tbuckley/cabot-search huggingface dataset:
Abstract 2545: Nek2 and other mitotic kinases are downstream of the E2F activators, and may modulate the epithelial-to-mesenchymal transition in breast cancer
Authors: Yainyrette Rivera-Rivera, Mihaela Marina, Harold I. Saavedra
Journal: Cancer Research (2019)

Abstract The E2F transcription factors have been extensively studied in cancer since they are known for their role in the regulation of cell cycle progression, centrosome duplication, cell survival, and other functions. We recently demonstrated that the E2F activators (E2F1, E2F2, and E2F3) regulate mitosis through the elevated expression of multiple mitotic proteins including Sgo1, Nek2, Hec1, BubR1, and Mps1. We have shown that Mps1 triggers EMT through multiple mechanisms. NIMA-related kinase 2 (Nek2) is a centrosome-associated protein kinase particularly abundant in cells during the G2-M phase, which primary function is to phosphorylate centrosome linker proteins to cause centrosome disjunction and the formation of the bipolar mitotic spindle. Previous results from our lab showed that overexpression of Nek2 in HCC1954 (Her2+ breast cancer cell line) with a knock down for E2F3 rescued a high centrosome amplification pattern and enhances the formation of invasive protrusions. cBioportal analysis using the TCGA database showed Nek2 mRNA alterations in 9.1% of breast cancer patients and is predominantly present in tumors that are ER-, PR-, and Her2- (25%). Similarly, analysis using the METABRIC database showed Nek2 mRNA alterations in 6.1% of breast cancer patients and is predominantly present in tumors from basal (24%), Her2+ (10%), and luminal B (13.9%) subtypes. Based on these results, we hypothesize that Nek2 overexpression has a role in the epithelial-to-mesenchymal (EMT) pathway leading to cell migration and invasion as prelude to metastasis in breast cancer. To address this, we used MCF10A non-tumorigenic mammary cells with or without the overexpression of Nek2 (MCF10A/GFP and MCF10A/GFP-Nek2). Our preliminary data indicates that overexpression of GFP-Nek2 in mammary epithelial cells enhances levels of vimentin, whereas decreased the levels of E-cadherin, suggesting a role of Nek2 in a mesenchymal state. Likewise, siRNA-mediated silencing of Nek2 in mesenchymal breast cancer cells modulates markers of EMT. Because inhibitors are available for Nek2, it would be feasible to target this kinase to combat metastatic HR- breast cancers. Our work will allow the identification of mechanistic molecular pathways influenced by Nek2 role in driving invasion and metastasis to highlight this mitotic kinase as a potential prognostic marker for high-risk breast tumors. Citation Format: Yainyrette Rivera-Rivera, Mihaela Marina, Harold I. Saavedra. Nek2 and other mitotic kinases are downstream of the E2F activators, and may modulate the epithelial-to-mesenchymal transition in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2545.
Immunomodulatory EFFECTS of Lenalidomide and Pomalidomide ON INTERACTION of TUMOR and BONE MARROW Accessory CELLS IN MULTIPLE MYELOMA.
Authors: Gullu Gorgun, Elisabetta Calabrese, Teru Hideshima, Giulia Perrone, Giada Bianchi, Hiroshi Ikeda, Mala Mani, Yiguo Hu, Diana Cristea, Loredana Santo, Yu-Tzu Tai, Nikhil Munshi, Paul Richardson, Kenneth C. Anderson
Journal: Blood (2009)
ULCER OF THE JEJUNUM FOLLOWING GASTRO-ENTEROSTOMY
Journal: JAMA (1921)

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
Phase II trial of concurrent split course hyperfractionated radiotherapy (Hfx RT), cisplatin (DDP) and paclitaxel (P) in patients with recurrent, previously irradiated squamous cell carcinoma of the head and neck (SCCHN): Results of RTOG 9911
Authors: C. J. Langer, J. Harris, E. Horwitz, N. Nicolaou, M. Kies, W. Curran, S. Wong, K. K. Ang
Journal: Journal of Clinical Oncology (2004)

5509 Background: Recurrent SCCHN, if not curable by surgery or RT, is almost always fatal. Chemotherapy (CTx) alone (eg. DDP, 5FU) yields median survival times (MST) of 8–10 mos and 1 yr survival (OS) of ≤ 35% at best. For limited relapse or patients (pts) with new unresectable SCCHN within previous RT portals, a potential role for re-irradiation combined with radiosensitizing CTx, exists. In a prior phase I trial of HFx RT/ DDP/ P, we observed ≥ 2 yr disease-free survival in 5 of 31 pts (ASCO 1999, A-1551), and therefore exported this regimen to RTOG for broader assessment. Methods: Eligibility stipulated recurrent SCCHN or second 1° tumors (SPT) in a previous RT field; measurable tumor; ≥ 75% of tumor volume previously treated to 45 Gy-75 Gy; ≥ 6 mos elapsed from prior RT, ECOG PS 0–1; ANC ≥1500, plts ≥ 100K, bili ≤1.5 mg/dl, creat ≤ 1.5 mg/dl, and absence of distant mets. Pts received HFx RT (1.5 Gy/Fx BID x 5d every 2 wks x 4), in combination with DDP 15 mg/m2 IV QD x 5 and P 20 mg/m2 IV QD x 5 q 2 wks x 4. G-CSF was given days 6 through 13 of each 2 wk cycle. Results: 105 pts were entered between 3/00 and 6/03. We analyzed the first 60 eligible pts (min potential F/U of 1 yr): median age 59; 77% male; 60% PS 1. 22% had SPTs. Oropharynx (37%) and oral cavity (32%) were the predominant 1° sites. Median prior RT dose was 65.4 Gy (range, 45–73 Gy). 77% of pts received all 4 scheduled cycles of chemo. Gr ≥ 4 acute toxicity (tox) occurred in 30%, Gr ≥ 4 acute heme tox in 27%. There were 4 fatal (Gr 5) toxicities: 2 in the acute period (dehydration, pneumonitis) and 2 late (carotid hemorrhage). In the full cohort of 105 pts, 7 Tx-related deaths (7%) occurred. At a median follow-up of 26.1 mos, MST is 13 mos with est. 1- and 2-yr OS rates of 53.2% (CI: 40.6, 65.9) and 27.5% (CI:16.1, 38.9). Conclusions: Despite a fairly high inc. of Gr 5 tox, 1- and 2-yr OS rates for split course HFxRT/DDP/P exceed results generally seen with chemotherapy alone. A phase III trial directly comparing CTx alone to concurrent CTx and re-irradiation is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb AstraZeneca Amgen; Bristol-Myers Squibb
Phase II Study of Phenylacetate in Patients With Recurrent Malignant Glioma: A North American Brain Tumor Consortium Report
Authors: Susan M. Chang, John G. Kuhn, H. Ian Robins, S. Clifford Schold, Alexander M. Spence, Mitchel S. Berger, Minesh P. Mehta, Michael E. Bozik, Ian Pollack, David Schiff, Mark Gilbert, Cathy Rankin, Michael D. Prados
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the response rate, time to treatment failure, and toxicity of phenylacetate in patients with recurrent malignant glioma and to identify plasma concentrations achieved during repeated continuous infusion of this agent. PATIENTS AND METHODS: Adult patients with recurrent malignant glioma were treated with phenylacetate. The schedule consisted of a 2-week continuous, intravenous infusion followed by a 2-week rest period (14 days on, 14 days off). A starting dose of 400 mg/kg total body weight per day of phenylacetate was initially used and subsequently changed to 400 mg/kg/d based on ideal body weight. Intrapatient dose escalations were allowed to a maximum of 450 mg/kg ideal body weight/d. Tumor response was assessed every 8 weeks. The National Cancer Institute common toxicity criteria were used to assess toxicity. Plasma concentrations achieved during the patients' first two 14-day infusions were assessed. RESULTS: Forty-three patients were enrolled between December 1994 and December 1996. Of these, 40 patients were assessable for toxicity and response to therapy. Reversible symptoms of fatigue and somnolence were the primary toxicities, with only mild hematologic toxicity. Thirty (75%) of the 40 patients failed treatment within 2 months, seven (17.5%) had stable disease, and three (7.5%) had a response defined as more than 50% reduction in the tumor. Median time to treatment failure was 2 months. Thirty-five patients have died, with a median survival of 8 months. Pharmacokinetic data for this dose schedule showed no difference in the mean plasma concentrations of phenylacetate between weeks 1 and 2 or between weeks 5 and 6. CONCLUSION: Phenylacetate has little activity at this dose schedule in patients with recurrent malignant glioma. Further studies with this drug would necessitate an evaluation of a different dose schedule.
Medical applications of fetal tissue transplantation. Council on Scientific Affairs and Council on Ethical and Judicial Affairs
Journal: JAMA (1990)

Fetal tissue transplantation has been attempted for a limited number of clinical disorders, including Parkinson's disease, diabetes, immunodeficiency disorders, and several metabolic disorders. Fetal tissue has intrinsic properties--ability to differentiate into multiple cell types, growth and proliferative ability, growth factor production, and reduced antigenicity--that make it attractive for transplantation research. At this time the results from fetal tissue grafts for Parkinson's disease and diabetes have not demonstrated significant long-term clinical benefit to patients with these disorders. Further research will be necessary to determine the potential value of fetal tissue transplantation. For these clinical investigations to proceed, specific ethical guidelines are needed to ensure that fetal tissue derived from elective abortions is used in a morally acceptable manner. These guidelines should separate, to the greatest extent possible, the decision by a woman to have an abortion from her consent to donate the postmortem tissue for transplantation purposes. Such ethical guidelines are offered in this report.This report by the American Medical Association's Council on Scientific Affairs and Council on Ethical and Judicial Affairs reviews the data on fetal tissue transplantation in animals and in specific clinical disorders such as diabetes and Parkinson's disease, surveys the legal and ethical issues surrounding fetal tissue transplants, and provides ethical guidelines for the use of fetal tissue for transplantation. The report concludes that further research is necessary to determine the value of fetal tissue transplantation, and that ethical guidelines should separate as much as possible a woman's decision to abort from her decision to donate fetal tissue for transplantation.
THE NATURE OF ECLAMPSIA.
Journal: JAMA (1906)

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
Effect of Dextro-Isomers of Thyroid Hormones on Serum Cholesterol Levels in Euthyroid Hypercholesterolemic Patients.
Authors: L. E. Hollister
Journal: Annals of Internal Medicine (1961)

s1 May 1961Effect of Dextro-Isomers of Thyroid Hormones on Serum Cholesterol Levels in Euthyroid Hypercholesterolemic Patients.L. E. Hollister, M.D., F.A.C.P., W. L. Arons, M. D., (Assoc.)L. E. Hollister, M.D., F.A.C.P.Search for more papers by this author, W. L. Arons, M. D., (Assoc.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1045_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptBoth of the naturally-occurring thyroid hormones, 1-thyroxine and 1-tri-iodothyronine, have been found to lower serum cholesterol levels in euthyroid and hypothyroid hypercholesterolemic subjects. The effects of the dextro-isomers, especially d-tri-iodothyronine, on serum lipids will be presented in this paper. Eleven euthyroid patients with elevated serum cholesterol levels have been treated with d-tri-iodothyronine for one year with doses of from 0.2 to 1.5 mg. per day. The minimal effective dose was 0.2 mg./day, which decreased serum cholesterol by 23% in one patient. Four patients experienced decreases of from 21 to 26% on doses of 0.4 mg. daily. Four patients required doses... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Palo Alto, Calif. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1961Volume 54, Issue 5Page: 1045-1045KeywordsCholesterolEffective doseHypercholesterolemiaLipidsThyroid hormones ePublished: 1 December 2008 Issue Published: 1 May 1961 PDF downloadLoading ...
BUCHAREST
Journal: JAMA (1933)

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 3277: IACS-9779, a development candidate that inhibits 2,3-dioxygenase (IDO) activity by blocking heme incorporation into IDO apoenzyme
Authors: Faika Mseeh, Matthew M. Hamilton, Joseph R. Marszalek, Norma E. Rogers, Connor A. Parker, Simon S. Yu, Zhen Liu, Naphtali J. Reyna, Timothy McAfoos, Brett W. Virgin-Downey, Paul G. Leonard, Jason B. Cross, Ningping Feng, Angela L. Harris, Andy M. Zuniga, Keith Mikule, Martin Tremblay, Yongying Jiang, Mikhila Mahendra, Jihai Pang, Qi Wu, Quanyun Xu, Timothy P. Heffernan, Philip Jones, Richard T. Lewis
Journal: Cancer Research (2019)

Abstract Increased expression of IDO1 is believed to create a tumor microenvironment that is immunosuppressive. In the course of our research directed at identifying potent and selective inhibitors of IDO1, we identified a class of compounds that inhibited IDO1 activity in a cellular context, but not in isolated enzymatic assays. We have conducted detailed mechanistic studies and shown that these molecules inhibit IDO1 by binding to the apo-enzyme, thus preventing the incorporation of the heme-cofactor into the active site of the holo-enzyme. Through an extensive medicinal chemistry campaign, we optimized a series of orally bioavailable, highly potent and selective inhibitors of IDO1 that possess excellent pharmacological properties. For several lead molecules, pharmacokinetic (PK) - pharmacodynamic (PD) relationships were established in whole blood and SKOV3 xenograft assays. The inhibition of IDO1 in a human whole-blood assay correlated well with the suppression of tumor kynurenine (KYN) that was observed in SKOV3 xenografts. At plasma concentrations of 3 µM, IACS-9779 supressed tumor KYN levels by 90%. IACS-9779 was well tolerated with excellent in vivo PK properties across multiple preclinical species, and a human PK prediction consistent with a low daily dose needed for full suppression of KYN production via IDO1. Note: This abstract was not presented at the meeting. Citation Format: Faika Mseeh, Matthew M. Hamilton, Joseph R. Marszalek, Norma E. Rogers, Connor A. Parker, Simon S. Yu, Zhen Liu, Naphtali J. Reyna, Timothy McAfoos, Brett W. Virgin-Downey, Paul G. Leonard, Jason B. Cross, Ningping Feng, Angela L. Harris, Andy M. Zuniga, Keith Mikule, Martin Tremblay, Yongying Jiang, Mikhila Mahendra, Jihai Pang, Qi Wu, Quanyun Xu, Timothy P. Heffernan, Philip Jones, Richard T. Lewis. IACS-9779, a development candidate that inhibits 2,3-dioxygenase (IDO) activity by blocking heme incorporation into IDO apoenzyme [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3277.
Widespread pulmonary lesions in a cyanotic woman
Authors: R. A. Boedecker
Journal: JAMA (1980)

<h3>History</h3> A 16-year-old girl presented with digital clubbing and peripheral cyanosis. She was first seen at 12 years of age for evaluation of shortness of breath with exertion. Circumoral and peripheral cyanosis had appeared during the previous several years. No family history of cardiac or vascular lesions or other medical problems was elicited. The patient's medical history was unremarkable. Her physical examination was normal with the exception of the circumoral and digital cyanosis with clubbing. Cardiac and chest examinations were normal without murmur or bruit. The ECG was normal. Laboratory tests showed an RBC count of 5.5 million/cu mm; hemoglobin level, 17 g/dL; and hematocrit reading, 50%. Arterial blood gas values on room air were as follows: oxygen saturation, 83%; Po2, 41 mm Hg; and Pco2, 34 mm Hg. The patient had a chest roentgenogram (Fig 1), showing multiple pulmonary nodules. Dye dilution and catheterization were done. <h3>Diagnosis</h3> Pulmonary micro-arteriovenous
Osthole increases glycosylation of hepatitis B surface antigen and suppresses the secretion of hepatitis B virus in vitro
Authors: R Huang
Journal: Hepatology (1996)

During screening of Chinese herbal medicines for the activities against hepatitis B virus (HBV), a known pure compound, osthole, was found to inhibit the secretion of HBV surface antigens in vitro. The secretion of hepatitis B surface antigen (HBsAg) in culture medium of MS-G2 and HuH-7 cells transfected with HBV DNA decreased by 60% to 70% after osthole treatment, without any detectable cytotoxic effects. Both 42-nm Dane particles and 22-nm subviral HBsAg particles were significantly reduced as revealed by density gradient analysis of viral particles and the endogenous; HBV DNA polymerase assay. The production of naked HBcAg particles was not changed by osthole treatment. The steady-state level of HBV-specific messenger RNA (mRNA) was not altered by osthole treatment, as revealed by Northern blot analysis, Immunoprecipitation of culture medium showed that the ratio of glycosylated versus nonglycosylated HBsAg increased after osthole treatment. Kinetic studies revealed that osthole increased the glycosylation rate of HBsAg, thus altering the ratio of glycosylated to unglycosylated HBsAg. The increase of glycosylation of HBsAg by osthole was blocked by tunicamycin, an inhibitor of protein glycosylation. We conclude that osthole suppresses the secretion of HBV in cell culture probably because of its novel function in increasing the glycosylation of HBsAg. (Hepatology 1996 Sep;24(3):508-15)
Teaching psychological medicine in the family practice office
Authors: R. N. Zabarenko
Journal: JAMA (1971)

An educational experiment was performed in which a psychiatrist and family physician met in the latter's office for a year at weekly intervals. Both participants felt the experiment was useful in teaching the addition of practical and useful psychological understanding in a directly applicable way. We are not yet in a position to estimate the cost/benefit ratio for changes in physician performance, but the early indications from this experiment suggest further field trials might be useful, not only in the private practice setting, but in many of the new family medicine programs.
Addressing Mental Health Needs of Balkan Refugees
Authors: M. J. Friedrich
Journal: JAMA (1999)

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