A common justification for high cancer drug prices is the sizable research and development (R&D) outlay necessary to bring a drug to the US market. A recent estimate of R&D spending is $2.7 billion (2017 US dollars). However, this analysis lacks transparency and independent replication.
To provide a contemporary estimate of R&D spending to develop cancer drugs.
Analysis of US Securities and Exchange Commission filings for drug companies with no drugs on the US market that received approval by the US Food and Drug Administration for a cancer drug from January 1, 2006, through December 31, 2015. Cumulative R&D spending was estimated from initiation of drug development activity to date of approval. Earnings were also identified from the time of approval to the present. The study was conducted from December 10, 2016, to March 2, 2017.
Median R&D spending on cancer drug development.
Ten companies and drugs were included in this analysis. The 10 companies had a median time to develop a drug of 7.3 years (range, 5.8-15.2 years). Five drugs (50%) received accelerated approval from the US Food and Drug Administration, and 5 (50%) received regular approval. The median cost of drug development was $648.0 million (range, $157.3 million to $1950.8 million). The median cost was $757.4 million (range, $203.6 million to $2601.7 million) for a 7% per annum cost of capital (or opportunity costs) and $793.6 million (range, $219.1 million to $2827.1 million) for a 9% opportunity costs. With a median of 4.0 years (range, 0.8-8.8 years) since approval, the total revenue from sales of these 10 drugs since approval was $67.0 billion compared with total R&D spending of $7.2 billion ($9.1 billion, including 7% opportunity costs).
The cost to develop a cancer drug is $648.0 million, a figure significantly lower than prior estimates. The revenue since approval is substantial (median, $1658.4 million; range, $204.1 million to $22 275.0 million). This analysis provides a transparent estimate of R&D spending on cancer drugs and has implications for the current debate on drug pricing.
", "publicationTitle": "JAMA Internal Medicine", "publisher": "", "place": "", "date": "2017/11/01", "volume": "177", "issue": "11", "section": "", "partNumber": "", "partTitle": "", "pages": "1569-1575", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "JAMA Intern Med", "DOI": "10.1001/jamainternmed.2017.3601", "citationKey": "", "url": "https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2653012", "accessDate": "2018-04-30T16:12:28Z", "PMID": "", "PMCID": "", "ISSN": "2168-6106", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "en", "libraryCatalog": "jamanetwork.com", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2018-04-30T16:12:28Z", "dateModified": "2018-04-30T16:12:28Z" } }, { "key": "YEHUYY8U", "version": 264, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/YEHUYY8U", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/YEHUYY8U", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2350795, "username": "joyyw", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/joyyw", "type": "text/html" } } }, "creatorSummary": "AKHTAR", "parsedDate": "2015-10", "numChildren": 0 }, "data": { "key": "YEHUYY8U", "version": 264, "itemType": "journalArticle", "title": "The Flaws and Human Harms of Animal Experimentation", "creators": [ { "creatorType": "author", "firstName": "AYSHA", "lastName": "AKHTAR" } ], "abstractNote": "Nonhuman animal (“animal”) experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.", "publicationTitle": "Cambridge Quarterly of Healthcare Ethics", "publisher": "", "place": "", "date": "2015-10", "volume": "24", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "407-419", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Camb Q Healthc Ethics", "DOI": "10.1017/S0963180115000079", "citationKey": "", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594046/", "accessDate": "2018-04-30T16:12:10Z", "PMID": "", "PMCID": "", "ISSN": "0963-1801", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "PubMed Central", "callNumber": "", "rights": "", "extra": "PMID: 26364776\nPMCID: PMC4594046", "tags": [], "collections": [], "relations": {}, "dateAdded": "2018-04-30T16:12:10Z", "dateModified": "2018-04-30T16:12:10Z" } }, { "key": "Q5WTSJLH", "version": 261, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/Q5WTSJLH", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/Q5WTSJLH", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2350795, "username": "joyyw", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/joyyw", "type": "text/html" } } }, "creatorSummary": "Sambuy et al.", "parsedDate": "2005-01", "numChildren": 0 }, "data": { "key": "Q5WTSJLH", "version": 261, "itemType": "journalArticle", "title": "The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics", "creators": [ { "creatorType": "author", "firstName": "Y.", "lastName": "Sambuy" }, { "creatorType": "author", "firstName": "I.", "lastName": "De Angelis" }, { "creatorType": "author", "firstName": "G.", "lastName": "Ranaldi" }, { "creatorType": "author", "firstName": "M. L.", "lastName": "Scarino" }, { "creatorType": "author", "firstName": "A.", "lastName": "Stammati" }, { "creatorType": "author", "firstName": "F.", "lastName": "Zucco" } ], "abstractNote": "The human intestinal Caco-2 cell line has been extensively used over the last twenty years as a model of the intestinal barrier. The parental cell line, originally obtained from a human colon adenocarcinoma, undergoes in culture a process of spontaneous differentiation that leads to the formation of a monolayer of cells, expressing several morphological and functional characteristics of the mature enterocyte. Culture-related conditions were shown to influence the expression of these characteristics, in part due to the intrinsic heterogeneity of the parental cell line, leading to selection of sub-populations of cells becoming prominent in the culture. In addition, several clonal cell lines have been isolated from the parental line, exhibiting in general a more homogeneous expression of differentiation traits, while not always expressing all characteristics of the parental line. Culture-related conditions, as well as the different Caco-2 cell lines utilized in different laboratories, often make it extremely difficult to compare results in the literature. This review is aimed at summarizing recent, or previously unreviewed, data from the literature on the effects of culture-related factors and the influence of line sub-types (parental vs. different clonal lines) on the expression of differentiation traits important for the use of Caco-2 cells as a model of the absorptive and defensive properties of the intestinal mucosa. Since the use of Caco-2 cells has grown exponentially in recent years, it is particularly important to highlight these methodological aspects in order to promote the standardization and optimisation of this intestinal model.", "publicationTitle": "Cell Biology and Toxicology", "publisher": "", "place": "", "date": "Jan 2005", "volume": "21", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "1-26", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Cell Biol. Toxicol.", "DOI": "10.1007/s10565-005-0085-6", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0742-2091", "archive": "", "archiveLocation": "", "shortTitle": "The Caco-2 cell line as a model of the intestinal barrier", "language": "eng", "libraryCatalog": "PubMed", "callNumber": "", "rights": "", "extra": "PMID: 15868485", "tags": [ { "tag": "Autocrine Communication", "type": 1 }, { "tag": "Caco-2 Cells", "type": 1 }, { "tag": "Cell Adhesion", "type": 1 }, { "tag": "Cell Count", "type": 1 }, { "tag": "Cell Culture Techniques", "type": 1 }, { "tag": "Cell Differentiation", "type": 1 }, { "tag": "Cell Physiological Phenomena", "type": 1 }, { "tag": "Clone Cells", "type": 1 }, { "tag": "Culture Media", "type": 1 }, { "tag": "Enterocytes", "type": 1 }, { "tag": "Extracellular Matrix", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Intestinal Mucosa", "type": 1 }, { "tag": "Membrane Transport Proteins", "type": 1 }, { "tag": "Paracrine Communication", "type": 1 }, { "tag": "Sucrase-Isomaltase Complex", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2018-04-05T02:15:38Z", "dateModified": "2018-04-05T02:15:38Z" } }, { "key": "Q2AKH8J4", "version": 260, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/Q2AKH8J4", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/Q2AKH8J4", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353756, "username": "jyau1", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jyau1", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "Q2AKH8J4", "version": 260, "itemType": "webpage", "title": "Caco-2 [Caco2] ATCC ® HTB-37™ Homo sapiens Colon Colorectal", "creators": [], "abstractNote": "", "websiteTitle": "", "websiteType": "", "date": "", "publisher": "", "place": "", "DOI": "", "citationKey": "", "url": "https://www.atcc.org/products/all/HTB-37.aspx", "accessDate": "2018-04-04T03:36:59Z", "shortTitle": "", "language": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2018-04-04T03:36:59Z", "dateModified": "2018-04-04T03:36:59Z" } }, { "key": "HPSPSCQN", "version": 259, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/HPSPSCQN", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/HPSPSCQN", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353756, "username": "jyau1", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jyau1", "type": "text/html" } } }, "creatorSummary": "O’Connell et al.", "parsedDate": "2017-10-04", "numChildren": 0 }, "data": { "key": "HPSPSCQN", "version": 259, "itemType": "journalArticle", "title": "Efficacy of Oral Vancomycin, Oral Metronidazole, or IV Metronidazole Prophylaxis at Reducing the Risk of Clostridium difficile Recurrence", "creators": [ { "creatorType": "author", "firstName": "Matthew", "lastName": "O’Connell" }, { "creatorType": "author", "firstName": "Judianne", "lastName": "Slish" }, { "creatorType": "author", "firstName": "Mark", "lastName": "Shelly" } ], "abstractNote": "Background\nSecondary prophylaxis (SP) for Clostridium difficile infection (CDI) with oral vancomycin or oral/IV metronidazole when initiating antibiotics is common, though few studies are available to support this practice. The purpose of this study was to assess the efficacy of prophylaxis within a year of index CDI.\n\nMethods\nThis retrospective chart review looks at subsequent courses of antibiotics and CDI in patients with initial positive CDI testing in 2013–16. A positive CDI test within 90 days of antibiotics was a recurrence. The use of antibiotics for SP was noted, along with other factors associated with CDI relapse. Non-parametric and exact tests were used for univariate analysis. These variables were included in a multivariate proportional hazards model.\n\nResults\nWe found 597 antibiotic episodes in 230 patients. 130 episodes (21.8%) received SP. The difference of recurrence rates with and without antibiotics, 9.2 % vs 10.7%, was not statistically significant. No difference was seen when metronidazole was used, but vancomycin SP reduced the rate to 7.5% (6/80, P = 0.45). Probiotics were associated with a higher rate of recurrence (16.7 vs. 8.9%, P = 0.025). Proton pump inhibitors were also associated with a slightly higher rate of CDI recurrence (13.0% vs. 8.4%). The rate of relapse fell significantly with increasing time since the index case of CDI by logistic regression (P = 0.011). In multivariate regression, relapse was associated with shorter time from index CDI, shorter durations of antibiotics, and the use of probiotics.\n\nConclusion\nThis retrospective study does not support the routine use of metronidazole in subsequent antibiotic courses following CDI. The use of probiotics paradoxically increased the rate of CDI relapse in this study. The limitations of this retrospective study do not eliminate the possibility of utility of vancomycin as prophylaxis, but this requires further evaluation.\n\nDisclosures\n\nAll authors: No reported disclosures.", "publicationTitle": "Open Forum Infectious Diseases", "publisher": "", "place": "", "date": "2017-10-04", "volume": "4", "issue": "Suppl 1", "section": "", "partNumber": "", "partTitle": "", "pages": "S384", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Open Forum Infect Dis", "DOI": "10.1093/ofid/ofx163.952", "citationKey": "", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5631053/", "accessDate": "2018-04-04T03:35:46Z", "PMID": "", "PMCID": "", "ISSN": "2328-8957", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "PubMed Central", "callNumber": "", "rights": "", "extra": "PMID: null\nPMCID: PMC5631053", "tags": [], "collections": [], "relations": {}, "dateAdded": "2018-04-04T03:35:46Z", "dateModified": "2018-04-04T03:35:46Z" } }, { "key": "2T4IYV37", "version": 258, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/2T4IYV37", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/2T4IYV37", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353756, "username": "jyau1", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jyau1", "type": "text/html" } } }, "creatorSummary": "Gray et al.", "parsedDate": "2012-04-09", "numChildren": 0 }, "data": { "key": "2T4IYV37", "version": 258, "itemType": "journalArticle", "title": "Electrodeposition of a biopolymeric hydrogel: potential for one-step protein electroaddressing", "creators": [ { "creatorType": "author", "firstName": "Kelsey M.", "lastName": "Gray" }, { "creatorType": "author", "firstName": "Benjamin D.", "lastName": "Liba" }, { "creatorType": "author", "firstName": "Yifeng", "lastName": "Wang" }, { "creatorType": "author", "firstName": "Yi", "lastName": "Cheng" }, { "creatorType": "author", "firstName": "Gary W.", "lastName": "Rubloff" }, { "creatorType": "author", "firstName": "William E.", "lastName": "Bentley" }, { "creatorType": "author", "firstName": "Alexandra", "lastName": "Montembault" }, { "creatorType": "author", "firstName": "Isabelle", "lastName": "Royaud" }, { "creatorType": "author", "firstName": "Laurent", "lastName": "David" }, { "creatorType": "author", "firstName": "Gregory F.", "lastName": "Payne" } ], "abstractNote": "The electrodeposition of hydrogels provides a programmable means to assemble soft matter for various technological applications. We report an anodic method to deposit hydrogel films of the aminopolysaccharide chitosan. Evidence suggests the deposition mechanism involves the electrolysis of chloride to generate reactive chlorine species (e.g., HOCl) that partially oxidize chitosan to generate aldehydes that can couple covalently with amines (presumably through Schiff base linkages). Chitosan's anodic deposition is controllable spatially and temporally. Consistent with a covalent cross-linking mechanism, the deposited chitosan undergoes repeated swelling/deswelling in response to pH changes. Consistent with a covalent conjugation mechanism, proteins could be codeposited and retained within the chitosan film even after detergent washing. As a proof-of-concept, we electroaddressed glucose oxidase to a side-wall electrode of a microfabricated fluidic channel and demonstrated this enzyme could perform electrochemical biosensing functions. Thus, anodic chitosan deposition provides a reagentless, single-step method to electroaddress a stimuli-responsive and biofunctionalized hydrogel film.", "publicationTitle": "Biomacromolecules", "publisher": "", "place": "", "date": "Apr 09, 2012", "volume": "13", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "1181-1189", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Biomacromolecules", "DOI": "10.1021/bm3001155", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "1526-4602", "archive": "", "archiveLocation": "", "shortTitle": "Electrodeposition of a biopolymeric hydrogel", "language": "eng", "libraryCatalog": "PubMed", "callNumber": "", "rights": "", "extra": "PMID: 22414205", "tags": [ { "tag": "Biopolymers", "type": 1 }, { "tag": "Biosensing Techniques", "type": 1 }, { "tag": "Chitosan", "type": 1 }, { "tag": "Cross-Linking Reagents", "type": 1 }, { "tag": "Electrochemical Techniques", "type": 1 }, { "tag": "Electrodes", "type": 1 }, { "tag": "Electroplating", "type": 1 }, { "tag": "Glucose Oxidase", "type": 1 }, { "tag": "Hydrogels", "type": 1 }, { "tag": "Hydrogen-Ion Concentration", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2018-04-04T03:34:16Z", "dateModified": "2018-04-04T03:34:16Z" } }, { "key": "F7289VJU", "version": 257, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/F7289VJU", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/F7289VJU", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353756, "username": "jyau1", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jyau1", "type": "text/html" } } }, "creatorSummary": "Gray et al.", "parsedDate": "2012-04-09", "numChildren": 0 }, "data": { "key": "F7289VJU", "version": 257, "itemType": "journalArticle", "title": "Electrodeposition of a Biopolymeric Hydrogel: Potential for One-Step Protein Electroaddressing", "creators": [ { "creatorType": "author", "firstName": "Kelsey M.", "lastName": "Gray" }, { "creatorType": "author", "firstName": "Benjamin D.", "lastName": "Liba" }, { "creatorType": "author", "firstName": "Yifeng", "lastName": "Wang" }, { "creatorType": "author", "firstName": "Yi", "lastName": "Cheng" }, { "creatorType": "author", "firstName": "Gary W.", "lastName": "Rubloff" }, { "creatorType": "author", "firstName": "William E.", "lastName": "Bentley" }, { "creatorType": "author", "firstName": "Alexandra", "lastName": "Montembault" }, { "creatorType": "author", "firstName": "Isabelle", "lastName": "Royaud" }, { "creatorType": "author", "firstName": "Laurent", "lastName": "David" }, { "creatorType": "author", "firstName": "Gregory F.", "lastName": "Payne" } ], "abstractNote": "The electrodeposition of hydrogels provides a programmable means to assemble soft matter for various technological applications. We report an anodic method to deposit hydrogel films of the aminopolysaccharide chitosan. Evidence suggests the deposition mechanism involves the electrolysis of chloride to generate reactive chlorine species (e.g., HOCl) that partially oxidize chitosan to generate aldehydes that can couple covalently with amines (presumably through Schiff base linkages). Chitosan’s anodic deposition is controllable spatially and temporally. Consistent with a covalent cross-linking mechanism, the deposited chitosan undergoes repeated swelling/deswelling in response to pH changes. Consistent with a covalent conjugation mechanism, proteins could be codeposited and retained within the chitosan film even after detergent washing. As a proof-of-concept, we electroaddressed glucose oxidase to a side-wall electrode of a microfabricated fluidic channel and demonstrated this enzyme could perform electrochemical biosensing functions. Thus, anodic chitosan deposition provides a reagentless, single-step method to electroaddress a stimuli-responsive and biofunctionalized hydrogel film.", "publicationTitle": "Biomacromolecules", "publisher": "", "place": "", "date": "April 9, 2012", "volume": "13", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "1181-1189", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Biomacromolecules", "DOI": "10.1021/bm3001155", "citationKey": "", "url": "https://doi.org/10.1021/bm3001155", "accessDate": "2018-04-04T03:33:42Z", "PMID": "", "PMCID": "", "ISSN": "1525-7797", "archive": "", "archiveLocation": "", "shortTitle": "Electrodeposition of a Biopolymeric Hydrogel", "language": "", "libraryCatalog": "ACS Publications", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2018-04-04T03:33:42Z", "dateModified": "2018-04-04T03:33:42Z" } }, { "key": "S2H23UY5", "version": 256, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/S2H23UY5", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/S2H23UY5", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353756, "username": "jyau1", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jyau1", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "S2H23UY5", "version": 256, "itemType": "webpage", "title": "Electrodeposition of Carbon Nanotubes Triggered by Cathodic and Anodic Reactions of Dispersants: Materials and Manufacturing Processes: Vol 30, No 6", "creators": [], "abstractNote": "", "websiteTitle": "", "websiteType": "", "date": "", "publisher": "", "place": "", "DOI": "", "citationKey": "", "url": "https://www.tandfonline.com/doi/abs/10.1080/10426914.2014.994771", "accessDate": "2018-04-04T03:32:42Z", "shortTitle": "", "language": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2018-04-04T03:32:42Z", "dateModified": "2018-04-04T03:32:42Z" } }, { "key": "Y9U4MHS2", "version": 255, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/Y9U4MHS2", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/Y9U4MHS2", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353756, "username": "jyau1", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jyau1", "type": "text/html" } } }, "creatorSummary": "Tateda et al.", "parsedDate": "2003-10", "numChildren": 0 }, "data": { "key": "Y9U4MHS2", "version": 255, "itemType": "journalArticle", "title": "The Pseudomonas aeruginosa autoinducer N-3-oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils", "creators": [ { "creatorType": "author", "firstName": "Kazuhiro", "lastName": "Tateda" }, { "creatorType": "author", "firstName": "Yoshikazu", "lastName": "Ishii" }, { "creatorType": "author", "firstName": "Manabu", "lastName": "Horikawa" }, { "creatorType": "author", "firstName": "Tetsuya", "lastName": "Matsumoto" }, { "creatorType": "author", "firstName": "Shinichi", "lastName": "Miyairi" }, { "creatorType": "author", "firstName": "Jean Claude", "lastName": "Pechere" }, { "creatorType": "author", "firstName": "Theodore J.", "lastName": "Standiford" }, { "creatorType": "author", "firstName": "Masaji", "lastName": "Ishiguro" }, { "creatorType": "author", "firstName": "Keizo", "lastName": "Yamaguchi" } ], "abstractNote": "Quorum-sensing systems are critical regulators of the expression of virulence factors of various organisms, including Pseudomonas aeruginosa. Las and Rhl are two major quorum-sensing components, and they are regulated by their corresponding autoinducers, N-3-oxododecanoyl homoserine lactone (3-oxo-C(12)-HSL) and N-butyryl-L-homoserine lactone (C(4)-HSL). Recent progress has demonstrated the potential of quorum-sensing molecules, especially 3-oxo-C(12)-HSL, for modulation of the host immune system. Here we show the specific ability of 3-oxo-C(12)-HSL to induce apoptosis in certain types of cells. When bone marrow-derived macrophages were incubated with synthetic 3-oxo-C(12)-HSL, but when they were incubated not C(4)-HSL, significant loss of viability was observed in a concentration (12 to 50 micro M)- and incubation time (1 to 24 h)-dependent manner. The cytotoxic activity of 3-oxo-C(12)-HSL was also observed in neutrophils and monocytic cell lines U-937 and P388D1 but not in epithelial cell lines CCL-185 and HEp-2. Cells treated with 3-oxo-C(12)-HSL revealed morphological alterations indicative of apoptosis. Acceleration of apoptosis in 3-oxo-C(12)-HSL-treated cells was confirmed by multiple criteria (caspases 3 and 8, histone-associated DNA fragments, phosphatidylserine expression). Structure-activity correlation experiments demonstrated that the fine structure of 3-oxo-C(12)-HSL, the HSL backbone, and side chain length are required for maximal activity. These data suggest that Pseudomonas 3-oxo-C(12)-HSL specifically promotes induction of apoptosis, which may be associated with 3-oxo-C(12)-HSL-induced cytotoxicity in macrophages and neutrophils. Our data suggest that the quorum-sensing molecule 3-oxo-C(12)-HSL has critical roles in the pathogenesis of P. aeruginosa infection, not only in the induction of bacterial virulence factors but also in the modulation of host responses.", "publicationTitle": "Infection and Immunity", "publisher": "", "place": "", "date": "Oct 2003", "volume": "71", "issue": "10", "section": "", "partNumber": "", "partTitle": "", "pages": "5785-5793", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Infect. Immun.", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0019-9567", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "PubMed", "callNumber": "", "rights": "", "extra": "PMID: 14500500\nPMCID: PMC201082", "tags": [ { "tag": "4-Butyrolactone", "type": 1 }, { "tag": "Animals", "type": 1 }, { "tag": "Apoptosis", "type": 1 }, { "tag": "Cell Line", "type": 1 }, { "tag": "Chemokine CCL2", "type": 1 }, { "tag": "Chemokine CXCL2", "type": 1 }, { "tag": "Chemokines", "type": 1 }, { "tag": "Homoserine", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "In Vitro Techniques", "type": 1 }, { "tag": "Macrophages", "type": 1 }, { "tag": "Mice", "type": 1 }, { "tag": "Mice, Inbred C57BL", "type": 1 }, { "tag": "Neutrophils", "type": 1 }, { "tag": "Pseudomonas Infections", "type": 1 }, { "tag": "Pseudomonas aeruginosa", "type": 1 }, { "tag": "U937 Cells", "type": 1 }, { "tag": "Virulence", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2018-04-04T03:10:41Z", "dateModified": "2018-04-04T03:10:41Z" } }, { "key": "3ULPU56Q", "version": 254, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/3ULPU56Q", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/3ULPU56Q", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353756, "username": "jyau1", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jyau1", "type": "text/html" } } }, "creatorSummary": "Smith et al.", "parsedDate": "2002-02", "numChildren": 0 }, "data": { "key": "3ULPU56Q", "version": 254, "itemType": "journalArticle", "title": "The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)homoserine lactone contributes to virulence and induces inflammation in vivo", "creators": [ { "creatorType": "author", "firstName": "Roger S.", "lastName": "Smith" }, { "creatorType": "author", "firstName": "Sarah G.", "lastName": "Harris" }, { "creatorType": "author", "firstName": "Richard", "lastName": "Phipps" }, { "creatorType": "author", "firstName": "Barbara", "lastName": "Iglewski" } ], "abstractNote": "Pseudomonas aeruginosa has two well-characterized quorum-sensing systems, Las and Rhl. These systems are composed of LuxR-type proteins, LasR and RhlR, and two acyl homoserine lactone (AHL) synthases, LasI and RhlI. LasI catalyzes the synthesis of N-(3-oxododecanoyl)homoserine lactone (3O-C12-HSL), whereas RhlI catalyzes the synthesis of N-butyryl-homoserine lactone. There is little known about the importance of AHLs in vivo and what effects these molecules have on eukaryotic cells. In order to understand the role of AHLs in vivo, we first tested the effects that deletions of the synthase genes in P. aeruginosa had on colonization of the lung. We demonstrate that in an adult mouse acute-pneumonia model, deletion of the lasI gene or both the lasI and rhlI genes greatly diminished the ability of P. aeruginosa to colonize the lung. To determine whether AHLs have a direct effect on the host, we examined the effects of 3O-C12-HSL injected into the skin of mice. In this model, 3O-C(12)-HSL stimulated a significant induction of mRNAs for the cytokines interleukin-1alpha (IL-1alpha) and IL-6 and the chemokines macrophage inflammatory protein 2 (MIP-2), monocyte chemotactic protein 1, MIP-1beta, inducible protein 10, and T-cell activation gene 3. Additionally, dermal injections of 3O-C12-HSL also induced cyclooxygenase 2 (Cox-2) expression. The Cox-2 enzyme is important for the conversion of arachidonic acid to prostaglandins and is associated with edema, inflammatory infiltrate, fever, and pain. We also demonstrate that 3O-C12-HSL activates T cells to produce the inflammatory cytokine gamma interferon and therefore potentially promotes a Th1 environment. Induction of these inflammatory mediators in vivo is potentially responsible for the significant influx of white blood cells and subsequent tissue destruction associated with 3O-C12-HSL dermal injections. Therefore, the quorum-sensing systems of P. aeruginosa contribute to its pathogenesis both by regulating expression of virulence factors (exoenzymes and toxins) and by inducing inflammation.", "publicationTitle": "Journal of Bacteriology", "publisher": "", "place": "", "date": "Feb 2002", "volume": "184", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "1132-1139", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J. Bacteriol.", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0021-9193", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "PubMed", "callNumber": "", "rights": "", "extra": "PMID: 11807074\nPMCID: PMC134808", "tags": [ { "tag": "4-Butyrolactone", "type": 1 }, { "tag": "Animals", "type": 1 }, { "tag": "Cells, Cultured", "type": 1 }, { "tag": "Chemokines", "type": 1 }, { "tag": "Cyclooxygenase 2", "type": 1 }, { "tag": "Cytokines", "type": 1 }, { "tag": "Homoserine", "type": 1 }, { "tag": "Immunophenotyping", "type": 1 }, { "tag": "Isoenzymes", "type": 1 }, { "tag": "Keratinocytes", "type": 1 }, { "tag": "Lung", "type": 1 }, { "tag": "Mice", "type": 1 }, { "tag": "Mice, Inbred C57BL", "type": 1 }, { "tag": "NF-kappa B", "type": 1 }, { "tag": "Prostaglandin-Endoperoxide Synthases", "type": 1 }, { "tag": "Pseudomonas aeruginosa", "type": 1 }, { "tag": "Skin", "type": 1 }, { "tag": "T-Lymphocytes", "type": 1 }, { "tag": "Th1 Cells", "type": 1 }, { "tag": "Virulence", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2018-04-04T03:09:45Z", "dateModified": "2018-04-04T03:09:45Z" } }, { "key": "CFV7P9G9", "version": 253, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/CFV7P9G9", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/CFV7P9G9", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353756, "username": "jyau1", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jyau1", "type": "text/html" } } }, "creatorSummary": "Williams et al.", "parsedDate": "2004-04", "numChildren": 0 }, "data": { "key": "CFV7P9G9", "version": 253, "itemType": "journalArticle", "title": "Pseudomonas aeruginosa autoinducer enters and functions in mammalian cells", "creators": [ { "creatorType": "author", "firstName": "Simon C.", "lastName": "Williams" }, { "creatorType": "author", "firstName": "Erin K.", "lastName": "Patterson" }, { "creatorType": "author", "firstName": "Nancy L.", "lastName": "Carty" }, { "creatorType": "author", "firstName": "John A.", "lastName": "Griswold" }, { "creatorType": "author", "firstName": "Abdul N.", "lastName": "Hamood" }, { "creatorType": "author", "firstName": "Kendra P.", "lastName": "Rumbaugh" } ], "abstractNote": "Quorum sensing (QS) is a cell density-dependent signaling mechanism used by many bacteria to control gene expression. Several recent reports indicate that the signaling molecules (autoinducers) that mediate QS in Pseudomonas aeruginosa may also modulate gene expression in host cells; however, the mechanisms are largely unknown. Here we show that two P. aeruginosa autoinducers, N-3-oxododecanoyl-homoserine lactone and N-butyryl-homoserine lactone, can both enter eukaryotic cells and activate artificial chimeric transcription factors based on their cognate transcriptional activators, LasR and RhlR, respectively. The autoinducers promoted nuclear localization of chimeric proteins containing the full LasR or RhlR coding region, and the LasR-based proteins were capable of activating transcription of a LasR-dependent luciferase gene. Responsiveness to autoinducer required the N-terminal autoinducer-binding domains of LasR and RhlR. Truncated proteins consisting of only the C-terminal helix-turn-helix DNA-binding domains of both proteins attached to a nuclear localization signal efficiently translocated to the nucleus in the absence of autoinducer, and truncated LasR-based proteins functioned as constitutively active transcription factors. Chimeric LasR proteins were only activated by their cognate autoinducer ligand and not by N-butyryl-L-homoserine lactone. These data provide evidence that autoinducer molecules from human pathogens can enter mammalian cells and suggest that autoinducers may influence gene expression in host cells by interacting with and activating as-yet-unidentified endogenous proteins.", "publicationTitle": "Journal of Bacteriology", "publisher": "", "place": "", "date": "Apr 2004", "volume": "186", "issue": "8", "section": "", "partNumber": "", "partTitle": "", "pages": "2281-2287", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J. Bacteriol.", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0021-9193", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "PubMed", "callNumber": "", "rights": "", "extra": "PMID: 15060029\nPMCID: PMC412166", "tags": [ { "tag": "4-Butyrolactone", "type": 1 }, { "tag": "Animals", "type": 1 }, { "tag": "Bacterial Proteins", "type": 1 }, { "tag": "COS Cells", "type": 1 }, { "tag": "Cell Nucleus", "type": 1 }, { "tag": "Cercopithecus aethiops", "type": 1 }, { "tag": "DNA-Binding Proteins", "type": 1 }, { "tag": "Gene Expression Regulation, Bacterial", "type": 1 }, { "tag": "Homoserine", "type": 1 }, { "tag": "Promoter Regions, Genetic", "type": 1 }, { "tag": "Pseudomonas aeruginosa", "type": 1 }, { "tag": "Recombinant Fusion Proteins", "type": 1 }, { "tag": "Signal Transduction", "type": 1 }, { "tag": "Trans-Activators", "type": 1 }, { "tag": "Transcription Factors", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2018-04-04T03:08:40Z", "dateModified": "2018-04-04T03:08:40Z" } }, { "key": "8IV8YHQ4", "version": 252, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/8IV8YHQ4", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/8IV8YHQ4", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353756, "username": "jyau1", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jyau1", "type": "text/html" } } }, "creatorSummary": "Hidalgo et al.", "parsedDate": "1989-03", "numChildren": 0 }, "data": { "key": "8IV8YHQ4", "version": 252, "itemType": "journalArticle", "title": "Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability", "creators": [ { "creatorType": "author", "firstName": "I. J.", "lastName": "Hidalgo" }, { "creatorType": "author", "firstName": "T. J.", "lastName": "Raub" }, { "creatorType": "author", "firstName": "R. T.", "lastName": "Borchardt" } ], "abstractNote": "Caco-2 cells develop morphologic characteristics of normal enterocytes when grown on plastic dishes or nitrocellulose filters. The purpose of this study was to determine whether Caco-2 cells undergo similar differentiation when grown on Transwell polycarbonate membranes, and to study the suitability of Caco-2 monolayers as an intestinal epithelial transport model system. Transepithelial electrical resistance values after confluence were 173.5 omega.cm2 and remained unchanged through day 17. Permeabilities to the water-soluble fluid-phase markers that do not permeate the membrane, Lucifer yellow CH, [14C]inulin, [14C]polyethylene glycol, and [3H] dextran were less than 0.25% of the administered amount per hour after day 10. Qualitative evaluation of uptake and permeability to horseradish peroxidase confirmed the similarity in uptake and barrier properties between this cell system and the small intestinal epithelial layer. We conclude that Caco-2 cells grown on collagen-coated polycarbonate membranes should represent a valuable transport model system for the small intestinal epithelium.", "publicationTitle": "Gastroenterology", "publisher": "", "place": "", "date": "Mar 1989", "volume": "96", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "736-749", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Gastroenterology", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0016-5085", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "PubMed", "callNumber": "", "rights": "", "extra": "PMID: 2914637", "tags": [ { "tag": "Adenocarcinoma", "type": 1 }, { "tag": "Biological Transport", "type": 1 }, { "tag": "Cell Line", "type": 1 }, { "tag": "Cell Membrane Permeability", "type": 1 }, { "tag": "Colonic Neoplasms", "type": 1 }, { "tag": "Culture Media", "type": 1 }, { "tag": "Electric Conductivity", "type": 1 }, { "tag": "Gastrointestinal Motility", "type": 1 }, { "tag": "Horseradish Peroxidase", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "In Vitro Techniques", "type": 1 }, { "tag": "Intestinal Absorption", "type": 1 }, { "tag": "Membranes, Artificial", "type": 1 }, { "tag": "Tumor Cells, Cultured", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2018-04-04T03:03:09Z", "dateModified": "2018-04-04T03:03:09Z" } }, { "key": "KFRZGZU8", "version": 262, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/KFRZGZU8", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/KFRZGZU8", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353745, "username": "ysanth", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/ysanth", "type": "text/html" } } }, "creatorSummary": "Gray et al.", "parsedDate": "2012-04-09", "numChildren": 0 }, "data": { "key": "KFRZGZU8", "version": 262, "itemType": "journalArticle", "title": "Electrodeposition of a Biopolymeric Hydrogel: Potential for One-Step Protein Electroaddressing", "creators": [ { "creatorType": "author", "firstName": "Kelsey M.", "lastName": "Gray" }, { "creatorType": "author", "firstName": "Benjamin D.", "lastName": "Liba" }, { "creatorType": "author", "firstName": "Yifeng", "lastName": "Wang" }, { "creatorType": "author", "firstName": "Yi", "lastName": "Cheng" }, { "creatorType": "author", "firstName": "Gary W.", "lastName": "Rubloff" }, { "creatorType": "author", "firstName": "William E.", "lastName": "Bentley" }, { "creatorType": "author", "firstName": "Alexandra", "lastName": "Montembault" }, { "creatorType": "author", "firstName": "Isabelle", "lastName": "Royaud" }, { "creatorType": "author", "firstName": "Laurent", "lastName": "David" }, { "creatorType": "author", "firstName": "Gregory F.", "lastName": "Payne" } ], "abstractNote": "", "publicationTitle": "Biomacromolecules", "publisher": "", "place": "", "date": "2012-04-09", "volume": "13", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "1181-1189", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1021/bm3001155", "citationKey": "", "url": "http://pubs.acs.org/doi/10.1021/bm3001155", "accessDate": "2018-04-01T21:41:27Z", "PMID": "", "PMCID": "", "ISSN": "1525-7797, 1526-4602", "archive": "", "archiveLocation": "", "shortTitle": "Electrodeposition of a Biopolymeric Hydrogel", "language": "en", "libraryCatalog": "CrossRef", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2018-04-01T21:41:27Z", "dateModified": "2018-04-01T21:41:27Z" } }, { "key": "5F7NKFHI", "version": 247, "library": { "type": 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"joyyw", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/joyyw", "type": "text/html" } } }, "creatorSummary": "Xia and Whitesides", "parsedDate": "1998", "numChildren": 1 }, "data": { "key": "ZX4AV8MQ", "version": 245, "itemType": "journalArticle", "title": "Soft lithography", "creators": [ { "creatorType": "author", "firstName": "Younan", "lastName": "Xia" }, { "creatorType": "author", "firstName": "and George M.", "lastName": "Whitesides" } ], "abstractNote": "Soft lithography represents a non-photolithographic strategy based on selfassembly and replica molding for carrying out micro- and nanofabrication. It provides a convenient, effective, and low-cost method for the formation and manufacturing of micro- and nanostructures. In soft lithography, an elastomeric stamp with patterned relief structures on its surface is used to generate patterns and structures with feature sizes ranging from 30 nm to 100 μm. Five techniques have been demonstrated: microcontact printing (μCP), replica molding (REM), microtransfer molding (μTM), micromolding in capillaries (MIMIC), and solvent-assisted micromolding (SAMIM). In this chapter we discuss the procedures for these techniques and their applications in micro- and nanofabrication, surface chemistry, materials science, optics, MEMS, and microelectronics.", "publicationTitle": "Annual Review of Materials Science", "publisher": "", "place": "", "date": "1998", "volume": "28", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "153-184", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1146/annurev.matsci.28.1.153", "citationKey": "", "url": "http://dx.doi.org/10.1146/annurev.matsci.28.1.153", "accessDate": "2015-09-20T03:30:05Z", "PMID": "", "PMCID": "", "ISSN": "", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "Annual Reviews", "callNumber": "", "rights": "", "extra": "", "tags": [ { "tag": "elastomers", "type": 1 }, { "tag": "microfabrication", "type": 1 }, { "tag": "nanofabrication", "type": 1 }, { "tag": "patterning", "type": 1 }, { "tag": "self-assembled monolayers", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2016-02-12T19:16:07Z", "dateModified": "2016-02-12T21:39:18Z" } }, { "key": "TUJISZGB", "version": 244, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/TUJISZGB", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/TUJISZGB", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2353756, "username": "jyau1", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jyau1", "type": "text/html" } } }, "lastModifiedByUser": { "id": 2350795, "username": "joyyw", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/joyyw", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "TUJISZGB", "version": 244, "itemType": "webpage", "title": "Sterile vancomycin hydrochloride 500 mg USP single dose vial", "creators": [], "abstractNote": "", "websiteTitle": "", "websiteType": "", "date": "", "publisher": "", "place": "", "DOI": "", "citationKey": "", "url": "http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=27810", "accessDate": "2015-11-03T19:36:42Z", "shortTitle": "", "language": "", "rights": "", "extra": "", "tags": [], "collections": [ "JBNDCS57" ], "relations": {}, "dateAdded": "2015-11-03T19:36:42Z", "dateModified": "2016-02-12T21:35:34Z" } }, { "key": "ANQMH99S", "version": 243, "library": { "type": "group", "id": 354539, "name": "Team BioCHIPS", "links": { "alternate": { "href": "https://www.zotero.org/groups/team_biochips", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/354539/items/ANQMH99S", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/team_biochips/items/ANQMH99S", "type": "text/html" } }, "meta": { "createdByUser": { "id": 2350795, "username": "joyyw", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/joyyw", "type": "text/html" } } }, "creatorSummary": "Aslam et al.", "parsedDate": "2005-09", "numChildren": 0 }, "data": { "key": "ANQMH99S", "version": 243, "itemType": "journalArticle", "title": "Treatment of clostridium difficile-associated disease: old therapies and new strategies", "creators": [ { "creatorType": "author", "firstName": "Saima", "lastName": "Aslam" }, { "creatorType": "author", "firstName": "Richard J", "lastName": "Hamill" }, { "creatorType": "author", "firstName": "Daniel M", "lastName": "Musher" } ], "abstractNote": "Summary\nClostridium difficile-associated disease (CDAD) causes substantial morbidity and mortality. The pathogenesis is multifactorial, involving altered bowel flora, production of toxins, and impaired host immunity, often in a nosocomial setting. Current guidelines recommend treatment with metronidazole; vancomycin is a second-line agent because of its potential effect on the hospital environment. We present the data that led to these recommendations and explore other therapeutic options, including antimicrobials, antibody to toxin A, probiotics, and vaccines. Treatment of CDAD has increasingly been associated with failure and recurrence. Recurrent disease may reflect relapse of infection due to the original infecting organism or infection by a new strain. Poor antibody responses to C difficile toxins have a permissive role in recurrent infection. Hospital infection control and pertinent use of antibiotics can limit the spread of CDAD. A vaccine directed against C difficile toxin may eventually offer a solution to the CDAD problem.", "publicationTitle": "The Lancet Infectious Diseases", "publisher": "", "place": "", "date": "September 2005", "volume": "5", "issue": "9", "section": "", "partNumber": "", "partTitle": "", "pages": "549-557", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "The Lancet Infectious Diseases", "DOI": "10.1016/S1473-3099(05)70215-2", "citationKey": "", "url": "http://www.sciencedirect.com/science/article/pii/S1473309905702152", "accessDate": "2015-09-20T12:40:12Z", "PMID": "", "PMCID": "", "ISSN": "1473-3099", "archive": "", "archiveLocation": "", "shortTitle": "Treatment of Clostridium difficile-associated disease", "language": "", "libraryCatalog": "ScienceDirect", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [ "RD25ZPXM" ], "relations": {}, "dateAdded": "2015-09-20T16:30:52Z", "dateModified": "2016-02-12T21:34:23Z" } } ]