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Amita Shukla-Dave, Mireia Castillo-Martin, Ming Chen, Jose Lobo, Nataliya Gladoun, Ana C Lorduy, Faisal M Khan, Vladimir Ponomarev, Zhengzi Yi, Weijia Zhang, Pier P Pandolfi, Hedvig Hricak, Carlos Cordon-Cardo
Increased polyamine synthesis is known to play an important role in prostate cancer. We aimed to explore its functional significance in prostate tumor initiation and its link to androgen receptor (AR) signaling. For this purpose, we generated a new cell line derived from normal epithelial prostate cells (RWPE-1) with overexpression of ornithine decarboxylase (ODC) and used it for in vitro and in vivo experiments. We then comprehensively analyzed the expression of the main metabolic enzymes of the polyamine pathway and spermine abundance in 120 well-characterized cases of human prostate cancer and high-grade prostate intraepithelial neoplasia (HGPIN)...
October 19, 2016: American Journal of Pathology
Michael L Schulte, Matthew R Hight, Gregory D Ayers, Qi Liu, Yu Shyr, M Kay Washington, H Charles Manning
PURPOSE: This study aimed to study whether cancer cells possess distinguishing metabolic features compared with surrounding normal cells, such as increased glutamine uptake. Given this, quantitative measures of glutamine uptake may reflect critical processes in oncology. Approximately, 10 % of patients with colorectal cancer (CRC) express BRAF (V600E) , which may be actionable with selective BRAF inhibitors or in combination with inhibitors of complementary signaling axes. Non-invasive and quantitative predictive measures of response to these targeted therapies remain poorly developed in this setting...
October 21, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Wenjin Chen, Shengdong Guo, Shenggang Wang
BACKGROUND The purpose of our study was to determine the functional role of microRNA (miR)-16 in chronic inflammatory pain and to disclose its underlying molecular mechanism. MATERIAL AND METHODS Inflammatory pain was induced by injection of complete Freund's adjuvant (CFA) to Wistar rats. The pWPXL-miR-16, PcDNA3.1- Ras-related protein (RAB23), and/or SB203580 were delivered intrathecally to the rats. Behavioral tests were detected at 0 h, 4 h, 1 d, 4 d, 7 d, and 14 d after CFA injection. After behavioral tests, L4-L6 dorsal spinal cord were obtained and the levels of miR-16, RAB23, and phosphorylation of p38 (p-p38) were evaluated by quantitative real-time PCR (qRT-PCR)...
October 22, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
(no author information available yet)
Findings from a phase I/II study indicate a higher response rate among patients with BRAF-mutant metastatic colorectal cancer treated with an EGFR inhibitor alongside dual, as opposed to single-level, MAPK blockade. Panitumumab combined with trametinib and dabrafenib only modestly increased median progression-free survival, however; a short-lived decrease in responders' BRAF V600E mutant allele fraction and the emergence of RAS mutations may have been contributing factors.
October 21, 2016: Cancer Discovery
Min-Min Shi, Yuan Kong, Yang Song, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang
Poor graft function (PGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Murine studies suggest that endothelial progenitor cells (EPCs) are preferential supporting cells for hematopoietic stem cells (HSCs) in the bone marrow (BM) microenvironment. Our previous work found that a reduced number of BM EPCs was an independent risk factor for the occurrence of PGF after allo-HSCT. However, little is known about the functional role of BM EPCs and how to improve impaired BM EPCs in PGF...
October 21, 2016: Blood
Long-Xing Xue, Zhong-Hang Xu, Jiao-Qi Wang, Cui Yang, Hong-Yu Liu, Wen-Zhao Liang, Qiu-Ye Ji, Jin-Ting He, Yan-Kun Shao, Jing Mang, Zhong-Xin Xu
Activin A (Act A), a member of the transforming growth factor-beta (TGF-β), reduces neuronal apoptosis during cerebral ischemia through Act A/Smads signaling pathway. However, little is known about the effect of Act A/Smads pathway on autophagy in neurons. Here, we found that oxygen-glucose deprivation (OGD)-induced autophagy was suppressed by exogenous Act A in a concentration-dependent manner and enhanced by Act A/Smads pathway inhibitor (ActRIIA-Ab) in neuronal PC12 cells. These results indicate that Act A/Smads pathway negatively regulates autophagy in OGD-treated PC12 cells...
October 18, 2016: Biochemical and Biophysical Research Communications
Dan Li, Nan Liu, Liang Zhao, Lei Tong, Hitoshi Kawano, Hong-Jing Yan, Hong-Peng Li
Nigrostriatal pathway injury is one of the traumatic brain injury models that usually lead to neurological dysfunction or neuron necrosis. Resveratrol-induced benefits have recently been demonstrated in several models of neuronal degeneration diseases. However, the protective properties of resveratrol against neurodegeneration have not been explored definitely. Thus, we employ the nigrostriatal pathway injury model to mimic the insults on the brain. Resveratrol decreased the p-ERK expression and increased the p-JNK expression compared to the DMSO group, but not alter the p38 MAPK proteins around the lesion site by Western blot...
October 18, 2016: Brain Research
Binyi Lin, Tianchi Chen, Qijun Zhang, Xiaoxiao Lu, Zhiyun Zheng, Jun Ding, Jinfeng Liu, Zhe Yang, Lei Geng, Liming Wu, Lin Zhou, Shusen Zheng
To investigate the potential oncogene promoting recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT), throughput RNA sequencing was performed in a subgroup of HCC patients. The up-regulated FAM83D in HCC tissues was found and further verified in 150 patients by real-time PCR and immunohistochemistry. FAM83D overexpression significantly correlated with high HCC recurrence rate following LT and poor HCC characteristics such as high AFP, poor differentiation. Of cancer stem cells (CSCs) markers, CD44 expression was effectively suppressed when FAM83D was knocked down by siRNA...
October 18, 2016: Oncotarget
Tiejun Chen, Hu Hou, Yan Fan, Shikai Wang, Qianru Chen, Leilei Si, Bafang Li
Chronic exposure to ultraviolet (UV) irradiation causes skin photoaging. This study was undertaken to identify the anti-photoaging mechanisms of gelatin hydrolysate (CH) derived from pacific cod skin. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA assays were used to investigate the effects of CH on matrix metalloproteinases (MMPs) and the signaling pathways after UV irradiation by using a mice skin photoaging model. The average molecular weight of CH was 1200Da, and 273/1000 residues were hydrophobic, Gly-Pro and Gly-Leu sequences and Arg at C-terminus appeared frequently in CH...
October 14, 2016: Journal of Photochemistry and Photobiology. B, Biology
Fufa Qu, Zhiming Xiang, Yang Zhang, Jun Li, Shu Xiao, Yuehuan Zhang, Fan Mao, Haitao Ma, Ziniu Yu
p38 mitogen-activated protein kinases (MAPKs) are conserved serine/threonine-specific kinases that are activated by various extracellular stimuli and play crucial regulatory roles in immunity, development and homeostasis. However, the function of p38s in mollusks, the second most diverse group of animals, is still poorly understood. In this study, a novel molluscan p38 (designated Chp38) was cloned and characterized from the Hong Kong oyster Crassostrea hongkongensis. Its full-length cDNA encoded a putative protein of 353 amino acids with a calculated molecular weight of approximately 40...
October 18, 2016: Molecular Immunology
Ruobing Zhang, Gilbert O Fruhwirth, Oana Coban, James E Barrett, Thomas Burgoyne, Sang Hak Lee, Paul Dennis Simonson, Murat Baday, Boris Kholodenko, Clare E Futter, Tony Ng, Paul R Selvin
Heterogeneity of mitogen-activated protein kinase (MAPK) activation in genetically identical cells, which occurs in response to epidermal growth factor receptor (EGFR) signaling, remains poorly understood. MAPK cascades integrate signals emanating from different EGFR spatial locations, including the plasma membrane and endocytic compartment. We previously hypothesized that in EGF-stimulated cells the MAPK phosphorylation (pMAPK) level and activity are largely determined by the spatial organization of the EGFR clusters within the cell...
October 21, 2016: ACS Nano
Rui-Li Zhang, Jun-Ping Yang, Li-Xia Peng, Li-Sheng Zheng, Ping Xie, Meng-Yao Wang, Yun Cao, Zhi-Ling Zhang, Fang-Jian Zhou, Chao-Nan Qian, Yong-Xing Bao
Clear cell renal cell carcinoma (ccRCC) is a common pathological subtype of renal cancer. Although the recent application of molecular-targeted agents has modestly improved the prognosis of ccRCC patients, their outcome is still poor. It is therefore important to characterize the molecular and biological mechanisms responsible for the development of ccRCC. Approximately 25% ccRCC patients involves the loss of RNA-binding protein QKI at 6q26, but the role of QKI in ccRCC is unknown. Here, we found that QKI-5 was frequently downregulated in ccRCC patients and its down-regulation was significantly associated with clinical features including T status, M status, and differentiation grade, and poorer patient prognosis...
October 21, 2016: Cell Cycle
K K Dey, R Bharti, G Dey, I Pal, Y Rajesh, S Chavan, S Das, C K Das, B C Jena, P Halder, J G Ray, I Kulavi, M Mandal
Oral cancer consists of squamous cell carcinoma within the oral cavity or on the lip. The clinical prognosis of this cancer is mostly poor owing to delayed diagnosis and a lack of appropriate early detection biomarkers to identify the disease. In the current study, we investigated the role of the S100A7 calcium-binding protein in oral squamous cell carcinoma as an activator of the p38/MAPK and RAB2A signaling pathway. The aim of the present study was to determine whether S100A7 and RAB2A have a role in tumor progression and to assess their potential as early detection biomarkers for oral cancer...
October 21, 2016: Cancer Gene Therapy
Ying Bai, Yuan Zhang, Jun Hua, Xiangyu Yang, Xiaotian Zhang, Ming Duan, Xinjian Zhu, Wenhui Huang, Jie Chao, Rongbin Zhou, Gang Hu, Honghong Yao
MicroRNA-143 (miR-143) plays a critical role in various cellular processes; however, the role of miR-143 in the maintenance of blood-brain barrier (BBB) integrity remains poorly defined. Silencing miR-143 in a genetic animal model or via an anti-miR-143 lentivirus prevented the BBB damage induced by methamphetamine. miR-143, which targets p53 unregulated modulator of apoptosis (PUMA), increased the permeability of human brain endothelial cells and concomitantly decreased the expression of tight junction proteins (TJPs)...
October 21, 2016: Scientific Reports
Chengxing Zhu, Jiong Yu, Qiaoling Pan, Jinfeng Yang, Guangshu Hao, Yingjie Wang, Lanjuan Li, Hongcui Cao
Human placenta-derived mesenchymal stem cells (hPMSCs) reside in a physiologically low-oxygen microenvironment. Hypoxia influences a variety of stem cell cellular activities, frequently involving hypoxia-inducible factor-2 alpha (HIF-2α). This research showed that hPMSCs cultured in hypoxic conditions (5% O2) exhibited a more naïve morphology and had a higher proliferative capability and higher HIF-2α expression than hPMSCs cultured in normoxic conditions (21% O2). Similar to the hypoxic cultures, hPMSCs over-expressing HIF-2α showed higher proliferative potential and higher expression of CCND1 (CyclinD1), MYC (c-Myc), POU5F1 (Oct4) and the components of the MAPK/ERK pathway...
October 21, 2016: Scientific Reports
Eun Ho Kim, Mi-Sook Kim, Kyung-Hee Lee, Jae-Soo Koh, Won-Gyun Jung, Chang-Bae Kong
To overcome radioresistance in the treatment of osteosarcoma, a primary malignant tumor of the bone, radiotherapy is generally combined with radiosensitizers. The purpose of this study was to investigate a third-generation bisphosphonate, zoledronic acid (ZOL), as a radiosensitizer for osteosarcoma. We found that exposure of KHOS/NP osteosarcoma cells to 20 μM ZOL decreased the γ-radiation dose needed to kill 90% of cells. This radiosensitizing effect of ZOL was mediated through decreased mitochondrial membrane potential, increased levels of reactive oxygen species, increased DNA damage (as assessed by counting γ-H2AX foci), decreased abundance of proteins involved in DNA repair pathways (ATR, Rad52, and DNA-PKcs), and decreased phosphorylation of PI3K-Akt and MAPK pathway proteins (Raf1, MEK1/2, ERK1/2, and Akt), as compared to γ-irradiation alone...
September 27, 2016: Oncotarget
Chae Lim Jung, Hyemin Mun, Se-Young Jo, Ju-Hee Oh, ChuHee Lee, Eun-Kyung Choi, Se Jin Jang, Young-Ah Suh
Mutation of p53 occasionally results in a gain of function, which promotes tumor growth. We asked whether destabilizing the gain-of-function protein would kill tumor cells. Downregulation of the gene reduced cell proliferation in p53-mutant cells, but not in p53-null cells, indicating that the former depended on the mutant protein for survival. Moreover, phenformin and 2-deoxyglucose suppressed cell growth and simultaneously destabilized mutant p53. The AMPK pathway, MAPK pathway, chaperone proteins and ubiquitination all contributed to this process...
October 19, 2016: Oncotarget
Yujie Jiang, Yi Zeng, Xia Huang, Yueqiu Qin, Weigui Luo, Shulin Xiang, Suren R Sooranna, Liao Pinhu
Acute respiratory distress syndrome (ARDS) is characterized by inflammatory injury to the alveolar and capillary barriers that results in impaired gas exchange and severe acute respiratory failure. Nuclear orphan receptor Nur77 has emerged as a regulator of gene expression in inflammation and its role in the pathogenesis of ARDS is not clear. The objective of this study is to investigate the potential role of Nur77 and its underlying mechanism in the regulation of endothelin-1 (ET-1) expression in LPS-induced A549 cells and an ARDS rat model...
October 7, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
N C N Perera, G I Godahewa, Jehee Lee
Mitogen-activated protein kinase (MAPK) is involved in the regulation of cellular events by mediating signal transduction pathways. MAPK1 is a member of the extracellular-signal regulated kinases (ERKs), playing roles in cell proliferation, differentiation, and development. This is mainly in response to growth factors, mitogens, and many environmental stresses. In the current study, we have characterized the structural features of a homolog of MAPK1 from disk abalone (AbMAPK1). Further, we have unraveled its expressional kinetics against different experimental pathogenic infections or related chemical stimulants...
October 17, 2016: Fish & Shellfish Immunology
IbDanelo Cortez, Dmitry V Bulavin, Ping Wu, Erica L McGrath, Kathryn A Cunningham, Maki Wakamiya, John Papaconstantinou, Kelly T Dineley
A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38α(AF/+)) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38α(AF/+)) and kinase activity. As a result, aged DN-p38α(AF/+) mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates...
October 17, 2016: Behavioural Brain Research
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