Engineering Ethics and Self-Organizing Models of Human Development: Opportunities and Challenges

Publication date: Available online 21 September 2017
Source:Cell Stem Cell
Author(s): Insoo Hyun
Incorporating engineering ethics early during the planning stages of organoid and gastruloid research may help prevent future confusion about the moral status of complex models of human development. However, the intrinsic self-organizing behavior of organoids and gastruloids may pose a slight challenge to this novel ethical approach.

Teaser

Incorporating engineering ethics early during the planning stages of organoid and gastruloid research may help prevent future confusion about the moral status of complex models of human development. However, the intrinsic self-organizing behavior of organoids and gastruloids may pose a slight challenge to this novel ethical approach.


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Generation of Mouse and Human Organoid-Forming Intestinal Progenitor Cells by Direct Lineage Reprogramming

Publication date: Available online 21 September 2017
Source:Cell Stem Cell
Author(s): Shizuka Miura, Atsushi Suzuki
Intestinal organoids hold great promise as a valuable tool for studying and treating intestinal diseases. The currently available sources of human intestinal organoids, tissue fragments or pluripotent stem cells, involve invasive procedures or complex differentiation protocols, respectively. Here, we show that a set of four transcription factors, Hnf4α, Foxa3, Gata6, and Cdx2, can directly reprogram mouse fibroblasts to acquire the identity of fetal intestine-derived progenitor cells (FIPCs). These induced FIPCs (iFIPCs) form spherical organoids that develop into adult-type budding organoids containing cells with intestinal stem cell properties. The resulting stem cells produce all intestinal epithelial cell lineages and undergo self-renewing cell divisions. After transplantation, the induced spherical and budding organoids can reconstitute colonic and intestinal epithelia, respectively. The same combination of four defined transcription factors can also induce human iFIPCs. This alternative approach for producing intestinal organoids may well facilitate application for disease analysis and therapy development.

Graphical abstract

Teaser

Miura and Suzuki describe direct conversion of mouse fibroblasts to cells resembling fetal intestine-derived progenitor cells that can give rise to intestinal stem cell organoids and reconstitute injured colonic tissues after transplantation. They also show that a similar approach can work to make human induced intestinal progenitor cells.


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Evolution in sentinel lymph node biopsy in breast cancer

Publication date: Available online 20 September 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Si-Qi Qiu, Guo-Jun Zhang, Liesbeth Jansen, Jakob de Vries, Carolien P. Schröder, Elisabeth G.E. de Vries, Gooitzen M. van Dam
Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node-negative (cN0) breast cancer patients without neoadjuvant chemotherapy (NAC). The application of SLNB in patients receiving NAC has also been explored. Evidence supports its use after NAC in pretreatment cN0 patients. Nonetheless, its routine use in all the pretreatment node-positive patients who become cN0 after NAC is unjustified due to the unacceptably high false-negative rate, which can be improved in a subset of patients. Axillary surgery omission in selected patients with a low risk of ALN metastasis has gained more and more research interest because the SLNs are tumor-free in more than 70% of all patients. To avoid drawbacks of conventional mapping methods, novel techniques for SLN detection have been developed and shown to be highly accurate in patients with early breast cancer. This article reviews the progress in SLNB in patients with breast cancer.



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Premature Atherosclerosis in Premenopausal Women: Does Cytokine Balance Play a Role?

Publication date: Available online 21 September 2017
Source:Medical Hypotheses
Author(s): Jo-Ann Eastwood, Doris A Taylor, B. Delia Johnson, Micheline Resende, Barry L.Sharaf, Bina Ahmed, Margo Minissian, Chrisandra Shufelt, Noel Bairey Merz
Contributory risk factors to premature coronary artery disease (CAD) in premenopausal women are poorly understood and data on this subset of women is lacking. There is growing evidence that the process of inflammation is a part of the atherosclerotic process. Mechanistic insights from animal work suggest that the profile of circulating cytokines reflects both endothelial integrity and the presence of immune and progenitor cells. Significant differences in pro- and anti-inflammatory cytokine concentrations between patients with and without CAD exist. Young women with obstructive CAD may experience differences in pro-inflammatory cytokines and the recruitment of reparative cells that secrete T-Helper (Th2 cytokines compared to women without CAD. Thus, cytokine balance may play a role in obstructive CAD in young women. In this pilot study we set out to identify an array of circulating inflammatory marker profiles which could be useful for the development of risk assessment and preventive strategies. We tested the hypothesis that an increase in serologic Th1 cytokines relative to Th2)/ hematopoietic regulatory (HR) cytokines is related to premature coronary atherosclerosis in premenopausal women.



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With or without you: predictive coding and Bayesian inference in the brain

Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Laurence Aitchison, Máté Lengyel
Two theoretical ideas have emerged recently with the ambition to provide a unifying functional explanation of neural population coding and dynamics: predictive coding and Bayesian inference. Here, we describe the two theories and their combination into a single framework: Bayesian predictive coding. We clarify how the two theories can be distinguished, despite sharing core computational concepts and addressing an overlapping set of empirical phenomena. We argue that predictive coding is an algorithmic/representational motif that can serve several different computational goals of which Bayesian inference is but one. Conversely, while Bayesian inference can utilize predictive coding, it can also be realized by a variety of other representations. We critically evaluate the experimental evidence supporting Bayesian predictive coding and discuss how to test it more directly.



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The diverse actions of astrocytes during synaptic development

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Alexandra P Bosworth, Nicola J Allen
In the developing brain, cortical circuits are established through a complex process of synaptogenesis, maturation, and synaptic pruning. Astrocytes carry out diverse functions during each of these stages to facilitate the formation of complex networks. Recent work has begun to demonstrate that these heterogeneous roles during excitatory synaptic development are determined by the astrocyte population, brain region, and neuron type. This review will focus on current findings which highlight cell type specific mechanisms of excitatory synaptogenesis, as well as multiple mechanisms engaged by astrocytes to facilitate synaptic maturation and pruning.



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Cortical inhibitory interneurons control sensory processing

Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Katherine C Wood, Jennifer M Blackwell, Maria Neimark Geffen
Inhibitory and excitatory neurons form intricate interconnected circuits in the mammalian sensory cortex. Whereas the function of excitatory neurons is largely to integrate and transmit information within and between brain areas, inhibitory neurons are thought to shape the way excitatory neurons integrate information, and they exhibit context-specific and behavior-specific responses. Over the last few years, work across sensory modalities has begun unraveling the function of distinct types of cortical inhibitory neurons in sensory processing, identifying their contribution to controlling stimulus selectivity of excitatory neurons and modulating information processing based on the behavioral state of the subject. Here, we review results from recent studies and discuss the implications for the contribution of inhibition to cortical circuit activity and information processing.



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Scholar : Oncology Reports - Volume:38 Number:4

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TABLE OF CONTENTS October-2017 Volume 38 Issue 4

Age at menopause and hormone replacement therapy as risk factors for head and neck and oesophageal cancer (Review) Caroline E. McCarthy, John K. Field, Michael W. Marcus View Abstract ❯

Long non-coding RNAs on the stage of cervical cancer (Review) Junxue Dong, Manman Su, Weiqin Chang, Kun Zhang, Shuying Wu, Tianmin Xu View Abstract ❯

Acid ceramidase confers radioresistance to glioblastoma cells Ninh B. Doan, Ha S. Nguyen, Mona M. Al-Gizawiy, Wade M. Mueller, Roger A. Sabbadini, Scott D. Rand, Jennifer M. Connelly, Christopher R. Chitambar, Kathleen M. Schmainda, Shama P. Mirza View Abstract ❯

Potential role of ZEB1 as a DNA repair regulator in colorectal cancer cells revealed by cancer-associated promoter profiling Miao Wang, Su-Fei He, Lei-Lei Liu, Xiao-Xia Sun, Fan Yang, Qian Ge, Wei-Kang Wong, Jing-Yan Meng View Abstract ❯

Atelocollagen-mediated in vivo siRNA transfection in ovarian carcinoma is influenced by tumor site, siRNA target and administration route Matthieu Meryet-Figuière, Charlotte Lecerf, Emilie Varin, Jean-Luc Coll, Marie-Hélène Louis, Soizic Dutoit, Florence Giffard, Cécile Blanc-Fournier, Siham Hedir, Nicolas Vigneron, Emilie Brotin, Laurent Pelletier, Véronique Josserand, Christophe Denoyelle, Laurent Poulain View Abstract ❯

Juglone reduces growth and migration of U251 glioblastoma cells and disrupts angiogenesis Jian Wang, Ke Liu, Xiao-Feng Wang, Dian-Jun Sun View Abstract ❯

TRPM7 is overexpressed in bladder cancer and promotes proliferation, migration, invasion and tumor growth Sheng-Lin Gao, Chui-Ze Kong, Zhe Zhang, Ze-Liang Li, Jian-Bin Bi, Xian-Kui Liu View Abstract ❯

miR-187 inhibits the growth of cervical cancer cells by targeting FGF9 Hua Liang, Ruoyu Luo, Xiaoqi Chen, Yuzi Zhao, Aili Tan View Abstract ❯

TP63 mutations are frequent in cutaneous melanoma, support UV etiology, but their role in melanomagenesis is unclear Paola Monti, Paola Ghiorzo, Paola Menichini, Giorgia Foggetti, Paola Queirolo, Alberto Izzotti, Gilberto Fronza View Abstract ❯

Downregulation of microRNA-15a suppresses the proliferation and invasion of renal cell carcinoma via direct targeting of eIF4E Gang Li, Tie Chong, Xiaolong Xiang, Jie Yang, Hongliang Li View Abstract ❯

Tumor-associated macrophages induce the expression of FOXQ1 to promote epithelial-mesenchymal transition and metastasis in gastric cancer cells Jian Guo, Yan Yan, Yu Yan, Qinyue Guo, Mingxin Zhang, Jia Zhang, David Goltzman View Abstract ❯

Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways Yan Li, Wanqi Zhou, Ke Tang, Xiaoguang Chen, Zhiqiang Feng, Jindong Chen View Abstract ❯

Upregulation of GNL3 expression promotes colon cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway Xi Tang, Lang Zha, Hui Li, Gang Liao, Zhen Huang, Xudong Peng, Ziwei Wang View Abstract ❯

IL‑33 enhances glioma cell migration and invasion by upregulation of MMP2 and MMP9 via the ST2-NF-κB pathway Jian-Fei Zhang, Peng Wang, Yu-Jin Yan, Yong Li, Min-Wu Guan, Jin-Jun Yu, Xin-Dong Wang View Abstract ❯

Identification of hub genes, key miRNAs and potential molecular mechanisms of colorectal cancer Shasha Wu, Feixiang Wu, Zheng Jiang View Abstract ❯

MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway Zehang Zhuang, Fengchun Hu, Jing Hu, Cheng Wang, Jinsong Hou, Zhiqiang Yu, Tony T. Wang, Xiqiang Liu, Hongzhang Huang View Abstract ❯

WRAP53β, survivin and p16INK4a expression as potential predictors of radiotherapy/chemoradiotherapy response in T2N0-T3N0 glottic laryngeal cancer Katharina Tiefenböck-Hansson, Aaro Haapaniemi, Lovisa Farnebo, Björn Palmgren, Jussi Tarkkanen, Marianne Farnebo, Eva Munck-Wikland, Antti Mäkitie, Stina Garvin, Karin Roberg View Abstract ❯

FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1 Qiangsheng Hu, Yi Qin, Bo Zhang, Chen Liang, Shunrong Ji, Si Shi, Wenyan Xu, Jinfeng Xiang, Dingkong Liang, Quanxing Ni, Xianjun Yu, Jin Xu View Abstract ❯

MicroRNA-616 promotes the growth and metastasis of non-small cell lung cancer by targeting SOX7 Danping Wang, Qifeng Cao, Meijun Qu, Zhaoqun Xiao, Minghui Zhang, Songbo Di View Abstract ❯

Zhi Zhen Fang formula reverses Hedgehog pathway mediated multidrug resistance in colorectal cancer Hua Sui, Peiwen Duan, Piaoting Guo, Lishuang Hao, Xuan Liu, Jinhua Zhang, Huirong Zhu, Miaomiao Zhao, Hao Wang, Qi Li, Songpo Wang View Abstract ❯

miR-198-induced upregulation of Livin may be associated with the prognosis and contribute to the oncogenesis of lung adenocarcinoma Yicheng Liang, Hetan Wang, Yuanyuan Sun, Sheng Chen, Haoyou Wang, Rong Huang, Xinyi Zhao, Weineng Fu, Chunlu Yang View Abstract ❯

Exogenous lipids promote the growth of breast cancer cells via CD36 Jing Zhao, Zheng Zhi, Chao Wang, Hanying Xing, Guangyao Song, Xian Yu, Yajun Zhu, Xing Wang, Xuemei Zhang, Yan Di View Abstract ❯

Downregulation of BZW2 inhibits osteosarcoma cell growth by inactivating the Akt/mTOR signaling pathway Dong-Dong Cheng, Shi-Jie Li, Bin Zhu, Ting Yuan, Qing-Cheng Yang, Cun-Yi Fan View Abstract ❯

Sanggenon C induces apoptosis of colon cancer cells via inhibition of NO production, iNOS expression and ROS activation of the mitochondrial pathway Li-Dong Chen, Zhi-Hui Liu, Lian-Feng Zhang, Jian-Ning Yao, Chun-Feng Wang View Abstract ❯

Killing effect of methionine enkephalin on melanoma in vivo and in vitro Dong-Mei Wang, Xue Jiao, Nicolas P. Plotnikoff, Noreen Griffin, Rui-Qun Qi, Xing-Hua Gao, Feng-Ping Shan View Abstract ❯

Benzo(a)pyrene enhances the EMT-associated migration of lung adenocarcinoma A549 cells by upregulating Twist1 Xi Chen, Hongbing Peng, Jian Xiao, Anqi Guan, Bin Xie, Bixiu He, Qiong Chen View Abstract ❯

Downregulation of microRNA-196a inhibits human liver cancer cell proliferation and invasion by targeting FOXO1 Liu Yang, Fei Peng, Jian Qin, Henghua Zhou, Bing Wang View Abstract ❯

MicroRNA-195 inhibits growth and invasion of laryngeal carcinoma cells by directly targeting DCUN1D1 Yu Shuang, Chao Li, Xuan Zhou, Yongwang Huang, Lun Zhang View Abstract ❯

Knockdown of RRS1 by lentiviral-mediated RNAi promotes apoptosis and suppresses proliferation of human hepatocellular carcinoma cells Jitao Wang, Zhi Li, Changzeng Zuo, Qingfan Xie, Hui Li, Junhong Jia, Zhongguang Zhen, Ruizhao Qi, Zhiwei Li, Dengxiang Liu, Baijun Sun View Abstract ❯

MicroRNA-144-3p suppresses tumor growth and angiogenesis by targeting SGK3 in hepatocellular carcinoma Manya Wu, Chaoyuan Huang, Xinping Huang, Rong Liang, Yan Feng, Xiaoling Luo View Abstract ❯

Upregulated exosomic miR‑23b‑3p plays regulatory roles in the progression of pancreatic cancer Dayang Chen, Xiongbo Wu, Min Xia, Fang Wu, Junli Ding, Yang Jiao, Qiang Zhan, Fangmei An View Abstract ❯

The mechanism of de novo expression of programmed cell death-ligand 1 in squamous cell carcinoma of the lung Tomoyuki Igarashi, Koji Teramoto, Mitsuaki Ishida, Jun Hanaoka, Yataro Daigo View Abstract ❯

STAT3 inhibition by WP1066 suppresses the growth and invasiveness of bladder cancer cells Yujiro Tsujita, Akio Horiguchi, Shinsuke Tasaki, Makoto Isono, Takako Asano, Keiichi Ito, Tomohiko Asano, Yoshine Mayumi, Toshihiro Kushibiki View Abstract ❯

FGF8 promotes cell proliferation and resistance to EGFR inhibitors via upregulation of EGFR in human hepatocellular carcinoma cells Yuanmin Pei, Xueling Sun, Xiwei Guo, Huashan Yin, Le Wang, Fugu Tian, Hongxi Jing, Xiaobo Liang, Jun Xu, Pengcheng Shi View Abstract ❯

Pseudolaric acid B inhibits neuroglioma cell proliferation through DNA damage response Fengmei Song, Xiaoyan Yu, Haipeng Zhang, Zengyan Wang, Yue Wang, Xiangling Meng, Jinghua Yu View Abstract ❯

Screening and identification of potential biomarkers in triple-negative breast cancer by integrated analysis Jilong Guo, Guohua Gong, Bin Zhang View Abstract ❯

Zinc finger protein 307 functions as a tumor‑suppressor and inhibits cell proliferation by inducing apoptosis in hepatocellular carcinoma Yonghao Liang, Qisheng Li, Keli Chen, Wen Ni, Zetao Zhan, Feng Ye, Yiyi Li, Yuan Fang, Fengjiao Zhang, Longhua Chen, Yi Ding View Abstract ❯

A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect Masahiro Uchibori, Ken-Ichi Aoyama, Yoshihide Ota, Kagemasa Kajiwara, Masafumi Tanaka, Minoru Kimura View Abstract ❯

MicroRNA-212 functions as a tumor-suppressor in human non-small cell lung cancer by targeting SOX4 Tingting Tang, Liting Huan, Shujuan Zhang, Hui Zhou, Lei Gu, Xiaohui Chen, Liang Zhang View Abstract ❯

EVI5 is a novel independent prognostic predictor in hepatocellular carcinoma after radical hepatectomy Jintian Tang, Jianghua Ou, Chunyan Xu, Chao Yi, Feng Xue, Lin Xu, Fenju Lai, Jianjun Tang, Shengping Li, Tiebang Kang, Wei Ding, Boqing Wang View Abstract ❯

Preclinical evaluation of cisplatin-incorporated bio-nanocapsules as chemo-radiotherapy for human hepatocellular carcinoma Seol Hwa Shin, Seok Soon Park, Kyoung Jin Lee, Eun Jin Ju, Jin Park, Eun Jeong Ko, Joohee Jung, Shun'ich Kuroda, Seung-Mo Hong, Jung Jin Hwang, Jung Shin Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi View Abstract ❯

Tetramethylpyrazine suppresses lipid accumulation in macrophages via upregulation of the ATP-binding cassette transporters and downregulation of scavenger receptors Jie Duan, Dong Xiang, Hongli Luo, Guojun Wang, Yun Ye, Chao Yu, Xiuying Li View Abstract ❯

Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer Soichiro Funaki, Yasushi Shintani, Tomohiro Kawamura, Ryu Kanzaki, Masato Minami, Meinoshin Okumura View Abstract ❯

FTO expression is associated with the occurrence of gastric cancer and prognosis Dong Xu, Weiwei Shao, Yasu Jiang, Xi Wang, Ying Liu, Xianchen Liu View Abstract ❯

Scutellaria barbata D. Don inhibits 5-fluorouracil resistance in colorectal cancer by regulating PI3K/AKT pathway Jiumao Lin, Jianyu Feng, Hong Yang, Zhaokun Yan, Qiongyu Li, Lihui Wei, Zijun Lai, Yiyi Jin, Jun Peng View Abstract ❯

ABT-737 potentiates cisplatin-induced apoptosis in human osteosarcoma cells via the mitochondrial apoptotic pathway Fengtian Zhang, Xiaolong Yu, Xuqiang Liu, Tonghua Zhou, Tao Nie, Ming Cheng, Hucheng Liu, Min Dai, Bin Zhang View Abstract ❯

Functional expression, characterization, and application of human S100B Lei Wu, Xuesi Zhou, Zhigang Xiao, Xiujie Gao, Ziquan Liu, Zhiqing Zhang, Kun Wang, Yulin Zhu, Hanlin Ren, Tianhui Wang View Abstract ❯

Smad4 re-expression increases the sensitivity to parthenolide in colorectal cancer Xuemei Li, Huike Yang, Jia Ke, Baoquan Liu, Xiaohong Lv, Xinlei Li, Yafang Zhang View Abstract ❯

EGF-induced urokinase plasminogen activator receptor promotes epithelial to mesenchymal transition in human gastric cancer cells Pingping Wang, Maoyuan Ma, Shanhui Zhang View Abstract ❯

Combined analysis of ChIP-seq and gene microarray datasets identify the E2-mediated genes in ERα-dependent manner in osteosarcoma Kangsong Tian, Wei Qi, Qian Yan, Feng Zhang, Delei Song, Haiyang Zhang, Ming Lv View Abstract ❯

A novel chalcone-based molecule, BDP inhibits MDA‑MB‑231 triple-negative breast cancer cell growth by suppressing Hsp90 function Yong Jin Oh, Young Ho Seo View Abstract ❯

miR-217 targeting DKK1 promotes cancer stem cell properties via activation of the Wnt signaling pathway in hepatocellular carcinoma Chunlin Jiang, Miao Yu, Xiaoyan Xie, Guangliang Huang, Yao Peng, Dong Ren, Manxia Lin, Baoxian Liu, Ming Liu, Wei Wang, Ming Kuang View Abstract ❯

Betulinic acid increases radiosensitization of oral squamous cell carcinoma through inducing Sp1 sumoylation and PTEN expression Dao-Ying Yuan, Zhen Meng, Kai Xu, Qiao-Feng Li, Cheng Chen, Ke-Yi Li, Bin Zhang View Abstract ❯

MACC1 induces autophagy to regulate proliferation, apoptosis, migration and invasion of squamous cell carcinoma Jian Wu, Dawei Zhang, Jun Li, Xin Deng, Guannan Liang, Yang Long, Xuemei He, Tianyang Dai, Delian Ren View Abstract ❯

RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma Wei-Na Zhou, Yi-Fei Du, Jin Bai, Xiao-Meng Song, Yang Zheng, Hua Yuan, Wei Zhang, Zheng-Dong Zhang, Yu-Nong Wu View Abstract ❯

EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab Xiaohong Wang, Runjia Fu, Ying Hu, Hong Du, Shuangxi Li, Ziyu Li, Yiqiang Liu, Qixiang Li, Lianhai Zhang, Jiafu Ji View Abstract ❯

Low co-expression of epidermal growth factor receptor and its chaperone heat shock protein 90 is associated with worse prognosis in primary glioblastoma, IDH-wild-type Elsa Sartori, Rupert Langer, Erik Vassella, Ekkehard Hewer, Philippe Schucht, Inti Zlobec, Sabina Berezowska View Abstract ❯

miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast cancer Shihua Chu, Geng Liu, Peixuan Xia, Guoqing Chen, Feng Shi, Tao Yi, Hongying Zhou View Abstract ❯

Long non-coding RNA MEG3 inhibits cell growth of gliomas by targeting miR-93 and inactivating PI3K/AKT pathway Ling Zhang, Xin Liang, Yuxiong Li View Abstract ❯

Attenuation of MUC4 potentiates the anticancer activity of auranofin via regulation of the Her2/Akt/FOXO3 pathway in ovarian cancer cells Jun Sang Bae, Jongsung Lee, Yoonkook Park, Kyungmoon Park, Jung Ryul Kim, Dong Hyu Cho, Kyu Yun Jang, See-Hyoung Park View Abstract ❯

B7-H3 is related to tumor progression in ovarian cancer Jingjing Zhang, Lu Liu, Sai Han, Yi Li, Qiuhong Qian, Qianqian Zhang, Hui Zhang, Ziyan Yang, Youzhong Zhang View Abstract ❯

MicroRNA-1297 contributes to tumor growth of human breast cancer by targeting PTEN/PI3K/AKT signaling Chao Liu, Zhikui Liu, Xiao Li, Xiaojiang Tang, Jianjun He, Shaoying Lu View Abstract ❯

HSP47 is associated with the prognosis of laryngeal squamous cell carcinoma by inhibiting cell viability and invasion and promoting apoptosis Xiaoxiao Song, Zhisu Liao, Chunchun Zhou, Renyu Lin, Jianglong Lu, Lin Cai, Xiaohua Tan, Wenjian Zeng, Xianghe Lu, Weiming Zheng, Jianfu Chen, Zhipeng Su View Abstract ❯

Comprehensive analysis of aberrantly expressed microRNA profiles reveals potential biomarkers of human lung adenocarcinoma progression Jing Sui, Ru-Song Yang, Si-Yi Xu, Yan-Qiu Zhang, Cheng-Yun Li, Sheng Yang, Li-Hong Yin, Yue-Pu Pu, Ge-Yu Liang View Abstract ❯

Corilagin sensitizes epithelial ovarian cancer to chemotherapy by inhibiting Snail‑glycolysis pathways Luoqi Jia, Jiayi Zhou, Hongbo Zhao, Hongyan Jin, Minzhi Lv, Naiqing Zhao, Zhizhong Zheng, Yiling Lu, Yanlin Ming, Yinhua Yu View Abstract ❯

Knockdown of c‑Myc activates Fas-mediated apoptosis and sensitizes A549 cells to radiation Jing Zhang, Ling Zhou, Zhaodi Nan, Qing Yuan, Jie Wen, Maolei Xu, Youjie Li, Baosheng Li, Pingyu Wang, Changmin Liu, Ying Ma, Shaoshui Chen, Shuyang Xie View Abstract ❯

Knockdown of tripartite motif-59 inhibits the malignant processes in human colorectal cancer cells Wei Wu, Jingdi Chen, Jicheng Wu, Jun Lin, Sheng Yang, Honggang Yu View Abstract ❯

Chaetocin induces cell cycle arrest and apoptosis by regulating the ROS-mediated ASK-1/JNK signaling pathways Jingliang He, Xiaoxun Chen, Bowei Li, Wenjie Zhou, Jinfeng Xiao, Ke He, Jinqian Zhang, Guoan Xiang View Abstract ❯

c‑Myc promotes cholangiocarcinoma cells to overcome contact inhibition via the mTOR pathway Guosong Luo, Bin Li, Chunyan Duan, Ying Cheng, Bin Xiao, Fuli Yao, Mei Wei, Qinghua Tao, Chunhong Feng, Xianming Xia, Hong Zhou, Xiaofang Zhao, Rongyang Dai View Abstract ❯

Aspirin inhibits the proliferation of human uterine leiomyoma cells by downregulation of K‑Ras‑p110α interaction Min Gao, Kai-Min Guo, Ying-Mei Wei, Ming-Ming Ma, Jia-Rong Cai, Ting-Ting Xia, Qing-Jian Ye View Abstract ❯

Daidzein inhibits choriocarcinoma proliferation by arresting cell cycle at G1 phase through suppressing ERK pathway in vitro and in vivo Wei Zheng, Rong Sun, Lei Yang, Xianling Zeng, Yan Xue, Ruifang An View Abstract ❯

Pomolic acid induces apoptosis and inhibits multidrug resistance protein MRP1 and migration in glioblastoma cells Lívia Paes Tavares Pacheco Guimarães, Gleice da Graça Rocha, Rafaela Muniz Queiroz, Carollina Araujo Martins, Christina Maeda Takiya, Cerli Rocha Gattass View Abstract ❯

Complex analysis of the TP53 tumor suppressor in mantle cell and diffuse large B-cell lymphomas Lenka Zlamalikova, Mojmir Moulis, Barbora Ravcukova, Kvetoslava Liskova, Jitka Malcikova, David Salek, Jiri Jarkovsky, Miluse Svitakova, Renata Hrabalkova, Jan Smarda, Jana Smardova View Abstract ❯

A decrease in ubiquitination and resulting prolonged life-span of KIT underlies the KIT overexpression-mediated imatinib resistance of KIT mutation-driven canine mast cell tumor cells Masato Kobayashi, Shiori Kuroki, Sena Kurita, Ryo Miyamoto, Hiroyuki Tani, Kyoichi Tamura, Makoto Bonkobara View Abstract ❯

Wild-type p53 controls the level of fibronectin expression in breast cancer cells Daeun You, Seung Pil Jung, Yisun Jeong, Soo Youn Bae, Sangmin Kim View Abstract ❯

Cepharanthine hydrochloride reverses P‑glycoprotein-mediated multidrug resistance in human ovarian carcinoma A2780/Taxol cells by inhibiting the PI3K/Akt signaling pathway Chen-Zheng Huang, Ya-Feng Wang, Yan Zhang, You-Mei Peng, Yi-Xian Liu, Fang Ma, Jin-Hua Jiang, Qing-Duan Wang View Abstract ❯

Inhibition of the growth of hepatocellular carcinoma cells through fibroblast growth factor 18 suppressed by miR-139 Li Yang, Dian Yin, Yilang Wang , Lili Cao View Abstract ❯

Inhibition of NOB1 by microRNA-330-5p overexpression represses cell growth of non-small cell lung cancer Ranran Kong, Wei Liu, Yurui Guo, Jie Feng, Chuantao Cheng, Xinwu Zhang, Yuefeng Ma, Shaomin Li, Jiantao Jiang, Jin Zhang, Zhe Qiao, Jie Qin, Teng Lu, Xijing He View Abstract ❯

5-7 October, 2017, Metropolitan Hotel, Athens, Greece 22nd World Congress on Advances in Oncology & 20th International Symposium on Molecular Medicine 3-4 October 2017, Pre-Congress Workshop: 'Next-Generation Sequencing – Library construction and quality control'

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JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia

Abstract

Oncologic patients subjected to chemotherapy frequently present aphagia, malnutrition, and cachexia. The purpose of this study was to investigate whether selected growth hormone secretagogues including hexarelin, JMV2894 and JMV2951 could antagonize body weight loss and wasting induced by cisplatin administration in rats. The three growth hormone secretagogues behaved as full agonists of the growth hormone secretagogues receptor both in terms of ability to stimulate calcium mobilization in Chinese hamster ovary cells and stimulation of growth hormone release in neonatal rats. Adult rats were (i) treated with vehicle throughout (controls), or (ii) treated with cisplatin (days 1–3) and a growth hormone secretagogues or vehicle, (days 1–12). Body weight and food consumption were measured daily. Although all growth hormone secretagogues caused initial transient acute increases in food intake, the total amount of food eaten by controls and growth hormone secretagogues treated groups over the 12 experimental days was not significantly different. All groups pre-treated with cisplatin lost up to 5–10 % body weight in the first 4 days; they subsequently gained weight at a rate comparable with controls. Interestingly, rats which received JMV2894 demonstrated a faster gain in body weight than any other growth hormone secretagogues treated group and at the end of the protocol reached a weight similar to that of controls. JMV2894 did not stimulate perirenal and epididymal fat accumulation but reduced MuRF mRNA levels in skeletal muscles. In conclusion, our findings demonstrate that JMV2894 antagonizes cisplatin induced weight loss in rats and may prove useful in antagonizing cachexia associated with cancer and chemotherapy in humans.

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Is the hypothalamic–pituitary–adrenal axis disrupted in type 2 diabetes mellitus and is this relevant for bone health?

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Full title with Editorial board members

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336





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A motorized pellet dispenser to deliver high intensity training of the single pellet reaching and grasping task in rats

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Abel Torres-Espín, Juan Forero, Emma K.A. Schmidt, Karim Fouad, Keith K. Fenrich
The single pellet reaching and grasping (SPG) task is widely used to study forelimb motor performance in rodents and to provide rehabilitation after neurological disorders. Nonetheless, the time necessary to train animals precludes its use in settings where high-intensity training is required. In the current study, we developed a novel high-intensity training protocol for the SPG task based on a motorized pellet dispenser and a dual-window enclosure. We tested the protocol in naive adult rats and found 1) an increase in the intensity of training without increasing the task time and without affecting the overall performance of the animals, 2) a reduction in the variability within and between experiments in comparison to manual SPG training, and 3) a reduction in the time required to conduct experiments. In summary, we developed and tested a novel protocol for SPG training that provides higher-intensity training while reducing the variability of results observed with other protocols.



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The delta opioid receptor agonist KNT-127 in the prelimbic medial prefrontal cortex attenuates veratrine-induced anxiety-like behaviors in mice

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Akiyoshi Saitoh, Satoshi Suzuki, Akinobu Soda, Masanori Ohashi, Misa Yamada, Jun-Ichiro Oka, Hiroshi Nagase, Mitsuhiko Yamada
We previously reported that systemic administration of the selective delta opioid receptor (DOP) agonist KNT-127 produces potent anxiolytic-like effects in rats. Although a higher distribution pattern of DOPs was reported in the prelimbic medial prefrontal cortex (PL-PFC) of rodents, the role of DOPs in PL-PFC and in anxiolytic-like effects have not been well examined. Recently, we demonstrated that activation of PL-PFC with the sodium channel activator veratrine increases glutamatergic neurotransmission and produces anxiety-like behaviors in mice. Therefore, we investigated the effects of co-perfusion with KNT-127 in PL-PFC on veratrine-induced anxiety-like behaviors in mice. We also simultaneously measured extracellular glutamate and GABA levels. In addition, we assessed the effect of KNT-127 on the expression of c-Fos in sub-regions of the amygdala.Extracellular glutamate levels were measured in seven-week-old male C57BL/6N mice using an in vivo microdialysis-HPLC/ECD system, and behaviors were assessed simultaneously in an open field test. Basal levels of glutamate were measured by collecting samples every 10min for 60min. The drug-containing medium was perfused for 30min, and the open field test was performed during the last 10min of drug perfusion. After drug treatments, the perfusion was switched from drug-containing medium to control medium without drugs and samples were collected for another 90min.KNT-127 co-perfusion completely diminished veratrine-induced anxiety-like behaviors and attenuated the veratrine-induced increase in extracellular glutamate levels in PL-PFC. Interestingly, KNT-127 perfusion alone in PL-PFC did not affect anxiety-like behaviors. Local perfusion of veratrine in PL-PFC induced c-Fos immunoreactivity in sub-regions of amygdala. Co-perfusion of KNT-127 diminished c-Fos expression.Here we demonstrate that the DOP agonist KNT-127 in PL-PFC attenuates veratrine-induced anxiety-like behaviors in mice. These effects may be caused by the presynaptic suppression of activated glutamatergic transmission in PL-PFC, which projects to sub-regions of the amygdala. We propose that compounds like KNT-127, which inhibit glutamatergic transmission in PL-PFC, are candidates for novel anxiolytics.



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Sex and the housing: Effects on behavior, cortisol levels and weight in zebrafish

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Gustavo Kellermann Reolon, Gabriela Madalena de Melo, João Gabriel dos Santos da Rosa, Leonardo José Gil Barcellos, Carla Denise Bonan
Studies with zebrafish use acclimatizing periods of at least one week immediately before the experiments. During this time, animals can be housed in sexually segregated conditions (only females or males in the tank) or in mixed-sex conditions (both sexes in the tank). The influence of sex and housing conditions regarding the presence of one or two sexes is largely unknown in zebrafish. Our aim was to evaluate the influence that sex and housing regarding the sex of animals had in the open tank task, in the inhibitory avoidance memory test, in cortisol levels and weight in zebrafish. Four groups of animals were used: 1) segregated housed females (only females were kept in the tank); 2) segregated housed males (only males were kept in the tank); 3) mixed-sex housed females (only females were analyzed from a tank containing 50% ratio of each sex); 4) mixed-sex housed males (only males were analyzed from a tank containing 50% ratio of each sex). Males showed higher total distance travelled and mean speed when compared to females. In the inhibitory avoidance memory, sexually segregated animals had higher latencies than their mixed-sex counterparts in the 1day test and sexually segregated females presented a memory that persisted longer and was able to be reinstated. Whole-body cortisol levels were higher in mixed-sex animals while weight was lower in these fish. To the best of our knowledge, this is the first time that effects of sex and housing regarding sex were investigated in behavior and physiology of zebrafish.



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Differential effects of relaxin-3 and a selective relaxin-3 receptor agonist on food and water intake and hypothalamic neuronal activity in rats

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Camila de Ávila, Sandrine Chometton, Christophe Lenglos, Juliane Calvez, Andrew L. Gundlach, Elena Timofeeva
The neuropeptide relaxin-3 (RLN3) binds with high affinity to its cognate receptor, relaxin-family peptide receptor 3 (RXFP3), and with lower affinity to RXFP1, the cognate receptor for relaxin. Intracerebroventricular (icv) administration of RLN3 in rats strongly increases food and water intake and alters the activity of the hypothalamic-pituitary-adrenal (HPA) and gonadal (HPG) axes, but the relative involvement of RXFP3 and RXFP1 in these effects is not known. Therefore, the effects of icv administration of equimolar (1.1 nmol) amounts of RLN3 and the RXFP3-selective agonist RXFP3-A2 on food and water intake, plasma levels of corticosterone, testosterone, and oxytocin and c-fos mRNA expression in key hypothalamic regions in male rats were compared. Food intake was increased by both RLN3 and RXFP3-A2, but the orexigenic effects of RXFP3-A2 were significantly stronger than RLN3, 30 and 60min after injection. Water intake and plasma corticosterone and testosterone levels were significantly increased by RLN3, but not by RXFP3-A2. Conversely, RXFP3-A2 but not RLN3 decreased oxytocin plasma levels. RLN3, but not RXFP3-A2, increased c-fos mRNA levels in the parvocellular (PVNp) and magnocellular (PVNm) paraventricular and supraoptic (SON) hypothalamic nuclei, in the ventral medial preoptic area (MPAv), and in the organum vasculosum of the lamina terminalis (OVLT). A significant increase in c-fos mRNA expression was induced in the perifornical lateral hypothalamic area (LHApf) by RLN3 and RXFP3-A2. These results suggest that RXFP1 is involved in the RLN3 stimulation of water intake and activation of the HPA and HPG axes. The reduced food intake stimulation by RLN3 compared to RXFP3-A2 may relate to activation of both orexigenic and anorexigenic circuits by RLN3.

Graphical abstract

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Reduction in open field activity in the absence of memory deficits in the AppNL−G−F knock-in mouse model of Alzheimer’s disease

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Lauren S. Whyte, Kim M. Hemsley, Adeline A. Lau, Sofia Hassiotis, Takashi Saito, Takaomi C. Saido, John J. Hopwood, Timothy J. Sargeant
The recent development of knock-in mouse models of Alzheimer's disease provides distinct advantages over traditional transgenic mouse models that rely on over-expression of amyloid precursor protein. Two such knock-in models that have recently been widely adopted by Alzheimer's researchers are the App^NL−F and App^NL−G−F mice. This study aimed to further characterise the behavioural phenotype and amyloid plaque distribution of App^{NL−G−F/NL−G−F} (C57BL/6J background) mice at six-months of age. An attempt to replicate a previous study that observed deficits in working memory in the Y-maze, showed no difference between App^{NL−G−F/NL−G−F} and wild-type mice. Further assessment of these mice using the novel object recognition test and Morris water maze also revealed no differences between App^{NL−G−F/NL−G−F} and wild-type mice. Despite a lack of demonstrated cognitive deficits, we report a reduction in locomotor/exploratory activity in an open field. Histological examination of App^{NL−G−F/NL−G−F} mice showed widespread distribution of amyloid plaques at this age. We conclude that whilst at six-months of age, memory deficits are not sufficiently robust to be replicated in varying environments, amyloid plaque burden is significant in App^{NL−G−F/NL−G−F} knock-in brain.



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Dopamine D1 receptor activation maintains motor coordination in injured rats but does not accelerate the recovery of the motor coordination deficit

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Alberto Avila-Luna, Arturo Gálvez-Rosas, Alfonso Alfaro-Rodríguez, Celia Reyes-Legorreta, Paloma Garza-Montaño, Rigoberto González-Piña, Antonio Bueno-Nava
The sensorimotor cortex and the striatum are interconnected by the corticostriatal pathway, suggesting that cortical injury alters the striatal function that is associated with skilled movements and motor learning, which are functions that may be modulated by dopamine (DA). In this study, we explored motor coordination and balance in order to investigate whether the activation of D1 receptors (D1Rs) modulates functional recovery after cortical injury. The results of the beam-walking test showed motor deficit in the injured group at 24, 48 and 96h post-injury, and the recovery time was observed at 192h after cortical injury. In the sham and injured rats, systemic administration of the D1R antagonist SCH-23390 (1mg/kg) alone at 24, 48, 96 and 192h significantly (P<0.01) increased the motor deficit, while administration of the D1R agonist SKF-38393 alone (2, 3 and 4mg/kg) at 24, 48, 96 and 192h post-injury did not produce a significant difference; however, the co-administration of SKF-38393 and SCH-23390 prevented the antagonist-induced increase in the motor deficit. The cortical+striatal injury showed significantly increased the motor deficit at 24, 48, 96 and 192h post-injury (P<0.01) but did not show recovery at 192h. In conclusion, the administration of the D1R agonist did not accelerate the motor recovery, but the activation of D1Rs maintained motor coordination, confirming that an intact striatum may be necessary for achieving recovery.



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A role for nucleus accumbens glutamate in the expression but not the induction of behavioural sensitization to ethanol

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Christina N. Nona, José N. Nobrega
Mechanisms underlying differential sensitivity to behavioural sensitization to ethanol (EtOH) remain poorly understood, although accumulating evidence suggests a role for glutamatergic processes in the ventral striatum. Efforts to address this issue can benefit from the well-documented fact that in any given cohort, some of the mice (High sensitized; HS) show robust sensitization, while others (Low sensitized; LS) show little, if any, sensitization. Here, we examined whether this variability might be differentially associated with nucleus accumbens (NAc) glutamate processes. Male DBA mice received 5 EtOH (2.2g/kg) or saline injections twice a week and were challenged with EtOH (1.8g/kg) 2 weeks after injection 5. When an EtOH challenge was administered 2 weeks following the induction of sensitization, HS, but not LS, mice showed a robust increase in glutamate levels (67%, P<0.01) as measured by in vivo microdialysis. In a separate cohort, the mGlu2/3 agonist LY354740 (10mg/kg), given prior to the EtOH challenge, abolished the expression of sensitization. To ascertain whether enhanced release could also be observed during the induction of sensitization, glutamate levels were measured after the 1st and 5th EtOH injection and were found to be unchanged in HS mice, although briefly elevated in LS mice at injection 5. To further assess possible glutamate involvement during the induction of sensitization, sensitizing EtOH injections were co-administered with NMDAR antagonists. At the doses used, MK-801 (0.25mg/kg) and CGS 19755 (10mg/kg) blocked the expression of sensitization, but did not significantly interfere with the development of EtOH sensitization. Within the limitations of the present design, the results suggest an important role for EtOH-induced glutamate release in the NAc when sensitization is well established, but not necessarily during the development of sensitization.



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Different effects of running wheel exercise and skilled reaching training on corticofugal tract plasticity in hypertensive rats with cortical infarctions

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): ChanJuan Zhang, Yan Zou, Kui Li, Chao Li, YingPing Jiang, Ju Sun, Ruifang Sun, HongMei Wen
The approaches that facilitate white matter plasticity may prompt functional recovery after a stroke. The effects of different exercise methods on motor recovery in stroke rats have been investigated. However, it is not clear whether their effects on axonal plasticity different. The aim of this study was to compare the effects of the forced running wheel exercise (RWE) and skilled reaching training (SRT) on axonal plasticity and motor recovery. Cortical infarctions were generated in stroke-prone renovascular hypertensive rats. The rats were randomly divided into the following three groups: the control (Con) group, the RWE group, and the SRT group. A sham group was also included. The mNSS and forelimb grip strength tests were performed on days 3, 7, 14, 21, 28, 35, and 42 after ischemia. The anterograde tract tracer biotinylated dextran amine (BDA) was injected into the rats to trace the axonal plasticity of the contralesional corticofugal tracts. Compared with the Con group, the mNSS scores in the SRT and RWE groups decreased on day 28 (P<0.05) and on days 35 and 42 (P<0.01). The grip strength in the SRT group increased relative to that in the RWE group at 42day post-ischemia (P<0.01). Both the RWE and SRT groups exhibited enhanced plasticity of the contralesional corticofugal tract axons at the level of the red nucleus (P<0.01) and the cervical enlargement (P<0.01). More contralateral corticorubral tract remodeling was observed at the red nucleus level in the SRT group than in the RWE group (P<0.001). Taken together, these results suggest that SRT may enhance axon plasticity in the corticorubral tract more effectively than the forced RWE and is associated with better motor recovery after cerebral ischemia.



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Enhanced expression of heme oxygenase-1 in the locus coeruleus can be associated with anxiolytic-like effects

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Rafael Alves Cazuza, Olga Pol, Christie Ramos Andrade Leite-Panissi
Some researchers have shown that carbon monoxide (CO) plays a role in emotional behavior modulation through intracellular 3′-5′-guanosine monophosphate mechanisms in the locus coeruleus (LC). In fact, the LC region has a high expression of the heme-oxygenase (HO) enzymes, which are responsible for the production of CO. However, the physiological mechanism by which the HO-CO pathway participates in the modulation of emotional responses in the LC still needs clarification. This study evaluates whether a systemic intraperitoneal treatment is able to alter behavioral responses (in the elevated plus-maze and the light-dark box test) and the expression of the HO-1 and HO-2 enzymes in the LC. The tested treatments are acute (3h before) or chronic (twice daily for 10days) and with a carbon monoxide releaser (tricarbonyldichlororuthenium [II] dimer, or CORM-2) or with a HO-1 inducer compound (cobalt protoporphyrin IX, CoPP). The results for the elevated plus-maze show that CO–for both acute or chronic administration of either drug–ncreased the number of entries into the open arms and the percentage of time spent in the open arms. Regarding the light-dark box test, chronic treatment with either drug increased the time spent in the light compartment. Additionally, treatment with CORM-2 or CoPP, either acutely or chronically, increased HO-1 enzyme expression in the LC cells. This study shows that systemic CO treatment can promote an anxiolytic-like effect and the expression of HO-1 enzymes in LC cells.



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