Oncology Research 20(4) Abstracts

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Oncology Research, Vol. 20, pp. 139–147, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13522227232156
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Identification of miR-375 as a Potential Biomarker in Distal Gastric Adenocarcinoma

Wen-Hui Zhang,*†1 Jun-Hao Gui,‡1 Chang-Zheng Wang,* Qing Chang,* Shi-Ping Xu,* Chang-Hao Cai,* Ying-Nan Li,* Ya-Ping Tian,‡ Li Yan,* and Benyan Wu*

*Department of Geriatric Gastroenterology, Chinese PLA General Hospital, Beijing, China
†Department of Gastroscope, Chinese PLA 302 Hospital, Beijing, China
‡Department of Clinical Biochemistry, Chinese PLA General Hospital, Beijing, China

MicroRNAs (miRNAs) are endogenous small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level and play an important role in carcinogenesis. Herein, we characterized the global expression of miRNA in distal gastric adenocarcinomas and determined if circulating miRNAs could be used as biomarkers for distal gastric adenocarcinoma. We used a microarray screening system to detect dysregulated miRNAs in distal gastric adenocarcinoma tissues. The expression of a subset of five aberrantly expressed miRNAs (miR-375, -196b, -204, -18b, and -93) were further quantified in an independent set of clinical samples of distal gastric adenocarcinoma by real-time quantitative RT-PCR (rt-qRT-PCR). We also used rt-qRT-PCR to investigate the expression levels of putative miRNA biomarkers in serum and tumor cell lines. In our study, the expression of a subset of microRNAs was altered in distal gastric adenocarcinoma compared to normal tissue. miR-375 was significantly downregulated in distal gastric adenocarcinoma tissues, to a level that was significantly lower than cardia adenocarcinoma (p < 0.05). The circulating serum levels of miR-375 in patients who had distal gastric adenocarcinoma were also much lower than normal controls (p < 0.001). As a biomarker, miR-375 yielded a receiver operating characteristic area under the curve of 0.835. The specificity and sensitivity was 80% and 85%, respectively, in the discrimination of distal gastric adenocarcinoma from control, at a normalized cutoff of 0.218. The expression of miR-375 was downregulated both in distal gastric adenocarcinoma tissues and serum of patients with distal gastric adenocarcinoma. These data suggest miR-375 is a potential biomarker for distal gastric adenocarcinoma.

Key words: Distal gastric adenocarcinoma (DGAC); MicroRNAs; Serum; miR-375; Biomarker

1These authors provided equal contribution to this work.
Address correspondence to Ben-Yan Wu, Department of Geriatric Gastroenterology, Chinese PLA General Hospital, 28 Fuxing Rd, Beijing 100853, China. Tel: +86-10-66876265; Fax: +86-10-66876265. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 149–156, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13522227232237
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

c-Myc Overexpression Promotes Osteosarcoma Cell Invasion Via Activation of MEK–ERK Pathway

Gang Han, Yan Wang, and Wenzhi Bi

Department of Orthopaedics, General Hospital of PLA, Beijing, China

Osteosarcoma is a highly metastatic malignancy often with poor prognosis. c-Myc amplification is implicated in osteosarcoma pathogenesis. However, the role of c-myc overexpression in osteosarcoma cell invasion remains unexplored. This study showed that c-myc overexpression enhanced MG-63 and SAOS-2 osteosarcoma cell invasion. Treatment of MEK inhibitor PD98059 or PI3K inhibitor LY294002 decreased cell invasion along with downregulation of MMP-2 and MMP-9 expression. c-Myc overexpression stimulated MEK–ERK pathway whereas inhibited the activity of PI3K–AKT pathway. Specifically, inhibition of MEK–ERK pathway by PD98509 blocked the enhancement effect on cell invasion as well as MMP-2 and MMP-9 expression. The present study demonstrates that c-myc overexpression promotes osteosarcoma cell invasion, probably via activation of MEK–ERK pathway.

Key words: c-Myc; Osteosarcoma; Invasion; MEK–ERK pathway

Address correspondence to Dr. Yan Wang, Department of Orthopaedics, General Hospital of PLA, No28 FuXing Road, Haidian District, Beijing, 100853, China. Tel/fax: 86-010-66938370; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 157–162, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13522227232273
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Downregulation of JWA Expression in Human Esophageal Squamous Cell Carcinoma and its Clinical Significance

Jian Zhou,*1 Zhijun Ge,†1 Yongfei Tan,* Guojun Jiang,* Juncheng Feng,* Hongmin Wang,* and Guozhen Shi*

*Department of Thoracic Surgery, Affiliated Yixing People’s Hospital, Jiangsu University, Jaingsu Province, China
†Department of Intensive Care Unit, Affiliated Yixing People’s Hospital, Jiangsu University, Jaingsu Province, China

JWA is involved in the regulation of many cellular processes. Recent studies have indicated a potential role for altered JWA expression and function in tumor development and progression. The purpose of this study was to investigate the expression and prognostic significance of JWA in human esophageal squamous cell carcinoma (ESCC). Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot assays were performed to detect the expression of JWA mRNA or protein in paired sample tissues from 20 ESCC patients. Expression levels of JWA protein in archival 292 formalin-fixed, paraffin-embedded specimens were also analyzed by immunohistochemistry. Finally, the correlation between JWA expression, clinicopathological factors, and patient survival was evaluated. RT-qPCR results showed that the levels of JWA mRNA were significantly lower in tumor tissue specimens than in the matched nontumor tissues. This finding was supported by Western blot analysis. Immunohistochemical staining data indicated that JWA protein level was correlated closely with the tumor cell differentiation, tumor invasion, lymph node metastasis, and distant metastasis. Kaplan-Meier survival analysis showed that low expression level of JWA resulted in a significantly poor prognosis of ESCC patients. Cox regression analysis revealed that the JWA expression level was an independent prognostic parameter for the overall survival rate of ESCC patients. In conclusion, our data suggest that JWA plays an important role in the occurrence and progress of human ESCC and that high expression level of JWA may predict a favorable prognosis in ESCC patients.

Key words: JWA; Esophageal squamous cell carcinoma (ESCC); Clinicopathologic factors; Prognostic indicator

1These authors provided equal contribution to this work.
Address correspondence to Professor Yongfei Tan, Department of Cardiothoracic Surgery, Yixing People’s Hospital, 75 Tongzhenguan Rd, Jiangsu Province, 214200, P.R. China. Tel: 86-510-87330725; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 163–170, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13522227232354
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Mir-373 Affects Human Lung Cancer Cells’ Growth and its E-Cadherin Expression

Weihua Wu,*† Xiaoyan He,‡ Jing Kong,*† and Bin Ye*†

*Research Center for Molecular Medicine and Tumor, Chongqing Medical University, Chongqing, P.R. China
†Department of Pathogenic Biology, Chongqing Medical University, Chongqing, P.R. China
‡Center for Clinical Molecular Medicine, Children’s Hospital, Chongqing Medical University, Chongqing, P.R. China

The aims of this study was to elucidate whether the expression of E-cadherin can be affected by the recombinant has-mir-373 eukaryotic expression plasmid vector through tests in vitro, and to analyze the relationship between the expression of E-cadherin and tumor growth. According to the has-mir-373 sequence in miRBase database, two template DNA sequences were designed. The has-mir-373 sequence and a control sequence were synthesized and cloned into pGenesil-1 eukaryotic expression plasmid vector. The recombinant plasmids were transfected into human lung cancer A549 cells by liposome-mediated method. The mir-373 expression in A549 cells was detected by using real-time quantitative polymerase chain reaction (real-time PCR). MTT (methyl thiazolyl tetrazolium) was used to analyze the growth of cancer cell cycle. RT-PCR and Western blotting were used to evaluate the levels of E-cadherin mRNA and protein expression, respectively. The expression of E-cadherin in cells was determined by immunocytochemistry. The mobility capability of transfected cells were evaluated by using wound healing assay in vitro. The fluorescent light was observed under fluorescent microscope. RT-PCR indicated that the mRNA of E-cadherin increased, and the Western blotting results also displayed that mir-373 promoted the expression of the E-cadherin protein. Compared with the control groups, MTT method and wound healing assay demonstrated that both the growth rate and migration of A549 cells transfected with the recombinant has-mir-373 eukaryotic expression plasmid was also decreased significantly (p < 0.001). The differences between the other two control groups were not significant (p > 0.05). The immunocytochemistry demonstrated a significant increase of E-cadherin protein levels in the cells transfected with mir-373, but not in the cells of the control group. Mir-373 could increase the expression levels of the E-cadherin and decrease the migration ability of human lung cancer A549 cells in vitro.

Key words: has-mir-373; E-Cadherin; Gene expression; Human lung cancer A549 cells

Address correspondence to Bin Ye, Department of Pathogenic Biology, Chongqing Medical University, Chongqing 400016, P.R. China. Tel/Fax: 86-23-68485898; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 171–178, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13548165987493
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Role of ZFX in Non-Small Cell Lung Cancer Development

Mei Jiang,*1 Shaofa Xu,†1 Wentao Yue,* Xiaoting Zhao,* Lina Zhang,* Chunyan Zhang,* and Yue Wang*

*Department of Cellular & Molecular Biology, Beijing TB and Thoracic Tumor Research Institution/Beijing Chest Hospital, Capital Medical University, Beijing, China
†Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, China

Zinc finger protein, X-linked (ZFX) is a transcription factor encoded by its gene on the mammalian X chromosome, and functions to control survival and activity of stem cells and lymphocytes. However, little is known about the role of ZFX in tumorigenesis. The function of ZFX in cell proliferation was investigated by the lentivirus-mediated short hairpin RNA interference (shRNA) approach in non-small cell lung cancer (NSCLC) cell culture lines. The expression profiles of ZFX in 49 pairs of tumors and corresponding matched adjacent normal tissues from NSCLC patients were examined by real-time PCR. The specific knockdown of ZFX by shRNA significantly inhibited cell viability and reduced colony formation of 95D cells. And ZFX silencing resulted in cell cycle arrest in G0/G1 phase. In addition, ZFX was overexpressed and correlated with lymph node metastasis in samples from 49 NSCLC patients. We reported for the first time that ZFX may play an important role in cell growth control and cell cycle progression of 95D cells. Furthermore, ZFX was overexpressed in samples of NSCLC and ZFX mRNA expression associated with lymph node metastasis. Therefore, our findings suggest that ZFX would be a potential target to development of therapies for NSCLC.

Key words: Zinc finger protein, X-linked (ZFX); Cell proliferation; Cell cycle arrest; Non-small cell lung cancer (NSCLC); shRNA

1These authors provided equal contribution to this work.
Address correspondence to Wentao Yue, M.D., Ph.D., Department of Cellular & Molecular Biology, Beijing Chest Hospital, Capital Medical University, 97 Beimachang, Tongzhou, Beijing, China 101149. Tel: +86-10-89509372; Fax: +86-10-80507349; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 179–185, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13522227232192
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Factors Exacerbating Peripheral Neuropathy Induced by Paclitaxel Plus Carboplatin in Non-small Cell Lung Cancer

Kazuyoshi Kawakami,*† Takashi Tunoda,* Tomomi Takiguchi,* Keiko Shibata,† Takayuki Ohtani,‡ Junko Kizu,‡ Makoto Nishio,§ Takeshi Horai,§ Toshihiro Hama,* and Kyoji Taguchi†

*Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
†Department of Medicinal Pharmacology, Showa Pharmaceutical University, Tokyo, Japan
‡Department of Practical Pharmacy, Faculty of Pharmacy, Keio University, Tokyo, Japan
§Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

No established supportive therapy to prevent and treat chemotherapy-induced peripheral neuropathy (PN) is available. Minimizing the severity of PN is therefore critical in clinical use. We aimed to determine when and how often PN occurs in association with paclitaxel plus carboplatin (PC therapy), a regimen used to treat non-small cell lung cancer, and factors that exacerbate this condition. Patients who received PC therapy for non-small cell lung cancer at the Japanese Foundation for Cancer Research, Cancer Institute Hospital, between May 20, 2009, and November 30, 2010, were included. PN was evaluated by the study pharmacist using specific questions based on the Common Terminology Criteria for Adverse Events Version 3.0. Univariate analysis was used to compare a group with no, Grade 1, or Grade 2 PN (non-serious) and a group with Grade 3 PN (serious). Analyses were conducted using the Cox proportional hazard model with patient characteristics having p ≤ 0.20 when assessed as independent variables. Of 50 patients, 38 (76.0%) developed PN by day 6 of the first course of anticancer treatment. Grade 3 PN had an incidence of 25.0% in the fourth course. In multivariate analysis with the Cox proportional hazard model, pack-year [hazard ratio = 1.029; 95% confidence interval (CI): 1.009–1.050, p = 0.005] and creatinine clearance (hazard ratio = 0.957; 95% CI: 0.920–0.996, p = 0.031) were significant factors. A high pack-year and a low creatinine clearance exacerbated PN in patients treated with PC. PN must be carefully evaluated in patients with exacerbating factors.

Key words: Paclitaxel + carboplatin ± bevacizumab; Peripheral neuropathy; Non-small cell lung cancer; Cox proportional hazard analysis; Pack-year; Creatinine clearance

Address correspondence to Kazuyoshi Kawakami, Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo 135-8550, Japan. Tel: +81-3-3570-0383; Fax: +81-3-3520-0141; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it