Oncology Research 21(4) Abstracts

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Oncology Research, Vol. 21, pp. 173–180, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13887748696707
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Combined Inhibition of NF-κB and Bcl-2 Triggers Synergistic Reduction of Viability and Induces Apoptosis in Melanoma Cells

Mariko Watanabe,* Kazuo Umezawa,† Masaaki Higashihara,* and Ryouichi Horie*

*Department of Hematology, School of Medicine, Kitasato University, Sagamihara, Kanagawa, Japan
†School of Medicine, Aichi Medical University, Nagakute, Aichi, Japan

Constitutive activation of nuclear factor κB (NF-κB) characterizes melanoma cells. To explore the molecular mechanism of melanoma cell survival by constitutive NF-κB activation, we used the NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ), which directly binds to NF-κB. DHMEQ abrogated constitutive NF-κB activity, which included RelA (p65)/p50 in melanoma cell lines G361 and HMV-II; however, the reduction of the viability was marginal. Expression of c-FLIP was not observed in the melanoma cell lines tested, and DHMEQ could not repress the expression of the Bcl-2 family proteins Bcl-2 and Bcl-xL. Concomitant treatment with DHMEQ and the inhibitor of antiapoptotic Bcl-2 family proteins, GX15-070, triggered synergistic reduction of the viability and induced apoptosis of G361 cells. These results indicate that abrogation of the NF-κB pathway alone is not sufficient to suppress the survival of melanoma cells. The NF-κB and the antiapoptotic Bcl-2 pathways cooperatively support the survival, and the dual targeting triggers synergistic reduction of the viability and induces apoptosis of melanoma cells.

Key words: Nuclear factor κB (NF-κB); Melanoma cells; Apoptosis

Address correspondence to Ryouichi Horie, M.D., Ph.D., Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Minami-ku, Sagamihara, Kanagawa 252-0374, Japan. Tel: +81-42-778-8111; Fax: +81-42-778-8441; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 181–191, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13887748696743
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Phase II Study of Bevacizumab, Capecitabine, and Oxaliplatin Followed by Bevacizumab Plus Erlotinib as First-Line Therapy in Metastatic Colorectal Cancer

Alberto Muñoz,* Carles Pericay,† Carlos García-Girón,‡ Vicente Alonso,§ Rosario Dueñas,¶ Luis Cirera,# Fernando Rivera,** Esther Falcó,†† Iñaki Alvarez Bustos,‡‡ and Antonieta Salud§§

*Hospital de Cruces, Barakaldo, Spain
†Hospital Parc Taulí, Sabadell, Spain
‡Hospital General Yagüe, Burgos, Spain
§Hospital Miguel Servet, Zaragoza, Spain
¶Complejo Hospitalario de Jaén, Jaén, Spain
#Hospital Mutua de Terrasa, Terrassa, Spain
**Hospital Marqués de Valdecilla, Santander, Spain
††Hospital Son Llatzer, Carretera Manacor, Palma, Mallorca, Spain
‡‡Hospital San Jorge, Huesca, Spain
§§Hospital Arnau de Vilanova, Lérida, Lleida, Spain

This phase II trial investigated the efficacy of an induction regimen of bevacizumab, capecitabine plus oxaliplatin (XELOX) followed by maintenance therapy with bevacizumab plus erlotinib as first-line therapy in patients with metastatic colorectal cancer. Patients with metastatic colorectal cancer received intravenous bevacizumab 7.5 mg/kg plus oxaliplatin 130 mg/m2 on day 1 followed by oral capecitabine 1,000 mg/m2 twice daily on days 1–14 every 3 weeks for six cycles. In the absence of disease progression, patients then received bevacizumab 7.5 mg/kg every 3 weeks plus oral erlotinib 150 mg once daily. The primary study endpoint was progression-free survival. In the intention-to-treat population (n = 90), the median progression-free survival was 9.2 [95% confidence interval (CI): 7.9–11.9] months, and the median overall survival was 25.8 (95% CI: 18.0–30.9) months. In the patient subpopulation who received both induction and maintenance therapy (n = 52), median progression-free survival was 11.1 (95% CI: 9.0–15.7) months, and the median overall survival was 29.5 (95% CI: 23.7–36.7) months. KRAS status did not predict efficacy. The most common grade 3/4 adverse events were diarrhea, asthenia, and neutropenia. XELOX–bevacizumab for 6 cycles followed by bevacizumab–erlotinib maintenance therapy has been shown to be a highly active and well-tolerated first-line regimen in patients with metastatic colorectal cancer.

Key words: Bevacizumab; Capecitabine; Oxaliplatin; Metastatic colorectal cancer

Address correspondence to Dr. Alberto Muñoz, Hospital de Cruces, Plaza de Cruces, 12, 48903 San Vicente de Barakaldo, Vizcaya, Spain. Tel: +34-944-85-00-86; Fax: +34-944-99-29-45; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 193–200, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13887748696789
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Cancer/Testis Antigen HCA587-Derived Long Peptide Vaccine Generates Potent Immunologic Responses and Antitumor Effects in Mouse Model

Lijie Zhang,1 Juanjuan Chen,1 Xiao Song, Weigang Wen, Yan Li, Yu Zhang, and Yanhui Yin

Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing, People’s Republic of China

The cancer/testis antigen HCA587 (also known as MAGE-C2), one of the most immunogenic tumor antigens, is overexpressed in a wide spectrum of malignant tumors and can serve as a target for immunotherapy. In this study, we synthesized 14 overlapping (25–35 amino acids) long peptides representing the sequence of the most immunogenic part of the HCA587 protein and evaluated the antigen-specific immune responses and antitumor effects generated by immunization with the synthetic long peptide (SLP) vaccine in a mouse model. HCA587 SLPs in combination with adjuvants CFA and CpG ODN induced potent T-cell responses, which were dominated by type 1 cytokine IFN-γ-producing CD4+ T cells as measured by ELISPOT and intracellular cytokine staining assay. Moreover, HCA587 SLP vaccination conferred protection against challenge with HCA587-expressing B16 melanoma in a therapeutic setting. Our findings may provide a scientific basis for the use of HCA587-derived long overlapping peptide vaccine for the treatment of patients with cancer in future clinical trials.

Key words: Cancer/testis antigen; HCA587 (MAGE-C2); Tumor; Synthetic long peptide (SLP); Vaccine

1These authors provided equal contribution to this work.
Address correspondence to Yanhui Yin, M.D., Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China. Tel: +86-10-82805648; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 201–207, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13890370410203
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Propofol Inhibits Proliferation and Invasion of Osteosarcoma Cells by Regulation of MicroRNA-143 Expression

Zhang Ye,* Li Jingzhong,* Liu Yangbo,† Chen Lei,† and Yuan Jiandong†

*Department of Orthopedics, 161 Hospital of PLA, Huangpu Road, Wuhan, Hubei, China
†Department of Orthopedics, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, China

Propofol is one of the extensively commonly used intravenous anesthetic agents. Previous studies have indicated that propofol has the ability to influence the biological behavior of several human cancer cells. However, the effect of propofol on osteosarcoma and its related molecular mechanisms are still not clear. Here we found that propofol significantly elevated the expression of miR-143, inhibited cell proliferation and invasion, and promoted apoptosis in osteosarcoma cell line MG63. Propofol also efficiently decreased protein expression of matrix metalloproteinase 13 (MMP-13). Moreover, the overexpression of miR-143 decreased MMP-13 protein level. Finally, the neutralization of miR-143 by anti-miR-143 antibody reversed the effect of propofol on cell proliferation, apoptosis, and invasion and upregulated MMP-13 expression in MG63 cells. Taken together, propofol may have antitumor potential in osteosarcoma, which is partly due to the downregulation of MMP-13 expression by miR-143.

Key words: Propofol; Osteosarcoma; miR-143; Matrix metalloproteinase 13 (MMP-13); Proliferation; Invasion

Address correspondence to Yuan Jiandong, M.D., Department of Orthopedics, The First Affiliated Hospital of Wen Zhou Medical University, 2 Fuxue Road, Wenzhou 325000, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 209–216, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13907540404798
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Synergistic Antitumoral Effect of IL-12 Gene Cotransfected With Antiangiogenic Genes for Angiostatin, Endostatin, and Saxatilin

Hong Sung Kim,* Hwa Yeon Jeong,† Yeon Kyung Lee,† Keun Sik Kim,‡ and Yong Serk Park†

*Department of Biomedical Laboratory Science, Korea Nazarene University, Cheonan, Korea
†Department of Biomedical Laboratory Science, Yonsei University, Wonju, Korea
‡Department of Biomedical Laboratory Science, Konyang University, Daejeon, Korea

Previously, it was reported that the cotransfection of angiostatin K1-3, endostatin, and saxatilin genes using cationic liposomes significantly inhibited tumor progression. IL-12 is a well-known immune modulator that promotes Th1-type antitumor immune responses and also induces antiangiogenic effects. In this study, we have examined the antitumoral function of the IL-12 gene cotransfected with antiangiogenic genes for angiostatin K1-3, endostatin, and saxatilin by O,O′-dimyristyl-N-lysyl glutamate (DMKE) cationic liposomes in a mouse tumor model. According to our results, the administration of the IL-12 gene or the genes for angiostatin K1-3, endostatin, and saxatilin exhibited effective inhibition of B16BL6 melanoma growth in mice. In particular, intravenous administration of the IL-12 gene along with intratumoral administration of the three antiangiogenic genes synergistically inhibited the B16BL6 tumor growth. These results suggest that systemically expressed IL-12 enhances antitumoral efficacy of locally expressed antiangiogenic proteins.

Key words: IL-12; Angiostatin; Endostatin; Saxatilin; O,O′-Dimyristyl-N-lysyl glutamate (DMKE) cationic liposomes; Combinatorial gene therapy

Address correspondence to Yong Serk Park, Ph.D., Department of Biomedical Laboratory Science, Yonsei University, Wonju, Gangwon 220-710, Republic of Korea. Tel: +82-33-760-2448; Fax: +82-33-760-2561; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it .k


Oncology Research, Vol. 21, pp. 209–216, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504014X13907540404879
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Stromal Cell-Derived Factor-1 (SDF-1)/CXCR4 Axis Enhances Cellular Invasion in Ovarian Carcinoma Cells Via Integrin β1 and β3 Expressions

Yuecheng Yu,*1 Xiaoyan Shi,†1 Zhen Shu,*1 Tingting Xie,* Kan Huang,* Li Wei,* Hui Song,* Wei Zhang,‡ and Xiaochang Xue‡

*Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xian, PR China
†Department of Obstetrics and Gynecology, Yanan University Affiliated Hospital, Ya’an, PR China
‡State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi’an, PR China

Accumulating evidence has showed that stromal cell-derived factor-1 (SDF-1/CXCR4 axis played important roles in cancer metastases, but the detailed function in ovarian cancer is still largely unknown. In the present study, we determined the location of CXCR4 and lipid rafts, a specialized structure on cell membrane, in ovarian cancer tissues and ovarian cancer cell line SKOV3 cells by immunofluorescence. To analyze the role of SDF-1/CXCR4 and lipid rafts in tumor cell migration and invasion, Transwell assay and wound healing assay were also performed. Cytoflowmetry was carried out to determine the participation of integrins. Our data showed that CXCR4 and GM1 (marker of lipid rafts) were expressed in both ovarian cancer tissue and SKOV3 cells, and SDF-1 promoted the invasion and migration of SKOV3 cells, which was mediated by complete lipid rafts. Further studies uncovered that SDF-1 upregulated the expression of integrin b1 and b3, two molecules closely related with cancer metastasis. These results indicated that SDF-1 might promote the invasion and metastasis of ovarian cancer by regulating these two integrin molecules.

Key words: Ovarian cancer; Invasion; Migration; Metastasis; Integrin

1These authors provided equal contribution to this work.
Address correspondence to Yuecheng Yu, Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, 17 Changle West Road, Xian 710032, PR China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Xiaochang Xue, State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Fourth Military Medical University, 17 Changle West Road, Xi’an 710032, PR China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it