Guoxian Long

Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma: Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio

Pretreatment hematological markers of inflammatory response have emerged as prognostic factors for patients with cancer. In this study, we evaluated the prognostic significance of various hematologic parameters in patients with nasopharyngeal carcinoma (NPC).

Interleukin-6 promotes the migration and invasion of nasopharyngeal carcinoma cell lines and upregulates the expression of MMP-2 and MMP-9

Nasopharyngeal carcinoma (NPC) shows the highest invasive and metastatic features among head and neck cancers. Distant metastasis remains the predominant mode of treatment failure in NPC patients. The role of interleukin-6 (IL-6) in NPC progression is not fully understood. In this study, we explored whether IL-6 could promote the migration and invasion activity of NPC cell lines, as well as whether the effect of IL-6 on cell migration and invasion is mediated through regulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. Our results revealed that IL-6 and its receptors are broadly expressed in various NPC cell lines including HNE1, HONE1, CNE1, CNE1-LMP1 and 5-8F. Exogenous IL-6 enhanced cell proliferation slightly, but promoted cell migration and invasion significantly in both HNE1 and CNE1-LMP1 cell lines. In addition, an elevation in the expression of MMP-2 and MMP-9 could be induced by IL-6 stimulation. On the contrary, combining treatment with monoclonal anti-human IL-6R antibody (anti-IL-6R mAb) resulted in decreased proliferation, migration and invasion capabilities of NPC cells. Anti-IL-6R mAb also inhibited the expression of MMP-2 and MMP-9 in IL-6-stimulated HNE1 and CNE1-LMP1 cells. In summary, our data suggested that IL-6 mainly promotes the cell migration and invasion of NPC cells. The effect of IL-6 on cell migration and invasion may be mediated through regulation of the expression of MMP-2 and MMP-9. Thus, IL-6 or its related signaling pathways may be a promising target for preventing and inhibiting NPC metastasis.

Decreased expression of the carboxyl terminus of heat shock cognate 70 interacting protein in human gastric cancer and its clinical significance.

The carboxyl terminus of heat shock cognate 70 interacting protein (CHIP) is an E3 ubiquitin ligase, which can promote ubiquitylation and degradation of many tumor-related proteins. However, the expression of CHIP in human gastric cancer has not been investigated. In this study, the mRNA and protein levels of CHIP expression in 53 cases of gastric cancer and matched normal tissues were determined by quantitative real-time PCR, western blotting and immunohistochemistry. We showed that CHIP was registered from basal to middle portions of normal gastric mucosa. CHIP expression was notably decreased or lost in human gastric cancer samples compared with the matched normal non-cancer samples. The correlations between CHIP downregulation and the clinicopathological characteristics were also evaluated. The expression of CHIP was significantly lower in the gastric cancer samples compared to the matched normal samples at both mRNA and protein levels (P<0.05 and P<0.05, respectively). More importantly, the downregulation of CHIP was correlated with TNM stage (P=0.048) and lymph node metastasis (P=0.010) at the mRNA levels. In addition, the downregulation of CHIP was correlated with lymph node metastasis (P=0.021) and tumor differentiation (P=0.009) at the protein levels. Taken together, at both mRNA and protein levels, the decreased expression of CHIP was correlated with lymph node metastasis. Furthermore, our study suggests that a negative correlation exists between CHIP expression and tumor malignancy in human gastric cancer.

Prognostic role of epidermal growth factor receptor in nasopharyngeal carcinoma: a meta-analysis.

Various studies have assessed the prognostic value of epidermal growth factor receptor (EGFR) overexpression in nasopharyngeal carcinoma (NPC), but their results remain controversial.

DJ-1 knockdown inhibits growth and xenograft‑induced tumor generation of human hepatocellular carcinoma cells

The aim of this study was to identify potential downstream effectors of the oncogene DJ-1 in hepatocellular carcinoma (HCC) cell lines, and examine its role in the Akt signaling pathway and HCC oncogenesis. Expression of the DJ-1 protein was assessed by immunoblotting in several human HCC cell lines. Knockdown of DJ-1 was achieved by transfecting DJ-1-specific short hairpin RNAs into the HepG2 HCC cell line. The effect of DJ-1 downregulation on phosphatase and tensin homolog (PTEN) and phosphorylated Akt was evaluated. In addition, cell cycle, proliferation, adhesion and invasion were analyzed in the DJ-1 knockdown of HepG2 cells. The growth of HepG2‑induced tumor was evaluated in a nude mouse model after DJ-1 silencing. Stable DJ-1 knockdown was achieved in HepG2 cells using a shRNA eukaryotic expression vector. Downregulation of DJ-1 increased PTEN expression but decreased phosphorylation of Akt in HepG2 cells. In addition, DJ-1 knockdown resulted in the decreased proliferation, adhesion and invasion of HepG2 cells in vitro, and inhibited the growth of HepG2-induced tumor in vivo. DJ-1 knockdown altered the malignant behavior of HepG2 cells, potentially through the Akt signaling pathway, suggesting a crucial role for DJ-1 in the oncogenesis of HCC.

Predictive value of a serum-based proteomic test in non-small-cell lung cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitors: a meta-analysis

Abstract Objective: Several studies have demonstrated that a serum-based proteomic test (VeriStrat) is able to predict the clinical outcome of non-small-cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, these studies have limited power to draw a precise conclusion because of their small sample sizes and inconsistent results. Therefore, a meta-analysis was carried out in an attempt to provide more persuasive evidence. Research design and methods: Electronic searches for relevant articles in PubMed, Embase, Medline, and Web of Science published up to May 2013 were conducted. Stata Statistical Software version 12.0 was applied for statistical analysis. The combined hazard ratio (HR) and 95% confidence interval (CI) were estimated using fixed-effects models. Results: Eleven cohorts involving 706 patients collected from seven studies were subjected to final analysis. This serum-based proteomic test’s ‘good’ status predicted a better clinical outcome with a pooled HR of 0.40 (95% CI 0.32 to 0.49; p < 0.001) for overall survival (OS), and 0.49 (95% CI 0.39 to 0.60; p < 0.001) for progression-free survival (PFS). There was no significant heterogeneity, but a slight publication bias in this study. Conclusions: Our meta-analysis demonstrated that this serum-based proteomic test has a predictive value for NSCLC patients treated with EGFR-TKIs. Future data are needed to validate and update our results.

Specific targeting of nasopharyngeal carcinoma cell line CNE1 by C225-conjugated ultrasmall superparamagnetic iron oxide particles with magnetic resonance imaging

An accurate definition of clinical target volume (CTV) is essential for the application of radiotherapy in nasopharyngeal carcinoma (NPC) treatment. A novel epidermal growth factor receptor (EGFR)-targeting contrast agent (C225-USPIO) was designed by conjugating ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with cetuximab (C225), to non-invasively define the CTV of tumor. The immunobinding activity of C225-USPIO to NPC cell line CNE1 was confirmed by flow cytometry and immunofluorescence. The time-dependent accumulation of C225-USPIO in CNE1 cells was evaluated using Prussian blue staining. Targeted internalization and subcellular localization of C225-USPIO was confirmed by transmission electron microscope. The results indicated that C225-USPIO specifically bound to EGFR on the surface of CNE1 cells and was taken up into the cell. The uptake of C225-USPIO by CNE1 cells increased significantly with time, when compared with human IgG-USPIO. In addition, 4.7 T magnetic resonance imaging (MRI) revealed that C225-USPIO had a capacity to accumulate in the CNE1 cells, with a resultant marked decrease in MRI T2-weighted signal intensity over time. These findings imply that C225-USPIO has the potential as an MRI contrast agent and can be employed to non-invasively detect early-stage NPC with EGFR overexpression. This provides sufficient theoretical basis for commencing in vivo experiments with the compound.

Primary tumor volume should be included in the TNM staging system of nasopharyngeal carcinoma.

TNM staging system based on anatomic location, cranial nerve and conventional radiation therapy is currently the widely used classification for nasopharyngeal carcinoma (NPC). However, the T classification in separation of primary tumor volume fail to predict the radiosensitivity of primary tumor. And with the advent of intensity-modulated radiation therapy (IMRT), increasing studies show the significance of the primary tumor volume on the treatment outcome of NPC patients and primary tumor volume significantly improve the prognostic validity of T classification in NPC. Whats more, the current T staging system has limitations to provide appropriate treatment for different subgroup NPC patients. Therefore, we propose that primary tumor volume should be included in the TNM staging system of nasopharyngeal carcinoma to guide our clinical decision.

Twist1 promotes radioresistance in nasopharyngeal carcinoma

With the development of advanced imaging and radiation technologies, radiotherapy has been employed as the principal treatment approach for nasopharyngeal carcinoma (NPC). So far, a number of patients still suffer from the failure of this treatment due to the acquired radioresistance, but the underlying mechanisms are still poorly defined. In this study, we found that Twist1, participating in a variety of cell biological process, was associated with the malignancy of NPC and could induce NPC radioresistance in vitro and in vivo. Mechanically, Twist1 could promote the accumulation of DNA damage repair and inhibit the apoptosis of NPC cells. Therefore, our study not only elucidates the significant role of Twist1 in radioresistance of NPC, but also highlights Twist1 as a potential therapeutic target for NPC.

Brief Report: Human Mesenchymal Stem‐Like Cells Facilitate Floating Tumorigenic Cell Growth via Glutamine‐Ammonium Cycle

How mesenchymal stem cells (MSCs) promote tumor growth remains incompletely understood. Here, we show that mesenchymal stem‐like cells (MSLCs) are commonly present in malignant pleural effusion or ascites of cancer patients, where they directly interact with tumor cells. Chemokines and chemokine receptors, especially the CCL2/CCR2 pathway, are involved in this interaction. As a result, MSLCs exert tumor‐promoting effects by enhancing the proliferation and colony formation of tumor‐repopulating cells. The underlying molecular basis involves MSLC release of glutamine to tumorigenic cells. Inhibition of glutamine uptake impedes MSC‐mediated tumor‐promoting effects. More intriguingly, MSLCs take up tumor cell‐released ammonium that, in turn, favors MSLC growth. Thus, glutamine and ammonium form a vicious cycle between MSLCs and tumorigenic cells. These findings suggest a potential clinical application by targeting MSLCs in patients with malignant pleural effusions or ascites. Stem Cells 2015;33:2877—2884