tbuckley/cabot-search huggingface dataset:
621. Translational Restriction of Protein Expression of a Modifed Suicide Gene and Cytotoxicity in Human Mammary Tumor Cells Expressing High Levels of the Translation Initiation Factor eIF4E
Authors: Don A. Sibley, James M. Mathis, Yoshi Odaka, B. J. Williams, Arrico DeBenedetti
Journal: Molecular Therapy (2004)

Two technical hurdles, gene delivery and target specificity, have hindered the development of effective cancer gene therapies. In order to circumvent the problem of tumor specificity, the suicide gene, HSV-1 thymidine kinase (HSV-Tk), was modified with a complex 5' upstream-untranslated region (5'-UTR) that limits efficent translation to cells that express high levels of the translation initiation factor, eIF4E. Previous study data have shown that most tumor cells express elevated levels of eIF4E. Gene delivery was optimized by incorporation of the modified suicide gene (HSV-UTk) into an adenovirus vector (Ad) that infects a broad range of cells. The goal of this project in the development of Ad-HSV-UTk was to target infection of a broad population of cells and yet limit translation of the suicide gene to those cells expressing elevated levels of eIF4E. The efficacy of this novel approach of targeting suicide gene expression and cytotoxicity by means of translational restriction was tested in vitro with the use of the human mammary tumor cells [MCF-7, MDA-MB435, ZR 75-1, MCF-10A and MCF10A cells that over express eIF4E (MCF10A-4E)], as well as primary cultures of human mammary epithelial cells (HMEC) and human mammary stromal cells (HMSC) that express relatively low levels of eIF4E. Real time rt-PCR was used to quantify transcription levels of HSV-Tk for both Ad-HSV-Tk and Ad-HSV-UTk infected cells, as well as the translation initiation factor eIF4E. Translation of HSV-Tk in both Ad-HSV-Tk and Ad-HSV-UTk infected cells was measured by Western blot analysis. In addition, cytotoxicity was determined by assessing cell viability following treatment with the prodrug GCV in Ad-HSV-Tk and Ad-HSV-UTk infected cells with the use of the reductase activity indicator MTT. These data demonstrated enhanced cytotoxicity for the Ad-HSV-UTk /GCV treatment in high eIF4E expressing cells compared to low eIF4E expressing cells, whereas the Ad-HSV-Tk/GCV treatment showed similar cytotoxicity in both high and low eIF4E expressing cells. These results indicate that translational targeting of suicide gene expression in tumor cells in vitro is effective and may provide a platform for enhanced cancer gene therapy specificity in vivo.
Abstract 153: High neuropilin-1 expression on monocytes is positively associated with trastuzumab-mediated antibody-dependent cellular cytotoxicity of the HER2-overexpressing breast cancer cell line
Authors: Kosuke Kawaguchi, Eiji Suzuki, Masao Kawashima, Masakazu Toi
Journal: Cancer Research (2014)

Abstract Purpose Neuropilin-1 (Nrp1) was initially characterized as a guide for migrating cells and axons in developing nervous systems and is essential for the precise formation of neurons and vasculature. However, it was recently reported to also play an important role in the immune system. This study aimed to investigate the role of Nrp1 on monocytes in trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC) targeting the HER2-positive human breast cancer cell line SKBR3. In addition, we evaluated the gene expression profile of monocytes expressing high and low levels of Nrp1. Methods Peripheral blood mononuclear cells from healthy volunteers were prepared using BD Vacutainer CPT Cell Preparation Tubes. The cells were stained with fluorescein isothiocyanate-conjugated anti-CD14 and allophycocyanin-conjugated anti-Nrp1 antibodies, and Nrp1high and Nrp1low monocyte subsets were sorted using FACSAria. These cells were used as effector cells in a conventional ADCC assay with SKBR3 as target cells and trastuzumab as the antibody. Target cell cytotoxicity was measured using the LDH cytotoxic test kit. The effector cell to target cell ratios of 20:1 and 10:1 were used. Gene expression analysis was performed by Affymetrix GeneChip microarrays. All study protocols were approved by the Ethics Committee for Clinical Research, Kyoto University Hospital, Kyoto, Japan (authorization number G424). Results The LDH cytotoxic test revealed significantly higher target cancer cell cytotoxicity in sorted Nrp1high monocytes than in Nrp1low monocytes (75% vs. 45%, p&amp;lt;0.01). Trastuzumab-mediated ADCC was significantly suppressed by Nrp1 neutralization antibodies in a dose-dependent manner (Control arm 14.3%, Treatment arm 6%; p&amp;lt;0.01). Gene expression analysis revealed that 308 genes were up-regulated in the Nrp1high population, including monocyte-specific chemokine receptor and hematopoietic transcriptional factor. Conclusion These results suggest that determination of Nrp1 expression can be used to classify monocytes as populations with and without cellular cytotoxic activity. Analysis of Nrp1 expression levels in monocytes can therefore be used to identify HER2-positive breast cancer patients for whom trastuzumab therapy will be less effective. Citation Format: Kosuke Kawaguchi, Eiji Suzuki, Masao Kawashima, Masakazu Toi. High neuropilin-1 expression on monocytes is positively associated with trastuzumab-mediated antibody-dependent cellular cytotoxicity of the HER2-overexpressing breast cancer cell line. [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 153. doi:10.1158/1538-7445.AM2014-153
Low-dose electron beam radiation and romidepsin therapy for symptomatic cutaneous T-cell lymphoma lesions
Authors: O.E. Akilov, C. Grant, R. Frye, S. Bates, R. Piekarz, L.J. Geskin
Journal: British Journal of Dermatology (2012)

Romidepsin is a structurally unique histone deacetylase inhibitor approved by the U.S. Food and Drug Administration for therapy of relapsed or refractory cutaneous T-cell lymphoma (CTCL). Localized electron beam radiation therapy (LEBT) is standard practice in the care of patients with chronically traumatized and painful lesions. Combination therapy of those two modalities may be beneficial for the therapy of CTCL.
Glucosamine sulfate slows-down osteoarthritis progression in postmenopausal women: pooled analysis of two large, independent, randomised, placebo-controlled, double-blind, prospective 3-year trials
Authors: Jean-Yves Reginster, Lucio Rovati, Rita Deroisy, Yves Henrotin, J. Gatterova, S. Machacek, C. Gonzalez, Giampaolo Giacovelli, K. Pavelka
Journal: Annals of the Rheumatic Diseases (2002)
The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25
Authors: Darryl Y. Nishimura, Ruth E. Swiderski, Wallace L. M. Alward, Charles C. Searby, Shivanand R. Patil, Steven R. Bennet, Adam B. Kanis, Julie M. Gastier, Edwin M. Stone, Val C. Sheffield
Journal: Nature Genetics (1998)
Abstract P115: How Many Coronary Heart Disease Deaths In Poland In 2020 Might Be Prevented By Further Reductions In Population Risk Factor Levels?
Authors: Piotr Bandosz, Maria Guzman-Castillo, Simon Capewell, Tomasz Zdrojewski, Julia Critchley, Marcin Rutkowski, Martin O'Flaherty
Journal: Circulation (2014)

Background: Poland has experienced one of the most dramatic declines in coronary heart disease (CHD) mortality rates in recent decades. This decline reflects the use of evidence based treatments and, crucially, population wide changes in diet. Our aim is to explore the potential for further gains in Poland by achieving population wide reductions in smoking, dietary salt and saturated fat intake and physical inactivity levels. Methods: A validated and updated policy model was used to forecast potential decreases in CHD deaths by 2020 as consequence of lifestyle and dietary changes in the population. Data from the most recent Polish risk factor survey was used for the baseline (2011). We modeled two different policy scenarios regarding possible future changes in risk factors: A) conservative scenario: reduction of smoking prevalence and physically inactivity rates by 5% between 2011 and 2020, and reduction of dietary consumption of energy from saturated fats by 1% and of salt by 10%. B) ideal scenario: reduction of smoking and physically inactivity prevalence by 15%, and dietary reduction of energy from saturated fats by 3% and of salt by 30%. We also conducted extensive sensitivity analysis using different counterfactual scenarios of future mortality trends. Results: Baseline scenarios. By assuming continuing declines in mortality and no future improvements in risk factors the predicted number of CHD deaths in 2020 would be approximately 13,600 (9,838-18,184) while if mortality rates remain stable, the predicted number of deaths would approximate 22,200 (17,792-26,688). Conservative scenario. Assuming continuing declines in mortality, small changes in risk factors could result in approximately 1,500 (688-2,940) fewer deaths. This corresponds to a 11% mortality reduction. Under the ideal scenario, our model predicted some 4,600 (2,048-8,701) fewer deaths (a 34% mortality reduction). Reduction in smoking prevalence by 5% (conservative scenario) or 15% (ideal scenario) could result in mortality reductions of 4.5% and 13.8% respectively. Decreases in salt intake by 10% or 30% might reduce CHD deaths by 3.0% and 8.6% respectively. Replacing 1% or 3% of dietary saturated fats by poly-unsaturates could reduce CHD deaths by 2.6% or 7.7% Lowering the prevalence of physically inactive people by 5%-15% could decrease CHD deaths by 1.2%-3.7%. Conclusion: Small and eminently feasible population reductions in lifestyle related risk factors could substantially decrease future number of CHD deaths in Poland, thus consolidating the earlier gains.
Abstract 18575: The Transcriptional Cofactor Eyes Absent 4 is a Critical Regulator for Maintaining Normal Cardiac Function
Authors: Tatjana Williams, Moritz Hundertmark, Peter Nordbeck, Sabine Voll, Anahi Paula Arias-Loza, Ines Elsner, Daniel Oppelt, Silvana Olivares, Jost Schoenberger, Oliver Ritter
Journal: Circulation (2014)

Introduction: E193, a human mutation in the transcription cofactor Eyes absent 4 (EYA4) causes hearing impairment followed by terminal heart failure, defining an important role for Eya4 in maintaining normal cardiac function. METHODS AND RESULTS: First, in-vitro experiments show that overexpression of Eya4 and the mutant isoform alter the expression of p27kip1 on both, transcript and protein levels. Next, we generated transgenic mice with cardiomyocyte-specific Eya4 or E193 overexpression to elucidate the in vivo function of Eya4 upon cardiac physiology. Luciferase and CHIP assays revealed that Eya4 and E193 bind to and regulate p27 expression in a contradictory manner, as already seen in vitro. Activity and phoshorylation of the downstream molecules CK2α and HDAC2 were significantly elevated in Eya4 mice, whereas they were significantly reduced in E193 animals compared to WT littermates. MRI and hemodynamic analysis indicate that a constitutive overexpression of Eya4 results in the age-dependent development of hypertrophy already under baseline conditions with no obvious functional effects, whereas E193 overexpressing animals develop onset of dilative cardiomyopathy as seen in human patients carrying the E193 mutation. Morphometric analysis proved ventricular hypertrophy or dilation of the LV associated with a thinning of the myocardial wall, interstitial fibrosis of myocardial tissue and alterations in cell size. Re-activation of fetal genes also occured in both TG models, characteristic for cardiac disease. Both cardiac phenotypes were aggravated upon pressure overload. Finally, we identified a new human heterozygous truncating Eya4 mutation, E215, which leads to similar clinical features of disease and a stable myocardial expression of the mutant protein. Conclusion: Our results implicate that Eya4 plays a critical role in regulating normal cardiac physiology and function via Six1/p27/CK2α/HDAC2 and that an imbalance within the Eya4/Six1 transcriptional complex leads to an age dependent onset of cardiomyopthy and heart failure.
Abstract 3838: Differential expression of Notch1 in lung, ovarian and breast cancers
Authors: Dat Nguyen, Larry Rubinstein, Mark E. Sherman, Joseph E. Tomaszewski, Naoko Takebe, Percy Ivy, James H. Doroshow, Sherry X. Yang
Journal: Cancer Research (2014)

Abstract Targeting the Notch signaling pathway for cancer treatment is currently the subject of early clinical trials. However, treatment-related toxicities, particularly gastrointestinal adverse events, have limited clinical development of this class of agents. The development of efficacy biomarkers to gamma-secretase inhibitors and antibodies to Notch ligands and receptors could speed clinical testing. Mutations in Notch1, a dominant Notch receptor, are rare in human solid tumors, and clinical activity has not been observed in patients with tumors bearing Notch1 activating mutations, including T-cell acute lymphoblastic leukemia from available clinical data. Identification of tumors with abundant target expression and/or active Notch signaling status characteristic of Notch intracellular domain (NICD) expression by immunohistochemistry may have clinical utility. All levels of tumor Notch1 expression comprised of low, moderate and high detected by immunohistochemistry and quantitated by digital imaging technology were observed in 52% (34/66) of lung cancers, 51% (35/68) of ovarian cancers, and 11% (7/63) of breast cancers (lung or ovary vs. breast, P&amp;lt;0.0001 by 2-sided Fisher Exact Test). Notch1 was expressed at high levels in 20% of lung cancers including sarcoma, neuroendocrine, small cell and undifferentiated carcinomas, as well as adenocarcinoma and squamous cell carcinomas. High expression of Notch1 was observed in 9% of ovarian tumors including undifferentiated carcinoma, serous adenocarcinoma, and endometrioid adenocarcinoma. In breast cancer, it was noted in one case of infiltrating ductal carcinoma with triple-negative phenotype. Expression of high-level Notch1 varies in lung cancer vs. ovarian cancer vs. breast cancer (P=0.002 by Chi-square statistic), and was frequently associated with NICD expression. Notch1 was not significantly associated with estrogen receptor, progesterone receptor or HER2 status in breast cancer. These data suggest that the frequency of all levels of Notch1 expression is significantly higher in lung cancer and ovarian cancer than breast cancer; and high-level Notch1 is more frequent in lung cancer than in ovarian cancer, and, likewise, more frequent in ovarian cancer than in breast cancer. For the first time, expression of Notch1/NICD has been identified in undifferentiated carcinomas. The findings may provide useful information for the rational design of Notch inhibitor clinical trials. Citation Format: Dat Nguyen, Larry Rubinstein, Mark E. Sherman, Joseph E. Tomaszewski, Naoko Takebe, Percy Ivy, James H. Doroshow, Sherry X. Yang. Differential expression of Notch1 in lung, ovarian and breast cancers. [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 3838. doi:10.1158/1538-7445.AM2014-3838
Arginine Vasopressin in Vasodilatory Shock
Authors: Flávio Danni Fuchs, João Wilney Franco Filho
Journal: Circulation (2003)

Arginine Vasopressin in Vasodilatory ShockTo the Editor:Dünser et al 1 concluded that the combined infusion of vasopressin and norepinephrine is superior to infusion of norepinephrine alone in the treatment of shock resistant to catecholamine.We believe that this study is flawed and do not support such a conclusion.First of all, the design included two interventions in parallel, one of arginine vasopressin (and its control group in the other arm, without such treatment) and the other with two different doses of norepinephrine.They concluded that the combination group required a lower dose of norepinephrine, which was a consequence of the experimental protocol.The major shortcoming of this study, however, is an evident mistake in the statistical interpretation of their main results.The authors concluded that patients treated with the combination had improved cardiac performance, an effect that did not occur at all.Table 2 of the article shows that the cardiac index (CI) was different between groups among all experiments, a finding that resulted in the P value of 0.001 presented in the table (significant group effect).In fact, the CI was different between groups at the time of the beginning of the infusion, and it remained different for 48 hours.In the ANOVA for multiple measurements and factors, the treatment effect is tested by the time-group interaction, with its corresponding F and P values and not by the group or time effect in isolation.It is clear that there is no time-group interaction in the case of CI and probably not also in the evaluation of mean arterial pressure.On the basis of such findings, the authors stated that norepinephrine is cardiotoxic.Their conclusion is not supported by the reference cited, 2 which does not address the potential deleterious effect of norepinephrine in vasodilatory shock.It addresses instead the role of the sympathetic nervous system in the genesis of ventricular arrhythmia.
Working to Shift Clinician Perceptions—Reply
Authors: John J. You, Daren K. Heyland
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Sun awareness in school teachers
Authors: None Fleming, None Nicolson, None Toal, None Mackie
Journal: British Journal of Dermatology (1998)

School children are important targets for sun awareness education, but the knowledge, attitudes and behaviour of school teachers with respect to sun awareness are poorly understood. A questionnaire‐based survey of 76 school teachers was undertaken. Twenty‐four per cent of teachers indicated previous experience in teaching sun awareness, but 93% of teachers had no classroom resources for teaching sun awareness. Sun awareness was perceived by respondents as unimportant relative to other health education issues. There was considerable scope for improvement in attitudes and behaviour of teachers with respect to sun awareness. Teachers need more information about environmental factors which affect strength of sunlight, individual risk factors for sunburn and sunscreen strength. Intervention strategies involving school teachers need simple messages, emphasizing the importance of shade, clothing and hats in sun avoidance.
Declining Incidence of Hepatitis A—Reply
Authors: Annemarie Wasley, Beth Bell
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract P1-09-26: Surgery for breast cancer in the elderly is associated with better outcomes
Authors: Yasmin A Jauhari, Pam Chaichanavichkij, Richard J Sainsbury
Journal: Cancer Research (2015)

Abstract Background Breast cancer often presents differently in the elderly with more neglected disease. There is patchy evidence to support surgery as a preferred management tool with a positive survival outcome. The objective of this study was to 1. Understand disease presentation and management of patients diagnosed with breast cancer over the age of 80, and 2. To review survival outcome between conservative and surgically managed elderly breast cancer patients. Method A retrospective single centre case series was conducted from 2008 to 2014 on patients aged 80 and over at breast cancer diagnosis. Survival outcome between conservative and surgical treatment groups were reported by Kaplan Meier analysis, with comparison by log-rank test. Results There were 156 patients, with a median age of 86.6 years (range 80 – 107). 67.9% had invasive ductal carcinoma. At presentation, 9.6% had T4 fungating lesions and 11.9% had distant metastatic disease. The median tumour size was 25mm (range 4 – 85mm) and 81.5% were oestrogen receptor positive. Conservative treatment (44.9%, n = 70) was accounted for in 80% of cases by patient choice and/or pre-morbid status precluding surgery. 55.1% of patients underwent surgical resections, the majority of which were performed with curative intent (96.4%). 11 patients had surgery under local anaesthetic with no complications. Median duration of hospital stay was 1 day. Conservative vs. surgical cohorts were comparable in co-morbidities aside from age (89.6 +/- 5.1 vs. 85.2 +/- 4.2 years, p = 0.005)) and dementia (18 vs. 9 (p = 0.015). The overall survival for those treated conservatively was 29 +/- 4.1 months compared to 40 +/- 6.1 months (p = 0.004) for those having surgery. Conclusion The elderly are more likely to present with advanced or neglected breast cancer. Those undergoing surgery had a significant survival advantage and this modality should be offered unless co-morbidities are severe. Citation Format: Yasmin A Jauhari, Pam Chaichanavichkij, Richard J Sainsbury. Surgery for breast cancer in the elderly is associated with better outcomes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-26.