Oncology Research : Featuring Preclinical and Clinical Cancer Therapeutics

Co-Editors-in-Chief

American Continent:
Edward Chu
University of Pittsburgh Cancer Institute, USA
Email:  chueyale@yahoo.com

Asia and Pacific Rim:
Kazuo Umezawa
Aichi Medical University School of Medicine, Japan
Email:  umezawa@aichi-med-u.ac.jp

European Continent:
Enrico Mini
University of Florence, Italy
Email:  enrico.mini@unifi.it

Associate Editor: Lois Malehorn

EDITORIAL ADVISORY BOARD

Alan C. Sartorelli,† Founding Editor

American Continent: Edward Chu, Co-Editor-in-Chief
L. J. Appleman, University of Pittsburgh, USA
N. Bahary, University of Pittsburgh, USA
J. R. Bertino, Rutgers Cancer Institute of New Jersey, USA
J. H. Beumer, Hillman Cancer Center, USA
M. Boyiadzis, University of Pittsburgh, USA
Y.-C. Cheng, Yale University School of Medicine, USA
M. S. Copur, University of Nebraska, USA
A. Krishnamurthy, University of Pittsburgh, ISA
J. J. Lee, University of Pittsburgh, USA
Y. Li, Sorrento Therapeutics, USA
G. D. Roodman, Indiana University, USA
M. Rudek, Johns Hopkins University, USA
J. C. Schmitz, University of Pittsburgh, USA
L. Zhang, University of Pittsburgh, USA

European Continent: Enrico Mini, Co-Editor-in-Chief
A. H. Calvert, University of Newcastle upon Tyne, UK
A. Di Paolo, University of Pisa, Italy
P. Workman, CRC Center for Cancer Therapeutics, UK

Asia and Pacific Rim: Kazuo Umezawa, Co-Editor-in-Chief
A. Deguchi, Tokyo Women’s Medical University, Japan
S. Gantsev, Bashkirian State Medical University, Russia
R. Horie, Kitasato University, Japan
Y. Horiguchi, Tokyo Medical University, Japan
M. Imoto, Keio University, Japan
H. Kakeya, Kyoto University, Japan
M. Kawatani, RIKEN, Japan
E. Kikuchi, Keio University, Japan
Y. Lin, Aichi Medical University, Japan
J. Neuzil, Griffith University, Gold Coast Campus, Australia
O. Ohno, Keio University, Japan
T. Ohsugi, Rakuno Gakuen University, Japan
H. Osada, RIKEN, Japan
M. Oya, Keio University, Japan
M. Ozaki, Hokkaido University, Japan
Y. Sasazawa, Keio University, Japan
W. Seubwai, Khon Kaen University, Thailand
K. Sidthipong, Mahidol University, Thailand
S. Simizu, Keio University, Japan
M. Takeiri, Kyoto University, Japan
E. Tashiro, Keio University, Japan
T. Ueno, Kyoto University Hospital, Japan
M. Yamamoto, Waseda University, Japan

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Access Current Articles (Volume 28, Number 1)

Volume 28, Number 1

Table of Contents:

In Memoriam: Naoki Koide 1968–2019 – 1
DOI: https://doi.org/10.3727/096504020X15795276404798

Kazuo Umezawa

Original Contributions

VASH2 Promotes Cell Proliferation and Resistance to Doxorubicin in Non-Small Cell Lung Cancer via AKT Signaling – 3
DOI: https://doi.org/10.3727/096504019X15509383469698

Xiangbin Tan,* Zefei Liao,† Shuangyou Zou,* Liangyun Ma,† and Aimin Wang*

*Department of Oncology, No. 175 Hospital of People’s Liberation Army, Zhangzhou, Fujian, P.R. China
†Department of Thoracic Surgery, No. 180 Hospital of People’s Liberation Army, Quanzhou, Fujian, P.R. China

Vasohibin2 (VASH2), a proangiogenic factor, has been demonstrated to play an oncogenic role in some common human cancers. However, the detailed function of VASH2 in non-small cell lung cancer (NSCLC) has not previously been studied. In this study, we found that VASH2 was significantly upregulated in NSCLC tissues and cell lines, and its increased expression was associated with NSCLC progression and poor prognosis of patients. Knockdown of VASH2 markedly inhibited cell proliferation and P-glycoprotein expression in NSCLC cells. Overexpression of VASH2 enhanced cell proliferation, P-glycoprotein expression, as well as doxorubicin resistance in NSCLC cells. Moreover, the expression levels of VASH2 were significantly increased in newly established doxorubicin-resistant NSCLC cells. Molecular mechanism investigation revealed that inhibition of VASH2 expression in NSCLC cells suppressed the activity of AKT signaling, and overexpression of VASH2 enhanced the activity of AKT signaling. We further showed that downregulation of AKT signaling activity using AKT inhibitor LY294002 markedly inhibited NSCLC cell proliferation and resistance to doxorubicin induced by VASH2. In conclusion, the findings in the present study indicate that VASH2 promotes NSCLC cell proliferation and resistance to doxorubicin via modulation of AKT signaling. Thus, we suggest that VASH2 may become a potential therapeutic target for the treatment of NSCLC.

Key words: Non-small cell lung cancer (NSCLC); Vasohibin2 (VASH2); Doxorubicin; Chemoresistance

MicroRNA-152 Inhibits Cell Proliferation, Migration, and Invasion in Breast Cancer – 13
DOI: https://doi.org/10.3727/096504019X15519249902838

Adilijiang Maimaitiming,* Ailijiang Wusiman,† Abulajiang Aimudula,† Xuekelaiti Kuerban,* and Pengcheng Su*

*Department of Breast and Thyroid Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, P.R. China
†Department of Surgery, Hospital of Xinjiang Traditional Uyghur, Urumqi, P.R. China

The aim of the present study was to investigate the roles of microRNA-152 (miR-152) in the initiation and progression of breast cancer. The expression level of miR-152 was detected in human breast cancer tissue and a panel of human breast cancer cell lines using qRT-PCR. Results found that miR-152 expression was significantly downregulated in breast cancer tissue samples compared to adjacent noncancerous tissues as well as in breast cancer cell lines. Overexpression of miR-152 significantly suppressed breast cancer cell proliferation, migration, and invasion. Luciferase reporter assay results found that ROCK1 is a direct and functional target gene of miR-152 in breast cancer. In addition, downexpression of ROCK1 could inhibit breast cancer cell proliferation, migration, and invasion. These findings indicate that miR-152 inhibited breast cancer growth and metastasis through negative regulation of ROCK1 expression. These data suggest that miR-152/ROCK1 pathway may be a useful therapeutic target for breast cancer treatment.

Key words: Breast cancer; MicroRNA-152; Growth; Metastasis; Therapy; Rho-associated protein kinase 1 (ROCK1)

miR-632 Promotes Laryngeal Carcinoma Cell Proliferation, Migration, and Invasion Through Negative Regulation of GSK3β – 21
DOI: https://doi.org/10.3727/096504018X15213142076069

Zhong-xin Zhou,* Zu-ping Zhang,† Ze-zhang Tao,* and Ting-zhao Tan‡

*Department of Otorhinolaryngology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China
†Department of Otorhinolaryngology, Liaocheng People’s Hospital, Liaocheng, Shandong, P.R. China
‡Department of Oncology, Liaocheng Tumor Hospital, Liaocheng, Shandong, P.R. China

Laryngeal cancer, one of the most common head and neck malignancies, is an aggressive neoplasm. Increasing evidence has demonstrated that microRNAs (miRNAs) exert important roles in oncogenesis and progression of diverse types of human cancers. miR-632, a tumor-related miRNA, has been reported to be dysregulated and implicated in human malignancies; however, its biological role in laryngeal carcinoma remains to be elucidated. The present study aimed at exploring the role of miR-632 in laryngeal cancer and clarifying the potential molecular mechanisms involved. In the current study, miR-632 was found to be significantly upregulated both in laryngeal cancer tissues and laryngeal cancer cell lines. Functional studies demonstrated that miR-632 accelerated cell proliferation and colony formation, facilitated cell migration and invasion, and enhanced the expression of cell proliferation-associated proteins, cyclin D1 and c-myc. Notably, miR-632 could directly bind to the 3¢-untranslated region (3′-UTR) of glycogen synthase kinase 3b (GSK3β) to suppress its expression in laryngeal cancer cells. Mechanical studies revealed that miR-632 promoted laryngeal cancer cell proliferation, migration, and invasion through negative modulation of GSK3b. Pearson’s correlation analysis revealed that miR-632 expression was inversely correlated with GSK3β mRNA expression in laryngeal cancer tissues. Taken together, our findings suggest that miR-632 functions as an oncogene in laryngeal cancer and may be used as a novel therapeutic target for laryngeal cancer.

Key words: miR-632; Cell proliferation; Cell invasion; Laryngeal carcinoma; Glycogen synthase kinase 3β (GSK3β)

Changes in DNA Damage Repair Gene Expression and Cell Cycle Gene Expression Do Not Explain Radioresistance in Tamoxifen-Resistant Breast Cancer – 33
DOI: https://doi.org/10.3727/096504019X15555794826018

Annemarie E. M. Post,*† Johan Bussink,* Fred C. G. J. Sweep,† and Paul N. Span*

*Radboud University Medical Center, Department of Radiation Oncology, Radiotherapy and OncoImmunology Laboratory, Nijmegen, The Netherlands
†Radboud University Medical Center, Department of Laboratory Medicine, Nijmegen, The Netherlands

Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that DNA damage repair or cell cycle genes are involved, and could therefore be targeted to preclude the occurrence of cross-resistance. We aimed to characterize the observed cross-resistance by investigating gene expression of DNA damage repair genes and cell cycle genes in estrogen receptor-positive MCF-7 breast cancer cells that were cultured to tamoxifen resistance. RNA sequencing was performed, and expression of genes characteristic for several DNA damage repair pathways was investigated, as well as expression of genes involved in different phases of the cell cycle. The association of differentially expressed genes with outcome after radiotherapy was assessed in silico in a large breast cancer cohort. None of the DNA damage repair pathways showed differential gene expression in tamoxifen-resistant cells compared to wild-type cells. Two DNA damage repair genes were more than two times upregulated (NEIL1 and EME2), and three DNA damage repair genes were more than two times downregulated (PCNA, BRIP1, and BARD1). However, these were not associated with outcome after radiotherapy in the TCGA breast cancer cohort. Genes involved in G₁, G₁/S, G₂, and G₂/M phases were lower expressed in tamoxifen-resistant cells compared to wild-type cells. Individual genes that were more than two times upregulated (MAPK13) or downregulated (E2F2, CKS2, GINS2, PCNA, MCM5, and EIF5A2) were not associated with response to radiotherapy in the patient cohort investigated. We assessed the expression of DNA damage repair genes and cell cycle genes in tamoxifen-resistant breast cancer cells. Though several genes in both pathways were differentially expressed, these could not explain the cross-resistance for irradiation in these cells, since no association to response to radiotherapy in the TCGA breast cancer cohort was found.

Key words: Treatment resistant; Tamoxifen treatment; Radiotherapy; DNA damage repair; Cell cycle control

miR-122 Inhibits Hepatocarcinoma Cell Progression by Targeting LMNB2 – 41
DOI: https://doi.org/10.3727/096504019X15615433287579

Xiao-Na Li,* Hong Yang,† and Tao Yang‡

*The Department of General Surgery, Tongde Hospital of Zhejiang Province, Zhejiang Province, P.R. China
†The Department of Medical Oncology, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, P.R. China
‡The Department of Hepatological Surgery, Tongde Hospital of Zhejiang Province, Zhejiang Province, P.R. China

In the present study, we investigated the role of miR-122 in hepatocarcinoma progression and explored the mechanism. In hepatocarcinoma tissues and cells, we used qRT-PCR to validate the miR-122 expression level. Next, we used colony formation by crystal violet staining assay to compare cell proliferation ability, and we used scratch test or Transwell assay to compare cell migration or invasion ability. We then conducted bioinformatics or luciferase reporter gene assay to prove the regulation effect of miR-122 on lamin B2 (LMNB2), and the biological function of LMNB2 was analyzed. We used nude mouse tumorigenicity assay to test the inhibition effect of miR-122 ASO therapy against hepatocarcinoma. miR-122 was reduced in hepatocarcinoma tissues compared to the paracarcinoma tissues, which was relatively low or high in hepatocarcinoma cell line SMMC7721 or Hep3B, and overexpressed miR-122 inhibited proliferation, migration, and invasion in hepatocarcinoma cells. Additionally, some reports showed that LMNB2 was regulated by miR-122, which inhibited the expression of LMNB2. Moreover, LMNB2 functioned to promote cell proliferation, migration, and invasion. We could achieve the inhibition of hepatocarcinoma using miR-122 therapy through decreasing LMNB2 expression in vivo. Our data indicated that miR-122 could inhibit hepatocellular carcinoma cell progression by targeting LMNB2 and as a therapeutic target for hepatocarcinoma treatment.

Key words: miR-122; Hepatocarcinoma; Progression; Lamin B2 (LMNB2); Target

The lncRNA FEZF1-AS1 Promotes the Progression of Colorectal Cancer Through Regulating OTX1 and Targeting miR-30a-5p – 51
DOI: https://doi.org/10.3727/096504019X15619783964700

Jing Li,*† Lian-mei Zhao,‡ Cong Zhang,‡ Meng Li,§ Bo Gao,† Xu-hua Hu,† Jian Cao,† and Gui-ying Wang†

*Medical Examination Center, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei, P.R. China
†The Second General Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei, P.R. China
‡Research Center, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei, P.R. China
§Pediatric Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China

Long noncoding RNAs (lncRNAs) participate in and regulate the biological process of colorectal cancer (CRC) progression. Our previous research identified differentially expressed lncRNAs in 10 CRC tissues and 10 matched nontumor tissues by next-generation sequencing (NGS). In this study, we identified an lncRNA, FEZF1 antisense RNA 1 (FEZF1-AS1), and further explored its function and mechanism in CRC. We verified that FEZF1-AS1 is highly expressed in CRC tissues and cell lines. Through functional experiments, we found that reduced levels of FEZF1-AS1 significantly suppressed CRC cell migration, invasion, and proliferation and inhibited tumor growth in vivo. Mechanistically, we discovered that reduced levels of the lncRNA FEZF1-AS1 inhibited the activation of epithelial–mesenchymal transition (EMT); the overexpression of orthodenticle homeobox 1 (OTX1) partially rescued the FEZF1-AS1-induced inhibition of protein expression. It indicated that FEZF1-AS1 may play a role in the occurrence and development of CRC by regulating the FEZF1-AS1/OTX1/EMT pathway. Furthermore, it was reported that FEZF1-AS1 is located in both the nucleus and cytoplasm of HCT116 cells. Dual-luciferase reporter assays verified that FEZF1-AS1 directly binds miR-30a-5p and negatively regulated each other. Further, we showed that 5′-nucleotidase ecto (NT5E) is a direct target of miR-30a-5p, and the inhibition of miR-30a-5p expression partially rescued the inhibitory effect of FEZF1-AS1 on NT5E. Our results indicated that the mechanism by which FEZF1-AS1 positively regulates the expression of NT5E is through sponging miR-30a-5p. Our study demonstrated that lncRNA FEZF1-AS1 is involved in the development of CRC and may serve as a diagnostic and therapeutic target for CRC patients.

Key words: Colorectal cancer (CRC); FEZF1 antisense RNA 1 (FEZF1-AS1); miR-30a-5p; 5′-Nucleotidase ecto (NT5E); Orthodenticle homeobox 1 (OTX1); Epithelial–mesenchymal transition (EMT)

Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis – 65
DOI: https://doi.org/10.3727/096504019X15656904013079

Huasong Liu,* Jun Zhang,* Xiangyu Luo,* Min Zeng,* Liqiang Xu,* Qunxian Zhang,* Hua Liu,* Jialong Guo,* and Lanlan Xu†

*Department of Cardiothoracic Surgery, Taihe Hospital Affiliated to Hubei University of Medicine, Shiyan, Hubei, P.R. China
†Hubei University of Medicine, Hubei, P.R. China

Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) mediate the development of esophageal squamous cell carcinoma (ESCC) via various pathophysiological pathways. This study explored the impact of the lncRNA FOXD2-AS1 on cisplatin resistance in ESCC and its possible mechanisms. Upregulation of FOXD2-AS was detected in patients with ESCC and ESCC cells that are resistant to cisplatin. In an in vitro assay, knockdown of FOXD2-AS1 noticeably inhibited cell invasion and growth, triggered cell death, and repressed the stimulation of the Akt/mTOR axis in cisplatin-resistant ESCC cells (TE-1/DDP). Conversely, the overexpression of FOXD2-AS1 remarkably increased cell invasion and growth, repressed cell death, and triggered the stimulation of the Akt/mTOR axis in TE-1/DDP cells. These findings, along with bioinformatics and validation tests, showed that FOXD2-AS1 targeted miR-195 by acting as a competing endogenous RNA. FOXD2-AS1/miR-195/Akt/mTOR axis plays a crucial role in resistance to cisplatin in ESCC cells, offering an innovative strategy to treat ESCC.

Key words: FOXD2-AS1; Esophageal squamous cell carcinoma (ESCC); Cisplatin resistance; miR-195; Akt/mTOR signal pathway

Efficacy and Safety of Drug-Eluting Beads Transarterial Chemoembolization by CalliSpheres® in 275 Hepatocellular Carcinoma Patients: Results From the Chinese CalliSpheres® Transarterial Chemoembolization in Liver Cancer (CTILC) Study – 75
DOI: https://doi.org/10.3727/096504019X15662966719585

Junhui Sun,*1 Guanhui Zhou,*1 Xiaoxi Xie,† Wenjiang Gu,‡ Jing Huang,§ Dedong Zhu,¶ Wenhao Hu,# Qinming Hou,** Changsheng Shi,†† Tiefeng Li,‡‡ Xin Zhang,§§ Wenbin Ji,¶¶ Shihong Ying,§§ Zhiyi Peng,§§ Jian Zhou,## Zhihai Yu,*** Jiansong Ji,††† Haijun Du,‡‡‡ Xiaohua Guo,§§§

Jian Fang,¶¶¶ Jun Han,### Huanhai Xu,**** Zhichao Sun,†††† Wenqiang Yu,‡‡‡‡ Guoliang Shao,§§§§ Xia Wu,¶¶¶¶ Hongjie Hu,¶¶¶¶ Ling Li,# Jiaping Zheng,§§§§ Jun Luo,§§§§ Yutang Chen,§§§§ Guohong Cao,#### and Tingyang Hu‡‡‡‡

*Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P.R. China
†Interventional Center, Xinchang People’s Hospital, Shaoxing, P.R. China
‡Department of Intervention, Jiaxing Second Hospital, Jiaxing, P.R. China
§Department of Hepatobiliary Surgery, Ningbo Medical Center, Lihuili Eastern Hospital, Ningbo, P.R. China
¶Department of Liver Oncology, Ningbo No. 2 Hospital, Ningbo, P.R. China
#Department of Intervention, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
**Department of Radiology, Xixi Hospital of Hangzhou, Hangzhou 6th People’s Hospital, Hangzhou, P.R. China
††Department of Intervention, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, P.R. China
‡‡Department of Radiology, Beilun District People’s Hospital of Ningbo, Ningbo, P.R. China
§§Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P.R. China
¶¶Department of Radiology, Taizhou Hospital of Zhejiang Province, Linhai, P.R. China
##Department of Radiology, Hangzhou Cancer Hospital, Hangzhou, P.R. China
***Department of Vascular and Interventional Radiology, The Affiliated Hospital of Medical College of Ningbo University, Ningbo, P.R. China
†††Department of Radiology, Lishui Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, P.R. China
‡‡‡Department of Intervention, Dong Yang People’s Hospital, Dongyang, P.R. China
§§§Department of Intervention, Jinhua Central Hospital, Jinhua, P.R. China
¶¶¶Department of Hepatobiliary Surgery, Quzhou People’s Hospital, Quzhou, P.R. China
###Department of Intervention, Jiaxing First Hospital, Jiaxing, P.R. China
****Division of Digestive Endoscopy, YueQing City People’s Hospital, Yueqing, P.R. China
††††Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, P.R. China
‡‡‡‡Department of Intervention, Zhejiang Provincial People’s Hospital, Hangzhou, P.R. China
§§§§Department of Intervention, Zhejiang Cancer Hospital, Hangzhou, P.R. China
¶¶¶¶Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, Hangzhou, P.R. China
####Department of Radiology, Shulan (Hangzhou) Hospital, Zhejiang University International Hospital, Hangzhou, P.R. China

The purpose of this study was to investigate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment in Chinese hepatocellular carcinoma (HCC) patients and the prognostic factors for treatment response as well as survival. A total of 275 HCC patients were included in this prospective study. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST), and progression-free survival (PFS) as well as overall survival (OS) were determined. Liver function and adverse events (AEs) were assessed before and after DEB-TACE operation. Complete response (CR), partial response (PR), and objective response rate (ORR) were 22.9%, 60.7%, and 83.6%, respectively. The mean PFS was 362 (95% CI: 34.9–375) days, the 6-month PFS rate was 89.4 ± 2.1%, while the mean OS was 380 (95% CI: 370–389) days, and the 6-month OS rate was 94.4 ± 1.7%. Multivariate logistic regression revealed that portal vein invasion (p = 0.011) was an independent predictor of worse clinical response. Portal vein invasion (p = 0.040), previous cTACE treatment (p = 0.030), as well as abnormal serum creatinine level (BCr) (p = 0.017) were independent factors that predicted worse ORR. In terms of survival, higher Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.029) predicted for worse PFS, and abnormal albumin (ALB) (p = 0.011) and total serum bilirubin (TBIL) (p = 0.009) predicted for worse OS. The number of patients with abnormal albumin, total protein (TP), TBIL, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were augmented at 1 week posttreatment and were similar at 1–3 months compared with baseline. The most common AEs were pain, fever, nausea, and vomiting, and no severe AEs were observed in this study. DEB-TACE was effective and tolerable in treating Chinese HCC patients, and portal vein invasion, previous cTACE treatment, abnormal BCr, ALB, and TBIL appear to be important factors that predict worse clinical outcome.

Key words: Drug-eluting beads transarterial chemoembolization (DEB-TACE); Hepatocellular carcinoma (HCC); Clinical efficacy; Safety; Prognostic factors; Liver function

Inhibition of Long Noncoding RNA CRNDE Increases Chemosensitivity of Medulloblastoma Cells by Targeting miR-29c-3p – 95
DOI: https://doi.org/10.3727/096504019X15742472027401

Xiao-hui Sun,* Wen-jie Fan,† Zong-jian An,‡ and Yong Sun‡

*Medical Department, Qingdao Infectious Disease Hospital, Qingdao, Shandong, P.R. China
†Department of Anesthesia, Qingdao Women and Children’s Hospital, Qingdao, Shandong, P.R. China
‡Department of Pediatric Neurosurgery, Qingdao Women and Children’s Hospital, Qingdao, Shandong, P.R. China

Long noncoding RNA CRNDE (CRNDE) recently emerged as a carcinogenic promoter in various cancers including medulloblastoma. However, the functions and molecular mechanisms of CRNDE to the acquired drug resistance of medulloblastoma are still unclear. The transcript levels of CRNDE were examined in four medulloblastoma cell lines exposed to cisplatin treatment, and IC₅₀ values were calculated. Effects of CRNDE knockdown or miR-29c-3p overexpression on cell viability, colony formation, apoptosis, migration, and invasion were assessed using the CCK-8, colony formation assay, flow cytometry, and Transwell assays, respectively. RNA pulldown and RNA-binding protein immunoprecipitation (RIP) were performed to confirm the molecular interactions between CRNDE and miR-29c-3p involved in medulloblastoma cells. The in vivo role of CRNDE knockdown or miR-29c-3p overexpression on tumor growth and apoptosis was evaluated in a xenograft mouse model of human medulloblastoma. The transcript levels of lncRNA CRNDE were significantly higher in cisplatin-treated tumor cells with higher IC50 values. Depletion of CRNDE inhibited tumor cell proliferation and colony formation, induced cell apoptosis, and suppressed migration and invasion in medulloblastoma cells. Moreover, overexpression of miR-29c-3p inhibited tumor cell proliferation and colony formation, migration, and invasion, and enhanced apoptosis and chemosensitivity to cisplatin. In addition, CRNDE was found to act as a miR-29c-3p sponge. Furthermore, in vivo experiments showed the CRNDE/miR-29c-3p interactions involved in medulloblastoma. Our study demonstrates that CRNDE acts as a critical mediator of proliferation, apoptosis, migration, invasion, and resistance to chemotherapeutics via binding to and negatively regulating miR-29c-3p in medulloblastoma cells. These results provide novel molecular targets for treatment of medulloblastoma.

Key words: Medulloblastoma; Long noncoding RNA (lncRNA); CRNDE; miR-29c-3p

Case Report/Review

Loss of Fingerprints as a Side Effect of Capecitabine Therapy: Case Report and Literature Review – 103
DOI: https://doi.org/10.3727/096504019X15605078731913

Jian Zhao,*1 Xia Zhang,†1 Xiaonan Cui,* Di Wang,* Bin Zhang,*‡ and Liying Ban*

*Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, P.R. China
†Department of Oncology, The Fifth People’s Hospital of Dalian, Dalian, P.R. China
‡Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, P.R. China

Hand–foot syndrome (HFS) is the main side effect of capecitabine and affects the compression zones of the body such as the palms and soles, causing numbness, paresthesias, skin swelling or erythema, scaling, chapping, hard nodule-like blisters, and severe pain. Loss of fingerprints is also observed in some cases. Severe cases of HFS are common in the review of clinical reports. However, loss of fingerprints has not received significant attention. Two reported cases of loss of fingerprints in The New England Journal of Medicine and The BMJ have drawn attention to this side effect of capecitabine. Loss of fingerprints has a serious impact on patients’ daily life, especially on personal identification. This report describes a patient who lost her fingerprints during the early stage of chemotherapy. Our aim is to draw the medical profession’s attention to this problem.

Key words: Hand–foot syndrome (HFS); Capecitabine; Loss of fingerprints; Breast cancer

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Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics is indexed and abstracted in: Current Contents/Life Sciences, Science Search, Science Citation Index, Research Alert, MEDLARS, MEDLINE, Index Medicus, BIOSIS, SIIC (Sociedad Iberoamericana de Información Cientifica) Database, and CABS (Current Awareness in Biological Sciences).