tbuckley/cabot-search huggingface dataset:
Abstract 2828: miR-19a-3p inhibits breast carcinoma metastasis via reversing M2 phenotype of TAMs.
Authors: Jian Yang, Na Li, Zhuhong Zhang, Qin Si, Chong Chen, Yan Liu, Ralph A. Reisfeld, Peiqing Sun, Dwayne Stupack, Rong Xiang, Yunping Luo
Journal: Cancer Research (2013)

Abstract Tumor-associated macrophages (TAMs), most of which exhibit M2 phenotype, function as immunosuppressive cells in tumor microenvironment (TME). Polarization of TAMs from a pro-immune (M1 like) phenotype to an immune-suppressive (M2-like) phenotype is one of the hallmarks of malignancy, but their molecular basis is still remains unknown. It has been reported that microRNAs are involved in monocyte-macrophage differentiation. In this study, we found that miR-19a-3p, broadly conserved in vertebrate, could reverse the M2 phenotype of RAW macrophage cells. When mouse breast tumor cells such as 4T1, 4TO7 and EMT6 were co-cultured with RAW macrophage cells which over express miR-19a-3p, the invasion capacity was suppressed. Meanwhile, when the conditional medium of RAW cells which were transfected with miR-19a-3p mimic was added into culturing medium of tumor cells, the migration capacity of 4T1 and EMT6 breast cancer cells was inhibited. Moreover, when miR-19a-3p was injected intratumor, consistent with the in vitro experiments, we found that the M2 phenotype of TAMs was suppressed significantly. Although 4T1 xengraft breast tumor growth was not affected by miR-19a-3p, lung metastasis of tumor cells was significantly suppressed. Taken together, our findings indicate that miR-19a-3p is down-regulated in M2 phenotype RAW macrophage and TAMs in TME. The low expression of miR-19a-3p plays an important role in inducing M2 macrophage polarization and promoting migration and invasion capacity and metastasis. Citation Format: Jian Yang, Na Li, Zhuhong Zhang, Qin Si, Chong Chen, Yan Liu, Ralph A. Reisfeld, Peiqing Sun, Dwayne Stupack, Rong Xiang, Yunping Luo. miR-19a-3p inhibits breast carcinoma metastasis via reversing M2 phenotype of TAMs. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2828. doi:10.1158/1538-7445.AM2013-2828 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
The challenge of risk characterization: current practice and future directions.
Authors: G M Gray, J T Cohen, J D Graham
Journal: Environmental Health Perspectives (1993)

Risk characterization is perhaps the most important part of risk assessment. As currently practiced, risk characterizations do not convey the degree of uncertainty in a risk estimate to risk managers, Congress, the press, and the public. Here, we use a framework put forth by an ad hoc study group of industry and government scientists and academics to critique the risk characterizations contained in two risks assessments of gasoline vapor. After discussing the strengths and weaknesses of each assessment's risk characterization, we detail an alternative approach that conveys estimates in the form of a probability distribution. The distributional approach can make use of all relevant scientific data and knowledge, including alternative data sets and all plausible mechanistic theories of carcinogenesis. As a result, this approach facilitates better public health decisions than current risk characterization procedures. We discuss methodological issues, as well as strengths and weaknesses of the distributional approach.
Etoposide Plus Cisplatin With or Without the Combination of 4'-Epidoxorubicin Plus Cyclophosphamide in Treatment of Extensive Small-Cell Lung Cancer: a French Federation of Cancer Institutes Multicenter Phase III Randomized Study
Authors: J.-L. Pujol, J.-P. Daures, A. Riviere, E. Quoix, V. Westeel, X. Quantin, J.-L. Breton, E. Lemarie, M. Poudenx, B. Milleron, D. Moro, D. Debieuvre, T. Le Chevalier
Journal: JNCI Journal of the National Cancer Institute (2001)

The combination of etoposide plus cisplatin (EP) is considered to be standard therapy for small-cell lung cancer (SCLC). To determine whether drug intensification improves survival of patients with extensive SCLC, we compared this treatment with a four-drug regimen containing EP plus cyclophosphamide and 4'-epidoxorubicin (PCDE).In a phase III clinical trial organized by the French Federation of Cancer Institutes, patients were randomly assigned to receive either EP (n = 109; etoposide at a dose of 100 mg/m(2) on days 1-3 plus cisplatin at 100 mg/m(2) on day 2) or PCDE (n = 117; etoposide and cisplatin given as in EP plus cyclophosphamide at 400 mg/m(2) on days 1-3 and 4'-epidoxorubicin at 40 mg/m(2) on day 1) every 4 weeks. Both groups received a total of six cycles. Survival differences were analyzed by Wilcoxon and log-rank tests. Associations of treatment group and putative prognostic variables with survival were tested in the Cox proportional hazards model. Quality of life was assessed from the responses to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (C30, health status and lung cancer module 13). All statistical tests were two-sided.Patients in the PCDE arm had a statistically significant higher frequency of combined complete plus partial responses compared with those in the EP arm (21% plus 55% versus 13% plus 48%, respectively; P =.02 for difference in combined objective responses). Patients in the PCDE arm survived longer than those in the EP arm (1-year survival rate: 40% and 29%, respectively; median survival: 10.5 and 9.3 months, respectively; log-rank P =.0067). In the Cox model, the relative risk of death for patients in the PCDE arm compared with those in the EP arm was 0.70 (95% confidence interval = 0.51 to 0.95); the disease also progressed more slowly in patients in the PCDE arm. Hematologic toxicity was higher in the PCDE arm (22% with documented infections compared with 8% in the EP arm; P =.0038), and the toxicity-related death rate was 9% in the PCDE arm versus 5.5% in the EP arm (P =.22). The global health status showed similar improvement in both arms during treatment.Compared with the EP regimen, the PCDE regimen yielded higher response rates and better survival rates in patients with extensive SCLC without affecting the quality of life of the patients during chemotherapy.
Rationale for Treatment of Hyperglyceridemia
Authors: MARGARET J. ALBRINK
Journal: Annals of Internal Medicine (1963)

Editorial1 October 1963Rationale for Treatment of HyperglyceridemiaMARGARET J. ALBRINK, M.D.MARGARET J. ALBRINK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-59-4-581 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe chairman of the Board of a large and successful industrial organization once told me the secret of his success in the business world. "As soon as I am 60 per cent sure," he said, "I take action. If I had waited until I was 100 per cent sure, I would still be delivering newspapers." He then proceeded to level a tirade of criticism against the members of the medical profession for withholding information from the public on the—to him—poor excuse that they were not 100 per cent sure of how to prevent coronary artery disease. Whether or not he...References1. VASTESSAEGERDELCOURT MMR: The natural history of atherosclerosis. Circulation 26: 841, 1962. CrossrefMedlineGoogle Scholar2. WATERS LL: Studies on the pathogenesis of vascular disease: The effect of a short-term, cholesterol-rich diet on inflammatory lesions of the coronary arteries of dogs. Yale J. Biol. Med. 35: 113, 1962. MedlineGoogle Scholar3. BÖTTCHERBOELSMA-VAN HOUTEROMENY-WACHTERTER HAARWOODFORDVAN GENT CJECCFBCM: Lipid and fatty acid composition of coronary and cerebral arteries at different stages of atherosclerosis. Lancet ii. 1162, 1960. CrossrefGoogle Scholar4. ALBRINK MJ: Triglycerides, lipoproteins and coronary artery disease. Arch. Intern. Med. (Chicago) 109: 345, 1962. CrossrefMedlineGoogle Scholar5. ALBRINKMEIGSMAN MJJWEB: Serum lipids, hypertension and coronary artery disease. Amer. J. Med. 31: 4, 1961. CrossrefMedlineGoogle Scholar6. AHRENSHIRSCHEOETTEFARQUHARSTEIN EHJAJWY: Carbohydrate-induced and fat-induced lipemia. Trans. Ass. Amer. Physicians 74: 134, 1961. MedlineGoogle Scholar7. : Evaluation of serum lipoprotein and cholesterol measurements as predictors of clinical complications of atherosclerosis. Circulation 14: 691, 1956. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MARGARET J. ALBRINK, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byManagement of the Hyperlipidemic PatientChapter 16. AtherosclerosisThe epidemiology of coronary heart diseaseSerum lipid changes following myocardial infarctionSerum Lipids and Glucose Tolerance in Subjects with a Family History of Diabetes MellitusFactors Affecting Lipoprotein Metabolism1 1This work was supported by grants from the Public Health Service (HE 08727-01) and from the Chicago and Illinois Heart Associations.2 2Literature published after June 30, 1964, is not included in this survey. 1 October 1963Volume 59, Issue 4Page: 581-584KeywordsStable coronary artery disease ePublished: 1 December 2008 Issue Published: 1 October 1963 PDF downloadLoading ...
Genomic Alterations Indicate Tumor Origin and Varied Metastatic Potential of Disseminated Cells from Prostate Cancer Patients
Authors: Ilona N. Holcomb, Douglas I. Grove, Martin Kinnunen, Cynthia L. Friedman, Ian S. Gallaher, Todd M. Morgan, Cassandra L. Sather, Jeffrey J. Delrow, Peter S. Nelson, Paul H. Lange, William J. Ellis, Lawrence D. True, Janet M. Young, Li Hsu, Barbara J. Trask, Robert L. Vessella
Journal: Cancer Research (2008)

Abstract Disseminated epithelial cells can be isolated from the bone marrow of a far greater fraction of prostate-cancer patients than the fraction of patients who progress to metastatic disease. To provide a better understanding of these cells, we have characterized their genomic alterations. We first present an array comparative genomic hybridization method capable of detecting genomic changes in the small number of disseminated cells (10–20) that can typically be obtained from bone marrow aspirates of prostate-cancer patients. We show multiple regions of copy-number change, including alterations common in prostate cancer, such as 8p loss, 8q gain, and gain encompassing the androgen-receptor gene on Xq, in the disseminated cell pools from 11 metastatic patients. We found fewer and less striking genomic alterations in the 48 pools of disseminated cells from patients with organ-confined disease. However, we identify changes shared by these samples with their corresponding primary tumors and prostate-cancer alterations reported in the literature, evidence that these cells, like those in advanced disease, are disseminated tumor cells (DTC). We also show that DTCs from patients with advanced and localized disease share several abnormalities, including losses containing cell-adhesion genes and alterations reported to associate with progressive disease. These shared alterations might confer the capability to disseminate or establish secondary disease. Overall, the spectrum of genomic deviations is evidence for metastatic capacity in advanced-disease DTCs and for variation in that capacity in DTCs from localized disease. Our analysis lays the foundation for elucidation of the relationship between DTC genomic alterations and progressive prostate cancer. [Cancer Res 2008;68(14):5599–608]
Cardiac Transplantation for Patients Requiring Mechanical Circulatory Support
Authors: Keith Reemtsma, Ronald Drusin, Richard Edie, David Bregman, William Dobelle, Mark Hardy
Journal: New England Journal of Medicine (1978)

MECHANICAL circulatory support with the intra-aortic balloon has permitted preoperative evaluation of patients in low-output cardiac failure.1 2 3 Such studies show surgically correctable problems in many cases, and temporary assistance with the intra-aortic balloon is maintained until these problems are corrected at operation. In occasional patients, however, studies show that the cardiac disease cannot be corrected by the usual types of cardiac operations, and such patients die when mechanical circulatory support is stopped.In two patients with prior coronary-artery operations and no correctable lesions, we have maintained the circulation with the intra-aortic balloon pump for six days in each while an . . .
The evolution of clinical trials for infant acute lymphoblastic leukemia
Authors: R S Kotecha, N G Gottardo, U R Kees, C H Cole
Journal: Blood Cancer Journal (2014)

Acute lymphoblastic leukemia (ALL) in infants has a significantly inferior outcome in comparison with older children. Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has plateaued in recent years. Historically, infants were treated on risk-adapted childhood ALL protocols. These studies were pivotal in identifying the need for infant-specific protocols, delineating prognostic categories and the requirement for a more unified approach between study groups to overcome limitations in accrual because of low incidence. This subsequently led to the development of collaborative infant-specific studies. Landmark outcomes have included the elimination of cranial radiotherapy following the discovery of intrathecal and high-dose systemic therapy as a superior and effective treatment strategy for central nervous system disease prophylaxis, with improved neurodevelopmental outcome. Universal prospective identification of independent adverse prognostic factors, including presence of a mixed lineage leukemia rearrangement and young age, has established the basis for risk stratification within current trials. The infant-specific trials have defined limits to which conventional chemotherapeutic agents can be intensified to optimize the balance between treatment efficacy and toxicity. Despite variations in therapeutic intensity, there has been no recent improvement in survival due to the equilibrium between relapse and toxicity. Ultimately, to improve the outcome for infants with ALL, key areas still to be addressed include identification and adaptation of novel prognostic markers and innovative therapies, establishing the role of hematopoietic stem cell transplantation in first complete remission, treatment strategies for relapsed/refractory disease and monitoring and timely intervention of late effects in survivors. This would be best achieved through a single unified international trial.
Volume history effects and airway responsiveness in middle-aged and older men. The Normative Aging Study.
Authors: D Sparrow, G T O'Connor, S T Weiss, D DeMolles, R H Ingram
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

In persons with asthma, a deep inhalation (DI) to total lung capacity may lead to bronchoconstriction. The intensity of this effect has been shown to correlate positively with the severity of inflammatory airflow obstruction and the level of methacholine airway responsiveness. The correlates of lung volume history effects in the general population, however, are unknown. We analyzed combined maximal and partial expiratory flow-volume data, pre- and postbronchodilator spirometry data, and methacholine challenge data from 89 middle-aged and older men participating in the Normative Aging Study. The ratio of maximal to partial expiratory flow rates (VM/VP) was significantly correlated with methacholine airway responsiveness, even after adjustment for age and baseline FEV1. The direction of this correlation indicated that men with higher VM/VP ratios (i.e., greater dilator effect of a DI) tended to have greater methacholine airway responsiveness. Subjects with a higher VM/VP ratio also tended to have a greater response to a bronchodilator. These results suggest that, in the general population, airway responsiveness relates in part to airway smooth muscle tone. The correlations suggest that this relatively simple maneuver might play a role in future epidemiologic studies.
A case of stunted development? Existential reasoning is contingent on a developing theory of mind
Authors: E. Margaret Evans, Henry M. Wellman
Journal: Behavioral and Brain Sciences (2006)

Missing from Bering's account of the evolutionary origins of existential reasoning is an explicit developmental framework, one that takes into account community input. If Bering's selectionist explanation was on target then one might predict a unique and relatively robust developmental trajectory, regardless of input. Evidence suggests instead that children's existential reasoning is contingent on their developing theory of mind.
Introducing aptitude testing into medicine.
Authors: M. Gough, J. Bell
Journal: BMJ (1989)

decisions than does measuring plasma total cholesterol alone.The methods for HDL determination need to be standardised, and the unacceptably high coefficient of variation of the methods reduced.Additional measurements of plasma HDL cholesterol concentration will have budgetary implications for departments ofclinical chemistry.In future, measuring HDL subfractions or apoprotein Al may give better estimates of risk than total HDL cholesterol alone.
Treatment of Helicobacter pylori in functional dyspepsia resistant to conventional management: a double blind randomised trial with a six month follow up
Authors: H R Koelz
Journal: Gut (2002)

<b>Background:</b> Previous studies on the treatment of <i>Helicobacter pylori</i> infection in functional dyspepsia have shown little, if any, effect on dyspeptic symptoms. However, whether such treatment might be of benefit in patients resistant to acid inhibitors has not been formally tested. <b>Aim:</b> The present study investigated the effect of <i>H pylori</i> treatment in patients with functional dyspepsia resistant to conventional treatment. <b>Patients:</b> A total of 181 <i>H pylori</i> positive patients with chronic functional dyspepsia who had not responded to a one week antacid run-in and two week double blind antisecretory or placebo treatment were included. <b>Methods:</b> Patients were randomised to two weeks of treatment with omeprazole 40 mg twice daily combined with amoxicillin 1 g twice daily or omeprazole 20 mg once daily alone. The primary outcome variable (“response”) was defined as no need for further therapy or investigations for dyspeptic symptoms 4–6 months after treatment. <b>Results:</b><i>H pylori</i> infection was healed in 10% of patients after omeprazole and in 52% after omeprazole plus amoxicillin. The respective “response” rates were 66% and 62% (NS). <i>H pylori</i> treatment and cure of <i>H pylori</i> infection had no effect on complete resolution of all dyspeptic symptoms, individual symptoms, or various aspects of quality of life. <b>Conclusion:</b> In functional dyspepsia, <i>H pylori</i> treatment and cure of <i>H pylori</i> are no more effective for symptoms over six months than short term acid inhibition. These results do not support treatment of <i>H pylori</i> in functional dyspepsia.
Oedipus in the Stone Age: A Psychoanalytic Study of Masculinization in Papua New Guinea
Authors: Thomas H. Lewis
Journal: JAMA (1989)

Freud used the myth of Oedipus to illustrate the ongoing dynamics of the child's relatedness to the parents and the consequences to character and neurosis. The opposition, envious perhaps but certainly lacking in further creative contribution, concerned itself mincingly with the unlikelihood that the model could be universal. Now that anthropologic and ethnographic studies of the hundreds of isolate cultures in New Guinea have gone on at such a pace, it is possible to review child developmental processes in that extraordinary land. Rearing practices there are, to say the very least, different from those in the model Western family. In Papua the child is not afforded a nuclear two-parent matrix. Instead, pervasive, religion-based male envy, fear, hostility, and avoidance of all things feminine leads men to live fastidiously apart in male lodges, surrounded by mysterious stories and sounds, without or with minimal contact with wives and their own children. Lacking
Epithelial cell binding of group A streptococci by lipoteichoic acid on fimbriae denuded of M protein.
Authors: E H Beachey, I Ofek
Journal: The Journal of Experimental Medicine (1976)

Group A streptococci were treated with various enzymatic and chemical agents in an attempt to dissociate the type-specific M protein from intact surface "fimbriae." Mild peptic digestion at pH 5.8, which was previously shown to extract serologically active M antigen from intact streptococci had little visible effect on the fimbriae even though virtually all of the M protein was removed as demonstrated by (a) increased susceptibility to phagocytosis, (b) lack of opsonic effect of homologous M antibody on the treated streptococci, and (c) loss of HCl-extractable M protein. These fimbriated streptococci which lacked M protein adhered to human oral mucosal cells equally as well as untreated, fimbriated organisms which retained their M protein. Removal of both fimbriae and M protein by digesting organisms with HCL at pH 2.0 at 94 degrees C. or with trypsin abolished their ability to bind mucosal cells. Electron microscopy of streptococci bound to epithelial cells demonstrated fimbriae radiating from the surface of the organisms to the membrane of the epithelial cells. It is apparent, therefore, that the determinants of streptococcal fimbriae involved in resistance to phagocytosis can be dissociated from those involved in epithelial cell binding. These results are consistent with our previous studies which suggested that fatty acids ester linked with glycerol teichoic acid rather than M protein of streptococci binds the organisms to epithelial cells.