tbuckley/cabot-search huggingface dataset:
Abstract 695: p70S6 kinase is a critical node that integrates HER-family and PI3 kinase signaling
Authors: Mark J. Axelrod, Rolando E. Mendez, Daniel G. Gioeli, Mark J. Jameson, Michael J. Weber
Journal: Cancer Research (2014)

Abstract Targeted cancer therapies often induce compensatory adaptive responses that blunt drug effectiveness, resulting in therapeutic resistance - intrinsic or acquired. Adaptive responses are characteristic of the complex nature of the cancer cell signaling network. Within this network, nodes of convergence between signaling modules are critical mediators of adaptive responses to targeted drugs. The critical nodes in an oncogenically-activated signaling network represent potential therapeutic vulnerabilities because their inhibition could result in collapse of the network and hence enhanced cytotoxicity. We have previously used high-throughput combinatorial drug screening to empirically identify adaptive survival responses to targeted therapies. We found that HER-family and PI3K represented compensatory signaling pathways, and combination therapy caused synergistic cytotoxicity in cases where inhibition of neither target was effective as a monotherapy. RPPA analysis identified ribosomal protein S6 as being synergistically down-regulated upon HER-family and PI3K co-inhibition. Expression of a constitutively active construct of the upstream activator of S6, p70S6K, was protective against apoptosis induced by combined HER-family and PI3K inhibition. Direct inhibition of p70S6K using small molecule inhibitors phenocopied the growth inhibition and apoptosis caused by HER-family and PI3K inhibition. These data implicate p70S6K as a critical node and druggable target in the HER-family / PI3K signaling network. The ability of direct inhibitors of p70S6K to phenocopy the co-inhibition of upstream signaling indicates that identification and targeting of critical nodes may be a way to overcome adaptive resistance to targeted therapies. Citation Format: Mark J. Axelrod, Rolando E. Mendez, Daniel G. Gioeli, Mark J. Jameson, Michael J. Weber. p70S6 kinase is a critical node that integrates HER-family and PI3 kinase signaling. [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 695. doi:10.1158/1538-7445.AM2014-695
The Crystalloid versus Hydroxyethyl Starch Trial: protocol for a multi-centre randomised controlled trial of fluid resuscitation with 6% hydroxyethyl starch (130/0.4) compared to 0.9% sodium chloride (saline) in intensive care patients on mortality
Authors: Rinaldo Bellomo, Alan Cass, Simon R. Finfer, J. French, D. Gattas, Parisa Glass, Joanne Lee, J. Lipman, Bette Liu, C. McArthur, S. McGuinness, D. Rajbhandari, Colman B. Taylor, S. Webb
Journal: Intensive Care Medicine (2011)
Value of galactomannan in bronchoalveolar lavage fluid for invasive pulmonary aspergillosis in critically ill chronic obstructive pulmonary disease
Authors: Lin Ding, YongHang He, Fang Li, Qingyuan Zhan
Journal: European Respiratory Journal (2011)

Backgroud:  Critically ill COPD patients who require ICU admission are at particular risk of invasive pulmonary aspergillosis (IPA).   Objective:  To investigate the value of galactomannan (GM) in BALF for rapid diagnosis and prognosis of IPA in critically ill COPD patients.   Design:  We investigated the clinical data of patients with severe COPD in RICU of Beijing Chaoyang Hospital from February 2009 to December 2009 prospectively. Patients were divided to proven, probable, possible, colonization and non-IPA group. Serum GM and BALF GM were done at the first day of RICU admission.   Results:  50 patients were recruited in the study,and 34 patients had BALF samples which were classified as probable IPA, possible IPA (n=6), 2 colonization (n=2) and non-IPA group (n=17); According to the ROC curve, when chose 0.795 as the cut-off of BALF GM test, the sensitivity, specificity, positive and negative predictive value for probable IPA were 88.9%, 95.1%, 100% and 93.7%, respectively;All of the patients of IPA group were dead. The result of GM test in BALF with IPA group were mush higher than control group (2.88 vs 0.49, p=0.009). The mortality was mush higher in the patients whose GM test in BALF above 0.795 than the patients lower 0.795 (80% vs 17% p=0.001);   Conclusions:  Compare to serum GM and aspergillus culture, GM in BALF prove to be more useful in early diagnosis of IPA with critically ill COPD patients. 0.795 maybe a best cut-off in BALF GM detection. Besides,high GM value in BALF was associated with high mortality in a certain sense.
SOX9 is a transcriptional activator of the human tumor suppressor CEACAM1
Authors: Hassan Zalzali, Philippe Jay, César Yaghi, Philippe Blache
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

141 

Overexpression of the transcription factor SOX9 in colon carcinoma cell line HT29Cl.16E increases apoptotic cell death and decreases the rate of cell proliferation. The carcinoembryonic antigen (CEA) family of cell adhesion molecules (CEACAMs) includes a group of highly homologous proteins. CEA, also named CEACAM5, is a tumor marker that is up-regulated in many types of human cancers. CEA protects colon cancers cells against apoptosis and we have previously shown that SOX9 down-regulated CEA expression in HT29Cl.16E cells. CEACAM1 is a human tumor suppressor, which is down regulated in 85% of early colorectal adenomas and carcinoma. Here, we report that CEACAM1 is up-regulated by SOX9 in HT29Cl.16E cells. We used stable transfectant HT29Cl.16E cells inducibly expressing SOX9 after doxycycline treatment and we observed a 2.5 fold increase of the SOX9 mRNA measured by real-time RT-PCR. In the same conditions, SOX9 overexpression revealed a 2.5 fold increase of CEACAM1 mRNA measured by real-time RT-PCR and an increase the CEACAM1 protein detected with the 4D1/C2 monoclonal antibody by immunoblot experiments. The functional promoter of the rat CEACAM1 has been previously characterized and a luciferase reporter plasmid containing a fragment of this promoter (-1609 to -21) exhibited a basal activity in HT29Cl.16E cells. This luciferase activity was enhanced 6.3 fold when SOX9 cDNA is co-transfected. We performed 5′ deletions in this promoter fragment and found that the -477 to -21 and the -289 to -21 fragments exhibited higher luciferase activities than the -1609 to -21 fragment suggesting that the region between -1609 and -477 contains down-regulator elements. SOX9 increased the luciferase activities of the -477 to -21 and the -289 to -21 fragments 5.8 and 19.8 folds, respectively. The sequence (A/T)(A/T)CAA(A/T) has been defined to be the SOX proteins consensus binging sequence by random oligonucleotide selection assay, later the sequence AGAACAATGG has been found to be the optimal SOX9 binding sequence using the same procedure. However, this high affinity SOX9 DNA-binding site has never been found in any promoter regulated by SOX9. We analyzed the -289 to -21 fragment of CEACAM1 promoter for the presence of SOX consensus sequence and surprisingly we found the AGAACAATGA sequence which contains the SOX core-binding element, AACAAT and only one mismatch with the SOX9 optimal sequence. That strongly suggests that SOX9 binds to this sequence to regulate the CEACAM1 gene expression. Our study shows that SOX9 is able to reverse the CEACAM1 down-regulation, which occurs in the majority of colon cancers cells.
Thin-Walled Microvessels in Human Coronary Atherosclerotic Plaques Show Incomplete Endothelial Junctions
Authors: Judith C. Sluimer, Frank D. Kolodgie, Ann P.J.J. Bijnens, Kimberly Maxfield, Erica Pacheco, Bob Kutys, Hans Duimel, Peter M. Frederik, Victor W.M. van Hinsbergh, Renu Virmani, Mat J.A.P. Daemen
Journal: Journal of the American College of Cardiology (2009)
Isomers of conjugated linoleic acid differ in their effects on angiogenesis and survival of mouse mammary adipose vasculature
Authors: Patricia A. Masso-Welch, Danilo Zangani, Clement Ip, Mary M. Vaughan, Suzanne F. Shoemaker, Sibel Oflazoglu Mcgee, Margot M. Ip
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1396 

Conjugated linoleic acid (CLA) is a cancer chemopreventive agent that inhibits angiogenesis in vivo and in vitro , and decreases the concentration of vascular endothelial growth factor (VEGF) and its receptor Flk-1 in the mouse mammary gland. To determine the CLA isomer which mediates the anti-angiogenic effect in vivo , mice were fed diets supplemented with 0.5% or 1% c9,t11-CLA or t10,c12-CLA for 6 weeks. The mice were then injected subcutaneously, adjacent to mammary gland four, with matrigel containing basic fibroblast growth factor and heparan sulfate. Functional vascularization of the matrigel pellet was evaluated 7 days later. Both isomers inhibited angiogenesis to a similar extent, with a ∼30% inhibition at the 0.5% dietary level, and 50-60% inhibition at 1%. Serum VEGF was also decreased 30-50% by both isomers; moreover, t10,c12-CLA, but not c9,t11-CLA decreased serum levels of the proangiogenic hormone leptin by ∼50%. Additionally, the t10,c12 isomer, but not c9,t11-CLA, rapidly induced apoptosis of the white and brown adipocytes as well as the pre-existing supporting vasculature of the mammary fat pad. This suggests the possibility that CLA may also induce apoptosis of the similarly fenestrated and unstable tumor vasculature, a possibility that will be investigated in future studies. Independent of the isomer-specific adipose apoptotic effect, both isomers induced a rapid and reversible decrease in the diameter of the unilocular adipocytes. Changes in the parenchymal stroma were also observed, with t10,c12-CLA inducing a thickened fibrocellular stroma with increased numbers of granulated mast cells. In the epithelium itself, both isomers at both levels of supplementation induced a rapid and significant increase in apoptotic (TUNEL-positive) epithelial cells in the ducts after 3 days of feeding; the higher dose of c9,t11- and t10,c12-CLA also induced a significant increase in TUNEL-positive cells in the terminal end buds. The ability of CLA isomers to modify the vascular, adipose, fibrocellular and epithelial compartments may contribute to their chemopreventive efficacy. Supported by AICR-02A112-REN, DAMD17-00-1-0286, NIH CA 61763, and by Cancer Center Support Grant CA 16056.
A CD8 T Cell/Indoleamine 2,3‐Dioxygenase Axis Is Required for Mesenchymal Stem Cell Suppression of Human Systemic Lupus Erythematosus
Authors: Dandan Wang, Xuebing Feng, Lin Lu, Joanne E. Konkel, Huayong Zhang, Zhiyong Chen, Xia Li, Xiang Gao, Liwei Lu, Songtao Shi, Wanjun Chen, Lingyun Sun
Journal: Arthritis & Rheumatology (2014)

Objective Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients. Methods The effects of allogeneic umbilical cord–derived MSCs (UC‐MSCs) on inhibition of T cell proliferation were determined. MSC functional molecules were stimulated with peripheral blood mononuclear cells from healthy controls and SLE patients and examined by real‐time polymerase chain reaction. CD4+ and CD8+ T cells were purified using microbeads to stimulate MSCs in order to determine cytokine expression by MSCs and to further determine which cell subset(s) or which molecule(s) is involved in inhibition of MSC–mediated T cell proliferation. The related signaling pathways were assessed. We determined levels of serum cytokines in lupus patients before and after UC‐MSC transplantation. Results Allogeneic UC‐MSCs suppressed T cell proliferation in lupus patients by secreting large amounts of indoleamine 2,3‐dioxygenase (IDO). We further found that interferon‐γ (IFNγ), which is produced predominantly by lupus CD8+ T cells, is the key factor that enhances IDO activity in allogeneic MSCs and that it is associated with IFNGR1/JAK‐2/STAT signaling pathways. Intriguingly, bone marrow–derived MSCs from patients with active lupus demonstrated defective IDO production in response to IFNγ and allogeneic CD8+ T cell stimulation. After allogeneic UC‐MSC transplantation, serum IDO activity increased in lupus patients. Conclusion We found a previously unrecognized CD8+ T cell/IFNγ/IDO axis that mediates the therapeutic effects of allogeneic MSCs in lupus patients.
Relating Genomic Research to Patient Care
Authors: M J Friedrich
Journal: JAMA (2000)

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
ACUTE DIVERTICULITIS OF THE CECUM
Authors: J A DI FIORE
Journal: Annals of Internal Medicine (1952)

Case Reports1 December 1952ACUTE DIVERTICULITIS OF THE CECUMJOHN A. DI FIORE, M.D.JOHN A. DI FIORE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-37-6-1245 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAcute diverticulitis of the cecum is a relatively rare condition in the experience of the average general surgeon. Ochsner and Bargen1reviewed 151 cases of uncomplicated diverticulosis of the colon and found that in about 2 per cent of the cases the diverticula occurred in the right half of the colon. The incidence of acute inflammation in the cecal diverticula is certainly extremely low. The average age incidence of such cases is approximately 39 years,2occurring about equally in both sexes. In one third of all cases, a history of previous attacks of right lower quadrant pain can be elicited....Bibliography1. OchsnerBargen HCJA: Diverticulosis of the large intestine: an evaluation of historical and personal observations, Ann. Int. Med. 9: 282, 1935. LinkGoogle Scholar2. Anderson L: Acute diverticulitis of the cecum, Surgery 22: 479, 1947. MedlineGoogle Scholar3. Henry FC: Acute diverticulitis of the cecum, Ann. Surg. 129: 109, 1949. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication February 8, 1952. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCaecal diverticulitis can be misdiagnosed as acute appendicitis: a systematic review of the literatureCecal diverticulitisSOLITARY DIVERTICULUM OF THE CAECUM A REPORT OF THREE CASES 1 December 1952Volume 37, Issue 6Page: 1245-1247KeywordsCecumColonDiverticulitisInflammationSurgeons ePublished: 1 December 2008 Issue Published: 1 December 1952 PDF downloadLoading ...
Abstract 267: Inhaled Nitric Oxide Lowers Pulmonary Artery Pressure During Cardiopulmonary Resuscitation but Does Not Increase Survival in a Model of Prolonged Cardiac Arrest in Pigs
Authors: Matthias Derwall, Andreas Ebeling, Anne Brücken, Michael Fries
Journal: Circulation (2014)

Introduction: We have previously shown that thoracic chest compressions during cardiac arrest (CA) result in elevated pulmonary vascular resistance (PVR), potentially impeding a return of spontaneous circulation (ROSC) by limiting circulation. Hypothesis: Applying inhaled nitric oxide (iNO) will lower PVR during cardiopulmonary resuscitation (CPR). Methods: 8 pigs were instrumented with an arterial line and a pulmonary artery catheter. CA was electrically induced and left untreated for 10 minutes before CPR was performed employing mechanical chest compressions and mechanical ventilation. Animals were randomized to either receive 20ppm of iNO (n = 3, iNO) or 100% Oxygen (n = 5, Control) during CPR. After 6 minutes of CPR, defibrillation was attempted. When no ROSC was achieved, chest compressions were restarted and continued for up to 30 minutes. Results: Mean pulmonary artery pressure (MPAP) rose significantly from 9 ± 4 following 10 minutes of VF to 21 ± 7 mmHg following 1 minute of CPR in Control animals (p=0.01). Animals receiving iNO showed a significantly lesser increase in MPAP from 5 ± 1 following 10 minutes of VF to 8 ± 3 mmHg following 1 minute of CPR (p=0.18). While MPAP did not differ on baseline or during 10 minutes of VF, iNO treatment resulted in significantly lower MPAP values averaged over the first 6 minutes of CPR (10 ± 1 vs. 22 ± 1 mmHg, p&lt;0.01 ; see Figure ; * indicates p&lt;0.01 for MPAP iNO vs. Control). This was reflected by similar changes in PVR, which remained significantly lower in iNO treated animals during CPR (80 ± 9 vs. 188 ± 17 dyn x sec x cm-5, p&lt;0.01). While no animal achieved ROSC in the iNO group, two of the five control animals could be successfully resuscitated. Conclusion: Ventilation with 20ppm nitric oxide during CPR reduces MPAP and PVR following prolonged CA, but does not improve survival in these preliminary experiments. Expanding the sample size will be necessary to determine potential impact of this intervention on survival or neurocognitive outcome.
The Allen Brothers (James and John Lee Allen)
Authors: M. Therese Southgate
Journal: JAMA (2004)

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
ANTIBIOTICS: YESTERDAY, TODAY, TOMORROW
Authors: C S KEFFER
Journal: Annals of Internal Medicine (1950)

Article1 September 1950ANTIBIOTICS: YESTERDAY, TODAY, TOMORROWCHESTER S. KEEFER, M.D., F.A.C.P.CHESTER S. KEEFER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-33-3-582 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo say that the discovery and development of antibiotics have completely revolutionized the management of infectious disease is to repeat a widely accepted statement. When one reflects that 10 years ago there were no antibiotics available for general use in man, and that today there are at least eight, it is a truly extraordinary state of change. These antibiotics include, in order of their discovery and use, tyrothricin, penicillin, streptomycin, bacitracin, polymyxin, aureomycin, chloromycetin, neomycin, and, most recently, terramycin. All of these antibiotics have a definite place in the the treatment of patients and in animal diseases. Today I shall... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Presented at the Thirty-first Annual Session, American College of Physicians, Boston, Mass., April 19, 1950. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAnaphylactoid Reaction to Penicillins V and G Administered OrallyAnaphylactic reaction from topical penicillin 1 September 1950Volume 33, Issue 3Page: 582-589KeywordsAntibioticsInfectious diseasesNeomycinsPatientsPenicillinPolymyxinsStreptomycin ePublished: 1 December 2008 Issue Published: 1 September 1950 PDF downloadLoading ...
Abstract 8573: L-carnitine Prevents Heart Failure with Preserved Ejection Fraction in Associated with Attenuation of Cardiac Fibrosis
Authors: Yosuke Omori, Tomohito Ohtani, Yasushi Sakata, Toshiaki Mano, Yasuharu Takeda, Shunsuke Tamaki, Yasumasa Tsukamoto, Daisuke Kamimura, Yoshihiro Aizawa, Yukitoshi Ikeya, Takeshi Miwa, Tomoyoshi Soga, Kazuhiro Yamamoto, Issei Komuro
Journal: Circulation (2011)

Backgrounds: Prognosis of heart failure with preserved ejection fraction (HFpEF) has not been improved because of unknown pathophysiology and unestablished therapeutic strategy. Cardiac fibrosis is known to play a crucial role in the development of HFpEF. Methods and Results: The comprehensive and quantitative analysis of metabolites with capillary electrophoresis time-of-flight mass spectrometry was conducted to find a substance which may be related to the development of HFpEF, and revealed decreased plasma free-carnitine levels in Dahl salt-sensitive rats (DSR) fed high-salt diet, a model of hypertensive HFpEF. We confirmed this result with enzymatic cycling method by showing decreased plasma and left ventricular (LV) free-carnitine levels with increased urinary free-carnitine excretion in HFpEF rats compared to control DSR fed normal chow. We also found that blood free-carnitine levels were decreased in HFpEF patients compared to age-matched normal volunteers. Expression of organic cation/carnitine transporter 2, which transports free-carnitine into cells, was decreased in the LV and kidney of HFpEF rats. L-carnitine administration to HFpEF rats increased plasma and LV levels of free-carnitine, and prevented HFpEF with decreased myocardial stiffness constant and decreased area of LV fibrosis. In cultured cardiac fibroblasts, L-carnitine attenuated the angiotensin II-induced increase in 3 H-proline incorporation. L-carnitine increased prostacyclin production and expression of fatty acid desaturase 1/2, rate-limiting enzymes in forming arachidonic acid, in the LV of DSR and cultured cardiac fibroblasts. LV arachidonic acid levels were increased in HFpEF rats by L-carnitine administration. Conclusions: L-carnitine may be effective in the prevention of HFpEF through enhanced production of prostacyclin and prevention of LV fibrosis and stiffening. L-carnitine supplementation may become a therapeutic option for HFpEF.