tbuckley/cabot-search huggingface dataset:
Decreased BRCA1 expression alters the response of MCF7 cells to estradiol and tamoxifen
Authors: Zhijiu Zhong, Alima Minkeu, Andrew Quong, Judy Quong
Journal: Cancer Research (2008)

2799   BRCA1 plays a role not only in inherited disease but also in sporadic breast cancer. Although genetic mutations are rare in sporadic breast cancers, several reports have found decreased BRCA1 protein levels in sporadic breast cancers. BRCA1 contains several functional domains that interact directly or indirectly with a variety of other molecules, including tumor suppressors, oncogenes, DNA damage repair proteins, cell-cycle regulators, transcriptional activators and repressors. Therefore, BRCA1 is likely to serve as an important central component in multiple biological pathways that regulate pathways involved in breast tumorigenesis. Furthermore, studies have shown a strong correlation between BRCA1 down-regulation and increased metastasis. The goal of this project is to investigate the effect of decreased BRCA1 protein expression estrogen signaling in MCF7 breast cancer cells stably expressing BRCA1 shRNA. To measure the effects of BRCA1 levels on proliferation, the MTT assay was conducted 1 through 5 days after cells were plated. Proliferation of MCF7/BRCA1 cells which have lower BRCA1 protein levels proliferate significantly faster than MCF7/scr cells. We found that decreased levels of the BRCA1 protein results in increased cell proliferation. Next, we looked at the effects of BRCA1 protein levels on response to estradiol and tamoxifen. Cells were treated with tamoxifen or estradiol and then the MTT assay was carried out 2, 3, 4 and 5 days after treatment. In the case of estradiol, we see a trend in that MCF7/BRCA1 cells proliferated at a higher rate than control MCF7/scr cells. In the case of tamoxifen, MCF7/BRCA1 cells were less responsive to tamoxifen compared to control MCF7/scr cells. After 5 days of treatment, 8 μM tamoxifen inhibited MCF7/scr cell proliferation by 10-15% greater than MCF7/BRCA1 cells. Overall, we found that decreasing BRCA1 protein levels increased baseline cell proliferation rates and desensitizes cells to the inhibitory effects of tamoxifen and shows a trend toward sensitizing cells to the proliferative effects of estradiol. To the mechanisms by which BRCA1 levels affect estrogen signaling, we performed two-dimensional liquid-chromatography mass spectrometry to identify proteins that are differential expressed in a BRCA1 dependent manner. As expected based on the increased proliferation seen in the MCF7/BRCA1 cells, many of the proteins increased in MCF7/BRCA1 represented metabolic proteins, suggesting a general in metabolic activity in cells where BRCA1 was decreased. Other proteins of potential interest include those involved in cell cycle control and tumor suppression, such as Mitotic Spindle Assembly Checkpoint Protein MAD1 and S-phase kinase-associated protein 1A. Our data shows that decreased BRCA1 expression induces changes in MCF7 cells consistent with a potential role of BRCA1 in metastasis and tamoxifen response in breast cancer.
P3.15-22 Validation of Eurolung Risk Models in a Japanese Population: A Retrospective Single-Center Analysis of 612 Cases
Authors: A. Nagoya, R. Kanzaki, N. Ose, T. Kanou, S. Funaki, M. Minami, Y. Shintani, M. Okumura
Journal: Journal of Thoracic Oncology (2018)
RNA-Modified T Cells Mediate Effective Delivery of Immunomodulatory Cytokines to Brain Tumors
Authors: Fernanda Pohl-Guimarães, Changlin Yang, Kyle A. Dyson, Tyler J. Wildes, Jeffrey Drake, Jianping Huang, Catherine Flores, Elias J. Sayour, Duane A. Mitchell
Journal: Molecular Therapy (2018)

With the presence of the blood-brain barrier (BBB), successful immunotherapeutic drug delivery to CNS malignancies remains a challenge. Immunomodulatory agents, such as cytokines, can reprogram the intratumoral microenvironment; however, systemic cytokine delivery has limited access to the CNS. To bypass the limitations of systemically administered cytokines, we investigated if RNA-modified T cells could deliver macromolecules directly to brain tumors. The abilities of T cells to cross the BBB and mediate direct cytotoxic killing of intracranial tumors make them an attractive tool as biological carriers. Using T cell mRNA electroporation, we demonstrated that activated T cells can be modified to secrete granulocyte macrophage colony-stimulating factor (GM-CSF) protein while retaining their inherent effector functions in vitro. GM-CSF RNA-modified T cells effectively delivered GM-CSF to intracranial tumors in vivo and significantly extended overall survival in an orthotopic treatment model. Importantly, GM-CSF RNA-modified T cells demonstrated superior anti-tumor efficacy as compared to unmodified T cells alone or in combination with systemic administration of recombinant GM-CSF. Anti-tumor effects were associated with increased IFN-γ secretion locally within the tumor microenvironment and systemic antigen-specific T cell expansion. These findings demonstrate that RNA-modified T cells may serve as a versatile platform for the effective delivery of biological agents to CNS tumors.
Intestinal dysbiosis in inflammatory bowel disease associated with primary immunodeficiency
Authors: Harry Sokol, Nizar Mahlaoui, Claire Aguilar, Perrine Bach, Olivier Join-Lambert, Aurélie Garraffo, Philippe Seksik, François Danion, Sarah Jegou, Marjolene Straube, Christelle Lenoir, Bénédicte Neven, Despina Moshous, Stéphane Blanche, Bénédicte Pigneur, Olivier Goulet, Frank Ruemmele, Felipe Suarez, Laurent Beaugerie, Stéphanie Pannier, Françoise Mazingue, Olivier Lortholary, Lionel Galicier, Capucine Picard, Geneviève de Saint Basile, Sylvain Latour, Alain Fischer
Journal: Journal of Allergy and Clinical Immunology (2018)
Nivolumab in non-small cell lung cancer: French evaluation of use, current practices and medico-economic approach
Authors: F. Grude, R. Corre, T. Urban, J. Bennouna, G. De Chabot, T. Chatellier, F. Denis, R. Descourt, J.-Y. Douillard, C. Ricordel, O. Molinier, F. Pinquie, G. Robinet, M. Travers, B. Moiteaux, D. Deniel Lagadec, F. Marhuenda
Journal: Annals of Oncology (2018)
Inhibition of GSK-3 to induce cardiomyocyte proliferation: a recipe for in situ cardiac regeneration
Authors: Anand Prakash Singh, Prachi Umbarkar, Yuanjun Guo, Thomas Force, Manisha Gupte, Hind Lal
Journal: Cardiovascular Research (2018)

Abstract With an estimated 38 million current patients, heart failure (HF) is a leading cause of morbidity and mortality worldwide. Although the aetiology differs, HF is largely a disease of cardiomyocyte (CM) death or dysfunction. Due to the famously limited amount of regenerative capacity of the myocardium, the only viable option for advanced HF patients is cardiac transplantation; however, donor’s hearts are in very short supply. Thus, novel regenerative strategies are urgently needed to reconstitute the injured hearts. Emerging data from our lab and others have elucidated that CM-specific deletion of glycogen synthase kinase (GSK)-3 family of kinases induces CM proliferation, and the degree of proliferation is amplified in the setting of cardiac stress. If this proliferation is sufficiently robust, one could induce meaningful regeneration without the need for delivering exogenous cells to the injured myocardium (i.e. cardiac regeneration in situ). Herein, we will discuss the emerging role of the GSK-3s in CM proliferation and differentiation, including their potential implications in cardiac regeneration. The underlying molecular interactions and cross-talk among signalling pathways will be discussed. We will also review the specificity and limitations of the available small molecule inhibitors targeting GSK-3 and their potential applications to stimulate the endogenous cardiac regenerative responses to repair the injured heart.
Abstract 17148: Transplant of Smooth Muscle cell-Endothelial Progenitor Cell Bi-level Cell-sheet Attenuated Cardiac Dysfunction and Microvascular Disease in Diabetic Cardiomyopathy
Authors: Masashi Kawamura, Andrew B Goldstone, Yasuhiro Shudo, Amanda N Steele, Michael Hopkins, Bryan Edwards, Jay Patel, Christopher Jensen, Lyndsay M Stapleton, Anahita Eskandari, Arnor B Ingason, Y J Woo
Journal: Circulation (2016)

Introduction: Diabetes mellitus (DM) is a risk factor for coronary artery disease and negatively impacts outcomes after CABG. Current treatments focus on macrorevascularization and neglect the micr...
Study of the activation of TLR receptors in neurospheres from glioblastoma cells in vitro
Authors: D. Albert Bellver, R. Gil-Benso, A. Martínez, T. San-Miguel, L. Muñoz-Hidalgo, A. Carratalá, D. Gozalbo, C. López-Ginés, M. Cerdá-Nicolás, M.L. Gil, J. Megías
Journal: Annals of Oncology (2018)
GW29-e1000 Reperfusion therapy and antithrombotic treatments in patients 75 years and older with ST-segment elevation myocardial infarction in China: findings from the CCC-ACS Project
Authors: Mengge ZHOU, Jing Liu, Yongchen Hao, Gregg C. Fonarow, Junbo Ge, Kathryn A. Taubert, Louise Morgan, Changsheng Ma, Yaling Han, Sidney C. Smith, Yong Huo, Dong Zhao
Journal: Journal of the American College of Cardiology (2018)
Abstract 20502: Reduction of Health Disparities in Appalachians With Multiple Cardiovascular Disease Risk Factors: A Randomized Controlled Trial
Authors: Debra K Moser, Frances Feltner, Martha J Biddle, Misook L Chung, Terry A Lennie
Journal: Circulation (2017)

Introduction: Appalachia is a socioeconomically austere environment with marked health disparities. People living in Appalachian Kentucky represent the top 1% for cardiovascular disease (CVD) risk,...
Long noncoding RNA Hoxaas3 contributes to hypoxia-induced pulmonary artery smooth muscle cell proliferation
Authors: Hongyue Zhang, Ying Liu, Lixin Yan, Siqi Wang, Min Zhang, Cui Ma, Xiaodong Zheng, He Chen, Daling Zhu
Journal: Cardiovascular Research (2018)

Abstract Aims Long noncoding RNAs (lncRNAs) are involved in the regulation of vascular smooth muscle cells and cardiovascular pathology. However, the contribution of lncRNAs to pulmonary hypertension (PH) remains largely unknown. The over-proliferation of pulmonary artery smooth muscle cells (PASMCs) causes pulmonary arterial smooth muscle hypertrophy and stenosis of the pulmonary vascular lumen, resulting in PH. Here, we investigated the biological role of a novel lncRNA, Hoxa cluster antisense RNA 3 (Hoxaas3), in the regulation of cell proliferation in PH. Methods and results Hoxaas3 was up-regulated in the lung vasculature of hypoxic mice and in PASMCs under hypoxic conditions. Histone H3 Lysine 9 acetylation of Hoxaas3 promoted gene expression. Moreover, high expression of Hoxaas3 was associated with cell proliferation and modulated cell cycle distribution by up-regulating Homeobox a3 at the mRNA and protein levels. Conclusion This study defined the role and mechanism of action of Hoxaas3 in the regulation of cell proliferation in PH, which should facilitate the development of new therapeutic strategies for the treatment of this disease.
Somatostatin Interneurons Facilitate Hippocampal-Prefrontal Synchrony and Prefrontal Spatial Encoding
Authors: Atheir I. Abbas, Marina J.M. Sundiang, Britt Henoch, Mitchell P. Morton, Scott S. Bolkan, Alan J. Park, Alexander Z. Harris, Christoph Kellendonk, Joshua A. Gordon
Journal: Neuron (2018)
GW29-e0513 Monitoring of myocardial viability in patients with myocardial infarction based on magnetocardiographic analysis of ventricular depolarisation
Authors: Illya Chaikovsky, Michael Primin, Igor Nedayvoda, Georg Mjasnikov, Anatoly Kazmirchyk, Michael Lutay, Leonid Stadnyk, Wenming Ji, Ming Lei
Journal: Journal of the American College of Cardiology (2018)
Abstract P234: Dairy Fat Intake and Risk of Type 2 Diabetes in 3 Cohorts of US Adults
Authors: Andres Ardisson Korat, Frank B Hu, Qi Sun
Journal: Circulation (2018)

Background: Previous studies have examined the association between dairy fat intake and incident Type 2 Diabetes (T2D) by conducting analyses of dairy products stratified by fat content, although data linking dairy fat intake and incident T2D and their substitution for other nutrients are sparse. Objective: The aim of this study is to evaluate the association between dairy fat intake and risk of T2D. We assessed the hypothesis that replacing calories from dairy fat for other animal fat or refined carbohydrates will result in modest increases in T2D risk. Methods: We followed up 41,670 men in the Health Professionals Follow-Up Study (1986-2010), 84, 685 women in the Nurses’ Health Study (NHS; 1980-2012), and 90,325 women in the NHSII (1991-2011). Diet was assessed every 4 years with the use of validated food-frequency questionnaires, and other health and lifestyle covariates were collected biennially. Dairy fat contents were determined for dairy products and food items that contain dairy. Dairy fat intake from all relevant food items was summed to calculate total intake, which was expressed as percent of total energy. Incident T2D cases were identified by self-reports during follow-up and confirmed by a validated supplementary questionnaire. A time-dependent Cox proportional hazards regression was used to estimate the hazard ratio for dairy fat intake and T2D risk. Results: During 4,661,518 years of follow-up, we documented 18,298 incident T2D cases. In multivariate models, a 5% increase in energy dairy fat was associated with a 2% risk increase in T2D (RR: 1.02; 95% CI: 1.00, 1.05). In isocaloric substitution models, the replacement of 5% of calories from dairy fat with the equivalent energy from other sources of animal fat or carbohydrate from refined grains was associated with an 7% [RR: 1.07; 95% CI: 1.04, 1.09], and a 7% [RR: 1.07; 95% CI: 1.04, 1.11] increased risk of T2D, respectively. Conversely, a 5% calorie substitution of carbohydrate from whole grains was associated with 7% lower risk of T2D [RR: 0.93; 95% CI: 0.89, 0.97]. Conclusions: In conclusion, dairy fat intake was modestly associated with a higher T2D risk. The replacement of dairy fat with carbohydrates from whole grains may decrease incident T2D risk. Further research is warranted to elucidate the role of other components in dairy products that may contribute to previously reported null associations with T2D.
Abstract 16566: TLR3 Mediates Neonatal Heart Repair and Regeneration Through Glycolysis-Dependent YAP/TAZ Mediated miR-152 Expression
Authors: Xiaohui Wang, Tuanzhu Ha, John Kalbfleisch, David Williams, Chuanfu Li
Journal: Circulation (2016)

Introduction: The neonatal heart possesses the capability of regenerating and repairing damaged myocardium which is lost when cardiac metabolism switches from predominate glycolysis to oxidative ph...
Abstract 222: Inhibition of Phosphodiesterase 1 Confers Striking Therapeutic Benefit to HFpEF in Mice
Authors: Hanming Zhang, Xuejun Wang
Journal: Circulation Research (2017)

Heart Failure with preserved Ejection Fraction (HFpEF) is the most prevalent HF but with virtually no effective treatment proven. Targeted removal of misfolded proteins by the ubiquitin-proteasome system (UPS) is pivotal to protein quality control. UPS function insufficiency contributes to HF genesis, making UPS priming an attractive strategy to treat HF. Previously we reported that protein kinase G (PKG) positively regulates cardiac UPS functioning while others showed PKA stimulates the proteasome. Thus, we propose that simultaneous activation of PKG and PKA might be a powerful strategy to improve cardiac UPS function and thereby benefit HF treatment. Here we provide the first evidence that strongly supports this proposition. We found that myocardial protein and mRNA levels of phosphodiesterase 1 (PDE1), a major cardiac PDE that degrades both PKG and PKA, were markedly elevated in CryAB R120G transgenic (tg) mice which are a classic model of cardiac proteinopathy with HFpEF as the major manifestation of its cardiac dysfunction. To test whether PDE1 inhibition (PDE1I) primes cardiac UPS and thereby ameliorates cardiac proteotoxicity, we performed cell cultures and mouse in vivo experiments taking advantage of a proven surrogate UPS substrate (GFPdgn) and a bona fide misfolded protein (CryAB R120 ), which demonstrates that pharmacological PDE1I significantly improves cardiac UPS performance and enhances degradation of the misfolded protein. We then treated CryAB R120G tg mice with PDE1 inhibitor LSN2790158 (3mg/kg/day x 28 days) or vehicle control via osmotic mini-pumps, starting at 4 months of age when HFpEF has clearly developed in the tg mice as reflected by significant decreases in left ventricular (LV) end-diastolic volume, stroke volume, and cardiac output and increases in end-diastolic LV posterior wall thickness along with unchanged EF, compared to littermate non-tg mice. Echocardiography revealed that that 4 weeks of PDE1 inhibitor treatment resulted in drastic improvement of HFpEF and Kaplan-Meier survival analysis shows striking delay of premature death in the PDE1I group vs. vehicle-treated group. Taken together, our data provide compelling evidence for the first time that PDE1I shall be explored as a new therapeutic strategy for HFpEF.
SPIRE: A phase Ib/ randomised IIa open label clinical trial combining guadecitabine with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer
Authors: S.J. Crabb, S.J. Danson, D. Dunkley, M. Kalevras, A. Whitehead, S. Hill, K. Fines, C. Robb, J. Bennett, L. Ksiazek, S.L. Brown, L. Evans, M. Serra, K. Jones, C. McDowell, J.W. Catto, R. Huddart, G. Griffths
Journal: Annals of Oncology (2018)
Abstract #4968: Evaluation and functional characterization of periostin isoforms in lung and kidney carcinoma
Authors: Laura Morra, Van Duc Luu, Adriana von Teichman, Peter Schraml, Alex Soltermann, Holger Moch
Journal: Cancer Research (2009)

Periostin (POSTN), also termed osteoblast-specific factor 2, is a secreted stromal protein of 93 kDa. Six different splice isoforms exist and have been reported, but only four of them have been sequenced. Periostin shares homology with the insect cell adhesion molecule fasciclin I and with human beta IgH3 and is induced by TGFbeta and BMP-2. Periostin promotes integrin-dependent cell adhesion and motility and supports osteoblastic cell lines attachment and spreading. It is expressed in few normal tissues (cardiac valves, placenta, embryonic periosteum and periodontal ligament) and is overexpressed in many cancerous tissues (lung, kidney, breast, ovarian, colon, prostate, head and neck cancer). It has been shown that high POSTN expression levels in serum correlate with tumor aggressivenes. Periostin also promotes epithelial mesenchymal transition of carcinoma cells which leads to invasion and metastasis. Therefore it is considered as a predictive marker and a potential target for tumor therapy. In our previous study periostin expression was analysed in a tissue microarray of 538 non-small cell lung cancers. We established that POSTN overexpression is associated with increasing TNM stage and grade. This study aims at the analysis of expression and localization of periostin isoforms in lung and kidney cancer and at their functional characterization. We performed: isoform-specific PCR; quantitative RT-PCR and immunoblot analysis on frozen tissues of 30 non-small cell lung cancer patients (adenocarcinoma and squamous cell carcinoma) and on frozen tissues of 30 kidney cancer patients (clear cell carcinoma and papillary carcinoma) and their matched non-neoplastic tissues. Furthermore we cloned and sequenced the region of periostin mRNA that undergoes alternative splicing (from exon 17 to exon 21), giving rise to different isoforms. Our current study identified four periostin isoforms in the lung and three isoforms in the kidney. Each of the isoforms was coexpressed in both tumor and matched non-neoplastic tissue. The cloning analysis of renal periostin isoforms revealed a new isoform which has to date not been reported in other human organs. The western blot analysis of lung and kidney cancer tissue and pleural effusions from lung cancer patients showed the presence of a cleaved form of periostin of 55 kDa. These results suggest potential novel tissue-specific functions of periostin isoforms in renal cell and lung carcinoma and open up the possibility of organ-specific targeted cancer therapy.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4968.
A prognostic model integrating clinical data and gene signatures in phase III neoadjuvant trial CALGB 40601 (Alliance)
Authors: Maki Tanioka, Joel S. Parker, Lynn N. Henry, Sara Tolaney, Chau Dang, Ian E. Krop, Lyndsay Harris, David Hillman, Mei Polley, Donald A. Berry, Eric P. Winer, Lisa A. Carey, Charles M. Perou
Journal: Annals of Oncology (2018)
Noise pollution: WHO sets limits on exposure to minimise adverse health effects
Authors: Susan Mayor
Journal: BMJ (2018)

Policy makers should consider how they can protect people’s health by minimising noise pollution from a variety of sources such as wind turbines, traffic, aircraft, railways, nightclubs, and sporting events, the World Health Organization has said.1

A report from WHO Europe set limits on exposure to environmental noise on the basis of a comprehensive review of available evidence on the impact of noise on human health.

Zsuzsanna Jakab, WHO regional director for Europe, said, “Noise is one of the most important environmental risks to health and continues to be …
Organic Foods for Cancer Prevention—Worth the Investment?
Authors: Elena C. Hemler, Jorge E. Chavarro, Frank B. Hu
Journal: JAMA Internal Medicine (2018)

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