tbuckley/cabot-search huggingface dataset:
Abstract 5630: Nanotherapeutic silencing of HuR: Targeting a tumor-promoting response in ovarian cancer
Authors: Janet A. Sawicki, Yu-Hung Huang, Charles J. Yeo, Radhika P. Gogoi, Kevin Love, Daniel G. Anderson, Agnieszka K. Witkiewicz, Jonathan R. Brody
Journal: Cancer Research (2012)

Abstract HuR is a RNA-binding protein that post-transcriptionally regulates genes involved in the normal cellular response to cancer-associated stressors (e.g., DNA damage, nutrient depletion, hypoxia, and therapeutic agents). When triggered by stress, HuR translocates from the nucleus to the cytoplasm where it potently influences translation of key tumor promoting mRNAs by mRNA stabilization and direct facilitation of translation. Previously, it has been shown that HuR expression is a prognostic marker in ovarian cancers. Thus, we tested the effects of manipulating HuR expression levels on ovarian tumor growth characteristics and tested the hypothesis that silencing HuR through delivery of an HuR siRNA would be effective in suppressing the growth of ovarian tumors. Following treatment of A2780 ovarian cancer cells in culture with an adenovirus containing the HuR coding sequence, HuR expression was increased by ∼40% above control cells as determined by qRT-PCR. When these cells were plated in soft agar, the Adeno-HuR-treated cells markedly enhanced anchorage independent growth properties compared to control cells treated with an Adeno-GFP virus. When OvCAR-3 xenografts in nude mice were injected with lipidoid-siHuR formulated nanoparticles (2 injections/wk, 7 mg/kg/injection), HuR expression was reduced by 80% as determined by immunoblot analysis of resected tumors, and tumor growth was suppressed 2.6-fold after 3 weeks compared to control tumors (siLuciferase- and PBS-treated) (p = 0.0004). After 4 weeks of treatment, all control mice were sacrificed due to large tumor size. siHuR-treated mice continued to receive 2 injections/week for an additional 4 weeks during which time tumor size was maintained at 4-5X the baseline size. In our patient cohort, we also detected HuR activation (i.e., cytoplasmic HuR positivity) in twenty-four of thirty-four patients (71%), providing evidence that the majority of patients have activated HuR. Mechanistically, in A2780 ovarian cancer cells, we detected HuR binding to tumor-promoting target mRNAs including dCK, DR5, and HuR itself. These data provide evidence that silencing HuR, even as a monotherapeutic strategy, may be a promising therapeutic approach for the treatment of ovarian cancer. Studies combining HuR inhibition with other chemotherapies (including gemcitabine), and studies exploring targeting strategies, are ongoing. This work was supported by the Marsha Rivkin Center for Ovarian Cancer Research. 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 5630. doi:1538-7445.AM2012-5630
S3 Guideline: Sedation for gastrointestinal endoscopy 2008
Authors: A. Riphaus, T. Wehrmann, B. Weber, J. Arnold, U. Beilenhoff, H. Bitter, S. von Delius, D. Domagk, A. Ehlers, S. Faiss, D. Hartmann, W. Heinrichs, M.-L. Hermans, C. Hofmann, S. In der Smitten, M. Jung, G. Kähler, M. Kraus, J. Martin, A. Meining, J. Radke, T. Rösch, H. Seifert, A. Sieg, B. Wigginghaus, I. Kopp
Journal: Endoscopy (2009)

Corrected by: S3 Guideline: Sedation for gastrointestinal endoscopy 2008Endoscopy 2009; 41(11): 996-996DOI: 10.1055/s-0029-1215262
Constitutive expression of c-fos and c-jun, overexpression of ets-2, and reduced expression of metastasis suppressor gene nm23-H1 in rheumatoid arthritis.
Authors: S Dooley, I Herlitzka, R Hanselmann, A Ermis, W Henn, K Remberger, T Hopf, C Welter
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVES: To identify genes that are involved in the development and progression of rheumatoid arthritis (RA). METHODS: We used a multiple gene analysis system and a set of available genes participating in processes such as proliferation, differentiation, tumour progression, and metastasis, to identify their RA related expression. Synovial tissues from 22 patients with RA were evaluated in comparison with those from six patients with osteoarthritis and two patients with non-inflamed joints as controls, using northern blot and reverse transcriptase polymerase chain reaction experiments. RESULTS: Our data confirm the role of c-fos and c-jun as constitutive signal transmitters in solid RA tissues, thus demonstrating the potential of the approach. Activation of both genes persisted through multiple passages of the cells in tissue cultures derived from the synovial lining of RA tissues. There was an increased expression of ets-2 in 30% of RA samples and an up to 30-fold decreased expression of the potential metastasis suppressor gene nm23-H1 in 90% of RA tissues, compared with control tissues. CONCLUSIONS: The data presented show for the first time a significant decrease of nm23-H1 expression in RA, which is possibly involved in local invasiveness, and a strong activation of the ets-2 nuclear oncogene in about one third of RA tissues, which may also be part of a pathway leading to advanced disease stages. The constitutive expression of c-fos and c-jun in RA tissue most probably results from a continuing inflammatory stimulus. These findings with cell cultures suggest an intrinsic activation mechanism of these early response genes in RA.
High Incidence of Somatic BAP1 Alterations in Sporadic Malignant Mesothelioma
Authors: Masaki Nasu, Mitsuru Emi, Sandra Pastorino, Mika Tanji, Amy Powers, Hugh Luk, Francine Baumann, Yu-an Zhang, Adi Gazdar, Shreya Kanodia, Maarit Tiirikainen, Erin Flores, Giovanni Gaudino, Michael J. Becich, Harvey I. Pass, Haining Yang, Michele Carbone
Journal: Journal of Thoracic Oncology (2015)
Abstract 1085: Glioma-infiltrating myeloid derived suppressor cells inhibit anti-tumor T cell responses
Authors: Neha Kamran, Hikmat Assi, Marianela Candolfi, Mariela Moreno, Youping Li, Pedro R. Lowenstein, Maria G. Castro
Journal: Cancer Research (2014)

Abstract Efficacy of immunotherapeutic approaches against glioma is limited by the immunosuppressive tumor microenvironment. Tumor derived TGF-β, IL-10 and Prostaglandin E2 along with the presence of regulatory T cells (Tregs) and tumor associated macrophages (TAMs) promote the immune escape in gliomas. Also, tumor derived factors induce the expansion of myeloid derived suppressor cells (MDSCs). MDSCs represent a heterogeneous population of myeloid cells at various stages of differentiation that have the potential to inhibit anti-tumor T cell responses. Herein we demonstrate the accumulation of MDSCs in GL26 brain tumor bearing mice. Absolute numbers of Ly-6G+ (Gr-1high) MDSCs showed a 200 fold increase within the tumor mass 28 days post-tumor implantation. In contrast, the numbers of Ly-6C+ (Gr-1low) MDSCs did not significantly change within the tumor microenvironment. While this massive influx of MDSCs was noted within intracranial tumors, the levels of Ly-6G+ or Ly-6C+ MDSCs did not increase in the tumor draining lymph nodes (dLNs), spleen, bone marrow or blood of intracranial tumor bearing mice. Mice bearing GL26 or B16-F0 tumors in the flank showed a ∼3 fold increased influx of Ly-6G+ MDSCs within the tumor mass, the spleen and circulating MDSCs. Ly-6G+ MDSCs isolated from the brain tumors and spleens of GL26 intracranial tumor bearing mice inhibited tumor antigen-specific CD8+ T cell proliferation and T cell proliferation mediated by CD3 ligation . On the other hand, Ly-6C+ MDSCs did not did not elicit inhibition of T cell proliferation. Preliminary experiments using tumor cells' conditioned media indicate that CXCR2 signaling mediates the migration of MDSCs in a transwell assay and suggest the possibility that it could mediate MDSCs' migration into the tumor microenvironment in vivo. Overall, our data shows that MDSCs accumulate within the glioma mass and inhibit tumor-specific T cell responses. Strategies that inhibit MDSC recruitment to the tumor microenvironment and/or block their activity may therefore enhance the T cell mediated tumor clearance and suppress glioma progression. Supported by National Institutes of Health/ National Institute of Neurological Disorders &amp; Stroke (NIH/NINDS) Grants RO1-NS074387 and RO1-NS054193 Citation Format: Neha Kamran, Hikmat Assi, Marianela Candolfi, Mariela Moreno, Youping Li, Pedro R. Lowenstein, Maria G. Castro. Glioma-infiltrating myeloid derived suppressor cells inhibit anti-tumor T cell responses. [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 1085. doi:10.1158/1538-7445.AM2014-1085
Acid-base relations in epithelium of turtle bladder: site of active step in acidification and role of metabolic CO2
Authors: Philip T. Steinmetz
Journal: Journal of Clinical Investigation (1969)

The acid-base relations across the two surfaces of the epithelium of the turtle bladder were examined. By means of the 5,5-dimethyl-2,4-oxazolidinedione (DMO) technique the intracellular OH(-) concentration was measured in the presence and absence of a transepithelial pH gradient. When both sides of the bladder were bathed with solutions free of exogenous CO(2) and bicarbonate at pH 7.41 ([OH(-)] = 239 nmoles/liter), the epithelial cells were alkaline, the mean intracellular [OH(-)] being 347nmoles/liter. This alkalinity of the cells was preserved in bladders that secreted H(+) against a gradient of over 2 pH units. In bathing solutions stirred with 4.85% CO(2) and buffered with 25 mM HCO(3) (-) at pH 7.41 the intracellular [OH(-)] was lower than in CO(2)-free solutions and close to the extracellular [OH(-)]. In the CO(2)-free system anaerobiosis caused increased alkalinity of the cells and inhibition of H(+) secretion presumably by decreased metabolic CO(2) production. Carbonic acid inhibitors reduced H(+) secretion, but had no significant effect on the alkalinity of the cells. An inactive analogue of acetazolamide had no effect on H(+) secretion. The results indicate that the active step in acidification is located near the mucosal surface of the epithelium and that the alkali formed within the epithelial cells moves passively into the serosal solution along an electro-chemical gradient. The inhibitory effect of certain sulfonamides on H(+) secretion by the bladder is directly correlated with their known carbonic anhydrase inhibitory activity, but not associated with a measurable change in the mean intracellular [OH(-)].
Lincomycins in the Treatment of Bacteroides Infections
Authors: O. Tracy, A. M. Gordon, F. Moran, W. C. Love, P. McKenzie
Journal: BMJ (1972)

Lincomycin, or the closely related derivative clindamycin, was used to treat six patients with bacteroides infection. In five of the six there was a rapid clinical response to the treatment. Lincomycin and clindamycin seem to be the antibiotics of choice for such infections.
Metabolic Vulnerabilities in Endometrial Cancer
Authors: Frances L. Byrne, Ivan K.H. Poon, Susan C. Modesitt, Jose L. Tomsig, Jenny D.Y. Chow, Marin E. Healy, William D. Baker, Kristen A. Atkins, Johnathan M. Lancaster, Douglas C. Marchion, Kelle H. Moley, Kodi S. Ravichandran, Jill K. Slack-Davis, Kyle L. Hoehn
Journal: Cancer Research (2014)

Women with metabolic disorders, including obesity and diabetes, have an increased risk of developing endometrial cancer. However, the metabolism of endometrial tumors themselves has been largely understudied. Comparing human endometrial tumors and cells with their nonmalignant counterparts, we found that upregulation of the glucose transporter GLUT6 was more closely associated with the cancer phenotype than other hallmark cancer genes, including hexokinase 2 and pyruvate kinase M2. Importantly, suppression of GLUT6 expression inhibited glycolysis and survival of endometrial cancer cells. Glycolysis and lipogenesis were also highly coupled with the cancer phenotype in patient samples and cells. To test whether targeting endometrial cancer metabolism could be exploited as a therapeutic strategy, we screened a panel of compounds known to target diverse metabolic pathways in endometrial cells. We identified that the glycolytic inhibitor, 3-bromopyruvate, is a powerful antagonist of lipogenesis through pyruvylation of CoA. We also provide evidence that 3-bromopyruvate promotes cell death via a necrotic mechanism that does not involve reactive oxygen species and that 3-bromopyruvate impaired the growth of endometrial cancer xenografts.
The Plastic Lightguide in Endoscopic Laser Photocoagulation
Authors: H. Reidenbach, F. Bodem, P. Frühmorgen, H. Brand, L. Demling
Journal: Endoscopy (1975)

Various core/cladding plastic lightguides have been investigated with respect to their optical properties and suitability for endoscopic photo-coagulation. Plastic fibres with a diameter of 1.5 mm and a polystyrene or polymethyl-methacrylate core proved to be best suited to meet the requirements of high optical-power performance, low optical attenuation, mechanical robustness, sufficient flexibility and capability of being integrated in existing endoscopes. No impairment of endoscopic manipulation could be observed in more than 200 endoscopic photo-coagulations performed in the canine gastrointestinal tract. The plastic fibre can easily be introduced into and withdrawn from the instrumental channel without restricting the flexibility of the endoscope. The easy sliding of the fibre within the instrumental channel permits a dynamic variation of the distance between fibre and tissue during a photocoagulation, thereby varying the spot size and power density of irradiation continuously. The optical and mechanical performance of the plastic fibre is far beyond the current requirements of laser endoscopy. The plastic fibre is thus a most promising and easy-to-handle optical transmission system for endoscopic photocoagulation.
950 TOLERANCE AND EFFICACY OF THE MARS SYSTEM IN PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS NON-RESPONDERS TO STEROIDS: A PILOT STUDY
Authors: J. Boitard, A. Louvet, B. Bismuth, S. Dharancy, F. Wartel, V. Canva-Delcambre, P. Deltenre, B. Jude, F. Fourrier, P. Mathurin
Journal: Journal of Hepatology (2008)
MicroRNA-29a and microRNA-142-3p are regulators of myeloid differentiation and acute myeloid leukemia
Authors: Xiao-Shuang Wang, Jia-Nan Gong, Jia Yu, Fang Wang, Xin-Hua Zhang, Xiao-Lin Yin, Zhen-Qing Tan, Zi-Mian Luo, Gui-Hua Yang, Chao Shen, Jun-Wu Zhang
Journal: Blood (2012)
Examining acute health outcomes due to ozone exposure and their subsequent relationship to chronic disease outcomes.
Authors: B D Ostro
Journal: Environmental Health Perspectives (1993)

Current evidence indicates that individuals exposed to short term elevations in ambient ozone may experience both upper and lower respiratory effects. Some respiratory symptoms and spirometric changes are mild and reversible in nature, while others involve more severe outcomes, including hospital admissions and emergency room visits. However, many questions remain about the effects of acute ozone exposure and the implications of this exposure for chronic disease outcomes. For example, the identification of sensitive subgroups, the delineation of the entire spectrum of health effects due to exposure to ozone, the potential synergy between viral infections and ozone exposure, and the nature of adaptation to ozone are not well characterized. In addition, studies that examine the association between acute responses to ozone and potential biological indicators of a chronic disease process would be desirable. This paper serves to provide an overview of the types of epidemiologic studies that may be appropriate and factors to consider in addressing these questions.
Relevance of Patient Diagnosis to Analysis of the Terri Schiavo Case
Authors: Thomas I. Cochrane
Journal: Annals of Internal Medicine (2006)

Letters21 February 2006Relevance of Patient Diagnosis to Analysis of the Terri Schiavo CaseThomas I. Cochrane, MD, MBAThomas I. Cochrane, MD, MBAFrom Harvard University, Boston, MA 02115.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-4-200602210-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The recent review and ethical analysis of the Terri Schiavo case by Perry, Churchill, and Kirshner is generally excellent (1). The authors do, however, make 1 important claim that is incorrect: that the Schiavo case “rests critically on the concept of the persistent vegetative state.” This mistake is made by most observers of the case and tends to detract from, rather than contribute to, the discourse regarding Terri Schiavo's case.Robert and Mary Schindler went to great lengths, including distributing videos of their daughter, to convince the court and the public that their daughter was not in ...References1. Perry JE, Churchill LR, Kirshner HS. The Terri Schiavo case: legal, ethical, and medical perspectives. Ann Intern Med. 2005;143:744-8. [PMID: 16287796] LinkGoogle Scholar2. Babington C. Viewing videotape, Frist disputes Fla. doctors' diagnosis of Schiavo. Washington Post. 19 March 2005:A15. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Harvard University, Boston, MA 02115.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Terri Schiavo Case: Legal, Ethical, and Medical Perspectives Joshua E. Perry , Larry R. Churchill , and Howard S. Kirshner Relevance of Patient Diagnosis to Analysis of Terri Schiavo Case Joshua E. Perry , Howard S. Kirshner , and Larry R. Churchill Metrics Cited ByLimitation et arrêt de traitements à la phase aiguë des AVC graves : peut-on aller jusqu’à l’arrêt de la nutrition et l’hydratation artificielles ?Disorders of Consciousness: Coma, Vegetative and Minimally Conscious States 21 February 2006Volume 144, Issue 4Page: 305KeywordsAutopsyConflicts of interestNutrition ePublished: 21 February 2006 Issue Published: 21 February 2006 CopyrightCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract LB-227: Preclinical pharmacology and clinical efficacy of AZD9150 (ISIS-STAT3Rx), a potent next-generation antisense oligonucleotide inhibitor of STAT3
Authors: David Hong, Youngsoo Kim, Anas Younes, John Nemunaitis, Nathan Fowler, Jeff Hsu, Tianyuan Zhou, Luis Fayad, Nancy Zhang, Sarina Piha-Paul, Richard Woessner, Murali V. Nadella, Deborah Lawson, Corinne Reimer, Minji Jo, Joanna Schmidt, Xiaokun Xiao, Sarah Greenlee, Gene Hung, Mason Yamashita, David C. Blakey, Brett P. Monia, A. Robert Macleod, Razelle Kurzrock
Journal: Cancer Research (2014)

Abstract Genomic technologies have greatly expanded our understanding of cancer biology, although they have not yet been effectively translated into improved cancer therapeutics, partly due to the inability of available therapeutic modalities to target the most promising cancer driver pathways. In contrast to other therapeutic approaches, antisense technology allows the rational design of potent, sequence-specific inhibitors based on genome sequencing information alone. Recent human clinical data have demonstrated the potent activity of antisense oligonucleotides (ASOs) targeted to genes expressed by the liver. Here we describe preclinical and clinical activity of a high affinity, new generation chemistry (constrained ethyl modified) ASO, AZD9150. AZD9150 targets the mRNA coding for the transcription factor STAT3, which is considered a difficult protein to target therapeutically. Systemic delivery of unformulated AZD9150 resulted in strong inhibition of STA3 RNA and protein levels in demonstrates in a broad range of preclinical cancer models in vivo including several patient-derived xenograft models. AZD9150 administration resulted in 2 partial responses highly treatment-refractory diffuse large B-cell lymphoma and in 2 mixed responses in Hodgkin's Lymphoma patients in the phase I dose escalation study. These findings suggest that this technology has the potential to help bridge the pharmacogenomic divide in cancer drug discovery. [D.H. and Y.K. contributed equally to this work.] Citation Format: David Hong, Youngsoo Kim, Anas Younes, John Nemunaitis, Nathan Fowler, Jeff Hsu, Tianyuan Zhou, Luis Fayad, Nancy Zhang, Sarina Piha-Paul, Richard Woessner, Murali VP Nadella, Deborah Lawson, Corinne Reimer, Minji Jo, Joanna Schmidt, Xiaokun Xiao, Sarah Greenlee, Gene Hung, Mason Yamashita, David C. Blakey, Brett P. Monia, A. Robert Macleod, Razelle Kurzrock. Preclinical pharmacology and clinical efficacy of AZD9150 (ISIS-STAT3Rx), a potent next-generation antisense oligonucleotide inhibitor of STAT3. [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 LB-227. doi:10.1158/1538-7445.AM2014-LB-227
Foot ulcers in previously undiagnosed diabetes mellitus.
Authors: J R Glynn, E K Carr, W J Jeffcoate
Journal: BMJ (1990)

<h3>Background</h3> Nivolumab is approved for patients with metastatic renal cell carcinoma (mRCC) refractory to prior antiangiogenic therapy. The clinical activity of nivolumab in patients with non-clear cell RCC subtypes remains unknown as these patients were excluded from the original nivolumab trials. <h3>Methods</h3> Patients from 6 centers in the United States who received at least one dose of nivolumab for non-clear cell mRCC between 12/2015 and 06/2017 were identified. A retrospective analysis including patient characteristics, objective response rate according to RECIST v1.1 and treatment-related adverse events (TRAEs) was undertaken. <h3>Results</h3> Forty-one patients were identified. Median age was 58&nbsp;years (33–82), 71% were male, and majority had ECOG PS 0 (40%) or 1 (47%). Histology included 16 papillary, 14 unclassified, 5 chromophobe, 4 collecting duct, 1 Xp11 translocation and 1 MTSCC (mucinous tubular and spindle cell carcinoma). Among 35 patients who were evaluable for best response, 7 (20%) had PR and 10 (29%) had SD. Responses were observed in unclassified, papillary and collecting duct subtypes. In the entire cohort, median follow-up was 8.5&nbsp;months and median treatment duration was 3.0&nbsp;months. Median PFS was 3.5&nbsp;months and median OS was not reached. Among responders, median time to best response was 5.1&nbsp;months, and median duration of response was not reached as only 2 out of 7 responders had disease progression during follow-up. TRAEs of any grade were noted in 37% and most commonly included fatigue (12%), fever (10%) and rash (10%). Nivolumab treatments were postponed in 34% and discontinued in 15% of patients due to intolerance. No treatment-related deaths were observed. <h3>Conclusions</h3> Nivolumab monotherapy demonstrated objective responses and was well tolerated in a heterogeneous population of patients with non-clear cell mRCC. In the absence of other data in this treatment setting, this study lends support to the use of nivolumab for patients with metastatic non-clear cell renal cell carcinoma.