Oncology Research 23(1-2) Abstracts

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Oncology Research, Vol. 23, pp. 1–5, 2016
0965-0407/16 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504015X14452563485986
E-ISSN 1555-3906
Copyright © 2016 Cognizant, LLC. 
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Review

What Is the Optimal Dose and Schedule for Dasatinib in Chronic Myeloid Leukemia: Two Case Reports and Review of the Literature

Caroline Jamison,* Debra Nelson,† Mete Eren,† Dron Gauchan,† Ryan Ramaekers,† Max Norvell,† and Mehmet Sitki Copur†

*University of Nebraska Medical Center College of Pharmacy, Omaha, NE, USA
†Saint Francis Cancer Treatment Center, Grand Island, NE, USA

Efficacy and safety of dasatinib in chronic phase (CP) chronic myelogenous leukemia (CML) patients has been well established. Initially approved dose and schedule of 70 mg twice daily has been changed to 100 mg once daily after demonstration of the same efficacy with less toxicity. Some patients require significant dose reductions to enable continued treatment with dasatinib. Even at a dose of 80 mg once daily, several patients may require further dose reductions due to substantial toxicity while maintaining good control of their disease. We report two CP-CML patients achieving and maintaining major molecular responses while on very low doses of dasatinib, ultimately achieving undetectable levels of BCR-ABL fusion transcript in their peripheral blood. Observations of several CP-CML cases responding remarkably well to dasatinib despite very low dose and frequent dose interruptions challenge our current understanding and the accuracy of the data regarding the optimum dose and schedule of this drug. In selected intolerant patients, low-dose dasatinib therapy may be a safe and effective alternative treatment option before a treatment discontinuation or change considered.

Key words: Chronic myeloid leukemia (CML); Dasatinib; Adverse events; Low-dose treatment; Undetectable BCR-ABL

Address correspondence to Mehmet Sitki Copur, M.D., Saint Francis Cancer Treatment Center, 2116 W Faidley Ave, Grand Island, NE 68803, USA. Tel: +1-3083985450; Fax: +1-3083985351; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 7–12, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14410238486649
E-ISSN 1555-3906
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Knockdown of Legumain Suppresses Cervical Cancer Cell Migration and Invasion

Fei Meng and Wei Liu

Department of Obstetrics and Gynecology, Affiliated Hospital of Shenyang Medical Center, Shenyang, China

Cervical cancer is the second leading type of cancer in women living in less developed countries. The pathological and molecular mechanisms of cervical cancer are not comprehensively known. Though legumain has been found to be highly expressed in various types of solid tumors, its expression and biological function in cervical cancer remain unknown. In this study, we aimed to investigate legumain expression and functions in cervical cancer. We found that legumain was highly expressed in cervical cancer cells. When knocked down, legumain expression in HeLa and SiHa cells significantly reduced its migration and invasion abilities compared with control cells. Furthermore, legumain silencing suppressed the activation of matrix metalloproteases (MMP2 and MMP3) in cervical cancer cells. This study indicates that legumain might play an important role in cervical cancer cell migration and invasion. Legumain might be a potential therapeutic target for cervical cancer therapy.

Key words: Cervical cancer; Legumain; Migration; Invasion

Address correspondence to Fei Meng, M.D., Department of Obstetrics and Gynecology, Affiliated Hospital of Shenyang Medical Center, No. 5, West Nanqi Road, Shenyang, China 110024. Tel/Fax: 0086-02462215829; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 13–20, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14410238486766
E-ISSN 1555-3906
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Tumor-Suppressor Gene NBPF1 Inhibits Invasion and PI3K/mTOR Signaling in Cervical Cancer Cells

Yun Qin,* Xicai Tang,† and Mingxing Liu‡

*Department of Obstetrics and Gynecology, AnKang City Central Hospital, Shanxi, China
†Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangdong, China
‡Department of Gynaecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangdong, China

The purpose of this study was to assess the effects of NBPF1 expression on cervical cancer cell invasion and apoptosis and to illustrate its potential mechanism. Human cervical cancer HeLa cells were transfected with the constructed siNBPF1 or pcDNA3.1-NBPF1 vectors. Effects of NBPF1 expression on cell invasion ability and cell apoptosis were analyzed using the Matrigel method and an Annexin V-FITC cell apoptosis kit, respectively. In addition, cell apoptosis-related proteins involved with the PI3K/mTOR signaling pathway were analyzed using Western blot. Remediation experiments were conducted to verify the effects of NBPF1 expression on cell invasion and apoptosis. Compared to the control, mRNA and protein expressions of NBPF1 were significantly decreased when cells were transfected with siNBPF1 (p < 0.05), which was contrary to the results of cells transfected with pcDNA3.1-NBPF1. Overexpression of NBPF1 significantly suppressed HeLa cell invasion but promoted cell apoptosis (p< 0.05). Overexpression of NBPF1 performed a significant inhibitory role on PI3K/mTOR signal pathway expression, while NBPF1 was silenced, showing contrary results. Our data suggested that NBPF1 overexpression may be a suppressor for cervical cancer via affecting cell invasion and apoptosis through regulating PI3K/mTOR signaling pathway. NBPF1 may be a potential therapeutic target for cervical cancer treatment.

Key words: Cervical cancer; Neuroblastoma breakpoint family member 1 (NBPF1); Cell apoptosis; Cell invasion; PI3K/mTOR pathway

Address correspondence to Yun Qin, Department of Obstetrics and Gynecology, AnKang City Central Hospital, No. 85 Rd. Jinzhou South, AnKang City, Shanxi Province 725000, China. Tel: +0915-3284140; Fax: +0915-3207850; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 21–28, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14424348426071
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Inhibition of NF-κB Activity Enhances Sensitivity to Anticancer Drugs in Cholangiocarcinoma Cells

Wunchana Seubwai,*†‡ Kulthida Vaeteewoottacharn,‡§ Ratthaphol Kraiklang,¶ Kazuo Umezawa,# Seiji Okada,** and Sopit Wongkham‡§

*Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
†Comprehensive Cancer Research Group, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
‡Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
§Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
¶Department of Nutrition, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand
#Department of Molecular Target Medicine, Aichi Medical University, Nagakute, Japan
**Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Honjo, Kumamoto, Japan

Cholangiocarcinoma (CCA) is a dismal cancer. At present, there is no effective chemotherapeutic regimen for CCA. This may be due to the marked resistance of CCA to chemotherapy drugs, for which a mechanism remains unknown. Nuclear factor-κB (NF-κB) is constitutively activated in a variety of cancer cells, including CCA. It has been shown to play roles in growth, metastasis, and chemoresistance of cancer. In the present study, we examined whether NF-κB is involved in the chemoresistance of CCA and whether dehydroxymethylepoxyquinomicin (DHMEQ), an effective NF-κB inhibitor, can overcome the drug resistance of CCA. Two CCA cell lines, KKU-M213 and KKU-M214, were treated with DHMEQ and/or chemotherapeutic drugs. Cell viability, apoptosis, and the expressions of the ATP-binding cassette (ABC) transporters were compared. The combination of chemotherapy drugs, 5-fluorouracil, cisplatin, and doxorubicin, with DHMEQ significantly enhanced the cytotoxicity of all chemotherapeutic drugs compared to DHMEQ or drug alone. Furthermore, the mRNA level of ABCB1, a multidrug-resistant protein, was significantly decreased in the 5-fluorouracil combined with DHMEQ-treated cells. These findings suggest that the inhibition of NF-κB by DHMEQ enhanced the chemoresponsiveness of CCA cells, possibly by reducing the expression of ABC transporter. Inhibition of NF-κB may be a potential chemodrug-sensitizing strategy for chemoresistant cancer such as CCA.

Key word: Dehydroxymethylepoxyquinomicin (DHMEQ); Nuclear factor-κB (NF-κB); Cholangiocarcinoma (CCA); ATP-binding cassette family (ABC) transporters; Chemotherapeutic drugs

Address correspondence to Wunchana Seubwai, Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Tel: 66-43-202-859; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 29–34, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14452563486011
E-ISSN 1555-3906
Copyright © 2016 Cognizant, LLC. 
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Curcumin Enhances the Effects of 5-Fluorouracil and Oxaliplatin in Inducing Gastric Cancer Cell Apoptosis Both In Vitro and In Vivo

Xiang Zhou,*1 Weiming Wang,†1 Pihong Li,* Zhiqiang Zheng,* Yangyang Tu,* Yi Zhang,* and Tao You*

*Department of Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
†Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

Despite the efficacy of fluoropyrimidines and oxaliplatin-based chemotherapy for patients, this treatment leads to significant patient inconvenience, toxicity, and cost. This study aims to validate a nontoxic agent, curcumin, to the current chemotherapeutic regimen. In in vitro experiments, curcumin induced apoptosis in gastric cancer cell line BGC-823. Synergistic antitumor effects of curcumin were observed in combination with 5-fluorouracil (5-FU) and oxaliplatin. These effects were accompanied by downregulation of the expression of Bcl-2 protein and mRNA and upregulation of the expression of Bax and caspase 3, 8, and 9. In addition, the in vivo study showed that the combination of curcumin and 5-FU/oxaliplatin exhibited potent growth inhibition of BGC-823 xenograft tumors. Furthermore, compared with the control group, no significant difference was observed in the body weight of curcumin-treated nude mice. In conclusion, curcumin may act synergistically with the chemotherapeutic regimen FOLFOX in gastric cancer in vitro and in vivo by inducing apoptosis via Bcl/Bax–caspase 8,9–caspase 3 pathway.

Key words: Gastric cancer; Curcumin; FOLFOX; Apoptosis; Chemotherapy

1These authors provided equal contribution to this work.
Address correspondence to Tao You, The Second Affiliated Hospital of Wenzhou Medical University, No. 109, West Xueyuan Road, Wenzhou 325027, China. Tel: +86 139 57706972; Fax: +86 577 88653538; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 35–41, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14452563486057
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Copyright © 2016 Cognizant, LLC. 
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Enhancement of Chemosensitivity by Stathmin-1 Silencing in Gastric Cancer Cells In Situ and In Vivo

Zhi-jian Meng* and Ke Tao†

*Department of Emergency, Zhengzhou People’s Hospital, Zhengzhou, China
†Burn Center of PLA, Xijing Hospital, the Fourth Military Medical University, Xi’an, China

Reports show that the stathmin gene may have a close relationship with tumor chemotherapeutic sensitivity. However, the effect of stathmin-1 on the chemosensitivity of gastric cancer to docetaxel has not been clearly determined. siRNA targeting stathmin-1 was introduced. The cell growth inhibition, expression of associated proteins, cell cycle, and apoptosis were evaluated by MTT, Western blot, and flow cytometric assays, respectively. The influence of silencing stathmin-1 was detected in situ and in vivo. SGC7901/docetaxel cells are the drug-resistant cells. After silencing stathmin-1, the resistance index (RI) reduced to 3.41, the expressions of STMN-1, MDR1, and ERCC1 were downregulated, but caspase 3 was upregulated. Stathmin-1 siRNA could improve the chemosensitivity of gastric cancer cells to docetaxel, making the percentage of cells at the sub-G1 stage increase and promote apoptosis. The growth of transplantation tumor was significantly suppressed. Therefore, stathmin-1 might be a potential target for enhancing the chemosensitivity of gastric cancer.

Key words: Stathmin-1 silencing; siRNA; Gastric cancer; Docetaxel; Chemosensitivity

Address correspondence to Ke Tao, Burn Center of PLA, Xijing Hospital, the Fourth Military Medical University, No.127, Changle West Road, Xi’an 710032, Shaanxi Province, China. Tel: +86-029-84775298; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 43–51, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14452563486093
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Overexpression of NDRG2 Increases Iodine Uptake and Inhibits Thyroid Carcinoma Cell Growth In Situ and In Vivo

Anqi Yin,*†1 Chengguo Wang,‡1 Jiachen Sun,*1 Jianjun Gao,§ Liang Tao,† Xilin Du,‡ Huadong Zhao,‡ Jiandong Yang,§ and Yan Li*†

*Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, China
†Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
‡Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China
§Department of General Surgery, 210 Hospital of Chinese People’s Liberation Army, Dalian, China

Medullary thyroid carcinoma (MTC) is an uncommon and highly aggressive tumor of the neuroendocrine system, which derives from the neuroendocrine C cells of the thyroid gland. Except for surgical resection, there are not very many effective systemic treatment options for MTC. N-Myc downstream-regulated gene 2 (NDRG2) had a significantly lower expression in MTC compared with normal thyroid tissue. However, the function of NDRG2 in MTC oncogenesis is largely unknown. In this study, we found that overexpression of NDRG2 inhibited the proliferation of TT cells (human medullary thyroid carcinoma cells) in vitro and suppressed the development of MTC in a nude mouse xenograft model. Further analysis revealed that NDRG2 arrested the cell cycle G0/G1 phase progression and induced TT cell apoptosis. Moreover, NDRG2 overexpression may mediate the antiproliferative effect by reducing cyclin D1 and cyclin E protein levels. We also found aberrant NDRG2-mitigated TT cell migration and invasion in vitro. Sodium/iodide symporter (NIS) mediates active I transport into the thyroid follicular cells, and radionuclide treatment is a promising therapy for MTC. Our current data revealed that NDRG2 overexpression enhanced NIS level in TT cells and increased their iodine uptake in vitro. Furthermore, 99mTcO4 radionuclide imaging of the xenograft tumors indicated that NDRG2 could promote NIS-mediated radionuclide transport. In conclusion, the present study suggested that NDRG2 is a critical molecule in the regulation of MTC biological behavior and a potential promoter in radioactive iodine therapy.

Key words: N-Myc downstream-regulated gene 2 (NDRG2); Medullary thyroid carcinoma (MTC); Sodium/iodide symporter (NIS); Tumor-suppressor gene

1These authors provided equal contribution to this work.
Address correspondence to Yan Li, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, 169 Changle West Road, Xi’an, Shaanxi 710032, China. Tel: +86-29-84774516-8024; Fax: +86-29-84774513; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  orJiandong Yang, Department of General Surgery, 210 Hospital of Chinese People’s Liberation Army, 80 Shengli Road, Dalian, Liaoning 116021, China. Tel: +86-412-85841193; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 53–59, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14459480491740
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Inhibition of Lung Carcinoma A549 Cell Growth by Knockdown of Hexokinase 2 In Situ and In Vivo

Feng Xi* and Jianghao Ye†

*Respiratory Department of Medicine, Shanghai Pudong New Area People’s Hospital, Shanghai, China
†Pharmaceutical Preparation Section, the Fourth Affiliated Hospital Zhenjiang University School of Medicine, Yiwu, Zhejiang, China

Hexokinase 2 (HK2) has been identified as an oncogene in some malignant diseases such as breast cancer and ovarian cancer. However, the role of HK2 in lung cancer remains unclear. In this study, we explored the functional role of HK2 in lung cancer cell proliferation and tumorigenesis and determine its expression profile in lung cancer. HK2 expression was increased in primary lung cancer tissues of patients. Knocking down HK2 expression by small interfering RNA (siRNA) inhibited cell proliferation in lung cancer cells and nude mice. Thus, HK2 is required for sustained proliferation and survival of tumor cells in vitro and in vivo, and its aberrant expression may contribute to the pathogenesis of lung cancer. Thus, our study provided evidence that HK2 functions as a novel oncogene in lung cancer and may be a potential therapeutic target for lung cancer.

Key words: Hexokinase 2 (HK2); Lung cancer; Tumorigenesis

Address correspondence to Feng Xi, Respiratory Department of Medicine, Shanghai Pudong New Area People’s Hospital, Number 490, Chuan Huan Nan Road, Chuan Sha, Pudong New Area, Shanghai 201200, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Jianghao Ye, Pharmaceutical Preparation Section, the Fourth Affiliated Hospital Zhenjiang University School of Medicine, Number 1, Kangyuan road, Yiwu, Zhejiang 322000, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 61–68, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14478843952861
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Reduced PDCD4 Expression Promotes Cell Growth Through PI3K/Akt Signaling in Non-Small Cell Lung Cancer

Yan Zhen,*1 Dongming Li,*†1 Wen Li,*†1 Weimin Yao,*†1 Aibing Wu,‡ Jing Huang,‡ Hongli Gu,*† Yujie Huang,*† Yajun Wang,* Jun Wu,*† Min Chen,*† Dong Wu,*† Quanchao Lyu,* WeiyiFang,§ and Bin Wu*†

*Institute of Respiratory Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China
†Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China
‡Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China
§Cancer Research Institute, Southern Medical University, Guangzhou, PR China

It is largely recognized that PDCD4 is frequently lost in tumors of various origins, including lung cancer, and its loss contributes to tumor progression. However, its role and molecular mechanism remain largely unexplored in non-small cell lung cancer (NSCLC). In this study, downregulated PDCD4 mRNA expression was found in NSCLC tissues compared to their corresponding paracarcinoma tissues and distal paracarcinoma tissues. Induced expression of PDCD4 inhibited cell growth and proliferation and cell cycle transition in vitro. Conversely, knocking down PDCD4 expression promoted cell growth and proliferation. Mechanistically, PDCD4 inactivated PI3K/Akt signaling and its downstream cell cycle factors CCND1 and CDK4 to regulate cell growth in NSCLC. Additionally, PI3K-specific inhibitor Ly294002 suppressed the expression of pPI3K (Tyr458), pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Furthermore, Akt-specific inhibitor MK2206 inhibited the expression of pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Taken together, our study provides evidence that PDCD4 inhibits cell growth through PI3K/Akt signaling in NSCLC and may be a potential therapeutic target for NSCLC.

Key words: PDCD4; Non-small cell lung cancer (NSCLC); Cell growth; PI3K/Akt

1These authors provided equal contribution to this work.
Address correspondence to Bin Wu, Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China. Tel: 86-0759-2386792; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Weiyi Fang, Cancer Research Institute, Southern Medical University, Guangzhou 510515, PR China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 69–78, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14478843952906
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Knockdown of microRNA-29a Changes the Expression of Heat Shock Proteins in Breast Carcinoma MCF-7 Cells

Encieh Choghaei,* Gholamreza Khamisipour,† Mojtaba Falahati,* Behrooz Naeimi,† Majid Mossahebi-Mohammadi,‡ Rahim Tahmasebi,† Mojtaba Hasanpour,† Shakib Shamsian,† and Zahra SadatHashemi§

*Department of Molecular and Cellular Sciences, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran
†The Persian Gulf Marine Biotechnology Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran
‡Department of Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
§Department of Medical Biotechnology, School of Advanced Technologies in Medicine (SATiM), Tehran University of Medical Sciences, Tehran, Iran

Breast cancer is the most commonly occurring cancer among women. MicroRNAs as noncoding small RNA molecules play pivotal roles in cancer-related biological processes. Increased levels of microRNA-29a in the serum of breast cancer patients have been reported. Since heat shock proteins (HSPs) play important roles in cell events, the quantitative fluctuations in their cellular levels could be deemed as key indicators of how the exerted treatment alters cell behavior. In this regard, using an antisense small RNA, we attempted to investigate the effects of miR-29a knockdown on the expression of HSPs genes in the MCF-7 breast cancer cell line. MCF-7 cells were cultured in high-glucose Dulbecco’s modified Eagle’s medium with 10% FBS. Studied cells were subdivided into five groups: treated with scramble, anti-miR-29a, anti-miR-29a + Taxol, Taxol, and control. Taxol was added 24 h post-anti-miR transfection and RNA extraction, and cDNA synthesis was done 48 h later. The changes in expression of HSP27, HSP40, HSP60, HSP70, and HSP90 were evaluated by real-time PCR. Our results revealed that inhibitors of microRNA-29a promote apoptosis through upregulation of HSP60 level and downregulation of HSP27, HSP40, HSP70, and HSP90 levels and could be contemplated as a compelling alternative for Taxol employment with similar effects and/or to sensitize cancer cells to chemotherapy with fewer side effects.

Key words: Breast cancer; miR-29a; Heat shock proteins (HSPs)

Address correspondence to Gholamerza Khamisipour, The Persian Gulf Marine Biotechnology Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran. Tel: +989123337806; Fax: +987733452247; 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. 23, pp. 79–86, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14478843952942
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Apoptotic Melanoma B16-F1 Cells Induced by Lidamycin Could Initiate the Antitumor Immune Response in BABL/c Mice

Jian-lin Yang,*1 Ye Qin,*1 Liang Li,† Chu-yu Cao,* Qing Wang,* Qian Li,* Ya-feng Lv,* and Yanlin Wang*

*China Three Gorges University Medical College, Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Yichang, Hubei, China
†Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

In the process of tumor cell apoptosis induced by specific regents, calreticulin (CRT) was transferred from endoplasmic reticulum (ER) onto the cell membrane. These tumor cells, when used as the cellular vaccine to immunize experimental animals, could initiate effective antitumor immunoresponse against homologous tumor cells. This is referred to as immunogenic cell death. Lidamycin (LDM) is an enediyne antibiotic, which has extremely potent cytotoxicity to cancer cells. In this study, the mouse melanoma B16-F1 cancer cells were used to investigate the ability of LDM in promoting immunogenic cell death. Our data showed that LDM could induce apoptosis of B16-F1 cancer cells, accompanied by CRT translocation onto the cell membrane. These LDM-treated B16-F1 cells could be recognized and phagocytosed more efficiently by macrophage and dendritic cells. When the LDM-treated apoptotic B16-F1 cells were used as a whole-cell tumor vaccine to immune mice, the mice obtained resistance against rechallenged B16-F1 living cells. At the same time, the specific antitumor immune response was observed in these vaccinated mice. The splenocytes from the mice vaccinated with LDM-treated B16-F1 cells showed significantly enhanced NK lymphocyte activities and also faster growth rate and increased secretion of IFN-γ when encountering the cellular antigens from B16-F1 cells. All these results suggested that LDM could promote immunogenic cell death in B16-F1 cells, and these LDM-treated B16-F1 cells could be used as a sort of cell vaccine to initiate effective antitumor immunoresponse in mice.

Key words: Lidamycin (LDM); Immunogenic cell death; Calreticulin; Melanoma; Immunotherapy; Mouse

1Joint first authors.
Address correspondence to Dr. Yanlin Wang, China Three Gorges University Medical College, Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Yichang, Hubei 443002, China. Tel: 86-717-6397979; Fax: 86-717-6397179; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 87, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14514194509664
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ERRATUM

The following was originally published in Volume 21, No. 5, pages 281-286, 2014 (DOI: http://dx.doi.org/10.3727/ 096504014X13890370410249). In Figure 4A, the image of b-actin was incorrect in the published article. The corrected version of Figure 4A is shown below. The corrected figure demonstrates the same findings as the original figure. This correction does not alter the interpretation of the results and conclusions.

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