tbuckley/cabot-search huggingface dataset:
Abstract #5377: Evaluation of G-quadruplex structures that stabilize the human PDGFR-beta promoter region as therapeutic targets for pancreatic cancer
Authors: Jessica Fortin, Misha Pangasa, Yong Qin, Robert Brown, Samantha Kendrick, Vanessa Gaerig, Tracy Brooks, Laurence Hurley
Journal: Cancer Research (2009)

Pancreatic cancer is the fourth leading cause of cancer deaths in the United States, with a dismal five-year survival of only 4%. This high mortality rate can be attributed to the lack of existing efficacious treatments for surgically unresectable tumors, specifically caused by an advanced stage of invasiveness at the time of diagnosis. PDGFR-beta has been implicated in the pathogenesis and angiogenesis of many tumor types, making it an attractive chemotherapeutic target. The receptor\#8217;s kinase activity initiates tumor invasion. In particular, phosphorylation of Muc1 by PDGFR-beta has been shown to increase pancreatic tumor invasiveness. Our research program focuses on the characterization, by molecular cloning, of the human PDGFR-beta promoter to understand and ascertain mechanisms that control its expression, and the evaluation of targeting the promoter for novel therapeutics. Promoter deletion experiments emphasized the crucial importance of the proximal highly GC-rich region (-165 to -139) on the human PDGFR-beta for basal promoter activity. This region consists of seven runs of at least two consecutive guanines separated by one or more bases. CD, DMS footprinting, and Taq polymerase assay showed that the G-rich strand in this region forms a mixture of parallel/antiparallel G-quadruplex structures that involve a series of runs of four guanines. Interestingly, the middle runs of guanines in the GC-rich region form the more stable G-quadruplex structures, as confirmed by CD and DMS footprinting. FRET-based screening of over 400 compounds (10 micromolar) with the full-length G-quadruplex-forming region identified 29 putative interactive agents. Of these, only three compounds that did not interact with another oncogenic G-quadruplex were selected to move forward. These agents were then confirmed to interact with the PDGFR-beta promoter by CD, and lead agents are being examined in vitro. We have screened a series of six pancreatic cancer cell lines for PDGFR-beta expression. Both high-expressing (BxPc3) and low-expressing (Panc1) cell lines were chosen for further study. shRNA plasmids were selected for both lines on the basis of maximum knockdown of target mRNA, as determined by real time PCR; stable knockouts are being examined to determine the biological effect of PDGFR-beta in pancreatic cancer cells. The compounds that stabilize G-quadruplex formation are being tested in BxPc3 and Panc1 control and PDGFR-beta knockout cells for cytotoxicity and to confirm target specificity and downregulation. This data has highlighted potential lead compounds targeting PDGFR-beta to enhance the chemotherapeutic treatment options for pancreatic cancer.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5377.
Abstract P038: Dietary Capsaicin May Decrease Blood Pressure Through Enhancing NO With eNOS Activation in 2-Kidney, 1-Clip Hypertensive Rats
Authors: Yukiko Segawa, Hiroko Hashimoto, Tomoko Osera, Nobutaka Kurihara
Journal: Circulation (2015)

Objective: Capsaicin, a component of chili peppers, is reported to have beneficial effects on cardiovascular system through the vasodilative effects. We recently demonstrated the alleviation of blood pressure (BP) elevation by consuming a low concentration of capsaicin diet in 2-kidney, 1-clip (2K1C) hypertensive rats. Since the alleviation was diminished when 2K1C rats took NG-nitro-L-arginine methyl ester, a NO synthase (NOS) inhibitor, during the protocol, we hypothesized that NO has a key role in the effect of capsaicin in 2K1C rats. In this study, we observed eNOS mRNA expression and protein expressions of eNOS and phosphorylated eNOS in 2K1C rats fed a diet containing capsaicin. Methods: Six-week old male Sprague-Dawley rats were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). One week after the surgery, each group of rats were further divided into 2 groups randomly, which received either a control diet (CTL) or a diet containing 0.006% capsaicin (CAP) for 6 weeks. The systolic BP was measured by a tail-cuff method once per week throughout the protocol. At the end of the protocol, rats were euthanized and the abdominal aortas were collected for extracting mRNA and protein. Then, the expression of eNOS mRNA and protein in aorta was evaluated in each group of rats by real time RT-PCR and Western blotting. Results: As shown in Table, capsaicin diet alleviated BP elevation in 2K1C rats. After the dietary protocol, eNOS mRNA expression in 2K1C-CAP was significantly higher than in 2K1C-CTL. Although there were no significant differences in eNOS protein expression among four groups, phosphorylated eNOS protein expression in 2K1C-CAP was marginally significantly higher than in 2K1C-CTL. The expression was also significantly higher in 2K1C rats than in SHAM. Discussion: The present data suggested that dietary capsaicin decreases BP through enhancing NO with activation of eNOS in 2K1C hypertensive rats. It may be a clue for developing a dietary therapy for prevention of hypertension.
Hsp90 and histone deactylase inhibitor have synergistic activity against synovial sarcoma.
Authors: Anne Nguyen, Jefferson Terry, Suzanne Liu, Torsten O. Nielsen
Journal: Clinical Cancer Research (2006)

B50  Clinically-applicable Hsp90 and histone deacetylase inhibitors have independently been shown to suppress growth and induce apoptosis in synovial sarcoma; this study tests the hypothesis that such agents may be synergistic, which would permit increased efficacy while reducing dose and minimizing potential side effects. Synovial sarcoma is an aggressive soft tissue malignancy of unknown cellular origin, which typically affects young adults and often proves fatal. The chromosomal translocation t(X;18)(p11.2;q11.2) resulting in the fusion oncoprotein SYT-SSX is characteristic of this disease, but its function in oncogenesis is unclear. Synovial sarcoma exhibits an undifferentiated mesenchymal phenotype that suggests its malignant transformation involves dysfunctional cellular differentiation. The Hsp90 inhibitor 17AAG is being tested in clinical trials in a variety of cancers including leukemias, lymphomas, and sarcomas. Histone deacetylase inhibitors (including MS-275) are also currently involved in clinical trials of several cancers including leukemias and lymphomas and are considered to be promising new therapies for a wide range of cancers. Recently, we (Terry J et al. Clin Cancer Res 2005;11:5641) and others (Ito T et al. Cancer Lett 2005;224:311) have found that both 17AAG and histone deacetylase inhibitors, as single agents, are successful in arresting growth of synovial sarcoma in vitro and slowing growth in xenografts. We therefore tested combinations of 17AAG with the histone deacetylase inhibitor MS-275 by MTT proliferation assays and by Annexin V flow cytometry apoptosis assay, using established synovial sarcoma cell line models. Synergism was assessed by the median-effect principle of Chou and Talalay. As single agents, the IC50 for 17AAG is 2.1 uM and for MS275 is 4.5 uM at 24 hours in these assays. In synovial sarcoma cell line SYO-1, 50% reduction in MTT absorbance at 24 hours was achieved by a combination of 0.1 uM 17AAG with 0.25 uM MS-275. This result is nine times more effective than if the drugs were simply additive. Synergistic effects were still present at later assay time points, and in the synovial sarcoma cell line Fuji. These results show, for the first time, that 17AAG and histone deacetylase inhibitors are synergistic against synovial sarcoma in vitro and suggest that low dose combination therapies may be effective against this disease.
Etanercept suppresses regenerative hyperplasia in psoriasis by acutely downregulating epidermal expression of interleukin (IL)-19, IL-20 and IL-24
Authors: F. Wang, N. Smith, L. Maier, W. Xia, C. Hammerberg, H. Chubb, C. Chen, M. Riblett, A. Johnston, J.E. Gudjonsson, Y. Helfrich, S. Kang, G.J. Fisher, J.J. Voorhees
Journal: British Journal of Dermatology (2012)

Psoriasis is a Th17/Th1-mediated skin disease that often responds to antitumour necrosis factor (TNF)-α therapies, such as etanercept.To better define mechanisms by which etanercept improves psoriasis and to gain insight into disease pathogenesis.We investigated the early biochemical and cellular effects of etanercept on skin lesions in responder patients prior to substantial clinical improvement (≤ 4 weeks).By 1 week, etanercept acutely suppressed gene expression of the interleukin (IL)-20 subfamily of cytokines (IL-19, IL-20, IL-24), which were found to be predominantly epidermis-derived and which are implicated in stimulating epidermal hyperplasia. Additionally, by 1 week of therapy, suppression of other keratinocyte-derived products (chemokines, antimicrobial proteins) occurred, while suppression of epidermal regenerative hyperplasia occurred within 1-3 weeks. Th17 elements (IL-23p19, IL-12p40, IL-17A, IL-22) were suppressed by 3-4 weeks. In vitro, TNF-α and IL-17A coordinately stimulated the expression of the IL-20 subfamily in normal keratinocytes.Based on the rapid suppression of regenerative hyperplasia, chemokines and other keratinocyte-derived products, including the IL-20 subfamily, we propose that epidermal activation is a very early target of etanercept. As many of these keratinocyte markers are stimulated by TNF-α, their rapid downregulation is likely to reflect etanercept's antagonism of TNF-α. Additionally, decreased epidermal hyperplasia might result specifically from acute suppression of the IL-20 subfamily, which is also a likely consequence of etanercept's antagonism of TNF-α. Thus, the IL-20 subfamily has potential importance in the pathogenesis of psoriasis and therapeutic response to etanercept.
GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c+MHCII+ Macrophages and Dendritic Cells
Authors: Julie Helft, Jan Böttcher, Probir Chakravarty, Santiago Zelenay, Jatta Huotari, Barbara U. Schraml, Delphine Goubau, Caetano Reis e Sousa
Journal: Immunity (2015)
A memorable patient: You can but try
Authors: P. C Nolan
Journal: BMJ (1999)

In conclusion, this study shows that the scale of infectious intestinal disease in England is large, with an estimated 9.4 million cases occurring in the community annually, and 1.5 million cases presenting to general practitioners.Greater understanding is needed of the risk factors to guide preventive strategies.The spectrum of microbiological agents in the population differs from that found in surveillance data.Surveillance figures for important bacterial pathogens that cause food poisoning, such as campylobacter and salmonella, are more representative of community rates than surveillance figures for common viruses.Methods of supplementing the national surveillance system for infectious intestinal diseases should be considered.
Corpulence and Carbs in 1892
Authors: Ruth Berkelman
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
Abstract 14922: Elevated Heart Rate Variability, Measured As Increased SDNN, During Therapeutic Hypothermia Can Predict Better Outcomes Among Post-resuscitation Rats
Authors: Shih-Heng Chang, Chien-Hua Huang, Wei-Tien Chang, Min-Shan Tsai, Chiung-Yuan Hsu, Hsiao-Ju Cheng, Shyr-Chyr Chen, Wen-Jone Chen
Journal: Circulation (2010)
Reply to “Reply to ‘The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rates in hematologic malignancy patients: outcome of a pilot clinical study’ by Ning H et al.” by Behre et al.
Authors: H Ning, F Yang, M Jiang, L Hu, K Feng, J Zhang, Z Yu, B Li, C Xu, Y Li, J Wang, J Hu, X Lou, H Chen
Journal: Leukemia (2008)
Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma
Authors: Richard A Moffitt, Raoud Marayati, Elizabeth L Flate, Keith E Volmar, S Gabriela Herrera Loeza, Katherine A Hoadley, Naim U Rashid, Lindsay A Williams, Samuel C Eaton, Alexander H Chung, Jadwiga K Smyla, Judy M Anderson, Hong Jin Kim, David J Bentrem, Mark S Talamonti, Christine A Iacobuzio-Donahue, Michael A Hollingsworth, Jen Jen Yeh
Journal: Nature Genetics (2015)
Transcription factors of mast cells in comparison with monocytes and granulocytes*1Characterization of the mature human mast cell as C/EBP$alpha;low, C/EBP$epsi;$minus;, PU.1low, GATA-1low, GATA-2+, Elf-1+, SCL+, MITFhigh
Authors: M. Babina, S. Guhl, Y. Schulke, L. Kirchhof, B.M. Henz, A.F. Gombart
Journal: Journal of Allergy and Clinical Immunology (2004)
Das menschliche Knochenmark: Seine Anatomie, Physiologie und Pathologie nach Ergebnissen der intravitalen Sternalpunktion
Authors: K. Rohr
Journal: JAMA (1941)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract P1-09-02: BMI and metabolic factors in long-term breast cancer survivors: Changes from diagnosis and comparison to non-breast cancer controls
Authors: Ana Elisa Lohmann, Marguerite Ennis, Pamela J Goodwin
Journal: Cancer Research (2015)

Abstract Background: The metabolic syndrome is associated with poor breast cancer (BC) outcome. We evaluated changes from diagnosis in metabolic factors and BMI in long-term survivors and compared their status at long-term follow-up (LTFU) to that of age-matched women with no history of BC. Methods: A total of 535 women with early breast cancer were enrolled between 1989 and 1996 and followed prospectively. From 2005 to 2007, those alive without distant recurrence were re-contacted to participate in a long-term followed-up study and 285 agreed. A control group of 167 age-matched women without cancer history was recruited from women presenting for screening mammograms. Mean changes in metabolic factors from diagnosis to long-term follow-up were assessed with paired t-tests. In spite of matching, controls were younger and had higher income than survivors and the comparison to controls was made using age-adjusted regression models. Variables were transformed to normality before statistical testing. Results: With a median follow-up of 12.5 years, BC survivors gained on average 2.35 kg and BMI, waist and hip circumference, waist-hip ratio, glucose, insulin, HOMA, total cholesterol and its components (but not triglycerides) increased significantly. After age adjustment, waist circumference, glucose, HOMA and total triglycerides were significantly higher in BC survivors compared to controls Comparison of LTFU BC survivors to non-cancer controls Unadjusted mean ± standard deviationUnadjusted mean ± standard deviation BC patientscontrolsP-value for age-adjusted differencewaist circumference (cm)85 ± 1281 ± 10.01Glucose (mmol/L)5.5 ± 1.05.2 ± 0.9.01Insulin (pmol/L)60.9 ± 50.547.1 ± 28.3.06HOMA2.25 ± 2.241.64 ± 1.24.03Triglycerides (mmol/L)1.28 ± 0.641.10 ± 0.57.01BMI (kg/m2)26.3 ± 4.925.4 ± 4.5.26 Despite exclusion of BC patients with diabetes at study entry, 24.9% of BC survivors self reported diabetes or pre-diabetes (1.99%/year) versus 12.6% in controls (OR 2.3, p= .0017). Conclusion: The metabolic status of long-term BC survivors deteriorated over time and age-adjusted at LTFU were worse with respect to a number of factors compared to the control group. Citation Format: Ana Elisa Lohmann, Marguerite Ennis, Pamela J Goodwin. BMI and metabolic factors in long-term breast cancer survivors: Changes from diagnosis and comparison to non-breast cancer controls [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-02.
Novel ligands against prostate cancer for targeted drug delivery
Authors: Wataru Aizu, Etgar Levy-Nissenbaum, Frank Alexis, Omid Farokhzad
Journal: Clinical Cancer Research (2008)

B14   The development of drug delivery vehicles using robust targeting moieties has the potential to provide powerful new therapeutics for cancer. Most current targeted systems rely on a single antigen which makes them effective on limited patient populations and ineffective when certain cell changes occur. We isolated pools of nuclease-resistant oligonucleotides that bind and get taken up by cancer cells while not interacting with normal cells. These pools feature hundreds of modified RNA sequences that provide a robust targeting platform for multiple targets on the cancer cells. We used these molecules to deliver Doxorubicin, a chemotherapy drug, and demonstrated an efficient transport of drug into PC3 and LNCaP prostate-cancer cells that led to a specific and significant cell death of the target cells. Additionally, we conjugated these oligonucleotides to 80nm polymeric nanoparticles and demonstrated similar specific uptake only by the targeted cells. Currently our efforts are focused on the identification of the proteins responsible for the internalization of aptamers, which will possibly be the novel marker for human prostate cancer. We also launched the project, in which our nanotechnology will be thoroughly applied on anti-PSMA antibody as an alternative targeting ligand for human prostate cancer. The developed technology for the described delivery vehicle can potentially be designed to target other types of cancer and may deliver various molecules into cells, such as drugs and siRNA.
Does Dimethicone Increase the Efficacy of Antacids in the Treatment of Reflux Oesophagitis?
Authors: A L Ogilvie, Michael Atkinson
Journal: Journal of the Royal Society of Medicine (1986)

Dimethicone is a common additive to antacids, although its value in the treatment of reflux oesophagitis is unproven. Its efficacy was assessed by comparing the effect of a dimethicone-containing antacid gel (Asilone Gel) with a simple antacid gel in a double-blind trial in 45 patients with reflux oesophagitis. Thirty-eight patients completed the eight-week course of therapy. Antacid therapy alone resulted in a significant improvement of both symptoms and oesophagitis in gastro-oesophageal reflux. The inclusion of dimethicone in the antacid gel preparation did not confer any benefit in terms of symptomatic assessment but did confer a small advantage with regard to objective markers of oesophageal inflammation, suggesting that a dimethicone-containing antacid is of value in the treatment of symptomatic gastro-oesophageal reflux.
Novel approach for the genome-wide identification of predictive DNA methylation marker candidates in cell lines.
Authors: Tamas Rujan, Joern Lewin, Christoph Sachsenmaier, Carolina Haefliger, Christina Dahlstroem, Thomas Hildmann, Achim Plum
Journal: Clinical Cancer Research (2006)

A93   Aberrant changes in DNA methylation are causative for the development of cancer and other diseases and can be predictive of a patient9s response to certain drugs. Here, a rapid and highly efficient approach to identify methylation based predictive biomarkers in cell lines will be presented for an EGFR inhibitor, as an example.The genome-wide methylation profiles of 60 treatment-naive cell lines were obtained using Differential Methylation Hybridization (DMH) - a customized, microarray-based approach that allows for the rapid methylation analysis of more than 50,000 selected human genomic regions. Furthermore, the sensitivity profile of an EGFR inhibitor was determined using the same cell lines. Methylation marker candidates that correlate with EGFR inhibitor sensitivity were extracted by correlating the sensitivity data with the methylation profiles using statistical and biological selection criteria.Several highly promising biomarker candidates were identified in untreated human cancer cell lines that strongly correlated with EGFR inhibitor sensitivity in these cell lines. The majority of genes exhibited relative hypermethylation in resistant cell lines and hypomethylation in sensitive lines. The marker genes fell into several functional classes and included expected members of the EGFR-dependent regulatory networks as well as genes not known to be directly related to EGFR signaling.These data represent the first systematic approach to identify predictive DNA methylation marker candidates in cell lines. Further studies in human tumor samples with and without clinical follow-up will be necessary to assess the validity of these marker candidates.
Rift Valley Fever Outbreak
Authors: Rebecca Voelker
Journal: JAMA (1998)

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