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Raghav Sundar, Anand D Jeyasekharan, Brendan Pang, Richie Chuan Teck Soong, Nesaretnam Barr Kumarakulasinghe, Samuel Guan Wei Ow, Jingshan Ho, Joline Si Jing Lim, David Shao Peng Tan, Einar P V Wilder-Smith, Aishwarya Bandla, Stacey Sze Hui Tan, Bernadette Reyna Asuncion, Zul Fazreen, Michal Marek Hoppe, Thomas Choudary Putti, Lay Mui Poh, Boon Cher Goh, Soo-Chin Lee
INTRODUCTION: Sensory peripheral neuropathy caused by paclitaxel is a common and dose limiting toxicity, for which there are currently no validated predictive biomarkers. We investigated the relationship between the Charcot-Marie-Tooth protein NDRG1 and paclitaxel-induced neuropathy. METHODS/MATERIALS: Archived mammary tissue specimen blocks of breast cancer patients who received weekly paclitaxel in a single centre were retrieved and NDRG1 immunohistochemistry was performed on normal nerve tissue found within the sample...
2016: PloS One
Boris Vassilev, Riku Louhimo, Elina Ikonen, Sampsa Hautaniemi
A modern biomedical research project can easily contain hundreds of analysis steps and lack of reproducibility of the analyses has been recognized as a severe issue. While thorough documentation enables reproducibility, the number of analysis programs used can be so large that in reality reproducibility cannot be easily achieved. Literate programming is an approach to present computer programs to human readers. The code is rearranged to follow the logic of the program, and to explain that logic in a natural language...
2016: PloS One
Xin Li, Mengyou Li, Xiuli Tian, Qingzhe Li, Qingyang Lu, Qingbin Jia, Lianqun Zhang, Jinqiang Yan, Xueyuan Li, Xingang Li
BACKGROUND Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. Our previous study showed that GOLPH3 expression in glioma tissues was related to the severity of the malignancy of the cancer. However, the mechanism by which GOLPH3 affects cell apoptosis is largely unknown. The present study was designed to explore the possible mechanism of GOLPH3 in cell apoptosis. MATERIAL AND METHODS To analyze the biological role of GOLPH3 in glioma cells, we used GOLPH3 small interference RNA in apoptosis of glioma cells...
October 4, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Graham Dominick, Jacqueline Bowman, Xinna Li, Richard A Miller, Gonzalo G Garcia
Studies of the mTOR pathway have prompted speculation that diminished mTOR complex-1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long-lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy-associated protein-A (PAPPA-KO). The ways in which lower mTOR signals slow aging and age-related diseases are, however, not well characterized...
September 13, 2016: Aging Cell
Jehn-Chuan Lee, Kun-Chun Chiang, Tsui-Hsia Feng, Yu-Jen Chen, Sung-Ting Chuang, Ke-Hung Tsui, Li-Chuan Chung, Horng-Heng Juang
Oral squamous cell carcinoma (OSCC) is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG) family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin) gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO), and deferasirox) all significantly inhibit SAS cell growth...
2016: International Journal of Molecular Sciences
Hao Ping, Feiya Yang, Mingshuai Wang, Yinong Niu, Nianzeng Xing
IκB kinase (IKK)/nuclear factor κB (NF-κB) pathway activation is a key event in the acquisition of invasive and metastatic capacities in prostate cancer. A potent small-molecule compound, BMS-345541, was identified as a highly selective IKKα and IKKβ inhibitor to inhibit kinase activity. This study explored the effect of IKK inhibitor on epithelial-mesenchymal transition (EMT), apoptosis and metastasis in prostate cancer. Here, we demonstrate the role of IKK inhibitor reducing proliferation and inducing apoptosis in PC-3 cells...
September 2016: Oncology Reports
Runna Ai, Yulin Sun, Zhimin Guo, Wei Wei, Lanping Zhou, Fang Liu, Denver T Hendricks, Yang Xu, Xiaohang Zhao
N-myc down-regulated gene 1 (NDRG1) has been shown to regulate tumor growth and metastasis in various malignant tumors and also to be dysregulated in esophageal squamous cell carcinoma (ESCC). Here, we show that NDRG1 overexpression (91.9%, 79/86) in ESCC tumor tissues is associated with poor overall survival of esophageal cancer patients. When placed in stable transfectants of the KYSE 30 ESCC cell line generated by lentiviral transduction with the ectopic overexpression of NDRG1, the expression of transducin-like enhancer of Split 2 (TLE2) was decreased sharply, however β-catenin was increased...
September 2016: Cancer Biology & Therapy
Keita P Mori, Hideki Yokoi, Masato Kasahara, Hirotaka Imamaki, Akira Ishii, Takashige Kuwabara, Kenichi Koga, Yukiko Kato, Naohiro Toda, Shoko Ohno, Koichiro Kuwahara, Tomomi Endo, Kazuwa Nakao, Motoko Yanagita, Masashi Mukoyama, Kiyoshi Mori
The amount of albumin filtered through the glomeruli and reabsorbed at the proximal tubules in normal and in diabetic kidneys is debated. The megalin/cubilin complex mediates protein reabsorption, but genetic knockout of megalin is perinatally lethal. To overcome current technical problems, we generated a drug-inducible megalin-knockout mouse line, megalin(lox/lox);Ndrg1-CreER(T2) (iMegKO), in which megalin expression can be shut off at any time by administration of tamoxifen (Tam). Tam administration in adult iMegKO mice decreased the expression of renal megalin protein by 92% compared with that in wild-type C57BL/6J mice and almost completely abrogated renal reabsorption of intravenously injected retinol-binding protein...
July 6, 2016: Journal of the American Society of Nephrology: JASN
Junli Ma, Quanli Gao, Shan Zeng, Hong Shen
BACKGROUND: NDRG1 plays important roles in tumor growth and metastasis of colorectal cancer (CRC). The relation between NDRG1 and metastatic colorectal cancer (mCRC) has not been identified and the mechanism of NDRG1 involving in mCRC needs to be elucidated. METHODS: Correlations between NDRG1 and clinicopathological characteristics and prognosis of 164 patients with mCRC were evaluated. Sensitivity of NDRG1-knockdown colon cancer cell to irinotecan (CPT-11) was determined by MTT assay...
September 2016: Journal of Surgical Oncology
Kyung Chan Park, Leyla Fouani, Patric J Jansson, Danson Wooi, Sumit Sahni, Darius J R Lane, Duraippandi Palanimuthu, Hiu Chuen Lok, Zaklina Kovačević, Michael L H Huang, Danuta S Kalinowski, Des R Richardson
Copper is an essential trace metal required by organisms to perform a number of important biological processes. Copper readily cycles between its reduced Cu(i) and oxidised Cu(ii) states, which makes it redox active in biological systems. This redox-cycling propensity is vital for copper to act as a catalytic co-factor in enzymes. While copper is essential for normal physiology, enhanced copper levels in tumours leads to cancer progression. In particular, the stimulatory effect of copper on angiogenesis has been established in the last several decades...
September 1, 2016: Metallomics: Integrated Biometal Science
Onder Bozdogan, Ibrahim Vargel, Tarik Cavusoglu, Ayse A Karabulut, Gurbet Karahan, Nilufer Sayar, Pınar Atasoy, Isik G Yulug
Cutaneous squamous cell carcinomas (cSCCs) are common human carcinomas. Despite having metastasizing capacities, they usually show less aggressive progression compared to squamous cell carcinoma (SCC) of other organs. Metastasis suppressor proteins (MSPs) are a group of proteins that control and slow-down the metastatic process. In this study, we established the importance of seven well-defined MSPs including NDRG1, NM23-H1, RhoGDI2, E-cadherin, CD82/KAI1, MKK4, and AKAP12 in cSCCs. Protein expression levels of the selected MSPs were detected in 32 cSCCs, 6 in situ SCCs, and two skin cell lines (HaCaT, A-431) by immunohistochemistry...
July 2016: Pathology, Research and Practice
Xiaojing Chang, Xiaoyang Xu, Xiaoying Xue, Jinguo Ma, Zhenhua Li, Peng Deng, Jing Chen, Shuanglong Zhang, Yu Zhi, Dongqiu Dai
The purpose of this study is to detect the clinical significance of NDRG1 and its relationship with MMP-9 in gastric cancer metastatic progression. 101 cases of gastric cancer specimens were utilized to identify the protein expression of NDRG1 and MMP-9 by immunohistochemistry, their clinical significance was also analyzed. The suppression by siRNA-NDRG1 was employed to detect the role of NDRG1 in gastric cancer progression and its relationship with MMP-9. NDRG1 expression was correlated inversely with the degree of tumor cell differentiation (p < 0...
October 2016: Pathology Oncology Research: POR
Ke-Hung Tsui, Yu-Hsiang Lin, Li-Chuan Chung, Sung-Ting Chuang, Tsui-Hsia Feng, Kun-Chun Chiang, Phei-Lang Chang, Chi-Ju Yeh, Horng-Heng Juang
Prostate-derived Ets (E-twenty six) factor (PDEF), an epithelium-specific member of the Ets family of transcription factors, has been shown to play a role in suppressing the development of many epithelium-derived cancers such as prostate and breast cancer. It is not clear, however, whether PDEF is involved in the development or progression of bladder cancer. In a comparison between normal urothelium and bladder tumor tissue, we identified significant decreases of PDEF in the tumor tissue. Further, the immunohistochemistry assays indicated a significantly higher immunostaining of PDEF in low-grade bladder tumors...
May 28, 2016: Cancer Letters
Jung Hye Choi, Jung Soon Kim, Young Woong Won, Jieun Uhm, Byeong Bae Park, Young Yiul Lee
BACKGROUND: Iron is a crucial element for cell proliferation, growth, and metabolism. However, excess iron and altered iron metabolism are both associated with tumor initiation and tumor growth. Deferasirox is an oral iron chelator. Although some studies have indicated that deferasirox is a promising candidate for anti-cancer therapies, its effectiveness against gastric cancer has not yet been determined. This study was conducted to determine whether deferasirox exerts anti-tumor effects in gastric cancer cell lines and whether deferasirox and cisplatin act synergistically...
2016: World Journal of Surgical Oncology
Wei Li, Guixue Hou, Dianrong Zhou, Xiaomin Lou, Yang Xu, Siqi Liu, Xiaohang Zhao
The aldo-keto reductase (AKR) superfamily of enzymes is critical for the detoxification of drugs and toxins in the human body; these enzymes are involved not only in the development of drug resistance in cancer cells but also in the metabolism of polycyclic aromatic hydrocarbons. Here, we demonstrated that AKR1C1/C2 increased the metabolism of ethyl-3,4-dihydroxybenzoate (EDHB) in esophageal squamous cell carcinoma (ESCC) cells. Previous studies have shown that EDHB can effectively induce esophageal cancer cell autophagy and apoptosis, and the AKR1C family represents one set of highly expressed genes after EDHB treatment...
April 19, 2016: Oncotarget
Darius J R Lane, Federica Saletta, Yohan Suryo Rahmanto, Zaklina Kovacevic, Des R Richardson
No abstract text is available yet for this article.
2016: PloS One
Xiao Xu, Zhikun Liu, Jianguo Wang, Haiyang Xie, Jie Li, Jili Cao, Lin Zhou, Shusen Zheng
The more accurate biomarkers have long been desired for hepatocellular carcinoma (HCC). Here, we characterized global large-scale proteomics of multistep hepatocarcinogenesis in an attempt to identify novel biomarkers for HCC. Quantitative data of 37874 sequences and 3017 proteins during hepatocarcinogenesis were obtained in cohort 1 of 75 samples (5 pooled groups: normal livers, hepatitis livers, cirrhotic livers, peritumoral livers, and HCC tissues) by iTRAQ 2D LC-MS/MS. The diagnostic performance of the top six most upregulated proteins in HCC group and HSP70 as reference were subsequently validated in cohort 2 of 114 samples (hepatocarcinogenesis from normal livers to HCC) using immunohistochemistry...
March 22, 2016: Oncotarget
En-Yu Li, Wei-Yung Huang, Ya-Chu Chang, Mong-Hsun Tsai, Eric Y Chuang, Qian-Yu Kuok, Shih-Ting Bai, Lo-Yun Chao, Yuh-Pyng Sher, Liang-Chuan Lai
Hypoxia has been intensively investigated over the past several decades based on the observations that hypoxic tumors are more resistant to therapy and have a worse prognosis. Previously, we reported that N-myc downstream-regulated gene 1 (NDRG1) is strongly up-regulated under hypoxia and may play an important role in tumor adaptation to fluctuating oxygen concentrations. However, the regulatory mechanism of NDRG1 under hypoxia remains elusive. Therefore, the purpose of this study was to identify the transcription factors that regulate NDRG1 and to investigate the functional roles of NDRG1 in hypoxia...
2016: Scientific Reports
Xianghu Qu, Jing Li, H Scott Baldwin
NDRG4 is a member of the NDRG family (N-myc downstream-regulated gene), which is highly expressed in brain and heart. Previous studies showed that Ndrg1-deficient mice exhibited a progressive demyelinating disorder of peripheral nerves and Ndrg4-deficient mice had spatial learning deficits and vulnerabilities to cerebral ischemia. Here, we report generation of Ndrg4 mutant alleles that exhibit several development defects different from those previously reported. Our homozygous mice showed growth retardation and postnatal lethality...
February 12, 2016: Biochemical and Biophysical Research Communications
Kosuke Watari, Tomohiro Shibata, Hiroshi Nabeshima, Ai Shinoda, Yuichi Fukunaga, Akihiko Kawahara, Kazuyuki Karasuyama, Jun-Ichi Fukushi, Yukihide Iwamoto, Michihiko Kuwano, Mayumi Ono
N-myc downstream regulated gene 1 (NDRG1) is a responsible gene for a hereditary motor and sensory neuropathy-Lom (Charcot-Marie-Tooth disease type 4D). This is the first study aiming to assess the contribution of NDRG1 to differentiation of macrophage lineage cells, which has important implications for bone remodeling and inflammatory angiogenesis. Ndrg1 knockout (KO) mice exhibited abnormal curvature of the spine, high trabecular bone mass, and reduced number of osteoclasts. We observed that serum levels of macrophage colony-stimulating factor (M-CSF) and macrophage-related cytokines were markedly decreased in KO mice...
2016: Scientific Reports
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