Downregulated ECRG4 is correlated with lymph node metastasis and predicts poor outcome for nasopharyngeal carcinoma patients.

OBJECTIVE: Esophageal cancer-related gene 4 (ECRG4) is a new candidate tumor suppressor gene. In this retrospective study, we evaluated ECRG4 protein expression in patients with nasopharyngeal carcinoma (NPC) under curative treatment and examined its association with pathological features and clinical outcomes as a possible biomarker for diagnosis and prognosis of NPC. METHODS: We enrolled 122 patients with a first diagnosis between January 2001 and December 2003. Tumor tissue and control tissue from biopsies underwent immunohistochemical staining for ECRG4. ECRG4 expression was analyzed by clinicopathological variables. After Kaplan-Meier survival analysis, we used Cox proportional hazards regression to estimate the predictive effect of ECRG4 expression on overall survival. RESULTS: ECRG4 protein level was lower in NPC than control tissue (P < 0.01). It was inversely related to node status (P < 0.001) and clinical stage (P = 0.027). ECRG4 expression was associated with overall survival, and downregulated ECRG4 expression was an independent prognostic factor of poor survival (hazard ratio = 0.677, 95 % confidence interval 0.463-0.989, P = 0.044). CONCLUSIONS: A significant NPC patients showed downregulated ECRG4 expression, which is correlated with lymph node metastasis. The marker could be an independent prognostic factor for NPC patients. The precise function of ECRG4 in the progression of NPC, especially for lymphatic metastasis, deserves further investigation, which would bring a new target for personalized therapy.

Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro.

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 microM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 +/- 3.9% in HNE1-LMP1 cells vs 37.89 +/- 4.9% in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 +/- 3.5 vs 65.87 +/- 5.9%), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 +/- 3.7 and 27.91 +/- 2.1%), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 +/- 3.9 vs 29.19 +/- 6.27%) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.

Up-regulation of nuclear receptor coactivator amplified in breast cancer-1 in papillary thyroid carcinoma correlates with lymph node metastasis.

INTRODUCTION: Nuclear receptor coactivator amplified in breast cancer-1 (AIB1), a new oncogenic coactivator, is commonly overexpressed and amplified in variety of human cancers. However, the expression of AIB1 in papillary thyroid carcinoma (PTC), the major histologic type of thyroid cancer, and its clinical significance are still unclear. MATERIALS AND METHODS: AIB1 expression in PTC was examined by immunohistochemistry using tissue microarrays comprised of 90 primary PTC, 46 matched lymph node, and 20 normal thyroid tissue specimens in this study. RESULTS: In the normal thyroid specimens, AIB1 expression was either absent or at low levels. In contrast, AIB1 overexpression was detected in 50 of 83 (60.2 %) primary PTC specimens. Up-regulated AIB1 was evident in 39 of 46 (73.5 %) matched lymph nodes. Overexpression of AIB1 was observed more frequently in PTCs with lymph node metastasis [N1a/N1b, 39/46 (73.5 %)] versus PTCs without lymph node metastasis [N0, 14/34 (41.2 %)]. Furthermore, high-level AIB1 expression was only observed in the lymph node-positive specimens. Moreover, we found no correlation between AIB1 expression and ER expression in PTC tissues. CONCLUSIONS: Our findings suggest that overexpression of AIB1 may be a biomarker for tumorigenesis and progression of PTC and may play an important role in its acquisition of a metastatic phenotype.

Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts.

UNLABELLED: It has been shown that arsenic trioxide (ATO) induced apoptosis in human nasopharyngeal carcinoma cells and inhibited the growth of nasopharyngeal carcinoma xenografts (NPCX) in nude mice. AIM: The present study was designed to determine whether ATO at the non-toxic dose level could potentiate the therapeutic effectiveness of radiation therapy in nasopharyngeal carcinoma, using a BALB/C nude mouse xenograft model. METHODS: The mice bearing NPCX were treated with radiation alone (2, 4, and 6 Gy), ATO alone (4 mg/kg/day x 6 days), and ATO plus radiation at the same dosage levels. Time of tumor growth delay (defined as the time necessary for the tumor to grow four-fold of its initial volume after, compared with untreated tumors) and toxic effects were determined. RESULTS: The low dose ATO alone has no pronounced effects on tumor growth delay compared to untreated control. However, compared with radiation alone, the combined regimen delayed the tumor growth by 2-10 days and had no significant toxic effects such as the liver function damage. CONCLUSIONS: Combination of ATO at non-toxic dose level and radiation has synergistic effects on tumor growth inhibition in vivo and is well tolerated.

Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 æM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 ± 3.9 percent in HNE1-LMP1 cells vs 37.89 ± 4.9 percent in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 ± 3.5 vs 65.87 ± 5.9 percent), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 ± 3.7 and 27.91 ± 2.1 percent), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 ± 3.9 vs 29.19 ± 6.27 percent) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.