tbuckley/cabot-search huggingface dataset:
P4-09-08: Secretory Leukocyte Protease Inhibitor as a Differential Diagnostic Biomarker of Tumor Emboli in Inflammatory Breast Cancer.
Authors: FM Robertson, Z Ye, K Chu, AZ Luo, MC Wright, J Jin, SH Barsky, M Cristofanilli, S Krishnamurthy
Journal: Cancer Research (2011)

Abstract Background: Inflammatory breast cancer (IBC) is the most aggressive and lethal variant of locally advanced breast cancer. Pathologically, IBC is characterized by the presence of nests of cells, defined as tumor emboli, that undergo lymphovascular invasion into the skin and chest wall and represent the metastatic lesion of IBC. Due to the distinct presentation of IBC, it is often misdiagnosed due to a lack of defined biomarkers that are specific for tumor emboli in biopsy samples of IBC patients. To date, the only validated marker that has shown to consistently identify IBC tumor emboli is the surface glycoprotein E-cadherin. Materials and Methods: With the goal of identifying genes specifically expressed by IBC tumor emboli, the present studies performed whole transcriptome analysis of tumor emboli from skin punch biopsy samples from IBC patients and tumor emboli from the Mary-X pre-clinical model of IBC which were isolated using laser capture microdissection. Results: Secretory leukocyte peptidase inhibitor (SLPI) was a gene identified as being highly expressed by tumor emboli. This gene was previously identified as a metastasis related gene, has been reported to be associated with poor prognosis in serous ovarian carcinoma and is implicated in mediating resistance to paclitaxel. Immunofluorescence staining and confocal microscopy revealed that SLPI is a robust marker of tumor emboli in skin punch biopsies from IBC patient and in Mary-X tumor emboli. SLPI differentially delineates between IBC tumor emboli and hair follicles present in the skin, which also stain with E-cadherin. An additional marker, Cytokeratin 15 (CK15), can be used in combination with SLPI to differentially identify the components of the skin that are CK15 positive, and IBC tumor emboli that reside within the skin, which are CK15 negative. Use of podoplanin antibodies, which stain lymphovascular endothelium, demonstrate that IBC tumor emboli that express SLPI protein, are completely encircled within the dermal lymphovasculature. Conclusions: These studies are among the first to identify SLPI as a potential biomarker of tumor emboli in skin punch biopsy samples from IBC patients and in pre-clinical models of IBC. Studies are ongoing to establish the molecular function and role of SLPI in mediating the survival and invasion of IBC tumor emboli. Collectively, these studies are the first to identify SLPI as a potential biomarker of IBC tumor emboli in skin punch biopsy samples. In addition to serving as a potential biomarker of tumor emboli, SLPI may also serve as a therapeutic target for development of approaches to eradicate IBC tumor emboli. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-08.
DOES THE HIGHER DOSE OF BETA-BLOCKER THERAPY GUARANTEE THE BETTER OUTCOME IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION?
Authors: Se Yong Jang, Nam Kyun Kim, Chang-Yeon Kim, Jang Hoon Lee, Myung Hwan Bae, Dong Heon Yang, Hun Sik Park, Yongkeun Cho, Shung Chull Chae
Journal: Journal of the American College of Cardiology (2016)
MULTIVESSEL PCI FOR STEMI DURING INDEX HOSPITALIZATION COMPARED TO INFARCT-RELATED ARTERY PCI: A META-ANALYSIS OF RANDOMIZED TRIALS
Authors: Ramez S. Nairooz, Ahmed Almomani, Partha Sardar, Luke Kim, Rajesh Swaminathan, Dmitriy Feldman
Journal: Journal of the American College of Cardiology (2016)
Diphenylhydantoin Sodium in Cardiac Arrhythmias
Authors: Robert D. Conn
Journal: New England Journal of Medicine (1965)

THE time-honored drug armamentarium for cardiac arrhythmias of digitalis, quinidine and procainamide has proved successful in most clinical circumstances. Toxicity to each of these agents, however, remains of major concern to the clinician. The search for effective but less toxic antiarrhythmic drugs has involved a number of different compounds, including the antimalarials, antihistaminics, antispasmodics and various agents that alter the responses of the autonomic nervous system.1 In some of the early clinical studies on diphenylhydantoin (Dilantin) in the treatment of epilepsy, certain effects were observed on the heart. As early as 1942 Finkelman and Arieff2 noted that administration of the . . .
Multiorgan Uptake of Tc-99m MDP in a Patient With Stage 4 Alveolar Rhabdomyosarcoma
Authors: S J Freeman, A Parker, C Sandoval
Journal: Clinical Nuclear Medicine (1998)

Visceral calcification is a known complication of hypercalcemia with or without underlying malignant disease. It is well established that bone scanning with Tc-99m diphosphonate has been particularly sensitive in identifying extraosseous calcification, whether metastatic or dystrophic in nature. We present a case of metastatic multiorgan calcification in a 19-year-old man with Stage 4 alveolar rhabdomyosarcoma. This case is unusual in that there was uncommon splenic and thyroid involvement, in addition to the rare finding of pancreatic uptake.
P20 First report of the long-term efficacy of a novel endoscopic radiofrequency ablation technique for malignant biliary obstruction
Authors: Y. Kallis, N. Phillips, A. Steel, C. Baldwin, J. Nicholls, L. Jiao, P. Vlavianos, N. Habib, D. Westaby
Journal: Gut (2011)

<h3>Objective</h3> To measure knowledge and awareness of human papillomavirus (HPV) testing in the USA, the UK and Australia. <h3>Methods</h3> Participants in the USA, UK and Australia completed an anonymous web-based survey measuring awareness and knowledge of HPV (n=2409). We report analyses on a subsample of 1473 men and women in the USA (n=617), UK (n=404) and Australia (n=452) who had heard of HPV and completed questions about HPV testing. <h3>Results</h3> Overall, 50% of the sample (742/1473) had heard of HPV testing. Awareness of HPV testing was higher in the USA (62%) than in the UK (44%) and Australia (40%) (p&lt;0.001). Among those who had heard of HPV testing, the mean knowledge score (out of 6) was 2.78 (SD: 1.49). No significant differences in knowledge score were found between the countries but, overall, women scored significantly higher than men (2.96 vs 2.52, p&lt;0.001). <h3>Conclusions</h3> Awareness of HPV testing among people who have heard of HPV is higher in the USA than in the UK and Australia, but overall knowledge is low. This has important implications in those countries where HPV testing is being used in cervical screening. Increasing knowledge about the implications of HPV test results may help minimise any negative psychological consequences associated with HPV testing. Raising awareness in men could become increasingly important if HPV testing is introduced into the management of other cancers where HPV plays an aetiological role.
Acute Hemorrhagic Necrosis of the Gastrointestinal Tract
Authors: Si-Chun Ming, Ruven Levitan
Journal: New England Journal of Medicine (1960)

MASSIVE gastrointestinal bleeding has always been a serious diagnostic and therapeutic problem. The problem is even greater when the bleeding occurs in an old person who may simultaneously exhibit a multitude of serious organic disturbances interfering with proper investigation.In 1954 Wilson and Qualheim1 described a form of acute hemorrhagic enterocolitis in 20 chronically ill patients, many of whom presented massive gastrointestinal hemorrhage. Some underwent unnecessary surgical exploration because of an erroneous diagnosis. This condition has not been generally recognized, and not mentioned in the extensive review of the causes of the gastrointestinal hemorrhage by Brick and Jeghers.2 Kane et . . .
Abstract 865: Impact of race and health insurance on delays in breast cancer diagnosis and treatment in the District of Columbia
Authors: Heather J. Hoffman, Paul H. Levine, Steven R. Patierno, Heather A. Young, Lisa M. Alexander, Nancy L. LaVerda
Journal: Cancer Research (2010)

Abstract Background: Delays in follow-up after breast cancer screening are thought to contribute to disparities in breast cancer outcomes. The primary objective of this study is to determine the impact of race as well as health insurance status on the diagnostic delay time, defined as the number of days from abnormal screening to definitive diagnosis. In addition, we analyze the effects of race and health insurance status on the treatment delay time, defined as the number of days from definitive breast cancer diagnosis to treatment initiation. Methods: This is a retrospective study of 695 women examined for breast cancer between 1997 and 2009 at seven hospitals and clinics located in the District of Columbia. The outcomes of interest were the diagnostic delay time and the treatment delay time. We used full-factorial and main-effects ANOVA models to test for significant differences in these outcomes between African-American and white women with and without some type of health insurance. Results: The mean diagnostic delay time was 37 days for insured white women, 76 days for uninsured white women, 75 days for insured African-American women, and 73 days for uninsured African-American women. In fitting a full-factorial ANOVA model, we found that insured white women had a significantly shorter delay in diagnosis than insured African-American women (p=0.0001) as well as uninsured white women (p=0.0007). Furthermore, a main-effects ANOVA model showed that after controlling for insurance status, African-American women had a mean treatment delay time of 45 days, which was significantly longer than the mean treatment delay time of only 17 days for white women (p&amp;lt;0.0001). Insurance status, however, had no significant effect on the treatment delay time after controlling for race (p=0.72). Conclusions: Insured African-American women and uninsured white women waited more than twice as long to reach their definitive diagnosis than insured white women. African-American women also waited more than three times as long as white women for treatment initiation following definitive diagnosis. Lack of health insurance markedly decreased the speed of diagnostic resolution in white women, but having health insurance did not increase the speed of diagnostic resolution in African-American women. These results suggest that lack of health insurance may not be the primary barrier to optimal diagnostic resolution and treatment initiation in African-American women. It will be important to determine what other factors serve as the primary barriers, as well as if these delays affect the final breast cancer outcome for the patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 865.
7DNA methylation patterns at promoters of hypertrophy-associated genes in an engineered heart tissue model of cardiac hypertrophy
Authors: J Stenzig, MN Hirt, J-T Hensel, T Guenther, D Indenbirken, A Hansen, T Eschenhagen
Journal: Cardiovascular Research (2014)

Objectives: Engineered Heart Tissue (EHT) can be used to investigate cardiomyocyte hypertrophy in vitro. In this model coherently beating rat cardiomyocytes in 3D tissue culture are acutely forced to work against an increased afterload. They subsequently display hypertrophy and functional and transcriptional alterations stereotypically associated with heart failure. In the present study we used the model to investigate DNA methylation patterns of cardiomyocyte hypertrophy. We assessed two different approaches: An unbiased microarray and bisulfite sequencing of promoter regions of genes associated with pathological hypertrophy. Methods: EHTs were cultured on hollow silicone posts in a 24-well format for 2 weeks until maturation. Afterload was then acutely increased (“afterload enhanced”, AE) by inserting metal braces into the hollow silicone posts for one week. Additional EHTs were treated with phenylephrine to induce hypertrophy (PE), control EHTs were left untreated. Methylated DNA fragments were enriched by MBD2 pull-down and quantified by microarray. Data was evaluated and mapped using DEVA, R and DAVID software. Additionally, DNA from EHTs was sodium bisulfite treated to convert all non-methylated cytosines to thymidines. Promoter region fragments of Nppa, Nppb, Acta-1 and Atp2a2 (ANP, BNP, alpha skeletal muscle actin and Serca2a) and methylation positive and negativ controls Oxt and Ube2b were PCR amplified and subjected to next generation sequencing (NGS). Single-base resolution methylation data was extracted by Bismark software. Results: In the microarray analysis PE and AE clustered together. Methylation changes among AE or PE and controls respectively mapped to pathways relevant for pathological hypertrophy. Further analyses identified previously unidentified differentially methylated regions and confirmed differential methylation in well-studied genes such as Serca2a, supporting the validity of the approach. Targeted NGS confirmed subtle but reproducible DNA methylation alterations in promoter regions of hypertrophy associated genes. A region at -3000 bp of the Serca2a transcriptional start site was identified as differentially methylated using the microarray approach and confirmed by NGS. Conclusion: Exposing EHTs to enhanced afterload rapidly and specifically alters DNA methylation in cardiac myocytes. In vitro hypertrophy is accompanied by a common DNA methylation signature irrespective of the cause of hypertrophy. Its probable regulatory function and high plasticity suggest DNA methylation as a possible drug target in cardiac hypertrophy.
Single-Drug Therapy for Hypertension in Men -- A Comparison of Six Antihypertensive Agents with Placebo
Authors: Barry J. Materson, Domenic J. Reda, William C. Cushman, Barry M. Massie, Edward D. Freis, Mahendr S. Kochar, Robert J. Hamburger, Carol Fye, Raj Lakshman, John Gottdiener, Eli A. Ramirez, William G. Henderson
Journal: New England Journal of Medicine (1993)

Characteristics such as age and race are often cited as determinants of the response of blood pressure to specific antihypertensive agents, but this clinically important issue has not been examined in sufficiently large trials, involving all standard treatments, to determine the effect of such factors.In a randomized, double-blind study at 15 clinics, we assigned 1292 men with diastolic blood pressures of 95 to 109 mm Hg, after a placebo washout period, to receive placebo or one of six drugs: hydrochlorothiazide (12.5 to 50 mg per day), atenolol (25 to 100 mg per day), captopril (25 to 100 mg per day), clonidine (0.2 to 0.6 mg per day), a sustained-release preparation of diltiazem (120 to 360 mg per day), or prazosin (4 to 20 mg per day). The drug doses were titrated to a goal of less than 90 mm Hg for maximal diastolic pressure, and the patients continued to receive therapy for at least one year.The mean (+/- SD) age of the randomized patients was 59 +/- 10 years, and 48 percent were black. The average blood pressure at base line was 152 +/- 14/99 +/- 3 mm Hg. Diltiazem therapy had the highest rate of success: 59 percent of the treated patients had reached the blood-pressure goal at the end of the titration phase and had a diastolic blood pressure of less than 95 mm Hg at one year. Atenolol was successful by this definition in 51 percent of the patients, clonidine in 50 percent, hydrochlorothiazide in 46 percent, captopril in 42 percent, and prazosin in 42 percent; all these agents were superior to placebo (success rate, 25 percent). Diltiazem ranked first for younger blacks (< 60 years) and older blacks (> or = 60 years), among whom the success rate was 64 percent, captopril for younger whites (success rate, 55 percent), and atenolol for older whites (68 percent). Drug intolerance was more frequent with clonidine (14 percent) and prazosin (12 percent) than with the other drugs.Among men, race and age have an important effect on the response to single-drug therapy for hypertension. In addition to cost and quality of life, these factors should be considered in the initial choice of a drug.
Abstract 4933: Functional properties of PPFIA1, located at the 11q13 amplification region, in epithelial cancer cells.
Authors: Henna Pehkonen, Tatiana Lepikhova, Riku Louhimo, Nina Peitsaro, Misa Imai, Rafael Martinez, Juha Kleftsröm, Sampsa Hautaniemi, Outi Monni
Journal: Cancer Research (2013)

Abstract PPFIA1 (liprin α1) is a member of the liprin (LAR protein-tyrosine phosphatase-interacting protein) family and is located at the 11q13 amplification region, which is one of the most common amplicons in multiple epithelial cancers. In squamous cell carcinoma of head and neck (HNSCC), this amplification occurs in 30-50% of the cases. In epithelial cancers, the size and structure of 11q13 amplicon is complex and consists of multiple amplicon cores that differ between different tumor types. In HNSCC, the amplicon core contains 10 genes that are amplified in cases with 11q13 amplification. This region contains well-established oncogenes, such as CCND1 and CTTN (cortactin), yet the role of several genes in this region is unknown. Our aim is to study the role of PPFIA1, which has recently been found to be involved in cell motility, modeling of the cell edge dynamics and axon guidance. PPFIA1 is amplified and overexpressed in several epithelial cancers, but the role of it is controversial. PPFIA1 is required for breast and cervical cancer cell invasion, but in contrast depletion of it results in increased invasion of HNSCC cells. We have overexpressed liprin α1 and cortactin in HNSCC cells with no 11q13 amplification and related phenotypes have been analysed in in vitro assays. Migration assays using matrigel coated inserts have shown that overexpression of cortactin increases invasive properties of the HNSCC cells with no 11q13 amplicon whereas liprin α1 has an opposite effect. We have also shown that liprin α1 localizes with cortactin in same vesicular structures, but they do not show physical interaction. Our aim is now to explore the molecular mechanisms behind these findings to assess the role of liprin α1 in vesicular transport and cell motility. We are also carrying out immunoprecipitation and mass spectrometry analyses to identify novel interaction partners for this protein. Our study will provide novel information on the potential specialized functions of liprin α1 in different epithelial cancers, which is likely to improve our understanding on the functional role of 11q13 amplification in malignant potential of cancer cells. Citation Format: Henna Pehkonen, Tatiana Lepikhova, Riku Louhimo, Nina Peitsaro, Misa Imai, Rafael Martinez, Juha Kleftsröm, Sampsa Hautaniemi, Outi Monni. Functional properties of PPFIA1, located at the 11q13 amplification region, in epithelial cancer cells. [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 4933. doi:10.1158/1538-7445.AM2013-4933
OP08 * CHARACTERISATION OF RESIDUAL CELLS IN GLIOBLASTOMA MULTIFORME
Authors: A. Kolb, A. Trecharichi, S. Piccirillo, C. Watts, S. Price
Journal: Neuro-Oncology (2014)

INTRODUCTION: Glioblastoma Multiforme(GBM) is the most severe type of brain malignancy, the median survival doesn't exceed 15 months. 5-Aminolevulinic acid (5-ALA) induced fluorescent-guided surgery has resulted in a more complete resection recently. After intake, 5-ALA is converted into the fluorescing PPIX, preferentially accumulating in GBM. The tumour margin is defined by lack of fluorescence, tumour cells within seem to display traits different from the mass. To gain a better understanding of these cells might prove beneficial for future therapies. Thus, we investigated differences in expression, growth and tumourigenicity in surgical specimen and patient-derived cell lines. METHOD: To investigate if there are cells other than tumour fluorescing, surgical specimen from mass and margin were subjected to flow cytometry. To be able to derive cell lines from the margin, the Cambridge protocol (Fael Al Mayhani 2009) was subjected to some changes. Next, surgical specimen and cell lines from mass and margin were analysed with regard to their expression of markers related to cell type, vascularisation, proliferation and resistance. RESULTS: Flow cytometry and analysis of different markers might point fluorescence being restricted to tumour cells. A protocol for derivation of margin derived cell lines could be generated successfully. Surgical specimen and patient derived cell lines from the margin of GBM showed a higher expression of SOX2, decreased proliferation and tumorigenicity and a trend towards higher resistance in vitro. CONCLUSION: Tumour cells residing in the margin might possess a quiescent phenotype and higher resistance. Thusly, it might be interesting to find a way to sensitise cells to conventional therapy.
99 FUNCTIONAL DEFECTS IN CIRCULATING MONOCYTES MAY CONTRIBUTE TO INCREASED SUSCEPTIBILTY TO INFECTION IN ALCOHOLIC HEPATITIS
Authors: N. Vergis, C.G. Antoniades, V. Zingarelli, R.D. Abeles, Y. Ma, D. Shawcross, D. Patch, W. Rosenberg, P. Kennedy, G. Foster, A. Barnabas, S. Khan, K. Agarwal, M. Heneghan, J. O'Grady, D. Vergani, J. Wendon, M.R. Thursz
Journal: Journal of Hepatology (2012)
P668Extracellular mitochondrial DNA induces cell death in cardiomyocytes
Authors: KO Stenslokken, M Bliksoen, L Mariero, K Ytrehus, A Baysa, JI Vaage, G Valen
Journal: Cardiovascular Research (2014)

Purpose: Acute myocardial infarction is associated with aseptic inflammation. Mitochondrial components can activate the innate immune system. Mitochondrial DNA is released into the circulation during acute myocardial ischemia in humans and mice. We hypothesized that mtDNA may induce an immune response through Toll like receptor 9 (TLR-9), injure cardiomyocytes in vitro, and activate nuclear factor kappa B (NFkB) in vivo.
582 INCREASED PERCENTAGE OF ACTIVATED REGULATORY T CELLS IN PATIENTS WITH DECOMPENSATED LIVER CIRRHOSIS CONTRIBUTE TO THE IMMUNOSUPPRESSIVE STATUS BY SHEDDING THE MEMBRANOUS TNFRII
Authors: C.-H. Huang, C.-Y. Lin, I.-S. Sheen, W.-J. Jeng, C.-W. Huang
Journal: Journal of Hepatology (2013)
Renal Cell Carcinoma Arising From Renal Allograft Detected by 18F-FDG PET-CT
Authors: Yuehong Guo, Tie Wang
Journal: Clinical Nuclear Medicine (2016)

Renal cell carcinoma arising from renal allograft is a rare condition. A 56-year-old man with a history of 3 renal transplantation due to renal failure presented poor appetite and weight loss for 3 months. Possibility of tumor of unknown origin was suspected. For this reason, an FDG PET/CT was performed, and the images showed a hypermetabolic focus in the lower pole of the left renal transplant, suggestive of a malignant lesion. Subsequent pathological examination following allograft nephrectomy confirmed grade 4 renal cell carcinoma.