Oncology Research 24(2) Abstracts

Return to Oncology Research>

Oncology Research, Vol. 24, pp. 73-80, 2016
0965-0407/16 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096504016X
14586627440156
E-ISSN 1555-3906
Copyright
© 2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Mitoxantrone and Etoposide for the Treatment of Acute Myeloid Leukemia Patients in First Relapse

Annie Im, Ali AmjadMounzer Agha, Anastasios Raptis, Jing-Zhou HouRafic Farah, Seah Lim, Alison Sehgal, Kathleen A. Dorritie, Robert L. Redner, Brian McLaughlin, Yongli ShuaiShrina Duggal, and Michael Boyiadzis

Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Relapsed acute myeloid leukemia (AML) represents a major therapeutic challenge. Achieving complete remission (CR) with salvage chemotherapy is the first goal of therapy for relapsed AML. However, there is no standard salvage chemotherapy. The current study evaluated outcomes and prognostic factors for achievement of CR in 91 AML patients in first relapse who were treated with the mitoxantrone–etoposide combination regimen. The overall response rate (CR and CRi) was 25%. Factors that were associated with a lower rate of CR included older age, shorter duration of first CR, low hemoglobin, and low platelet count. The median overall survival for all patients was 7.4 months. The survival of patients who achieved CR and underwent allogeneic hematopoietic cell transplantation (allo-HCT) was higher than those who achieved CR and did not undergo allo-HCT (35.3 months vs. 16.8 months, p = 0.057). The median duration of relapse-free survival was 12.7 months in the patients achieving CR. Older age at the time of AML relapse was associated with worse overall survival. The all-cause 4-week mortality rate was 4%, and the all-cause 8-week mortality rate was 13%. The findings of this study underscore the need for newer therapies, especially those that will improve the ability for patients with relapsed AML to achieve CR and to allow them to receive additional therapies.

Key words: Acute myeloid leukemia (AML); Relapse; Prognostic factors; Mitoxantrone; Etoposide

Address correspondence to Michael Boyiadzis, M.D., M.H.Sc., Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5150 Centre Ave, Suite 572, Pittsburgh, PA 15232, USA. Tel: 412-648-6589; Fax: 412-648-6579; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 81-87, 2016
0965-0407/16 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096504016X
14597766487717
E-ISSN 1555-3906
Copyright
© 2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Lung Cancer Cells and Inhibits Regulating Epithelial-to-Mesenchymal Transition

Shenggang Liu,* Hongzhong Yang,† Ying Chen,‡ Baimei He,§ and Qiong Chen§

*Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
†Department of Respiratory Medicine, Changsha Central Hospital, Hunan, China
‡Department of Internal Medicine, Hunan People’s Hospital, Changsha, Hunan, China
§Department of Geriatric and Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China

In order to improve therapeutic efficacy, it is a current emergency to better know the mechanisms underlying cisplatin resistance in lung cancer cells. In this study, we aim to investigate the role of Kruppel-like factor 4 (KLF4) in cisplatin-resistant lung cancer cells. We developed cisplatin-resistant lung cancer cell line A549/DDP, and then a battery of experiments was used to analyze the effects of KLF4 in cisplatin resistance of lung cancer. We found that KLF4 was significantly downregulated in cisplatin-resistant A549 cells and forced KLF4 expression inhibited cell growth and induced apoptosis. Further, we found that overexpression of KLF4 was able to inhibit cell migration and invasion, to inhibit the expression of Slug, Twist, and vimentin, and to increase the expression of E-cadherin and subsequent inhibition of the EMT process. Thus, overexpression of KLF4 may be a potential strategy for lung cancer treatment, especially for cisplatin-resistant cases.

Key words: Non-small lung cancer; Resistance; Cisplatin; Krüppel-like factor 4 (KLF4); Epithelial-to-mesenchymal transition

Address correspondence to Qiong Chen, Department of Geriatric and Respiratory Medicine, Xiangya Hospital, Central South University, Xiangya Road No. 87, Changsha, Hunan 410008, China. Tel: +86-13607443038; Fax: +86-13607443038; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 89-97, 2016
0965-0407/16 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096504016X
14597766487753
E-ISSN 1555-3906
Copyright
© 2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

miR-187-5p Regulates Cell Growth and Apoptosis in Acute Lymphoblastic Leukemia via DKK2

Ye Lou,*1 Lei Liu,†1 Lihui Zhan,‡ Xuewei Wang,§ and Hua Fan¶

*Department of Hematology, Daqing Oilfield General Hospital, Daqing, Heilongjiang Province, China
†Department of Oncology, Daqing Longnan Hospital, Daqing, Heilongjiang Province, China
‡Department of Ophthalmology, Daqing People’s Hospital, Daqing, Heilongjiang Province, China
§Department of Physical Diagnostics Division, Daqing People’s Hospital, Daqing, Heilongjiang Province, China
¶Department of Hematology, the Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and causes a high rate of mortality in affected adults. Many subtypes of ALL exist with disruptions in distinct genetic pathways, including those regulated by miRNAs. Here we identify miR-187-5p as being highly upregulated in B-cell ALL and a driver of cellular proliferation and suppressor of apoptosis. We show that miR-187-5p directly targets the 3
¢-UTR of DKK2 to mediate these effects. We further determine that inhibition of DKK2 by miR-187-5p in Nalm-6 B cells leads to inappropriate activation of Wnt/b-catenin signaling. Together, these findings reveal that the miR-187-5p–DKK2 pathway regulates Wnt/b-catenin signaling, cell growth, and apoptosis. Our findings provide the first evidence of a role for miR-187-5p in promotion of B-cell ALL.

Key words: Acute lymphoblastic leukemia (ALL); miR-187-5p; DKK2; Cell growth; Cell apoptosis

1These authors provided equal contribution to this work.
Address correspondence to Professor Hua Fan, Department of Hematology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China. Tel: +86-24-62255001; Fax: +86-24-62571119; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 99-108, 2016
0965-0407/16 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096504016X
14611963142173
E-ISSN 1555-3906
Copyright
© 2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

The Downregulation of MicroRNA-10b and its Role in Cervical Cancer

Dongling Zou,* Qi Zhou,† Dong Wang,† Lili Guan,* Li Yuan,*† and Shaolin Li*

*Department of Radiological Medicine, Chongqing Medical University, Chongqing, China
†Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, China

It has been demonstrated that microRNAs (miRNAs) act as oncogenes or tumor suppressors in a variety of cancers. Our previous work suggested that miR-10a/b functioned as a tumor suppressor in gastric cancer, and miR-10b was also reported to be significantly downregulated in advanced stage cervical cancer tissues. However, the aberrant expression of miR-10b in cervical cancer and its possible role in cervical carcinogenesis was largely unknown. In this study, we investigated the expression of miR-10b in cervical cancer tissues, carcinoma in situ tissues, mild dysplasia, moderate dysplasia, severe dysplasia tissues, and normal controls. We found that miR-10b was significantly downregulated during cervical cancer progression, and the lower level of miR-10b in cervical cancer was significantly associated with a more aggressive tumor phenotype. Moreover, overexpression of miR-10b in cervical cancer cells could inhibit the cell proliferation and invasion, and the further mechanism study suggested that its role was possibly through directly targeting HOXA1. These results suggested that the downregulation of miR-10b and the resulting elevated HOXA1 level in cervical cancer tissues might play critical roles in cervical cancer progression.

Key words: Cervical cancer; miR-10b; HOXA1; Tumor suppressor

Address correspondence to Shaolin Li, Department of Radiological Medicine, Chongqing Medical University, Chongqing 400016, China. Tel: 86-13983012321; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 109-116, 2016
0965-0407/16 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096504016X
14611963142254
E-ISSN 1555-3906
Copyright
© 2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

miR-34b Targets HSF1 to Suppress Cell Survival in Acute Myeloid Leukemia

Gangcan Li, Yanping Song, Yunjie Zhang, Hao Wang, and Jia Xie

Institute of Hematopathy, Xi’an Central Hospital, Xian, Shaanxi, China

Acute myeloid leukemia (AML) is the most lethal hematological malignancy, and the occurrence of chemoresistance prevents the achievement of complete remission following the standard therapy. MicroRNAs have been extensively investigated as critical regulators of hematopoiesis and leukemogenesis, and they represent a promising strategy for AML therapy. In this study, we identified miR-34b as a novel regulator in myeloid proliferation and apoptosis of leukemic cells. We found that miR-34b was developmentally upregulated in plasma and myeloid cells of healthy subjects, while it was significantly reduced in blood samples of patients with AML and AML cell lines. Moreover, the miR-34b mimicked transfection-mediated restoration of miR-34b inhibited cell viability and promoted cell apoptosis of HL-60 and OCI-AML3 cell lines. Using a miRNA predicting algorithm miRanda, we selected a potent target heat shock transcription factor 1 (HSF1) since that is a master regulator of the heat shock response and is associated with cancer aggressiveness and dissemination. In contrast to the level of miR-34b, HSF1 was highly expressed in blood samples of patients with AML and AML cell lines. The luciferase reporter assay revealed that miR-34b directly targeted the HSF1 gene. HSF1 silencing exhibited comparable inhibitory effects on AML cell proliferation and survival. The upregulated HSF1 elevated the activation of the Wnt–β-catenin pathway. In conclusion, miR-34b suppressed AML cell proliferation and survival by targeting HSF1, in turn leading to the inactivation of Wnt–β-catenin pathway, which may highlight a new therapeutic approach for AML.

Key words: miR-34b; Acute myeloid leukemia (AML); Heat shock transcription factor 1 (HSF1); Wnt pathway

Address correspondence to Yunjie Zhang, Institute of Hematopathy, Xi’an Central Hospital, Xi’an 710003, Shaanxi, China. Tel: +86-18991152239; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 117-128, 2016
0965-0407/16 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096504016X
14612603423511
E-ISSN 1555-3906
Copyright
© 2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Molecularly Targeted Drugs Plus Radiotherapy and Temozolomide Treatment for Newly Diagnosed Glioblastoma: A Meta-Analysis and Systematic Review

Jiahao Su,* Meiqin Cai,* Wensheng Li,* Bo Hou,† Haiyong He,† Cong Ling,† Tengchao Huang,† Huijiao Liu,† and Ying Guo*

*Department of Neurosurgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
†Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

Glioblastoma (GBM) is the most common primary malignant brain tumor that nearly always results in a bad prognosis. Temozolomide plus radiotherapy (TEM+RAD) is the most common treatment for newly diagnosed GBM. With the development of molecularly targeted drugs, several clinical trials were reported; however, the efficacy of the treatment remains controversial. So we attempted to measure the dose of the molecularly targeted drug that could improve the prognosis of those patients. The appropriate electronic databases (PubMed, MEDLINE, EMBASE, and the Cochrane Library) were searched for relevant studies. A meta-analysis was performed after determining which studies met the inclusion criteria. Six randomized, controlled trials (RCTs) were identified for this meta-analysis, comprising 2,637 GBM patients. The benefit of overall survival (OS) was hazard ratio (HZ), 0.936 [95% confidence interval (CI), 0.852–1.028]. The benefit with respect to progression-free survival (PFS) rate was HZ of 0.796 (95% CI, 0.701–0.903). OS benefit of cilengitide was HZ of 0.792 (95% CI, 0.642–0.977). The adverse effects higher than grade 3 were 57.7% in the experimental group and 44.1% in the placebo group (odds ratio, 1.679; 95% CI, 1.434–1.967). The addition of molecularly targeted drugs to TEM + RAD did not improve the OS of patients with GBM; however, it did improve PFS in patients treated by cilengitide who could not get improvement in OS. The rate of adverse effects was higher in the experimental group than in the placebo group.

Key words: Molecularly targeted drugs; Radiotherapy and temozolomide; Treatment; Glioblastoma (GBM); Newly diagnosed; Overall survival (OS)

Address correspondence to Ying Guo, Department of Neurosurgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China. Tel: +86-15013228659; Fax: +86-021-64085875; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 129-135, 2016
0965-0407/16 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096504016X
14618564639213
E-ISSN 1555-3906
Copyright
© 2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Gemcitabine Plus Vinorelbine as Second-Line Therapy in Patients With Metastatic Esophageal Cancer Previously Treated With Platinum-Based Chemotherapy

Yue-shen Wang,*1 Jing Tian,†1 Yong Han,† Shu-mei Han,† and Sheng-bin Shi†

*Department of Oncology, Jilin People’s Hospital, Jilin, Jilin, P.R. China
†Department of Medical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China

We evaluated the efficacy and feasibility of the combination of gemcitabine plus vinorelbine in patients with platinum-based chemotherapy-refractory esophageal cancer. We enrolled 35 patients who received gemcitabine plus vinorelbine as second-line treatment after platinum-based chemotherapy failure between May 2009 and April 2012. Dosage: gemcitabine 1,000 mg/m2
plus vinorelbine 25 mg/m2; all drugs were administered on days 1 and 8 of a 21-day cycle, and this was continued until failure or unacceptable toxicity. A total of 125 cycles of treatment were administered, and all patients received at least two cycles of treatment (two to five cycles; median number of cycles: three). Thirty-two patients were evaluable for response. The response rate was 31.3%, and the disease control rate (partial response plus stable disease) was 62.5%. The progression-free survival (PFS) was 4.3 ± 0.2 months [95% confidence interval (CI), 4.0–4.6], and the median overall survival (OS) was 7.3 ± 0.3 months (95% CI, 6.7–7.8). In the subgroup analysis, median PFS was 4.0 ± 0.2 months (95% CI, 3.6–4.3) in patients with high expression of miRNA-214, while it was 4.6 ± 0.3 months (95% CI, 4.1–5.1) in patients with low expression of miRNA-214 (log rank = 0.023). Myelosuppression with neutropenia and thrombocytopenia was the most common side effect observed with this combination regimen, and higher than grade 3 neutropenia and thrombocytopenia were observed in 10 (31.3%) and 8 patients (25.0%), respectively. Grade 3 fatigue was the most common nonhematologic toxicity, which was observed in 2 (6.1%) patients. The combination of gemcitabine plus vinorelbine was well tolerated as second-line treatment for platinum-based chemotherapy-refractory esophageal cancer patients and appeared to provide enhanced clinical activity especially in patients with low expression of miRNA-214.

Key words: Advanced esophageal cancer; Second-line treatment; Gemcitabine plus vinorelbine; Platinum-based chemotherapy; miRNA-214; Progression-free survival

1These authors provided equal contribution to this work.
Address correspondence to Jing Tian, M.D., Department of Medical Oncology, Shandong Tumor Hospital, Jiyan Road 440#, Huaiyin District, Jinan, Shandong Province 250117, China. Tel: 86+53167626351; Fax: 86+53167626981; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it