tbuckley/cabot-search huggingface dataset:
Abstract A18: Evaluating the potential to repurpose statins for ovarian cancer therapy
Authors: Paul T. Kroeger, Ronny Drapkin
Journal: Clinical Cancer Research (2020)

Abstract The recent success of PARP inhibitors in patients with BRCA1/2 mutant ovarian tumors highlights the importance of identifying druggable vulnerabilities in this disease. The fact that not all ovarian cancer patients will benefit from PARP inhibitors or experience durable responses places great emphasis on the need to identify additional therapies. Repurposing existing FDA-approved drugs offers an opportunity to accelerate the progress of drug development. Statins are drugs primarily prescribed for hypercholesterolemia and have been scrutinized for decades. Some studies demonstrated, through epidemiologic approaches and experimental studies, that statins have anticancer properties. We hypothesized that statins can be repositioned as part of a therapeutic regimen for HGSOC. Here, we demonstrate that certain ovarian cancer cell lines are exquisitely sensitive to treatment with statins. In addition, we show that the sensitivity to statins is an on-target effect by rescuing with downstream members of the mevalonate pathway. Our ongoing studies reveal that HGSOC cells that are sensitive to stain treatment manifest an amplification of chromosome 1q21. Within this genomic region are the S100 proteins, previously identified as potential biomarkers in several cancers, as well as the antiapoptotic protein MCL1. Using reverse phase protein arrays (RPPA) we found that MCL1 levels were altered in statin-sensitive cell lines, while there was no such change in non-sensitive lines. After identifying MCL1 as a potential marker of response, Western blot analysis demonstrated a dose-dependent decrease in the protein level of MCL1 with increasing statin concentration. Additionally, a short, proapoptotic splice variant of MCL1 was produced upon statin treatment, but only in the sensitive lines. Mechanistically, we find that phospho-YAP (inactive) is upregulated after statin treatment. Using a syngeneic cell line system, we were able to demonstrate that overexpression of YAP increases sensitivity to statins. Interestingly, a constitutively active form of YAP (nonphosphorylatable) remains insensitive, suggesting the importance of the phosphorylation event itself. This data corroborated previous research that suggested that multiple different statins decrease nuclear YAP and suggest a mechanism for statin sensitivity. Given its role as an oncogene, the apparent ability of statins to deactivate YAP and downregulate MCL1 steers statins in a promising direction for their repositioning for future therapeutic use. Citation Format: Paul T. Kroeger, Jr., Ronny Drapkin. Evaluating the potential to repurpose statins for ovarian cancer therapy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A18.
BRAZIL
Journal: JAMA (1949)

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
BUENOS AIRES
Journal: JAMA (1928)

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Letterbox finger
Authors: D Menzies
Journal: BMJ (1988)

to baseline values within seven days; creatinine clearance was slightly but not significantly reduced (from 81 (9) to 77 (12) ml/min) two days after embolisation but seven days after embolisation was 92 (9) ml/min.Serum creatinine concentration and creatinine clearance were unchanged from baseline values throughout the follow up.
Part 6: Advanced Cardiovascular Life Support
Authors: All who respond to cardiorespiratory emergencies should arrive well trained in a simple, easy-to-remember approach. The ACLS Provider Course teaches the, to emergency cardiovascular care. This memory aid describes 2 sets of 4 steps:, (8 total steps). With each step the responder performs an, and then, if the assessment so indicates
Journal: Circulation (2000)
In Brief
Journal: JAMA (1976)

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A Text-Book of Medicine
Journal: JAMA (1934)

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T3 Thyrotoxicosis
Authors: Kenneth Sterling
Journal: JAMA (1970)

Thyrotoxicosis may be caused by elevated serum triiodothyronine (T3) in the presence of normal thyroxine (T4) concentration. Of a series of 26 selected cases, 12 have been observed in patients with toxic nodular goiter, most typically with a solitary hyperfunctioning nodule, but also with multinodular goiters. The disorder has also been observed in seven patients with classical toxic diffuse goiter (Graves' disease) including two patients with typical infiltrative ophthalmopathy. The diagnosis of T3 thyrotoxicosis should be suspected when there are clinics and laboratory evidences of hypermetabolism in the presence of normal serum T4 and the absence of thyroxine-binding globulin (TBG) abnormalities. Until T3 measurement becomes more readily available, it is advisable to employ screening with the T3 suppression test, regardless of the initial 24-hour thyroidal radioactive iodine uptake value.
Medical News
Journal: JAMA (1970)

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National Cancer Institute begins laetril clinical trial
Journal: JAMA (1980)

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The Cover
Authors: —Jody Zylke
Journal: JAMA (1987)

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Stillings pseudo-isochromatische Tafeln zur Prüfung des Farbensinnes.
Journal: JAMA (1926)

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TENNESSEE PRACTITIONERS AND THE VERBATIM RECORDING OF LICENSES.
Journal: JAMA (1907)

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FOOTBALL MORTALITY AMONG BOYS.
Journal: JAMA (1907)

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
Human Wart Virus Found in Many Papillomas
Journal: JAMA (1980)

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
Dissecting the factors involved in the pathogenesis of sodium retention in cirrhosis with ascites using TIPS . Depts of Medicine*, Radiology? &amp; Nuclear Cardiology?, Toronto Hospital, Toronto, Canada
Journal: Hepatology (1995)

Endothelin (ET), a potent endothelium-derived vasoconstrictor peptide [1] contributes to the regulation of glomerular function both through changes in hemodynamics and through changes in glomerular configuration. Three structurally and pharmacologically distinct isoforms of the peptide have been identified with a molecular weight of 2.5 kDa, each consisting of 21 amino acids. These isopeptides share a common structure with a hydrophobic C-terminal end and two disulfide bonds, thus forming a hairpin loop at the amino terminus. ET-1 differs from ET-2 by only two amino acids, and from ET-3 by six amino acids. Each ET isopeptide is encoded by separate genes at distinct chromosomal loci [2].All ETs are synthesized via proteolytical cleavage from specific prohormones (Fig. 1). Prepro ETs are long polypeptide chains consisting of ∼203 amino acids [1] which exhibit specific differences among the isopeptides. ET isopeptide precursors are proteolytically cleaved by processing endopeptidases that recognize paired basic amino acids (Arg-Arg or Lys-Arg) and thus form pro or big ET. Pro ET-1 is then converted to mature ET-1 by cleavage of the Trp21-Val22 bond via a highly specific endothelin-1-converting enzyme, which is a Phosphoramidon-sensitive, membrane bound metalloprotease (Fig. 1) [3–5]. Pro ET-3 is less susceptible to this protease, so that the presence of other types of endothelin-converting enzyme are suspected [5].ETs bind to two G-protein coupled receptors of ∼43 to ∼73 kD molecular weight [6–8], consisting of ∼415 to ∼427 amino acids and having seven transmembrane domains [6, 7]. The ETA receptor binds ET-1 with 2- to 10-fold higher affinity than ET-2 and > 100-fold higher affinity than ET-3 [6–9], whereas the ETB receptor has similar affinities to all three peptides [7, 8].Little is known about the fate of ET. ETs are either inactivated by receptor internalization or by enzymatic cleavage of the peptide prior to receptor coupling [10–13].
COMPARISON OF EFFICACY AND SAFETY BETWEEN SIROLIMUS, PACLITAXEL, EVEROLIMUS–ELUTING STENT AND SEQUENT™ PLEASE, A DRUG–ELUTING BALLOON ON THE OUTCOME OF PATIENTS WITH DIFFUSE IN–STENT RESTENOSIS AFTER BARE METAL STENT IMPLANTATION
Authors: Sunao Nakamura, Hisao Ogawa, Hans Yeo, Wasan Udayachalerm, Damras Tresukosol
Journal: Journal of the American College of Cardiology (2013)
Announcements
Authors: Patricia L. Dobkin, Robert O. Pihl, Claude Breault, M.J. Christie, D. French, L. Weatherstone, A. West, M. Rigatelli, M. Marcon, A.R. Morritti, R. Rizzardo, S. Novarin, G. Forza, M. Cosentino, Hideki Teshima, Hiroshi Sogawa, Koji Mizobe, Naoko Kuroki, Tetsuya Nakagawa, Brian Baker, Paul Dorian, Nadia Woloshyn, Shahe Kazarian, Caroline Lanphier, Julian Hafner, Robyn J. Miller, Michèle Montreuil, Roland Jouvent, Solange Carton, Catherine Bungener, Daniel Widlöcher, Jussi Kauhanen, Juhani Julkunen, Jukka T. Salonen
Journal: Psychotherapy and Psychosomatics (1991)
Iatrogenic dermatitis.
Authors: I Sneddon
Journal: BMJ (1969)

DICJou 49prodromal and headache stages.'In each case the cortex perfusion rates were measured simultaneously in both hemispheres during the attack and later when the patients were fully recovered.I found a reduction in per- fusion rate of 22-5% during the prodromal phase (P>0005), but only a small, though significant, increase of 8-3% (P>0-02) in the headache stage.This small increase is quite compatible with a reactive hyperaemia fol- lowing vasoconstriction in the prodromal stage, but is hardly sufficient to cause symptoms such as headache.Drs.Skinh0j and Paulson found a 47% increase in flow in the headache stage compared with their normal values, but this figure should be treated with some caution, since the resting flow in their patient is not known and this, together with the error associated with the method, means that no certain conclusions can be drawn from a single observation in one patient.-