Oncology Research 21(5) Abstracts

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Oncology Research, Vol. 21, pp. 227–235, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13890370410285
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Inhibition of Tumor Angiogenesis by Interferon-γ by Suppression of Tumor-Associated Macrophage Differentiation

Tao Sun, Ye Yang, Xiaoguang Luo, Ying Cheng, Mingyu Zhang, Kun Wang, and Chunlin Ge

First Hospital of China Medical University, Shenyang, P.R. China

Tumor-associated macrophages (TAMs) differentiate from monocytes and are the M2-polarized macrophages in most human tumors, secreting generous vascular endothelial growth factor (VEGF) to promote angiogenesis. Although it has been shown in vitro that interferon-γ (IFN-γ) can inhibit monocytes differentiating to M2 macrophages in the tumor microenvironment and switch TAMs from M2 into M1, suppressing the ability of secreting VEGF, its effects on TAMs in vivo remains unknown. Here we tried to examine the effects of IFN-γ on the recruitment of monocyte/macrophage differentiation of TAMs and tumor angiogenesis in vivo. We built a gallbladder cancer model by inoculating subcutaneously the human gallbladder cancer cell line (GBC-SD) into BALB/C nude mice and injected the recombinant mouse IFN-γ intratumorally. We found that in the IFN-γ group, the number of monocytes/macrophages was significantly higher than that in the control group (p < 0.01), and TAM differentiation rate, which we defined as the number of TAMs/the number of monocytes/macrophages × 100%, mice-VEGF concentration, and microvessels density (MVD) were significantly lower than those in the control group (p < 0.01, p < 0.05, and p < 0.01). Our results suggest that IFN-γ can induce monocytes/macrophages recruiting into the tumor microenvironment, but inhibit them, differentiating to TAMs in vivo, which may reduce the concentration of VEGF and angiogenesis in tumor.

Key words: Interferon-γ (IFN-γ); Tumor-associated macrophages (TAMs); Angiogenesis; Immunotherapy; Gallbladder cancer

Address correspondence to Chunlin Ge, First Hospital of China Medical University, Nanjing Street 155, Shenyang, 110001, P.R. China. Tel: +86-13998303666; Fax: +86-024-83283330; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 237–246, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13907540404833
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Efficacy and Predictors of EGFR Tyrosine Kinase Inhibitors in Chinese Advanced Lung Adenocarcinoma: Analyses of 253 Cases From a Single Institute

Jinghui Wang,*1 Jingying Nong,*1 Hongyan Jia,† Na Qin,* Xi Li,* Hui Zhang,* Quan Zhang,* Zongde Zhang,† and Shucai Zhang*

*Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
†Department of Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China

The aim of this study was to analyze the efficacy according to EGFR status and predictors of TKIs in Chinese advanced lung adenocarcinoma patients in a single institute. We retrospectively enrolled 253 patients with advanced or recurrent adenocarcinoma and history of EGFR-TKI treatment attended at Beijing Chest Hospital in Beijing, China, from July 2007 to August 2012. Overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were analyzed according to EGFR status and in different treatment lines. The predictors of outcomes were also evaluated. Of all of the patients, the ORR was 36.0%, DCR was 66.0%, the median PFS time was 6.0 months, and the median OS time was 14.2 months. Compared with patients with EGFR wild type and EGFR status unknown, the ORR and PFS in patients with EGFR-activating mutations were significantly better (p < 0.001, p < 0.001; p < 0.001, p = 0.004, respectively). In patients harboring activating mutations, the ORR in first line and second line or beyond were 62.1%, 54.3%; DCR were 79.3%, 89.1%; PFS were 8.7 months and 7.8 months (p = 0.633, 0319, 0.320, respectively). The multivariate analysis showed that EGFR mutations and nonsmoking were independent factors of better ORR. In Cox regression analysis, ECOG performance status (PS) 0–1, nonsmoking, low number of metastatic organs, EGFR-activating mutations were independent factors of longer PFS. ECOG PS 0–1 and low number of metastatic organs were independent factors of longer OS. In conclusion, patients harboring EGFR-activating mutations had better ORR and longer PFS in TKI treatment. There was no difference in the ORR and PFS in patients with activating mutations in the first line and the second line or beyond.

Key words: Lung adenocarcinoma; Epidermal growth factor receptor; Epidermal growth factor receptor tyrosine kinase inhibitor; Mutation

1These authors provided equal contribution to this work.
Address correspondence to Zongde Zhang, M.D., Department of Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Thoracic Tumor and Tuberculosis Research Institute, No. 97, Beimachang, Tongzhou District, Beijing 101149, China. Tel: +861089509155; Fax: +8610695486819; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Shucai Zhang, Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Thoracic Tumor and Tuberculosis Research Institute, No. 97, Beimachang, Tongzhou District, Beijing 101149, China. Tel: +861089509304; Fax: +861080507685; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 247–259, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13946388748910
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Clove Extract Inhibits Tumor Growth and Promotes Cell Cycle Arrest and Apoptosis

Haizhou Liu,*†‡ John C. Schmitz,†‡ Jianteng Wei,* Shousong Cao,§ Jan H. Beumer,‡¶ Sandra Strychor,‡ Linyou Cheng,* Ming Liu,* Cuicui Wang,* Ning Wu,* Xiangzhong Zhao,* Yuyan Zhang,* Joshua Liao,# Edward Chu,†‡ and Xiukun Lin*

*Department of Pharmacology, Capital Medical University, Beijing, China
†Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
‡Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA
§Roswell Park Cancer Institute, Buffalo, NY, USA
¶Departmentof Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA
#Hormel Institute, University of Minnesota, Austin, MN, USA

Cloves (Syzygium aromaticum) have been used as a traditional Chinese medicinal herb for thousands of years. Cloves possess antiseptic, antibacterial, antifungal, and antiviral properties, but their potential anticancer activity remains unknown. In this study, we investigated the in vitro and in vivo antitumor effects and biological mechanisms of ethyl acetate extract of cloves (EAEC) and the potential bioactive components responsible for its antitumor activity. The effects of EAEC on cell growth, cell cycle distribution, and apoptosis were investigated using human cancer cell lines. The molecular changes associated with the effects of EAEC were analyzed by Western blot and (qRT)-PCR analysis. The in vivo effect of EAEC and its bioactive component was investigated using the HT-29 tumor xenograft model. We identified oleanolic acid (OA) as one of the components of EAEC responsible for its antitumor activity. Both EAEC and OA display cytotoxicity against several human cancer cell lines. Interestingly, EAEC was superior to OA and the chemotherapeutic agent 5-fluorouracil at suppressing growth of colon tumor xenografts. EAEC promoted G0/G1 cell cycle arrest and induced apoptosis in a dose-dependent manner. Treatment with EAEC and OA selectively increased protein expression of p21WAF1/Cip1 and γ-H2AX and downregulated expression of cell cycle-regulated proteins. Moreover, many of these changes were at the mRNA level, suggesting transcriptional regulation by EAEC treatment. Our results demonstrate that clove extract may represent a novel therapeutic herb for the treatment of colorectal cancer, and OA appears to be one of the bioactive components.

Key words: Syzygium aromaticum; Traditional Chinese medicine; Colorectal cancer; Oleanolic acid (OA)

Address correspondence to Dr. Xiukun Lin, Department of Pharmacology, Capital Medical University, Beijing 100069, China. Tel: +86-532-82898916; Fax: +86-532-82898916; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Dr. Joshua Liao, Hormel Institute, University of Minnesota, Austin, MN, 55912, USA. Tel: +1-507-437-9665; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 261–269, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13946388748992
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Inhibition of Beclin 1 Expression Enhances Cisplatin-Induced Apoptosis Through a Mitochondrial-Dependent Pathway in Human Ovarian Cancer SKOV3/DDP Cells

Yang Sun,* Jia-hua Liu,* Long Jin,† Yu-xia Sui,‡ Li Lai,§ and Yin Yang*

*Department of Gynecology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
†Department of Pathology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
‡Department of Pharmacy, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
§Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Hospital, Fuzhou, Fujian, China

The purpose of this study was to determine the influence of autophagy on cisplatin-induced ovarian cancer SKOV3/DDP cell line death through regulation of the expression of the autophagy gene, Beclin 1, and to explore the potential mechanism underlying the relationship between autophagy and apoptosis. When compared with a blank control group, the proportion of apoptotic cells undergoing Beclin 1 interfering increased significantly after cisplatin treatment, accompanied by reduction in mitochondrial membrane potential, increase in activities of caspase-9/3 and cytoplasmic cytochrome C, elevation of Bax expression, and reduction in Bcl-2 expression. However, the proportion of apoptotic cells with Beclin 1 overexpression reduced. These findings suggest that Beclin 1 plays an important role in the regulation of potent antitumor activity through a mitochondrial-dependent pathway in SKOV3/DDP cell line, and inhibition of Beclin 1 expression may become a new target for the sensitization therapy of ovarian cancer with cisplatin.

Key words: Autophagy; Apoptosis; Beclin 1; Cisplatin; Ovarian cancer

Address correspondence to Yang Sun, Department of Gynecology, Fujian Provincial Hospital, No. 134, Dong Street, Fuzhou, Fujian, 350001, PR China. Tel: +86 591 83755833; Fax: +86 591 87557768; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 271–279, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13946737557031
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

SiRNA-Mediated Flotillin-2 (Flot2) Downregulation Inhibits Cell Proliferation, Migration, and Invasion in Gastric Carcinoma Cells

Ke Cao,* Dingfang Xie,* Peiguo Cao,* Qiong Zou,† Can Lu,* Sheng Xiao,† Jianda Zhou,‡ and Xiaowei Peng§

*Department of Oncology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
†Department of Pathology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
‡Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
§Department of Head and Neck Surgery, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China

The flotillin (Flot) protein family has been demonstrated to be involved in the development and progression of various cancers. However, the role of Flot2 in gastric carcinomas remains unknown. The present study aimed to investigate the clinical significance and the role of Flot2 in gastric carcinomas. Data of tissue microarray including 90 cases of gastric carcinoma samples and their matched adjacent tissues showed that, among 90 cases of adjacent tissues, 65 cases showed no Flot2 expression, and 25 cases showed low expression of Flot2, and its positive expression rate was only 38.5% (25/90); however, among 90 cases of gastric carcinomas, 6 cases showed no Flot2 expression, 26 cases showed low Flot2 expression, 28 cases showed moderate expression of Flot2, and 30 cases showed high expression of Flot2, and its positive expression rate was 93.3% (84/90). Moreover, the Flot2 expression was significantly associated with the histological grade, depth of invasion, lymph node metastasis, and TNM stage. Furthermore, data of survival analysis suggested that Flot2 protein expression was an independent prognostic factor of poor survival. After that, Flot2-specific siRNA was used to decrease the Flot2 expression in gastric cancer AGS and SGC7901 cells. Forced downregulation of Flot2 remarkably inhibited cellular proliferation, migration, and invasion in gastric carcinoma cells. In conclusion, the present study suggests that the Flot2 protein expression is significantly correlated with cancer progression and poor prognosis in gastric carcinomas, probably due to its role in the regulation of cell proliferation, migration, and invasion in gastric carcinoma cells.

Key words: Flotillin2 (Flot2); Gastric carcinoma; Prognosis; Proliferation; Migration; Invasion

Address correspondence to Peiguo Cao (Professor), Department of Oncology, The Third Xiangya Hospital of Central South University, Tongzipo Road, Changsha, Hunan 410013, P.R. China. Tel: +86-731-8861-8804; Fax: +86-731-8529-5260; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 281–286, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13890370410249
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Novel HDAC Inhibitor OBP-801/YM753 Enhances the Effects of 5-Fluorouracil With Radiation on Esophageal Squamous Carcinoma Cells

Akinobu Furutani,*† Yoshihiro Sowa,* Hitoshi Fujiwara,† Eigo Otsuji,† and Toshiyuki Sakai*

*Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan
†Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan

Histone deacetylase (HDAC) inhibitors have been shown to enhance the effects of 5-fluorouracil (5-FU) against various cancer cells; however, no report has shown that an HDAC inhibitor may enhance the effects of 5-FU with radiation. Therefore, we investigated whether the novel HDAC inhibitor OBP-801/YM753 could enhance the effects of 5-FU with radiation on esophageal squamous carcinoma KYSE170 cells. The inhibition of the cell growth was significantly stronger with the combination of OBP-801/YM753 with 5-FU than with the 5-FU treatment only. Furthermore, inhibition of the colony formation was the most effective with the combined treatment of OBP-801/YM753, 5-FU, and radiation. Western blot analysis showed that OBP-801/YM753 suppressed the expression of thymidylate synthase induced by 5-FU. Therefore, this three-combined therapy is promising for patients with esophageal squamous carcinoma.

Key words: 5-Fluorouracil (5-FU); Radiation; Histone deacetylase (HDAC) inhibitor; Esophageal squamous carcinoma

Address correspondence to Yoshihiro Sowa, Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Tel: +81-75-251-5338; Fax: +81-75-241-0792; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it