乳腺增生莫紧张多吃丝瓜

烧丝瓜
　　乳腺增生困扰无数女性，据调查，有70%—80％的女性有不同程度的乳腺增生。防治乳腺增生，除了药物治疗以外，膳食调理也很重要。平时可多吃些具有行气通络、化淤散结功效的食物，如丝瓜、南瓜、茄子、橘饼、青皮、玫瑰花等。
　　中医中丝瓜是甘凉之品，入肺、肝两经，具有清热化痰，凉血解毒，解暑除烦，通经活络的功效。现代研究发现，丝瓜中含有一种干扰素诱生剂，可以在人体内催生干扰素，因此具有很好的抗癌作用。此外，丝瓜中还含有丰富的能防止皮肤老化的B族维生素和有增白皮肤作用的维生素C，是不可多得的美容佳品。
　　烧丝瓜：丝瓜800克，水发香菇50克，姜汁适量。锅内加油烧热，用姜汁烹，再加丝瓜片、香菇、料酒、精盐、味精，煮沸至香菇、丝瓜入味，勾芡，淋入麻油，调匀即成。此菜肴具有益气血、通经络的功效。
　　丝瓜炒蛋：丝瓜250克，鸡蛋150克，大葱适量。将鸡蛋加少许精盐搅打均匀；丝瓜去皮切块；锅内加油烧热，下葱段炝锅，放入丝瓜炒熟，倒入蛋液翻炒，加入精盐搅匀，淋入香油，撒入味精即可。
　　在烹制丝瓜时不能过熟，以免破坏其中的营养成分；同时由于丝瓜性寒滑，体虚者多吃易导致泄泻，不可多吃。

PNAS：阐明酗酒及丙肝引发肝癌机制

科学家弄清了把酗酒和丙型肝炎感染与肝细胞癌风险增加联系起来的复杂分子事件。肝细胞癌是一种肝癌，它是全世界第五常见的癌症。此前的研究表明大量饮酒可以极大地增加感染丙型肝炎病毒（HCV）的患者出现肝细胞癌的几率。
美国南加州大学Keigo Machida及其同事分析了一种称为NS5A的病毒蛋白质，此前的实验表明它可以诱导一种细菌内毒素受体的更高水平的表达。酒精摄入增加了细菌感染的风险，这组科学家认为，如果患者也感染了HCV，它会导致内毒素受体信号传导的过度激活。如果人体的自然抗癌应答减弱，过多的抗菌应答然后会导致肿瘤生长风险的增加。这组科学家证实了实验小鼠体内有高浓度的NS5A，并检查了来自感染HCV的人类患者的肝脏活检样本。在那些也酗酒的患者子集中，这组科学家发现了抗菌应答增加的迹象。这组科学家提出，有可能用药物针对性地应对内毒素受体信号传导，从而抵消患肝细胞癌的风险。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS Published online before print January 26, 2009, doi: 10.1073/pnas.0807390106
Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog Keigo Machidaab1, Hidekazu Tsukamotoacd, Hasmik Mkrtchyana, Lewei Duanb, Alla Dynnyka, Helene Minyi Liub, Kinji Asahinaa, Sugantha Govindarajanac, Ratna Raye, Jing-hsiung James Ouab, Ekihiro Sekif, Raymond Deshaiesg, Kensuke Miyakeh and Michael M.-C. Laibi
aSouthern California Research Center for Alcoholic, Liver, and Pancreatic Diseases and Cirrhosis, and Departments of bMolecular Microbiology and Immunology and cPathology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033; dVA Greater Los Angeles Healthcare System, Los Angeles, CA 90033; eDepartment of Pathology, Saint Louis University, St. Louis, MO 63103; fUniversity of California at San Diego, La Jolla, CA 92093; gHoward Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125; hInstitute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; and iDepartment of Microbiology and Immunology, National Cheng Kung University, Tainan 701, Taiwan
Alcohol synergistically enhances the progression of liver disease and the risk for liver cancer caused by hepatitis C virus (HCV). However, the molecular mechanism of this synergy remains unclear. Here, we provide the first evidence that Toll-like receptor 4 (TLR4) is induced by hepatocyte-specific transgenic (Tg) expression of the HCV nonstructural protein NS5A, and this induction mediates synergistic liver damage and tumor formation by alcohol-induced endotoxemia. We also identify Nanog, the stem/progenitor cell marker, as a novel downstream gene up-regulated by TLR4 activation and the presence of CD133/Nanog-positive cells in liver tumors of alcohol-fed NS5A Tg mice. Transplantation of p53-deficient hepatic progenitor cells transduced with TLR4 results in liver tumor development in mice following repetitive LPS injection, but concomitant transduction of Nanog short-hairpin RNA abrogates this outcome. Taken together, our study demonstrates a TLR4-dependent mechanism of synergistic liver disease by HCV and alcohol and an obligatory role for Nanog, a TLR4 downstream gene, in HCV-induced liver oncogenesis enhanced by alcohol.

烟酒致癌率与变异基因有关

英国科学家日前公布的一项研究发现，有两种变异基因会增加人患上肺癌、皮肤癌等5种癌症的几率。这一研究有助于解释为什么嗜烟酗酒者有的早逝，有的却长寿。
英国利兹大学基因流行病学教授蒂姆·毕晓普领导的研究小组发现，过去人们一直认为肺癌、皮肤癌、膀胱癌、前列腺癌和子宫癌是不良生活习惯导致，但是现在发现，这5种癌症是变异基因和环境两种因素“复杂”的相互作用而引发。
研究小组对3．3万名癌症患者和4．5万名健康人的基因进行分析调查，并对比了这两类人群的生活习惯，结果发现体内含有致病变异基因的人，如果嗜烟酗酒，他们更容易患上癌症。
这些研究结果可以让科学家们根据变异基因和生活习惯，识别出最易患上这些致命疾病的人群。
然而，截至目前，科学家们仍不知道这两种变异基因在多大程度上增加人们患上述癌症的几率。（生物谷Bioon.com）

Cancer Research：胰腺肿瘤生长的蛋白质

美国斯坦福大学医学院研究人员日前发现一种对胰腺癌生长至关重要的蛋白质，抑制这种蛋白质的表达可以显著放缓甚至阻止胰腺肿瘤的生长。
这种蛋白质名为CCN2，是一种结缔组织生长因子。研究人员将CCN2表达水平各异的人类胰腺癌细胞注入不同实验鼠的皮下后发现，CCN2表达水平较高的胰腺癌细胞生长迅速，而CCN2表达被抑制的胰腺癌细胞基本不能在实验鼠体内生成肿瘤。
研究人员还发现，CCN2表达水平较高的癌细胞比表达水平低的癌细胞生长和转移速度都快，注射前种癌细胞的实验鼠很快就不治而死。
研究人员说，实体胰腺肿瘤常常会面对缺氧状况，此时肿瘤细胞会通过一系列信号来调节多种基因并促进肿瘤血管生成，使肿瘤细胞在适应缺氧微环境的同时，引起肿瘤自身的侵袭性增加以及对放射治疗的抵抗性增加。研究人员推测，CCN2可能在这一过程中发挥了重要作用。
研究人员表示，他们希望利用这项成果开发出治疗人类胰腺癌的新方法。这一成果已刊登在最新一期美国《癌症研究》杂志上。（生物谷Bioon.com）
生物谷推荐原始出处：
Cancer Research 69, 775-784, February 1, 2009. doi: 10.1158/0008-5472.CAN-08-0987
The Role of Tumor Cell–Derived Connective Tissue Growth Factor (CTGF/CCN2) in Pancreatic Tumor Growth
Kevin L. Bennewith1, Xin Huang1, Christine M. Ham1,2, Edward E. Graves1, Janine T. Erler1, Neeraja Kambham3, Jonathan Feazell1, George P. Yang2, Albert Koong1 and Amato J. Giaccia1
Departments of 1 Radiation Oncology, 2 Surgery, and 3 Pathology, Stanford University School of Medicine, Stanford, California
Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA–expressing clones showed dramatically reduced growth in soft agar and when implanted s.c. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by positron emission tomography imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed colocalization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell–derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer.

Nature Biotechnology：蛋白质作用情况或可预测乳腺癌患者病情发展

加拿大研究人员周日表示，观察各种蛋白质在肿瘤中互相作用的情况有助于预测乳腺癌患者幸存的概率，从而可以使医生更好地调整治疗方式。
如果一开始就知道患者病情不好的话，医生就能立即对其采取积极的治疗方式。但通常情况下，很难预测乳腺癌患者的病情发展情况。
研究人员对美国和欧洲约350名乳腺癌患者乳房肿瘤组织中的蛋白质网络进行了分析。结果显示，痊愈幸存者癌细胞中的蛋白质网络组织形式和死亡者的大不一样。
研究人员在《自然-生物技术》（Nature Biotechnology）上撰文指出，通过观测这些蛋白质的相互作用，对乳腺癌患者未来病情走势预测的准确率可以达到82%。
“这有助于对不同的患者采取适合她们的治疗方法。”
研究人员对约8,000种蛋白质的30,000种作用方式进行了研究，发现其中约250种蛋白质对预测病情发展至关重要。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Biotechnology Published online: 1 February 2009 doi:10.1038/nbt.1522
Dynamic modularity in protein interaction networks predicts breast cancer outcome
Ian W Taylor1,2, Rune Linding1,3, David Warde-Farley4,5, Yongmei Liu1, Catia Pesquita4, Daniel Faria4, Shelley Bull1,5, Tony Pawson1,2, Quaid Morris4 & Jeffrey L Wrana1,2
Changes in the biochemical wiring of oncogenic cells drives phenotypic transformations that directly affect disease outcome. Here we examine the dynamic structure of the human protein interaction network (interactome) to determine whether changes in the organization of the interactome can be used to predict patient outcome. An analysis of hub proteins identified intermodular hub proteins that are co-expressed with their interacting partners in a tissue-restricted manner and intramodular hub proteins that are co-expressed with their interacting partners in all or most tissues. Substantial differences in biochemical structure were observed between the two types of hubs. Signaling domains were found more often in intermodular hub proteins, which were also more frequently associated with oncogenesis. Analysis of two breast cancer patient cohorts revealed that altered modularity of the human interactome may be useful as an indicator of breast cancer prognosis.
1 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario M5G 1X5, Canada.2 Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Room 4396, Toronto, Ontario M5S 1A8, Canada.3 Cellular & Molecular Logic Team, Institute of Cancer Research (ICR), Section of Cell, Molecular & Systems Section, 237 Fulham Road, London, SW3 6JB, UK.4 The Terrence Donnelly Centre for Cellular and Biomolecular Research, 160 College St., Toronto, Ontario M5S 3E1, Canada.5 Department of Computer Science, University of Toronto, 10 King's College Road, Room 3303, Toronto, Ontario M5S 3G4, Canada.6 Faculty of Sciences, University of Lisbon, Campo Grande, 1749-016, Lisbon, Portugal.7 Dalla Lana, School of Public Health, University of Toronto, 155 College St., Toronto, ON M5T 3M7, Canada.

Nature Cell Biology：发现可抑制乳腺癌转移蛋白质

日本筑波大学一个研究小组发现，人体细胞中的蛋白质“CHIP”可以抑制乳腺癌细胞增殖和转移。这一成果2月9日发表在英国《自然—细胞生物学》（Nature Cell Biology）杂志网络版上。
研究人员说，他们注意到，在人体细胞中，蛋白质“CHIP”的水平随着乳腺癌的发展而降低，用实验鼠进一步研究发现，减少“CHIP”的量，实验鼠乳腺癌细胞形成大块肿瘤，且转移加快；增加“CHIP”的量，乳腺癌细胞增殖和转移能力则受到极大的抑制。
研究人员说，这一发现表明，可以通过提高“CHIP”蛋白质的量或促使其活跃来抑制乳腺癌细胞的增殖和转移。这项成果为开发防治乳腺癌新药提供了思路。
此外，由于“CHIP”蛋白质也存在于乳腺以外的组织，研究人员推测，它可能还能抑制其他癌症细胞的增殖和转移。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Cell Biology Published online: 8 February 2009 doi:10.1038/ncb1839
The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways
Masashi Kajiro1,6, Ryuichi Hirota1,6, Yuka Nakajima1, Kaori Kawanowa2, Kae So-ma1, Ichiaki Ito1, Yuri Yamaguchi3, Sho-hei Ohie1, Yasuhito Kobayashi2, Yuko Seino3, Miwako Kawano1, Yoh-ichi Kawabe1, Hiroyuki Takei2, Shin-ichi Hayashi4, Masafumi Kurosumi2, Akiko Murayama1,5, Keiji Kimura1 & Junn Yanagisawa1,5
CHIP is a U-box-type ubiquitin ligase that induces ubiquitylation and degradation of its substrates, which include several oncogenic proteins1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. The relationship between CHIP and tumour progression, however, has not been elucidated. Here, we show that CHIP suppresses tumour progression in human breast cancer by inhibiting oncogenic pathways. CHIP levels were negatively correlated with the malignancy of human breast tumour tissues. In a nude mouse xenograft model, tumour growth and metastasis were significantly inhibited by CHIP expression. In contrast, knockdown of CHIP (shCHIP) in breast cancer cells resulted in rapid tumour growth and metastastic phenotypes in mice. In cell-based experiments, anchorage-independent growth and invasiveness of shCHIP cells was significantly elevated due to increased expression of Bcl2, Akt1, Smad and Twist. Proteomic analysis identified the transcriptional co-activator SRC-3 (refs 13, 14, 15, 16, 17, 18, 19) as a direct target for ubiquitylation and degradation by CHIP. Knocking down SRC-3 in shCHIP cells reduced the expression of Smad and Twist, and suppressed tumour metastasis in vivo. Conversely, SRC-3 co-expression prevented CHIP-induced suppression of metastasis formation. These observations demonstrate that CHIP inhibits anchorage-independent cell growth and metastatic potential by degrading oncogenic proteins including SRC-3.
1 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.2 Department of Pathology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi- gun, Saitama 362-0806, Japan.3 Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi- gun, Saitama 362-0806, Japan.4 Department of Medical Technology, Course of Health Sciences, School of Medicine, Tohoku University, 2-1 Seiryou-machi, Aoba-ku, Sendai, 980-8575, Japan.5 Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.6 These authors contributed equally to this work.

Science Signaling：阻断mTOR信号治疗癌症

哺乳动物雷帕霉素标靶（ mTOR ）是一种对细胞生长和增殖至关重要的蛋白激酶。 mTOR 是作为 2 种独特的多蛋白复合物的一部分来发挥作用的。这 2 种复合物是 mTOR 复合物 -1 （ mTORC1 ）及 mTOR 复合物 -2 （ mTORC2 ），它们都参与 AKT 信号级联放大反应（这是一种据报道在许多人类癌症中都高度活跃的通路）。 丧失肿瘤抑制子 PTEN 会通过 AKT 而高度激活 mTOR ，这是人类前列腺癌症中最常见的事件之一。
在2009年1月27日刊《科学》杂志的一篇 Research Article 中， Nardella 等人研究显示，对 mTOR 的活性（可通过这 2 种复合物来消除信号通路）进行有条件地灭活对成年小鼠的前列腺影响甚小，但却能抑制前列腺的与 PTEN 的丧失所相关的肿瘤发生。这些发现因而支持这样一个基本原理，即研发以 mTORC1 和 mTORC2 为标靶的特殊 mTOR 抑制剂可治疗由于 PTEN 缺乏和异常 mTOR 信号而引发的肿瘤。 （生物谷Bioon.com）
生物谷推荐原始出处：
Sci. Signal., 27 January 2009 DOI: 10.1126/scisignal.2000189
Differential Requirement of mTOR in Postmitotic Tissues and Tumorigenesis
Caterina Nardella1, Arkaitz Carracedo1*, Andrea Alimonti1*, Robin M. Hobbs1, John G. Clohessy1, Zhenbang Chen1, Ainara Egia1, Alessandro Fornari2,3, Michelangelo Fiorentino2, Massimo Loda2,4, Sara C. Kozma5, George Thomas5, Carlos Cordon-Cardo6, and Pier Paolo Pandolfi1
1 Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.3 Department of Biomedical Sciences and Human Oncology, Molinette Hospital, University of Turin, 10126 Turin, Italy.4 Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.5 Department of Genome Science, Genome Research Institute, University of Cincinnati, Cincinnati, OH 45237, USA.6 Department of Pathology, Columbia University, New York, NY 10032, USA.
Abstract: The mammalian target of rapamycin (mTOR) is a crucial effector in a complex signaling network commonly disrupted in cancer. mTOR exerts its multiple functions in the context of two different multiprotein complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Loss of the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10) can hyperactivate mTOR through AKT and represents one of the most frequent events in human prostate cancer. We show here that conditional inactivation of mTor in the adult mouse prostate is seemingly inconsequential for this postmitotic tissue. Conversely, inactivation of mTor leads to a marked suppression of Pten loss–induced tumor initiation and progression in the prostate. This suppression is more pronounced than that elicited by the sole pharmacological abrogation of mTORC1. Acute inactivation of mTor in vitro also highlights the differential requirement of mTor function in proliferating and transformed cells. Collectively, our data constitute a strong rationale for developing specific mTOR inhibitors targeting both mTORC1 and mTORC2 for the treatment of tumors triggered by PTEN deficiency and aberrant mTOR signaling.

Nature：肌氨酸含量可帮助诊断前列腺癌

（图片来源： Nina Lampen / Science Photo Library ）
最新一期Nature刊发了一篇前列腺癌最新分子标记的文章，该研究成果为快速检测前列腺癌提供了新线索。
一直以来，临床肿瘤医生们在前列腺癌的诊治过程中备受打击，他们往往能轻易地诊断出前列腺癌患者，却无法诊断出该患者是恶性前列腺癌还是良性前列腺癌，这往往导致恶性前列腺癌患者丧失了最佳治疗的机会。而美国密歇根大学这项新的研究成果有助临床肿瘤医生走出这个困境。
这一项目是密歇根大学，霍华休斯医学院的研究者最新的研究成果。研究者对前列腺癌样品中的代谢物所做的一项系统分析，他们发现一个问题：肌氨酸（包括肌肉在内的很多生物组织中的一种常见氨基酸）在侵略性前列腺癌中含量显著升高。
值得关注的是，肌氨酸在男性前列腺癌患者的尿样中可检测出来。这一发现使得肌氨酸成为前列腺癌诊断的一个候选生物标记。
更令人振奋的是，用遗传技术将甘氨酸生成肌氨酸的酶定向剔除，小鼠动物实验发现，剔除了生成肌氨酸的酶将大大降低前列腺癌的恶性程度，这说明肌氨酸在癌细胞转移中可能扮演重要角色，因此肌氨酸通道可能成为前列腺癌的新治疗靶位。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 457, 910-914 (12 February 2009) doi:10.1038/nature07762
Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
Arun Sreekumar1,2,3,4, Laila M. Poisson5,13, Thekkelnaycke M. Rajendiran1,3,13, Amjad P. Khan1,3,13, Qi Cao1,3, Jindan Yu1,3, Bharathi Laxman1,3, Rohit Mehra1,3, Robert J. Lonigro1,4, Yong Li1,3, Mukesh K. Nyati4,6, Aarif Ahsan6, Shanker Kalyana-Sundaram1,3, Bo Han1,3, Xuhong Cao1,3, Jaeman Byun7, Gilbert S. Omenn2,7,8, Debashis Ghosh4,5,11, Subramaniam Pennathur2,4,7, Danny C. Alexander12, Alvin Berger12, Jeffrey R. Shuster12, John T. Wei4,9, Sooryanarayana Varambally1,3,4, Christopher Beecher1,2,3 & Arul M. Chinnaiyan1,2,3,4,9,10
1 The Michigan Center for Translational Pathology,2 Center for Computational Medicine and Biology,3 Department of Pathology,4 The Comprehensive Cancer Center,5 Department of Biostatistics,6 Department of Radiation Oncology,7 Department of Internal Medicine,8 Department of Human Genetics,9 Department of Urology,10 Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA11 Department of Statistics and Huck Institute of Life Sciences, Penn State University, Pennsylvania 16802, USA12 Metabolon, Inc. 800 Capitola Drive, Suite 1 Durham, North Carolina 27713, USA13 These authors contributed equally to this work.
Multiple, complex molecular events characterize cancer development and progression1, 2. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer (42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N-methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.

艾滋病发展速率与个体DNA有关

美国国家癌症研究所证实，艾滋病（HIV）病毒以何种速度演变为艾滋病可能取决于个人的DNA。线粒体内DNA的某种变异，可使艾滋病的发展速率显著提升。 美国国家癌症研究所的斯蒂芬·奥布莱恩及其同事在上世纪80年代至90年代早期开展了5项长期研究工作，对1833名HIV病毒携带者进行了追踪。由于研究阶段先于高效抗逆转录病毒疗法（HAART），研究小组可在不受干扰的情况下密切关注艾滋病患者病情的发展。 随着科学家对艾滋病相关疾病及其与遗传信息间联系研究的深入，研究小组发现某些线粒体DNA基因型与艾滋病的发展速率有关。例如：具有单倍型类群U5a1和单倍型类群J等特定变异的患者，其艾滋病的发展速率可比一般人群提升两倍。与此相反，具有单倍型类群H3变异的患者的发展速率则可比一般人群减缓2倍之多。这为线粒体与艾滋病发展进程有关的理论提供了有力支持。HIV病毒可导致免疫细胞的死亡，这在细胞内的线粒体只可产生少量能量时更易发生。研究小组成员谢尔·翰德森表示，线粒体产生越少的能量，越能加剧疾病的发展，而单倍型类群U5a1和单倍型类群J都可引发线粒体的能量缺失。 研究表明，线粒体DNA测试有朝一日可对HIV病毒携带者进行准确诊断，决定病人应在何时开始治疗。剑桥大学的HIV研究人员安德鲁·利威尔表示，通过研究线粒体DNA的类型可确定哪些病人对HIV病毒的反应更敏感，应比一般建议的时间更早地开始高效抗逆转录病毒疗法。此外，对线粒体DNA进行扫描也可为医生提供帮助，以确定最佳的药物组合治疗。（ 生物谷 Bioon.com）

Cell Metabolism：脂肪代谢研究

来自瑞典斯德哥尔摩大学，卡洛林斯卡医学院，北京大学分子医学研究院等处的研究人员就脂肪组织代谢与血管新生相关的分子机制这一未知的领域进行了研究，发现了一种新机制，对于脂肪代谢研究以及血管新生研究意义重大，并且也从理论上说明可以应用血管新生调控元件来治疗肥胖和代谢失调症。
体内脂肪细胞的代谢过程是一个非常活跃、从不间断的循环过程。正常情况下，机体内的脂肪细胞一方面不断地从血液中摄取食物分解后产生的游离脂肪酸，另一方面脂肪细胞内生成的磷酸三酰甘油又可被体内的脂肪酶催化分解成甘油和游离脂肪酸，后者中的一部分被重新释放人血液，供机体其他组织利用，另一部分则又被重新酯化。
这个生化过程目前科学家们了解的比较清楚，但是具体脂肪组织代谢与血管新生相关的分子机制仍然是属于这一领域的一个研究空白，在这篇文章中，研究人员将小鼠曝露在冷环境下，刺激白色脂肪细胞和棕色脂肪细胞的活性，并从实验结果中发现了一种新调控机制。
研究人员发现冷刺激会导致棕色脂肪相关蛋白，比如uncoupling protein-1 (UCP1)和PGC-1a的表达水平增加，同时VEGF等血管新生因子（Proangiogenic factors）也会增多，而内生性血管新生抑制子，比如血小板反应蛋白（thrombospondin）等则表达量会降低。野生型的小鼠在冷刺激下，脂肪组织会发生低氧现象，而UCP1－/ －小鼠则不会出现这种情况，有意思的是，VEGFR2阻断能消除这种血管新生，并极大的伤害非战栗产热（nonshivering）量。而且研究人员还发现VEGFR1阻断会导致相反的作用：增加脂肪的血管新生，以及非战栗产热量。
这些研究结果从理论上说明可以应用血管新生调控元件来治疗肥胖和代谢失调症。（ 生物谷 Bioon.com）
生物谷 推荐原始出处：
Cell Metabolism, 99-109, 7 January 2009 doi:10.1016/j.cmet.2008.11.009
Hypoxia-Independent Angiogenesis in Adipose Tissues during Cold Acclimation
Yuan Xue1,Natasa Petrovic2,Renhai Cao1,Ola Larsson3,Sharon Lim1,Shaohua Chen1,Helena M. Feldmann2,Zicai Liang4,Zhenping Zhu5,Jan Nedergaard2,Barbara Cannon2andYihai Cao1,,
1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden2 The Wenner-Gren Institute, the Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden3 Department of Biochemistry, McGill University, 3655 Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada4 Institute of Molecular Medicine, Peking University, Beijing 100871, China5 ImClone Systems Incorporated, 108 Varick Street, New York, NY 10014, USA
Summary
The molecular mechanisms of angiogenesis in relation to adipose tissue metabolism remain poorly understood. Here, we show that exposure of mice to cold led to activation of angiogenesis in both white and brown adipose tissues. In the inguinal depot, cold exposure resulted in elevated expression levels of brown-fat-associated proteins, including uncoupling protein-1 (UCP1) and PGC-1. Proangiogenic factors such as VEGF were upregulated, and endogenous angiogenesis inhibitors, including thrombospondin, were downregulated. In wild-type mice, the adipose tissues became hypoxic during cold exposure; in UCP1/ mice, hypoxia did not occur, but, remarkably, the augmented angiogenesis was unaltered and was thus hypoxia independent. Intriguingly, VEGFR2 blockage abolished the cold-induced angiogenesis and significantly impaired nonshivering thermogenesis capacity. Unexpectedly, VEGFR1 blockage resulted in the opposite effects: increased adipose vascularity and nonshivering thermogenesis capacity. Our findings have conceptual implications concerning application of angiogenesis modulators for treatment of obesity and metabolic disorders.

Nature：蛔虫的启示 少食而长寿

为了在严酷环境中生存，蛔虫的幼虫能进入一种所谓的“多尔（dauer）”状态，在处于这种状态期间，它们不吃东西，但仍能活动，对压力具有抵抗力，而且极为长寿。
在一个典型的“多尔”幼虫体内，胰岛素类信号作用减少，营养储备充分，而且其代谢过程发生全面变化。Patrick Narbonne 和 Richard Roy发现，如果没有AMPK (LKB1)信号作用，“多尔”幼虫会迅速耗尽其所储存的能量，并且会由于重要器官衰竭而过早死亡。在一个正常的“多尔”幼虫中，LKB1/AMPK通过减慢甘油三酸酯的水解来保证幼虫不需要食物而能长寿和具有活力，从而使体内所存储的脂肪能够维持更长时间，同时保持正确的渗透调节（osmoregulation）。这项工作触及在关于 衰老 、 糖尿病 和肥胖症研究中所涉及的体系。（ 生物谷 Bioon.com）
生物谷 推荐原始出处：
Nature 457, 210-214 (8 January 2009) doi:10.1038/nature07536
Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival
Patrick Narbonne1 & Richard Roy1
1 Department of Biology, McGill University, Montréal, Québec H3A 1B1, Canada
Many organisms can enter a dormant state or diapause to survive harsh environmental conditions for extended durations. When Caenorhabditis elegans larvae enter dauer they arrest feeding but remain active and motile, yet become stress-resistant, extremely long-lived and non-ageing1. Entry into dauer is associated with a reduction in insulin-like signalling, the accumulation of nutritive resources and a concomitant global change in metabolism2, 3, 4, 5, yet the precise molecular and physiological processes that enable long-term survival in the absence of caloric intake remain largely unknown. We show here that C. elegans larvae that lack LKB1/AMPK (AMP-activated protein kinase) signalling enter dauer normally, but then rapidly consume their stored energy and prematurely expire following vital organ failure. We found that this signalling pathway acts in adipose-like tissues to downregulate triglyceride hydrolysis so that these lipid reserves are rationed to last the entire duration of the arrest. Indeed, the downregulation of adipose triglyceride lipase (ATGL-1) activity suppresses both the rapid depletion of stored lipids and reduced life span of AMPK mutant dauers, while AMPK directly phosphorylates ATGL-1. Finally, we show that the slow release of energy during dauer is critical for appropriate long-term osmoregulation, which fails as triglyceride resources become depleted. These mechanisms may be essential for survival through diapause, hibernation, or long-term fasting in diverse organisms and may also underlie AMPK-dependent life span extension.

J.TEM：与NAD相关的生物学、代谢、以及在癌症中的作用

近期发表在Trends in Endocrinology & Metabolism上的一篇文章指出， 磷酸核糖转移酶（nicotinamide phosphoribosyltransferase，Nampt）在许多疾病包括2型 糖尿病 和癌症具有重要的生理功能。该文章详细描述了Nampt作为烟酰胺转化为烟酰胺单核苷酸过程的作用，其中最重要的是产生 烟酰胺腺嘌呤二核苷酸磷酸（nicotinamide adenine dinucleotide，NAD），最近由于NAD的生化、代谢、炎症方面的研究深入，Nampt可以调节消耗NAD酶如去乙酰化酶Sirtuin的活性，影响应急与代谢，从而也引起了极大的兴趣，Nampt似乎应该是具有免疫调节功能因子，在炎症中发挥作用。（ 生物谷 Bioon.com）
生物谷推荐原始出处：
Trends in Endocrinology & Metabolism doi:10.1016/j.tem.2008.10.004
Nampt: linking NAD biology, metabolism and cancer
Antje Garten1, , Stefanie Petzold1, Antje K?rner1, Shin-ichiro Imai2, and Wieland Kiess1
1University of Leipzig, Hospital for Children and Adolescents, Research Laboratory, Oststr. 21-25, 04317 Leipzig, Germany2Washington University School of Medicine, Department of Developmental Biology, Campus Box 8103, 660 South Euclid Avenue, St. Louis, MO 63110, USA
Nicotinamide phosphoribosyltransferase (Nampt) converts nicotinamide to nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD) intermediate. Previously identified as a cytokine pre-B-cell colony-enhancing factor and controversially claimed as an insulin-mimetic hormone visfatin, Nampt has recently drawn much attention in several fields, including NAD biology, metabolism and inflammation. As a NAD biosynthetic enzyme, Nampt regulates the activity of NAD-consuming enzymes such as sirtuins and influences a variety of metabolic and stress responses. Nampt also plays an important part in regulating insulin secretion in pancreatic β-cells. Nampt seems to have another function as an immunomodulatory cytokine and, therefore, has a role in inflammation. This review summarizes these various functional aspects of Nampt and discusses its potential roles in diseases, including type 2 diabetes and cancer.

PLoS Biology：揭示结核菌耐药性奥秘

结核分枝杆菌比想象得更加具有遗传多样性（图片来源：Flickr/AJC1）
科学家发现了结核菌的遗传秘密，这个秘密对于结核菌的多药耐药性的急剧增长可能有贡献。
这项研究是对全球结核菌多样性的首个调查，它发现了这些细菌比此前认为的更加具有遗传多样性。
这些科学家检查了结核病的致病菌结核分枝杆菌的99种菌株。他们还检查了9种只感染动物的菌株。
让他们感到震惊的是，他们发现人类结核菌菌株之间的遗传多样性要远远高于动物菌株，这与此前认为的所有人类结核菌菌株基本相同的观念相抵触。
“我们发现结核分枝杆菌不像我们此前认为的那样相同，”该研究的作者之一、曾在美国 系统生物学 研究所工作、如今在英国国立医学研究所的Sebastien Gagneux说。
这组科学家还发现这种细菌的遗传选择率低。它们通过一种称为遗传漂变（genetic drift）的过程积累它们的DNA的突变，而且几乎没有抑制这些突变的选择压力。由于这个原因，带来耐药性的突变不会从基因库中消失，而会持续存在于种群中。
通常，带来耐药性的遗传突变会对细菌造成损害，因为它们的获得是以细菌的其他机制被削弱为代价的。细菌的这种另外的机制抑制着它们的耐药性。但是这对于结核病并非如此。
这组科学家的研究发表在了12月16日出版的《公共科学图书馆·生物学》（PLoS Biology）杂志上，他们发现人类结核分枝杆菌可以分为两个独特的群体：仅见于西非以及印度洋沿岸的“古代”菌株，以及在欧洲、美洲、东亚、东非和印度占主流的“现代”世系。
这组科学家发现了遗传和地理距离之间的相关性，这提示了古代人类走出非洲的陆地移民路径把结核病向北携带到了欧洲，向东携带到了印度洋附近，但是现代菌株沿着海路迁移回了非洲。
“有可能古代菌株被现代菌株排挤掉了，例如，在加勒比地区，尽管古代菌株因为奴隶贸易而到达那里，现在那里只有现代菌株，” Gagneux告诉本网站说。
这组科学家说，由于这一因素，再加上今天的全球范围的旅行，结核病控制项目的设计者应该把地理上的菌株多样性考虑进去。 （ 生物谷 Bioon.com）
生物谷 推荐原始出处：
PLoS Biology，doi ：10.1371/journal.pbio.0060311，Ruth Hershberg，Sebastien Gagneux
High Functional Diversity in Mycobacterium tuberculosis Driven by Genetic Drift and Human Demography
Ruth Hershberg1, Mikhail Lipatov1, Peter M. Small2,3, Hadar Sheffer2, Stefan Niemann4, Susanne Homolka4, Jared C. Roach5, Kristin Kremer6, Dmitri A. Petrov1, Marcus W. Feldman1, Sebastien Gagneux2,7*
1 Department of Biology, Stanford University, Stanford, California, United States of America, 2 Institute for Systems Biology, Seattle, Washington, United States of America, 3 Bill and Melinda Gates Foundation, Seattle, Washington, United States of America, 4 Forschungszentrum Borstel, National Reference Center for Mycobacteria, Borstel, Germany, 5 Seattle Children's Hospital Research Institute, Seattle, Washington, United States of America, 6 Mycobacteria Reference Unit (CIb-LIS), National Institute of Public Health and the Environment, Bilthoven, The Netherlands, 7 MRC National Institute for Medical Research, London, United Kingdom
Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.

NEJM：疟疾疫苗即将进入最终阶段试验

在研究表明一种候选疟疾疫苗将肯尼亚和坦桑尼亚的婴幼儿疟疾风险降低一半之后，7个非洲国家的1.6万名儿童即将在明年早些时候参与该疫苗的最终阶段试验。
下一步的试验将扩展到布基纳法索、加蓬、加纳、马拉维和莫桑比克。试验定于2009年3月开始。
来自两个东非临床试验的结果12月8日发表在了《新英格兰医学杂志》（NEJM）上，这两个试验使用的疫苗目前被称为RTS,S。
“这些结果促进了一种前景，即疫苗有能力保护非洲的婴幼儿不受疟疾感染，”该研究的作者之一、肯尼亚医学研究所设在Kilifi的地理医学研究中心的Ally Olotu说。
其中一项试验证明了该疫苗——它能在这种凭借血液传播寄生虫到达肝脏之前制止它们——可以纳入非洲国家标准的儿童免疫规划中，而不会影响其他疫苗的有效性或破坏它自身的有效性。
第二项试验证实了这种疫苗对婴儿的安全和有效性，并发现它能降低疟疾的感染率一半（53%）。
Olotu说，接下来的试验的参与者是6—12周的新生儿以及5—17个月的婴儿，这些试验将提供关于该疫苗的有效性和安全性的更多信息。
坦桑尼亚Ifakara卫生研究所的Salim Abdulla说，在肯尼亚和坦桑尼亚进行的最新试验证实了早先在冈比亚成年人以及莫桑比克的学龄前儿童身上进行的更小规模的试验，在这些试验中疫苗提供了18个月到4年的保护。（参见 莫桑比克开始疟疾疫苗试验）
然而，Abdulla说，目前没有在非洲生产这种疫苗的计划，而且没有关于它的可能成本的信息。他告诉本网站说，科学家正在和非政府组织以及卫生发展机构协商开展一个社会营销运动，从而迅速扩大该疫苗在世界卫生组织以及其它免疫接种项目中的应用。
“这些发现为我们打算在非洲的11个地点进行的III期临床试验建立了强有力的基础，”Abdulla说。他在坦桑尼亚的坦噶医学研究中心参与了这些试验。（ 生物谷 Bioon.com）
生物谷 推荐原始出处：
NEJM，359, 2521 (2008)，Philip Bejon，Lorenz von Seidlein
Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of Age
Philip Bejon, Ph.D., John Lusingu, Ph.D., Ally Olotu, M.B., Ch.B., Amanda Leach, M.R.C.P.C.H., Marc Lievens, M.Sc., Johan Vekemans, Ph.D., Salum Mshamu, M.D., Trudie Lang, Ph.D., Jayne Gould, Ph.D., Marie-Claude Dubois, M.Sc., Marie-Ange Demoitié, M.Sc., Jean-Francois Stallaert, B.Sc., Preeti Vansadia, M.H.S., Terrell Carter, M.H.S., Patricia Njuguna, M.D., Ken O. Awuondo, H.N.D., Anangisye Malabeja, M.D., Omar Abdul, M.D., Samwel Gesase, M.D., Neema Mturi, M.R.C.Paed., Chris J. Drakeley, Ph.D., Barbara Savarese, R.N., Tonya Villafana, Ph.D., W. Ripley Ballou, M.D., Joe Cohen, Ph.D., Eleanor M. Riley, Ph.D., Martha M. Lemnge, Ph.D., Kevin Marsh, F.R.C.P., and Lorenz von Seidlein, Ph.D.
Background Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure.
Methods We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi, Kenya, and Korogwe, Tanzania. The primary end point was fever with a falciparum parasitemia density of more than 2500 parasites per microliter, and the mean duration of follow-up was 7.9 months (range, 4.5 to 10.5).
Results A total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P<0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P<0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P<0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria.

葡萄籽能治白血病？

一项新研究表明，当白血病细胞接触到一种葡萄籽提取物时，3／4的癌细胞在24小时之内死掉。
美国肯塔基大学的研究人员称，他们发现这种提取物能刺激JNK激酶的产生，JNK激酶可以调节导致细胞死亡的信号传输路径。该论文刊登在1月出版的美国《临床癌症研究》杂志上。
论文作者、肯塔基大学毒理学中心华人教授史香林（Xianglin　Shi）说：“这些研究表明，可以把葡萄籽提取物这样的制剂，纳入预防或治疗恶性血液病中来，也许还可以用来预防和治疗其他癌症。”史香林同时提醒：“该研究还处于初始阶段，是一项非常有前途的研究。但要说这种物质具有根本性的保护作用，还为时尚早。”
以前的研究已经证明，吃蔬菜和水果有助于抑制癌症的发展，类黄酮和葡萄籽提取物可能杀死癌细胞，使某些肿瘤变小。史香林利用一种葡萄籽提取物，使用不同的剂量来对付白血病细胞，结果发现，剂量越高，死亡的白血病细胞越多，却不会影响健康的细胞。
然而，当研究人员往这种提取物中加入抑制JNK激酶蛋白的制剂，或者利用基因工程关闭JNK激酶基因时，葡萄籽提取物就不再有效。（生物谷Bioon.com）