tbuckley/cabot-search huggingface dataset:
Abstract 4662: Shikonin causes cancer cell death by inducing mitochondrial dysfunction
Authors: Benjamin Wiench, Tolga Eichhorn, Thomas Efferth
Journal: Cancer Research (2012)

Abstract Shikonin, a naturally occurring napthoquinone, has been used in herbal formulations for the treatment of several inflammatory diseases in Traditional Chinese Medicine since decades. In recent studies, shikonin revealed remarkable anticancer activities and thereby is a promising candidate for cancer chemotherapy. However, the underlying cellular mechanisms and targets of shikonin are still unknown. Here, we showed that shikonin indeed exhibits strong cytotoxic effects on a panel of 15 different cancer cell lines also containing multi-drug resistant cells. The strongest effects were obtained on U937 leukemia cells. To better understand the underlying mechanisms, we performed a whole genome expression analysis of these cells after shikonin treatment. Thereby novel molecular key players and genetic networks responsible for the effects of shikonin were identified. Induction of cell cycle arrest, apoptosis and increased levels of reactive oxygen species and DNA damage were revealed as striking cellular effects of shikonin. Furthermore, whole sets of genes responsible for cytoskeletal formation and mitochondrial energy metabolism were deregulated after shikonin treatment. Using cell based assays we showed that shikonin indeed induces G1/S phase cell cycle arrest and caspase 3/7 dependent apoptosis. Furthermore we confirmed the induction of reactive oxygen species and quantified the subsequent DNA damage. In addition shikonin significantly prevents cancer cell migration and cytoskeleton formation by inhibiting the dynamics of the microtubule system. The reason for all this secondary effects was revealed by real-time kinetic uptake experiments based on the intrinsic fluorescence of shikonin. Thereby a rapid cellular uptake and a direct accumulation of the drug in the mitochondria were observed. This caused a breakdown of the mitochondrial membrane potential within the same time range of drug uptake, resulting in a failure of the respiratory chain and the cellular energy production. As the mitochondrial structure and metabolism differs strongly between cancer and normal cells, targeting of mitochondria is a very recent and promising approach in cancer therapy. Our results showed that mitochondria are the primary targets of shikonin in cancer cells and thus we believe that shikonin has the potential in future clinical application. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4662. doi:1538-7445.AM2012-4662
Chlormadinone contraceptive withdrawn.
Authors: L Poller
Journal: BMJ (1970)

wait eight weeks from the time of being diagnosed by bronchoscopy a,s having a lung cancer before being admitted to hospital for thoracotomy.If it had not been for my making a pest of myself by repeated letters and a telephone call, he would probably have waited 10 weeks.In fact, he jumped the queue for admission.Eight to ten weeks is long enough for an operable carcinoma to become inoperable.It is highly unethical for a National Health Service to be organized in such a way that there is a waiting list for cancer of two months' duration.In Manchester the waiting time for admission for treatment for lung cancer is two months; for iatrogenic abortion several days.Whether this is a local or national phenomenon I do not know, but it seems to be a highly unethical state of affairs.-I am, etc.,
Abstract 178: Pre-treatment with histone deacetylase inhibitor HDACI) synergizes the anti-cancer effect of sorafenib in renal cell carcinoma cells
Authors: Dong Eun Kim, Mi Joung Kim, Sejin Jang, Je-Hwan Lee, Jene Choi, Seonggu Ro, Choung-Soo Kim, Jung Jin Hwang
Journal: Cancer Research (2011)

Abstract Background: Renal cell carcinoma (RCC), account for 3% of all adult malignances and 75% of RCCs are clear cell renal cell carcinoma (ccRCC), which are highly vascularised tumors. Although a multi-kinase inhibitor, sorafenib has been used for treatment of advanced renal cell carcinoma, it has limitation such as toxicity and long term resistance. Recently, it was reported that histone deacetylase (HDAC) activity is increased in cancer, which leads to suppression of the genes that are related to tumor suppressor and differentiation. Therefore, histone deacetylase inhibitors (HDACIs) are considered as a new anti-cancer drug. In this study, we evaluated the effect of HDACI on anti-tumor effect of sorafenib in ccRCC cells. Materials and Methods: We used various types of RCC cells including Caki-1(VHL+/+), ACHN (VHL+/+), 786-O (VHL−/−), A498 (VHL−/−), SN12C, TK-10, RXF393, and MDR-over-expressing UO31 cells. We calculated the viability of RCC cells treated with HDACIs (belinostat or vorinostat) alone or in combination with sorafenib using MTS Assay. Combination indexes were determined by CalcuSyn software. We analyzed activation of caspases, and the levels of Mcl-1, Bcl-xl, p-Erk by Western Bolt. Levels of secreted vascular endothelial growth factor (VEGF) were measured by ELISA kit. Results: Mono-treatment with HDACI (belinostat or vorinostat) induced apoptosis via activation of intrinsic and extrinsic pathways in all RCC cells. Moreover, pre-treatment with belinostat or vorinostat synergistically potentiated cell death induced by sorafenib in Caki-1 and 786-O ccRCC cells. The combination treatment activated caspase-8, -3 and -9 and down-regulated Mcl-1, Bcl-xl, phosphorylation of Erk (p-Erk) and secretion of VEGF in Caki-1 and 786-O cells. Conclusions: HDACI alone induced apoptotic cell death in various RCC cells. In addition, combination treatment with HDACIs and sorafenib represented synergistic anti-cancer effect in ccRCC cells, indicating that this combination may be a new therapeutic modality for RCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 178. doi:10.1158/1538-7445.AM2011-178
Novel Primate miRNAs Coevolved with Ancient Target Genes in Germinal Zone-Specific Expression Patterns
Authors: Mary L. Arcila, Marion Betizeau, Xiaolu A. Cambronne, Elmer Guzman, Nathalie Doerflinger, Frantz Bouhallier, Hongjun Zhou, Bian Wu, Neha Rani, Danielle S. Bassett, Ugo Borello, Cyril Huissoud, Richard H. Goodman, Colette Dehay, Kenneth S. Kosik
Journal: Neuron (2014)
Metabolomics as a Novel Approach for Early Diagnosis of Pediatric Septic Shock and Its Mortality
Authors: Beata Mickiewicz, Hans J. Vogel, Hector R. Wong, Brent W. Winston
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Septic shock is a significant cause of morbidity and mortality in the pediatric population. Early recognition of septic shock and appropriate treatment increase survival rate; thus, developing new diagnostic tools may improve patients' outcomes.To determine whether a metabolomics approach could be useful in the diagnosis and prognosis of septic shock in pediatric intensive care unit (PICUs).Serum samples were collected from 60 patients with septic shock, 40 PICU patients with systemic inflammatory response syndrome (not suspected of having an infection), and 40 healthy children. Proton nuclear magnetic resonance spectroscopy spectra were analyzed and quantified using targeted profiling methodology.Multivariate statistical analysis was applied to detect specific patterns in metabolic profiles and to highlight differences between patient samples. Supervised analysis afforded good predictive models and managed to separate patient populations. Some of the metabolite concentrations identified in serum samples changed markedly, indicating their influence on the separation between patient groups. These metabolites represent a composite biopattern of the pediatric metabolic response to septic shock and might be considered as the basis for a biomarker panel for the diagnosis of septic shock and its mortality in PICU.Our results indicate that nuclear magnetic resonance metabolite profiling might serve as a promising approach for the diagnosis and prediction of mortality in septic shock in a pediatric population and that quantitative metabolomics methods can be applied in the clinical evaluations of pediatric septic shock.
IMPROVED DEVICE FOR ILLUMINATING THE OPERATING-ROOM
Authors: WILLARD BARTLETT
Journal: JAMA (1913)

Recently I suggested a focused system of operating-room lighting.<sup>1</sup>The use of six automobile head-lights focused on the operation field, for the past six months, has proved so eminently satisfactory that it has seemed worth while to make the principle more generally useful by applying it to the ordinary street lighting current of 110 volts. This might seem at first thought a most simple matter until one considers that the 6-volt automobile lamp has a vastly shorter filament than the common 110-volt incandescent bulb of like candle-power and offers, for all practical purposes, the "point of light" demanded by a parabolic reflector such as automobile makers employ. The relatively long filament of a standard 110-volt lamp, though coiled as tightly as is consistent with good practice, represents a luminous object about 1 inch in diameter enclosed in a glass bulb 25/16 inches in diameter.
Personalized Estimates of Benefit From Preventive Care Guidelines
Authors: Glen B. Taksler, Melanie Keshner, Angela Fagerlin, Negin Hajizadeh, R. Scott Braithwaite
Journal: Annals of Internal Medicine (2013)

Background: The U.S. Preventive Services Task Force (USPSTF) makes recommendations for 60 distinct clinical services, but clinicians rarely have time to fully evaluate and implement the recommendations. Objective: To complete a proof of concept for prioritization and personalization of USPSTF recommendations, using patient-specific clinical characteristics. Design: Mathematical model. Data Sources: USPSTF recommendations and supporting evidence and National Vital Statistics Reports. Target Population: Nonpregnant adults. Time Horizon: Lifetime. Perspective: Individual. Intervention: USPSTF grade A and B recommendations. Outcome Measures: Personalized gain in life expectancy associated with each recommendation. Results of Base-Case Analysis: Increases in life expectancy varied more than 100-fold across USPSTF recommendations, and the rank order of benefits varied considerably among patients. For an obese man aged 62 years who smoked and had hypercholesterolemia, hypertension, and a family history of colorectal cancer, the model's top 3 recommendations (from most to least gain in life expectancy) were tobacco cessation (adding 2.8 life-years), weight loss (adding 1.6 life-years), and blood pressure control (adding 0.8 life-year). Lower-ranked recommendations were a healthier diet, aspirin use, cholesterol reduction, colonoscopy, screening for abdominal aortic aneurysm, and HIV testing (each adding 0.1 to 0.3 life-years). For a person with the same characteristics plus uncontrolled type 2 diabetes mellitus, the model's top 3 recommendations were diabetes control, tobacco cessation, and weight loss (each adding 1.4 to 1.8 life-years). Results of Sensitivity Analysis: Robust to variation of model inputs and satisfied face validity criteria. Limitation: Expected adherence rates and quality of life were not considered. Conclusion: Models of personalized preventive care may illustrate how magnitude and rank order of benefit associated with preventive guidelines vary across recommendations and patients. These predictions may help clinicians to prioritize USPSTF recommendations at the patient level. Primary Funding Source: New York University School of Medicine. Chinese translation
Red cell morphology at high altitude.
Authors: W H Reinhart, P Bartsch
Journal: BMJ (1986)

stools were managed conservatively and had no sequelae.Only one serious complication occurred in this group, when the battery lodged in a Meckel's diverticulum, causing liquefaction necrosis and perforation.This patient underwent laparotomy and survived.On the basis ofthis information and our own experience we make the three following recommendations.Firstly, with few exceptions, ingestion of button batteries should be treated by observation alone.The obvious and important exception is when the battery is lodged in the oesophagus: this must always be treated as an emergency as oesophageal damage may occur within a few hours.Secondly, a chest radiograph should be obtained, especially if the battery is greater than 15 mm in diameter, as its size is the most important factor in determining whether it will pass beyond the oesophagus.Finally, if a battery that has gone beyond the oesophagus has split symptoms of mercury poisoning may occur and mercury concentrations should be measured.
Surgery for Perforated Duodenal Ulcer
Authors: R. M. Kirk
Journal: BMJ (1968)

In the article “Enhancement of GABA-Activated Membrane Currents in Aged Fischer 344 Rat Basal Forebrain Neurons” (W.H. Griffith and D.A. Murchison), which appeared on pages 2407–2416 in the March 1995 issue, the column headings in Table 1 were switched. The correct column labeling is “Young” on the left and “Aged” to the right.
Safety and efficacy of a new regimen of intravenous recombinant tissue-type plasminogen activator potentially suitable for either prehospital or in-hospital administration
Authors: George R. McKendall, Michael J. Attubato, Thomas M. Drew, Frederick Feit, Barry L. Sharaf, Edward S. Thomas, Sam Teichman, Mary Jane McDonald, David O. Williams
Journal: Journal of the American College of Cardiology (1991)
Treatment of "Bilateral Bundle-Branch Block" with Permanent Pacemakers.
Authors: W. J. Grace
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Treatment of "Bilateral Bundle-Branch Block" with Permanent Pacemakers.W. J. Grace, M.D., F.A.C.P., E. F. Conklin, M.D., S. Giannelli Jr., M.D., H. Mueller, M.D., F.A.C.P., S. M. Ayres, M.D., F.A.C.P.W. J. Grace, M.D., F.A.C.P.Search for more papers by this author, E. F. Conklin, M.D.Search for more papers by this author, S. Giannelli Jr., M.D.Search for more papers by this author, H. Mueller, M.D., F.A.C.P.Search for more papers by this author, S. M. Ayres, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-864_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFifty-four patients exhibiting the electrocardiographic pattern of left axis diviation and right bundle-branch block ("bilateral bundle-branch block") have been treated with permanent transvenous pacemakers at the St. Vincent's Hospital and Medical Center, New York, since August 1967. Thirty-eight of these patients, all followed to death or for a minimum of 18 months, are reported. Thirty-three of the 38 presented with syncope. Four others were resuscitated from cardiac arrest in the emergency room. The average age at implantation was 68 years. Twenty-eight patients were men, 10 women. Ventricular triggered demand pacemakers were used exclusively. There were no complications nor morbidity attending... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: W. J. Grace, M.D., F.A.C.P.; E. F. Conklin, M.D.; S. GiannelliJr., M.D.; H. Mueller, M.D., F.A.C.P.; S. M. Ayres, M.D., F.A.C.P.Affiliations: New York, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTransvenous Pacemakers in Clinical Practice 1 May 1972Volume 76, Issue 5Page: 864-864KeywordsElectrocardiographyEmergency departmentHeartMorbidityPacemakersPatient advocacyRight bundle branch blockSyncope ePublished: 1 December 2008 Issue Published: 1 May 1972 PDF downloadLoading ...
Use of laminar flow and unstirred layer models to predict intestinal absorption in the rat.
Authors: M D Levitt, J M Kneip, D G Levitt
Journal: Journal of Clinical Investigation (1988)

Carbon monoxide (CO) and [14C]warfarin were used to measure the preepithelial diffusion resistance resulting from poor luminal stirring (RL) in the constantly perfused rat jejunum at varying degrees of distension (0.05, 0.1, and 0.2 ml/cm). RL was much greater than epithelial cell resistance, indicating that poor stirring was the limiting factor in absorption and that an appropriate model of stirring should accurately predict absorption. A laminar flow model accurately predicted the absorption rate of both probes at all levels of gut distension, as well as the absorption of glucose when RL was the rate-limiting factor in absorption. In contrast, an unstirred layer model would not have predicted that gut distension would have little influence on absorption, and would have underestimated [14C]warfarin absorption relative to CO. We concluded that in the perfused rat jejunum, laminar flow accurately models luminal stirring and an unstirred layer should be considered to be a unit of resistance in laminar flow, rather than a model of luminal stirring.
Destruction of articular cartilage by alpha2 macroglobulin elastase complexes: role in rheumatoid arthritis
Authors: A. R Moore, A. Appelboam, K. Kawabata, J. A P Da Silva, D. D'Cruz, G. Gowland, D. A Willoughby
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> Neutrophil elastase accounts for the ability of some fresh rheumatoid synovial fluids to degrade cartilage matrix in vitro. The aim of this study was to determine if enzyme activity could result from depletion of synovial fluid inhibitors or protection of the enzyme from inhibition. <h3>METHODS</h3> The ability of synovial fluids to inhibit porcine pancreatic elastase was investigated together with chemical pretreatments capable of inactivating alpha<sub>1</sub> protease inhibitor (α<sub>1</sub>PI) or preventing formation of alpha<sub>2</sub> macroglobulin (α<sub>2</sub>M) elastase complexes. Subsequently, complexes of human neutrophil elastase with α<sub>2</sub>M were prepared and applied to frozen sections of cartilage. Proteoglycan loss was quantified by alcian blue staining and scanning and integrating microdensitometry. Parallel studies were carried out using a low molecular weight chromogenic elastase substrate. The effects of α<sub>1</sub>PI and SF on these systems were investigated. Finally, synovial fluids were subjected to gel filtration and the fractions assayed for elastase activity. High molecular weight fractions were pooled, concentrated, and tested for their ability to degrade cartilage sections. <h3>RESULTS</h3> All synovial fluids reduced the activity of porcine pancreatic elastase, the inhibition mainly being attributable to α<sub>1</sub>PI, whereas remaining activity resulted from complexes of elastase with α<sub>2</sub>M. Complexes of human neutrophil elastase with α<sub>2</sub>M were shown to cause proteoglycan degradation in frozen sections of human articular cartilage. Alpha<sub>1</sub>PI prevented α<sub>2</sub>M elastase complexes from degrading cartilage but not the chromogenic substrate. The data suggested that α<sub>1</sub>PI does not inhibit elastase bound to α<sub>2</sub>M but sterically hinders the complex. However, only one of five synovial fluids was able to completely block the actions of α<sub>2</sub>M elastase complexes against cartilage. Gel filtration of rheumatoid synovial fluids showed elastase and cartilage degrading activity to be associated with fractions that contained α<sub>2</sub>M, and not with fractions expected to contain free enzyme. <h3>CONCLUSIONS</h3> The data suggest that synovial fluid α<sub>2</sub>M elastase complexes can degrade cartilage matrix in rheumatoid arthritis.
SOME OBSERVATIONS OF THE THORACIC DUCT LYMPH AFTER INJECTION OF OIL OF TURPENTINE INTO THE PERITONEAL CAVITY OF THE DOG
Authors: Robert L. Dixon
Journal: The Journal of Experimental Medicine (1912)

Injection of oil of turpentine into the peritoneal cavity of a dog calls forth immediately an exudate of fluid from the surrounding tissues. The amount of fluid reaches the maximum on the third day and has practically disappeared on the fifth day. The cell content of this fluid is very small at first, but increases rapidly. The type of the predominating cells also changes. In the early exudate the small mononuclear cells are numerous and the large mononuclears few. Later the number of large mononuclear cells is increased and ultimately the polymorphonuclear cells preponderate. Various forms of atypical cells also occur. Much of the fluid and many of the cells are removed by way of the thoracic duct. The counts of the cells in the thoracic duct and the estimates based on these indicate that the duct does not remove all of the fluid or cells from the peritoneal cavity. Much fluid is probably taken back directly into the blood, as are many of the cells. Some of the cells make their way to the lymph nodes, while many perhaps undergo complete autolysis in the serous cavity. The polymorphonuclear cells do not enter the thoracic duct in great numbers. Examination of the lymph from the thoracic duct in the case of my dogs showed the types of cells that are usually found there. The variation in small mononuclear cells is so related to the cell content of the peritoneal effusion as to indicate that the supply in the blood is maintained from this source. The form and staining qualities of the cells indicate that many of the small mononuclear cells are returned to the thoracic duct. The ratio of polymorphonuclear cells present in the lymph bears no definite relation to the other features of the process. The transitional cells were increased in number and in their ratio to other cells. The increase in the transitional types accompanies an increase in large mononuclear cells and a decrease in small mononuclears. None of the atypical forms of cells found in the effusion were seen in the lymph. The number of eosinophils is without apparent relation to the other features of the process. No polymorphonuclear cells containing the pigment injected were found in the lymph of the thoracic duct, and the number of mononuclear cells containing pigment was small. Much pigment was deposited in the lymph nodes. Detailed and definite conclusions as to the relation between the cells of the lymph and those of the effusion cannot be arrived at satisfactorily without repeated observations on the same animal. Dr. Warthin examined many of the smears from these cases and frequently controlled the conclusions regarding the various types of cells. Dr. P. F. Morse assisted me frequently with the operative procedures and with the routine counting of the cells.
Synchronous Pulmonary MALT Lymphoma and Pulmonary Adenocarcinoma after Metachronous Gastric MALT Lymphoma and Gastric Adenocarcinoma
Authors: Eiki Ichihara, Masahiro Tabata, Nagio Takigawa, Yumiko Sato, Eisaku Kondo, Motoi Aoe, Katsuyuki Kiura, Mitsune Tanimoto
Journal: Journal of Thoracic Oncology (2008)