tbuckley/cabot-search huggingface dataset:
Abstract #LB-151: Identification and in vitro characterization of a human monoclonal antibody against IGF-II
Authors: Edward Cohen, Qing Chang, Timothy Adams, Leah Cosgrove, Lindsay Sparrow, John Bentley, Olan Dolezal, Xiaowen Xiao, Tom Peat, Janet Newman, Pat Pilling, Tram Phan, Gemma Brierley, Niksa Katrapeli, Kris Kopacz, Diana Martik, Dina Wassaf, Doug Rank, Greg Conley, Daniel Dransfield
Journal: Cancer Research (2009)

Elevated expression of insulin-like growth factor-II (IGF-II) is frequently observed in a variety of human malignancies including breast, colon and liver cancer. As IGF-II can deliver a mitogenic signal through both the IGF-IR and an alternately spliced form of the insulin receptor (IR-A), neutralizing the biological activity of this growth factor directly is a potential alternative option to IGF-IR directed agents. Utilizing a Fab-displaying phage library and a biotinylated precursor form of IGF-II (1-104aa) as a target, we isolated Fabs specific for the E-domain C-terminal extension form of IGF-II and for mature IGF-II. One of these Fabs which bound to both forms of IGF-II was reformatted into a full-length IgG, expressed, purified and subjected to further analysis. This antibody (DX-2647) displayed a very high affinity for mature IGF-II (K D  value of 23 pM). The antibody blocked binding of IGF-II to the IGF-IR and IR-A, to a panel of insulin-like growth factor binding proteins (IGFBPs), and the mannose-6-phosphate receptor. A crystal complex of the parental Fab of DX-2647 bound to IGF-II was resolved to 2.4A o . DX-2647 inhibited IGF-II-induced 1) receptor tyrosine phosphorylation, 2) cellular proliferation, and 3) anchorage-dependent as well as anchorage-independent colony formation in various cell lines. The efficacy of DX-2647 in blocking the progression of human tumor xenografts is currently under study.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-151.
Outcome prediction by extranodal involvement, IPI, R-IPI, and NCCN-IPI in the PET/CT and rituximab era: A Danish-Canadian study of 443 patients with diffuse-large B-cell lymphoma
Authors: Tarec Christoffer El‐Galaly, Diego Villa, Musa Alzahrani, Jakob Werner Hansen, Laurie H. Sehn, Don Wilson, Peter de Nully Brown, Annika Loft, Victor Iyer, Hans Erik Johnsen, Kerry J. Savage, Joseph M. Connors, Martin Hutchings
Journal: American Journal of Hematology (2015)

18F-fluorodeoxyglucose PET/CT (PET/CT) is the current state-of-the-art in the staging of diffuse large B-cell lymphoma (DLBCL) and has a high sensitivity for extranodal involvement. Therefore, reassessment of extranodal involvement and the current prognostic indices in the PET/CT era is warranted. We screened patients with newly diagnosed DLBCL seen at the academic centers of Aalborg, Copenhagen, and British Columbia for eligibility. Patients that had been staged with PET/CT and treated with R-CHOP(-like) 1(st) line treatment were retrospectively included. In total 443 patients met the inclusion criteria. With a median follow-up of 2.4 years, the 3-year overall (OS) and progression-free survival (PFS) were 73% and 69%, respectively. The Ann Arbor classification had no prognostic impact in itself with the exception of stage IV disease (HR 2.14 for PFS, P<0.01). Extranodal involvement was associated with a worse outcome in general, and in particular for patients with involvement of >2 extranodal sites, including HR 7.81 (P < 0.001) for PFS for >3 sites. Bone/bone marrow involvement was the most commonly involved extranodal site identified by PET/CT (29%) and was associated with an inferior PFS and OS. The IPI, R-IPI, and NCCN-IPI were predictive of PFS and OS, and the two latter could identify a very good prognostic subgroup with 3-year PFS and OS of 100%. PET/CT-ascertained extranodal involvement in DLBCL is common and involvement of >2 extranodal sites is associated with a dismal outcome. The IPI, R-IPI, and NCCN-IPI predict outcome with high accuracy.
Abstract 2547: Peripheral immune signatures and survival in stage IV melanoma
Authors: Graham P. Pawelec, Alexander Martens, Claus Garbe, Benjamin Weide, Evelyna Derhovanessian, Dirk Schadendorf, Anna Maria Di Giacomo, Michele Maio, Jolanda de Vries, Henning Zelba
Journal: Cancer Research (2014)

Abstract The presence of peripheral T-cells recognizing the melanoma-associated antigens NY-ESO-1 or Melan-A, as well as low frequencies of circulating CD14+ HLA-DR-/low myeloid-derived suppressor cells (MDSCs), is associated with prolonged survival in stage IV melanoma (n=94). In addition, the two of 12 patients with partial responses or stable disease in pilot studies of ipilimumab treatment both tended to have lower levels of MDSCs at baseline which decreased further on treatment. In contrast, two patients with progressive disease had high baseline MDSC levels, which increased further after treatment. These patients are being followed up to determine whether another mechanism of action of ipilimumab may be via an effect on MDSCs. A correlation was observed between the presence of antigen-reactive T cells and the frequency of MDSCs. Our results indicate that patients lacking antigen-reactive T cells had significantly higher levels of MDSCs. In addition, high frequencies of MDSCs correlated with lower frequencies of NY-ESO-1- and Melan-A-reactive T cells that also produced lower levels of IFN-gamma. NY-ESO-1 was recognized more frequently by CD4+ than by CD8+ T cells, whereas Melan-A more often stimulated CD8+ T cells. Possession of NY-ESO-1-reactive T cells conferred a survival advantage whether the response was mediated by CD4+ or CD8+ T cells or both. However, recognition of Melan-A by CD4+ T cells was associated with poorer clinical outcome even when the patient also possessed CD8+ reactive T cells. This negative effect was mediated by CD4+ T cells with a Th2- or Th17-type but not Th1-type cytokine response. Thus, tumor antigen-specificity and function of peripheral T cells and their interactions with MDSCs in advanced melanoma carries significant prognostic weight for predicting survival and may provide mechanistic insights into tumor immunosurveillance in such patients. Citation Format: Graham P. Pawelec, Alexander Martens, Claus Garbe, Benjamin Weide, Evelyna Derhovanessian, Dirk Schadendorf, Anna Maria Di Giacomo, Michele Maio, Jolanda de Vries, Henning Zelba. Peripheral immune signatures and survival in stage IV melanoma. [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 2547. doi:10.1158/1538-7445.AM2014-2547
Abstract 11505: Arterial Inflammation in HIV-Infected Patients Assessed by 18F-Fluorodeoxyglucose Positron Emission Tomography
Authors: Rasmus S Ripa, Andreas Knudsen, Anne Mette F Hag, Annika Loft, Eric von Benzon, Sune H Keller, Holger J Møller, Anne-Mette Lebech, Andreas Kjær
Journal: Circulation (2014)

Introduction: HIV-infected patients are at increased risk of myocardial infarction and arterial inflammation has been suggested as an explanation. Vascular inflammation can be assessed in vivo by 18F-fluorodeoxyglucose (FDG) PET. Hypothesis: Well-treated HIV-infected patients without known cardiovascular disease will have increased uptake of FDG in different arterial regions as compared to healthy controls. Methods: We prospectively included 26 HIV-infected patients on stable antiretroviral therapy and 25 healthy volunteers. All underwent whole-body PET/CT 3 hours after injection of FDG. FDG uptake was assessed (SUV) in the carotid arteries, the ascending, descending, and abdominal aorta. Carotid intima-media thickness was determined by ultrasound. Soluble biomarkers of endothelial dysfunction and inflammation were measured by ELISA. Known cardiovascular risk factors were recorded for all included. Results: The HIV-infected patients were on stable antiretroviral therapy with full viral suppression. The HIV-infected group was older (50 vs 41 yrs; p = 0.01), had higher blood pressure and total cholesterol, and accordingly a higher Framingham risk score. FDG uptake was similar in the two groups quantified as SUVmax (figure) in the carotid region (1.67 ± 0.04 vs. 1.67 ± 0.04, p = 0.98), the ascending aorta (1.84 ± 0.06 vs. 1.97 ± 0.06, p = 0.15), the descending aorta (1.89 ± 0.08 vs. 1.93 ± 0.08, p = 0.70), and the abdominal aorta (1.70 ± 0.06 vs. 1.65 ± 0.06, p = 0.56) even when adjusting for differences in risk profile. No significant correlations between SUV, carotid intima-media thickness, known cardiovascular risk factors and soluble biomarkers were found. Conclusions: We found no evidence of increased arterial inflammation among HIV-infected patients with full viral suppression compared to controls. This may challenge the idea of chronic inflammation as the cause of cardiovascular disease among optimally treated HIV-infected patients.
Abstract 4490: A novel tumor-targeting construct aimed at c-Met
Authors: mitra mastali, Jessica D Sims, Jan M Taguiam, Chris Hanson, Felix Alonso Valenteen, Lali K. Medina-Kauwe
Journal: Cancer Research (2014)

Abstract C-Met is a receptor tyrosine kinase (RTK) that is activated by the binding of its ligand, hepatocyte growth factor (HGF). The HGF/c-Met pathway contributes to embryonic development, wound healing, cell proliferation and survival, motility and morphogenesis. It is also one of the most frequently dysregulated pathways in a variety of human cancers, including breast, ovarian, prostate, lung, and pancreatic. Importantly, cell surface elevation of c-Met has been associated with drug-resistance, including acquired resistance to current signal-blocking therapies. Tumor-targeting strategies that do not require signal inhibition may prove more effective on c-Met positive cancer cells. This may be addressed by ligands that recognize c-Met to trigger cell uptake of attached therapeutics, thus bypassing the need to block signaling. HGF has the potential to accomplish this but its requirement for tetramerization and disulfide bonding presents technical complications for therapeutics development. An alternative, and potentially superior ligand for c-Met targeting may possibly be derived from a bacterium that causes food-poisoning. The human pathogen, Listeria monocytogenes, binds c-Met to invade host cells through its surface proteins called Internalins. Specifically, Internalin B (InlB) triggers receptor-mediated endocytosis after c-Met binding. InlB and HGF recognize different regions of c-Met, and InlB does not require tetramerization or disulfide bonds for binding. Consequently, InlB is more suitable for recombinant protein production than HGF. We have previously shown that PBK10, a recombinant protein derived from the adenovirus capsid penton base, can mediate gene and drug delivery into cells through the membrane penetrating activity of the penton base. Moreover, PBK10 can be targeted to tumor cells via recombinant fusion to tumor-homing ligands. Here, we explore the possibility of fusing the receptor-binding site of InlB to PBK10 for targeting attached cytotoxic agents to c-Met positive cancer cells, and transporting such agents directly into these cells via receptor-mediated endocytosis and membrane penetration. Citation Format: mitra mastali, Jessica D Sims, Jan M Taguiam, Chris Hanson, Felix Alonso Valenteen, Lali K. Medina-Kauwe. A novel tumor-targeting construct aimed at c-Met. [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 4490. doi:10.1158/1538-7445.AM2014-4490
Abstract 2756: Ceramide analog targets xIAP and cIAP1 to sensitize metastatic colon carcinoma cells to apoptosis induction to suppress tumor progression
Authors: Amy Paschall, Mary Zimmerman, Christina Torres, Dafeng Yang, May Chen, Xia Li, Erhard Bieberich, Aiping Bai, Jacek Bielawski, Alicja Bielawska, Kebin Liu
Journal: Cancer Research (2014)

Abstract Sphingolipids are bioeffectors that mediate various cellular processes. We aimed to identify molecular targets of ceramide in the apoptosis pathway and to determine the efficacy of a ceramide analog in overcoming cancer cell resistance to apoptosis induction. We observed that exposure of human colon carcinoma cells to ceramide analog LCL85 results in apoptosis in a dose-dependent manner. Interestingly, a sublethal dose of LCL85 increased C16 ceramide content and overcame tumor cell resistance to FasL-induced apoptosis. Subsequently, treatment of tumor cells with exogenous C16 ceramide resulted in increased tumor cell sensitivity to FasL-induced apoptosis. LCL85 resembles Smac mimetic in sensitization of colon carcinoma cells to FasL-induced apoptosis by inducing proteasomal degradation of cIAP1 and xIAP proteins. Consistent with its apoptosis sensitization activity, LCL85 suppressed colon carcinoma cell metastatic potential in an experimental colon carcinoma lung metastasis mouse model. Taken together, we determined that a sublethal dose of LCL85 is effective as a sensitizer in overcoming apoptosis resistance of metastatic human colon carcinoma cells, and LCL85 is effective in suppressing tumor metastasis in vivo. Citation Format: Amy Paschall, Mary Zimmerman, Christina Torres, Dafeng Yang, May Chen, Xia Li, Erhard Bieberich, Aiping Bai, Jacek Bielawski, Alicja Bielawska, Kebin Liu. Ceramide analog targets xIAP and cIAP1 to sensitize metastatic colon carcinoma cells to apoptosis induction to suppress tumor progression. [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 2756. doi:10.1158/1538-7445.AM2014-2756
Abstract 19873: Relationship Between Jet Direction and Mitral Valve Tethering in Patients With Ischemic Mitral Regurgitation: Real-Time Three Dimensonal Transesophageal Echocardiography Study
Authors: Eiji Kuwahara, Masaki Izumo, Yoko Fukuoka, Swaminatha V Gurudevan, Kirsten Tolstrup, Robert J Siegel, Takahiro Shiota
Journal: Circulation (2010)

Background: Mitral regurgitant (MR) jet direction with ischemic etiology is usually central or posterior. We hypothesized that severely restricted posterior mitral leaflet (PML) is a cause of relat...
Preventive Measures in Mite Asthma
Authors: Jens Korsgaard
Journal: Allergy (1983)

To evaluate the effect of preventive measures 46 patients, all allergic to house‐dust mites ( Dermatophagoides spp.), were randomly allocated to a study and a control group. According to the patients' subjective recordings of symptom score and use of medicine, compared with the control group, the study group had improved. There was, however, no improvement when comparing the objective recordings of morning and evening peak flow and use of medicine, and it is concluded that the preventive measures in this programme are not very effective for patients allergic to house‐dust mites. The reduction in indoor humidity in the study group was limited and, as a high indoor humidity is the cause of huge populations of house‐dust mites in homes, it is emphasized that future programmes of preventive measures should focus more on damp problems, particularly those related to bad housing construction.
DR. RICHARD SHUCKBURGH AND YANKEE DOODLE
Authors: Louis H. Roddis
Journal: Annals of Internal Medicine (1934)

Article1 June 1934DR. RICHARD SHUCKBURGH AND YANKEE DOODLELOUIS H. RODDIS, F.A.C.P.LOUIS H. RODDIS, F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-7-12-1548 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOur national airs and patriotic songs, like the weather, have always been considered the legitimate subject of criticism. The words are unsuitable, the music is not good, it is beyond the range of the average voice, or some other objection is advanced. No other patriotic song has come under fire more often than has the old fashioned tune and words of the Revolutionary War song, Yankee Doodle. The words are mere nonsense, say the critics, and the music is ridiculous, a mere hurdy-gurdy style of composition. Yet like many things that are nonsense—Mother Goose rhymes, for instance—it remains a popular...Bibliography1. Sonneck OG Report by Library of Congress on the Star Spangled Banner and other patriotic songs, 1909, . Google Scholar2. Elson LC National Music of America, 1900, . Google Scholar3. Lossing BJ Field book of the American Revolution, 1860, . Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: U. S. Navy Washington, D. C.*Received for publication January 16, 1934.This is the sixth of a series of portraits of medical poets. Those which have previously appeared in the ANNALS OF INTERNAL MEDICINE are:Joseph Rodman Drake—February 1929Oliver Wendell Holmes—June 1930Oliver Goldsmith—May 1932Wm. Savage Pitts—January 1933Lieutenant Colonel John McCrae—June 1933 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1934Volume 7, Issue 12Page: 1548-1552 ePublished: 1 December 2008 Issue Published: 1 June 1934 PDF downloadLoading ...
PSYCHOSOMATIC MEDICINE LOOKS AT MEDICAL SPECIALIZATION
Authors: S RUBIN
Journal: Annals of Internal Medicine (1951)

Article1 November 1951PSYCHOSOMATIC MEDICINE LOOKS AT MEDICAL SPECIALIZATIONSIDNEY RUBIN, M.D.SIDNEY RUBIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-35-5-999 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Excerpt"Psychosomatic medicine no longer needs an apology. It has passed that stage. One may consider the acceptance of this fact as the first phase of the problem. The second phase which we are now entering consists of the task of teaching this new discipline to students and to those physicians who are interested in reorienting themselves to medicine." The above quotation comes not from one of our psychiatric journals but from an excellent and comprehensive article in the American Journal of Medicine.1This paper will concern itself with the problems of this second phase, i.e., the teaching of this new...Bibliography1. Raginsky BB: Psychosomatic medicine, its history, development and teaching, Am. J. Med. 5: 857, 1948. CrossrefMedlineGoogle Scholar2. Editorial: Holistic medicine, J. A. M. A. 138: 1158, 1948. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Topeka, Kansas*Received for publication April 3, 1950.From the Medical Service, Veterans Hospital, Topeka, Kansas.Read at the Regional (Kansas) Meeting of the American College of Physicians, March 17, 1950, Topeka, Kansas.Sponsored by the VA and published with the approval of the Chief Medical Director. The statements and conclusions published by the authors are a result of their own study and do not necessarily reflect the opinion or policy of the Veterans Administration. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1951Volume 35, Issue 5Page: 999-1007KeywordsMedical services Issue Published: 1 November 1951 PDF downloadLoading ...
Of Mice and Genomes
Authors: Joan Stephenson
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
Pathway activation signatures of breast cancer predict molecular subtype and drug sensitivity
Authors: Zachary Boyd, Jenny Wu, Yibing Yan, Lukas Amler, Mark Lackner
Journal: Clinical Cancer Research (2008)

A31  Breast cancer represents the highest incidence of cancer in women in the United States and Europe, with an estimated 182,460 new cases expected to occur in the US this year (1). Gene-expression profiling of breast cancer has confirmed the hypothesis that breast cancer is not a single disease, but can in fact be classified as subtypes that exhibit distinct histopathology, clinical outcomes, and therapeutic sensitivity. Basal-like tumors are a subtype that has been shown to be particularly associated with poor prognosis. The molecular pathways that underlie and drive the progression of basal-like tumors are poorly understood, and there are currently no approved targeted therapies for basal-like breast cancer. Therefore, basal-like breast cancer represents a serious unmet medical need.  Recent efforts at understanding breast cancer subtypes have typically focused on gene expression analysis. In this poster, we demonstrate classification of cell lines representing breast cancer subtypes can be accomplished through pathway activation profiling using reverse phase protein microarrays to detect phosphorylation of pathway-specific proteins. Bioinformatic analysis revealed distinct pathway activation signatures between respective subtypes and that phosphoprotein endpoints largely recapitulate molecular classification determined by gene expression analyses. We were able to correlate observed pathway activation to sensitivity of targeted therapies to components of specific cellular pathways. Basal-like breast cancer cells in particular demonstrated high activation of the EGFR signaling pathway, including Erk1/2. Conversely, we show that luminal and HER2 amplified cell lines are enriched in phosphorylation of components of the PI3 kinase/Akt and mTor pathways. Finally, we show that activation of particular pathway modules is predictive of in vitro response to targeted inhibitors of MEK1/2 and PI3 kinase and that these modules are activated in a subtype-specific manner in breast cancer.