluation Criteria in Solid Tumors (RECIST), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were used to assess the efficacy. The efficacy was assessed by comparing changes in MTV and TLG. Result After the treatment of crizotinib, the tumor volume was decreased. However, bevacizumab combined with crizotinib had not improved the prognosis. The change of MTV and TLG was consistent with the efficacy. The increase of MTV and TLG is an early indicator of the poor prognosis of patients. Conclusion The treatment of the crizotinib patient with the mutation of ALK R401 was effective. The values of MTV and TLG reflected the prognosis earlier than RECIST.

Perioperative chemotherapy with pemetrexed and cisplatin for pulmonary large-cell neuroendocrine carcinoma: a case report and literature review

Background Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is associated with poor prognosis, and its treatment strategy is still controversial, especially regarding chemotherapy regimens. Case report We present the case of a 49-year-old Chinese male with primary pulmonary LCNEC treated with neoadjuvant and adjuvant chemotherapy with cisplatin plus pemetrexed. A suspected quasi-circular mass in the left lower pulmonary lobe and an enlarged mediastinal lymph node were found. The patient was diagnosed with adenocarcinoma with neuroendocrine differentiation based on computerized tomography-guided percutaneous lung biopsy. An EGFR gene mutation test showed negative results. Cisplatin and pemetrexed were administered as the neoadjuvant chemotherapy regimen. The primary lesion had reduced markedly, and the enlarged mediastinal lymph node had disappeared after two cycles of neoadjuvant chemotherapy. A left lower lobectomy and mediastinal lymph node dissection were performed. The lesion was confirmed as LCNEC based on postoperative histopathological analysis and immunohistochemical results. The patient underwent four cycles of adjuvant chemotherapy with cisplatin and pemetrexed for a month postoperatively, followed by postoperative adjuvant radiotherapy. The patient was still alive after a follow-up of 24 months, with no evidence of tumor recurrence. Conclusion Cisplatin combined with pemetrexed is effective and safe for patients with pulmonary LCNEC.

Reduction of AZGP1 predicts poor prognosis in esophageal squamous cell carcinoma patients in northern China

Background As a key regulator in lipid mobilization, AZGP1 has been reported to play a significant role in various cancers. This study was carried out to investigate the role of AZGP1 in the development of esophageal squamous cell carcinoma (ESCC) patients in Northern China. Materials and methods Through the application of quantitative real-time polymerase chain reaction and immunohistochemical staining, AZGP1 expression in ESCC tissues from Northern China was examined. Results Decreased expression of AZGP1 was observed in ~60% ESCC patients. AZGP1 downregulation was significantly associated with lymph node metastasis (P=0.035), advanced clinical stage (P=0.018), poor prognosis for 5-year disease-specific survival (DSS; P<0.001), local recurrence-free survival (LRFS; P=0.016), and metastasis-free survival (MeFS; P=0.014). In addition, Cox multivariate analysis revealed that AZGP1 downregulation remained to be an independent prognosticator for shorter DSS (P=0.001), LRFS (P=0.011), and MeFS (P=0.004). Conclusion AZGP1 might be a candidate tumor suppressor and a potential novel prognostic biomarker for ESCC patients in Northern China.