tbuckley/cabot-search huggingface dataset:
Abstract 1306: SR48692 inhibits EGF receptor transactivation and proliferation of lung cancer cells.
Authors: Terry W. Moody, Robert T. Jensen
Journal: Cancer Research (2013)

Abstract Neurotensin (NTS) is an autocrine growth factor for some lung cancer cells (Moody et al., 1985;Life Sci 36:1727). NTS binds with high affinity to the GPCR NTSR1 causing phosphatidyl inositol turnover and proliferation of lung cancer cells; SR48692 is a NTSR1 antagonist (Moody et al., 2001; Peptides 22:109). NTSR1 expression is associated with poor survival of non-small cell lung cancer (NSCLC) patients (Alfano et al., 2010; Clin Cancer Res 16:4401). NSCLC cells express the epidermal growth factor receptor (EGFR) whose tyrosine kinase activity is inhibited by gefitinib. Here the abillity of SR48692 to block EGFR transactivation caused by NTS was investigated. NTS and NTS8-13 but not NTS1-8 addition to NSCLC cell lines NCI-H1299 or A549 cells increased phosphorylation of Tyr1068 of the EGFR after 2 min which was blocked by 10 uM SR48692 or 10 ug/ml gefitinib. The ability of NTS to regulate EGF receptor transactivation was blocked by GM6001 (matrix metalloprotease inhibitor), PP2 (Src inhibitor), N-acetylcysteine (anti-oxidant) and transforming growth factor TGF) α antibody. By ELISA, NTS significantly increased secretion of TGFα from lung cancer cells. NTS but not levocabastine (NTSR2 agonist) increased cytosolic Ca2+ within seconds after addition to NCI-H1299 cells which was antagonized by SR48692. NTS addition to NCI-H1299 cells increased tyrosine phosphorylation of beta-catenin, ERK, FAK, PYK-2 and Src which was antagonized by SR48692. SR48692 inhibited the proliferation of NCI-H1299 and A549 cells which have wild type EGFR. Also, SR48692 potentiated the ability of gefitinib to inhibit growth of NCI-H1299 and A549 cells. These results indicate that SR48692 is a NTSR1 antagonist which increases the potency of gefitinib in lung cancer cells. Citation Format: Terry W. Moody, Robert T. Jensen. SR48692 inhibits EGF receptor transactivation and proliferation of lung cancer cells. [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 1306. doi:10.1158/1538-7445.AM2013-1306
Bhagabat Charan Das
Authors: S. S. Das
Journal: BMJ (2014)

Bhagabat Charan Das was born the second of right children in the village of Bagalpur in Orissa, India. His father was the leader of his village and a landowner. The family’s livelihood depended on cultivation and farming of his land. Although they had plenty of food to feed themselves and indeed the whole village, they did not have much money. This created problems as none of the sons wanted to stay farming the land in the village. They wanted to be educated, go to university, and do professional jobs—like their eldest cousin, who became a school teacher and role model for them and encouraged them to get higher education. Without sufficient money, B C Das had to struggle, but his mind was set on becoming a doctor as he had seen so much illness and suffering among the people in his village, and he wanted to help them. He got a scholarship to study medicine at Cuttack Medical College and gained his licentiateship in 1942. During this time he joined the non-violent “Quit India Movement” against British rule in India and was jailed for four months by the British. He joined the army as a doctor for a couple of years. Even then he endured a lot of financial hardship in helping his younger siblings to receive an education and two of his sisters to get married.

In the second world war in 1943-5 he served as a frontline medical officer for the British Army. He was first posted as regional medical officer for four months on the Burma front, where the British army were fighting the Japanese forces. Forced to retreat to Rangoon by the advancing Japanese army, they had to walk 75 miles in the Burmese jungle in the night, hiding in ditches during the day. It took …
Androgens and Erythropoiesis
Authors: Frank H. Gardner, James C. Pringle
Journal: New England Journal of Medicine (1961)

ERYTHROLEUKOBLASTIC changes in the peripheral blood have been associated with extramedullary hematopoiesis. In recent years a large proportion of patients manifesting such changes associated with hepatosplenomegaly have been classified as having agnogenic myeloid metaplasia.1 Most of them have had evidence of myelosclerosis and myelofibrosis of the bone marrow. Often, the disorder follows as a sequela to polycythemia vera. In the patient with myeloid metaplasia the characteristic findings of chronic or acute myelocytic leukemia may eventually develop. As one views the spectrum of altered bone-marrow activity, the pattern may be part of a generalized myeloproliferative disorder of bone marrow.2 In this . . .
SAT0355 Real World Risk of Infusion Reactions with Pegloticase Treatment: Findings from Post-Approval us Safety Data
Authors: R. Malamet, T. Howson, A. Yeo, K. Bahrt
Journal: Annals of the Rheumatic Diseases (2013)

The global response to the SARS-Cov-2 pandemic has consisted of two main strategies both involving non-pharmaceutical interventions to control spread: mitigation, ultimately relying on herd immunity from vaccination, and elimination of infections locally. While simple theory for controlling an epidemic through herd immunity exist, there is no corresponding simple theory for the strategy of elimination with non-pharmaceutical interventions. Here we quantify an important aspect of the elimination strategy: the time to extinction without herd immunity, based solely on non-pharmaceutical interventions. Using a simple well-mixed stochastic SIR model, we find two new results: 1) using random walk theory we calculate a simple approximation of the mean extinction time and 2) using branching process theory the full distribution of times to extinction, which we show is given by the extreme value Gumbel distribution. We compare these results against complex spatially-resolved stochastic simulations to show very good quantitative agreement, demonstrating the validity of this simple approach. Overall, for SARS-Cov-2 our results predict rapid extinction — of order months — of an epidemic or pandemic if the reproductive number is kept to <i>R</i><sub><i>e</i></sub><i>&lt;</i> 0.5; in a counterfactual scenario with global adoption of an elimination strategy in June 2020, SARS-Cov-2 could have been eliminated world-wide by early January 2021.
Emergence of Vancomycin Resistance in<i>Staphylococcus aureus</i>
Authors: Theresa L. Smith, Michele L. Pearson, Kenneth R. Wilcox, Cosme Cruz, Michael V. Lancaster, Barbara Robinson-Dunn, Fred C. Tenover, Marcus J. Zervos, Jeffrey D. Band, Elizabeth White, William R. Jarvis
Journal: New England Journal of Medicine (1999)

Since the emergence of methicillin-resistant Staphylococcus aureus, the glycopeptide vancomycin has been the only uniformly effective treatment for staphylococcal infections. In 1997, two infections due to S. aureus with reduced susceptibility to vancomycin were identified in the United States.
Uptake of Tc-99m Pertechnetate By Lactating Breasts During a Thyroid Scan in a Postpartum Patient
Authors: CHONG G. CHEW, PAUL SOTIROPOULOS
Journal: Clinical Nuclear Medicine (2003)

CHEW, CHONG G. M.B.B.S., F.R.A.C.P.; SOTIROPOULOS, PAUL B. Medical Radiation Author Information
DOOR-TO-BALLOON TIME CORRELATES BETTER WITH PATIENTS OUTCOMES THAN SYMPTOM-TO-BALLOON TIME
Authors: Li-Ling Tan, Huili Zheng, Khuan-Yew Chow, Joshua Loh, Terrance Chua, Huay-Cheem Tan, David Foo, Hean Yee Ong, Khim-Leng Tong, Mark Richards, Mark Chan
Journal: Journal of the American College of Cardiology (2016)
Abstract 601: <i>In vitro</i> and <i>in vivo</i> inhibition of β-catenin by two novel β-catenin RNA antagonists, EZN-3889 and 3892
Authors: Yixian Zhang, Steven Kim, Victoria Shi, Zhengxing Qu, Stephen Castaneda, Maoliang Wang, Peifang Zhu, David Filpula, Lee M. Greenberger, Ivan D. Horak
Journal: Cancer Research (2010)

Abstract Background: β-Catenin is a subunit of the cadherin protein complex and a key integral component in the Wnt signaling pathway. Therefore, it not only plays an important role in cell-cell adhesion but also in tumorgenesis. β-catenin is activated in most colon cancers due to either mutations in APC or activating mutations in β-catenin itself. Furthermore, activating β-catenin mutations have been found in a variety of other tumors such as melanomas, hepatocellular carcinomas, breast, and prostate cancer, whereas β-catenin is not activated in most normal tissues. Therefore, inhibition of β-catenin is likely to have therapeutic effects in many cancers. Unfortunately, because β-catenin is devoid of any enzymatic activity, the development of inhibitors of β-catenin has been slow. We present here both in vitro and in vivo evidence that the lack of specificity of small-molecule inhibitors may be overcome by two novel β-catenin LNA-based mRNA antagonists, EZN-3889 and EZN-3892. Material and Methods: In vitro, the ability of the compounds to inhibit mRNA, cell growth, and reporter gene were evaluated by qRT-PCR, MTS, and luciferase assays respectively, in multiple cell lines. In vivo, β-catenin mRNA down-modulation in liver and human tumors, which were grown on the flank of nude mice, was evaluated after intravenous administration of the compounds. Results: Without lipofection, we found that these two antagonists could specifically down modulate β-catenin mRNA and protein effectively in multiple cell lines with a long-lasting effect. Additionally, these two molecules effectively inhibited β-catenin transcriptional activity in SW480 colorectal and H1581 lung cancer cells stably expressing a TCF/LEF luciferase reporter gene, resulting in growth inhibition. Combination of EZN-3889 or 3892 with sulindac demonstrated improved activities in both growth and reporter assay. Moreover, EZN-3889 and 3892 inhibited the spontaneous growth of spheroids in SW480 culture and convert SW480 spheroids to monolayers. Preliminary data suggest that these spheroids were more tumorgenic than the monolayer cells. In mice, both molecules significantly down modulated β-catenin mRNA in the liver. Conclusions: Without lipofection, β-catenin antagonists potently and specifically inhibited β-catenin mRNA expression both in vitro and in vivo after intravenous injection. Target inhibition correlated with growth inhibition and phenotypical change of SW480 spheroids. Further studies will examine the significance of the inhibition of the spheroids and the effect of these antagonists on tumor growth. 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 601.
Neointimal and Tubulointerstitial Infiltration by Recipient Mesenchymal Cells in Chronic Renal-Allograft Rejection
Authors: Paul C. Grimm, Peter Nickerson, John Jeffery, Rashmin C. Savani, James Gough, Rachel M. McKenna, Elzbieta Stern, David N. Rush
Journal: New England Journal of Medicine (2001)

Tissue remodeling depends on mesenchymal cells (fibroblasts and myofibroblasts) and is a prominent feature of chronic renal-transplant rejection. It is not known whether the mesenchymal cells that participate in remodeling originate locally or from circulating precursor cells.We obtained biopsy specimens of renal allografts from six male recipients of an allograft from a female donor, four female recipients of an allograft from a male donor, two male recipients of an allograft from a male donor, and two female recipients of an allograft from a female donor. All the allografts were undergoing chronic rejection. All but two specimens were obtained within six months after transplantation. We used immunohistochemical methods to identify mesenchymal cells with smooth-muscle alpha-actin and in situ hybridization to identify mesenchymal cells with Y-chromosome DNA.No Y-chromosome bodies were identified in the case of the two renal-allograft specimens in which both the donor and the recipient were female. In the case of the two renal-allograft specimens in which both the donor and the recipient were male, approximately 40 percent of mesenchymal cells contained a Y-chromosome body. In the case of the six specimens in which the donor was female and the recipient was male, a mean (+/-SD) of 34+/-16 percent of mesenchymal cells in the neointima, 38+/-12 percent of such cells in the adventitia, and 30+/-7 percent of such cells in the interstitium contained the Y-chromosomal marker, indicating that they originated from the recipient rather than the donor. In the case of the four renal-allograft specimens in which the donor was male and the recipient was female, the respective values were 24+/-15 percent, 33+/-9 percent, and 23+/-8 percent, indicating a persistent population of donor mesenchymal cells.The presence of mesenchymal cells of host origin in the vascular and interstitial compartments of renal allografts undergoing chronic rejection provides evidence that a circulating mesenchymal precursor cell has the potential to migrate to areas of inflammation.
Effect of Thyroid Hormone on Body Composition in Myxedema and Obesity
Authors: L. H. Kyle, M. F. Ball, P. D. Doolan
Journal: New England Journal of Medicine (1966)

AS judged by its widespread use, thyroid hormone is considered of value in the treatment of obesity by both physician and patient. In contrast to such use there are meager data concerning the effect of thyroid hormone on body composition, and no precise studies of its effects on adipose tissue in either obesity or myxedema have been reported.Materials and MethodsThis report concerns changes in body composition, particularly those of adipose tissue, in 2 patients with myxedema given physiologic amounts of desiccated thyroid hormone and 2 obese subjects treated with pharmacologic doses. Body fat and the fat-free body were . . .
Abstract 415: Human embryonic stem cell-derived endothelial cells as cellular delivery vehicles for targeting therapy of metastatic breast cancer
Authors: Weijun Su, Lina Wang, Manqian Zhou, Lingling Tong, Rong Xiang, Zongjin Li
Journal: Cancer Research (2012)

Abstract Recent reports revealed that endothelial progenitor cells (EPCs) isolated from bone marrow, cord blood or embryos have been experimentally utilized to deliver therapeutic agents for cancer treatment. Their potential in cancer therapy highlights the need for a consistent and renewable source of endothelial cells for clinical applications. Moreover, one of the most critical issues for ensuring success of endothelial therapy is the development of technologies for non-invasive monitoring of the distribution of transplanted cells and kinetic of tumor progression or regression. We generated human embryonic stem cell-derived endothelial cells (hESC-ECs) from H9 cell line. The hESC-ECs resemble adult endothelial cells HUVEC in endothelial markers and angiogenesis potential. In vitro study revealed the paracrine effects of hESC-ECs on tumor cells using conditioned medium (EC-CM). After treated with EC-CM, human breast cancer cells MDA-MB-231 proliferated slower and exhibited a higher apoptosis rate in low-serum condition, and the migration ability was impaired. Furthermore, we introduced a multitude of non-invasive, quantitative, functional imaging techniques with reporter gene methods to probe breast cancer model processes, and to track the hESC-ECs for targeting therapy in vivo by firefly luciferase (Fluc)/renilla luciferase (Rluc) imaging. We transduced hESC-ECs with triple fusion (TF) reporter gene containing the herpes simplex virus truncated thymidine kinase (HSV-ttk), renilla luciferase (Rluc) and RFP (RL-RFP-HSV-ttk). The NOD/SCID mice breast cancer metastasis model was established by tail vein injection of 1.5×106 MDA-MB-231 cells, which carry a reporter system encoding the gene of Fluc and GFP. Bioluminescence imaging (BLI) revealed that hESC-ECs can be sequenced in tumor sites for more than 72 hours. When given pro-drug ganciclovir (GCV), targeting HSV-ttk gene, the MDA-MB-231 tumor was inhibited by the indication of Fluc imaging. And immunofluorescence staining also confirmed that hESC-EC can exclusively home to tumor lesions instead of normal lung tissue. Taken together, our results revealed that hESC-ECs can specifically target tumor sites and kill nearby tumor cells by bystander effect when GCV is given. These finds suggest that hESC-ECs are attractive targeting vehicles for cancer therapy, and molecular imaging in small animals is an invaluable part of cancer diagnosis, prediction of tumor response to available therapies and monitoring response to therapy as well as developing drugs prior to clinical translation. 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 415. doi:1538-7445.AM2012-415
Abstract 1587: Loss of LZAP inactivates p53 in head and neck cancer and regulates sensitivity of cells to DNA damage in the p53-dependent manner.
Authors: Dan Liu, Natalia Issaeva, Wendell G. Yarbrough
Journal: Cancer Research (2013)

Abstract We previously reported that tumor suppressor LZAP is lost in a portion of head and neck squamous cell carcinomas and that LZAP inhibits NF-kB, while activating p53 in ARF-dependent and -independent fashions. The ability of LZAP to regulate p53 in the absence of ARF has been largely unexplored. Here, we show that LZAP depletion diminished expression of mutant and wild-type p53 protein. LZAP activity toward p53 was independent of ARF and the known p53 regulators, Wip1 and HDM2. Loss of LZAP decreased p53 translation and destabilized p53 protein due, at least partially, to increased nucleolin expression. Knockdown of LZAP abrogated p53 stabilization induced by ionizing radiation, and LZAP depletion protected wild-type p53 cells from radiation or chemotherapeutic agents, while rendering cells expressing mutant or no p53 more sensitive. In human HNSCC, LZAP levels correlated with p53 levels, and remarkably, tumors with low LZ were less likely to have p53 mutations. These data suggest that loss of LZAP represents a novel mechanism of p53 inactivation in human cancer. Given these findings, inhibition of LZAP activity toward p53 for patients with tumors harboring p53 mutations may represent a therapeutic strategy to simultaneously sensitize tumors while protecting normal tissues from radiation or chemotherapy. Citation Format: Dan Liu, Natalia Issaeva, Wendell G. Yarbrough. Loss of LZAP inactivates p53 in head and neck cancer and regulates sensitivity of cells to DNA damage in the p53-dependent manner. [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 1587. doi:10.1158/1538-7445.AM2013-1587
SP0081 Investigator-Initiated Clinical Trials - How to BE Successful
Authors: C.F. Allaart
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> What is “to be successful” regarding investigator-initiated clinical trials? To get started with the right hypothesis, forging collaborations with co-investigators, producing a trial protocol, finding financial resources to put it into action, steering the protocol through medical ethics committees, hiring and training the best trial personnel, including sufficient numbers of patients in the estimated available time, motivating patients to remain in the trial and doctors to follow the protocol (and making sure that everyone does), ensuring that data collection is complete and usable, analysing the results and finding methods to overcome unforeseen complications, writing a paper and publishing the results in a respected journal ... each activity completed may be considered “being successful”, and any mishap along the way may prevent the whole enterprise from becoming successful in the end. Some experiences and potential tips from the BeSt and IMPROVED studies will be shared. To make the trial successful beyond being published, abstract presentation at national and international conferences is an effective way to summarize the background and outcomes of the trial. Also, presenting the data as well as him- or herself, the investigator can now begin to feel a bit successful too. Continued success lies in being able to expand on the initial papers and presentations with new data, combined with repetition of the results, either by the original presenters or by others. It helps to have a trial sponsor who is interested in getting the investigators into contact with colleagues in the field. Implementation in daily practice of the trial results could mean that it, and the investigators if this was their intention, were successful. However, implementation often requires a whole new strategy and financial support structure. Collaboration and data sharing is the next step, potentially leading to more exposure for both the clinical trial and the investigators. This in turn may be of benefit when the next trial is considered, which may also become successful if the above milestones are once again achieved. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6336
P197 The effect of CPAP therapy on insulin sensitivity and CV risk factors in patients with OSA
Authors: M. Paracha, D. Ahearn, W. Flight, V. Gupta, M. Abdelhalim
Journal: Thorax (2010)

In a prospective study, we assessed the effect of CPAP therapy on the insulin sensitivity and CV risk factors such as blood pressure (BP), glycaemia status, and lipid profile in patients with obstructive sleep apnoea (OSA). Only patients with confirmed presence of cardinal features and diagnostic apnoea/hypopnoea index (AHI) for OSA were enrolled in the study. All patients were studied before the initiation of CPAP therapy. Following an initial screening visit before CPAP treatment, patients were then studied at 6 and 12 weeks following the initiation of CPAP. We studied 41 patients with confirmed OSA, aged 56 ± 13 (mean ± SD) years, 33 male and 8 female, who had their weight, BP and fasting blood samples checked in a screening visit and two study visits, at least 6 weeks apart. The fasting blood samples were used to assess fasting plasma glucose, HbA<sub>1c</sub>, fasting insulin, lipid profile, and CRP. Following CPAP treatment baseline systolic BP had significantly improved compared to BP following CPAP therapy (135 ± 17 vs 123 ± 12 mm Hg, p=0.001) and so did diastolic BP (83 ± 9 vs 77 ± 9 mm Hg, p=0.01). There were also improvement in fasting plasma glucose (5.6 ± 1.7 vs 4.9 ± 2.0 mmol/l, p&gt;0.05) and HbA<sub>1c</sub> (5.8 ± 1.3 vs 5.4 ± 1.7%, p&gt;0.05), but that was not statistically significant. There had been non-significant improvement of fasting insulin level (17.9 ± 25 vs 12.7 ± 15.5 pmol/l, p&gt;0.05), but no improvement on insulin sensitivity. Lipid profile had also improved, as total cholesterol was decreased (5.2 ± 2.0 vs 4.8 ± 1.9 mmol/l, p&gt;0.05), and so did triglycerides (2.7 ± 4.4 vs 2.0 ± 2.0 mmol/l, p&gt;0.05), but these changes were not statistically significant. CRP had also improved but that was not statistically significant (4.5 ± 10 vs 2.4 ± 2.0 mg/l, p&gt;0.05). In conclusion, this study demonstrates that CPAP therapy in patients with OSA can result in significant improvement in systolic and diastolic BP, as well as non-significant improvement in lipid profile and glycaemia status.
P1247 EVALUATION OF FERRITIN &gt;1000 CUTOFF POINT TO DIAGNOSE LIVER IRON OVERLOAD
Authors: E. Zapata, A. Castiella, I. Urreta, L. Zubiaurre, A. Iribarren, J.I. Alustiza, E. Salvador, A. Azkune, E. Zubillaga, L. Rincon, J.I. Emparanza, Burnia Taldea
Journal: Journal of Hepatology (2014)
Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia – a cDNA array study
Authors: T Niini, K Vettenranta, J Hollmén, ML Larramendy, Y Aalto, H Wikman, B Nagy, JK Seppänen, A Ferrer Salvador, H Mannila, UM Saarinen-Pihkala, S Knuutila
Journal: Leukemia (2002)