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Author Kane, S.P.; Hanes, S.D.
Title (down) Unexplained increases in serum vancomycin concentration in a morbidly obese patient Type Journal Article
Year 2017 Publication Intensive & Critical Care Nursing Abbreviated Journal Intensive Crit Care Nurs
Volume 39 Issue Pages 55-58
Keywords Anti-Bacterial Agents/administration & dosage/therapeutic use; Cross Reactions/physiology; Drug-Related Side Effects and Adverse Reactions/*physiopathology; Female; Humans; Middle Aged; Obesity, Morbid/*drug therapy/physiopathology; Pneumonia, Ventilator-Associated/drug therapy/prevention & control; Vancomycin/*administration & dosage/therapeutic use; Central venous catheters; Critical care; Drug monitoring; Infectious disease; Medication safety; Vancomycin
Abstract INTRODUCTION: To report a case of increases in vancomycin concentrations without additional vancomycin doses being given. CASE STUDY: A 64 year-old morbidly obese female received three total doses of vancomycin for surgical prophylaxis and for ventilator-associated pneumonia. Subsequent vancomycin concentrations from the patient's central venous catheter (CVC) demonstrated increasing drug levels from 27.1 to 45.9mcg/mL despite no additional vancomycin being given and proper line flushing prior to sample collection. There is no clear explanation for the increase in the patient's vancomycin concentration. Drug leaching from the CVC, enterohepatic recycling, drug redistribution from adipose or other tissues, and assay cross-reactivity with other medications are all potential explanations for the increased vancomycin concentrations. CONCLUSION: This case report describes an unexplained increase in vancomycin concentrations and reinforces both the fallibility of laboratory testing and that unusual circumstances do occur. Several potential causes are hypothesised with CVC drug leaching being the most likely. Nurses and other healthcare providers with similar scenarios should consider a peripheral blood sample to rule out the potential for CVC drug leaching as a possible explanation.
Address Department of Pharmacy Practice, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States. Electronic address: scott.hanes@rosalindfranklin.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0964-3397 ISBN Medium
Area Expedition Conference
Notes PMID:27899248 Approved no
Call Number ref @ user @ Serial 98971
Permanent link to this record
 

 
Author Kane, S.P.; Hanes, S.D.
Title (down) Unexplained increases in serum vancomycin concentration in a morbidly obese patient Type Journal Article
Year 2017 Publication Intensive & Critical Care Nursing Abbreviated Journal Intensive Crit Care Nurs
Volume 39 Issue Pages 55-58
Keywords Anti-Bacterial Agents/administration & dosage/therapeutic use; Cross Reactions/physiology; Drug-Related Side Effects and Adverse Reactions/*physiopathology; Female; Humans; Middle Aged; Obesity, Morbid/*drug therapy/physiopathology; Pneumonia, Ventilator-Associated/drug therapy/prevention & control; Vancomycin/*administration & dosage/therapeutic use; Central venous catheters; Critical care; Drug monitoring; Infectious disease; Medication safety; Vancomycin
Abstract INTRODUCTION: To report a case of increases in vancomycin concentrations without additional vancomycin doses being given. CASE STUDY: A 64 year-old morbidly obese female received three total doses of vancomycin for surgical prophylaxis and for ventilator-associated pneumonia. Subsequent vancomycin concentrations from the patient's central venous catheter (CVC) demonstrated increasing drug levels from 27.1 to 45.9mcg/mL despite no additional vancomycin being given and proper line flushing prior to sample collection. There is no clear explanation for the increase in the patient's vancomycin concentration. Drug leaching from the CVC, enterohepatic recycling, drug redistribution from adipose or other tissues, and assay cross-reactivity with other medications are all potential explanations for the increased vancomycin concentrations. CONCLUSION: This case report describes an unexplained increase in vancomycin concentrations and reinforces both the fallibility of laboratory testing and that unusual circumstances do occur. Several potential causes are hypothesised with CVC drug leaching being the most likely. Nurses and other healthcare providers with similar scenarios should consider a peripheral blood sample to rule out the potential for CVC drug leaching as a possible explanation.
Address Department of Pharmacy Practice, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States. Electronic address: scott.hanes@rosalindfranklin.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0964-3397 ISBN Medium
Area Expedition Conference
Notes PMID:27899248 Approved no
Call Number ref @ user @ Serial 100001
Permanent link to this record
 

 
Author Yin, J.; Oh, Y.T.; Kim, J.-Y.; Kim, S.S.; Choi, E.; Kim, T.H.; Hong, J.H.; Chang, N.; Cho, H.J.; Sa, J.K.; Kim, J.C.; Kwon, H.J.; Park, S.; Lin, W.; Nakano, I.; Gwak, H.-S.; Yoo, H.; Lee, S.-H.; Lee, J.; Kim, J.H.; Kim, S.-Y.; Nam, D.-H.; Park, M.-J.; Park, J.B.
Title (down) Transglutaminase 2 Inhibition Reverses Mesenchymal Transdifferentiation of Glioma Stem Cells by Regulating C/EBPbeta Signaling Type Journal Article
Year 2017 Publication Cancer Research Abbreviated Journal Cancer Res
Volume 77 Issue 18 Pages 4973-4984
Keywords
Abstract Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPbeta, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-kappaB activation and further degraded DNA damage-inducible transcript 3 (GADD153) to induce C/EBPbeta expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. Cancer Res; 77(18); 4973-84. (c)2017 AACR.
Address Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0008-5472 ISBN Medium
Area Expedition Conference
Notes PMID:28754668 Approved no
Call Number ref @ user @ Serial 96575
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Author Jahan, N.; Lee, J.M.; Shah, K.; Wakimoto, H.
Title (down) Therapeutic targeting of chemoresistant and recurrent glioblastoma stem cells with a proapoptotic variant of oncolytic herpes simplex virus Type Journal Article
Year 2017 Publication International Journal of Cancer Abbreviated Journal Int J Cancer
Volume 141 Issue 8 Pages 1671-1681
Keywords Animals; Apoptosis/physiology; Brain Neoplasms/drug therapy/*therapy/virology; Cell Line, Tumor; Cohort Studies; Dacarbazine/analogs & derivatives/pharmacology; Drug Resistance, Neoplasm; Glioblastoma/drug therapy/*therapy/virology; HEK293 Cells; Humans; Mice; Neoplasm Recurrence, Local/drug therapy/therapy/virology; Neoplastic Stem Cells/drug effects/pathology/*virology; Oncolytic Virotherapy/*methods; Simplexvirus/genetics/*physiology; TNF-Related Apoptosis-Inducing Ligand/biosynthesis/genetics; TNF-related apoptosis inducing ligand (TRAIL); glioblastoma; oncolytic herpes simplex virus; recurrence; temozolomide
Abstract Temozolomide (TMZ) chemotherapy, in combination with maximal safe resection and radiotherapy, is the current standard of care for patients with glioblastoma (GBM). Despite this multimodal approach, GBM inevitably relapses primarily due to resistance to chemo-radiotherapy, and effective treatment is not available for recurrent disease. In this study we identified TMZ resistant patient-derived primary and previously treated recurrent GBM stem cells (GSC), and investigated the therapeutic activity of a pro-apoptotic variant of oHSV (oHSV-TRAIL) in vitro and in vivo. We show that oHSV-TRAIL modulates cell survival and MAP Kinase proliferation signaling pathways as well as DNA damage response pathways in both primary and recurrent TMZ-resistant GSC. Utilizing real time in vivo imaging and correlative immunohistochemistry, we show that oHSV-TRAIL potently inhibits tumor growth and extends survival of mice bearing TMZ-insensitive recurrent intracerebral GSC tumors via robust and selective induction of apoptosis-mediated death in tumor cells, resulting in cures in 40% of the treated mice. In comparison, the anti-tumor effects in a primary chemoresistant GSC GBM model exhibiting a highly invasive phenotype were significant but less prominent. This work thus demonstrates the ability of oHSV-TRAIL to overcome the therapeutic resistance and recurrence of GBM, and provides a basis for its testing in a GBM clinical trial.
Address Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0020-7136 ISBN Medium
Area Expedition Conference
Notes PMID:28567859 Approved no
Call Number ref @ user @ Serial 96584
Permanent link to this record
 

 
Author Sullivan, K.E.; Rojas, K.; Cerione, R.A.; Nakano, I.; Wilson, K.F.
Title (down) The stem cell/cancer stem cell marker ALDH1A3 regulates the expression of the survival factor tissue transglutaminase, in mesenchymal glioma stem cells Type Journal Article
Year 2017 Publication Oncotarget Abbreviated Journal Oncotarget
Volume 8 Issue 14 Pages 22325-22343
Keywords Aldehyde Oxidoreductases/genetics/*metabolism; Biomarkers, Tumor/metabolism; Brain Neoplasms/genetics/*metabolism; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dacarbazine/analogs & derivatives/pharmacology; GTP-Binding Proteins/genetics/*metabolism; Gene Expression Regulation, Neoplastic; Glioma/genetics/*metabolism; Humans; Mesenchymal Stromal Cells/*physiology; Neoplastic Stem Cells/*physiology; RNA, Small Interfering/genetics; Stem Cells/*physiology; Transglutaminases/genetics/*metabolism; Tretinoin/metabolism; Up-Regulation; aldehyde dehydrogenase; cancer stem cells; glioblastoma; retinoic acid; tissue transglutaminase
Abstract Tissue transglutaminase (tTG), a dual-function enzyme with GTP-binding and acyltransferase activities, has been implicated in the survival and chemotherapy resistance of aggressive cancer cells and cancer stem cells, including glioma stem cells (GSCs). Using a model system comprising two distinct subtypes of GSCs referred to as proneural (PN) and mesenchymal (MES), we find that the phenotypically aggressive and radiation therapy-resistant MES GSCs exclusively express tTG relative to PN GSCs. As such, the self-renewal, proliferation, and survival of these cells was sensitive to treatment with tTG inhibitors, with a benefit being observed when combined with the standard of care for high grade gliomas (i.e. radiation or temozolomide). Efforts to understand the molecular drivers of tTG expression in MES GSCs revealed an unexpected link between tTG and a common marker for stem cells and cancer stem cells, Aldehyde dehydrogenase 1A3 (ALDH1A3). ALDH1A3, as well as other members of the ALDH1 subfamily, can function in cells as a retinaldehyde dehydrogenase to generate retinoic acid (RA) from retinal. We show that the enzymatic activity of ALDH1A3 and its product, RA, are necessary for the observed expression of tTG in MES GSCs. Additionally, the ectopic expression of ALDH1A3 in PN GSCs is sufficient to induce the expression of tTG in these cells, further demonstrating a causal link between ALDH1A3 and tTG. Together, these findings ascribe a novel function for ALDH1A3 in an aggressive GSC phenotype via the up-regulation of tTG, and suggest the potential for a similar role by ALDH1 family members across cancer types.
Address Department of Molecular Medicine, Cornell University, Ithaca, NY, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1949-2553 ISBN Medium
Area Expedition Conference
Notes PMID:28423611 Approved no
Call Number ref @ user @ Serial 96595
Permanent link to this record