tbuckley/cabot-search huggingface dataset:
Dicer1-mediated miRNA processing shapes the mRNA profile and function of murine platelets
Authors: Jesse W. Rowley, Stéphane Chappaz, Aurélie Corduan, Mark M. W. Chong, Robert Campbell, Amanda Khoury, Bhanu Kanth Manne, Jeremy G. T. Wurtzel, James V. Michael, Lawrence E. Goldfinger, Michele M. Mumaw, Marvin T. Nieman, Benjamin T. Kile, Patrick Provost, Andrew S. Weyrich
Journal: Blood (2016)
Abstract MP17: Testosterone Change Relates to Lipid Change on Statins
Authors: Beatrice A Golomb, Sabrina Koperski
Journal: Circulation (2013)

Background: Cholesterol is a precursor for steroid hormones. We sought to assess whether as well as how lipid change in men on statins relates to testosterone change. Methods: 694 men over age 20 without DM or CVD were randomized equally to simvastatin 20mg, pravastatin 40mg or placebo for 6 months in a double blind RCT. For each arm, final (6mo) testosterone (ng/mL) was compared to baseline testosterone (paired t-tests). Testosterone-change-on-statin was compared to testosterone-change-on-placebo (unpaired t-tests). Regression examined how change in testosterone related to change in lipid elements (mg/dL), stratified by statin. Results: Baseline testosterone was comparable across arms (~4.4ng/mL). Testosterone on-treatment was significantly lower than at baseline (paired t-tests) on statins but not on placebo (Table). Testosterone drop was significantly greater in the statin than the placebo group (unpaired t-test, Table). Change in testosterone on simvastatin (but not pravastatin) related significantly to change in LDL (P&lt;0.001). In contrast, change in testosterone on pravastatin (but not simvastatin) related significantly to change in HDL (P=0.005). Discussion: Statins produced modest but significant average declines in testosterone in men. Change in testosterone on statins related significantly to change in lipids, differently for simvastatin and pravastatin.
Employment Advice for Job-Seeking Smokers: Quit
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2016)

Judith J. Prochaska, PhD, MPH; Anne K. Michalek, BA; Catherine Brown-Johnson, PhD; Eric J. Daza, DrPH; Michael Baiocchi, PhD; Nicole Anzai, BA; Amy Rogers, OTR/L; Mia Grigg, MS, MFT; Amy Chieng, BA
Abstract 5345: A novel small molecule, XZH-5 inhibits constitutive and interleukin-6-induced STAT3 phosphorylation in human rhabdomyosarcoma cells
Authors: Aiguo Liu, Yan Liu, Zhenghu Xu, Wenying Yu, Hong Wang, Chenglong Li, Jiayuh Lin
Journal: Cancer Research (2011)

Abstract Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite the fact the improved treatment for Rhabdomyosarcoma has resulted in a remarkable increase of overall survival, the children with metastatic Rhabdomyosarcoma still have only a 3-year failure-free survival rate of less than 30%. Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) signaling is frequently detected in most types of cancer including human RMS. STAT3 is considered to be an oncogene due to its ability to promote malignancy in mice. Given the oncogenic functions of STAT3 and the promise of inhibiting it, directly targeting STAT3 signaling represents a potential therapeutic approach to treating Rhabdomyosarcoma. Using structure-based drug design, we developed a novel small molecule, named XZH-5. In this study, we characterized the inhibitory effects of XZH-5 on STAT3 phosphorylation in four Rhabdomyosarcoma cell lines. XZH-5 competes with/inhibits the STAT3-SH2 dimerization through phosphorylated Tyr705 in all four Rhabdomyosarcoma cell lines. We also demonstrated a similar inhibition of STAT3 phosphorylation and induction of apoptosis by a previously known small molecular STAT3 inhibitor Stattic in Rhabdomyosarcoma cells. These results supporting Rhabdomyosarcoma cell lines are sensitive to STAT3 inhibition. In addition, XZH-5 inhibited STAT3 DNA binding activity and the expression of STAT3 downstream genes including Bcl-2, Bcl-xl, Cyclin D1 and Survivin. The inhibition of STAT3 in Rhabdomyosarcoma cells resulted in the induction of apoptosis, reduction of colony forming ability, and inhibition of cell migration. Furthermore, XZH-5 inhibited IL-6-induced STAT3 phosphorylation and STAT3 nuclear translocation. In contrast, it had no effect on IFN-γ-induced STAT1 phosphorylation, indicating the more selective effects on STAT3. These results demonstrated that Rhabdomyosarcoma cells are sensitive to STAT3 inhibition and STAT3 is a therapeutic target. Our results also suggested that XZH-5 may serve as a potential therapeutic agent for targeting STAT3 for Rhabdomyosarcoma treatments. 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 5345. doi:10.1158/1538-7445.AM2011-5345
The efficacy of the Cook-Swartz implantable doppler in the detection of free flap compromise: A systematic review and meta-analysis
Authors: R. Agha, B. Gundogan, A. Fowler, T. Bragg, D. Orgill
Journal: International Journal of Surgery (2015)

Background  Reducing free-flap failure rates is a key goal of any microsurgical unit. The Cook–Swartz implantable Doppler (CSD) can be used to monitor flap vascularity. We conducted a systematic review and meta-analysis to compare the efficacy of the CSD with clinical monitoring to prevent flap failure.      Methods  A comprehensive literature search was performed using MEDLINE, EMBASE, PsycINFO, EBSCO, the Cochrane Library, CINAHL, SCOPUS, SciELO, NHS evidence, and online clinical trial registers from 1966 until December 31, 2015. Studies comparing flap failure rates in the CSD and clinically monitored groups were considered. Screening and data extraction was performed by two independent researchers.      Results  Overall, eight articles met the inclusion criteria, involving 3,756 patients and 3,801 flaps. The average failure rate in the clinical group was 3.5% and in the Doppler group was 2.0%. A fixed effects meta-analysis was performed and found a reduced failure rate with the use of the CSD (odds ratio= 0.37 [0.21–0.64],  p  = 0.0005).      Conclusion  Deployment of the CSD can lower flap failure rates and has the potential to be a useful adjunct to clinical monitoring of free flaps. Further research is needed to confirm its benefits and refine its indications to optimize cost-effectiveness.
The Management of Thyrotoxicosis in Pregnancy
Authors: Gerard N. Burrow
Journal: New England Journal of Medicine (1985)

THYROID disease is much more common in women than in men, and hyperthyroidism occurring during pregnancy is not rare; its prevalence is about 0.2 per cent. Thyrotoxicosis results in a significant increase in the prevalence of low birth weight and a trend toward increased neonatal mortality.1 Graves' disease is the major cause of thyrotoxicosis in women of childbearing age, although other causes are possible, including trophoblastic tumors and hydatidiform mole.2 Patients with the thyrotoxicosis of Graves' disease tend to have remission during pregnancy and exacerbation during the postpartum period.3 An explanation for fluctuations in the intensity of Graves' disease during . . .
Abstract 2554: HSP90 inhibition induced cytotoxicity via downregulation of Rad51 expression and DNA repair capacity in non-small cell lung cancer cells
Authors: Yun-Wei Lin, Shao-Hsing Weng, Jen-Chung Ko, Huang-Jen Chen, Sheng-Chieh Tseng, Yu-Ching Huang, Min-Shao Tsai, Robin Y.-Y. Chiou
Journal: Cancer Research (2012)

Abstract Heat shock protein 90 (HSP90) is an exciting target in cancer therapy. Our previous studies indicated that repair protein Rad51 involved in protecting non-small lung cancer (NSCLC) cell lines against chemotherapeutic agents induced cytotoxicity. In this study, the role of Rad51 expression in HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) induced cytotoxicity in two NSCLC cell lines, A549 and H1975, were investigated. 17-AAG treatment decreased cellular Rad51 protein and mRNA levels and phosphorylated MKK1/2-ERK1/2 protein levels. 17-AAG treatment disrupted the HSP90 and Rad51 interaction and triggered Rad51 protein degradation through 26S proteasome pathway. Moreover, 17-AAG treatment decreased DNA repair capacity in NSCLC cells, which could restore by enforced expression of Flag-Rad51 vector. Specific inhibition of Rad51 expression by siRNA could further enhance the 17-AAG-induced cytotoxicity. Enhancement of ERK1/2 activation by constitutively active MKK1/2 (MKK1/2-CA) vector significantly restored the 17-AAG-reduced Rad51 protein levels as well as cell viability. Moreover, arachidin-1, antioxidant stilbenoids, has demonstrated beneficial effects on human health. It could further decrease Rad51 expression and augment the cytotoxic effect and growth inhibition by 17-AAG. Moreover, 17-AAG and arachidin-1-induced synergistic cytotoxic effect and DNA repair capacity decrease could be abrogated in lung cancer cells with MKK1/2-CA or Flag-Rad51 expression vector transfection. Our results suggested that HSP90 inhibition induced cytotoxicity via downregulation of Rad51 expression and DNA repair capacity in NSCLC cells. 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 2554. doi:1538-7445.AM2012-2554
Tc-99m Dextran: A New and Sensitive General Purpose Scintigraphic Agent for Diagnosing Intestinal Inflammation
Authors: DEEPAK LAHOTI, ASEEM BHATNAGAR, AJAY K. SINGH, SUMATI SUNDARAIYA, KISHAN SAWROOP, THAKURI SINGH
Journal: Clinical Nuclear Medicine (1999)

Purpose: This feasibility study was undertaken to compare the sensitivity of Tc-99m dextran with that of Tc-99m human immunoglobulin G to diagnose ulcerative colitis, and to explore its possible role in disease follow-up. Materials and Methods: Twenty-six patients with active disease and six patients in remission underwent serial Tc-99m dextran scanning for as long as 3 hours or more after injection. Eight of the patients with active disease also underwent Tc-99m human immunoglobulin G imaging. Results: Twenty-four of 26 (92%) patients with active ulcerative colitis had a positive result of the Tc-99m dextran study, mainly within 1 hour. In comparison, Tc-99m human immunoglobulin G accumulated abnormally in four of eight (50%) patients and had a relatively poor target localization with high persisting background even after 6 hours. Four of the six patients in remission still had a positive result of the dextran scan, but the abnormal uptake was less than that in the patients with active disease. The disease has recurred already in one of these patients. A patient with pancolitis who was receiving steroid enema therapy had intense uptake of Tc-99m dextran in the ascending colon, probability because it was outside the range of the enema. Conclusions: Tc-99m dextran is a sensitive and cost-effective agent to diagnose ulcerative colitis, and it may have a role in disease follow-up.
Abstract 1942: Vδ1+ γδ T cells are cytotoxic against glioblastoma multiforme
Authors: Andrea Knight, Hilal Arnouk, William Britt, G Yancey Gillespie, Mark W. Lowdell, Gretchen A. Cloud, James M. Markert, Catherine P. Langford, Yun Su, Lawrence S. Lamb
Journal: Cancer Research (2010)

Abstract Prior evidence of cytomegalovirus (CMV) infection has been documented in a large proportion of high-grade brain tumors such as glioblastoma multiforme (GBM), suggesting a potential role for CMV infection in GBM pathogenesis. Vδ2+ γδ T cells, which recognize tumor-derived mevolonate metabolites, have been shown to be highly cytotoxic to GBM cell lines and primary tumor explants. The specific role of Vδ1+ T cells, which respond to CMV infected cells in immunosuppressed patients and recognize NKG2D ligands MIC A/B and UL-16 binding proteins (ULBP), has not previously been investigated. Vδ1+ T cells were purified (93-95%) from CMV+ and CMV- donors by immunomagnetic selection and cultured on irradiated allogeneic MNC in RPMI + 10% human serum (HS) supplemented with phytohemagglutinin (PHA) and 200U IL-2. Vδ2+ T cells were expanded from mononuclear cells in RPMI/Clicks + 7.5% HS, 1mM Zoledronic acid, and 200U IL-2, all over 14-21 days. Cytotoxicity was assessed by flow cytometry against two primary GBM explants and CMV+/- GBM cell lines U251 and U373. The expression of MIC A/B and UL-16 binding proteins was assessed using flow cytometry. Vδ1+ T cells from CMV+ donors were significantly more cytotoxic to primary GBM explants than Vδ1+ cells from a CMV- donor (p=0.0021 for GBM 1042 and p= 0.0053 for GBM 1016) but did not significantly differ against CMV+ and CMV- U251 and U373 cells, although CMV infected cells significantly down-regulated ULBP-2 and −3 expression. Blocking of MIC A/B and ULBP-1, −2, and −3 decreased cytotoxicity of γδ T cells by 10-40% based on the expression of the respective antigen. ZOL/IL-2 expanded Vδ2+ T cells were cytotoxic to primary GBM and GBM lines regardless of donor CMV status. These findings suggest that Vδ1+ T cells, particularly Vδ1+ cells expanded from CMV+ donors, recognize GBM independently from Vδ2+ cells and and have a potential role in strategies involving CMV-directed cellular immunotherapy of high-grade brain tumors. This study was supported by NIH NCI Grant # P50 CA 097247, NINDS Grant # 5R21 NS 57341 and the National Brain Tumor Society Samuel Gerson Leadership Chair. 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 1942.
AB0137 Characterization of joint disease in mucopolysaccharidosis type I mice and the effects of enzyme replacement therapy
Authors: P.G. Oliveira, G. Baldo, F.Q. Mayer, B. Martinelli, L. Meurer, R. Giugliani, U. Matte, R.M. Xavier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Mucopolysaccharidosis type I (MPS I) is a lysosomal disorder caused by deficiency of alpha-L-iduronidase, which leads to storage of the glycosaminoglycans heparan sulphate and dermatan sulphate. Patients with MPS I present destructive changes in their joints in a process not well understood. The MPS I animal model is a useful tool to study the disease pathogenesis; however the changes in the MPS I joints were never investigated in more detail. This work aimed to describe the joint disease progression in the murine model of MPS I. <h3>Objectives</h3> Create a score to characterize the histological abnormalities in the MPS I mice knee joints. It allowed us to systematically study the age of onset of joint disease, as well as its progression. In addition, based on the results from the histological analysis, we tried to find possible mechanisms responsible for the disease. Finally, we verified if intravenous ERT was effective in preventing this complication of MPS I. <h3>Methods</h3> Normal (wild type) and untreated MPS I mice were killed at different time points (2, 4, 6, 8, and 12 months). In addition, some MPS I mice were treated with enzyme replacement therapy (ERT) and sacrificed at 6 months. The knee joints were collected and hematoxylin and eosin staining was used to evaluate the articular architecture. Safranin-O staining was used to analyze proteoglycans (PGs) content. In addition we analyzed the expression of matrix-degrading metalloproteinases (MMPs), MMP-2 and -9, by immunohistochemistry. <h3>Results</h3> MPS I mice did not present any significant joint changes at 2 and 4 months. From 6 months, we observed progressive joint alterations, including presence of synovial inflammatory infiltrate, destruction and thickening of the cartilage extracellular matrix and PGs depletion. Also, we observed an increase in the expression of MMP-2 and -9, which could explain the degenerative changes. We also investigated the effect of ERT when started at 2 months, which showed no benefits, suggesting that the poorly vascularized cartilage is difficult to reach, and an ancillary therapy might be needed for patients. <h3>Conclusions</h3> Our results suggest that the degenerative joint and bone disease in MPS I animals presents some similarities to osteoarthritis. More important, our results evidence the importance of understanding the pathologic processes of joint disease associated with MPS I in the search for new treatments. <h3>Disclosure of Interest</h3> None Declared
Abstract 5281: The effect of RF through JAG/Notch pathway in tumorigenesis, angiogenesis and migration
Authors: Mi Hwa Kim, Ho Jin You
Journal: Cancer Research (2010)

Abstract RF has known as multifunctional protein with the two of domains, redox and repair domains. Although RF is highly expressed in a lot of cancer cell lines, its function has not been exactly reported. The Jagged1/Notch proteins participate in a variety of cellular processes, such as cell fates specification, proliferation, differentiation, apoptosis, adhesion, epithelial-mesenchymal transition, migration, and angiogenesis. In the present study, Jagged1 and Notch-1 are overexpressed in RF-transfected fibroblast cell(GM00637/RF) and several human cancer cell lines. Through DNA microarray, we show that JAGGED1/Notch1 expression is up-regulated by RF. In promoter study, RF regulates the expression of JAGGED1 by binding Egr-1 on JAGGED1 promoter. Also, immunofluorescence confocal microscopy shows Notch active form(Notch intracellular domain) is in the nucleus. Furthermore, down-regulation of RF or JAG by RNA interference reduces the activities of focal adhesion molecules(vinculin, pFAK) and MMP-2 which have known to be involved in cell migration and invasion in cancer. In nude mouse model, RF or JAG siRNA significantly reduces tumor size and angiogenesis. We suggest that RF may act as a potential regulator in tumorigenesis, angiogenesis and migration through JAGGED1/Notch pathway. 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 5281.
Abstract 5566: CARP-1 functional mimetics (CFMs): a novel class of small molecule inhibitors (SMIs) of medulloblastoma cell growth.
Authors: Abdelkader E. Ashour, Shazia Jamal, Vino Cheryan, Ahmed M. Alafeefy, Edi Levi, Adi L. Tarca, Lisa A. Polin, Arun K. Rishi
Journal: Cancer Research (2013)

Abstract Medulloblastomas (MBs) are an aggressive class of intracranial pediatric tumors. Current multimodality treatments for MBs include surgery, ionizing radiation, and chemotherapy. Toxic side effects of therapies coupled with high incidence of recurrence and the metastatic spread warrants development of more effective, less toxic therapies for this disease. CARP-1/CCAR1 is a peri-nuclear phospho-protein that is a co-activator of the cell cycle regulatory anaphase promoting complex/cyclosome (APC/C) E3 ligase. CARP-1 functional mimetics (CFMs) are a novel class of small molecule compounds that interfere with CARP-1 binding with APC/C subunit APC-2, and suppress growth of a variety of cancer cells in part by promoting apoptosis. Here we investigated MB growth inhibitory potential of the CFM-1, 4, and 5, and found that CFMs inhibit growth of MB cells. CFM suppression of MB cell growth involved elevated CARP-1 expression, activation of pro-apoptotic stress-activated protein kinase (SAPK) p38, and apoptosis. Gene-array-based analysis of the CFM-4-treated Daoy MB cells indicated down-regulation of a number of key cell growth and metastasis-promoting genes including cell motility regulating small GTP binding protein p21Rac1, and extracellular matrix metallopeptidase (MMP)-10. Moreover, CFM-4 treatment stimulated expression of a number of growth inhibitory and apoptosis-inducing molecules such as neurotropin (NTF)3, while knock-down of NTF3 interfered with MB growth inhibitory effects of CFM-4. CFMs also attenuated biological properties of the MB cells by blocking their abilities to migrate, form colonies in suspension, and invade through the matrix-coated membranes. Together our data support anti-MB properties of CFM-4, and provide a proof-of-concept basis for further development of CFMs as potential anti-cancer agents for MBs. Citation Format: Abdelkader E. Ashour, Shazia Jamal, Vino Cheryan, Ahmed M. Alafeefy, Edi Levi, Adi L. Tarca, Lisa A. Polin, Arun K. Rishi. CARP-1 functional mimetics (CFMs): a novel class of small molecule inhibitors (SMIs) of medulloblastoma cell growth. [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 5566. doi:10.1158/1538-7445.AM2013-5566
P125Endoplasmic reticulum stress responses to disrupted endoplasmic reticulum ca2+ homeostasis
Authors: J Groenendyk, C Hetz, L Kurgan, M Michalak
Journal: Cardiovascular Research (2014)

The disruption of the energy or nutrient balance is the fundamental cause of endoplasmic reticulum (ER) stress, a process that mobilizes corrective strategies to reestablish ER and cellular homeostasis known as the unfolded protein response (UPR). In cardiac tissue, numerous conditions can disrupt this balance, resulting in ER stress and disease states. In this study, we focused on identifying ER stress coping responses (pathways) induced by disruption of the ER homeostasis by ER Ca2+ stores depletion. We employed a small interfering RNA (siRNA) library screen combined with deep sequencing analysis of micro RNA (miRNA) to identify factors that mediate UPR modulation. We utilized the XBP1 splicing luciferase reporter, a target of IRE1α endoribonuclease activity, to screen for modulators of the IRE1α branch of the UPR. We uncovered an ER oxidoreductase (PDIA6) and miR-322-dependent mechanism that regulates the IRE1α branch of UPR. PDIA6 is a recently discovered ER stress response protein and is involved in the protection of cardiomyocytes from ischemia/reperfusion-mediated cell death. We show that PDIA6 interacts with the luminal domain of IRE1α via cysteine residues. PDIA6 is required to maintain IRE1α activity as monitored by IRE1α phosphorylation and XBP1 mRNA splicing. Deep sequencing analysis identified miR-322 as one of the miRNAs that was down-regulated after ER Ca2+ store depletion-induced ER stress. The PDIA6 gene is a target of miR-322, and miR-322 abundance is sensitive to changes in ER and cytosolic Ca2+ concentrations. ER Ca2+ depletion and activation of store operated Ca2+ entry, critical during cardiac function, reduces the abundance of different miRNAs including miR-322, which increases PDIA6 mRNA stability and consequently stabilizes IRE1α activity during the ER stress response. We discovered that silencing of the gene encoding PDIA6 affected ER Ca2+ depletion-dependent activation of the IRE1α signaling branch. This work identifies PDIA6 as a unique component of the UPR and demonstrates interplay between ER and cytosolic Ca2+, PDIA6, IRE1α and miR-322 as a part of a novel pathway (coping mechanisms) activated by disrupted ER Ca2+ homeostasis and activation of SOCE as an adaptive response to cope with ER stress during cardiac function.
Palliation of a malignant gastrocolic fistula with the use of an atrial septal defect occlusion device
Authors: Miguel Malespin, Jonathan Gaspar, Brian Boulay
Journal: Endoscopy (2014)

A 51-year-old Asian man with metastatic gastric adenocarcinoma presented with a 3-month history of profound diarrhea and weight loss. Laboratory evaluation was significant for anemia and hypokalemia. Computed tomography showed large tumor burden from the gastric antrum with invasion into the ascending colon. Esophagogastroduodenoscopy (EGD) revealed a gastrocolic fistula 30 mm in diameter within the posterior wall of the gastric antrum, extending for 6 cm and opening into the ascending colon ([Fig. 1]) along with partial obstruction of the pyloric channel.