Oncology Research 20(9) Abstracts

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Oncology Research, Vol. 20, pp. 383–392, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689382653
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

CD40 Signal Regulates CXCR4 Mediating Ovarian Carcinoma Cell Migration: Implications for Extrapelvic Metastastic Factors

Qiu-Xia Qu,*† Qin Huang,*‡ Jian Xu,*† Li-Ting Duan,‡ Yi-Bei Zhu,† and Xue-Guang Zhang*†

*Clinical Immunology Institute, The First Affiliated Hospital of Soochow University, Suzhou, China
†School of Biology & Basic Medical Sciences, Soochow University, Suzhou, China
‡Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China

Ovarian carcinomas are highly invasive, especially in the peritoneal cavity. SDF-1a and its receptor, CXCR4, play a crucial role in migration of cancer cells. Here, SDF-1a directed HO8910 cell migration, but not SKOV3 cells. After being educated to express CXCR4 in vivo or by treating with sCD40L, SDF-1a reexhibited the ability of directing SKOV3 cell migration, which could be antagonized by CXCR4-neutralizing antibody. Furthermore, concomitant expression of CXCR4/CD40 in ovarian carcinoma tissues had stronger correlation with pelvic metastasis than did each alone. It is suggest that SDF-1a acts through CXCR4 to induce ovarian cancer cell migration, which could be facilitated by CD40 activation. Simultaneously examining the expression of CXCR4 and CD40 will provide valuable diagnosis of pelvic metastasis for ovarian carcinomas.

Key words: Ovarian cancer; CD40; CXCR4; Migration; Pelvic metastasis

Address correspondence to Xue-Guang Zhang, Clinical Immunology Institute, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, People’s Republic of China. Tel/Fax: +86-512-65104908; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 393–402, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689382770
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Hepatocyte Growth Factor-Mediated Gastrin-Releasing Peptide Induces IL-8 Expression Through Ets-1 in Gastric Cancer Cells

Kyung Hee Lee,* Sung Ae Koh,* and Jae-Ryong Kim†‡

*Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu, Korea
†Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea
‡Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, Korea

Gastric cancer cells secrete a variety of proangiogenic molecules, including IL-8 and VEGF. However, factors regulating the expression of proangiogenic genes for gastric cancer remain largely undefined. We investigated the role of HGF-induced activation of GRP and Ets-1 transcription factor in expression of the proangiogenic factor IL-8. The genes associated with angiogenesis induced by HGF were screened using cDNA microarray technology in two gastric cancer cell lines (NUGC-3 and MKN-28). First, GRP RNA and protein were confirmed to be upregulated. Then, expression of GRP, Ets-1, and IL-8 were further estimated by Western blot analysis. A role for Ets-1 in HGF-induced upregulation of IL-8 was determined by knockdown of Ets-1 with Ets-1 sh-RNA and a chromatin immune precipitation assay. The levels of GRP, Ets-1, and IL-8 were upregulated in cells treated with HGF in a dose-dependent manner. HGF-induced expression of Ets-1 and IL-8 was increased more by GRP treatment and inhibited by pretreatment with an ERK 1/2 inhibitor (PD098059). HGF-induced upregulation of IL-8 was repressed by Ets-1 knockdown. HGF enhanced the binding activity of Ets-1 to the IL-8 promoter in control cells, but not in the Ets-1 shRNA cells. We confirmed the functional role of HGF-induced Ets-1 in activation of the IL-8 promoter by the reporter gene assay. Downregulation of IL-8 also decreased in vitro cell invasion. In conclusion, HGF mediated the GRP induction of IL-8 expression through Ets-1, which thus might serve as a promising target for gastric cancer therapy.

Key words: Hepatocyte growth factor (HGF); Gastrin-releasing peptide (GRP); Ets-1; IL-8

Address correspondence to Jae-Ryong Kim, M.D., Ph.D., Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong, Daegu 705-717, Republic of Korea. Tel: +82-53-620-4342; Fax: +82-53-654-6651; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 403–410, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689383058
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Invasion of Histiocytic Sarcoma Into the Spinal Cord of HTLV-1 Tax Transgenic Mice With HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis-Like Disease

Takeo Ohsugi,* Makoto Wakamiya,* Saki Morikawa,* Kumi Matsuura,* Jerald Mahesh Kumar,*† Toshio Kumasaka,‡ and Kazunari Yamaguchi§

*Division of Microbiology and Genetics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan
†Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad, India
‡Department of Pathology, Japanese Red Cross Medical Center, Tokyo, Japan
§Department of Safety Research on Blood and Biologics, National Institute of Infectious Diseases, Tokyo, Japan

Human T-cell leukemia virus type 1 (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATLL) as well as inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Transgenic (Tg) mice expressing HTLV-1 Tax also develop T-cell leukemia/lymphoma and an inflammatory arthropathy that resembles rheumatoid arthritis. We found that 8 of 297 Tax-Tg mice developed HAM/TSP-like disease with symmetrical paraparesis of the hind limbs, but these symptoms were absent in non-Tg littermates and in other mice strains at our animal facilities. We could perform detailed evaluations for five of these mice. These evaluations showed that the disease was not inflammatory, unlike that in HAM/TSP patients, but instead involved the invasion of histiocytic sarcoma cells into the lumbar spinal cord from the bone marrow where they had undergone extensive proliferation.

Key words: Human T-cell leukemia virus type 1 (HTLV-1); Histiocytic sarcoma; HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP); Spastic paraparesis; Spinal cord tumor; Mice

Address correspondence to Takeo Ohsugi, Division of Microbiology and Genetics, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. Tel: +81-96-373-6549; Fax: +81-96-373-6550; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 411–417, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689383094
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Inhibition of Gastric Cancer Cell Growth In Vivo by Overexpression of Adeno-Associated Virus-Mediated Survivin Mutant C84A

Yuan Weng,* Bojian Fei,† Alfred L. Chi,‡ and Ming Cai*

*Department of Thoracic and Cardiovascular Surgery, No. 4 People’s Hospital of Wuxi City, Wuxi City, PR China
†Department of Surgical Oncology, No. 4 People’s Hospital of Wuxi City, Wuxi City, PR China
‡CHI Scientific, Inc., Maynard, MA, USA

Survivin is overexpressed in most of human cancer cells and tissues. Its overexpression is associated with apoptosis inhibition, drug resistance, and poor prognosis. In this study, we investigated the effect of adeno-associated virus (AAV)-mediated survivin mutant Cys84Ala [rAAV-Sur-Mut(C84A)] on gastric cancer growth. Sur-Mut(C84A) was subcloned into the AAV expression vector pAM/CAG to generate recombinant (r)AAVSur-Mut(C84A) virus. Cell survival was determined by the MTT method. Apoptosis was measured by FACS analysis and TUNEL. Tumor growth was assessed using a xenograft mouse model. Results showed that treatment of rAAV-Sur-Mut(C84A) virus significantly reduced cell survival, induced apoptosis, and sensitized gastric cancer cells to 5-fluorouracil in vitro. Furthermore, treatment of rAAV-Sur-Mut(C84A) virus markedly induced apoptosis and inhibited gastric cancer growth in vivo. Moreover, rAAV-Sur-Mut(C84A) treatment strongly enhanced the antitumor activity of 5-fluorouracil. Our results suggest that the combination of rAAVSur-Mut(C84A) with chemotherapy may be a promising strategy for gastric cancer therapy.

Key words: Survivin; Survivin mutant C84A; Adeno-associated virus (AAV); Gastric cancer; Apoptosis; Gene therapy

Address correspondence to Bojian Fei, M.D., Department of Surgical Oncology, No. 4 People’s Hospital of Wuxi City, Wuxi City 214062, PR China. Tel: +86-0510-88682999; Fax: +86-0510-88682225; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 419–425, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689383139
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Therapeutic Effect of Oncolytic Adenovirus Expressing Relaxin in Radioresistant Oral Squamous Cell Carcinoma

Sei Young Lee,* Haeng Ran Park,† Junghoon Rhee,* Young Min Park,† and Se-Heon Kim†

*Department of Otolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea
†Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea

Radioresistance is one of the main determinants of treatment outcome in oral squamous cell carcinoma (OSCC), and treatment of radioresistant OSCC is difficult due to cross resistance to other conventional treatments. We aimed to identify whether genetically modified oncolytic adenovirus expressing relaxin (RLX), which affects collagen metabolism, can effectively inhibit growth of the radioresistant OSCC. Therapeutic effect of oncolytic adenovirus was compared between radiosensitive and radioresistant OSCC cell lines in vitro and in vivo, and spread of adenovirus throughout the tumor mass was verified by immunohistochemistry (IHC). Oncolytic adenovirus effectively killed cancer cells and there was no significant difference in the cytotoxic effect between radiosensitive and radioresistant OSCC cell lines. In animal experiments, the adenovirus significantly reduced the size of tumor, and there was no significant difference between radiosensitive and radioresistant OSCC. In IHC, RLX expressing adenovirus showed better proliferation and eliminated collagens more effectively compared to RLX nonexpressing adenovirus. These findings suggested that genetically modified oncolytic adenovirus can effectively inhibit growth of the radioresistant OSCC and might be a new therapeutic option in radioresistant OSCC.

Key words: Oral cancer; Radioresistance; Adenovirus; Relaxin (RLX); Oral squamous cell carcinoma (OSCC)

Address correspondence to Se-Heon Kim, M.D., Department of Otorhinolaryngology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Korea. Tel: +82-2-2228-3622; Fax: +82-2-393-0580; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 427–435, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689383175
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Reactive Center Loop Moiety Is Essential for the Maspin Activity on Cellular Invasion and Ubiquitin–Proteasome Level

Chakkrit Khanaree,* Kongthawat Chairatvit,† Sittiruk Roytrakul,‡ and Ariyaphong Wongnoppavich*

*Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
†Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand
‡Proteomics Research Laboratory, Genome Institute, National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathumthani, Thailand

Maspin, a tumor suppressor (SERPINB5), inhibits cancer migration, invasion, and metastasis in vitro and in vivo. The tumor-suppressing effects of maspin depend in part on its ability to enhance cell adhesion to extracellular matrix. Although the molecular mechanism of maspin’s action is still unclear, its functional domain is believed to be located at the reactive center loop (RCL). We have elucidated the role of maspin RCL on adhesion, migration, and invasion by transfecting the highly invasive human breast carcinoma MDA-MB-231 cell line with pcDNA3.1-His/FLAG containing wild-type maspin, ovalbumin, or maspin/ovalbumin RCL chimeric mutants in which maspin RCL is replaced by ovalbumin (MOM) and vice versa (OMO). MDA-MB-231 cells transfected with maspin- or OMO-containing recombinant expression plasmid manifested significant increase in adhesion to fibronectin and reduction in in vitro migration and invasion through Matrigel compared with mock transfection or cells transfected with ovalbumin or MOM. Proteomics analysis of maspin- or OMO-transfected MDA-MB-231 cells revealed reduction in contents of proteins known to promote cancer metastasis and those of ubiquitin–proteasome pathway, while those with tumor-suppressing properties were increased. Furthermore, MDA-MB-231 cells containing maspin or OMO transgene have significantly higher levels of ubiquitin and ubiquitinated conjugates, but reduced 20S proteasome chymotrypsin-like activity. These results clearly demonstrate that the tumor-suppressive properties of maspin reside in its RCL domain.

Key words: Breast cancer; Maspin; SERPIN; Proteomic; Tumor suppressor; Reactive center loop (RCL)

Address correspondence to Ariyaphong Wongnoppavich, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. Tel: +66 5394-5323; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it