Study links legal marijuana to more trips to emergency room

Kim says the study didn’t look at whether those ending up at the emergency room were eating or smoking marijuana products, but he suspects one factor was that people eating a brownie or cookie laces with cannabis “often don’t feel any effect immediately, leading them to eat another edible. Then, they’ve ingested multiple products. So, when the effect finally kicks in, it is much stronger.”

Glob Health Action. 2016 Feb 18;9:28772. doi: 10.3402/gha.v9.28772. eCollection 2016.

Global public health today: connecting the dots.

Lomazzi M1,2, Jenkins C1, Borisch B1,3.

Author information

• 1World Federation of Public Health Associations, c/o Campus Biotech, University of Geneva, Geneva, Switzerland.
• 2Institute of Global Health, c/o Campus Biotech, University of Geneva, Geneva, Switzerland; marta.lomazzi@unige.ch.
• 3Institute of Global Health, c/o Campus Biotech, University of Geneva, Geneva, Switzerland.

Abstract

BACKGROUND:

Global public health today faces new challenges and is impacted by a range of actors from within and outside state boundaries. The diversity of the actors involved has created challenges and a complex environment that requires a new context-tailored global approach. The World Federation of Public Health Associations has embarked on a collaborative consultation with the World Health Organization to encourage a debate on how to adapt public health to its future role in global health.

DESIGN:

A qualitative study was undertaken. High-level stakeholders from leading universities, multilateral organizations, and other institutions worldwide participated in the study. Inductive content analyses were performed.

RESULTS:

Stakeholders underscored that global public health today should tackle the political, commercial, economic, social, and environmental determinants of health and social inequalities. A multisectoral and holistic approach should be guaranteed, engaging public health in broad dialogues and a concerted decision-making process. The connection between neoliberal ideology and public health reforms should be taken into account. The WHO must show leadership and play a supervising and technical role. More and better data are required across many programmatic areas of public health. Resources should be allocated in a sustainable and accountable way. Public health professionals need new skills that should be provided by a collaborative global education system. A common framework context-tailored to influence governments has been evaluated as useful.

CONCLUSIONS:

The study highlighted some of the main public health challenges currently under debate in the global arena, providing interesting ideas. A more inclusive integrated vision of global health in its complexity, shared and advocated for by all stakeholders involved in decision-making processes, is crucial. This vision represents the first step in innovating public health at the global level and should lead to a serious rethinking of education curricula to allow the next generation to engage within political contexts for restructuring global public health.

From Somak Roy and colleagues: Next-Generation Sequencing Informatics

Somak Roy,William A. LaFramboise,Yuri E. Nikiforov,Marina N. Nikiforova,Mark J. Routbort,John Pfeifer,Rakesh Nagarajan,Alexis B. Carter,Liron Pantanowitz, (2016) Next-Generation Sequencing Informatics. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

Next-Generation Sequencing Informatics

Challenges and Strategies for Implementation in a Clinical Environment

Somak Roy, MD; William A. LaFramboise, PhD; Yuri E. Nikiforov, MD, PhD; Marina N. Nikiforova, MD; Mark J. Routbort, MD, PhD; John Pfeifer, MD, PhD; Rakesh Nagarajan, MD, PhD; Alexis B. Carter, MD; Liron Pantanowitz, MD

Reprints: Somak Roy, MD, Department of Pathology, University of Pittsburgh Medical Center, 3477 Euler Way, Rm 7028, Clinical Laboratory Building (CLB), Pittsburgh, PA 15213 (email: roys@upmc.edu).

Context.—Next-generation sequencing (NGS) is revolutionizing the discipline of laboratory medicine, with a deep and direct impact on patient care. Although it empowers clinical laboratories with unprecedented genomic sequencing capability, NGS has brought along obvious and obtrusive informatics challenges. Bioinformatics and clinical informatics are separate disciplines with typically a small degree of overlap, but they have been brought together by the enthusiastic adoption of NGS in clinical laboratories. The result has been a collaborative environment for the development of novel informatics solutions. Sustaining NGS-based testing in a regulated clinical environment requires institutional support to build and maintain a practical, robust, scalable, secure, and cost-effective informatics infrastructure.

Objective.—To discuss the novel NGS informatics challenges facing pathology laboratories today and offer solutions and future developments to address these obstacles.

Data Sources.—The published literature pertaining to NGS informatics was reviewed. The coauthors, experts in the fields of molecular pathology, precision medicine, and pathology informatics, also contributed their experiences.

Conclusion.—The boundary between bioinformatics and clinical informatics has significantly blurred with the introduction of NGS into clinical molecular laboratories. Next-generation sequencing technology and the data derived from these tests, if managed well in the clinical laboratory, will redefine the practice of medicine. In order to sustain this progress, adoption of smart computing technology will be essential. Computational pathologists will be expected to play a major role in rendering diagnostic and theranostic services by leveraging Big Data and modern computing tools.

"Since high blood pressure is the leading cause of stroke, the first line of defense often involves treating that condition."

Stroke Prevention - One, Two, Three

"Since high blood pressure is the leading cause of stroke, the first line of defense often involves treating that condition. Patients may be prescribed any number of medications including diuretics, alpha blockers, beta blockers or ACE inhibitors, just to name a few. Patients with high cholesterol may also take drugs called statins. A small daily dose of baby aspirin to thin the blood and prevent clots helps lower stroke risk."

"...college students who attended religious services were less likely to use alcohol than those who did not attend religious services."

J Relig Health. 2016 Feb 25. [Epub ahead of print]

Assessing Whether Religious Behaviors and Positive and Negative Affect are Associated with Alcohol Use and Abuse Among a Sample of College Students Living in the Midwest.

Carmack CC1, Lewis RK2.

Author information

• 1Department of Psychological, Health and Learning Sciences, College of Education, University of Houston, 491 Farrish Hall, Houston, TX, 77204, USA. ccarmack@central.uh.edu.
• 2Wichita State University, 1845 N. Fairmount, Box 34, Wichita, KS, 67260, USA. rhonda.lewis@wichita.edu.

Abstract

Alcohol use and abuse are a problem on college campuses. Religious behaviors (religious attendance, prayer, and importance) have been shown to be a protective factor against alcohol use among college students. This study examined the role religious behaviors and positive and negative affect had on drinking (alcohol use and alcohol to intoxication). College students (765) completed an online survey. The results showed that college students who attended religious services were less likely to use alcohol than those who did not attend religious services. The results have important implications for college administrators and policy makers. Limitations and future research will be discussed.

Nepal J Epidemiol. 2015 Sep 30;5(3):511-5. doi: 10.3126/nje.v5i3.13609. eCollection 2015.

Failure to Apply for Ethical Approval for Health Studies in Low-Income Countries.

van Teijlingen E, Simkhada P.

Abstract

On too many occasions researchers conduct public health and/or epidemiological studies in low-income countries without the appropriate in-countryethical approval. This article reflects on some of the underlying reasons for not applying for ethical approval. The piece concludes that we need to start by educating our (junior) researchers and research students about the importance of research ethics. We conclude with a number of recommendations for researchers, scientific journal editors and reviewers and ethical committees in high-income countries to bring the message home to researchers that ethical approval should be sought in low-income countries if and when required!

Obesity linked to 'worse memory'

"Hunger hormones play a huge role in how much we eat, but it is already recognised that our minds have a key role too.

People watching TV while they have their dinner have been shown to eat more or feel hungrier sooner.

And those with amnesia will have repeated meals in a short period of time.

Dr Cheke concluded: "It is too early to talk in terms of advice, but we are certainly beginning to observe the mechanisms that obesity perpetuates itself."

US Obesity Rate Surpasses 30 Percent: CDC

The figures, posted on the CDC website, indicate:

• 30.4 percent of Americans are obese — up from 29.8 percent in 2014 (defined as a body mass index of 30 or more).
• More than 45 percent of black females ages 20 and over are obese — compared to nearly 28 percent of white females and more than 33 percent of Hispanic females.
• Nearly 35 percent of black males are obese, compared to about 30 percent of whites and 31 percent of Hispanics.
• For both sexes combined, the prevalence of obesity was highest among adults ages 40–59 (34.9 percent), followed by adults ages 60 and up (30.1 percent), and ages 20–39 (26.7 percent).
• By comparison, in 1997, the prevalence of obesity among adults ages 20 and over was 19.5 percent.

Read more: American Obesity Rate Surpasses 30 Percent: CDC 

Cell Death Differ. 2016 Feb 19. doi: 10.1038/cdd.2015.165. [Epub ahead of print]

Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease.

Chernova T1, Sun XM1, Powley IR1, Galavotti S1, Grosso S1, Murphy FA1, Miles GJ1, Cresswell L2, Antonov AV1, Bennett J3, Nakas A3, Dinsdale D1, Cain K1,Bushell M1, Willis AE1, MacFarlane M1.

Author information

• 1MRC Toxicology Unit, University of Leicester, Leicester, UK.
• 2UHL NHS Trust, Leicester Royal Infirmary, Leicester, UK.
• 3UHL NHS Trust, Glenfield Hospital, Leicester, UK.

Abstract

Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the 'gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies.

No: "Can You Blame Your Weight on Your Spouse?"

Can You Blame Your Weight on Your Spouse?

"In fact, the University of Edinburgh researchers who conducted the study found that, by middle age choices made by couples — including those linked to diet and exercise — have a much greater impact on obesity risk than genetics or lifestyle factors they experienced growing up."


Read more: Is Your Spouse Partly to Blame for Your Weight?

Biol Res. 2016 Feb 20;49(1):11. doi: 10.1186/s40659-016-0070-y.

Neuroethics: the pursuit of transforming medical ethics in scientific ethics.

Figueroa G1.

Author information

• 1Departamento de Psiquiatría, Escuela de Medicina, Universidad de Valparaíso, Valparaíso, Chile. gfigueroacave@gmail.com.

Abstract

Ethical problems resulting from brain research have given rise to a new discipline termed neuroethics, representing a new kind of knowledge capable of discovering the neural basis for universal ethics. The article (1) tries to evaluate the contributions of neuroethics to medical ethics and its suitability to outline the foundations of universal ethics, (2) critically analyses the process of founding this universal ethic. The potential benefits of applying neuroimaging, psychopharmacology and neurotechnology have to be carefully weighed against their potential harm. In view of these questions, an intensive dialogue between neuroscience and the humanities is more necessary than ever.

Joint Pain on the Rise — Obesity May Be the Culprit

"One strong hypothesis for the reason behind these increases is simply the increased prevalence of obesity in the United States. According to the CDC, the prevalence of obesity has been increasing nationally. Nebraska has not had the greatest prevalence of obesity compared to other states — yet it too has seen an increase. And obesity, it is well known, is linked to a myriad of illnesses such as metabolic disorders (gout would likely fall here) as well as type 2 diabetes and worsening of arthritic conditions. It would seem that getting a handle on obesity — finding reliable methods of prevention and cure — would go a long way towards managing  a number of other illnesses and dealing with the inflation of healthcare costs."

'Partner more influential than upbringing' in chances of becoming obese

'Partner more influential than upbringing' in chances of becoming obese

"By middle age, the choices made by couples - including those linked to diet and exercise - will have a much greater impact than the lifestyle they shared with their siblings and parents when growing up, the study found."



Read more: http://www.dailymail.co.uk/wires/pa/article-3456580/Partner-influential-upbringing-chances-obese.html#ixzz40l7hO1vB 
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Forensic Sci Rev. 2016 Jan;28(1):37-66.

International trends in alcohol and drug use among vehicle drivers.

Christophersen AS1,2, Mørland J1, Stewart K3, Gjerde H1.

Author information

• 1Division of Forensic Sciences, Norwegian Institute of Public Health, Oslo, Norway.
• 2Department of International Public Health, Norwegian Institute of Public Health, Oslo, Norway.
• 3Prevention Research Center, Safety and Policy Analysis International, Oakland, CA, USA.

Abstract

Trends in the use of alcohol and drugs among motor vehicle drivers in Australia, Brazil, Norway, Spain, and the United States have been reviewed. Laws, regulations, enforcement, and studies on alcohol and drugs in biological samples from motor vehicle drivers in general road traffic and fatal road traffic crashes (RTCs) are discussed. Roadside surveys showed a reduction of drunk driving over time in the studied countries; however, the pattern varied within and between different countries. The reduction of alcohol use may be related to changes in road traffic laws, public information campaigns, and enforcement, including implementation of random breath testing or sobriety checkpoints. For non-alcohol drugs, the trend in general road traffic is an increase in use. However, drugs were not included in older studies; it is therefore impossible to assess the trends over longer time periods. Data from the studied countries, except Brazil, have shown a significant decrease in fatal RTCs per 100,000 inhabitants over the last decades; from 18.6 to 4.9 in Australia, 14.5 to 2.9 in Norway, 11.1 to 3.6 in Spain, and 19.3 to 10.3 in the United States. The number of alcohol-related fatal RTCs also decreased during the same time period. The proportion of fatal RTCs related to non-alcohol drugs increased, particularly for cannabis and stimulants. A general challenge when comparing alcohol and drug findings in biological samples from several countries is connected to differences in study design, particularly the time period for performing roadside surveys, biological matrix types, drugs included in the analytical program, and the cutoff limits used for evaluation of results. For RTC fatalities, the cases included are based on the police requests for legal autopsyor drug testing, which may introduce a significant selection bias. General comparisons between high-income countries and low- and middle-income countries as well as a discussion of possible future trends are included.

Schoolwork, advocacy place strain on student activists

Students struggle with mental health, academic pressures as they act on social justice responsibilities

"Other students have also seen their academic work impacted by their efforts to advance social justice causes. This past semester, David spent class time on his activist work in order to address a time-sensitive issue. As a result, one of David’s professors lowered his grade because he was distracted in class, he said."

HT:AP

Hum Gene Ther. 2016 Feb;27(2):166-83. doi: 10.1089/hum.2015.144.

Transfer of the Cystic Fibrosis Transmembrane Conductance Regulator to Human Cystic Fibrosis Cells Mediated by Extracellular Vesicles.

Vituret C1,2, Gallay K1, Confort MP1, Ftaich N1, Matei CI3, Archer F1, Ronfort C1, Mornex JF1, Chanson M4, Di Pietro A2, Boulanger P1, Hong SS1,5.

Author information

• 11 Viral Infections & Comparative Pathology, UMR-754 UCBL-INRA-EPHE, Université Lyon 1 , Lyon Cedex 07, France .
• 22 Institut de Biologie et Chimie des Protéines, Unité BMSSI, UMR 5086 CNRS-Université Lyon 1 , Lyon Cedex 07, France .
• 33 Centre Technologique des Microstructures, Université Claude Bernard-Lyon , Villeurbanne, France .
• 44 Département de Physiologie Cellulaire & Métabolisme, Centre Médical Universitaire , Geneva, Switzerland .
• 55 Institut National de la Santé et de la Recherche Médicale , Paris, France .

Abstract

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in a deficiency in chloride channel activity. In this study, extracellular vesicles (EVs), microvesicles, and exosomes were used as vehicles to deliver exogenous CFTR glycoprotein and its encoding mRNA (mRNA(GFP-CFTR)) to CF cells to correct the CFTR chloride channel function. We isolated microvesicles and exosomes from the culture medium of CFTR-positive Calu-3 cells, or from A549 cells transduced with an adenoviral vector overexpressing a GFP-tagged CFTR (GFP-CFTR). Both microvesicles and exosomes had the capacity to package and deliver the GFP-CFTR glycoprotein and mRNA(GFP-CFTR) to target cells in a dose-dependent manner. Homologous versus heterologous EV-to-cell transfer was studied, and it appeared that the cellular uptake of EVs was significantly more efficient in homologous transfer. The incubation of CF15 cells, a nasal epithelial cell line homozygous for the ΔF508 CFTR mutation, with microvesicles or exosomes loaded with GFP-CFTR resulted in the correction of the CFTR function in CF cells in a dose-dependent manner. A time-course analysis of EV-transduced CF cells suggested that CFTR transferred as mature glycoprotein was responsible for the CFTR-associated channel activity detected at early times posttransduction, whereas GFP-CFTR translated from exogenous mRNA(GFP-CFTR) was responsible for the CFTR function at later times. Collectively, this study showed the potential application of microvesicles and exosomes as vectors for CFTR transfer and functional correction of the genetic defect in human CF cells.

All Apple’s writs are belong to US*

"Here’s the key thing to understand about the current situation: It is not about encryption. No part of Judge Pym’s order comes close to requiring Apple to decrypt, assist in decrypting, or weaken the encryption used on the iPhone. Rather, Apple has designed its products with an easily enabled self-destruct feature. That is, they have designed their products to destroy evidence that the government routinely would otherwise have legitimate need for and access to. Judge Pym’s order requires Apple to assist the FBI in disarming the booby traps that Apple designed and distributed."

HT:DF

J Psychoactive Drugs. 2016 Feb 18:1-3. [Epub ahead of print]

Prevention of Youthful Marijuana Use.

Cermak TL1,2,3, Banys P1,2,4,5.

Author information

• 1a Past President , California Society of Addiction Medicine , San Francisco , CA , USA.
• 2b Private Practice, General & Addiction Psychiatry , San Francisco , CA , USA.
• 3c Co-Chair , Youth Education & Prevention Working Group, Lt. Governor's Blue Ribbon Commission on Marijuana Policy , California , USA.
• 4d Clinical Professor of Psychiatry , University of California San Francisco , San Francisco , CA , USA.
• 5e Technical Advisor , General & Addiction Psychiatry , Hanoi , Vietnam.

Abstract

Considerable money and effort have been expended in attempts to prevent drug use by youth, with disappointing results. Too often, prevention programs have singled out youth with simplistic messages of exaggerated risk and the same politically acceptable solution for all-abstinence. Historically, prevention efforts have been less effective by not being soundly based in science and failing also to address adult drug and alcohol use as part of the problem. The Institute of Medicine continuum of care model developed in 1994 offers a framework for a more sophisticated, three-tiered approach to prevention, defined as all services provided prior to a clinical diagnosis of a substance use disorder. By dividing prevention efforts into universal (delivered to broad populations without consideration of individual risk for developing substance use disorder), selected (targeting sub-groups of individuals identified on the basis of characteristics known to create an elevated risk for substance use disorder), and indicated (addressing individuals identified on the basis of manifest risk behaviors), prevention can be better tailored to meet different levels of need. Student Assistance Programs (SAPs) and community coalitions provide examples of how IOM's continuum of care model can be integrated into drug prevention programs for youth.

Is breathing making some of us fat?

"According to the new study, breathing bad air could cause us to get fat by promoting inflammation that in turn triggers a cascade of metabolic events that can cause weight gain. The mice gained weight after just 19 days of being exposed to air pollution."

"There are so many ways to tear down a quarterback that don’t involve a 4-3 blitz, and it’s more vicious than ever before."

'Yeah, but' moments are the new norm for NFL quarterbacks

"There are so many ways to tear down a quarterback that don’t involve a 4-3 blitz, and it’s more vicious than ever before.

That’s the social media age, and Manning is the latest and most unexpected quarterback to get dragged through the retweets. The '80s and '90s would have been a lot more interesting in this environment. Imagine how John Elway would have been toasted on Facebook after refusing to play for the Baltimore Colts. Jim Kelly spurning the Buffalo Bills for the USFL. Dan Marino's party image at Pittsburgh. Joe Montana's relationship with Steve Young."

Biopreserv Biobank. 2016 Feb 18. [Epub ahead of print]

Fundamental Considerations for Biobank Legacy Planning.

Matzke LA1, Fombonne B2, Watson PH1,3, Moore HM2.

Author information

• 11 Department of Pathology and Laboratory Medicine, Office of Biobank Education and Research (OBER), University of British Columbia , Vancouver, British Columbia, Canada .
• 22 Biorepositories and Biospecimen Research Branch, National Cancer Institute , Bethesda, Maryland.
• 33 Tumour Tissue Repository (TTR), BC Cancer Agency, Vancouver Island Centre, Victoria , British Columbia, Canada .

Abstract

Biobanking in its various forms is an activity involving the collection of biospecimens and associated data and their storage for differing lengths of time before use. In some cases, biospecimens are immediately used, but in others, they are stored typically for the term of a specified project or in perpetuity until the materials are used up or declared to be of little scientific value. Legacy planning involves preparing for the phase that follows either biobank closure or a significant change at an operational level. In the case of a classical finite collection, this may be brought about by the completion of the initial scientific goals of a project, a loss of funding, or loss of or change in leadership. Ultimately, this may require making a decision about when and where to transfer materials or whether to destroy them. Because biobanking in its entirety is a complex endeavour, legacy planning touches on biobank operations as well as ethical, legal, financial, and governance parameters. Given the expense and time that goes into setting up and maintaining biobanks, coupled with the ethical imperative to appropriately utilize precious resources donated to research, legacy planning is an activity that every biobanking entity should think about. This article describes some of the fundamental considerations for preparing and executing a legacy plan, and we envisage that this article will facilitate dialogue to help inform best practices and policy development in the future.

But it does: "Obesity fight shouldn’t depend on counting calories"

Opinion

Obesity fight shouldn’t depend on counting calories

Public Health Genomics. 2016 Feb 19. [Epub ahead of print]

Genomics Politics through Space and Time: The Case of Bioinformatics in Brazil.

Bicudo E1.

Author information

• 1Department of Political Economy, King's College London, London, UK.

Abstract

The emergence of scientific disciplines, as well as the policies aimed to steer them, have geographical implications. This becomes visible in areas such as genomics and related fields. In this paper, the relation between scientific evolution, political decisions and geographical configuration is studied. The recent formation of bioinformatics in Brazil is focused on. The study involves an analysis of data collected on the website of CNPq, a funding agency attached to the Ministry of Science and Technology. Furthermore, I conducted fieldwork in four cities, interviewing 15 bioinformaticians. In the history of Brazilian bioinformatics, three periods can be identified. In the first period (1900-1996), bioinformatics was actually absent, but biology research groups were formed which would subsequently explore bioinformatics. The second period (1997-2006) was marked by the emergence of the discipline and geographical concentration of major research groups in the southern part of Brazil. A third period can be pointed to (2007-2014), in which political choices have turned geographical diffusion and institutional equality into a national target. As a consequence of the recent shifts, genomics and bioinformatics researchers have been involved in a debate, some defending the existence of few specialized research and sequencing platforms, whereas others welcoming the constitution of a scientific scenario based on decentralized platforms. I defend an intermediate solution, whereby some places would be selected to be genomics hubs. This would fit the regional diversity of this vast country, in addition to tackling the scientific weaknesses of the northern area.

Br J Cancer. 2016 Feb 18. doi: 10.1038/bjc.2015.470. [Epub ahead of print]

A proteomics-based approach identifies secreted protein acidic and rich in cysteine as a prognostic biomarker in malignant pleural mesothelioma.

Kao SC1,2,3, Kirschner MB1, Cooper WA3,4,5, Tran T4, Burgers S6, Wright C1, Korse T6, van den Broek D6, Edelman J7, Vallely M3,7,8, McCaughan B3,9,Pavlakis N3,10, Clarke S3,10, Molloy MP11, van Zandwijk N1,3, Reid G1,3.

Author information

• 1Asbestos Diseases Research Institute, PO Box 3628, Rhodes, Sydney, NSW2139, Australia.
• 2Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, NSW 2050, Australia.
• 3Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
• 4Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
• 5University of Western Sydney, Sydney, NSW 2150, Australia.
• 6Division of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands.
• 7Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
• 8Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia.
• 9Sydney Cardiothoracic Surgeons, RPAH Medical Centre, Sydney, NSW 2050, Australia.
• 10Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW 2065, Australia.
• 11Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW 2109, Australia.

Abstract

BACKGROUND:

We aimed to identify prognostic blood biomarkers using proteomics-based approaches in malignant pleural mesothelioma (MPM).

METHODS:

Plasma samples from 12 MPM patients were used for exploratory mass spectrometry and ELISA analyses. The significance of secreted protein acidic and rich in cysteine (SPARC) was examined in sera from a Dutch series (n=97). To determine the source of the circulating SPARC, we investigated SPARC expression in MPM tumours and healthy controls, as well as the expression and secretion from cell lines and xenografts.

RESULTS:

Secreted protein acidic and rich in cysteine was identified as a putative prognostic marker in plasma. Validation in the Dutch series showed that the median survival was higher in patients with low SPARC compared with those with high SPARC (19.0 vs 8.8 months; P=0.01). In multivariate analyses, serum SPARC remained as an independent predictor (HR 1.55; P=0.05). In MPM tumour samples, SPARC was present in the tumour cells and stromal fibroblasts. Cellular SPARC expression was higher in 5 out of 7 cell lines compared with two immortalized mesothelial lines. Neither cell lines nor xenograft tumours secreted detectable SPARC.

CONCLUSIONS:

Low circulating SPARC was associated with favourable prognosis. Secreted protein acidic and rich in cysteine was present in both tumour cells and stromal fibroblasts; and our in vitro and in vivo experiments suggest that stromal fibroblasts are a potential source of circulating SPARC.British Journal of Cancer advance online publication,