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Author Thomas, A.A.; Abrey, L.E.; Terziev, R.; Raizer, J.; Martinez, N.L.; Forsyth, P.; Paleologos, N.; Matasar, M.; Sauter, C.S.; Moskowitz, C.; Nimer, S.D.; DeAngelis, L.M.; Kaley, T.; Grimm, S.; Louis, D.N.; Cairncross, J.G.; Panageas, K.S.; Briggs, S.; Faivre, G.; Mohile, N.A.; Mehta, J.; Jonsson, P.; Chakravarty, D.; Gao, J.; Schultz, N.; Brennan, C.W.; Huse, J.T.; Omuro, A. url  doi
openurl 
  Title Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma Type Journal Article
  Year 2017 Publication Neuro-Oncology Abbreviated Journal Neuro Oncol  
  Volume 19 Issue 10 Pages 1380-1390  
  Keywords 1p/19q codeletion; anaplastic oligodendroglioma; autologous stem cell transplant; temozolomide  
  Abstract Background: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) as a potential strategy to defer radiotherapy. Methods: Patients with AO/AOA received 6 cycles of TMZ (200 mg/m2 x 5/28 day). Responding patients were eligible for HDC (thiotepa 250 mg/m2/day x 3 days, then busulfan 3.2 mg/kg/day x 3 days), followed by ASCT. Genomic characterization was performed using next-generation sequencing. Results: Forty-one patients were enrolled; 85% had 1p/19q codeleted tumors. After induction, 26 patients were eligible for HDC-ASCT and 21 agreed to proceed. There were no unexpected adverse events or toxic deaths. After median follow-up of 66 months, 2-year progression-free survival (PFS) for transplanted patients was 86%, 5-year PFS 60%, and no patient has died. Among all 1p/19q codeleted patients (N = 33), 5-year PFS was 50% and 5-year overall survival (OS) 93%, with median time to radiotherapy not reached. Next-generation sequencing disclosed typical oligodendroglioma-related mutations, including IDH1, TERT, CIC, and FUBP1 mutations in 1p/19q codeleted patients, and glioblastoma-like signatures in 1p/19q intact patients. Aside from IDH1, potentially oncogenic/actionable mutations were variable, depicting wide molecular heterogeneity within oligodendroglial tumors. Conclusions: TMZ followed by HDC-ASCT can be safely administered to patients with newly diagnosed 1p/19q codeleted AO. This strategy was associated with promising PFS and OS, suggesting that a chemotherapy-based approach may delay the need for radiotherapy and radiation-related toxicities. Raw data for further genomic and meta-analyses are publicly available at http://cbioportal.org/study?id=odgmsk2017, accessed 6 January 2017. Clinicaltrials.gov registry: NCT00588523.  
  Address Memorial Sloan Kettering Cancer Center, New York, New York,USA; Northwestern Memorial Hospital, Chicago, Illinois, USA; NorthShore University, Evanston, Illinois,USA; University of Calgary, Calgary, Alberta, Canada; Massachusetts General Hospital, Boston, Massachusetts, USA; MD Anderson Cancer Center, Houston, Texas, 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 1522-8517 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28472509 Approved no  
  Call Number ref @ user @ Serial 96586  
Permanent link to this record
 

 
Author Ma, H.X.; He, L.; Cai, S.W.; Xin, X.L.; Shi, H.D.; Zhou, L.; Shi, X.J. url  openurl
  Title [Analysis of the spectrum and resistance of pathogen causing sepsis in patients with severe acute pancreatitis] Type Journal Article
  Year 2017 Publication Zhonghua wai ke za zhi [Chinese Journal of Surgery] Abbreviated Journal Zhonghua Wai Ke Za Zhi  
  Volume 55 Issue 5 Pages 378-383  
  Keywords Adult; Aged; Anti-Bacterial Agents/*therapeutic use; Cross Infection; *Drug Resistance, Bacterial; Escherichia coli; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pancreatitis/*complications; Retrospective Studies; Sepsis/*drug therapy; Vancomycin/therapeutic use; Young Adult; Bacteria spectrum; Drug resistance; Pancreatitis, acute necrotizing; Sepsis  
  Abstract Objective: To investigate the characteristics of spectrum and drug resistance of pathogens causing sepsis in patients with severe acute pancreatitis(SAP). Methods: The clinical data of 63 SAP patients with sepsis admitted in Department of Hepatobiliary, People's Liberation Army General Hospital from January 2014 to December 2015 were retrospectively studied. There were 47 males and 16 females, aged from 22 to 73 years, with an average age of (52+/-11)years. Samples were collected mainly from: (1)pancreatic and peripancreatic necrosis and abdominal drainage; (2)bile; (3) blood or deep venous catheter; (4) sputum and tracheal catheter and thoracic drainage; (5) urine. Strain identification and drug-resistance test were preformed on positive specimens. Results: Of 244 pathogenic isolates, mainly derived from abdominal cavity(36.0%), blood stream (14.0%), central venous catheter(11.8%), necrotic tissue(9.1%) and sputum(8.1%); 154(63.1%) were gram-negative bacteria, 68 cases(27.9%) were gram-positive bacteria and 22 cases(9.0%) were fungi respectively. The top six common pathogens isolated were E. coli(16.0%), E.faecium and faecalis(15.2%), P.aeruginosa(10.7%), K.pneumonia(9.8%), Acinetobacter baumanni(8.2%), Stenotrophomonas maltophilia(5.3%)respectively. The detection rate of E. coli and K. pneumonia extended-spectrum beta-lactamases(ESBL) was 84.6%(33/39) and 70.8%(17/24), the resistance rate to imipeniem was 12.8% and 25.0%, to cefperazone-sulbactam was 28.2% and 29.2%. As to P. aeruginosa and Acinetobacter bacillus, the resistance rate to imipeniem was 50.0% and 75.0%, to cefperazone-sulbactam was 42.3% and 70.0%; Stenotrophomonas maltophilia was completely resistant to cefperazone-sulbactam, but sensitive to minocycline, SMZ-TMP with the resistance rate less than 40.0%. Gram-positive bacterium strains mainly included E. faecium(38.2%, 26/68), E.faecalis(16.2%, 11/68) and Staphylococcus(35.3%, 24/68) which maintained high sensitivity to vancomycin, teicoplanin and linezolid, there was only one isolate resistant to vancomycin. Candida were the sole pathogens of fungal infections, sensitive to common antifungal drugs overall. Conclusions: The gram-negative bacteria are the predominant pathogens mainly including ESBL-producing isolates(E.coli and K. pneumonia) and non-fermentation bacteria(P.aeruginosa and Acinetobacter bacillus) causing sepsis in SAP. The infection rate and drug-resistance rate of these two kinds of pathogens are relatively higher.  
  Address Department of Hepatobiliary, People's Liberation Army General Hospital, Beijing 100853, China  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Chinese Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0529-5815 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28464580 Approved no  
  Call Number ref @ user @ Serial 99094  
Permanent link to this record
 

 
Author Ma, H.X.; He, L.; Cai, S.W.; Xin, X.L.; Shi, H.D.; Zhou, L.; Shi, X.J. url  openurl
  Title [Analysis of the spectrum and resistance of pathogen causing sepsis in patients with severe acute pancreatitis] Type Journal Article
  Year 2017 Publication Zhonghua wai ke za zhi [Chinese Journal of Surgery] Abbreviated Journal Zhonghua Wai Ke Za Zhi  
  Volume 55 Issue 5 Pages 378-383  
  Keywords Adult; Aged; Anti-Bacterial Agents/*therapeutic use; Cross Infection; *Drug Resistance, Bacterial; Escherichia coli; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pancreatitis/*complications; Retrospective Studies; Sepsis/*drug therapy; Vancomycin/therapeutic use; Young Adult; Bacteria spectrum; Drug resistance; Pancreatitis, acute necrotizing; Sepsis  
  Abstract Objective: To investigate the characteristics of spectrum and drug resistance of pathogens causing sepsis in patients with severe acute pancreatitis(SAP). Methods: The clinical data of 63 SAP patients with sepsis admitted in Department of Hepatobiliary, People's Liberation Army General Hospital from January 2014 to December 2015 were retrospectively studied. There were 47 males and 16 females, aged from 22 to 73 years, with an average age of (52+/-11)years. Samples were collected mainly from: (1)pancreatic and peripancreatic necrosis and abdominal drainage; (2)bile; (3) blood or deep venous catheter; (4) sputum and tracheal catheter and thoracic drainage; (5) urine. Strain identification and drug-resistance test were preformed on positive specimens. Results: Of 244 pathogenic isolates, mainly derived from abdominal cavity(36.0%), blood stream (14.0%), central venous catheter(11.8%), necrotic tissue(9.1%) and sputum(8.1%); 154(63.1%) were gram-negative bacteria, 68 cases(27.9%) were gram-positive bacteria and 22 cases(9.0%) were fungi respectively. The top six common pathogens isolated were E. coli(16.0%), E.faecium and faecalis(15.2%), P.aeruginosa(10.7%), K.pneumonia(9.8%), Acinetobacter baumanni(8.2%), Stenotrophomonas maltophilia(5.3%)respectively. The detection rate of E. coli and K. pneumonia extended-spectrum beta-lactamases(ESBL) was 84.6%(33/39) and 70.8%(17/24), the resistance rate to imipeniem was 12.8% and 25.0%, to cefperazone-sulbactam was 28.2% and 29.2%. As to P. aeruginosa and Acinetobacter bacillus, the resistance rate to imipeniem was 50.0% and 75.0%, to cefperazone-sulbactam was 42.3% and 70.0%; Stenotrophomonas maltophilia was completely resistant to cefperazone-sulbactam, but sensitive to minocycline, SMZ-TMP with the resistance rate less than 40.0%. Gram-positive bacterium strains mainly included E. faecium(38.2%, 26/68), E.faecalis(16.2%, 11/68) and Staphylococcus(35.3%, 24/68) which maintained high sensitivity to vancomycin, teicoplanin and linezolid, there was only one isolate resistant to vancomycin. Candida were the sole pathogens of fungal infections, sensitive to common antifungal drugs overall. Conclusions: The gram-negative bacteria are the predominant pathogens mainly including ESBL-producing isolates(E.coli and K. pneumonia) and non-fermentation bacteria(P.aeruginosa and Acinetobacter bacillus) causing sepsis in SAP. The infection rate and drug-resistance rate of these two kinds of pathogens are relatively higher.  
  Address Department of Hepatobiliary, People's Liberation Army General Hospital, Beijing 100853, China  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Chinese Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0529-5815 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28464580 Approved no  
  Call Number ref @ user @ Serial 100124  
Permanent link to this record
 

 
Author Oliva, C.R.; Zhang, W.; Langford, C.; Suto, M.J.; Griguer, C.E. url  doi
openurl 
  Title Repositioning chlorpromazine for treating chemoresistant glioma through the inhibition of cytochrome c oxidase bearing the COX4-1 regulatory subunit Type Journal Article
  Year 2017 Publication Oncotarget Abbreviated Journal Oncotarget  
  Volume 8 Issue 23 Pages 37568-37583  
  Keywords chlorpromazine; cytochrome c oxidase; glioblastoma; inhibitor; stem cells  
  Abstract Patients with glioblastoma have one of the lowest overall survival rates among patients with cancer. Standard of care for patients with glioblastoma includes temozolomide and radiation therapy, yet 30% of patients do not respond to these treatments and nearly all glioblastoma tumors become resistant. Chlorpromazine is a United States Food and Drug Administration-approved phenothiazine widely used as a psychotropic in clinical practice. Recently, experimental evidence revealed the anti-proliferative activity of chlorpromazine against colon and brain tumors. Here, we used chemoresistant patient-derived glioma stem cells and chemoresistant human glioma cell lines to investigate the effects of chlorpromazine against chemoresistant glioma. Chlorpromazine selectively and significantly inhibited proliferation in chemoresistant glioma cells and glioma stem cells. Mechanistically, chlorpromazine inhibited cytochrome c oxidase (CcO, complex IV) activity from chemoresistant but not chemosensitive cells, without affecting other mitochondrial complexes. Notably, our previous studies revealed that the switch to chemoresistance in glioma cells is accompanied by a switch from the expression of CcO subunit 4 isoform 2 (COX4-2) to COX4-1. In this study, chlorpromazine induced cell cycle arrest selectively in glioma cells expressing COX4-1, and computer-simulated docking studies indicated that chlorpromazine binds more tightly to CcO expressing COX4-1 than to CcO expressing COX4-2. In orthotopic mouse brain tumor models, chlorpromazine treatment significantly increased the median overall survival of mice harboring chemoresistant tumors. These data indicate that chlorpromazine selectively inhibits the growth and proliferation of chemoresistant glioma cells expressing COX4-1. The feasibility of repositioning chlorpromazine for selectively treating chemoresistant glioma tumors should be further explored.  
  Address Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, 35294 Alabama, 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:28455961 Approved no  
  Call Number ref @ user @ Serial 96587  
Permanent link to this record
 

 
Author Kim, M.Y.; Park, S.-J.; Shim, J.W.; Song, Y.J.; Yang, K.; Park, S.-J.; Heo, K. url  doi
openurl 
  Title Accumulation of low-dose BIX01294 promotes metastatic potential of U251 glioblastoma cells Type Journal Article
  Year 2017 Publication Oncology Letters Abbreviated Journal Oncol Lett  
  Volume 13 Issue 3 Pages 1767-1774  
  Keywords Bix01294; epithelial-mesenchymal transition; glioblastoma stem cells; metastasis  
  Abstract BIX01294 (Bix) is known to be a euchromatic histone-lysine N-methyltransferase 2 inhibitor and treatment with Bix suppresses cancer cell survival and proliferation. In the present study, it was observed that sequential treatment with low-dose Bix notably increases glioblastoma cell migration and metastasis. It was demonstrated that U251 cells sequentially treated with low-dose Bix exhibited induced characteristic changes in critical epithelial-mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, beta-catenin and zinc finger protein SNAI2. Notably, sequential treatment with Bix also increased the expression of cancer stem cell-associated markers, including sex determining region Y-box 2, octamer-binding transcription factor 4 and cluster of differentiation 133. Neurosphere formation was significantly enhanced in cells sequentially treated with Bix, compared with control cells (control: P=0.011; single treatment of Bix, P=0.045). The results of the present study suggest that accumulation of low-dose Bix enhanced the migration and metastatic potential of glioblastoma cells by regulating EMT-associated gene expression, which may be the cause of the altered properties of glioblastoma stem cells.  
  Address Research Center, Dongnam Institute of Radiological and Medical Science (DIRAMS), Busan 619-953, Republic of 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 1792-1074 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28454322 Approved no  
  Call Number ref @ user @ Serial 96588  
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