tbuckley/cabot-search huggingface dataset:
Abstract 4035: A mitochondrial switch promotes tumor metastasis
Authors: Paolo E. Porporato, Valéry L. Payen, Jhudit Pérez-Escuredo, Pierre Danhier, Olivier Feron, Bernard Gallez, Pierre Sonveaux
Journal: Cancer Research (2014)

Abstract Cancers evolve a subpopulation of tumor cells that metabolically rely on glycolysis uncoupled from oxidative phosphorylation irrespectively of oxygen availability (aerobic glycolysis). Given that most metastases are abnormally avid for glucose (which is the rationale for their clinical detection using FDG-PET) and because clinical data show a positive correlation between lactate production and tumor metastasis, we reasoned that cells performing aerobic glycolysis could constitute a population of metastatic progenitor cells that would remain glycolytic in the blood stream. We found a different metabolic phenotype, though. Indeed, using serial rounds of in vitro selection of highly invasive tumor cells (starting from wild-type SiHa human cervix adenocarcinoma cells) and in vivo selection of supermetastatic tumor cells (starting from B16-F10 mouse melanoma cells), we identified a mitochondrial switch corresponding to an overload of the TCA cycle with preserved mitochondrial functions (including ATP production) but increased mitochondrial superoxide production. The switch provided a metastatic advantage which was phenocopied by moderate OXPHOS inhibition associated with mild mitochondrial superoxide increase. Thus, two different events, OXPHOS overload or moderate OXPHOS inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis; demonstrating the central role of mitochondrial superoxide generation in the pathogenesis of metastasis. Consequently, we report that mitochondria-specific superoxide scavenging (using mitoTEMPO or mitoQ) inhibits metastatic dissemination from primary mouse and human tumors, which opens a new avenue for the therapeutic prevention of tumor metastasis. Citation Format: Paolo E. Porporato, Valéry L. Payen, Jhudit Pérez-Escuredo, Pierre Danhier, Olivier Feron, Bernard Gallez, Pierre Sonveaux. A mitochondrial switch promotes tumor metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4035. doi:10.1158/1538-7445.AM2014-4035
Effect of Poverty on Emotional Symptoms in Children
Authors: Brady Case
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Atrial Fibrillation and Risk of Postoperative Complications—Reply
Authors: Joseph P. Mathew, Manuel L. Fontes, Dennis T. Mangano
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Possible involvement of mast‐cell activation in aspirin provocation of aspirin‐induced asthma
Authors: H. Mita, S. Endoh, M. Kudoh, Y. Kawagishi, M. Kobayashi, M. Taniguchi, K. Akiyama
Journal: Allergy (2001)

Background: Although there is increasing evidence of the importance of cysteinyl leukotrienes (LT) as mediators of aspirin‐induced bronchoconstriction in aspirin‐sensitive asthma, the cellular origin of the LT is not yet clear. Methods: Urinary concentrations of leukotriene E 4 (LTE 4 ), 11‐dehydrothromboxane B 2 , 9α,11β‐prostaglandin F 2 , and N τ ‐methylhistamine were measured during the 24 h following cumulative intravenous administration of increasing doses of lysine aspirin to asthmatic patients. In addition, the urinary concentrations of these metabolites were measured on 5 consecutive days in a patient who suffered an asthma attack after percutaneous administration of nonsteroidal anti‐inflammatory drugs. Results: In aspirin‐induced asthma patients (AIA, n =10), the basal concentration of urinary LTE 4 , but not the other metabolites, was significantly higher than that in aspirin‐tolerant asthma patients (ATA, n =10). After intravenous aspirin provocation, the AIA group showed a 13.1‐fold (geometric mean) increase in excretion of LTE 4 during the first 3 h, and 9α,11β‐prostaglandin F 2 also increased in the AIA group during the first 0–3 h and the 3–6 h collection period. N τ ‐methylhistamine excretion was also increased, but to a lesser degree. Adminis‐tration of aspirin caused significant suppression of 11‐dehydrothromboxane B 2 excretion in both the AIA and ATA groups. When the percentage of maximum increase of each metabolite from the baseline concentrations was compared between the AIA group and the ATA group, a significantly higher increase in excretion of LTE 4 , 9α,11β‐prostaglandin F 2 , and N τ ‐methylhistamine was observed in the AIA group than the ATA group. An increased excretion of LTE 4 and 9α,11β‐prostaglandin F 2 has been detected in a patient who suffered an asthma attack after percutaneous administration of nonsteroidal anti‐inflammatory drugs. Conclusions: Considering that human lung mast cells are capable of producing LTC 4 , prostaglandin D 2 , and histamine, our present results support the concept that mast cells, at least, may participate in the development of aspirin‐induced asthma.
High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase
Authors: Ivan S. Yuhanna, Yan Zhu, Blair E. Cox, Lisa D. Hahner, Sherri Osborne-Lawrence, Ping Lu, Yves L. Marcel, Richard G.W. Anderson, Michael E. Mendelsohn, Helen H. Hobbs, Philip W. Shaul
Journal: Nature Medicine (2001)
The Singapore 5-Fluorouracil Trial
Authors: Melissa H.Y. Wong, Rahat Husain, Bryan C.H. Ang, Gus Gazzard, Paul J. Foster, Hla M. Htoon, Tina T. Wong, Francis T. Oen, Peng T. Khaw, Steve K. Seah, Tin Aung
Journal: Ophthalmology (2013)
ABC of learning and teaching in medicine: Learning and teaching in the clinical environment
Authors: J. Spencer
Journal: BMJ (2003)

Clinical teaching—that is, teaching and learning focused on, and usually directly involving, patients and their problems—lies at the heart of medical education. At undergraduate level, medical schools strive to give students as much clinical exposure as possible; they are also increasingly giving students contact with patients earlier in the course. For postgraduates, “on the job” clinical teaching is the core of their professional development. How can a clinical teacher optimise the teaching and learning opportunities that arise in daily practice? Learning in the clinical environment has many strengths. It is focused on real problems in the context of professional practice. Learners are motivated by its relevance and through active participation. Professional thinking, behaviour, and attitudes are “modelled” by teachers. It is the only setting in which the skills of history taking, physical examination, clinical reasoning, decision making, empathy, and professionalism can be taught and learnt as an integrated whole. Despite these potential strengths, clinical teaching has been much criticised for its variability, lack of intellectual challenge, and haphazard nature. In other words, clinical teaching is an educationally sound approach, all too frequently undermined by problems of implementation. #### Common problems with clinical teaching #### Challenges of clinical teaching
484. Longevity of Expression Following Liposome-Mediated Gene Transfer
Authors: Adrian Vilalta, Michal Margalith, Tom Evans, David C. Kaslow, Peter Hobart
Journal: Molecular Therapy (2004)

Top of pageAbstract
We are testing a number of expression plasmids (pDNA) encoding SARS-CoV antigens to support potential development of a pDNA vaccine against this emerging pathogen. Our constructs are all derived from SARS-CoV Urbani and include the complete coding sequence for the nucleocapsid antigen, the soluble (extracellular) portion of the spike antigen, and two subdomains of the spike antigen termed S1 and S2. The codons used in these constructs were optimized for expression in human cells. These pDNAs were assayed for expression both in vitro and in vivo. Western blots of in vitro transfected cell lysates and culture supernatants were probed with a rabbit polyclonal antibody specific to either spike or nucleocapsid peptides. These assays indicate that the spike antigen is efficiently released from cells in culture whereas the nucleocapsid antigen remains predominately intracellular. All four pDNAs were formulated in either cationic lipid or poloxamer and injected into mouse (50 mg) or rabbit (1 mg) muscle tissue (i.e. 3X @ two week intervals). Sera from pDNA-vaccinated animals will be tested for virus neutralization in vitro. The use of one or more of these pDNA vaccines will be further evaluated for their immunogenicity and safety in animal models.
Abstract 3611: Cardiovascular risk factors and venous thromboembolism: A meta-analysis
Authors: Pieter Kamphuisen, Cecilia Becattini, Timothy Brighton, Rita Selby, Walter Ageno
Journal: Circulation (2007)

Background: The concept that venous thromboembolism (VTE) and atherosclerosis are two distinct entities has recently been challenged. Patients with spontaneous VTE had more asymptomatic carotid atherosclerotic lesions and a higher incidence of cardiovascular disease than patients with VTE secondary to known risk factors and controls. However, no clear relationship between cardiovascular risk factors and VTE has ever been determined. We performed a meta-analysis to assess the potential association between well known cardiovascular risk factors and VTE. Methods: Medline and EMBASE databases were searched to identify studies that evaluated the prevalence of major cardiovascular risk factors in VTE patients and in controls. The studies were selected using a priori defined criteria and each study was reviewed by two authors who abstracted data on study characteristics, study quality and outcomes. Odds Ratio (OR) or weighted mean differences and 95% confidence intervals (CI) were calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated using the I 2 statistic. Results: Twenty-one case-control and cohort studies with a total of 63.552 patients met the inclusion criteria. Compared to controls, the risk of VTE was 2.33 for obesity (95% CI 1.68 –3.24), 1.51 for hypertension (1.23–1.85), 1.42 for diabetes (1.12–1.77), 1.18 for smoking (0.95–1.46), and 1.16 for hypercholesterolemia (0.67–2.02). Weighted mean HDL cholesterol levels were significantly lower in VTE patients compared to controls, whereas no difference was observed in total cholesterol and LDL cholesterol levels. Significant heterogeneity among studies was detected in all subgroups, except for diabetes. Higher quality studies were more homogeneous and, except for hypertension, the significant associations remained unchanged. Discussion: Common cardiovascular risk factors are associated with an increased risk of VTE. This association between VTE and atherothrombosis has obvious clinical implications with respect to screening, risk factor modification and future therapy. Future prospective studies could investigate underlying mechanisms of this two-way relation.
Roles of P2-purinoceptors in the cardiovascular system.
Authors: V Ralevic, G Burnstock
Journal: Circulation (1991)

Characterization of P2-purinoceptor subtypes has facilitated understanding of the many diverse effects produced by purine nucleotides. P2X-Purinoceptors are located on vascular smooth muscle where they mediate vasoconstriction resulting from ATP released as a cotransmitter with noradrenaline from sympathetic nerves. P2Y-Purinoceptors are usually located on the vascular endothelium where they have a role as mediators of vascular relaxation by locally produced ATP. In some vessels, P2Y-purinoceptors are also located on the smooth muscle, perhaps in association with purinergic or sensory nerves, where they can elicit direct relaxation to neuronally released ATP. The net effect of ATP and its analogues on isolated vessels or on vascular beds will be the results of actions mediated by P2X- and P2Y-purinoceptor subtypes, although changes in vascular tone and in integrity of nerves and endothelial cells may alter the balance of the response. Such changes have been observed in diseased states (e.g., atherosclerosis) and may have important implications for the involvement of P2-purinoceptors in, for example, vasospasm. The development of selective and potent antagonists to P2X- and P2Y-purinoceptors has so far remained elusive, and their therapeutic potential can only be guessed.
Preferential potentiation of paclitaxel and doxorubicin cytotoxicity in drug-resistant breast tumor cells by tesmilifene.
Authors: Stacey L. Hembruff, David J. Villeneuve, Amadeo M. Parissenti
Journal: Cancer Research (2006)

5421   A phase III study of anthracycline-naive women with metastatic breast cancer by the National Cancer Institute of Canada Clinical Trials Group (MA.19) revealed that treatment of patients with doxorubicin in combination with N,N-Diethyl-2-[4-(Penylmethyl)Phenoxy]Ethanamine (tesmilifene) was superior to doxorubicin alone in terms of overall survival (P=0.021), with no difference seen in response rate or progression free survival (J. Clin. Oncol. 22: 269-276, 2004). One possible explanation for this observation may be that tesmilifene specifically increases the cytotoxicity of chemotherapy drugs only in rare drug-resistant cells, thus inhibiting the development of drug-resistant tumors over time. To assess this hypothesis, we examined in a clonogenic assay the effect of tesmilifene (at concentrations ranging from 0.1 to 6 μM) on the ability of doxorubicin or paclitaxel to kill wildtype MCF-7 breast tumor cells and isogenic MCF-7 cells resistant to doxorubicin or paclitaxel (MCF-7 DOX  and MCF-7 TAX  cells, respectively). Consistent with the above hypothesis, tesmilifene decreased the concentration at which 50% of MCF-7 TAX  cells were killed by paclitaxel (the IC 50 ) in a dose-dependent manner by as much as 4-fold (at 6 μM tesmilifene), while having little effect or increasing the IC 50  for paclitaxel in wildtype MCF-7 cells, even at the highest concentration of tesmilifene. Cross resistance to doxorubicin in MCF-7 TAX  cells was also reduced in a dose-dependent manner by as much as 4-fold by tesmilifene, while only slightly increasing the IC 50  for doxorubicin in wildtype MCF-7 cells at the highest concentration of tesmilifene. The IC 50  for doxorubicin was decreased by as much as 2.5-fold upon the addition of tesmilifene to MCF-7 DOX  cells (also in a dose-dependent manner), with little change in the IC 50  for doxorubicin in wildtype cells. Since our MCF-7 TAX  cell line overexpresses P-glycoprotein (P-gp), while our MCF-7 DOX  cell line does not, it would appear that the effect of DPPE on the cytotoxicity of chemotherapy drugs in drug-resistant cells is not P-gp-specific, although this may be enhanced in P-gp-expressing cell lines. While accumulation of paclitaxel or doxorubicin was reduced in MCF-7 TAX  and MCF-7 DOX  cells, respectively, tesmilifene (at a 3 μM concentration) had no effect on the uptake of paclitaxel or doxorubicin into MCF-7, MCF-7 TAX , and MCF-7 DOX  cells. Taken together, our data demonstrate that tesmilifene augments the cytotoxicity of paclitaxel and doxorubicin but only in drug-resistant cells through a mechanism unrelated to drug accumulation defects inherent in these cell lines.
EARLY ACCESS TO CARDIAC CATHETERIZATION LABORATORY FOR PATIENTS RESUSCITATED FROM CARDIAC ARREST DUE TO A SHOCKABLE RHYTHM: THE MINNESOTA RESUSCITATION CONSORTIUM TWIN CITIES UNIFIED PROTOCOL
Authors: Santiago Garcia, Brian Mahoney, Ralph Frascone, Gregory Helmer, Charles Lick, Marc Conterato, Kenneth Baran, Bradley Bart, Steven Roh, Carmelo Panetta, Randall Stark, Mark Haughland, Michael Mooney, Demetris Yannopoulos
Journal: Journal of the American College of Cardiology (2014)
Foxp3+ regulatory T cells and related cytokines differentially expressed in plaque vs. guttate psoriasis vulgaris
Authors: K-X. Yan, X. Fang, L. Han, Z-H. Zhang, K-F. Kang, Z-Z. Zheng, Q. Huang
Journal: British Journal of Dermatology (2010)

Journal Article Foxp3+ regulatory T cells and related cytokines differentially expressed in plaque vs. guttate psoriasis vulgaris Get access K‐X. Yan, K‐X. Yan Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai 200040, China Search for other works by this author on: Oxford Academic Google Scholar X. Fang, X. Fang Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai 200040, China Search for other works by this author on: Oxford Academic Google Scholar L. Han, L. Han Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai 200040, China Search for other works by this author on: Oxford Academic Google Scholar Z‐H. Zhang, Z‐H. Zhang Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai 200040, China Search for other works by this author on: Oxford Academic Google Scholar K‐F. Kang, K‐F. Kang Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai 200040, China Search for other works by this author on: Oxford Academic Google Scholar Z‐Z. Zheng, Z‐Z. Zheng Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai 200040, China Search for other works by this author on: Oxford Academic Google Scholar Q. Huang Q. Huang Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai 200040, China Qiong Huang. E‐mail: blueqiong@medmail.com.cn Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 1, 1 July 2010, Pages 48–56, https://doi.org/10.1111/j.1365-2133.2010.09742.x Published: 01 July 2010
Abstract 17674: Cell Damage and Even Death Detected in Peripheral T-Lymphocytes in Patients Undergoing Cardiac Computed Tomographic Angiography
Authors: Patricia Nguyen, Won Hee Lee, Wan Xing Hong, Shijun Hu, Sang-Ging Ong, Jared Churko, Charles Chan, Jia Wang, Michael T Longaker, Mark Hlatky, Dominik Fleischmann, Joseph C Wu
Journal: Circulation (2014)

Background: It is well known that radiation can cause cell damage and even cell death at high doses. Whether a similar albeit less pronounced effect exists at low dose remains unclear.

Objective: The purpose of this study is to determine whether low dose radiation from cardiac computed tomographic angiography (CCTA) is associated with cellular damage.

Methods: Blood was collected from 56 adult patients immediately before and after CCTA. Changes in protein phosphorylation and gene expression were analyzed by quantitative flow cytometry and single cell gene expression profiling, respectively. The presence of cell death was analyzed by flow cytometry in a subset of patients (n=25).

Results: Activation of multiple proteins and genes were detected by quantitative flow cytometry and single cell expression profiling after exposure to ≥25 mSv of radiation in vitro. Similarly, blood collected from patients undergoing CCTA showed increased protein (i.e., H2AX, p53, and ATM) and gene (i.e., p53, BAX, MDM2, CDK4, ATF6, and DDB2) activation. A linear-dose response relationship was found in phosphorylated ATM, CDK4 and DDB2 in vivo. Sixty-eight percent (n=17/25; average % cell death 1.4%±0.9%; n=100,000 events) of patients had evidence of T-lymphocyte death after exposure. Patients with DNA damage (i.e. affected patients) as indicated by phosphorylation of H2AX, ATM and/or p53 had more cell death than those without DNA damage (3.7 vs. 1.09 fold, p=0.005) (Figure 1A). Patients with increased cell death were exposed to higher amounts of radiation (38.5 ± 18.4 mSv vs. 15.1 ± 13.4 mSv, p=0.004). With the exception of two patients, most patients who had significant cell death (i.e., >2 fold) had exposure to at least 20 mSv of radiation (Figure 1B).

Conclusion: Radiation exposure from CCTA activates multiple proteins and genes involved in the DNA damage response pathway. Cell death was detected in over half of the patients although the magnitude was small.

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