癌细胞疯了吗? 有点标题党的味道,这里讨论的话题为: 失去神经联络是细胞癌变的标志性起点? ——lost of connection with nerve system could be the initial step of tumorigenesis? 神经在组织发生、发育,体液调节,免疫调节以及细胞代谢、增殖、分化、凋亡、应激反应和癌变中具有重要意义;个人认为癌起源于无家可归的正常体细胞,细胞失去神经系统联络是癌变的起点。无家可归的细胞命运出现了不确定性,在恶劣微环境中被反复重编程(niche reprogramming)唯一的幸存者最终返回到单细胞生存状态,获得了永生(癌变): 1. 癌是多细胞动物的专属特征 ◆单细胞动物本身具有永生性(癌性),细胞只有应激反应而没有神经反射,不需要发神经; ◆多数植物一般是自养或腐生生物,不进行神经支配的捕食和拒捕行为(含羞草、捕食植物等例外),另一方面,植物细胞具有发育全能性但被细胞壁牢牢锚定没有机会迁移,因此,多数植物肿瘤表现为组织异常增生,类似于动物体内没有迁移能力的良性肿瘤; ◆多细胞动物均有组织分化,组织服从神经系统的统一调配,分化的细胞丧失了永生性,组织中成体细胞夺回永生权利就是癌变(Carcinogenesis) 2. 神经系统是多细胞动物机体的最高统帅 ◆多细胞动物的捕食和拒捕行为依赖于神经系统调动机体组织的快速响应,没有神经就无需组织,也就就没有多细胞动物; ◆神经发生是多细胞动物个体生命的起点,神经失功能(如脑死亡)是多细胞动物个体生命的终点,神经调节伴随多细胞动物的一生; ◆神经发生是多细胞动物组织发生的伴随条件,神经系统参与个体形态发生、发育、衰退全过程; ◆神经系统可参与内分泌或体液调节,有些内分泌腺本身直接或间接地受到神经系统的调节,在这种情况下,体液调节是神经调节的一个传出环节,是反射传出道路的延伸。很多类型的体液调节,是通过神经影响激素分泌,再由激素对机体功能实行调节的方式。 ◆一些内分泌细胞可以直接感受内环境中某种理化因素的变化,直接作出相应的反应,细胞的“自身调节-体液调节-神经调节”是细胞群分形的基础; ◆神经系统与免疫系统间存在复杂的交流网络,压力信号会降低免疫系统抗体的效力,除调节免疫系统外,神经调控还对非神经活动,细胞寿命、脂肪储存都具有调控作用。 3. 失去神经联络是成体细胞是癌变的第一步 ◆神经调节的一般特点是比较迅速而精确,自身调节和体液调节的一般特点是比较缓慢、持久而弥散;越是精密的系统越是脆弱,精准和迅速信号系统在恶劣微环境中更容易率先发生障碍; ◆受精卵到神经发生之前胚胎组织具有致瘤性,神经形成后组织丧失致瘤性;胚胎神经发生是决定胚胎组织细胞致瘤性的节点; ◆丧失神经控制的组织缺乏神经营养因子( neurotrophin )引起失功能和萎缩,失去神经联系的细胞将无家可归; ◆神经系统一旦形成终生不再更新,神经损伤修复易于出错,造成一些体细胞“去组织化(disorganization)”; ◆体外培养(in vitro,去组织化)的细胞缺乏神经联系,易于形成细胞系(永生化); ◆机体除了神经调节和体液调节的方式外,许多组织细胞自身也能对周围环境变化发生适应性的反应,这种反应是组织细胞本身的生理特性,并不依靠于外来神经或体液因素的作用,称之为自身调节;细胞失去神经调节“去组织化”的细胞自身调节得以强化。 ◆去组织化的部位出现的某些神经修复因子参与了细胞癌变活动; 推论:癌的发生可能与神经发育和衰退同步 肿瘤的发生与年龄密切相关,神经发育不全或神经功能衰退也与年龄密切相关 。0~5岁儿童神经发育尚不健全,45岁以后神经功能逐渐衰退。神经发育不全或神经功能衰退从某种意义上可以理解为“去组织化”,由于神经的损伤、衰退、炎症等因素造成局部组织与系统失去神经信号联络,这部分组织中的细胞将面临怎样的命运:凋亡、坏死、纤维化? 有没有一种可能是细胞走上了一条探索自主生存的道路?因此失去神经联络有可能是细胞癌变的起点。失去神经联络包含两层意思:其一,神经传导通路发生障碍,信号无法正确送达相关细胞;其二、细胞对神经信号接收异常,无法正确执行神经命令; 肿瘤的发病率见于各年龄段,但集中表现在高、低两个年龄段,以高龄者发病率为最高,恶性肿瘤为一中老年人高发的疾病。发病率在45岁以后快速增长,在75岁以后,发病率增长趋缓并有所下降。 这种现象与各个体发育过程中的神经功能不全及神经功能衰退从统计学上十分可能会相关 。 有趣的是高龄老人肿瘤发病率反而下降,恐怕是能活到那个年龄的耄耋差不多已经修成了正果,他们大多睿智、心态平和、懂得生活,神智健全。 任何事物发生都有一个起点,生儿育女从交配开始,但交配不一定生儿育女;跑步从学爬行开始,但会爬不一定就能跑;打仗从当新兵开始,当兵也不一定就打仗;同理,细胞失去神经联系不一定发生癌变,这个话题的目的是努力寻找正常细胞进入癌变漫漫征程的标志性起点; reference: 1. Pro-nerve Growth Factor Induces Autocrine Stimulation of Breast Cancer Cell Invasion through Tropomyosin-related Kinase A (TrkA) and Sortilin Protein J. Biol. Chem. 2012 287 : 1923 - 1931 . First Published on November 29, 2011 , 2. Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways. Molecular Cancer 2010, 9:157 doi:10.1186/1476-4598-9-157 3. Effects of recombinant human nerve growth factor on cervical cancer.African Journal of Biotechnology Vol. 10(38), pp. 7503-7509, 25 July, 2011
Oct 30 2010 View This On A Web Page. The only SCI-indexed journal in neuroscience published in China Neural Regeneration Research Table of Contents 1. Aim and Scopes 2. Editorial Board 3. Current Issue 4. Why Publish in NRR? 1. Aim and Scopes To publish novel studies addressing inhibition, promotion, or intervention of neuronal/nerve tissue rgeneration and related mechanisms, as well as functional changes and correlation with diseases. FULL ARTICLE Hot topics Translational medicine in the field of neural regeneration manuscripts focused on randomized, controlled trials with multidensional results. Evidence-based medicine in the field of neural regeneration case reports with specific significance, including pathology, imaging, small-sample sizes, and randomized, controlled case reports.. Submit your manuscript to nrr@nrronline.org . Online Submission 2. Editorial Board A total of 266 international editorial board members with academic authority from 38 countries, as well as 171 Chinese peer reviewers from mainland China, Hong Kong, Macao, and Taiwan, participate in the review process. Under the guidance of these experts, we guarantee the peer-review process to be objective, fair, timely, and normative. APPLICATION FORM 3. Current Issue Volume 5 Number 18, September 2010 Research and Reports Neurodegenerative diseases and Neuroregeneration High-frequency magnetic stimulation attenuates beta-amyloid protein 1-42 neurotoxicity in organotypic hippocampal slices Don-Kyu Kim, Young Chul Yoon, Soo Ahn Chae, Kyung Mook Seo, Tai Ryoon Han, Si-Hyun Kang Regeneration Research, 2010;5(18): 1365 | Abstract | Submission | Synaptic plasticity effects on FeCl2-induced post-traumatic epilepsy onset in the rat Yuanxiang Lin, Feng Wang, Ruxiang Xu, Xiaodan Jiang, Dezhi Kang, Yiquan Ke, Mouxuan Du, Lishuang Xu Regeneration Research, 2010;5(18): 1373 | Abstract | Submission | 2-aminoethoxydiphenyl borate or lanthanum potentiates transient receptor potential-like channels in rat CA1 hippocampal neurons Fengpeng Sun, Tian-ming Gao Regeneration Research, 2010;5(18): 1378 | Abstract | Submission | Effects of human mesenchymal stem cell transplantation in the bilateral corpus striatum in a rat model of Tourette's syndrome Xiumei Liu, Yuwei Wang, Mingji Yi Regeneration Research, 2010;5(17): 1285 | Abstract | Submission | Platelet-rich plasma-induced bone marrow mesenchymal stem cells versus autologous nerve grafting for sciatic nerve repair Changsuo Xia, Yajuan Li, Wen Cao, Zhaohua Yu Regeneration Research, 2010;5(17): 1291 | Abstract | Submission | Traditional Chinese Medicine and Neuroregeneration Berberine inhibits inflammatory activation of rat brain microglia Kyong Nyon Nam, Jae-Hong Kim, Hoon-Ji Jung, Jung-Mi Park, Sang-Kwan Moon, Young-Suk Kim, Sun Yeou Kim, Eunjoo H. Lee Regeneration Research, 2010;5(18): 1384 | Abstract | Submission | Antioxidative effects of berberine pre-treatment on hydrogen peroxide-induced PC12 cell toxicity Daohua Xu, Chenhui Zhou Regeneration Research, 2010;5(18): 1391 | Abstract | Submission | Xiaoyaosan-containing serum inhibits corticosterone-induced apoptosis in PC12 cells by downregulating i overload Lin Li, Xuanhong Zhang, Tingting Yan, Qian Li, Shukao Liu, Lili Wu, Can Yan, Hongmei Tan Regeneration Research, 2010;5(18): 1396 | Abstract | Submission | Picroside II down-regulates matrix metalloproteinase-9 expression following cerebral ischemia/reperfusion injury in rats Xiang Li, Xinying Xu, Zhen Li, Yunliang Guo, Qin Li, Xiaodan Li, Zhen Zhou Regeneration Research, 2010;5(18): 1403 | Abstract | Submission | Electroacupuncture-attenuated ischemic brain injury increases insulin-like growth factor-1 expression in a rat model of focal cerebral ischemia Huanmin Gao, Ling Wang, Yunliang Guo Regeneration Research, 2010;5(18): 1408 | Abstract | Submission Techniques and Methods Reception of infrasound and audio current in derma nerves Jianwen Li, Ziyu Li, Xuezong Ma Regeneration Research, 2010;5(18): 1413 | Abstract | Submission | Muscarinic receptor-mediated calcium changes in a rat model of facial nerve nucleus injury Dawei Sun, Huamin Liu, Fugao Zhu, Yanqing Wang, Junfeng Wen, Rui Zhou, Yanjun Wang, Banghua Liu Regeneration Research, 2010;5(18): 1418| | Abstract | Submission | Special Topics and Review Alpha-synuclein gene structure, evolution, and protein aggregation Lili Xiong, Peng Zhao, Zhiyun Guo, Jianhua Zhang, Diqiang Li, Canquan Mao Regeneration Research, 2010;5(18): 1423 | Abstract | Submission | Role of DYT1 gene in early-onset primary torsion dystonia Xiaohui Hu, Xueping Chen, Rui Huang, Huifang Shang Regeneration Research, 2010;5(18): 1429 | Abstract | Submission | Investigation and Analysis Interaction between semantic and phonological processes in stuttering: evidence from the dual-task paradigm Luping Song, Danling Peng, Ning Ning Regeneration Research, 2010;5(18): 1435 | Abstract | Submission | Evaluation of non-typical diffuse axonal injury by magnetic resonance techniques Haijian Xia, Xiaochuan Sun, Zongduo Guo, Weidong Fang, Fajin L, Haitao Wu, Tianyou Luo, Wenyuan Tang Regeneration Research, 2010;5(17): 1337 | Abstract | Submission | Polymorphisms of the maternal Slug gene in fetal neural tube defects in a Chinese population Li Guo, Hong Zhao, Yuheng Pei, Quanren He, Wan-I Li, Ting Zhang, Xiaoying Zheng,Ran Zhou, Jun Xie Regeneration Research, 2010;5(17): 1342 | Abstract | Submission | MORE... Request for articles of NRR. 4. Why Publish in NRR? Specialty . The only journal in neuroregeneration research indexed in Science Citation Index Expanded(SCI-E). Fast peer reviewed. Each manuscript will be reviewed by 2-4 referees. Wide dissemination. NRR is easily accessed online by the world's leading colleges and universities; midical schools; hospitals and healthcare systems and etc via multiple specialised databases. Publicity. NRR has a great reputation in China, which increases the exposure and visibility of your research in China. Post-publication customizable service. We are pleasured to provide the opportunity for you to make the acquaintance of Chinese clinicians, professionals, researchers and policy makers in the field. Feel free to contact me at nrr@nrronline.org . Call for papers Neural Regeneration Research , an English language semi-monthly journal, is dedicated to presenting peer-reviwed, evidenced based scholarly research in neuroregeneration, including neural stem cells, nerve tissue engineering, gene therapy, traditional Chinese medicine. Each manuscript submitted to the Journal is subjected to a critical review process involving the foremost authorities in the subject area of the manuscript before it is accepted for publication. The Editor and Editorial Staff encourage all potential authors to submit manuscripts to the Journal. Qunyuan Xu Editor in Chief Neural Regeneration Research Abstracted in Sciece Citation Index Expanded Biosis Previews Chmical Abstracts EMBASE SCOPUS Index Copernicus Full articles available on Journals@OvidSP. Readers of Neural Regeneration Research attending the 40th Annual Meeting of the Society for Neuroscience, in San Diego, November 1317, 2010, are invited to participate in the Professional Development Workshop How to write a manuscript: getting your paper accepted, Room 4, 9AM12PM, November 14. We will be honoured to meet you there. See you in San Diego. Please contact our editor Megan at nrr@nrronline.org or +86 1380 4998 773. Nomination to Editorial Board In order to promote the international dissemination of Neural Regeneration Research (NRR), we sincerelly invite you to become our editorial board member and reviewer. We would greatly appreciate if you would accept our invitation. Get the application form here . Request for articles of NRR. Editor's Choice This Month In this issue of NRR, five papers have been included that attempt to serach for the optimal means of repair for sciatic nerve defects from the viewpoint of scaffold materials, extracellular matrix, and seed cell selection with regard to tissue engineered nerves. These papers also investigated the feasibility of sciatic neve defect repair using in vitro tracing of seed cells and bridging of autologous nerve segments. Feridex-labeled bone marrow stromal cells for analysis of sciatic nerve defects in rabbits. Neural Regen Res. 2010;5(11):846-852. Transplantation of mesenchymal stem cells from human umbilical cord versus human umbilical cord blood for peripheral nerve regeneration. Neural Regen Res. 2010;5(11):838-845. Immunological rejection of acellular heterogeneous nerve transplant for bridging the sciatic nerve in rats. Neural Regen Res. 2010;5(9):673-677. Chitosan tube bridging autologous nerve segments for the repair of long-segmental sciatic nerve defects. Neural Regen Res. 2010;5(9):668-672. Bridging sciatic nerve gap using tissue-engineered nerves constructed with neural tissue-committed stem cells derived from bone marrow. Neural Regen Res. 2009;4(5):344-349. Published papers regarding... Stem Cells and neuroregeneration Cardiac autonomic nerve fiber regeneration in chronic heart failure More... Tissue engineering and neuroregeneration Immunological rejection of acellular heterogeneous nerve transplant for bridging the sciatic nerve in rats More... Nerve factors and neuroregeneration Basic fibroblast growth factor improves learning and memory deficits in a mouse model of vascular dementia Associated with the role of free radicals clearance? More... Gene engineering and neuroregeneration Role of DYT1 gene in early-onset primary torsion dystonia More.. . Neurodegenerative disease and neuroregeneration Alpha-synuclein gene structure, evolution, and protein aggregation More... Traditional Chinese medicine and neuroregeneration Xiaoyaosan-containing serum inhibits corticosterone-induced apoptosis in PC12 cells by downregulating i overload More... Acupuncture and neuroregeneration Electroacupuncture-attenuated ischemic brain injury increases insulin-like growth factor-1 expression in a rat model of focal cerebral ischemia More... Brain injury and neuroregeneration Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in glioma U87 cells More... Spinl cord injury and neuroregeneration Effects of brain-derived neurotrophic factor on synapsin expression in rat spinal cord anterior horn neurons cultured in vitro More... Peripheral nerve injury and neuroregeneration Muscarinic receptor-mediated calcium changes in a rat model of facial nerve nucleus injury More... Autonomic nerve injury and neuroregeneration Morphological changes in interstitial cells of Cajal in the deep muscular plexus and enteric motor neurons of the intestine in rats with multiple organ dysfunction syndrome More... Eletrophysiology and neuroregeneration Reception of infrasound and audio current in derma nerves More... Neuroimaging and neuroregeneration Electroacupuncture at Tianshu (ST 25) for diarrhea-predominant irritable bowel syndrome using positron emission tomography Changes in visceral sensation center More... Cognitive function and neuroregeneration Interaction between semantic and phonological processes in stuttering:Evidence from the dual-task paradigm More... You may unsubscribe at any time. Our mailing address is: Neural Regeneration Research PO Box 1234, Shenyang, China 110004 Have a suggestion? Email us at nrr@nrronline.org Explore your business opportunities in China Contact Megan at (86) 13804998773. 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