tbuckley/cabot-search huggingface dataset:
Abstract 18162: Does Transcatheter Aortic Valve Replacement Have Acute Impact on Right Ventricular Function ?
Authors: Youssef Nasr, Dee Dee Wang, George Dirani, David Yanoschik, Swadia Tanmay, Meredith Mahan, Mayra Guerrero, Adam Greenbaum, William O’Neill, Karthik Ananthasubramaniam
Journal: Circulation (2014)

Background and Aim: Transcatheter aortic valve replacement (TAVR) is now an established alternative to surgical aortic valve replacement in selected high risk aortic stenosis patients. Whether early changes in right ventricular function (RVF) are seen immediately post-TAVR is not known. We aimed to evaluate the impact of TAVR on acute changes in RVF using detailed quantitative analysis.

Methods and Results: 103 patients who underwent TAVR at a single-center were retrospectively studied. Each patient’s pre-TAVR echocardiogram (TTE) and immediate post-TAVR TTE performed prior to discharge date from TAVR hospital admission were analyzed along with baseline demographic and clinical variables. RVF was assessed with M-mode, Tissue Doppler and global performance index (Tei index; TEI 1 = pulsed doppler, TEI 2=tissue doppler) on pre and post-TAVR TTE. Pre and post comparisons were done using paired t-tests and data are presented as mean and 95% confidence interval (CI). The mean patient population age was 81.9, with 49% males. Table 1 outlines the pre and post-TAVR echocardiographic changes in quantitative RV function assessed in the early post-TAVR follow-up period. An acute improvement in RVF with Tei index indicates that TAVR may have beneficial effects both on systolic and diastolic function accompanied by a decline in RV-RA pressure difference suggesting lower post TAVR RV systolic pressure.

Conclusion: Our study is the first study demonstrating an improvement in RVF acutely post-TAVR utilizing a comprehensive RV TTE analysis. A more global RVF index combining systolic and diastolic RV performance (Tei index) may be a better marker than regional systolic function parameters . Thus, Tei index could be integrated into part of the pre-post RVF assessment evaluation in patients undergoing TAVR.

Table1: Right Ventricular Function Pre and Post-TAVR

TAPSE: tricuspid annular plane systolic excursion, FAC: fractional area change, TR: tricuspid regurgitation

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<i>All-trans</i>retinoic acid promotes the repair of tortuosity of elastic fibres in rat skin
Authors: None Tsukahara, None Takema, None Fujimura, None Moriwaki, None Kitahara, None Imayama, None Imokawa
Journal: British Journal of Dermatology (1999)

To elucidate the repair effects of all-trans retinoic acid (t-RA) on ultraviolet (UV)-induced tortuosity of elastic fibres in rat skin, the hind limbs of Sprague-Dawley rats were irradiated at a suberythemal dose of UV (three times/week for 6 weeks) and 0.025% t-RA in ethanol was applied topically five times/week for 6 weeks. The three-dimensional arrangement of elastic fibres with special reference to their linearity was quantified by image analysis using a scanning electron microscope following a combination of intravascular resin injection and selective digestion using formic acid. When t-RA was topically applied for 6 weeks on wrinkles formed by 6 weeks' exposure of the skin of rat hind limbs to UV radiation, the wrinkles disappeared to control levels, concomitant with an improvement in skin elasticity. The linearity of the elastic fibres was significantly (P < 0.01) increased compared with age-matched UV-irradiated controls. These findings suggest that the degeneration and deposition of elastic fibres accompanied by an increase in their linearity is involved in the process of wrinkle repair by topical application of t-RA.
Effect of Nutritional Status on Response to Therapy
Authors: Jan van Eys
Journal: Cancer Research (1982)

Abstract  The evidence for the effect of nutritional status on outcome is reviewed. It is concluded that poor nutritional status is reversible, whether therapy is given or not, and that initial malnutrition presages poor outcome. However, reversal of the nutritional state does not affect outcome unless the antineoplastic therapy is inherently effective.
1034. The Optimization of Cancer Gene Therapy Using the Measurement of Viral Gene Expression Magnitude and Distribution
Authors: Kenneth N. Barton, Stephen L. Brown, Jae Ho Kim, Svend O. Freytag
Journal: Molecular Therapy (2004)

Cancer gene therapy effectiveness depends on many factors including the number and spacing of adenoviral deposits, the concentration of virus and total volume of injection, and the vehicle used. Previously we demonstrated our ability to measure gene expression magnitude and distribution with sub-millimeter resolution using the sodium iodide symporter reporter gene, NIS. Cells expressing NIS took up iodide or pertechnetate ion (99mTcO4-). Autoradiographs of sections of hNIS transfected tissue allowed for three-dimensions images of gene expression. In order to assess potential improvements in injection parameters that mimicked conditions consistent with our prostate cancer gene therapy program, we adopted a dog prostate model. One prostate lobe was given the standard virus deposit (3×1011 Ad5-CD/TKrep-NIS viral particles, a replication competent virus that incorporates the two suicide genes cytosine deaminase and thymidine kinase) while the other lobe received virus under the conditions to be tested (different volume, vehicle, number of injections, etc). One day after viral delivery, dogs were administered a clinically-relevant dose of radioisotope and after 1 hour of uptake, excised prostates were frozen and sectioned for autoradiography. The technique allowed for head-to-head comparisons of conditions that are thought to improve adenoviral-delivered gene expression. Our results predict that more than 150 viral deposits (100 ml each) are needed for complete prostate coverage using a simple linear extrapolation of spatial distribution from a single viral injection when the vehicle is saline. The number of viral deposits needed to cover the organ drops to between 40 and 80 when virus was suspended in PEG 400 instead of saline. We have begun testing the prediction experimentally and have found that adenovirus administered in four small volume deposits (100 ml) provided better gene coverage than adenovirus deposited in a single large deposit (1000 ml). The methodology presented provides the framework for optimized adenoviral delivered gene therapy.
Localized peeling skin syndrome: case report with ultrastructural study
Authors: None Brusasco, None Veraldi, None Tadini, None Caputo
Journal: British Journal of Dermatology (1998)

We report a young woman in whom the history, clinical features, histopathological and ultrastructural findings led to a diagnosis of peeling skin syndrome (PSS). PSS is a rare and not well classified genodermatosis, mainly characterized by the spontaneous separation of the stratum corneum from the stratum granulosum. The unusual feature in our patient was the strict localization to the palm. PSS has been described as a more generalized disease frequently sparing palms and soles. We propose the diagnosis label of 'localized PSS' for this previously undescribed variant of a rare keratinization defect.
Abstract P273: Enhancing Documentation and Control of Lipids in a University-Based Cardiology Clinic
Authors: Keerthana K Karumbaiah, Mazen B Omar, Bassam A Omar
Journal: Circulation (2014)

Background: Non-compliance with laboratory appointments, separate from clinic visit appointments, for measuring fasting cholesterol may hinder documentation and control of patients’ lipids. Methods: A university-based cardiologist’s clinic notes, from a single year (yr 1), when patients were asked to have a fasting cholesterol a week prior to the clinic visit, were analyzed (100 patients). The poor compliance prompted a same day as the clinic visit measurement (fasting or non-fasting) of lipids, for patients who could not comply with their laboratory appointment, during the following year (yr 2; 130 patients). Lipid values were managed by a subsequent call to the patient. All patients had coronary artery disease or risk equivalent mandating LDL levels &lt; 100 mg/dL. Results: In yr 1, 62% (62/100) of patients had documented lipid profiles compared to 83% (108/130) of patients in yr 2. The average LDL in yr 1 was 115 +/- 36 mg/dL compared with 96 +/- 31 mg/dL in yr 2 (P &lt; 0.01). Only 22% of the patients in yr 1 reached goal of &lt; 100 mg/dL, compared with 65% in yr 2. There were no significant differences in the HDL, TG levels or blood pressures documented during the concurrent visits. Conclusion: Better documentation and control of lipids may be obtained when lipid profiles are done on clinic visit day, with fewer burdens on the patients who cannot comply with a separate laboratory appointment. Although there were many non-fasting levels as a result, the triglyceride levels where not significantly different among the two groups, probably reflecting an overall more intensive lipid management in yr 2, commensurate with the better documentation. Therefore, as has been shown by others, a lipid profile does not necessarily have to be fasting, especially in patients being treated for stricter targets such as our cohort, which may decrease the burden on patients unable to comply with a fasting state or added clinic visits.
Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization
Authors: Niklas Zojer, Robert Königsberg, Jutta Ackermann, Elke Fritz, Susanne Dallinger, Elisabeth Krömer, Hannes Kaufmann, Lucia Riedl, Heinz Gisslinger, Susanne Schreiber, Renate Heinz, Heinz Ludwig, Heinz Huber, Johannes Drach
Journal: Blood (2000)
Reproducibility of Macular Thickness and Volume Using Zeiss Optical Coherence Tomography in Patients with Diabetic Macular Edema
Authors: Krzystolik Mg, Strauber Sf, Aiello Lp, Beck Rw, Berger Bb, Bressler Nm, Browning Dj, Chambers Rb, Danis Rp, Davis, Glassman Ar, Gonzalez Vh, Greenberg Pb, Gross Jg, Kim Je, Kollman C
Journal: Ophthalmology (2007)
Abstract 4178: Global assessment of the protein tyrosine phosphatome in cancer
Authors: Nicholas Tonks, Robert Lucito
Journal: Cancer Research (2014)

Abstract Receptor tyrosine kinases and non-receptor tyrosine kinases are an important class of molecules controlling a large number of processes from growth to metabolic regulation. These tyrosine kinases have been well studied and scrutinized for their role in these normal processes as well as abnormal processes, such as cancer. Parallel to these kinases are more that 100 tyrosine phosphatases, which also fall into either receptor or non receptor classifications. While some of these phosphatases antagonize the tyrosine kinases others including many of the receptor bound phosphatases are critical in their own right in signaling processes such as pro survival, proliferation, etc. Although tyrosine kinases have been well studied, the study of tyrosine phosphatases has lagged. Numerous tyrosine phosphatases have been identified that are misregulated and important for cancer growth including PTPRD in breast cancer, and PTPRZ1 in small cell lung cancer as well as many others. However there has been no comprehensive study of all PTPs or the protein tyrosine phosphatome (PTPome), to identify which have a role in cancer. We as a cancer community are fortunate to have access to such a wide array of data types from a number of data sources such as TCGA, where we can determine if the PTPs are mis regulated in more than 20 types of cancers. We used TCGA data for all tumor types and subsetted the data to analyze the PTPome for all data types including expression, methylation, copy number and sequence data where available. Thus far we have identified known PTPs involved in a number of cancers, including PTPRD and PTPRZ1, but have also identified a number of PTPs altered in cancers that were less characterized such as the alteration of PTPRD in melanoma which is predominantly by mutations with much fewer deletions. While many of these mutations are missense and are difficult to characterize there are also a number of non-sense mutations, which would severely alter function as well as a number of splice site mutation of which some severely alter function and others are likely to alter function. The identification of this PTP is but one example to demonstrate the richness of this dataset. This analysis has been extremely useful to identify the PTPs that are altered in cancer and these results will be useful to many in the research community that are interested in PTP involvement in cancer but will also be of even greater use to those researchers who have not appreciated the vast importance of these under studied proteins. Citation Format: Nicholas Tonks, Robert Lucito. Global assessment of the protein tyrosine phosphatome in cancer. [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 4178. doi:10.1158/1538-7445.AM2014-4178
Recent developments in the medical and surgical treatment of melanoma
Authors: Vita Saranga‐Perry, Chenwi Ambe, Jonathan S. Zager, Ragini R. Kudchadkar
Journal: CA A Cancer Journal for Clinicians (2014)

Abstract Answer questions and earn CME/CNE Increasing knowledge of the biology of melanoma has led to significant advances in drug development to fight this disease. Surgery is the primary treatment for localized disease and is an integral part of management in patients with more advanced disease. The last decade has become the era of targeted therapy in melanoma and has revolutionized the treatment of this disease. Since 2011, 4 new agents have been approved for the treatment of patients with metastatic melanoma: ipilimumab, vemurafenib, dabrafenib, and trametinib. Several new agents are currently in phase 3 trials with hopes of even more agents being approved for this once “untreatable” disease. How to integrate surgical options with more effective systemic therapies has become a new challenge for physicians. This review will provide an update on current surgical options, highlight the pathway to the development of the newly approved agents, and further discuss new treatments that are on the horizon. CA Cancer J Clin 2014;64:171–185. © 2014 American Cancer Society.
Abstract 751: Preclinical efficacy of the novel PIM inhibitor, JP_11646, in pancreatic cancer
Authors: Yi Ding, Vun-Sin Lim, Carmen M. Baldino, Justin Caserta, Yvonne Flanders, Stephane Dumas, Gerald Fetterly, Alex A. Adjei
Journal: Cancer Research (2014)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is often first diagnosed at an advanced stage with a poor prognosis. Current systemic treatment approaches have limited efficacy, pointing to an urgent need to develop novel therapies. Recent studies have shown that inhibition of Pim-2 activity via JP_11646, a novel pan-PIM inhibitor, resulted in decreased anchorage-independent growth of PDAC. The aim of this work is to examine the ability of JP_11646 alone and in combination with gemcitabine to inhibit the growth of pancreatic cancer cells in vitro and in vivo. Cell viability was assessed using the MTS assay in two pancreatic cancer cell lines, MiaPaCa2 and PANC1. Cells were seeded at an average of 5x103 per well on 96-well plates and exposed to JP_11646 in a range of concentrations (0.01 - 5 µM) for 72 hours. Exposure to JP_11646 inhibited PANC1 and MiaPaCa2 cell growth in a dose-dependent manner, with IC50 values of 0.15 µM and 0.054 µM, respectively. For in vivo experiments, SCID mice were implanted subcutaneously with 3x 106 MiaPaCa2 cells. Upon successful establishment of tumors (approximately 100 mm3), animals were randomly divided into groups for drug and control treatments. JP_11646 was given at 5 or 10 mg/kg by intraperitoneal injection (i.p. injection) once a day for 5 consecutive days from Monday to Friday for a total of six weeks. Gemcitabine i.p. was given at 45 mg/kg in combination treatment or 90 mg/kg as a single agent twice a week every Monday and Friday for a total of six weeks. In a dose-dependent manner, JP_11646 at 5 and 10 mg/kg significantly suppressed the growth of the pancreatic xenograft by 36% and 77% respectively, compare with control PBS treatment in SCID mice. Moreover, the combination of JP-11646 5 mg/kg and gemcitabine 45 mg/kg resulted in a greater tumor inhibition (83%) than either single agent alone [JP_11646 5 mg/kg (36%) or gemcitabine 90 mg/kg (69%)]. Taken together, our results suggest that JP_11646 is a potent inhibitor of pancreatic cancer growth with equivalent efficacy to the maximum tolerated dose of gemcitabine, and is synergistic in combination with gemcitabine. Citation Format: Yi Ding, Vun-Sin Lim, Carmen M. Baldino, Justin Caserta, Yvonne Flanders, Stephane Dumas, Gerald Fetterly, Alex A. Adjei. Preclinical efficacy of the novel PIM inhibitor, JP_11646, in pancreatic cancer. [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 751. doi:10.1158/1538-7445.AM2014-751
Abstract 14880: Neutrophil Gelatinase-Associated Lipocalin Compared to Cystatin C and Estimated Glomerular Filtration Rate in Risk Stratification of Patients with Suspected Acute Coronary Syndrome
Authors: Till Keller, Francisco Ojeda, Tanja Zeller, Stergios Tzikas, Anne Schauer, Christoph Bickel, Karl Lackner, Stephan Baldus, Thomas Munzel, Stefan Blankenberg
Journal: Circulation (2011)

Background: Early and adequate risk stratification is essential in patients with suspected acute coronary syndrome (ACS). In these patients renal impairment reflected by estimated glomerular filtra...
Modulation of Gene Expression in Precancerous Rat Esophagus by Dietary Zinc Deficit and Replenishment
Authors: Chang-Gong Liu, Liang Zhang, Yubao Jiang, Devjani Chatterjee, Carlo M. Croce, Kay Huebner, Louise Y.Y. Fong
Journal: Cancer Research (2005)

Zinc deficiency in rats enhances esophageal cell proliferation, causes alteration in gene expression, and promotes esophageal carcinogenesis. Zinc replenishment rapidly induces apoptosis in the esophageal epithelium thereby reversing cell proliferation and carcinogenesis. To identify zinc-responsive genes responsible for these divergent effects, we did oligonucleotide array-based gene expression profiling analyses in the precancerous zinc-deficient esophagus and in zinc-replenished esophagi after treatment with intragastric zinc compared with zinc-sufficient esophagi. Thirty-three genes (21 up-regulated and 12 down-regulated) showed a > or = 2-fold change in expression in the hyperplastic zinc-deficient versus zinc-sufficient esophageal epithelia. Expression of genes involved in cell division, survival, adhesion, and tumorigenesis were markedly changed. The zinc-sensitive gene metallothionein-1 (MT-1 was up-regulated 7-fold, the opposite of results for small intestine and liver under zinc-deficient conditions. Keratin 14 (KRT14, a biomarker in esophageal tumorigenesis), carbonic anhydrase II (CAII, a regulator of acid-base homeostasis), and cyclin B were up-regulated >4-fold. Immunohistochemistry showed that metallothionein and keratin 14 proteins were overexpressed in zinc-deficient esophagus, as well as in lingual and esophageal squamous cell carcinoma from carcinogen-treated rats, emphasizing their roles in carcinogenesis. Calponin 1 (CNN1, an actin cross-linking regulator) was down-regulated 0.2-fold. Within hours after oral zinc treatment, the abnormal expression of 29 of 33 genes returned to near zinc-sufficient levels, accompanied by reversal of the precancerous phenotype. Thus, we have identified new molecular markers in precancerous esophagus and showed their restoration by zinc replenishment, providing insights into the interaction between zinc and gene expression in esophageal cancer development and prevention.
Abstract 4222: Targeting PI3K and mTOR with BEZ235, a dual inhibitor, is efficacious in trastuzumab refractory and HER2+/<i>PIK3CA-</i>mutated breast cancer models
Authors: Casey Williams, Yuliang Sun, Jennifer Carlson, Brian Leyland-Jones, Nandini Dey, Pradip De
Journal: Cancer Research (2014)

Abstract Background: PI3K pathway activation is a common event in HER2+ breast cancer (BC) either through inactivation of the tumor suppressor gene, PTEN, or activation of PIK3CA. This PIK3CA mutation leads to an oncogenic activity of the PI3K pathway and contributes to therapeutic resistance to trastuzumab (T). The PI3K pathway inhibitor is therefore an attractive drug for HER2+ BC, especially in T-resistant and PIK3CA mutated conditions. Methodology: Here we have studied the in vitro and in vivo effects of BEZ235 in HER2+/T-sensitive (BT474), HER2+/T-resistant (BT474HerR) and HER2+/PIK3CA (HCC1954) mutated models. We assessed in vitro anti-proliferative and activation status of the PI3K-AKT-mTOR signaling pathway following BEZ235 treatment in HER2+ BC cell lines. We next evaluated the impact of BEZ235 on tumor growth and angiogenesis using xenograft models. Results: 1) BEZ235 inhibited downstream activation of the PI3K signaling pathway effectors, p-AKT (Ser473, The308), p-P70S6K, p-S6RP and p-4EBP1, 2) the anti-proliferative activity of BEZ235 was observed by 3D-ON-TOP clonogenic assay, 3) consistent with anti-proliferative effects of BEZ235, the proportion of cells in the G1 phase of the cell cycle increased in all three cell lines with a concomitant decrease in the S phase of their treatment with BEZ235, 4) the initiation of apoptotic activity (annexin V) of BEZ235 was significantly superior to that of RAD001, an allosteric inhibitor of mTOR, and 5) in the HER2+/T-sensitive, HER2+/T-resistant and HER2+/PIK3CA mutated BC xenograft models, BEZ235 inhibited PI3K signaling and had potent anti-tumor activity. Along with its anti-tumor effect, BEZ235 effectively decreased tumor angiogenesis (tumor micro-vessel density via CD31 staining). These inhibitions were more pronounced when BEZ235 was combined with T. Conclusions: BEZ235 inhibits the PI3K-AKT-mTOR signaling pathway and results in anti-proliferative and anti-tumor activity in HER2+ breast cancer cells with both wild type and mutated PIK3CA. Citation Format: Casey Williams, Yuliang Sun, Jennifer Carlson, Brian Leyland-Jones, Nandini Dey, Pradip De. Targeting PI3K and mTOR with BEZ235, a dual inhibitor, is efficacious in trastuzumab refractory and HER2+/PIK3CA-mutated breast cancer models. [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 4222. doi:10.1158/1538-7445.AM2014-4222
Genetic basis of autoimmunity
Authors: Alexander Marson, William J. Housley, David A. Hafler
Journal: Journal of Clinical Investigation (2015)

Autoimmune diseases affect up to approximately 10% of the population. While rare Mendelian autoimmunity syndromes can result from monogenic mutations disrupting essential mechanisms of central and peripheral tolerance, more common human autoimmune diseases are complex disorders that arise from the interaction between polygenic risk factors and environmental factors. Although the risk attributable to most individual nucleotide variants is modest, genome-wide association studies (GWAS) have the potential to provide an unbiased view of biological pathways that drive human autoimmune diseases. Interpretation of GWAS requires integration of multiple genomic datasets including dense genotyping, cis-regulatory maps of primary immune cells, and genotyped studies of gene expression in relevant cell types and cellular conditions. Improved understanding of the genetic basis of autoimmunity may lead to a more sophisticated understanding of underlying cellular phenotypes and, eventually, novel diagnostics and targeted therapies.