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| October 2011 Volume 17, Issue 10 |  | | |  |  Focus
Editorial
News
Book Review
Correspondence
News and Views
Community Corner
Between Bedside and Bench
Research Highlights
Commentaries
Brief Communications
Articles
Letters
Technical Report
Corrigenda | | | Advertisement | | | | 
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We speak to the Icelandic musician Björk about her new science-themed album Biophilia and explore new treatments for tuberculosis, tumor-induced seizure and MRSA.
Listen Now | | Editorial | Top | | | | Drug targets slip-sliding away p1155
doi:10.1038/nm.2530
The starting point for many drug discovery programs is a published report on a new drug target. Assessing the reliability of such papers requires a nuanced view of the process of scientific discovery and publication.
Full Text | PDF | | News | Top | | | | Cancer drugs find a companion with new diagnostic tests p1157
Charlotte Schubert
doi:10.1038/nm1011-1157
Full Text | PDF | | | | Mysteries about drug metabolism in the obese weigh on doctors p1158
Alisa Opar
doi:10.1038/nm1011-1158a
Full Text | PDF | | | | Ten years on from anthrax scare, analysis lags behind sequencing pp1158 - 1159
Amber Dance
doi:10.1038/nm1011-1158b
Full Text | PDF | | | | New fee structure proposed by FDA might lead to more talk p1159
Hannah Waters
doi:10.1038/nm1011-1159
Full Text | PDF | | | | Childhood tuberculosis treatment remains imprecise science p1160
Julie Manoharan
doi:10.1038/nm1011-1160a
Full Text | PDF | | | | NIH student training overhauled after HHMI pulls funding pp1160 - 1161
Hannah Waters
doi:10.1038/nm1011-1160b
Full Text | PDF | | | | Businesses ready whole-genome analysis services for researchers p1161
Trevor Stokes
doi:10.1038/nm1011-1161
Full Text | PDF | | | | Start-up tries bidding model to outsource academic research p1162
Elie Dolgin
doi:10.1038/nm1011-1162
Full Text | PDF | | | | Straight talk with... Mahendra Rao p1163
Elie Dolgin
doi:10.1038/nm1011-1163
In August, Mahendra Rao returned to the US National Institutes of Health (NIH) after a six-year hiatus to head the new Intramural Center for Regenerative Medicine. The [dollar]52-million center was launched in early 2010 by the agency to develop new therapies using stem cell approaches. Elie Dolgin spoke to Rao to find out how he plans to turn stem cell discoveries into cell-based therapies.
Abstract | Full Text | PDF | | | | News in brief: Biomedical briefing pp1164 - 1165
doi:10.1038/nm1011-1164
Full Text | PDF | | | | | News Features | | | | Networking for new drugs pp1166 - 1168
Claire Ainsworth
doi:10.1038/nm1011-1166
Many of today's most celebrated drugs are designed to hit only one biological target with great precision. But a novel clinical trial aims to turn this idea on its head by using 'network pharmacology' to more effectively tackle a common neurological disorder affecting limb movement. Claire Ainsworth looks into how medicine's proverbial 'magic bullet' might soon give way to a more sophisticated arsenal.
Full Text | PDF | | | | Biomedicine in Brazil p1169
doi:10.1038/nm1011-1169
Full Text | PDF | | | | Laws hinder drug development inspired by Amazonian biodiversity p1170
Carlos Henrique Fioravanti
doi:10.1038/nm1011-1170
Full Text | PDF | | | | Brazilian drug companies hope to benefit from foreign investment p1171
Mike May
doi:10.1038/nm1011-1171a
Full Text | PDF | | | | New framework needed to thwart Brazil's crippling bureaucracy p1171
Luisa Massarani
doi:10.1038/nm1011-1171b
Full Text | PDF | | | | In Brazil, basic stem cell research lags behind clinical trials p1172
Elie Dolgin
doi:10.1038/nm1011-1172
Full Text | PDF | | | | Brazilians lured back home with research funding and stability p1173
Anna Petherick
doi:10.1038/nm1011-1173
Full Text | PDF | | | | After years of neglect, Brazil takes aim at Chagas disease p1174
Anna Petherick
doi:10.1038/nm1011-1174a
Full Text | PDF | | | | Hopes build that new infrastructure can aid drug discovery pp1174 - 1175
Bernardo Esteves
doi:10.1038/nm1011-1174b
Full Text | PDF | | | | Hard line take on public health gives Brazil soft political power p1175
Anna Petherick
doi:10.1038/nm1011-1175
Full Text | PDF | | | | | Opinion | | | | The NIH translational research center might trade public risk for private reward p1176
Jerry Avorn and Aaron S Kesselheim
doi:10.1038/nm1011-1176
The new National Center for Advancing Translational Sciences planned for the US National Institutes of Health intends to help transform biological findings into new therapeutic products. But if taxpayer funding of risky biomedical research translates into lucrative new medicines, the public should share in the economic benefits as well.
Full Text | PDF | | Book Review | Top | | | | An epidemic and social taboos p1177
Stanley A. Plotkin reviews Dangerous Pregnancies by Leslie J. Reagan
doi:10.1038/nm.2509
Full Text | PDF | | Correspondence | Top | | | | Fractional synthesis and clearance rates for amyloid [beta] pp1178 - 1179
Steven D Edland and Douglas R Galasko
doi:10.1038/nm.2495
Full Text | PDF | | | | Reply to: Fractional synthesis and clearance rates for amyloid [beta] pp1179 - 1180
Donald L Elbert, Bruce W Patterson, Lindsay Ercole, Vitaliy Ovod, Tom Kasten, Kwasi Mawuenyega, Kevin Yarasheski, John C Morris, Tammie Benzinger, David M Holtzman and Randall J Bateman
doi:10.1038/nm.2496
Full Text | PDF | | | | The crucial role of hepatocyte growth factor receptor during liver-stage infection is not conserved among Plasmodium species pp1180 - 1181
Alexis Kaushansky and Stefan H I Kappe
doi:10.1038/nm.2456
Full Text | PDF | | | | The crucial role of hepatocyte growth factor receptor during liver-stage infection is not conserved among Plasmodium species p1181
Ana Rodriguez and Maria M Mota
doi:10.1038/nm.2487
Full Text | PDF | | News and Views | Top | | | | Memory in disguise pp1182 - 1183
Federica Sallusto and Antonio Lanzavecchia
doi:10.1038/nm.2502
Memory T cells can be maintained for a lifetime, but the underlying mechanism has been hard to pin down. A new study identifies a subset of memory T cells with stem cell properties in humans and shows that these cells mediate a superior antitumor response in a mouse model of adoptive T cell therapy (pages 1290-1297).
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See also: Article by Gattinoni et al. | | | | Epigenetic tumor suppression by BRCA1 pp1183 - 1185
Aneliya Velkova and Alvaro N A Monteiro
doi:10.1038/nm.2493
BRCA1 germline mutations lead to an increased risk of breast and ovarian cancer, but the mechanisms by which the product of this gene functions as a tumor suppressor have remained elusive. Now, analysis of a missense BRCA1 variant shows that it can epigenetically regulate an miRNA implicated in cancer, providing new mechanistic insights (pages 1275-1282).
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See also: Article by Chang et al. | | | | Tuberculosis vaccine promises sterilizing immunity pp1185 - 1186
Helen McShane and Ann Williams
doi:10.1038/nm.2503
In the search for an improved vaccine to combat tuberculosis, a potent candidate has unexpectedly emerged that induces potent efficacy against mycobacterial infection in mice (pages 1261-1268).
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See also: Article by Sweeney et al. | | | | Turning up the heat on colorectal cancer pp1186 - 1188
Andrew T Chan
doi:10.1038/nm.2500
Mutations in the microsatellite of the chaperone heat shock protein 110 (HSP110) yield a mutant protein that counteracts oncogenic potential, enhances responsiveness to chemotherapy and associates with increased survival in individuals with colorectal cancers that arise through defective DNA mismatch repair (pages 1283-1289).
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See also: Article by Dorard et al. | | | | EGFR signaling in podocytes at the root of glomerular disease pp1188 - 1189
Ray Harris
doi:10.1038/nm.2455
A study in a mouse model of immune-mediated glomerular disease and in people with rapidly progressive glomerulonephritis shows activation of epidermal growth factor receptor (EFGR) signaling in podocytes by a molecule expressed in the kidney (pages 1242-1250). Blocking this axis may open new doors to treat inflammatory kidney conditions.
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See also: Article by Bollee et al. | | | | Glioma-related seizures: glutamate is the key pp1190 - 1191
Matthias Simon and Marec von Lehe
doi:10.1038/nm.2510
Epilepsy complicates the clinical course of many patients with brain tumors, particularly gliomas. A mouse model of glioma now indicates that glioma cells release glutamate, causing tumor-related seizures (pages 1269-1274). Sulfasalazine, an approved therapeutic for Crohn's disease, can block glutamate release and improve seizures in these mice; therefore, this drug may also have potential antiepileptic effects in humans.
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See also: Article by Buckingham et al. | | | | | | | Community Corner | Top | | | | Zinc fingers hit off target pp1192 - 1193
doi:10.1038/nm1011-1192
Full Text | PDF | | Between Bedside and Bench | Top | | | | Moving ahead an HIV vaccine: Use both arms to beat HIV pp1194 - 1195
Bruce D Walker, Rafi Ahmed and Stanley Plotkin
doi:10.1038/nm.2529
Despite remarkable advances in managing disease progression in people infected with HIV, an effective vaccine to prevent infectivity and stop the HIV epidemic remains an unmet clinical need. The genetic variability of the virus and the poor natural immune response[mdash]humoral and cellular[mdash]generated against HIV are hurdles that pose challenges to vaccine development. In 'Bench to Bedside', Bruce Walker, Rafi Ahmed and Stanley Plotkin examine a study in rhesus macaques where a vector-based viral vaccine that elicits a persistent and rapid T effector cell response to SIV antigens results in control of the infection. Although only 50% of the rhesus macaques controlled the infection, this in vivo finding stresses how outdoing the natural immune cellular response can prove effective to clear systemic viruses. But a humoral response will still remain the 'holy grail' to avoid HIV infection and transmission. In 'Bedside to Bench' Tom Hope peruses recent vaccine trials to propose how to best achieve an effective antibody response against HIV by discussing the perks and perils of non-neutralizing versus broadly neutralizing antibodies.
Full Text | PDF | | | | Moving ahead an HIV vaccine: To neutralize or not, a key HIV vaccine question pp1195 - 1197
Thomas J Hope
doi:10.1038/nm.2528
Full Text | PDF | | Research Highlights | Top | | | | Neuroscience: Stressed out? | Metabolism: A lipid link for Parkin | Infection: Slow progress for malaria vaccines | Cancer: Silent cancer suppression | Metabolism: A new [beta] cell model | Genetic disease: GRASPing mutant CFTR | Infection: Hijacking an antibody | New from NPG: Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy | New from NPG: Genome-wide association study identifies five new schizophrenia loci | New from NPG: Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4 | New from NPG: Proteomic and phosphoproteomic comparison of human ES and iPS cells | New from NPG: The antiviral factor APOBEC3G enhances the recognition of HIV-infected primary T cells by natural killer cells | Commentaries | Top | | | | The card players of Caravaggio, Cezanne and Mark Twain: tips for getting lucky in high-stakes research pp1201 - 1205
Joseph L Goldstein
doi:10.1038/nm.2465
Full Text | PDF | | | | Chaperone-assisted protein folding: the path to discovery from a personal perspective pp1206 - 1210
F Ulrich Hartl
doi:10.1038/nm.2467
Full Text | PDF | | | | Protein folding in the cell: an inside story pp1211 - 1216
Arthur L Horwich
doi:10.1038/nm.2468
Full Text | PDF | | | | The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine pp1217 - 1220
Youyou Tu
doi:10.1038/nm.2471
Full Text | PDF | | | | The NIH Clinical Center and the future of clinical research pp1221 - 1223
John I Gallin
doi:10.1038/nm.2466
Full Text | PDF | | Brief Communications | Top | | | | Isolation and in vitro expansion of human colonic stem cells pp1225 - 1227
Peter Jung, Toshiro Sato, Anna Merlos-Suarez, Francisco M Barriga, Mar Iglesias, David Rossell, Herbert Auer, Mercedes Gallardo, Maria A Blasco, Elena Sancho, Hans Clevers and Eduard Batlle
doi:10.1038/nm.2470
This report describes the isolation and in vitro expansion of human colon stem cells from normal tissues. Cells with high levels of the membrane receptor EPHB2 are shown to have characteristics of intestinal stem cells, and the authors optimize culture conditions that allow their in vitro expansion as multipotent cells capable of differentiation into several intestinal lineages.
First paragraph | Full Text | PDF | | | | Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors pp1228 - 1230
Fabrizio Benedetti, Martina Amanzio, Rosalba Rosato and Catherine Blanchard
doi:10.1038/nm.2435
The placebo response involves a perceived effect of a drug that was not really received by the subject. Fabrizio Benedetti and colleagues demonstrate that the placebo response to NSAIDs in reducing pain is mediated by the endocannabinoid system in humans.
First paragraph | Full Text | PDF | | | | Evidence for osteocyte regulation of bone homeostasis through RANKL expression pp1231 - 1234
Tomoki Nakashima, Mikihito Hayashi, Takanobu Fukunaga, Kosaku Kurata, Masatsugu Oh-hora, Jian Q Feng, Lynda F Bonewald, Tatsuhiko Kodama, Anton Wutz, Erwin F Wagner, Josef M Penninger and Hiroshi Takayanagi
doi:10.1038/nm.2452
To date, the dogma in the field has been that RANKL, an essential cytokine in osteoclast maturation, is released by osteoblasts as a way to coordinate bone growth and bone loss during adult bone remodeling. Now, Hiroshi Takayanagi and colleagues, as well as Charles O'Brien and colleagues, have independently found that osteocytes are the predominant source of RANKL in the adult mouse. As RANKL signaling is a key target in treating osteoporosis, these results have potentially important implications for disease management.
First paragraph | Full Text | PDF | | Articles | Top | | | | Matrix-embedded cells control osteoclast formation pp1235 - 1241
Jinhu Xiong, Melda Onal, Robert L Jilka, Robert S Weinstein, Stavros C Manolagas and Charles A O'Brien
doi:10.1038/nm.2448
To date, the dogma in the field has been that RANKL, an essential cytokine in osteoclast maturation, is released by osteoblasts as a way to coordinate bone growth and bone loss during adult bone remodeling. Now, Hiroshi Takayanagi and colleagues, as well as Charles O'Brien and colleagues, have independently found that osteocytes are the predominant source of RANKL in the adult mouse. As RANKL signaling is a key target in treating osteoporosis, these results have potentially important implications for disease management.
Abstract | Full Text | PDF | | | | Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis pp1242 - 1250
Guillaume Bollee, Martin Flamant, Sandra Schordan, Cecile Fligny, Elisabeth Rumpel, Marine Milon, Eric Schordan, Nathalie Sabaa, Sophie Vandermeersch, Ariane Galaup, Anita Rodenas, Ibrahim Casal, Susan W Sunnarborg, David J Salant, Jeffrey B Kopp, David W Threadgill, Susan E Quaggin, Jean-Claude Dussaule, Stephane Germain, Laurent Mesnard, Karlhans Endlich, Claude Boucheix, Xavier Belenfant, Patrice Callard, Nicole Endlich and Pierre-Louis Tharaux
doi:10.1038/nm.2491
Rapidly progressive glomerulonephritis (RPGN) is a form of severe kidney injury that can lead to promptly lethal renal failure. Pierre-Louis Tharaux and colleagues report that HB-EGF is upregulated in RPGN, resulting in activation of EGFR in podocytes and their dysfunction. They further show that genetic loss of expression of HB-EGF or EGFR in a mouse model is protective, whereas pharmacological inhibition of EGFR, even after disease onset, is therapeutic. These results suggest a possible avenue of treatment for this potentially devastating condition.
Abstract | Full Text | PDF
See also: News and Views by Harris | | | | p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis pp1251 - 1260
Jaemin Lee, Cheng Sun, Yingjiang Zhou, Justin Lee, Deniz Gokalp, Hilde Herrema, Sang Won Park, Roger J Davis and Umut Ozcan
doi:10.1038/nm.2449
The activation of stress kinases, such as p38 MAPK, is believed to be detrimental to normal cellular processes. However, Umut Ozcan and his colleagues now show that p38 MAPK is actually beneficial, as in mice it increases the mRNA stability and nuclear localization of Xbp1s, a crucial factor in resolving endoplasmic reticulum stress and improving glucose homeostasis. These results suggest a possible indirect way of targeting XBP1s in the treatment of type 2 diabetes.
Abstract | Full Text | PDF | | | | A recombinant Mycobacterium smegmatis induces potent bactericidal immunity against Mycobacterium tuberculosis pp1261 - 1268
Kari A Sweeney, Dee N Dao, Michael F Goldberg, Tsungda Hsu, Manjunatha M Venkataswamy, Marcela Henao-Tamayo, Diane Ordway, Rani S Sellers, Paras Jain, Bing Chen, Mei Chen, John Kim, Regy Lukose, John Chan, Ian M Orme, Steven A Porcelli and William R Jacobs Jr
doi:10.1038/nm.2420
New vaccine candidates are urgently needed for the control and prevention of Mycobacterium tuberculosis (Mtb) infection. Kari Sweeney and her colleagues now report that an attenuated strain of Mycobacterium smegmatis expressing the esx-3 genes from Mtb induces effective CD4+ T cell dependent immunity against infection with Mtb in mice. The study offers a new avenue for the identification of protective immunogens in Mtb infection and a candidate vaccine platform warranting further study.
Abstract | Full Text | PDF
See also: News and Views by McShane & Williams | | | | Glutamate release by primary brain tumors induces epileptic activity pp1269 - 1274
Susan C Buckingham, Susan L Campbell, Brian R Haas, Vedrana Montana, Stefanie Robel, Toyin Ogunrinu and Harald Sontheimer
doi:10.1038/nm.2453
People with brain cancers called gliomas often have seizures due to secretion of the excitatory neurotransmitter glutamate from the tumor. Now, Harald Sontheimer and his colleagues report that blockade of a cystine-glutamate transporter in tumor cells by an FDA-approved drug can reduce glioma-induced epilepsy in mice.
Abstract | Full Text | PDF
See also: News and Views by Simon & von Lehe | | | | Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155 pp1275 - 1282
Suhwan Chang, Rui-Hong Wang, Keiko Akagi, Kyung-Ae Kim, Betty K Martin, Luca Cavallone, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab): Diana C Haines, Mark Basik, Phuong Mai, Elizabeth Poggi, Claudine Isaacs, Lai M Looi, Kein S Mun, Mark H Greene, Stephen W Byers, Soo H Teo, Chu-Xia Deng and Shyam K Sharan
doi:10.1038/nm.2459
BRCA1 loss of function is considered to promote tumorigenesis through impairment of the protein's role in DNA damage repair. By studying BRCA1 mutations that do not affect this function but still confer cancer predisposition, this report identifies a new function of BRCA1, the repression of miR-155 through modulation of HDAC activity. miR-155 increase correlates with BRCA1 loss or mutation in humans, and it likely to mediate some of the oncogenic effects of BRCA1 deficiency.
Abstract | Full Text | PDF
See also: News and Views by Velkova & Monteiro | | | | Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis pp1283 - 1289
Coralie Dorard, Aurelie de Thonel, Ada Collura, Laetitia Marisa, Magali Svrcek, Anais Lagrange, Gaetan Jego, Kristell Wanherdrick, Anne Laure Joly, Olivier Buhard, Jessica Gobbo, Virginie Penard-Lacronique, Habib Zouali, Emmanuel Tubacher, Sylvain Kirzin, Janick Selves, Gerard Milano, Marie-Christine Etienne-Grimaldi, Leila Bengrine-Lefevre, Christophe Louvet, Christophe Tournigand, Jeremie H Lefevre, Yann Parc, Emmanuel Tiret, Jean-Francois Flejou, Marie-Pierre Gaub, Carmen Garrido and Alex Duval
doi:10.1038/nm.2457
Microsatellite instability (MSI) due to alterations in DNA repair genes leads to carcinogenesis, but it also correlates with better prognosis and therapy response. Little is known of the contribution of altered noncoding sequences to MSI tumorigenesis. This report identifies a deletion in an MSI intronic region leading to the expression of a truncated chaperone, which shows dominant-negative effects on its wild-type counterpart. Acting as an endogenous inhibitor of a protumorigenic chaperone, the expression of the truncated variant associates with better prognosis in humans and may contribute to the overall limited malignancy of MSI tumors.
Abstract | Full Text | PDF
See also: News and Views by Chan | | | | A human memory T cell subset with stem cell-like properties pp1290 - 1297
Luca Gattinoni, Enrico Lugli, Yun Ji, Zoltan Pos, Chrystal M Paulos, Maire F Quigley, Jorge R Almeida, Emma Gostick, Zhiya Yu, Carmine Carpenito, Ena Wang, Daniel C Douek, David A Price, Carl H June, Francesco M Marincola, Mario Roederer and Nicholas P Restifo
doi:10.1038/nm.2446
Whether there exists a human memory T cell population with stem cell-like properties of self-renewal and multipotency is under active investigation. Here Gattinoni et al. characterize a subset of human T cells that phenotypically resemble naive T cells yet have properties associated with memory T cells. These T cells show enhanced ability to self renew and to give rise to differentiated memory cell subsets, suggesting a stem cell-like functionality.
Abstract | Full Text | PDF
See also: News and Views by Sallusto & Lanzavecchia | | Letters | Top | | | | Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch repair deficiency and drug resistance in human leukemia cells pp1298 - 1303
Barthelemy Diouf, Qing Cheng, Natalia F Krynetskaia, Wenjian Yang, Meyling Cheok, Deqing Pei, Yiping Fan, Cheng Cheng, Evgeny Y Krynetskiy, Hui Geng, Siying Chen, William E Thierfelder, Charles G Mullighan, James R Downing, Peggy Hsieh, Ching-Hon Pui, Mary V Relling and William E Evans
doi:10.1038/nm.2430
Loss of mismatch repair (MMR) genes is associated with poor cancer prognosis and has been reported to occur through genetic alterations that directly affect the expression of MMR genes such as MSH2. This report identifies a subset of leukemia patients with reduced levels of MSH2 protein but without alterations in the MSH2 gene, and it identifies concurrent deletions in regulators of MSH2 stability as potential contributors to the MSH2 deficiency and associated drug resistance in this and other cancers.
First paragraph | Full Text | PDF | | | | The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension pp1304 - 1309
Ewout J Hoorn, Stephen B Walsh, James A McCormick, Antje Furstenberg, Chao-Ling Yang, Tom Roeschel, Alexander Paliege, Alexander J Howie, James Conley, Sebastian Bachmann, Robert J Unwin and David H Ellison
doi:10.1038/nm.2497
Calcineurin inhibitors, such as tacrolimus, are widely used immunosuppressive agents, but they can cause hypertension. In studies of tacrolimus-treated mice, the authors show that hypertension is due to activation of the sodium chloride transporter NCC in the kidney, causing sodium retention. They found that NCC activation also occurred in kidney transplant recipients receiving tacrolimus. The authors suggest that thiazide diuretics, which are NCC inhibitors, might counteract the hypertensive effects of this class of immunosuppressants.
First paragraph | Full Text | PDF | | | | A Staphylococcus aureus pore-forming toxin subverts the activity of ADAM10 to cause lethal infection in mice pp1310 - 1314
Ichiro Inoshima, Naoko Inoshima, Georgia A Wilke, Michael E Powers, Karen M Frank, Yang Wang and Juliane Bubeck Wardenburg
doi:10.1038/nm.2451
Staphylococcus aureus produces pore-forming toxins, such as [alpha]-hemolysin, that damage epithelial cell layers, causing disease. In this issue, Inoshima et al. report that the cellular receptor for [alpha]-hemolysin[mdash]the metalloprotease ADAM10[mdash]is essential for lethal pneumonia caused by S. aureus infection in mice. The authors suggest that the combined effect of [alpha]-hemolysin on pore formation and in activating ADAM10 cleavage of the adherens junction protein E-cadherin disrupts the barrier function of the lung epithelium.
First paragraph | Full Text | PDF | | Technical Report | Top | | | | Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-[alpha] targeting: first in-human results pp1315 - 1319
Gooitzen M van Dam, George Themelis, Lucia M A Crane, Niels J Harlaar, Rick G Pleijhuis, Wendy Kelder, Athanasios Sarantopoulos, Johannes S de Jong, Henriette J G Arts, Ate G J van der Zee, Joost Bart, Philip S Low and Vasilis Ntziachristos
doi:10.1038/nm.2472
The prognosis for patients with advanced stage ovarian cancer is poor. Here, Gooitzen van Dam and colleagues demonstrate the first human application of a tumor-specific intraoperative fluorescence imaging methodology using a folate receptor-[alpha] (FR-[alpha])-targeted fluorescent agent that exploits the overexpression of FR-[alpha] in the majority of epithelial ovarian cancers. It is hoped this approach may lead to improved intraoperative staging and more radical cytoreductive surgery.
Abstract | Full Text | PDF | | Corrigenda | Top | | | | Corrigendum: Peroxisome proliferation-associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity p1320
Sabrina Diano, Zhong-Wu Liu, Jin Kwon Jeong, Marcelo O Dietrich, Hai-Bin Ruan, Esther Kim, Shigetomo Suyama, Kaitlin Kelly, Erika Gyengesi, Jack L Arbiser, Denise D Belsham, David A Sarruf, Michael W Schwartz, Anton M Bennett, Marya Shanabrough, Charles V Mobbs, Xiaoyong Yang, Xiao-Bing Gao and Tamas L Horvath
doi:10.1038/nm1011-1320a
Full Text | PDF | | | | Corrigendum: Pharmacologic inactivation of kinase suppressor of ras-1 abrogates Ras-mediated pancreatic cancer p1320
H Rosie Xing, Carlos Cordon-Cardo, Xinzhu Deng, William Tong, Luis Campodonico, Zvi Fuks and Richard Kolesnick
doi:10.1038/nm1011-1320b
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