Oncology Research 25(4) Abstracts

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Oncology Research, Vol. 25, pp. 463-470, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14685034103879
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

miR-126-5p Restoration Promotes Cell Apoptosis in Cervical Cancer by Targeting Bcl2l2

Changlin Wang,* Bin Zhou,† Min Liu,* Ying Liu,* and Rui Gao*

*Department of GynaecologyTaian City Central Hospital, Taian, P.R. China
†Department of Reproduction and Genetic, Taian City Central Hospital, Taian, P.R. China

Cervical cancer is one of the most common cancers in females, with a high incidence and mortality around the world. However, the pathogenesis in cervical cancer is not completely known. In the present study, we investigated the role of miR-126-5p and Bcl2l2 in cervical cancer cells. First, miR-126-5p expression was aberrantly downregulated in human cervical cancer tumor tissues in comparison with normal tissues, as evaluated by RT-PCR. Consistently, the levels of miR-126-5p were also significantly reduced in cervical cancer cell lines when compared to normal cervical epithelial cells. Flow cytometric analysis showed that the rate of apoptosis of cervical cancer cells was significantly increased by miR-126-5p overexpression but inhibited by miR-126-5p inhibitor. A similar change pattern was observed in the expression of apoptosis-regulated protein caspase 3 in cervical cancer cells transfected with miR-126-5p mimic or inhibitor. By bioinformatic prediction with online databases and verification using luciferase reporter assay, we then identified that Bcl2l2 is a direct target of miR-126-5p in cervical cancer cells. The expression of Bcl2l2 was strongly downregulated by the miR-126-5pmimic but upregulated by the miR-126-5p inhibitor in cervical cancer cells, and Bcl2l2 expression was significantly increased in human cervical cancer tumor tissues, which was negatively correlated with miR-126-5p levels. Furthermore, we confirmed that the rate of apoptosis was significantly increased by Bcl2l2 silencing in cervical cancer cells, which was not affected by the miR-126-5p inhibitor. In addition, the increased apoptosis of cells by the miR-126-5p mimic was inhibited by Bcl2l2 overexpression. In summary, miR-126-5p plays an inhibitory role in human cervical cancer progression, regulating the apoptosis of cancer cells via directly targeting Bcl2l2. This might provide a potential therapeutic target for cervical cancer.

Key words: miR-126-5p; Cervical cancer; Apoptosis; Caspase 3; Bcl2l2

Address correspondence to Changlin Wang, Department of GynaecologyTaian City Central Hospital, Longtan Road No. 29, Taian 271000, P.R. China. Tel: +86-0538-6298551; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 471-478, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14721217330657
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Prognostic Investigations of Expression Level of Two Genes FasL and Ki-67 as Independent Prognostic Markers of Human Retinoblastoma

Samaneh Kouzegaran,* Kourosh Shahraki,† Ali Makateb,‡ Farkhondeh Shahri,§ Negin Hatami,¶ Vahid Behnod,# and Amir Saber Tanha**

*Department of Pediatrics, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
†Department of Ophthalmology, Alzahra Eye Hospital, Zahedan University of Medical Sciences, Zahedan, Iran
‡Department of Ophthalmology, AJA University of Medical Sciences, Tehran, Iran
§Department of Optometry, School of Rehabilitation, Zahedan University of Medical Sciences, Zahedan, Iran
¶Department of Radiology, Stanford University, School of Medicine, Stanford, CA, USA
#Department of Molecular Biology, Baqiyatallah University of Medical Sciences, Tehran, Iran
**Department of Anesthesia, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran

In this study, expression of FasL and Ki-67 messenger RNA (FasL and Ki-67 mRNA) in human retinoblastoma (HRB) was examined by the immunohistochemistry method and quantitative real-time PCR. Positive expression of Ki-67 in tumor cells was detected in 16 of 30 patients (53.33%), and only 9 (30%) of the tissues from patients with retinoblastoma showed positive staining for FasL. Our results revealed that FasL expression was significantly higher in tumor tissue with invasion compared with the noninvasion form (p = 0.033). Ki-67 expression was markedly increased in tumor tissues with invasion compared with the noninvasion group (p = 0.04), but no significant correlation was found between FasL expression and differentiation (p > 0.05). In addition, Ki-67 expression was strongly linked to differentiation (p < 0.002). Expression of these FasL was correlated with shorter overall survival of patients, but its expression was not significantly associated with overall survival (p = 0.15). The impact of Ki-67 expression on survival in patients was also evaluated. Ki-67 expression level was not found to be significantly associated with shorter survival (Kaplan–Meier; p = 0.09). Univariate analysis revealed that massive choroidal invasion was correlated with poor prognosis. Taken together, the data suggest that massive choroidal invasion is also an important indicator of poor prognosis for HRB.

Key words: Retinoblastoma (RB); Ki-67 and FasL; Analysis; Expression; Molecular

Address correspondence to Amir Saber Tanha, Department of Anesthesia, Faculty of Medicine, Birjand University of Medical Sciences, Moallem Avenue, Behdarie ShahrestanBirjand 97178, Iran. Tel: +989151600384; Fax: +98 561 300 76; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 479-483, 2017
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DOI: https://doi.org/10.3727/096504016X
14721731148893
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Wnt Pathway Activator Induces Apoptosis and Cell Death in Mouse Monocytic Leukemia Cells

Yoshiro Kato,* Yoshikazu Naiki,† Takayuki Komatsu,† Kazuko Takahashi,† Jiro Nakamura,* and Naoki Koide†

*Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
†Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Wnt agonist, 2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl) pyrimidine, is a cellpermeable pyrimidine compound that has been shown to mimic the effect of Wnt. In this study, leukemic mouse cell lines, RAW 264.7 and J774.1, were incubated with the Wnt agonist. The Wnt agonist showed cell death in the concentration of 1–10 µM. The Wnt agonist did not show inhibition of GSK-3β activity but induced β-catenin accumulation in the nucleus. The Wnt agonist showed caspase-independent cell death, but no further involvement in cell death ER stress signaling. Here we discuss the possible mechanism of Wnt agonist-induced apoptotic cell death in RAW 264.7 cells.

Key words: RAW 264.7 cells; Wnt agonist; Cytotoxicity; β-Catenin; Endoplasmic reticulum (ER) stress

Address correspondence to Naoki Koide, Department of Microbiology and Immunology, Aichi Medical University School of Medicine, 1-1 YazakokarimataNagakute, Aichi 480-1195, Japan. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 485-493, 2017
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DOI: https://doi.org/10.3727/096504016X
14749340314441
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

High TRAF6 Expression Is Associated With Esophageal Carcinoma Recurrence and Prompts Cancer Cell Invasion

Xinyang Liu,*1 Zhichao Wang,†1 Guoliang Zhang,‡1 Qikun Zhu,‡ Hui Zeng,‡ Tao Wang,‡ Feng Gao,‡ Zhan Qi,‡ Jinwen Zhang,§ and Rui Wang‡

*Department of Internal Medicine, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
†Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
‡Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Hebei, P.R. China
§Department of Medical Affairs, Hebei Chest Hospital, Hebei, P.R. China

Esophageal cancer is one of the most common types of cancer, and it has a poor prognosis. The molecular mechanisms of esophageal cancer progression remain largely unknown. In this study, we aimed to investigate the clinical significance and biological function of tumor necrosis factor receptor-associated factor 6 (TRAF6) in esophageal cancer. Expression of TRAF6 in esophageal cancer was examined, and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of functional and mechanism assays were performed to further investigate the function and underlying mechanisms in esophageal cancer. Expression of TRAF6 was highly elevated in esophageal cancer tissues, and patients with high TRAF6 expression have a significantly shorter survival time than those with low TRAF6 expression. Furthermore, loss-of-function experiments showed that knockdown of TRAF6 significantly reduced the migration and invasion abilities of esophageal cancer cells. Moreover, the pro-oncogenic effects of TRAF6 in esophageal cancer were mediated by the upregulation of AEP and MMP2. Altogether, our data suggest that high expression of TRAF6 is significant for esophageal cancer progression, and TRAF6 indicates poor prognosis in esophageal cancer patients, which might be a novel prognostic biomarker or potential therapeutic target in esophageal cancer.

Key words: Tumor necrosis factor receptor-associated factor 6 (TRAF6); Esophageal cancer (EC); Prognosis; Invasion; Asparaginyl endopeptidase (AEP); Matrix metalloproteinase (MMP)

1These authors provided equal contribution to this work.
Address correspondence to Professor Wang Rui, Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, No. 12 Jian Kang Road, Shijiazhuang, Hebei 050011, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Dr. Jinwen Zhang, Department of Medical Affairs, Hebei Chest Hospital, Hebei 050041, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 495-501, 2017
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DOI: https://doi.org/10.3727/096504016X
14749735594687
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

High-Level Expression of RIPK4 and EZH2 Contributes to Lymph Node Metastasis and Predicts Favorable Prognosis in Patients With Cervical Cancer

Susan Azizmohammadi,* Sima Azizmohammadi,* Aghdas Safari,† Maria Kaghazian,‡ Mina Sadrkhanlo,§ Vahid Behnod,¶ and Mehri Seifoleslami#

*Department of Gynecology, Hajar Hospital, AJA University of Medical Sciences, Tehran, Iran
†Department of Gynecology, Imam Reza Hospital, AJA University of Medical Sciences, Tehran, Iran
‡Department of Biology, Jundishapur University of Medical Sciences, Ahvaz, Iran
§Department of Obstetrics and Gynecology, Tehran University of Medical Sciences, Tehran, Iran
¶Department of Molecular Biology, Baqiyatallah University of Medical Sciences, Tehran, Iran
#Department of Gynecology, Khanevadeh Hospital, AJA University of Medical Sciences, Tehran, Iran

The investigation of specific genes will establish more useful biomarkers for accurate detection and management of gynecological cancers, especially patients with cervical cancer (CCP). The aim of this study was to evaluate the expression level of RIPK4 and EZH2 messenger RNA (RIPK4 and EZH2 mRNA) in CCP. Expression of RIPK4 and EZH2 in the tissues was determined by immunohistochemistry and qRT-PCR methods. Correlations of RIPK4 and EZH2 mRNA with clinical and pathological parameters were analyzed using the Fisher’s exact test. The mRNA level of RIPK4 was significantly upregulated in tumor tissues compared with matched adjacent normal tissues (4.10 ± 0.89 vs. 1.5 ± 0.82; p = 0.021). EZH2 mRNA was increased in cancer tissues compared to normal tissues (3.54 ± 0.71 vs. 1.2 ± 0.65; p = 0.003). High expression of RIPK4 was observed in 25 patients (64.1%), whereas weak expression was seen in 14 cases (35.9%). Furthermore, the expression of RIPK4 was overexpressed in matched adjacent normal tissues (p = 0.004). FIGO stage and lymph node metastasis were significantly linked to a higher expression of RIPK4 (p < 0.05). Overexpression of EZH2 was found in 30 patients (76.9%) and was associated with FIGO stage, histological type, and lymph node metastasis (p < 0.05). In conclusion, our data suggest that RIPK4/EZH2 markers might be used as potential predictors of prognosis in cervical cancer.

Key words: Cervical cancer; Marker; Patient; Pathology; Immunohistochemistry (IHC)

Address correspondence to Mehri Seifoleslami, Department of Gynecology, Khanevadeh Hospital, AJA University of Medical Sciences, Shariati Street, Tee TaleghaniKaj Avenue, Tehran, Iran. Tel: 00989121540069; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 503-510, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14755368915591

E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Knockdown of Latent Transforming Growth Factor-b (TGF-b)-Binding Protein 2 (LTBP2) Inhibits Invasion and Tumorigenesis in Thyroid Carcinoma Cells

Fuqiang Wan,* Li Peng,* ChaoYu Zhu,† XinFa Zhang,‡ FangWen Chen,* and Tao Liu§

*Department of Head and Neck Surgery, Linyi Tumor Hospital, Linyi, P.R. China
†Department No. 2 of Abdominal Surgery, Linyi Tumor Hospital, Linyi, P.R. China
‡Department of Breast Surgery, Linyi Tumor Hospital, Linyi, P.R. China
§Department of General Surgery, Linyi People’s Hospital, Linyi, P.R. China

Latent transforming growth factor-
b (TGF-b)-binding protein 2 (LTBP2) is one of four proteins in the LTBP family of proteins (LTBP1–4) and was shown to play a vital role in tumorigenesis. However, little is known regarding the functional role of LTBP2 in thyroid carcinoma. Therefore, the current study aimed to evaluate the effect of LTBP2 expression on the proliferation, invasion, and tumorigenesis in thyroid carcinoma cells and to explore the molecular mechanism of LTBP2 in tumor progression. Our results showed that the expression of LTBP2 is upregulated in human thyroid carcinoma and cell lines. Knockdown of LTBP2 inhibits the proliferation, invasion, and EMT phenotype in thyroid carcinoma cells. Furthermore, knockdown of LTBP2 attenuates thyroid carcinoma growth in nude mice. Finally, knockdown of LTBP2 inhibits activation of the PI3K/Akt pathway in thyroid carcinoma cells. In summary, the present study has provided further evidence that knockdown of LTBP2 inhibits invasion and tumorigenesis in thyroid carcinoma cells. Our findings may help to further elucidate the molecular mechanisms underlying thyroid carcinoma progression and provide candidate targets for the prevention and treatment of thyroid carcinoma.

Key words: Thyroid carcinoma; Latent transforming growth factor-b (TGF-b)-binding protein 2 (LTBP2); Invasion; PI3K/Akt pathway

Address correspondence to Tao Liu, Department of General Surgery, Linyi People’s Hospital, No. 27 Jiefang Road, Linyi 276000, Shandong, P.R. China. Tel: +86-539-8314068; Fax: +86-539-8314068; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 511-522, 2017
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DOI: https://doi.org/10.3727/096504016X
14756226781802
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Overexpression of Interferon Regulatory Factor 7 (IRF7) Reduces Bone Metastasis of Prostate Cancer Cells in Mice

Yang Zhao, Wenxia Chen, Weiliang Zhu, Hui MengJie Chen, and Jian Zhang

Department of Oncology, Southern Medical University Affiliated Zhujiang Hospital, Guangzhou, P.R. China

The purpose of this study was to identify the role of interferon regulatory factor 7 (IRF7) in the bone metastasis of prostate cancer. Herein we demonstrated the lower expression of IRF7 in bone metastases of prostate cancer. Overexpression of IRF7 in prostate cancer cells had a marked effect on inhibiting bone metastases but not on tumor growth in xenograft nude mice. While in vitro, upregulation of IRF7 had little effect on the malignant phenotype of prostate cancer cells including proliferation, apoptosis, migration, and invasion. However, prostate cancer cells overexpressing IRF7 significantly enhanced the activity of NK cells, which resulted in the cytolysis of prostate cancer target cells. The underlying mechanism may be relevant to the increasing expression of IFN-
b induced by IRF7, as the downregulation of which could inversely inhibit the activity of NK cells. In conclusion, our findings indicate that IRF7 plays a role in reducing bone metastasis of prostate cancer by IFN-b-mediated NK activity.

Key words: Interferon regulatory factor 7 (IRF7); Prostate cancer; Bone metastasis

Address correspondence to Jian Zhang, Department of Oncology, Southern Medical University Affiliated Zhujiang Hospital, 253 Gongye Road, Guangzhou 510282, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 523-536, 2017
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DOI: https://doi.org/10.3727/096504016X
14756282819385
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression

Jianping Shi,*1 Yi Zhang,†1 Nuyun Jin,* Yuqin Li,* Shengtian Wu,* and Leiming Xu†

*Department of Digestion, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, P.R. China
†Department of Digestion, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China

Gastric carcinoma is one of the most common malignancies in men, and microRNA plays a critical role in regulating the signaling networks of gastric carcinoma tumorigenesis and metastasis. We first report the functional characteristics of miR-221-3p in gastric carcinoma. Quantification in gastric carcinoma cell lines and tumor samples reveals significantly increasing miR-221-3p expression. Moreover, a high level of miR-221-3p is correlated with a poor prognosis for gastric carcinoma patients. Ectopic miR-221-3p expression significantly promotes gastric carcinoma cell proliferation, invasion, and sphere formation, while silencing miR-221-3p significantly inhibits these abilities in gastric carcinoma cells. Tests in vivo showed that miR-221-3p significantly promotes tumor growth in xenograft mouse models. In this study, we reveal that miR-221-3p targets PTEN mRNA and downregulates PTEN, which is the possible mechanism of miR-221-3p-induced oncogenic properties. Collectively, we reveal a critical role for miR-221-3p in gastric carcinoma development and progression.

Key words: miR-221-3p; Gastric carcinoma; PTEN; Akt

1These authors provided equal contribution to this work.
Address correspondence to Leiming Xu, Department of Digestion, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 537-544, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14756640150695
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Empty Spiracles Homeobox 2 (EMX2) Inhibits the Invasion and Tumorigenesis in Colorectal Cancer Cells

Yan Zhang, Gang Cao, Qing-gong Yuan, Jun-hui Li, and Wen-Bin Yang

Department of General Surgery, The Second Affiliated Hospital of Medical School, Xi’an Jiaotong University, Xi’an, P.R. China

Empty spiracles homeobox 2 (EMX2) is a homeodomain-containing transcription factor that plays an essential role in tumorigenesis. However, to the best of our knowledge, the role of EMX2 in human colorectal cancer (CRC) is still unclear. Thus, the aim of this study was to investigate the expression and role of EMX2 in CRC. Our results demonstrated that the expression of EMX2 was greatly decreased in CRC tissues and cell lines. Overexpression of EMX2 significantly inhibited the proliferation in vitro and CRC tumor growth in nude mice. In addition, EMX2 also inhibited the migration and invasion of CRC cells. Mechanically, overexpression of EMX2 downregulated the expression levels of
b-catenin, cyclin D1, and c-Myc in CRC cells. Taken together, our study demonstrates that EMX2 inhibits proliferation and tumorigenesis through inactivation of the Wnt/b-catenin pathway in CRC cells. Therefore, EMX2 may be a potential therapeutic target for the treatment of CRC.

Key words: Empty spiracles homeobox 2 (EMX2); Colorectal cancer (CRC); Invasion; Wnt/b-catenin pathway

Address correspondence to Wen-Bin Yang, Department of General Surgery, The Second Affiliated Hospital of Medical School, Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an 710004, P.R. China. Tel: +86-02987679246; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 545-550, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14801968368898
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Significant Radiologic Response of Pancreatic Metastasis After Targeted Therapy of Ceritinib (LDK378) for ALK-Rearranged Lung Adenocarcinoma Presenting With Hyperglycemia

Jing Zheng, Jianya Zhou, Yanping Zhu, Qian Shen, and Jianying Zhou

Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P.R. China

Pancreatic metastasis from non-small cell lung cancer (NSCLC) is usually asymptomatic or presents with abdominal pain, acute pancreatitis, or jaundice. A lung primary is associated with worse survival compared to pancreatic metastases from other organs. Surgical treatment of solitary metastasis to the pancreas from NSCLC has been reviewed in several studies, one of which had a notable disease-free interval. To our knowledge, there are no prior reports of targeted therapy of pancreatic metastasis of NSCLC followed by a significant response. Herein we report the case of a 31-year-old female with a solitary pancreatic metastasis from
ALK-rearranged lung adenocarcinoma despite treatment with chemotherapy and crizotinib; she presented with symptoms of hyperglycemia. Targeted therapy with ceritinib (LDK378) led to symptomatic improvement and a significant radiologic response in the lung and pancreas, but not in the brain.

Key Words: Pancreatic metastasis; ALK; Lung cancer; Ceritinib; LDK378

Address correspondence to Professor Jianying Zhou, Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, XiachengDistrict, Hangzhou 310003, P.R. China. Tel: +86-571-87236876; Fax: +86-571-87236876; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 551-558, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14758370595285
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Tripartite Motif 16 Inhibits the Migration and Invasion in Ovarian Cancer Cells

Hongwei Tan, Jin Qi, Guanghua Chu, and Zhaoyang Liu

Department of Gynecology, Northwest Women and Children’s Hospital, Xi’an, Shaanxi, P.R. China

Tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite motif (TRIM) protein family, has been shown to play a role in tumor development and progression. However, the role of TRIM16 in ovarian cancer has never been revealed. Thus, in this study, we investigated the roles and mechanisms of TRIM16 in ovarian cancer. Our results demonstrated that TRIM16 expression was low in ovarian cancer cell lines. In addition, overexpression of TRIM16 significantly inhibited the migration and invasion in vitro, as well as suppressed the epithelial–mesenchymal transition (EMT) phenotype in ovarian cancer cells. Furthermore, overexpression of TRIM16 greatly inhibited the protein expression levels of ShhSmoPtc, Gli-1, MMP2, and MMP9 in ovarian cancer cells. Taken together, these results strongly suggest that TRIM16 inhibits the migration and invasion via suppressing the Sonic hedgehog signaling pathway in ovarian cancer cells. Thus, TRIM16 may be a novel potential therapeutic target for ovarian cancer.

Key words: Tripartite motif 16 (TRIM16); Ovarian cancer; Cell invasion; Epithelial–mesenchymal transition (EMT)

Address correspondence to Zhaoyang Liu, Department of Gynecology, Northwest Women and Children’s Hospital, No. 1616 Yanxiang Road, Xi’an 710061, Shaanxi, P.R. China. Tel: +86-029-89551081; Fax: +86-02989550875; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 559-569, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14759554689565
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Upregulation of MicroRNA-935 Promotes the Malignant Behaviors of Pancreatic Carcinoma PANC-1 Cells via Targeting Inositol Polyphosphate 4-Phosphatase Type I Gene (INPP4A)

Cuiyue Wang,*† Zhen Feng,‡ Kaitong Jiang,† and Xiuli Zuo*

*Department of Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China
†Department of Digestive Disease, Linyi People’s Hospital, Linyi, Shandong, P.R. China
‡Department of Joint Surgery, Linyi People’s Hospital, Linyi, Shandong, P.R. China

Our goal was to determine the roles and regulatory mechanism of microRNA-935 (miR-935) in the progression of pancreatic cancer. The results showed that, compared with normal pancreatic tissues and cells, the expression of miR-935 was markedly upregulated, while INPP4A expression was obviously downregulated in pancreatic cancer tissues and PANC-1 cells. After transfection with the miR-935 inhibitor, miR-935 was significantly suppressed, and suppression of miR-935 significantly inhibited cell proliferation, suppressed cell migration, and induced cell apoptosis of pancreatic cancer cells. Moreover, suppression of miR-935 resulted in a significant increase in the expression of p27. Also, suppression of miR-935 resulted in significant expression changes of EMT markers; E-cadherin was significantly upregulated, while N-cadherin, Snail, and vimentin were markedly downregulated. In addition, after suppression of miR-935, the expression of apoptosis-related proteins was also changed; Bax was significantly upregulated while Bcl-2, procaspase 3, and active caspase 3 were obviously downregulated. Importantly, opposite effects were obtained when miR-935 was overexpressed by transfection with the miR-935 mimic. In addition, INPP4A was a direct target of miR-935. Silencing of INPP4A significantly counteracted the effects of miR-935 suppression on cell migration and apoptosis, as well as the expression changes of the above EMT- and apoptosis-related molecules. Our findings indicate that upregulation of miR-935 may promote pancreatic cancer cell proliferation and migration and inhibit cell apoptosis by targeting INPP4A. miR-935 and INPP4A may serve as potential targets in the therapy of pancreatic cancer.

Key words: Pancreatic cancer; MicroRNA-935 (miR-935); INPP4A; Cell proliferation; Cell apoptosis; Cell migration

Address correspondence to Xiuli Zuo, Department of Digestive Disease, Qilu Hospital of Shandong University, No. 107 Wenhua West Road, Jinan 250012, Shandong, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 571-577, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14760478220149
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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ZNRF3 Inhibits the Invasion and Tumorigenesis in Nasopharyngeal Carcinoma Cells by Inactivating the Wnt/b-Catenin Pathway

Zhongwei Wang, Yali Wang, Hongtao Ren, Yingying Jin, and Ya Guo

Department of Medical Oncology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, P.R. China

Zinc and ring finger 3 (ZNRF3), which belongs to the E3 ubiquitin ligase family, is involved in the progression and development of cancer. However, the expression and function of ZNRF3 in human nasopharyngeal carcinoma (NPC) remain unclear. Thus, the aim of this study was to investigate the role of ZNRF3 in human NPC. Our results showed that ZNRF3 was downregulated in NPC cell lines. Restoration of ZNRF3 significantly inhibited the proliferation of NPC cells and tumor xenograft growth in vivo. In addition, overexpression of ZNRF3 suppressed migration and invasion, as well as attenuated the epithelial–mesenchymal transition (EMT) process in NPC cells. Furthermore, restoration of ZNRF3 obviously downregulated the expression levels of
b-catenin, cyclin D1, and c-Myc in NPC cells. In conclusion, these data suggest that ZNRF3 inhibited the metastasis and tumorigenesis via suppressing the Wnt/b-catenin signaling pathway in NPC cells. Thus, ZNRF3 may act as a novel molecular target for the treatment of NPC.

Key words: Zinc and ring finger 3 (ZNRF3); Nasopharyngeal carcinoma (NPC); Proliferation; Epithelial–mesenchymal transition (EMT)

Address correspondence to Zhongwei Wang, Department of Medical Oncology, The Second Affiliated Hospital, Xi’an Jiaotong University, 157 Xi’wu Road, Xi’an 710004, P.R. China. Tel: +86-029-87679789; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 579-585, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14760504645779
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

miR-1193 Suppresses Proliferation and Invasion of Human Breast Cancer Cells Through Directly Targeting IGF2BP2

Xianglei Li,1 Yanhua Li,1 and Hong Lu

Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, P.R. China

miRNAs are involved in breast cancer initiation and progression. In this study, we investigated the role of miR-1193, a newly found and poorly studied miRNA, in the proliferation and invasion of human breast cancer cells. Our results showed that compared with the adjacent tissues and MCF-10A human normal breast cells, miR-1193 was sharply reduced in breast cancer tissues and five breast cancer cell lines, including MDA-MB- 231, MDA-MB-468, MDA-MB-435, SKBR3, and MCF-7. The oligo miR-1193 mimic or anta-miR-1193 was then transfected into MDA-MB-231 and MCF-7 breast cancer cell lines. Our results showed that the miR-1193 mimic robustly increased the miR-1193 level and decreased the proliferation and invasion in MDA-MB-231 and MCF-7 cells. In contrast, anta-miR-1193 had an opposite effect on miR-1193 expression, cell proliferation, and cell invasion. Moreover, bioinformatic and luciferase reporter gene assays confirmed that miR-1193 targeted the mRNA 3
¢-UTR region of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an identified proto-oncogene.miR-1193 suppressed the protein level of IGF2BP2 and the activation of the ERK and PI3K/Akt signaling pathways. Moreover, suppression could be rescued by the transfection of pcDNAIGF2BP2. In conclusion, miR-1193 suppressed proliferation and invasion of human breast cancer cells via translational suppression of IGF2BP2.

Key words: Breast cancer; miR-1193; Cell proliferation; Cell invasion; Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)

1These authors provided equal contribution to this work.
Address correspondence to Hong Lu, Department of Oncology, Huaihe Hospital of Henan University, No. 8 Bao Hubei, Kaifeng 475000, P.R. China. Tel: +86-0371-23906821; Fax: +86-0371-23906821; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 587-593, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14761811155298
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

The Inhibitory Effect of PDIA6 Downregulation on Bladder Cancer Cell Proliferation and Invasion

He-Peng Cheng,1 Qian Liu,1 Yang Li, Xiao-Dong Li, and Chao-Yang Zhu

Department of Urinary Surgery, Huaihe Hospital, Henan University, Kaifeng, Henan Province, P.R. China

Protein disulfide isomerases A6 (PDIA6) belongs to the PDI family. Recently, PDIA6 was found to have a close association with various cancers. However, there has been little investigation into the biological functions of PDIA6 in bladder cancer (BC). In this study, we explored the expression pattern and functional significance of PDIA6 in BC. We found that PDIA6 was overexpressed in BC tissues and cell lines. The in vitro study showed that PDIA6 downregulation significantly inhibited BC proliferation and invasion. In addition, the in vivo experiment demonstrated that PDIA6 downregulation decreased the volume, weight, and metastasis of tumors. Furthermore, PDIA6 downregulation reduced the protein expression of
b-catenin, cyclin D1, and c-Myc and thus suppressed the Wnt/b-catenin signaling pathway. In conclusion, we suggest that PDIA6 could be targeted for the treatment of BC.

Key words: Protein disulfide isomerases A6 (PDIA6); Bladder cancer (BC); Proliferation; Invasion

1These authors provided equal contribution to this work.
Address correspondence to Chao-Yang Zhu, Department of Urinary Surgery, Huaihe Hospital, Henan University, No. 8 Baobei Road, Kaifeng 475000, Henan Province, P.R. China. Tel: +86-0371-23906691; Fax: +86-0371-23906691; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 595-603, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14765492198706
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Truncated Bid Overexpression Induced by Recombinant Adenovirus Cre/LoxP System Suppresses the Tumorigenic Potential of CD133+ Ovarian Cancer Stem Cells

Qifang Long,* Weipei Zhu,* Jundong Zhou,† Jinchang Wu,† Weixian Lu,‡ Cui Zheng,‡ Dongmei Zhou,‡ Ling Yu,‡ and Ru Yang‡

*Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
†Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China
‡Department of Gynecology and Obstetrics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China

Ovarian cancer is one of the most lethal malignant gynecologic tumors with a high relapse rate worldwide. Cancer stem cells (CSCs) have been identified in ovarian cancer and other malignant tumors as a small population of cells that are capable of self-renewal and multidifferentiation. CD133+ ovarian CSCs have been reported to be more tumorigenic and more resistant to chemotherapeutic treatment. Thus, CD133 has emerged as one of the most promising therapeutic markers for ovarian cancer treatment. In the current study, we constructed a recombinant adenovirus Cre/loxP regulation system to selectively introduce truncated Bid (tBid) expression specifically targeting CD133+ in ovarian CSCs. The results demonstrated that the coinfection of Ad-CD133-Cre and Ad-CMV-LoxP-Neo-LoxP-tBid significantly increased tBid expression in CD133+ ovarian CSCs. Moreover, the tBidoverexpression induced by a recombinant adenovirus Cre/loxP system dramatically inhibited cell proliferation and invasion, significantly elevated cell apoptosis, and activated the mitochondrial apoptosis pathway in CD133+ovarian CSCs. Additionally, recombinant adenovirus Cre/loxP system-mediated tBid overexpression suppressed the tumorigenic potential of CD133+ ovarian CSCs in a xenograft mouse model. In conclusion, our study successfully constructed a recombinant adenovirus Cre/loxP system and induced tBid overexpression in CD133+ ovarian CSCs, providing a new therapeutic approach for ovarian cancer treatment.

Key words: Truncated Bid (tBid); Cre/loxP system; Ovarian cancer; CD133; Cancer stem cells (CSCs)

Address correspondence to Ru Yang, Department of Gynecology and Obstetrics, Nanjing Medical University, Suzhou Municipal Hospital, No. 26 Daoqian Street, Suzhou, Jiangsu Province 215001, P.R. China. Tel: +86-0512-62364003; Fax: +86-0512-62362502; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 605-615, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14767450526417
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

CDGSH Iron Sulfur Domain 2 Activates Proliferation and EMT of Pancreatic Cancer Cells via Wnt/b-Catenin Pathway and Has Prognostic Value in Human Pancreatic Cancer

Yang Yang, Yuan-song Bai, and Qing Wang

Department of Oncology and Hematology, China–Japan Union Hospital of Jilin University, Changchun, P.R. China

Recently, increasing evidence has shown that CDGSH iron sulfur domain 2 (CISD2) is involved in the initiation and metastasis of several cancers. However, the evidence of its potential role in pancreatic cancer is still lacking. In our present study, CISD2 was found to be increased in pancreatic cancer samples and multiple cell lines. Moreover, statistical analysis revealed that a high level of CISD2 was related to advanced clinical stage, advanced T-stage, positive vascular invasion, positive distant metastasis, and larger tumor size. In addition, multivariate analysis suggests that CISD2 was an independent prognostic factor in pancreatic cancer. Importantly, downregulation of CISD2 was capable of inhibiting the survival and growth of pancreatic cancer cells. Mechanistic study showed that inactivation of the Wnt/
b-catenin pathway contributed to the CISD2 deficit-induced death of pancreatic cancer cells. Furthermore, we showed that CISD2 silencing significantly inhibited EMT via the Wnt/b-catenin pathway. Finally, in nude mice, the CISD2 deficit suppressed the tumorigenesis of pancreatic cancer cells. Collectively, our study demonstrated that CISD2 could be an independent prognostic factor for pancreatic cancer and suggested that the CISD2/Wnt/b-catenin pathway contributes to the proliferation of pancreatic cancer cells and EMT, hinting at a novel promising molecular target in the therapeutic strategy for pancreatic cancer.

Key words: Pancreatic cancer (PC); CDGSH iron sulfur domain 2 (CISD2); Proliferation; Prognosis; Epithelial-to-mesenchymal transition (EMT); Wnt/b-catenin

Address correspondence to Qing Wang, Department of Oncology and Hematology, China–Japan Union Hospital of Jilin University, 126 Xiantai Avenue, Changchun 130000, P.R. China. Fax: 0431-84995198; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 617-627, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14768374457986
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/b-Catenin Signaling Pathway

Chunsheng Li,* Jingrong Dong,† Zhenqi Han,† and Kai Zhang‡

*Department of Gastrointestinal Colorectal and Anal Surgery, China–Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China
†Endoscopic Center, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, P.R. China
‡Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, Changchun, Jilin, P.R. China

MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3
¢-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5poverexpression significantly decreased the Wnt/b-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.

Key words: Gastric cancer; Liver receptor homolog-1 (LRH-1); miR-219-5p; Wnt/b-catenin signaling

Address correspondence to Kai Zhang, Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Changchun, Jilin 130041, P.R. China. Tel: +86-0431-88796555; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 629-640, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14768383625385
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Fibroblast Activation Protein-a-Positive Fibroblasts Promote Gastric Cancer Progression and Resistance to Immune Checkpoint Blockade

Xuyang Wen,* Xiaoping He,† Feng Jiao,‡ Chunhui Wang,§ Yang Sun,‡ Xuequn Ren,¶ and Qianwen Li*

*Oncology Department, The 82nd Hospital of PLA, Huai’an City, Jiangsu Province, P.R. China
†IMR Residency Program of Florida Hospital, Orlando, FL, USA
‡Department of General Surgery, The 82nd Hospital of PLA, Huai’an City, Jiangsu Province, P.R. China
§Department of Cardiology, The 82nd hospital of PLA, Huai’an City, Jiangsu Province, P.R. China
¶Medical Institution, Nanjing University, Nanjing, P.R. China

Gastric cancer (GC) is one of the main causes of cancer death. The tumor microenvironment has a profound effect on inducing tumor growth, metastasis, and immunosuppression. Fibroblast activation protein-
a (FAP) is a protein that is usually expressed in fibroblasts, such as cancer-associated fibroblasts, which are major components of the tumor microenvironment. However, the role of FAP in GC progression and treatment is still unknown. In this study, we explored these problems based on GC patient samples and experimental models. We found that high FAP expression was an independent prognosticator of poor survival in GC patients. FAP+ cancer-associated fibroblasts (CAFs) promoted the survival, proliferation, and migration of GC cell lines in vitro. Moreover, they also induced drug resistance of the GC cell lines and inhibited the antitumor functions of T cells in the GC tumor microenvironment. More importantly, we found that targeting FAP+ CAFs substantially enhanced the antitumor effects of immune checkpoint blockades in GC xenograft models. This evidence highly suggested that FAP is a potential prognosticator of GC patients and a target for synergizing with other treatments, especially immune checkpoint blockades in GC.

Key words: Gastric cancer (GC); Fibroblast activation protein (FAP); Prognosis; Tumor progression; Immune checkpoint blockade

Address correspondence to Xuequn Ren, Medical Institution, Nanjing University, No. 22 Han Kou Road, Nanjing, P.R. China, 210093. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Qianwen Li, Oncology Department, The 82nd Hospital of PLA, No. 100 Jian Kang East Road, Qingjiangpu District, Huai’an City, Jiangsu Province, P.R. China, 223001. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 641-650, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14768398678750
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Validity of Osteoprotegerin and Receptor Activator of NF-kB Ligand for the Detection of Bone Metastasis in Breast Cancer

Gamal A. Elfar,*† Mohamed A. Ebrahim,‡ Nehal M. Elsherbiny,* and Laila A. Eissa*

*Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
†Clinical Pharmacy, Oncology Center, Mansoura University, Mansoura, Egypt
‡Medical Oncology Unit, Oncology Center, Mansoura University, Mansoura, Egypt

Osteoprotegerin (OPG) is a robust antiresorptive molecule that acts as a decoy receptor for the receptor activator of nuclear factor
kB ligand (RANKL), the mediator of osteoclastogenesis. This study was designed to explore the possible role of serum OPG and RANKL in detecting bone metastasis in breast cancer and its interaction with clinicopathologic parameters. Serum levels of RANKL and OPG were estimated in 44 metastatic and 36 nonmetastatic breast cancer patients using ELISA kits. Serum OPG levels were significantly reduced in patients with bone metastasis and correlated negatively with the number of bone lesions and CA 15-3 levels. At concentrations £82 pg/ml, OPG showed a high specificity in identifying the presence of bone metastasis (92%), albeit with low sensitivity (59%), which improved after the exclusion of diabetics and patients treated with aromatase inhibitors (AI). Serum RANKL levels were significantly higher in the presence of bone metastasis and hypercalcemia. At concentrations >12.5 pg/ml, RANKL had an associated sensitivity of 86%, albeit with low specificity (53%), in detecting bone metastasis. The RANKL/OPG ratio significantly increased in the presence of bone metastasis with appropriate sensitivity and specificity (73% and 72%, respectively) at a cutoff of ³0.14 for the detection of bone metastasis. Serum OPG and RANKL/OPG ratios are promising biomarkers for detecting bone metastasis in breast cancer patients.

Key words: Breast cancer; Bone metastasis; Osteoprotegerin (OPG); Receptor activator of nuclear factor kB ligand (RANKL)

Address correspondence to Mohamed A. Ebrahim, M.D., Associate Professor of Medical Oncology, Faculty of Medicine, Oncology Center, Mansoura University, Gehan Al Sadat, Mansoura, Dakahlia Governorate 3516, Egypt. Tel: +201002057451; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Laila A. Eissa, Ph.D., Professor and Head of Clinical Biochemistry Department, Faculty of Pharmacy, University of Mansoura, Mansoura 33516, Egypt. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it