tbuckley/cabot-search huggingface dataset:
SAT0318 Could Adrenomedullin be Considered as a Treatment for Osteoarthritis?
Authors: A. Chatron-Colliet, F. Velard, D. Côme, H. Lin, H. K. Ea, F. Lioté
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis (OA) is a frequent articular disease which generally affects elderly people. Major hallmarks of OA are chondrolysis, chondrocyte apoptosis and local inflammation. Of note, there is no treatment for OA. <h3>Objectives</h3> Previous data on collagen-induced arthritis (CIA) in mice have demonstrated that adrenomedullin (AM) and an AM-derived peptide (22-52AM) could modulate inflammation and chondrocyte apoptosis. Our purpose was to study the effect of AM) and 22-52AM on chondrocytes <i>in vitro</i> and in OA model <i>in vivo.</i> In one hand, we have investigated AM and AM receptor [Calcitonin Receptor Like Receptor (CLR)/Receptor Activating Modulated Protein (RAMP)] expression by articular chondrocytes under physiological (hypoxia) and OA (IL-1β) environment; in the other hand we brought evidence highlighting the effects of AM and 22-52 AM on cartilage breakdown and chondrocyte apoptosis <i>in vitro</i> and <i>in vivo</i>. <h3>Methods</h3> In normoxia or hypoxia (physiological condition), ADMand its receptor expression was investigated in bovine articular chondrocytes (BAC) at the mRNA (RT-qPCR) and protein levels (EIA, immunolfluorescence). ADM and 22-52ADM anti-apoptotic effects were assessed on Fas-ligand (FasL)-mediated apoptosis using caspase-specific fluorogenic substrates. To assess the ADM anti-inflammatory effect on IL1β-stimulated chondrocytes, RT-qPCR analyses were performed to assess production of pro-inflammatory factors. Meniscectomized mice were injected IP 3 times a week during 8 weeks with PBS, ADM or 22-52ADM (1.2 µg/g). Joints were then prepared for histological analysis to quantify chondrocyte apoptosis (TUNEL) and cartilage degradation (Safranin-O). <h3>Results</h3> Using immunofluorescence, we have demonstrated that CLR and RAMPs were more colocalized when chondrocytes were cultured in hypoxia, and especially in inflammatory environment. Coupled with AMPc measurements, those data suggest that the receptor is functional. Moreover, in such conditions, ADM secretion was significantly increased and exogenous ADM (10<sup>-6</sup>M) demonstrated anti-apoptotic activity. Nevertheless, ADM failed to modulate mRNA production of pro-inflammatory factors. Regarding joint degradation rate of meniscetomized mice, neither ADM nor the 22-52ADM have had a protective effect on apoptosis and chondrolysis. <h3>Conclusions</h3> In « physiological environment », BAC were able to produce both ADM and functional receptor components. In addition, ADM treatment prevented FasL-induced apoptosis in hypoxia although its anti-inflammatory effect was not confirmed in these cells. Contrary to our expectations based on the CIA model, ADM or its derived peptide 22-52ADM administered systemically did not disclose any effect on OA progression. Direct intra-articular effects of ADM might be investigated. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-38: VPS34 lipid kinase activity is positively regulated by Src phosphorylation and is required for Src-mediated cellular transformation.
Authors: Dianne S. Hirsch, Yi Shen, Milos Dokmanovic, Wen Jin Wu
Journal: Cancer Research (2013)

Abstract VPS34 is a phosphatidylinositol 3-kinase (PI3K) that catalyzes phosphorylation of phosphatidylinositol. In response to nutrients, VPS34 contributes to the activation of mTOR/S6K1 signaling which regulates proliferation, protein synthesis, and cell survival. Intracellular mechanisms leading to VPS34 activation are just beginning to be elucidated. Src is a non-receptor tyrosine kinase that signals downstream of numerous pathways to regulate cell proliferation, survival, and cancer metastasis. Here, we report that Src directly phosphorylates VPS34 leading to activation of VPS34 lipid kinase activity, and that VPS34 lipid kinase activity is required for Src-mediated cellular transformation. Silencing VPS34 specifically inhibits Src-Y527F-induced colony formation in soft agar, but not Ras-G12V-induced colony formation. We have identified two novel VPS34 mutations, which either eliminate lipid kinase activity (KD mutant) or reduce tyrosine phosphorylation (Y231F mutant) by Src-Y527F. When VPS34-KD is stably expressed in Src-Y527F-transformed cells, proliferation and anchorage independent growth are significantly inhibited. Additionally, stable expression of VPS34-KD causes an increased number of binucleate and multinucleate cells, suggesting that VPS34 kinase activity is also required for cytokinesis. Stable expression of VPS34-Y231F in Src-Y527F transformed cells also reduces colony formation. We additionally found that VPS34 protein levels and tyrosine phosphorylation correlate with the tumorigenic activity of breast cancer cell lines. Together these data suggest that Src to VPS34 signaling may contribute to the development and progression of human cancers. Citation Format: Dianne S. Hirsch, Yi Shen, Milos Dokmanovic, Wen Jin Wu. VPS34 lipid kinase activity is positively regulated by Src phosphorylation and is required for Src-mediated cellular transformation. [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 LB-38. doi:10.1158/1538-7445.AM2013-LB-38
Black Teens Not Smoking in Great Number
Authors: H. McIntosh
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Black Teens Not Smoking in Great Number Get access Hugh McIntosh Hugh McIntosh Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 8, 19 April 1995, Pages 564–565, https://doi.org/10.1093/jnci/87.8.564 Published: 19 April 1995
Cholera with severe renal failure in an Italian tourist returning from Cuba, July 2013
Authors: M Mascarello, M L Deiana, C Maurel, C Lucarelli, I Luzzi, R Luzzati
Journal: Eurosurveillance (2013)

In July 2013, an Italian tourist returning from Cuba was hospitalised in Trieste, Italy, for cholera caused by Vibrio cholerae O1 serotype Ogawa with severe renal failure. An outbreak of cholera was reported in Cuba in January 2013. Physicians should consider the diagnosis of cholera in travellers returning from Cuba presenting with acute watery diarrhoea.
In Support of Same-Sex Marriage
Authors: Edward W. Campion, Stephen Morrissey, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2015)

Eleven years ago, Massachusetts became the first state in the country to give same-sex marriages full legal recognition. Today, same-sex marriage is legal, through legislative or judicial action or by popular vote, in more than 35 states and the District of Columbia. It is recognized by the federal government. And polls consistently show that it is supported by a clear majority of Americans. However, in Ohio, Kentucky, Michigan, and Tennessee, the Sixth Circuit Court of Appeals has ruled in favor of laws and constitutional amendments that define marriage as a union between a man and a woman only, denying recognition . . .
Are welders more at risk of respiratory infections? Findings from a cross-sectional survey and analysis of medical records in shipyard workers: the WELSHIP project
Authors: Andrea Marongiu, Omar Hasan, Anila Ali, Sharoon Bakhsh, Bobby George, Nabeel Irfan, Cosetta Minelli, Cristina Canova, Susie Schofield, Sara De Matteis, Paul Cullinan
Journal: Thorax (2016)

Exposure to welding fume increases the risk of pneumococcal infection; whether such susceptibility extends to other respiratory infections is unclear. We report findings from a survey and from medical consultation data for workers in a large shipyard in the Middle East.Between January 2013 and December 2013, we collected cross-sectional information from 529 male workers variously exposed to welding fume. Adjusted ORs for respiratory symptoms (cough, phlegm, wheezing, shortness of breath and 'chest illness') were estimated using multivariable logistic regression. Subsequently, we examined consultation records from 2000 to 2011 for 15 954 workers who had 103 840 consultations for respiratory infections; the associations between respiratory infections and levels of welding exposure were estimated using a count regression model with a negative binomial distribution.13% of surveyed workers reported respiratory symptoms with a higher prevalence in winter, particularly among welders. The adjusted OR in welders versus other manual labourers was 1.72 (95% CI 1.02 to 3.01) overall and 2.31 (1.05 to 5.10) in winter months; no effect was observed in summer. The risk of consultation for respiratory infections was higher in welders than in manual labourers, with an adjusted incidence rate ratio of 1.45 (1.59 to 1.83) overall, 1.47 (1.42 to 1.52) in winter and 1.33 (1.23 to 1.44) in summer (interaction, p<0.001).The observation that respiratory symptoms and consultations for respiratory infection in welders are more common in winter may indicate an enhanced vulnerability to a broad range of infections. If confirmed, this would have important implications for the occupational healthcare of a very large, global workforce.
Coral-Red Fluorescence
Authors: Ivana Binic, Aleksandar Jankovic
Journal: New England Journal of Medicine (2011)

A 66-year-old man presented to a dermatologist with a pruritic, erythematous, scaly, and mildly hyperpigmented rash of 2 weeks' duration that involved the scrotum and both inguinal creases (Panel A). Under examination with ultraviolet A light from a Wood's lamp, the rash exhibited coral-red fluorescence (Panel B), a finding pathognomonic for erythrasma. This common disorder results from overgrowth of Corynebacterium minutissimum in the superficial stratum corneum of moist intertriginous and interdigital regions. The coral-red fluorescence is a result of the production of coproporphyrin III by C. minutissimum, and it helps to distinguish this disorder from dermatophytoses, candidal intertrigo, and psoriasis. . . .
Case 10-2001
Authors: Dorothy A. White, Eugene J. Mark
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 53-year-old woman was admitted to the hospital because of radiographically evident pulmonary nodules.The patient had a long history of seropositive rheumatoid arthritis, which was usually well controlled with naproxen. Six years before admission, a painful lump in the right Achilles tendon was excised; microscopical examination indicated that the mass was a rheumatoid nodule. When the patient was seen at this hospital three and a half years before admission, she was using an albuterol inhaler because of a cough productive of clear sputum. Bronchoconstriction was later diagnosed, and bronchodilator therapy was continued.At a subsequent visit, . . .
ASSOCIATION OF DUAL ANTIPLATELET THERAPY WITH REDUCED MAJOR ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH SYMPTOMATIC PERIPHERAL ARTERIAL DISEASE
Authors: Ehrin J. Armstrong, David Anderson, Walid Sherif, Satinder Singh, Heejung Bang, Debbie Chen, Khung Yeo, Ezra Amsterdam, John Laird
Journal: Journal of the American College of Cardiology (2014)
Abstract 1615: Gene expression profile predicts response to smoothened inhibitors in epithelial cancers
Authors: Fabrizio Galimberti, Alex Busch, Fadzai Chinyengetere, Tian Ma, David Sekula, Vincent Memoli, Konstantin Dragnev, Fang Liu, Angeline S. Andrew, Patricia Greninger, David Robbins, Jeff Settleman, Cyril Benes, Ethan Dmitrovsky
Journal: Cancer Research (2011)

Abstract The hedgehog (HH) signaling pathway is important for embryonic development as it controls cell fate and proliferation. Deregulation of the HH pathway is linked to the onset and maintenance of multiple cancers. Clinical trials revealed promising effects of targeting the HH pathway with smoothened (Smo) inhibitors, particularly in basal cell carcinomas and medulloblastomas where HH pathway activation occurs. This study sought to uncover a gene signature that would predict response to Smo inhibitors, such as cyclopamine or SANT-1. A panel of 705 human cancer cell lines from diverse epithelial cancers was interrogated for sensitivity to cyclopamine. A subset of cancer cell lines exhibited substantial growth inhibition across a broad array of epithelial cancers. Sensitivity was significantly linked to high Gli1, high cyclin E, and low insulin-like growth factor binding protein 6 (IGFBP6) expression levels (P &amp;lt; 0.05). Cyclin E overexpression and IGFBP6 knockdown conferred increased sensitivity to either cyclopamine or SANT-1 Smo inhibitors in lung cancer cell lines. This functionally validated the importance of this gene signature. To ascertain the biological impact of this profile, cyclin E transgenic mice that spontaneously developed premalignant and malignant lung lesions were studied. These lung cancers expressed the gene signature profile that predicts sensitivity to Smo inhibitors. As expected, cyclopamine treatment of these transgenic mice caused substantial immunohistochemical repression of cyclin D1 and Ki-67 in both premalignant and malignant lung lesions. To confirm and extend these findings, cyclopamine antineoplastic effects were examined using a previously described murine syngeneic and transplantable lung cancer model. Cyclopamine treatment significantly repressed lung cancer formation in these mice (P &amp;lt; 0.01). Notably, a subset of examined human lung cancers was found to express the same gene signature that predicted response to Smo inhibitors. Taken together, these findings reveal a gene expression profile that predicts response of diverse epithelial cancers to Smo inhibitors. Future work should discern whether this same gene signature also predicts response to HH inhibitors in epithelial cancers of patients. 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 1615. doi:10.1158/1538-7445.AM2011-1615
Encouraging preliminary results of FOLFOX-6 in first-line therapy of locally advanced or metastatic pancreatic cancer (APC)
Authors: F. Farhat, J. Kattan, G. Chahine, W. Moukadem, F. Nasr, F. Younes, M. Ghosn
Journal: Journal of Clinical Oncology (2005)

4094 Background: Pancreatic carcinoma has a poor prognosis and Chemotherapy remains the most common approach in advanced disease. Gemcitabine is the only approved drug to be used as single agent in APC. However, recent publications showed a promising results of the combination of Oxaliplatin and 5-FU (Ducreux et al Ann Oncol 2004). Therefore, we conducted a phase II trial investigating the efficacy of FOLFOX-6 in APC pts. Methods: From January 2003 through November 2004, 30 eligible patients were included. Objectives were: response rate, progression free survival and toxicity profile. Treatment plan was Oxaliplatin 100 mg/m2 and Folinic Acid 400 mg/m2 on day 1 followed by a 5-FU bolus 400 mg/m2 and 3000 mg/m2 46-h infusion every 2 weeks. Patients were evaluable according to the RECIST criteria. Results: 23 out of 30 pts had metastatic disease and 29 had adenocarcinoma. 176 cycles were delivered with a mean of 5.9 cycles/patient (extremes: 1 - 12). 25 patients were evaluable for response since 2 pts had an early death, 1 pt was lost of follow-up, and 2 pts are still early to be evaluated. There were 8 PR and 11 SD including one neuroendocrine tumor. So, clinical benefit was encountered in 63%. An important decrease in CA 19–9 (≥ 60%) was seen in 8 pts out of 12 tested pts. Toxicities grade 3/4 included febrile neutropenia in 2 pts, neutropenia in 4 pts, anemia and thrombocytopenia in 2 pts each, diarrhea in 1 pt and mucositis in 1 pt. Neurosensory toxicity was very mild (grade 2 neuropathy in 2 pts). The median survival was not reached yet. Conclusion: In APC patients, FOLFOX-6 regimen achieved an interesting response rate. The toxicity profile is acceptable. This regimen is still recruiting patients to confirm our encouraging Results: This work was partially supported by a grant from Sanofi Synthelabo. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo
Activatable albumin-photosensitizer nanoassemblies for triple-modal imaging and thermal-modulated photodynamic therapy of cancer
Authors: Dehong Hu, Zonghai Sheng, Guanhui Gao, Fungming Siu, Chengbo Liu, Qian Wan, Ping Gong, Hairong Zheng, Yifan Ma, Lintao Cai
Journal: Biomaterials (2016)
Diagnosis of Spine Metastases by FDG Imaging Using a Gamma Camera in the Coincidence Mode
Authors: PAUL D. SHREVE, ROBERT S. STEVENTON, MILTON D. GROSS
Journal: Clinical Nuclear Medicine (1998)

Purpose: To illustrate the detection of metastatic lung cancer using a conventional dual detector gamma camera modified to operate in the coincidence mode to image the static distribution of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG). Methods: A patient with known lung cancer underwent FDG imaging to evaluate the extent of metastatic disease. Twenty-three-minute emission image acquisition at one bed position using a dual detector coincidence gamma camera was performed to evaluate the entire chest and upper abdomen. Results: In addition to detecting the malignant lung nodule, mediastinal lymph node metastases and a rib metastasis, symptomatic metastases to lower thoracic and upper lumbar vertebral bodies, which were not identified on radiographs, CT, or bone scan, were shown clearly by FDG coincidence gamma camera imaging. Conclusion: FDG tumor imaging in the body is feasible using a dual detector gamma camera operating in coincidence mode and may find an important role in a certain subset of FDG tumor imaging.
NEOD001 DEMONSTRATES CARDIAC AND RENAL BIOMARKER RESPONSES IN A PHASE 1/2 STUDY IN PATIENTS WITH AMYLOID LIGHT CHAIN AMYLOIDOSIS AND PERSISTENT ORGAN DYSFUNCTION
Authors: Michaela Liedtke, Raymond Comenzo, Heather Landau, David Seldin, Brendan Weiss, Jeffrey Zonder, Jackie Walling, Gene Kinney, Martin Koller, Morie A. Gertz
Journal: Journal of the American College of Cardiology (2016)
Abstract 992: Regulation of ABCG2 lysosomal degradation by xanthines: Role of the PI3K/AKT pathway.
Authors: Rui Ding, Barton A. Kamen, Jia Shi, Kathleen W. Scotto
Journal: Cancer Research (2013)

Abstract ABCG2 confers multidrug resistance to a wide range of structurally unrelated chemotherapeutic drugs, often resulting in the failure of cancer chemotherapy. Accordingly, the downregulation of ABCG2 expression and/or function has been proposed as part of a regimen to improve cancer therapeutic efficacy. Previously, we have reported that a group of xanthines including caffeine, theophylline and dyphylline can dramatically decrease ABCG2 protein in drug resistant cells, causing a significant increase in the intracellular retention of ABCG2 substrates and sensitization of the cells to chemotherapeutic agents (Ding et al., Mol Pharmacol 81:328-337, 2012). This downregulation of ABCG2 is due to a selective acceleration of its lysosomal degradation by xanthines. We now show that xanthines induce the endocytosis and subsequent degradation of ABCG2. In addition, PI3K/AKT/mTORC1 signaling was found to be involved in mediating the effect of xanthines on ABCG2, since both caffeine and theophylline strongly inhibited activation of AKT and mTORC1, and inhibition of both AKT and mTORC1 mimicked the effect of xanthines on ABCG2. Furthermore, adenosine, a nucleoside vital for purine metabolism and energy homeostasis, fully reversed the downregulation effect of caffeine on ABCG2. Interestingly, this adenosine-mediated effect occurs intracellularly and independent of adenosine receptor signalling, identifying a novel mechanism whereby the xanthine-degradation of ABCG2 is influenced by intracellular levels of adenosine. Importantly, adenosine also blocked the lysosomal degradation of ABCG2 that was induced by PI3K/AKT inhibition, indicating that the adenosine-mediated intracellular events cross-talk with the PI3K/AKT pathway in regulating ABCG2 degradation. This study enhances our understanding of the regulation of ABCG2 internalization and degradation, and identifies new targets for the development of ABCG2 expression/function modulating agents for chemosensitization. Citation Format: Rui Ding, Barton A. Kamen, Jia Shi, Kathleen W. Scotto. Regulation of ABCG2 lysosomal degradation by xanthines: Role of the PI3K/AKT pathway. [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 992. doi:10.1158/1538-7445.AM2013-992
Effect of Gradual Withdrawal on the Rebound Sleep Disorder after Discontinuation of Triazolam
Authors: David J. Greenblatt, Jerold S. Harmatz, Miguel A. Zinny, Richard I. Shader
Journal: New England Journal of Medicine (1987)

Sixty volunteers with insomnia participated in a randomized, double-blind, controlled clinical trial. After an initial six nights of placebo, 30 subjects (the abrupt-withdrawal group) received 0.5 mg of triazolam nightly for 7 to 10 nights, after which they received placebo. The other 30 subjects (the tapered-dosage group) received the same initial placebo treatment, then triazolam at 0.5 mg for seven nights, at 0.25 mg for two nights, and at 0.125 mg for two nights, and then placebo. As compared with the initial placebo period, the triazolam period significantly reduced the interval before the onset of sleep (sleep latency), and it prolonged sleep duration, reduced the number of awakenings, and improved the self-rated soundness of sleep in all cohorts. In the abrupt-withdrawal group, plasma levels of triazolam were undetectable the morning after the first night of placebo substitution, and subjects reported prolongation of sleep latency (57 minutes longer than base line), reduction in sleep duration (1.4 hours less than base line), and increased awakenings (1.2 per night above base line). The symptoms of rebound sleep disorder lasted one or possibly two nights, and there was a reversion toward base line on subsequent placebo nights. In the tapered-dosage group, however, plasma triazolam levels fell gradually to zero, and rebound symptoms were decreased or eliminated. Thus, rebound sleep disorder following abrupt discontinuation of triazolam can be attenuated by a regimen of tapering.