tbuckley/cabot-search huggingface dataset:
Abstract B28: The stress phenotype makes ovarian cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase
Authors: Martina Olivero, Daniela Dettori, Sabrina Arena, Davide Zecchin, Erica Lantelme, Maria Flavia Di Renzo
Journal: Clinical Cancer Research (2013)

Abstract CDT2/L2DTL/RAMP is one of the substrate receptors that binds the CRL4 ubiquitin ligase and confers it specificity for a number of substrates, such as CDT1, p21 and CHK1. Previously, we reported that in ovarian cancer cell lines increased susceptibility to cisplatin is associated to the down-regulation of the CDT2 gene. Here we show that CDT2 depletion was alone able to induce the apoptotic death not only in ovarian cancer cell lines but also in 10/10 other human cancer cell lines from different tissues, irrespective of p53, ATM and ATR status and CDT2 expression level. Conversely, CDT2 depletion did not affect non-transformed human cells, such as immortalized kidney, lung and breast cell lines, and primary cultures of endothelial cells and osteoblasts. After CDT2 suppression, all cancer cells underwent rereplication associated to the inability to destroy CDT1 and to cell death. The ectopic over-expression of an activated oncogene, such as the mutation-activated RAS or the amplified MET in non-transformed immortalized breast cell lines and primary human osteoblasts, respectively, made cells transformed in vitro, tumorigenic in vivo, and susceptible to CDT2 loss. Conversely, the knock-down of the tumor suppressor genes PTEN or RB1 did not transform immortalized breast cells and did not sensitize them to CDT2 loss. These data show that transformation makes cells “addicted” to CDT2. The widespread effect of CDT2 depletion in different cancer cells suggests that CDT2 is not in a synthetic lethal interaction to another specific gene or pathway but becomes dominant in these cells because of their stress phenotype, due to DNA damage, replication and mitotic stress. Citation Format: Martina Olivero, Daniela Dettori, Sabrina Arena, Davide Zecchin, Erica Lantelme, Maria Flavia Di Renzo. The stress phenotype makes ovarian cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B28.
Abstract 3388: DDX5 modulates Notch signaling via interaction with the MAML1 co-activator and is required to optimal Notch signaling in leukemic cells
Authors: Liang Tian, Shuibin Lin, Yumei Gu, Zirong Chen, Huangxuan Shen, Lizi Wu
Journal: Cancer Research (2011)

Abstract Notch receptor-mediated signaling is essential for embryonic development and adult tissue homeostasis by regulating cell proliferation, differentiation and survival. Aberrant Notch signaling is linked to many epithelial cancers and hematological malignancies. For example, activated NOTCH1 mutations are detected in more than 50% of T cell acute lymphoblastic leukemia (T-ALL) patients. Since the constitutive activation of Notch signaling results in leukemic cell transformation and is required for the maintenance of the leukemic phenotype, the Notch pathway is a promising and highly specific molecular therapeutic target for T-ALL. We have previously identified the family of the MAML transcriptional co-activators as essential components of the core Notch transcription activation complex. The prototypic member MAML1 was found to be the major co-activator that regulates NOTCH1 oncogenic activities in leukemic cells. Hence, the modulation of MAML1 expression levels or functional activities is expected to affect Notch-induced leukemic initiation and progression. However, it remains unclear how MAML1 function is regulated. To gain insights into the molecular basis underlying MAML1 function, we undertook the task of identifying cellular factors that interact with MAML1 and characterizing their roles in regulating Notch signaling and Notch-mediated T cell leukemia. Through proteomic studies, we identified DDX5, an ATP-dependent DEAD-box RNA helicase, as a component in the MAML1 protein complex. Given the role of DDX5 as a transcriptional modulator, we reasoned that DDX5 might be a critical regulator of MAML1-mediated Notch target genes transcription. We showed that DDX5 interacts with MAML1 in vitro and in vivo, and is associated with the endogenous Notch1 transcription activation complex through interaction with MAML1. Lentiviral-mediated shRNA knockdown of DDX5 resulted in decreased expression of Notch target signature, along with reduced cell proliferation and survival in leukemic cells that carry activated NOTCH1 mutations. Our findings thus revealed an essential role of DDX5 in promoting efficient Notch-mediated transcription in leukemic cells where the Notch pathway is constitutively activated, suggesting that DDX5 might be critical for Notch-mediated T-ALL pathogenesis and could be a potential new target for modulating the Notch signaling in leukemia. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3388. doi:10.1158/1538-7445.AM2011-3388
Informed Decision Making About Prostate Cancer Screening
Authors: Andrew J. Vickers
Journal: Annals of Internal Medicine (2015)

Letters17 March 2015Informed Decision Making About Prostate Cancer ScreeningAndrew J. Vickers, PhDAndrew J. Vickers, PhDFrom Memorial Sloan Kettering Cancer Center, New York, New York.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-5063-2 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We stand by our original statement and are unclear with regard to the relevance of citing data from a largely unscreened population because the denominator will not include many men with biopsy-detectable cancer (that is, “men with prostate cancer”). The purpose of our statement is to reorient patients away from any perception that prostate cancer is generally fatal. Empirical data show that this perception is widespread (1).Dr. O'Callaghan and colleagues suggest that our statement will, of itself, “lead to a decrease in screening rates.” We find this concept questionable, especially because the statement is immediately followed by ...Reference1. Gigerenzer G, Mata J, Frank R. Public knowledge of benefits of breast and prostate cancer screening in Europe. J Natl Cancer Inst. 2009;101:1216-20. [PMID: 19671770] doi:10.1093/jnci/djp237 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Andrew J. Vickers, PhDAffiliations: From Memorial Sloan Kettering Cancer Center, New York, New York.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-0151. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Simple Schema for Informed Decision Making About Prostate Cancer Screening Andrew J. Vickers , Kelly Edwards , Matthew R. Cooperberg , and Alvin I. Mushlin A Simple Schema for Informed Decision Making About Prostate Cancer Screening Andrew J. Vickers , Kelly Edwards , Matthew R. Cooperberg , and Alvin I. Mushlin Informed Decision Making About Prostate Cancer Screening Michael E. O'Callaghan , Ganessan Kichenadasse , Sina Vatandoust , and Kim Moretti Informed Decision Making About Prostate Cancer Screening Michael E. O'Callaghan , Ganessan Kichenadasse , Sina Vatandoust , and Kim Moretti Metrics 17 March 2015Volume 162, Issue 6Page: 457-458KeywordsCancer screeningDecision makingDisclosurePerceptionProstate cancerProstate diseases ePublished: 17 March 2015 Issue Published: 17 March 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Mechanism of Antitumor Activity of Tumor Necrosis Factor With Hyperthermia in a Tumor Necrosis Factor -Resistant Tumor
Authors: J. M. Srinivasan, L. F. Fajardo, G. M. Hahn
Journal: JNCI Journal of the National Cancer Institute (1990)

Cells from a radiation-induced fibrosarcoma (RIF-1) are exceedingly resistant to tumor necrosis factor alpha (TNF-alpha) in vitro. We tested whether the addition of mild hyperthermia (42.5 degrees C, 30 minutes) could enhance TNF-alpha activity against RIF-1 tumors growing in syngeneic hosts (C3H mice). TNF-alpha was administered intratumorally. Tumor cell killing essentially was not measurable following TNF-alpha, hyperthermia, or a combination of the two. Single-modality treatments also had no effect on tumor growth delay or on the x-ray dose (given 24 hours after the primary treatment) required to sterilize 50% of the tumors. The combination of TNF-alpha and hyperthermia, however, resulted in a marked increase in tumor doubling time and a highly significant reduction in the x-ray dose required to sterilize the tumors. Syngeneic lymph nodal lymphocytes and blood leukocytes did not appear to mediate the action of TNF-alpha on RIF-1 cells in vitro. Necrosis and hemorrhage were the most prominent histopathological alterations in the treated tumors. Electron microscopic studies 6 hours after therapy showed increased damage to capillary endothelial cells and accumulation of neutrophils in the capillaries of tumors treated with TNF-alpha with or without heat, suggesting that neutrophils may mediate the endothelial cell injury. These observations indicate a greater than additive tumoricidal effect of TNF-alpha with hyperthermia. Furthermore, they support the concept that the interaction between the two agents damages the vasculature, compromising the microcirculation and ultimately causing ischemic tumor necrosis.
Insulin Aspart in a 30/70 Premixed Formulation: Pharmacodynamic properties of a rapid-acting insulin analog in stable mixture
Authors: Christian Weyer, Tim Heise, Lutz Heinemann
Journal: Diabetes Care (1997)

OBJECTIVE To study the pharmacodynamic properties of a 30/70 premixed formulation of the rapid-acting insulin analog insulin aspart (B28Asp) and its protamine-retarded preparation (30/70 IA) in comparison with a respective mixture of soluble human insulin and NPH insulin (30/70 HI). RESEARCH DESIGN AND METHODS In this single-center double-blind euglycemic glucose-clamp study, 24 healthy male volunteers (age, 26 ± 2 years; BMI, 23.7 ± 1.7 kg/m2) received single subcutaneous injections of 0.3 U/kg body wt of either 30/70 IA or 30/70 HI on 2 study days in randomized order. Glucose infusion rates (GIRs) were determined over a 24-h period after administration. RESULTS The injection of 30/70 IA resulted in an earlier onset and more pronounced peak of action (tmax, 127 ± 24 min; GIRmax 9.7 ± 2.3 mg · kg−1 · min−1) than 30/70 HI (tmax, 185 ± 52 min; GIRmax, 7.4 ± 1.7 mg · kg−1 · min−1_ (P &amp;lt; 0.001). The metabolic activity of 30/70 IA (measured as the sum of the glucose infused) within the first 4 h after injection was 37% &amp;gt; that of 30/70 HI (P &amp;lt; 0.0001), while the total metabolic potencies over 24 h of both preparations were comparable. CONCLUSIONS The 30/70 premixed formulation of insulin aspart shows a significantly greater metabolic effect in the first 4 h after subcutaneous injection than the 30/70 mixture of human insulin. Insulin aspart retains its pharmacodynamic properties in a premixed 30/70 formulation.
Lung-derived SSEA-1<sup>+</sup>stem/progenitor cells inhibit allergic airway inflammation in mice
Authors: C.-J. Chiu, T.-Y. Ling, B.-L. Chiang
Journal: Allergy (2015)

Asthma is characterized by chronic airway inflammation and airway hyperresponsiveness (AHR). Little is known about the role of pulmonary stem/progenitor cells (PSCs) in allergic airway inflammation.To identify and investigate the role of PSCs in the bronchial epithelium of neonatal mice, we developed an enzyme-based digestion method to obtain single-cell suspension from lung tissues. Characterization of PSCs was performed using flow cytometry, real-time PCR, immunofluorescence staining, confocal microscopy, and scanning electron microscopy. The effects of SSEA-1(+) (stage-specific embryonic antigen-1) PSCs was studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of cell-based regulation using flow cytometry, real-time PCR, and immune-blotting.Single-cell suspensions derived from neonatal lung tissue included populations that expressed either SSEA-1(+) or Sca-1(+) (stem cell antigen-1). The SSEA-1(+) PSCs were highly prevalent in neonatal mice, and they were rare in adult mice. Enriched neonatal SSEA-1(+) PSCs had the ability of self-renewal and differentiated into pneumocytes and tracheal epithelial cells. SSEA-1(+) PSCs reduced AHR and airway damage in asthmatic mice by decreasing eosinophil infiltration, inhibiting chemokines/cytokines production, and preserving the level of CCSP.Here, we demonstrated that neonatal SSEA-1(+) PSCs play an immunomodulatory role in the progression of asthma by reducing lung damage and inhibiting inflammatory responses. Further understanding the molecular mechanisms of neonatal SSEA-1(+) PSCs might shed light on exploring the novel therapeutic approaches for allergic airway inflammation.
Bayesian and Non-Bayesian Methods of Inference
Authors: ROBERT D. SMALL
Journal: Annals of Internal Medicine (1983)

Editorials1 December 1983Bayesian and Non-Bayesian Methods of InferenceROBERT D. SMALL, PH.D., STANLEY S. SCHOR, PH.D.ROBERT D. SMALL, PH.D.Search for more papers by this author, STANLEY S. SCHOR, PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-6-857 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptStatistics is an indispensable tool in clinical research. Disagreements over the use of various approaches such as those reflected in the letters-to-the-editor section of this issue (1,2) should not dissuade us from the basic issue of how to use statistics to improve research efforts. An understanding of what Bayesian and non-Bayesian methods have to offer will help us make intelligent decisions about which to use in particular situations. We should keep in mind a quotation from Box and Tiao (3), advocates of Bayesian methods, "It is, we believe, equally unhelpful for enthusiasts to seem to claim that Bayesian analysis can...References1. ELLENBERGWITTES SJ. Analysis of data from clinical tables [Letter]. Ann Intern Med. 1983;99:874. LinkGoogle Scholar2. DIAMONDFORRESTER GJ. Analysis of data from clinical tables [Letter]. Ann Intern Med. 1983;99:874-5. LinkGoogle Scholar3. BOXTIAO GG. Bayesian Inference in Statistical Analysis. Reading, Massachusetts: Addison-Wesley; 1973. Google Scholar4. SCHOR S. Statistical proof in inconclusive 'negative' trials [Editorial]. Arch Intern Med. 1981;191:1263-4. CrossrefGoogle Scholar5. FISHER R. The Design of Experiments. 7th ed. New York: Hafner; 1960. Google Scholar6. WONNACOTTWONNACOTT TR. Introductory Statistics. 3rd ed. New York: John Wiley & Sons; 1977:539-600. Google Scholar7. KEMPTHORNE O. Inference from experiments and randomization. In: SRIVASTAVA JN, ed. A Survey of Statistical Design and Linear Models. Amsterdam: North Holland; 1975. Google Scholar8. BOXHUNTERHUNTER GWJ. Statistics for Experimenters. New York: John Wiley & Sons; 1978. Google Scholar9. FRIEDMANFURBERGDEMETS LCD. Fundamentals of Clinical Trials. Boston: John Wright PSG; 1983. Google Scholar10. SHAPIROLOUIS ST eds. Clinical Trials. New York; Marcel Dekker; 1983. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Merck Sharp & Dohme Research Laboratories West Point, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDo multiple outcome measures require p-value adjustment?Bayesian Analysis in the Diagnostic Process 1 December 1983Volume 99, Issue 6Page: 857-859KeywordsBayesian method Issue Published: 1 December 1983 PDF DownloadLoading ...
Can Massive Prevention Efforts Avert 29 Million New Cases of HIV by 2010?
Authors: Joan Stephenson
Journal: JAMA (2002)

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
Herniation of Fat through Lumbodorsal Fascia as a Cause of Low-Back Pain
Authors: Charles D. Bonner, S. Charles Kasdon
Journal: New England Journal of Medicine (1954)

The syndrome discussed in this paper is not new. The following case is reported, however, because it illustrates some of the diagnostic difficulties encountered when there is a history of unexplained, severe and incapacitating pain.Case HistoryA 67-year-old obese woman was 1st admitted to a hospital in July, 1952, with the chief complaint of "pain in the region of the left buttock radiating medially to the tip of the spine." The pain had been present for 4 months, restricting her daily activities. At night she slept well, without pain. No orthopedic lesion could be found to account for the . . .
Relation of Staph. Pyogenes to Dental Caries
Authors: E. Matthews, H. F. Atkinson, P. Saunsbury, H. W. Clegg
Journal: BMJ (1949)

PREGNANCY COMPLICATED BY DIABETES MELLITUS X,There is a greater terfdency for the diabetic to develop late pregnancy toxaemia than the non-diabetic, and the relative incidence varies with the standard of severity of the toxaemia taken for comparison.The maternal prognosis is good, and pregnancy does not make the diabetes worse provided that it is well treated.The late foetal mortality was 55% in a first series of 43 pregnancies.'ln a second series of 15 pregnancies in which oestrogens were given there were only three deaths.The cause .of the foetal mortality is discussed, and it is suggested that the factor affecting the viability of the foetus probably arises in the maternal anterior pituitary lobe.The incidence of abortion does not appear to differ from that for non-diabetic pregnancies, and suggests, first, that diabetes mellitus is not a cause of abortion, and, secondly, that the factor which reduces foetal viability exerts its strongest influence towards the end of pregnancy.Congenital deformities, gigantism, and hypoglycaemia of the newborn are briefly discussed, and it is suggested that the tendency to gigantism is due to an excess of the growth hormone from the maternal pituitary gland.We should like to express our gratitude to Professor W. C. W. Nixon, Director of the Obstetric Unit, for his encouragement and permission to make use of the case records of the Obstetric Unit; to Professor H. P. Himsworth, Director of the Medical Unit, for permission to make use of the records of the Diabetic Clinic
Priority in a Method of Prevention of Perforation in Submucous Resection
Authors: Richard M. Nelson
Journal: JAMA (1910)

<h3>To the Editor:—</h3> <i>Nihil novum sub sole!</i>In to-day's mail I receivedThe Journalof November 19 containing (p. 1785) an article of mine entitled "An Original Method for Prevention of Perforation in Submucous Resection." In the same mail I received, from its author, Dr. William R. Murray of Minneapolis, a reprint of an article from the<i>St. Paul Medical Journal</i>of January, 1907, on "The Submucous Resection of the Nasal Septum for the Correction of Septal Irregularities," on page 4 of which I find this marked paragraph: "For this reason I prefer to make the incision through the cartilage a little posterior to the primary incision through the muco-perichondrium, if the character of the deviation will allow it, in order that the membrane on the convex side may cover any such accidental puncture of the opposite membranes." The assumption of originality in my article was made in good
Can We Predict Which Wheezy Infants Will Continue to Wheeze?
Authors: JOANNE B. CLOUGH, KATE A. KEEPING, LUCY C. EDWARDS, WENDY M. FREEMAN, JILL A. WARNER, JOHN O. WARNER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Early intervention strategies in infant wheezing will be dependent on the ability to predict persistence of disease. We undertook a prospective longitudinal study to determine which factors might be predictive for the persistence of wheeze. We examined a group of 107 children 3 to 36 mo of age with at least one atopic parent. Children were recruited within 12 wk of first wheeze. Factors assessed included: personal atopy (IgE > 1 SD above age-related normal and/or eczema and/or positive skin tests); parental atopy; number of siblings; age at first wheeze; sex; serum-soluble IL-2R; proliferation of peripheral blood mononuclear cells (PBMC) to β -lactoglobulin and to D. pteronyssinus; production of IFN- γ on stimulation of PBMC with β -lactoglobulin and with D. pteronyssinus. A positive clinical outcome (child requiring prophylactic antiasthma treatment after 1 yr) was observed in 53 (49.5%) children. Predictor variables were assessed by univariate and multivariate logistic regression. Wheeze was more likely to be persistent in older, atopic children with biparental atopy. The model offering best prediction of persistent wheeze with least risk of including asymptomatic subjects was age at presentation + sIL-2R. Trials of early intervention strategies using a logistic regression equation based on this model for patient recruitment can now be designed. Clough JB, Keeping KA, Edwards LC, Freeman WM, Warner JA, Warner JO. Can we predict which wheezy infants will continue to wheeze?
Theophylline-7-acetic acid: lack of absorption and therapeutic effectiveness.
Authors: J A Fleetham, J A Owen, B May, P W Munt, K Nakatsu
Journal: Thorax (1979)

A double-blind cross-over trial was conducted to evaluate the effectiveness of oral theophylline-7-acetic acid (T7AA) in 13 asthmatic patients. Pulmonary function tests showed no difference between T7AA and placebo. No T7AA or theophylline was found in the sera of these patients or of healthy volunteers who took T7AA tablets or syrup.
Photodynamic Therapy (PDT) for Lung Cancers
Authors: Jitsuo Usuda, Harubumi Kato, Tetsuya Okunaka, Kinya Furukawa, Hidemitsu Tsutsui, Kimito Yamada, Yasuhiro Suga, Hidetoshi Honda, Yoshitaka Nagatsuka, Tatsuo Ohira, Masahiro Tsuboi, Takashi Hirano
Journal: Journal of Thoracic Oncology (2006)
F14512, a polyamine-vectorized anti-cancer drug, currently in clinical trials exhibits a marked preclinical anti-leukemic activity
Authors: A Kruczynski, A Pillon, L Créancier, I Vandenberghe, B Gomes, V Brel, E Fournier, J-P Annereau, E Currie, Y Guminski, D Bonnet, C Bailly, N Guilbaud
Journal: Leukemia (2013)