tbuckley/cabot-search huggingface dataset:
Abstract 4002: Differential regulation of the ERGF-MAPK pathway by deoxycholic acid (DCA) and Ursodeoxycholic acid (UDCA) in colon cancer.
Authors: Sara M. Centuori
Journal: Cancer Research (2013)

Abstract Obesity and a western diet are risk factors for the development of colorectal cancer and correlate with high levels of bile acids. Specifically, the secondary bile acid deoxycholic acid (DCA) has been shown to act as a tumor promoter in animal studies. Interestingly, the tertiary bile acid Ursodeoxycholic acid (UDCA) was found to have chemopreventive activity in a clinical trial conducted in 1285 individuals with recently resected colorectal adenomas. The mechanism(s) of DCA's tumor promoting effects and UDCA's chemopreventive activities are unclear, however DCA and UDCA have been previously shown to regulate EGFR-MAPK signaling in a differential manner. Because this mitogenic pathway has been shown to play a role in colon cancer cell proliferation and survival, we hypothesize that DCA's tumor promoting effect may stem from its regulation of this mitogenic pathway. We therefore examined the role of DCA in the regulation of the EGFR MAPK pathway in human colon cancer cells as compared to UDCA. Our findings show that DCA can induce ERK1/2 phosphorylation in an EGFR-independent manner in HT-29 colon adenocarcinoma cells, and that this is at least partially dependent on PI3K activation. We also determined that UDCA pretreatment was able to suppress both EGF and DCA-induced EGFR-MAP signaling. By elucidating the mechanism by which DCA and UDCA differentially regulate colon cancer proliferation and survival, we may be able to skew the signaling in colon cancer cells to favor chemoprevention as opposed to tumorgenesis. Citation Format: Sara M. Centuori. Differential regulation of the ERGF-MAPK pathway by deoxycholic acid (DCA) and Ursodeoxycholic acid (UDCA) in colon cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4002. doi:10.1158/1538-7445.AM2013-4002
How does Epstein–Barr virus (EBV) complement the activation of Myc in the pathogenesis of Burkitt's lymphoma?
Authors: Martin J. Allday
Journal: Seminars in Cancer Biology (2009)

A defining characteristic of the aggressive B cell tumour Burkitt's lymphoma (BL) is a reciprocal chromosomal translocation that activates the Myc oncogene by juxtaposing it to one of the immunoglobulin gene loci. The consequences of activating Myc include cell growth and proliferation that can lead to lymphomagenesis; however, as part of a fail-safe mechanism that has evolved in metazoans to reduce the likelihood of neoplastic disease, activated oncogenes such as Myc may also induce cell death by apoptosis and/or an irreversible block to proliferation called senescence. For lymphoma to develop it is necessary that these latter processes are repressed. More than 95% of a subset of BL - known as endemic (e)BL because they are largely restricted to regions of equatorial Africa and similar geographical regions - carry latent Epstein-Barr virus (EBV) in the form of nuclear extra-chromosomal episomes. Although EBV is not generally regarded as a driving force of BL cell proliferation, it plays an important role in the pathogenesis of eBL. Latency-associated EBV gene products can inhibit a variety of pathways that lead to apoptosis and senescence; therefore EBV probably counteracts the proliferation-restricting activities of deregulated Myc and so facilitates the development of BL.
Dermoscopy for challenging melanoma; how to raise the 'red flag' when melanoma clinically looks benign
Authors: I. Zalaudek, G. Ferrara, A. Di Stefani, G. Argenziano
Journal: British Journal of Dermatology (2005)

Journal Article Dermoscopy for challenging melanoma; how to raise the ‘red flag’ when melanoma clinically looks benign Get access I. Zalaudek, I. Zalaudek Department of Dermatology, Medical University of Graz, Graz, AustriaDepartment of Dermatology, Second University of Naples, Via S. Pansini, 5, I‐80131 Naples, Italy Search for other works by this author on: Oxford Academic Google Scholar G. Ferrara, G. Ferrara Pathologic Anatomy Service, Gaetano Rummo General Hospital, Benevento, Italy Search for other works by this author on: Oxford Academic Google Scholar A. Di Stefani, A. Di Stefani Department of Dermatology, Medical University of Graz, Graz, AustriaDepartment of Dermatology, University of Rome Tor Vergata, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar G. Argenziano G. Argenziano Department of Dermatology, Second University of Naples, Via S. Pansini, 5, I‐80131 Naples, Italy Giuseppe Argenziano MD. E‐mail: argenziano@tin.it Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 1, 1 July 2005, Pages 200–202, https://doi.org/10.1111/j.1365-2133.2005.06617.x Published: 01 July 2005 Article history Accepted: 09 October 2004 Published: 01 July 2005
DEPRESSED CELL-MEDIATED IMMUNITY IN PATIENTS WITH PRIMARY INTRACRANIAL TUMORS
Authors: William H. Brooks, Martin G. Netsky, David E. Normansell, David A. Horwitz
Journal: The Journal of Experimental Medicine (1972)

Tumor immunity in patients with primary intracranial tumors was assessed in relation to the general status of host immunocompetence. Lymphocyte sensitization to tumor-specific membrane antigens was demonstrated by the proliferative response of lymphocytes in the presence of autochthonous tumor cells. Paradoxically, one-half of the patients could not be sensitized to a primary antigen, dinitrochlorobenzene; existing delayed hypersensitivity was also depressed, as measured by skin tests and lymphocyte transformation in response to common antigens. A heat-stable factor in patients' sera blocked cell-mediated tumor immunity. In addition, these "enhancing" sera consistently suppressed the blastogenic response of autologous and homologous lymphocytes to phytohemagglutinin and to membrane antigens on allogeneic cells in the one-way mixed lymphocyte culture. When patients' leukocytes were washed and autologous plasma replaced with normal plasma, reactivity in the mixed lymphocyte culture increased to normal values. In vitro immunosuppressive activity in patients' plasma or sera correlated with depressed delayed hypersensitivity. After removal of the tumor, suppressor activity disappeared. IgG fractions of patient sera contained strong immunosuppressive activity. These data suggest that the suppressor factor may be an isoantibody elicited by the tumor that also binds to receptors on the lymphocyte membrane. In addition to specifically blocking cell-mediated tumor immunity, enhancing sera may broadly depress host immunocompetence.
NAD(P)H oxidase activity in human neutrophils stimulated by phorbol myristate acetate.
Authors: Y Suzuki, R I Lehrer
Journal: Journal of Clinical Investigation (1980)

Phorbol myristate acetate activated in normal human neutrophils a single enzymatic entity that was dormant in unstimulated cells, optimally active at pH 7.0, and capable of oxidizing either NADH or NADPH, producing NAD(P)+ and superoxide (O27). Comparative fluorometric and spectrophotometric measurements supported the stoichiometry NAD(P)H + 20(2) leads to NAD(P)+ + 20(27) + H+. the seemingly considerable NAD(P)+ production at pH 5.5 and 6.0 was due largely to nonenzymatic oxidation of NAD(P)H by chain reactions initiated by HO27 (perhydroxyl radical), the conjugate acid of O27. This artifact, responsible for earlier erroneous assignments of an acid pH optimum for NAD(P)H oxidase, was prevented by including superoxide dismutase in fluorometric assays. NAD(P)H oxidase was more active towards NADPH (Km = 0.15 +/- 0.03 mM) than NADH (Km = 0.68 +/- 0.2 mM). No suggestion that oxidase activity was allosterically regulated by NAD(P)H was seen. Phorbol myristate acetate-induced O27 production was noted to be modulated by pH in intact neutrophils, suggesting that NAD(P)H oxidase is localized in the plasma membrane where its activity may be subject to (auto) regulation by local H+ concentrations.
The Effect of Radiotherapy on Local Regional Recurrence among Patients with Pathologic Complete Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.
Authors: C. Fasola, K. Godette, M. McDonald, R. O'Regan, A. Zelnak, J. Landry, M. Torres
Journal: Cancer Research (2009)

Abstract Background: Radiotherapy has been shown to reduce local recurrence rates of breast cancer after treatment with surgery and adjuvant chemotherapy. Indications for postmastectomy radiation have historically been based on pathology, but indications for radiation in the setting of pathologic complete response (pCR) to neoadjuvant chemotherapy are not well defined. The aim of this study was to evaluate the rates of local regional recurrence (LRR) among patients with pCR to neoadjuvant chemotherapy followed by surgery with or without radiation (XRT).Patients and Methods: The case histories of 337 patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, surgery with or without radiation from October 1997 to December 2006 were analyzed. Median age at diagnosis was 50.6 years (range: 25-84). The clinical stage at diagnosis was I in 3 (1%), IIA in 105 (31%), IIB in 94 (28%), and III in 135 (40%) patients. All patients received preoperative systemic therapy with a doxorubicin-based regimen (92%) or a single-agent taxane regimen (7%) or CMF (1%). A total of 272 patients received radiation following surgery and 65 did not receive any radiation. Median follow-up time was 40 months among all patients. The Kaplan-Meier method and log rank test were used to evaluate LRR rates and overall survival among both groups.Results: Patients treated with neoadjuvant chemotherapy followed by surgery and XRT had a lower incidence of LRR at 3 years with 24 cases of local recurrence among 272 patients who received XRT compared with 12 cases of local recurrence among the 65 patients who did not receive XRT (8.9% v 18.5%, P=0.02). Radiation also reduced local regional recurrence at 3 years among a subset of patients with clinical stage T2N1 disease (4.9% v 28.6%, P=0.03). There was no difference in overall survival or disease free survival among patients who received XRT compared to patients who did not receive XRT. There were 62 (18%) patients who achieved a pCR to neoadjuvant chemotherapy. Among patients with a pathologic complete response, radiation appeared to reduce the risk of LRR compared to patients who did not receive XRT (7.4% v 25%, P=0.17).Conclusion: Radiotherapy significantly reduced local regional recurrence rate among patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and surgery. Of particular interest, patients who achieve a pathologic complete response to neoadjuvant chemotherapy still had high LRR rates and may benefit from radiotherapy by lowering the risk of local regional recurrence. Further studies on the significance of LRR and overall survival among these patients are needed. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4114.
The Role of the Cerebrospinal Fluid in Human Acclimatization to High Altitude.
Authors: J. W. Severinghaus
Journal: Annals of Internal Medicine (1963)

s1 April 1963The Role of the Cerebrospinal Fluid in Human Acclimatization to High Altitude.J. W. Severinghaus, M.D.J. W. Severinghaus, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-729_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMeasurements of lumbar CSF during acclimatization to 3,800 m altitude in 4 normal males who live at sea level suggest that CSF pH and bicarbonate adequately represent the chemical environment of the medullary respiratory center chemoreceptor, as might be anticipated from Mitchell's recent localization of this chemoreceptor on the anterolateral surface of the medulla. The acute response to CO2and low and high O2was determined, permitting computation of ventilation response curves to alterations in CSF pH and alveolar Po2. This CSF pH—ventilation response curve (with PI02= 190 mm Hg) was identical before and after acclimatization, whereas the CO... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: San Francisco, Calif. (CS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 729-729KeywordsBicarbonatesCerebrospinal fluidColony stimulating factorPartial pressure of oxygen Issue Published: 1 April 1963 PDF DownloadLoading ...
Researchers Launch a Web-Based Resource for Smallpox Research
Authors: Joan Stephenson
Journal: JAMA (2001)

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
Evaluation of a novel bioartificial liver in rats with complete liver ischemia: treatment efficacy and species-specific α-GST detection to monitor hepatocyte viability
Authors: Leonard M Flendrig, Robert A.F.M Chamuleau, Martinus A.W Maas, Joost Daalhuisen, Brian Hasset, Cormac G Kilty, Sean Doyle, Nita C.J.J Ladiges, George G.A Jörning, John W.la Soe, Dirkje Sommeijer, Anje A.te Velde
Journal: Journal of Hepatology (1999)
Enzyme Immunoassay Screening for Hepatitis B Immunization
Authors: CONSTANCE A. BENSON
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 May 1986Enzyme Immunoassay Screening for Hepatitis B ImmunizationCONSTANCE A. BENSON, M.D., HAROLD A. KESSLER, M.D., ALAN A. HARRIS, M.D., KATHI KAPELL, M.S., SANDRA CHAKONAS, M.S., M.T.CONSTANCE A. BENSON, M.D.Search for more papers by this author, HAROLD A. KESSLER, M.D.Search for more papers by this author, ALAN A. HARRIS, M.D.Search for more papers by this author, KATHI KAPELL, M.S.Search for more papers by this author, SANDRA CHAKONAS, M.S., M.T.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-5-730_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Both the need for prevaccination screening for hepatitis B virus infection among health care workers and the most appropriate and cost-effective test for screening remain undecided. Kessler and colleagues (1) recommend testing for antibody to hepatitis B core antigen (anti-HBc) as a prevaccination screen. Their data suggest that currently available assays for antibody to hepatitis B surface antigen (anti-HBs) are inadequate when used as the sole test to detect all persons susceptible to hepatitis B virus infection. However, Werner and coworkers (2) suggest the most practical screening test is that for anti-HBs, but they propose a cutoff...References1. KESSLERHARRISPAYNEHUDSONPOTKINLEVIN HAJEBS. Antibodies to hepatitis B surface antigen as the sole hepatitis B marker in hospital personnel. Ann Intern Med. 1985;103:21-6. LinkGoogle Scholar2. WERNERDIENSTAGKUTER BJB. Isolated antibody to hepatitis B surface antigen and response to hepatitis B vaccination. Ann Intern Med. 1985;103:201-5. LinkGoogle Scholar3. . Inactivated hepatitis B virus vaccine: recommendation of the Immunization Practices Advisory Committee. MMWR. 1982;31:317-22, 327-8. (Reprinted in Ann Intern Med. 1982;97:379-383.) MedlineGoogle Scholar4. . Recommendations for protection against viral hepatitis: recommendation of the Immunization Practices Advisory Committee. MMWR. 1985;34:313-24. (Reprinted in Ann Intern Med. 1985;103:391-402.) MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: CONSTANCE A. BENSON, M.D.; HAROLD A. KESSLER, M.D.; ALAN A. HARRIS, M.D.; KATHI KAPELL, M.S.; SANDRA CHAKONAS, M.S., M.T.Affiliations: Rush-Presbyterian-St. Luke's Medical Center Chicago, IL 60612 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1986Volume 104, Issue 5Page: 730-731KeywordsAntigensEnzyme immunoassayHealth care providersHepatitis BHepatitis B surface antigen ePublished: 1 December 2008 Issue Published: 1 May 1986 PDF downloadLoading ...
Anatomy of the Steroid Receptor Zinc Finger Region
Authors: LEONARD P. FREEDMAN
Journal: Endocrine Reviews (1992)

LIKE many transcriptional regulatory proteins, nuclear hormone receptors are single polypeptides that are organized into relatively discrete functional domains (1). This common domain organization groups these receptors into a superfamily of functionally and most likely structurally related, hormonally regulable, transcription factors. The superfamily includes receptors for steroid hormones, such as glucocorticoids, progesterone, estrogen, aldosterone, and androgens, as well as hormonal forms of vitamins A and D, thyroid hormone, and peroxisomal activators (2–6). Several other receptorlike proteins whose ligands have yet to be identified have recently been isolated utilizing molecular cloning techniques. In the same way, several putative nuclear receptors from Drosophila that appear to act as regulators of early development (Refs. 7–10; reviewed in Ref. 11) have been identified, including a receptor for the insect steroid ecdysone (12). Upon association with a particular ligand, nuclear receptors, as soluble intracellular proteins, bind to specific DNA sites generally located upstream of responsive genes, and up- or down-regulate the transcription of those genes (13), presumably by functionally interacting with other components of the transcriptional apparatus. Domains for ligand binding (located in the carboxyterminal region), DNA binding (located toward the central or amino terminus), nuclear localization (within both the DNA- and ligand binding domains), and transcriptional modulation (localized to more variable regions of the receptors, including the N terminus) (Fig. 1) all can confer their specific functions when linked to unrelated, nonreceptor proteins (14–19). In addition, a putative dimerization region has been described that overlaps part of the ligand binding domain for some receptors (20–22).
Return to work after coronary artery surgery for angina.
Authors: I Graham, R Mulcahy, N Hickey
Journal: BMJ (1979)

goods vehicles was more successful.It was followed by a marked decrease in deaths and injuries among occupants of goods vehicles-3700 fewer were killed in 1977 than in 1970.2In 1977 in magistrates courts in England and Wales 1-2 million persons were found guilty of motoring offences; of these 97°were fined.3Penalties for serious transgressions were too mild.In 82 480 driving licence offences, including driving while disqualified, a fine of £20 or less was imposed in 830oi, and £50 or less in 970°.In 7899 cases of dangerous driving the penalty was £50 or less in 51°', and £100 or less in 96o0.Fines must be increased if they are to remain a credible deterrent.Disqualification and penalties are ineffective in a small minority of habitual offenders, who often also have a past history of other criminal offences.These cases present a social as well as a legal problem.Adequate enforcement with suitable penalties can improve road behaviour, but the real answer is to persuade the public that traffic regulations are an essential ingredient of road safety.
Abstract 5177: Molecular targeting of αvβ3 integrin by echistatin inhibits tumor progression and metastasis in osteosarcoma
Authors: Yasunori Tome, Hiroaki Kimura, Hiroki Maehara, Naotoshi Sugimoto, Katsuro Tomita, Hiroyuki Tsuchiya, Fuminori Kanaya, Michael Bouvet, Robert M. Hoffman
Journal: Cancer Research (2012)

Abstract Expression of αvβ3 integrin is associated with tumor progression and metastasis in several types of cancer, including metastatic osteosarcoma. We tested echistatin, an antagonist of αvβ3 integrin, as a molecular targeting drug, in an imageable orthotopic mouse model of human metastatic osteosarcoma. αvβ3 integrin expression was measured in a series of human osteosarcoma cell lines (143B parental and LM1-LM4) with increasing metastatic potential, using RT-PCR and immunoprecipitation. The cell lines expressed GFP in the nucleus and RFP in the cytoplasm and therefore could be imaged down to the subcellular level in vitro and in vivo. αvβ3 integrin expression correlated with the metastatic potential of the cells, with the LM4 cells showing the highest expression and highest metastatic capability, 6-fold and 18-fold, respectively, compared to parental 143B cells. In vitro cell proliferation of LM4 was inhibited by echistatin (p&amp;lt;0.01). In vitro migration, invasion, and adhesion of LM4 were also inhibited by echistatin (p&amp;lt;0.01). Tumor-induced angiogenesis by LM4 in the chick CAM model was also inhibited by echistatin (p&amp;lt;0.05). Mice treated with an echistatin-doxorubicin conjugate had significantly smaller primary tumors and longer survival compared to control untreated tumor-bearing mice (p&amp;lt;0.05 and p&amp;lt;0.01, respectively). Treatment with echistatin resulted in decreased experimental pulmonary metastases, imaged at the cellular level, in a nude mouse model compared to the untreated control (p&amp;lt;0.01). The results of this study indicate that αvβ3 integrin plays an essential role in osteosarcoma metastasis and that echistatin has potential to target αvβ3 integrin and inhibit tumor progression and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5177. doi:1538-7445.AM2012-5177
Planting mangoes for the future in Tibet.
Authors: K Murphy
Journal: BMJ (1986)

Journeys, like artists, are born and not made.A thousand differing circumstances contribute to them, few of them willed or determined by will-whatever we may think.They flower spontaneously out of our natures; and the best of them lead us not only outwards in space, but inwards as well.Travel can be one of the most rewarding forms of introspection.
Congenital Aortic Septal Defect with Communication between Aorta and Pulmonary Artery
Authors: HERTA SPENCER, HARVEY J. DWORKEN
Journal: Circulation (1950)

A case of congenital defect of the aortic septum is reported, together with a summary of thirteen previously described cases. The authors briefly describe their concept of the dynamics of the lesion and suggest a method of possible surgical correction, in instances where the diagnosis is made early.