tbuckley/cabot-search huggingface dataset:
Case 25-2000
Authors: Jess Mandel, Eugene J. Mark
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 69-year-old woman was admitted to the hospital because of a pulmonary arterial obstruction.The patient had been well until several months before admission, when an intermittent, nonproductive cough developed. Ten days before admission, she had left-sided subscapular pain after raking leaves. In the evening, the pain migrated to the region below the left breast. The next day, she had an episode of sudden, severe pleuritic pain below the left breast, with dizziness and sweating but without dyspnea or loss of consciousness. She went to another hospital, where she was told that her electrocardiogram was normal and . . .
Potentiation of Anticoagulant Effect of Warfarin by Phenylbutazone
Authors: Paul M. Aggeler, Robert A. O'Reilly, Lois Leong, Patricia E. Kowitz
Journal: New England Journal of Medicine (1967)

THE administration of the pyrazolone derivatives, phenylbutazone and oxyphenbutazone, to a patient already being treated with coumarin anticoagulant drugs can lead to serious hemorrhagic complications.1 2 3 4 5 6 The means whereby these drugs potentiate the prothrombinopenic effect of the coumarins is not clear. It is not caused by impaired liver function or defective vitamin K metabolism since these drugs do not alter blood coagulation when given alone.7 , 8 In 1956 Sigg et al.1 reported a decrease in the disappearance rate of ethylbiscoumacetate in 1 of their patients when phenylbutazone was given. They attributed this to delayed renal excretion of the coumarin drug. Weiner and . . .
Abstract P6-14-09: Acute-Phase Reactions Following Treatment with Zoledronic Acid or Denosumab: Results from a Randomized, Controlled Phase 3 Study in Patients with Breast Cancer and Bone Metastases
Authors: AT Stopeck, AA Lipton, C Campbell-Baird, R von Moos, M Fan, B Haddock, A. Braun
Journal: Cancer Research (2010)

Abstract Background: Intravenous (IV) bisphosphonates (BP) are currently used to treat bone metastases and prevent skeletal-related events (SRE) in patients with advanced breast cancer. In a phase 3 study, denosumab, a fully human monoclonal antibody against RANKL, was shown to be superior to zoledronic acid (ZA) in delaying or preventing SREs in patients with breast cancer and bone metastases. This prespecified analysis compares ZA and denosumab for the incidence of acute-phase reactions (flu-like syndrome including pyrexia, chills, flushing, bone pain, arthralgias, and myalgias) during the first 3 days after initial treatment in that study. Methods: Eligible patients were randomized in a double-blind, double-dummy fashion to receive IV ZA 4 mg (adjusted for creatinine clearance as specified by the Zometa label) or subcutaneous denosumab 120 mg every 4 weeks. Most patients (99%) were women; mean (SD) age was 57 (12) years, and baseline characteristics were balanced between groups. Safety analyses were conducted in patients who received ≥1 dose of denosumab (N=1020) or ZA (N=1013). Patient records were searched for adverse events (AEs) and serious AEs that occurred during the first 3 days after the first administration of study drug, using 37 prespecified MedDRA 12.0 preferred terms potentially indicating acute-phase reactions. Per study protocol, AEs were considered serious if they were fatal, life-threatening, required or prolonged in-patient hospitalization, resulted in a persistent or significant disability, or were considered to present a significant medical hazard. Results: AEs associated with acute-phase reactions in the first 3 days after treatment occurred in fewer patients in the denosumab group (10.4%) than in the ZA group (27.3%; P&amp;lt;0.0001), and no events were attributed to denosumab. The most common acute-phase reaction AEs included pyrexia (0.9% denosumab, 11.5% ZA), fatigue (2.4% denosumab, 4.0% ZA), bone pain (1.3% denosumab, 3.6% ZA), chills (0.3% denosumab, 3.6% ZA), and arthralgia (1.5% denosumab, 3.2% ZA). No patients (0%) in the denosumab group and 10 patients (1%) in the ZA group reported serious AEs associated with acute-phase reactions during the first 3 days. These events included pyrexia (n=7); bone pain (n=2); and asthenia, back pain, chest pain, chills, headache, and malaise (n=1 each). For 6 of the 10 patients, events of pyrexia, chest pain, chills, and bone pain were resolved within 4 days. Three patients with serious acute-phase reaction AEs discontinued ZA treatment after the first dose. Conclusion: Patients treated with denosumab experienced no serious AEs of acute-phase reaction and significantly fewer overall AEs of acute-phase reaction than patients receiving ZA. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-14-09.
Abstract 2659: A thermally targeted carrier of p50 NLS peptide inhibits cancer cell proliferation by preventing NFκB nuclear translocation
Authors: Emily H. Thomas, Drazen Raucher
Journal: Cancer Research (2010)

Abstract The application of rationally designed therapeutic peptides may improve outcomes in cancer treatment. These peptides hold the potential to directly target proliferative pathways and to inhibit their over-expression. The NFκB survival pathway is constitutively active in many cancers and plays a role in evading apoptosis. A p50 NLS-derived peptide has been shown to bind to the nuclear receptor and prevent NFκB translocation into the nucleus. This 10 amino acid peptide thus inhibits the transcriptional activation of NFκB's cellular targets that are implicated in cancer cell survival and metastasis. By conjugating the p50 derived peptide to a thermally targeted carrier and a cell penetrating peptide, the specificity and stability of peptide delivery can be enhanced. The addition of a cell penetrating peptide, SynB1, to the N-terminus of ELP enhances the cellular uptake of the conjugated peptide, SynB1-ELP1-p50. Elastin like polypeptide (ELP) is an elastin derived biopolymer that undergoes a thermally-mediated phase transition. By applying an external heat source, mild hyperthermic conditions (41°C) can induce aggregation and therefore can be used to specifically target ELP to solid tumors in cancer therapy. Uptake studies indicate that hyperthermia increases the accumulation of flourescein-labeled SynB1-ELP1-p50 in MCF-7 cells by 3 fold as compared to SynB1-ELP1-p50 treatment without heat. In addition to providing a level of targeting specificity, as a macromolecule, ELP may increase the plasma stability of small therapeutic peptides, like p50, and therefore creates the potential for viable delivery in vivo. Preliminary in vitro studies have demonstrated that two 1-hour treatments with 20μM of SynB1-ELP1-p50 inhibits cell proliferation by 20% and in combination with hyperthermia by 40%, in both MCF-7 and HeLa cell lines. No inhibitory effect was seen when the carrier control, SynB1-ELP1, was used. Confocal microscopy studies illustrate the predominantly cytoplasmic localization of rhodamine labeled SynB1-ELP1-p50 with some localization at the nuclear periphery. Immunofluorescence studies suggest that SynB1-ELP1-p50 may attenuate the nuclear translocation of NFκB following stimulation with TNF-α. Future studies will elucidate the anti-proliferative mechanisms of this conjugated peptide and quantify the inhibition of nuclear translocation of NFκB following treatment with SynB1-ELP1-p50. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2659.
IN PATIENTS WITH SEVERE ADVANCED HEART FAILURE THE USE OF ADAPTIVE SERVO-VENTILATION (ASV) DECREASES HEART FAILURE EVENTS: A POOLED META ANALYSIS OF 629 PATIENTS WITH CENTRAL SLEEP APNEA AND CHENEY STOKES RESPIRATION (CSA-CSR)
Authors: Francisco Y. Macedo, Vitor Pacheco, Ahmed Ansari, Jessica Brown, Jefferson Vieira, Roberta Bogaev, Reynolds Delgado, Andrew Civitello, Biykem Bozkurt
Journal: Journal of the American College of Cardiology (2015)
Abstract 1332: Cisd2 haploinsufficiency leads to non-alcoholic fatty liver disease (NAFLD) and accelerates hepatocarcinogenesis in mice
Authors: Cheng-Heng Kao, Zhao-Qing Shen, Yi-Fan Chen, Ting-Fen Tsai
Journal: Cancer Research (2012)

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Hepatic steatosis (fatty liver) is a vulnerable factor that could lead to liver damage, inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). However, despite the high prevalence of NAFLD, the genetic factor determining the disease progression remains poorly understood. CISD2 is a previously uncharacterized novel gene located within the overlapping region of HCC critical region and human longevity region on chromosome 4q. We have recently demonstrated for the first time that Cisd2 is a mitochondrial outer membrane protein which mediates mitochondrial integrity and lifespan in mammals. Surprisingly, we have observed phenotype similar to NAFLD in the liver of Cisd2 heterozygous (+/−) knockout mice. Cisd2 haplo-insufficiency led to abnormal lipid metabolism accompanying with fatty liver, cell death, severe inflammation and fibrosis in the liver. Moreover, there was a low incidence (1/18; 5.6%) of HCC developed at 16-18 months of age in the Cisd2+/− mice. Interestingly, our results revealed a significant increase of the Srebp1c which is the master regulator of lipogenesis; the increase in Srebp1-c seems to further up-regulate the expression of its target gene, fatty acid synthase (Fas), in the Cisd2+/− livers. In addition, we found that liver fibrosis was associated with activation of hepatic stellate cells, as revealed by increased expression of α-ΣMA, in the Cisd2+/− livers. Furthermore, we provide evidence that Cisd2 haplo-insufficiency promoted hepatocarcinogenesis and accelerated HCC development by 4-6 months in the transgenic mice expressing HBV X protein. In summary, our results suggested that Cisd2 is likely to be a haplo-insufficient tumor suppressor gene for HCC. Heterozygous deficiency of Cisd2 led to NAFLD, and accelerated the progression of HBV-associated HCC. Our data suggest that Cisd2 is a molecular target for the development of chemoprevention and therapeutic strategy for NAFLD. 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 1332. doi:1538-7445.AM2012-1332
Toluene Di-Isocyanate (TDI) Toxicity
Authors: Heinrich G. Brugsch, Hervey B. Elkins
Journal: New England Journal of Medicine (1963)

TOLUENE di-isocyanate, or tolylenedi-isocyanate (TDI), is a compound widely used today in the manufacture of polyurethane. Since the description of a procedure published by Bayer1 in 1947 polyisocyanates have been brought into interactions with a resin, and polyurethane obtained as the end product. If polyurethane contains carbon dioxide in varying quantities, depending upon the polyisocyanates and resins selected, it assumes a "foamy" character. Commercial tolylenedi-isocyanate, a liquid at room temperature, is usually a mixture of 2 isomers; it has a pungent, acrid odor, its color varies from colorless to a light green, its vapor pressure is 0.04 mm. at 20°C., . . .
AB0809 Educational programs for primary care physicians - effectiveness in diagnosis and treatment of ankylosing spondylitis in kazan
Authors: S. Lapshina, L. Myasoutova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The long period of time from the first signs of ankylosing spondylitis (AS) to the correct diagnosis (mean 7-8 years) presents a delay of potentially effective therapy. <h3>Objectives</h3> To evaluate the effectiveness of educational activities for primary contact physicians to AS diagnosis <h3>Methods</h3> Since 2010 schools for primary care physicians for early diagnosis and therapy tactics of patients with AS are held in Kazan. Evaluation of the results was carried out according to the analysis of reports receiving from outpatient Rheumatological City Center in Kazan in 2009 (base year) compared to the years 2010-2012 after schools. <h3>Results</h3> After schools (2010 – 2011 years) among all patients referred to rheumatologist for the first time in a given year, the proportion of patients with AS increased from 7.1% in the base 2009 to 9.6% in 2010, 10,1% in 2011, 11.2% in 2012. The number of patients with AS who have applied for the first time increased from 118 in 2009 to 190 in 2010, 204 pts in 2011, 237 pts in 2012. Significantly increased the number of primary patients coming to rheumatologist consultation with documentation satisfactory to the rheumatologist (a clear description of back pain, laboratory tests, determination HLAB27, X-ray and / or MRI) from 23.7% in 2009 to 67% of patients in 2012. Primary care physicians, following rheumatologist appointments, begin to recommend more frequently continuous using of non-steroid anti-inflammatory drugs (from 9.7% in 2009 to 44.9% in 2012) <h3>Conclusions</h3> Educational programs for primary care physicians are essential and contribute to early diagnosis of AS, the timely and proper destination therapy. <h3>Disclosure of Interest</h3> None Declared
Self‐medication of anaphylactic reactions due to Hymenoptera stings—an <scp>EAACI</scp> Task Force Consensus Statement
Authors: M. B. Bilò, E. Cichocka‐Jarosz, R. Pumphrey, J. N. Oude‐Elberink, J. Lange, T. Jakob, P. Bonadonna, J. Fernandez, M. Kosnik, A. Helbling, H. Mosbech, R. Gawlik, M. Niedoszytko, V. Patella, V. Pravettoni, R. Rodrigues‐Alves, G. J. Sturm, F. Rueff
Journal: Allergy (2016)

An anaphylactic reaction due to a Hymenoptera sting is a clinical emergency, and patients, their caregivers as well as all healthcare professionals should be familiar with its recognition and acute management. This consensus report has been prepared by a European expert panel of the EAACI Interest Group of Insect Venom Hypersensitivity. It is targeted at allergists, clinical immunologists, internal medicine specialists, pediatricians, general practitioners, emergency department doctors, and any other healthcare professional involved. The aim was to report the scientific evidence on self-medication of anaphylactic reactions due to Hymenoptera stings, to inform healthcare staff about appropriate patient self-management of sting reactions, to propose indications for the prescription of an adrenaline auto-injector (AAI), and to discuss other forms of medication. First-line treatment for Hymenoptera sting anaphylaxis is intramuscular adrenaline. Prescription of AAIs is mandatory in the case of venom-allergic patients who suffer from mast cell diseases or with an elevated baseline serum tryptase level and in untreated patients with a history of a systemic reaction involving at least two different organ systems. AAI prescription should also be considered in other specific situations before, during, and after stopping venom immunotherapy.
Abstract 102: Circulating C-reactive protein and colorectal cancer risk: a report from the Shanghai Men's Health Study.
Authors: Jie Wu, Qiuyin Cai, Honglan Li, Hui Cai, Jing Gao, Gong Yang, Wei Zheng, Yong-Bing Xiang, Xiao-ou Shu
Journal: Cancer Research (2013)

Abstract Chronic inflammation has been implicated in the pathogenesis of colorectal cancer. C-reactive protein (CRP), a biomarker of systemic inflammation, has been investigated in various populations for its association with colorectal cancer risk, but results have been inconsistent. We examined pre-diagnostic circulating levels of CRP with colorectal cancer risk among 288 colorectal cancer cases and 576 frequency-matched controls nested within the Shanghai Men's Health Study (2002-2006), a population-based cohort study of 61,483 men. Baseline plasma CRP levels were 47% higher among men who subsequently developed colorectal cancer than among those who remained free of the disease (1.12 μg/ml vs. 0.76 μg/ml; P&amp;lt;0.001). Multivariate analyses showed a dose-dependent relationship between CRP and colorectal cancer risk (P-trend=0.001); men in the highest tertile with CRP &amp;gt;1.19 μg/ml had 1.88-fold (95%CI: 1.24-2.86) increased odds of developing colorectal cancer compared with men in the lowest tertile with CRP &amp;lt;0.45 μg/ml. The association was observed for both colon and rectal cancers, became stronger after excluding subjects who took any antibiotics during past 7 days, and was restricted to cancer cases diagnosed within 4 years of blood collection (ORs for the highest tertile being 3.28 (95%CI: 1.28-8.37), 3.68 (95%CI: 1.62-8.38), and 1.05 (95%CI: 056-1.97), respectively for cases diagnosed within 2, 2-4 and 4 years after blood draw). The findings from our study suggest that circulating CRP level is positively associated with colorectal cancer risk in Chinese men, and this association, at least in part, is explained by inflammation related to cancerous or precancerous processes. Citation Format: Jie Wu, Qiuyin Cai, Honglan Li, Hui Cai, Jing Gao, Gong Yang, Wei Zheng, Yong-Bing Xiang, Xiao-ou Shu. Circulating C-reactive protein and colorectal cancer risk: a report from the Shanghai Men's Health Study. [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 102. doi:10.1158/1538-7445.AM2013-102
Abstract 1083: Alpha-santalol, a chemopreventive agent against skin cancer, causes G2/M cell cycle arrest in both p53 mutated human epidermoid carcinoma A431 cells, and p53 wild-type human melanoma UACC-62 cells
Authors: Xiaoying Zhang, Wei Chen, Ruth Guillermo, Gudiseva Chandrasekher, Radhey S. Kaushik, Hesham Fahmy, Chandradhar Dwivedi
Journal: Cancer Research (2010)

Abstract α-Santalol, an active component of sandalwood oil, has shown chemopreventive effects on skin cancer development in murine models by either chemical- or UVB-induced skin carcinogenesis. α-Santalol has shown induction of apoptosis in both murine models and epidermoid carcinoma A431 cells. However, to the best of our knowledge, effects of α-santalol on cell cycle have not been studied. Thus, the objective of this study was to investigate the effects of α-santalol on cell cycle progression and protein components involved in the regulation of cell cycle in both p53 mutated human epidermoid carcinoma A431 cells and p53 wide-type human melanoma UACC-62 cells to elucidate the mechanism(s) of action. MTT assay was used to determine cell viability in A431 cells, UACC-62 cells and monkey kidney CV-1 cells; fluorescence-activated cell sorting (FACS) analysis of propidium iodide staining was used for determining cell cycle distribution in A431 cells and UACC-62 cells, and Western immunoblotting was used for determining the expression of various proteins involved in the cell cycle progression. Results showed that α-santalol at concentration of 25 to 75 μM resulted in a concentration-and time-dependent decrease in cell viability from 24 h treatment in both A431 and UACC-62 cells. Cell cycle analysis by flow cytometry showed that α-santalol at 50 μM and 75 μM induced G2/M phase cell cycle arrest starting from 6 hour treatment in both UACC-62 and A431 cells. Furthermore, Western immunoblotting data showed that α-santalol altered the expressions of cell cycle proteins such as cyclin A, cyclin B1, cell division cycle 2 (cdc2), cdc25c and cyclin-dependent kinase 2 (Cdk2) in A431 cells which are required for G2/M transition. α-Santalol treatment upregulated the expression of p21CIP1/WAF1 and suppressed the expression of mutated p53 in A431 cells; whereas, α-santalol treatment increased the expressions of wide-type p53 in UACC-62 cells. Taken together, this study for the first time identifies the effects of α-santalol in G2/M phase arrest and describes the detailed mechanisms of G2/M phase arrest by this agent in both p53 mutated A431 cells and p53 wide-type UACC-62 cells, which might be contributing to its overall cancer preventive efficacy in various mouse skin cancer models in addition to induction of apoptosis by α-santalol. (Supported by 2010 Research Initiative Grant from the State of South Dakota funded as Translational Cancer Research Center). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1083.
DS-02 * INDUCTION OF AUTOPHAGY MARKERS IN GLIOMAS FOLLOWING PHARMACOLOGICAL NOTCH BLOCKADE
Authors: M. Natsumeda, H. Zhang, H. Kaur, L. Asnaghi, C. G. Eberhart
Journal: Neuro-Oncology (2014)

BACKGROUND: Induction of autophagy has been identified as a potential mechanism for chemotherapeutic resistance, and its manipulation has increasingly been explored as a treatment strategy in many cancers. However, there is minimal data on the effects of the Notch pathway on autophagy in cancer, and none in gliomas. We therefore examined if Notch pathway blockade using a gamma-secretase inhibitor (GSI) would induce autophagy in glioma neurosphere lines. METHODS: 500,000 cells from 3 neurosphere lines (HSR-GBM1, 040622, and 040821), maintained in Neurocult medium supplemented with EGF and FGF, were treated for 48 hours with DMSO, 2 µM or 5 µM levels of GSI. Protein was extracted from cell lysates and Western blotting was performed using primary antibodies specific for LC3B, pAkt, Akt, pERK, and ERK, as well as β-actin. RESULTS: A LC3B-II band, suggesting induction of autophagy, was observed after Notch pathway blockade at the higher (5 µM) GSI level in all three cell lines. Inhibition of pAkt was also seen at this dose, but a significant up-regulation of pERK was not observed. CONCLUSIONS: Induction of autophagy, possibly through inhibition of the Akt / mTor pathway, was seen after Notch inhibition in glioma neurospheres using a GSI. These results suggest a possible resistance mechanism to Notch inhibition in malignant gliomas.
Abstract 2650: KRIBB801 modulates STAT3 pathway via binding to JAK3
Authors: Byoung-Mog Kwon, Dae-Seop Shin, Dong Cho Han
Journal: Cancer Research (2011)

Abstract Constituent activation of STAT3 in human cancers causes abnormal proliferation and survival of cancer cell. Therefore, the small-molecules inhibiting STAT3 activity could be used for therapeutical drug in STAT3 dependent proliferating cancer cells. In this report, we screened small-molecules inhibiting STAT3 activity in chemical library containing 1,333 synthetic compounds obtained from “Korea Chemical Bank” through a cell-based luciferase assay system. KRIBB801 was selected as a novel inhibitor of STAT3 activation. KRIBB801 inhibits STAT3 phosphorylation at 1 hour and the expression of the STAT3-regulated genes at the same time point. Inhibition of STAT3 phosphorylation leads to apoptosis of MDA-MB-468. We postulated that inhibition of JAK family proteins or c-Src result in inhibition of STAT3 phosphorylation. Interestingly, phosphorylation of these kinases was mildly inhibited at 1 hr which phosphorylation of STAT3 was perfectly inhibitied. This result implies that inhibition of STAT3 phosphorylation by KRIBB801 is independent event with phosphorylation of upstream kinases. Co-immunoprecipitation shows that KRIBB101 inhibits the JAK3-STAT3 interaction. Moreover, JAK3 molecules were captured by biotylated KRIBB801. Finally, KRIBB801 inhibits kinase activity of JAK3 about 30% at 10 μM in vitro kinase assay. From these results, we suggest that KRIBB801 binds to JAK3 molecules and disturbs JAK3-STAT3 interaction which leads to inhibition of STAT3 phosphorylation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2650. doi:10.1158/1538-7445.AM2011-2650