Oncology Research 19(12) Abstracts

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Oncology Research, Vol. 19, pp. 519–525, 2012
0965-0407/12 $90.00 + .00
DOI: 10.3727/096504011X13148184434698
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Cyclin D1 G870A Polymorphism and Breast Cancer Risk: A Meta-Analysis Involving 23,998 Subjects

June Yang,* Hong Liu,†‡§ Su Lu,†‡§ Maolong Gao,¶ Qiuyue Du,# and Shou-Ching Tang†**

*Harrison International Peace Hospital, Department of Medical Oncology, Hebei, China
†Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Tianjin, China
‡Key Laboratory of Cancer prevention and Therapy, Tianjin, China
§Second Department of Breast Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
¶Senile Diseases Clinical and Rehabilitation Research Institute, Beijing Senior Hospital, Beijing, China
#Department of Pathology, Tianjin Central Gynecology and Obstetrics Hospital, Tianjin, China
**Virginia Piper Cancer Institute, Minneapolis, MN, USA

Cyclin D1 (CCND1) plays an essential role in tumor development and progression through regulating the cell transition from G1 to the proliferative S phase. The CCND1 G870A polymorphism has been associated with an increased susceptibility to squamous cell carcinoma of the head and neck, bladder, prostate, and gastric cardiac cancers. There are a number of studies that explored the relationship between CCND1 G870A polymorphism and breast cancer risk, with inconsistent conclusions. In order to better define the predictive value of CCND1 G870A polymorphism in breast cancer, we searched PubMed and EBSCO for relevant publications. A total of 13 studies were indentified, which included 11,235 cases and 12,763 controls. We calculated the summary odds ratios and the corresponding 95% confidence interval. Our meta-analysis showed that carriers of AA genotype have a significantly higher risk in developing breast cancer compared with that of GG genotype (OR = 1.08, 95% CI = 1.01–1.17, p> = 0.03) in overall population. Furthermore, in subgroup analysis, CCND1 G870A polymorphism was associated with a marginally increased risk of breast cancer for Chinese compared to Caucasian populations with an OR = 1.14, 95% CI = 1.00–1.20, p-trend = 0.06 for AA + GA versus GG, if the controls were hospital-based population with an OR = 1.21, 95% CI = 0.99–1.47, p = 0.06 for AA versus GG and if the distributions of genotypes in control groups were consistent with the Hardy-Weinberg equilibrium (HWE) with an OR = 1.08, 95% CI = 1.00–1.15, p = 0.04 for AA versus GA + GG. Our meta-analysis represents the largest study to date indicating that the G870A polymorphism in CCND1 confers an increased risk for breast cancer. Further studies are warranted to explore the preventive measures to detect and manage the breast cancers attributable to the G870A polymorphism.

Key words: Cyclin D1 (CCND1); G870A polymorphism; Breast cancer; Risk; Meta-analysis

Address correspondence to Hong Liu, M.D., Ph.D., Second Department of Breast Tumor, Tianjin Medical University Cancer Institute and Hospital, 300060 Tianjin, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Shou-Ching Tang, M.D., Ph.D., FACP, FRCPC, Martha Bacon Stimpson Endowed Chair in Medical Oncology, Director of Breast Cancer Research, Virginia Piper Cancer Institute, 800 E. 28th Street, Suite 602, Minneapolis, MN, 54407-3799, USA. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 527–534, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13340632812514
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

RIN1–Ras–ERK Pathway Plays an Important Role in Carcinogenesis in Colon Cancer Cell Line LoVo

Takeshi Inoue, Takanori Goi, Yasuo Hirono, Kanji Katayama, and Akio Yamaguchi

First Department of Surgery, Faculty of Medicine, University of Fukui, Fukui, Japan

The RIN1 protein has SH2, three domains, and H-Ras binding domains; thus, it is presumed to be an important molecule in an intracellular signaling pathway. We examined the effect of the introduction of a membrane protein-encoding, mutated (S351A)RIN1 gene into a colon cancer. In the LoVo colon cancer cell line, endogenous RIN1 protein was strongly expressed in the cytoplasmic fraction, and the RIN1 protein in the cytoplasmic fraction was strongly bound to the 14-3-3 protein. In the mutated (S351A)RIN1-transfected LoVo cells, the mutated (S351A)RIN1 protein was identified in the cell membrane, and was bound to HRas protein. Also, in vitro the proliferative capacity of the mutated (S351A)RIN1-transfected LoVo cells was significantly inhibited, compared with that of their empty vector-transfected counterparts. In the mutated (S351A)RIN1-transfected LoVo cells, the phosphorylation of ERK1/2 proteins downstream of the H-Ras molecule was inhibited, compared with the counterparts. This study is the first to show that the localization of RIN1 protein plays an important role in the carcinogenesis in colon cancer cells LoVo (i.e., signal transduction in the Ras–ERK pathway).

Key words: Colon cancer; RIN1 gene; Cell growth; Mutated (S351A)RIN1

Address correspondence to Takanori Goi, M.D., Ph.D., Department of Surgery I, University of Fukui, 23-3, Eiheiji-cho, Matsuoka, Yoshida-gun, Fukui 910-1193, Japan. Tel: 81-776-61-8372; Fax: 81-776-61-8113; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 535–541, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13340632812550
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Gene Silence-Induced Downregulation of Survivin Inhibits Bladder Cancer Cells

Xin Gou, Hua-An Yang, Wei-Yang He, Ming-Chao Xioa, and Ming Wang

The First Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China

Urinary bladder cancer accounts for approximately 3% of all cancers in humans. Treatment for urinary bladder is not satisfactory. The present study aims to elucidate the effect of gene silencing of survivin on the inhibition of bladder cancer cells. In this study, we constructed survivin shRNA-carrying lentiviral vectors. Bladder cancer cell lines, T24 cells and BJ cells, were transduced with the constructed shRNA of survivin. The frequency of apoptotic bladder cancer cells was assessed by flow cytometry. The results showed that transfection with survivin shRNA significantly inhibited cell proliferation of both T24 and BJ cells. Most T24 and BJ cells accumulated at the G2/M stage; a portion of them was at sub-G1 stage. An increase in the fraction of bladder cancer cells undergoing apoptosis was noted. Among eight apoptosis-associated proteins, the amounts of BAX and BAD were significantly increased in the survivin-deficient bladder cancer cells. The findings suggest that survivin may be a therapeutic target of bladder cancer to selectively inhibit cell proliferation of bladder cancer cells.

Key words: Survivin; shRNA; Bladder cancer; Apoptosis; Cell proliferation

Address correspondence to Professor Xin Gou, Department of Urology, The First Affiliated Hospital, Chongqing Medical University, No.1 Youyi Road of Yuzhong District, Chongqing, 400016, China. Tel: +86-23-8901-1411; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 534–554, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13340632812596
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Decrease of the Regulatory T-Cell Population by Adoptive T-Cell Transfer in a Mouse Colorectal Cancer Transplant Model

Tsuguhiro Matsumoto,* Satoshi Kokura,*† Takeshi Ishikawa,*† Jun Funaki,*† Satoko Adachi,† Koji Mori,† Naoyuki Sakamoto,‡ Kazuhiro Katada,* Kazuhiro Kamada,* Nobuaki Yagi,* Osamu Handa,* Tomohisa Takagi,* Kazuhiko Uchiyama,* Yuji Naito,* and Toshikazu Yosikawa*†

*Department of Molecular Gastroenterology & Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
†Department of Cancer Immunoregulation, Kyoto Prefectural University of Medicine, Kyoto, Japan
‡Iseikai Hyakumanben Clinic, Kyoto, Japan

We examined the effects of adoptive T-cell transfer (ACT) on the population of regulatory T cells (Tregs) in a mouse colorectal cancer transplant model. In an in vivo study, Treg populations in Balb/c mice colon26 transplant model after ACT were analyzed in peripheral blood, local lymph node, and tumor. In an in vitro study CD4+ cells were cultured in medium containing TGF-β to induce Tregs. LAK cells were added or not in this Treg induction system. Treg induction after coculture with LAK was investigated. We also studied the role of IFN-γ in the mechanism of Treg induction. Tregs in the draining lymph nodes and tumor were significantly suppressed by ACT. The induction of Tregs in vitro was inhibited by coculture with LAK cells. Furthermore, Tregs in the cultured cells were significantly inhibited by addition of exogenous IFN-γ. Moreover, Tregs were increased by addition of IFN-γ mAb. ACT may decrease Tregs in tumor-bearing hosts. One of the mechanisms is considered to be IFN-γ inhibiting the induction of Tregs.

Key words: Adoptive T-cell transfer (ACT); Regulatory T cells (Tregs); Cancer; Interferon-γ (INF-γ)

Address correspondence to Satoshi Kokura, Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Tel: 81-75-251-5519; Fax: 81-75-251-0710; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 555–561, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13340632812631
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

CXCR4-Positive Subset of Glioma Is Enriched for Cancer Stem Cells

Xuesheng Zheng,*1 QingSong Xie,†1 Shiting Li,* and Wenchuan Zhang*

*Department of Neurosurgery, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China
†Department of Neurosurgery, Cixi Municipal People’s Hospital, Zhejiang Province, China

CXC chemokine receptor 4 (CXCR4) is a cell surface molecule expressed in a distinct subset of glioma cells with enhanced tumorigenicity, and it is related to many important biological activities of the tumor. We supposed that this receptor might be a cell surface “marker” for glioma stem cells. This hypothesis was tested both in vitro and in vivo. The CXCR4+ and CXCR4 subsets were sorted from three human malignant glioma specimens. They were tested for the capability of colony formation in soft agar, generation of tumorosphere, self-renewal, and multipotent differentiation in vitro, and the capability of xenograft tumor in vivo. Drug and radiation resistance and coexpression with CD133 were studied for each subset. CXCR4+ glioma cells, but not CXCR4 cells, were capable of generating tumorospheres in serum-free medium. In addition, these spheres were able to self-renew after passage, and had multipotent differentiation after being induced in serum-containing medium. In soft agar assay, CXCR4+ cells generate much more colonies. The animal experiment revealed that CXCR4+ subpopulation had stronger tumorigenicity than the unsorted parental glioma cells, while the CXCR4 cells did not generate xenograft tumor. CXCR4-positive cells were more resistant to temozolomide and radiation treatment. Both CXCR4+ and CXCR4 subsets contained very few CD133+ cells. The CXCR4+ subsets of glioma cells fulfill the standard of “cancer stem cell.”

Key words: Cancer stem cell; Glioma; CXC chemokine receptor 4 (CXCR4)

1These authors provided equal contribution to this study.
Address correspondence to Xuesheng Zheng, Department of Neurosurgery, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China. Tel: 86-21-25078007; Fax: 86-21-52357635; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 563–571, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13340632812677
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

PIK3CA Is Critical for the Proliferation, Invasiveness, and Drug Resistance of Human Tongue Carcinoma Cells

Yu Chen,*1 Qingyi Hou,†1 Wangxiang Yan,* Jing Luo,‡ Dan Chen,* Zhiguo Liu,* Shuqi He,* and XueQiang Ding*

*Department of Oral & Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, P.R. China
†Department of Nuclear Medicine, People’s Hospital of Guangdong Province, Guangzhou, Guangdong Province, P.R. China
‡Department of Stomatology, Guanazhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong Province, P.R. China

PIK3CA is an oncogene component of phosphatidylinositol 3-kinase (PI3K) signaling pathway and is associated with cell proliferation and carcinogenesis in a variety of human cancers. PIK3CA mutation is correlated with the aggressiveness of many epithelial cancers. And so PIK3CA is considered as a major oncogene in many human epithelial malignancies. However, its role in tongue carcinoma is unknown. We used lentiviral-mediated interfering short hairpin RNAs (shRNAs) to knock down PIK3CA expression in tongue carcinoma Tca8113 cells, and then we tested the cell proliferation by MTT assay and cell invasiveness by cell invasion assay. To examine whether PIK3CA is involved in the response of Tca8113 cells to an anticancer drug, cisplatin, we further performed cell death analysis by fluorescence-activated cell sorting (FACS). We found that knocking down PIK3CA led to slower cell growth and lessened cell invasiveness. In addition, PIK3CA downregulation increased Tca8113 cell death after cisplatin treatment, suggesting that PIK3CA downregulation might be helpful to increase the effects of some anticancer drugs. Moreover, in a mouse model of established large sized OSCC, we showed that suppression of PIK3CA markedly diminished tumorigenicity in vivo. To understand its molecular mechanism of action, we measured expression of phospho-PTEN (Ser380) and phospho-AKT (Ser473) by Western blot and found that suppression of PIK3CA inhibited OSCC growth through downregulation of p-PTEN and p-AKT. Our study highlights critical roles for IK3CA in the tongue cancer, and suggests that PIK3CA gene might be considered as a therapeutic target for clinical tongue cancer.

Key words: PIK3CA; Lentivirus shRNA; Tongue cancer; Proliferation; Invasiveness

1These authors provided equal contribution to this work.
Address correspondence to Dr. XueQiang Ding, Department of Oral & Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Road Zhonshan Erlu, 58#, Guangzhou City, Guangdong Province, 510080, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 573–582, 2012
0965-0407/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504012X13342463747450
E-ISSN 1555-3906
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Inhibition of SPHK1 Suppresses Phorbol 12-Myristate 13-Acetate-Induced Metastatic Phenotype in Colorectal Cancer HT-29 Cells

Meng-Bin Qin, Jie-An Huang, Shi-Quan Liu, Guo-Du Tang, and Hai-Xing Jiang

Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Guangxi Zhuang Autonomous Region, China

Expression of sphingosine kinase 1 (SPHK1) plays a role in colorectal cancer progression. This study aimed to demonstrate the mechanism of human colorectal cancer cell metastatic phenotype through SPHK1 knockdown. Human colorectal cancer HT-29 cells were stimulated by phorbol 12-myristate 13-acetate (PMA) with or without SPHK1 siRNA transfection. Tumor cell phenotypic changes were analyzed by using invasion, motility, cell viability, and apoptosis assays. Gene expressions were assessed using Western blot. PMA induced a metastatic phenotype in colorectal cancer cells, as indicated by cell viability, migration and invasion capacity, and ERK1/2 phosphorylation, whereas SPHK1 siRNA transfection suppressed the metastatic phenotype of tumor cells and antagonized PMA’s effects. SPHK1 knockdown also inhibited secretion of MMP-2 and MMP-9 into the tumor cell conditioned medium. Suppression of SPHK1 expression suppresses the PMA-induced metastatic phenotype via ERK1/2 phosphorylation in human colorectal cancer cells.

Key words: Sphingosine kinase 1 (SPHK1); Phorbol 12-myristate 13-acetate (PMA); ERK1/2; Metastatic phenotype; Colorectal cancer

Address correspondence to Jie-An Huang, M.D., Ph.D., Department of Gastroenterology, First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Rd, Nanning 530021, China. Tel: +86-771-5356501; Fax: +86-771-5351574; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it