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Yukinori Akiyama, Yuusuke Kimura, Rei Enatsu, Takeshi Mikami, Masahiko Wanibuchi, Nobuhiro Mikuni
OBJECTIVE: To retrospectively determine the safety and efficacy of combined chemotherapy with carmustine (BCNU) wafer, bevacizumab, and temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma (GBM). METHODS: A total of 54 consecutive newly diagnosed GBMs were resected at our institution between 2010 and 2016. Twenty-nine patients underwent BCNU wafer implantation into the resection cavity followed by standard radiochemotherapy with with temozolomide (TMZ, Stupp regimen) plus additional bevacizumab treatment between 2013 and 2016...
February 21, 2018: World Neurosurgery
Ichiyo Shibahara, Mitsuto Hanihara, Takashi Watanabe, Mitsuru Dan, Sumito Sato, Hiroki Kuroda, Akinori Inamura, Madoka Inukai, Atsuko Hara, Yoshie Yasui, Toshihiro Kumabe
Biomaterials to treat cancers hold therapeutic potential; however, their translation to bedside treatment requires further study. The carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea; BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. However, how this wafer affects the surrounding tumor microenvironment is not well understood to date. We retrospectively reviewed all patients with glioblastoma treated with and without BCNU wafers who underwent repeat resection at tumor recurrence...
February 21, 2018: Journal of Neuro-oncology
Pierre Bourdillon, Tanguy Boissenot, Lauriane Goldwirt, Julien Nicolas, Caroline Apra, Alexandre Carpentier
In situ carmustine wafers containing 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are commonly used for the treatment of recurrent glioblastoma to overcome the brain-blood barrier. In theory, this chemotherapy diffuses into the adjacent parenchyma and the excipient degrades in maximum 8 weeks but no clinical data confirms this evolution, because patients are rarely operated again. A 75-year-old patient was operated twice for recurrent glioblastoma, and a carmustine wafer was implanted during the second surgery...
February 17, 2018: Journal of Materials Science. Materials in Medicine
Arif N Ali, Peixin Zhang, W K Alfred Yung, Yuhchyau Chen, Benjamin Movsas, Raul C Urtasun, Christopher U Jones, Kwang N Choi, Jeff M Michalski, A Jennifer Fischbach, Arnold M Markoe, Christopher J Schultz, Marta Penas-Prado, Madhur K Garg, Alan C Hartford, Harold E Kim, Minhee Won, Walter J Curran
From 1990 to 1994, patients with newly diagnosed malignant gliomas were enrolled and randomized between hyperfractionated radiation (HFX) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily. All patients received 80 mg/m2 of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1-3 q8 weeks for 1 year. Patients were stratified by age, KPS, and histology. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and toxicity...
March 2018: Journal of Neuro-oncology
Eileen P Smith, Hongli Li, Jonathan W Friedberg, Louis S Constine, Lisa M Rimsza, James R Cook, Ginna G Laport, Leslie L Popplewell, Leona A Holmberg, Sonali M Smith, Michael LeBlanc, Stephen J Forman, Richard I Fisher, Patrick J Stiff
Based on promising pilot data, a Phase II tandem autologous hematopoietic stem cell transplant (AHSCT) trial for relapsed/refractory Hodgkin Lymphoma (HL) was performed in the US intergroup setting to determine if long-term progression-free survival (PFS) could be improved. Patients were enrolled after salvage therapy and stem cell collection. Sensitivity to salvage was defined by 1999 Standardized Response Criteria and did not include FDG-PET. Cycle 1 consisted of melphalan 150 mg/m2 with half of the stem cells...
December 28, 2017: Biology of Blood and Marrow Transplantation
G-B Wang, J-H Liu, J Hu, K Xue
OBJECTIVE: Gliomas are accompanied with high mortality owning to their invasive peculiarity and vulnerability to drug resistance. miR-21 is a vital oncogenic miRNA that regulates drug resistance of tumor cells. This study aims to elucidate the function of miR-21 in human glioma cells resistant to carmustine (BCNU) and to demonstrate the underlying molecular mechanism. MATERIALS AND METHODS: BCNU-sensitive cells (SWOZ2 cells) were transfected with miR-21 agomir and negative control, and BCNU-resistance cells (SWOZ2-BCNU cells) were transfected with miR-21 antagomir and negative control...
November 2017: European Review for Medical and Pharmacological Sciences
Z-S Yuan, Y Cao, Z-Y Li
OBJECTIVE: Gliomas are accompanied with high mortality owning to their invasive peculiarity and vulnerability to drug resistance. miR-21 is a vital oncogenic miRNA that regulates drug resistance of tumor cells. This study aims to elucidate the function of miR-21 in human glioma cells resistant to carmustine (BCNU) and to demonstrate the underlying molecular mechanism. MATERIALS AND METHODS: BCNU-sensitive cells (SWOZ2 cells) were transfected with miR-21 agomir and negative control, and BCNU-resistance cells (SWOZ2-BCNU cells) were transfected with miR-21 antagomir and negative control...
November 2017: European Review for Medical and Pharmacological Sciences
Kevin O Lillehei, Steven N Kalkanis, Linda M Liau, Dellann Elliott Mydland, Jeffrey Olson, Nina A Paleologos, Timothy Ryken, Tania Johnson, Evan Scullin
Implantation of biodegradable wafers impregnated with carmustine (BCNU) is one of the few chemotherapeutic modalities that have been evaluated in Phase III trials and approved by the US FDA for treatment of newly diagnosed high-grade glioma and recurrent glioblastoma. Enrolling up to 500 patients for 3-year follow-up at over 30 sites, the prospective Vigilant ObservatIon of GlIadeL WAfer ImplaNT (VIGILANT) registry (NCT02684838) will evaluate BCNU wafers for treatment of CNS malignancies in contemporary practice and in the new era of molecular tumor analysis...
December 5, 2017: CNS Oncology
Khalil Saleh, Alina Danu, Serge Koscielny, Clémence Legoupil, Sylvain Pilorge, Cristina Castilla-Llorente, David Ghez, Julien Lazarovici, Jean-Marie Michot, Nadine Khalife-Saleh, Valerie Lapierre, Kamelia Alenxandrova, Julia Arfi-Rouche, Jean-Henri Bourhis, Vincent Ribrag
The combination of carmustine, etoposide, aracytin, and melphalan(BEAM) conditioning regimen in autologous stem-cell transplantation (ASCT) is widely used in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma. It is also an option in patients with very-high risk aggressive NHL in first complete remission (CR). Recently, a phase Ib-II feasibility study using bendamustine replacing carmustine (BCNU) was reported. We report herein a safety and efficacy analysis of bendamustine-EAM (BeEAM) with a control BEAM counterpart paired cohort (1/2)...
November 22, 2017: Leukemia & Lymphoma
Cristina Mihaela Ghiciuc, Aurel Lulu Strat, Lacramioara Ochiuz, Catalina Elena Lupusoru, Maria Ignat, Aurelia Vasile, Alexandru Grigorovici, Iulian Stoleriu, Carmen Solcan
Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms-hydrogen form (HCLI) and sodium form (NaCLI)-were prepared, allowing a loading degree of about 5-6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms...
November 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Zhong-Guang Li, Qian Nie, Cong-Li Yang, Yue Wang, Zhi-Hao Zhou
Methylglyoxal (MG) now is found to be an emerging signaling molecule. It can relieve the toxicity of cadmium (Cd), however its alleviating mechanism still remains unknown. In this study, compared with the Cd-stressed seedlings without MG treatment, MG treatment could stimulate the activities of glutathione reductase (GR) and gamma-glutamylcysteine synthetase (γ-ECS) in Cd-stressed wheat seedlings, which in turn induced an increase of reduced glutathione (GSH). Adversely, the activated enzymes related to GSH biosynthesis and increased GSH were weakened by N-acetyl-L-cysteine (NAC, MG scavenger), 2,4-dihydroxy-benzylamine (DHBA) and 1,3-bischloroethyl-nitrosourea (BCNU, both are specific inhibitors of GR), buthionine sulfoximine (BSO, a specific inhibitors of GSH biosynthesis), and N-ethylmaleimide (NEM, GSH scavenger), respectively...
November 16, 2017: Ecotoxicology and Environmental Safety
V Wais, L Kündgen, S R Bohl, S von Harsdorf, R F Schlenk, K Döhner, V Teleanu, L Bullinger, T M Nguyen, K Drognitz, J-C Moulin, M Binnenhei, M Bentz, H Döhner, D Bunjes, F Kuchenbauer, M Ringhoffer
No abstract text is available yet for this article.
November 13, 2017: Bone Marrow Transplantation
D Sivaraj, W Bacon, G D Long, D A Rizzieri, M E Horwitz, K M Sullivan, Y Kang, Z Li, N J Chao, C Gasparetto
Single-agent high-dose melphalan (HDM, 200 mg/m(2)) has been the most commonly used conditioning regimen prior to autologous stem cell transplant, since its introduction in 1992. We used a more aggressive alkylator-based conditioning regimen in an attempt to overcome early relapse and combat drug resistance. We present a retrospective comparison and long-term follow-up of newly diagnosed patients with multiple myeloma (MM) treated with induction followed by either high-dose carmustine (BCNU) and HDM, or HDM alone, both followed by autologous stem cell transplant (ASCT)...
October 30, 2017: Bone Marrow Transplantation
Olena Rudyk, Philip Eaton
BACKGROUND: Protein kinase G (PKG) Iα is the end-effector kinase that mediates nitric oxide (NO)-dependent and oxidant-dependent vasorelaxation to maintain blood pressure during health. A hallmark of cardiovascular disease is attenuated NO production, which in part is caused by NO Synthase (NOS) uncoupling, which in turn increases oxidative stress because of superoxide generation. NOS uncoupling promotes PKG Iα oxidation to the interprotein disulfide state, likely mediated by superoxide-derived hydrogen peroxide, and because the NO-cyclic guanosine monophosphate (cGMP) pathway otherwise negatively regulates oxidation of the kinase to its active disulfide dimeric state...
September 2017: Free Radical Biology & Medicine
Li Zhang, Huicui Yang, Wenbin Zhang, Zhongqin Liang, Qiang Huang, Guoqiang Xu, Xuechu Zhen, Long Tai Zheng
Chemoresistance remains a major challenge for the treatment of glioma. In this study, we investigated the role of Clock 1 (Clk1), which encodes an enzyme that is necessary for ubiquinone biosynthesis in glioma chemoresistance in vitro. The results showed that Clk1 was highly expressed in GL261 mouse glioma cells which were most sensitive to 1,3Bis (2-chloroethyl) 1 nitrosourea (BCNU) while was low expressed in BCNU resistant cells such as glioma cancer stem cells, T98G, U87MG and U251 glioma cells. Knockdown of Clk1 in GL261 glioma cells significantly reduced BCNU- or cisplatin-induced cell apoptosis, whereas the proliferative activity and the expression of multidrug resistance-related genes including MDR1, O6-methylguanine-DNA methyltransferase, and GSTP1 were not changed...
August 2017: Journal of Neurochemistry
Rosanda Illic, Teresa Somma, Dragan Savic, Federico Frio, Mihailo Milicevic, Domenico Solari, Marina Nikitovic, Slobodan Lavrnic, Savo Raicevic, Snezana Milosevic, Luigi Maria Cavallo, Paolo Cappabianca, Danica Grujicic
BACKGROUND: Current treatment protocol for glioblastoma multiforme (GBM) is based on maximal safe resection followed by the Stupp protocol. In Serbia, temozolomide was introduced as adjuvant therapy in 2011. The aims of this study were to confirm the safety and efficacy on overall and progression-free survival of the Stupp protocol and evaluate the influence of prognostic factors in one of the largest series of patients with GBM treated over a 2-year period. METHODS: Between January 2010 and December 2012, 110 patients with newly diagnosed GBM underwent surgical removal at the Neurooncology Department of the Clinic Center of Serbia...
August 2017: World Neurosurgery
H J Choi, B R Lim, Y J Park, W H Joo
Solvent hypertolerant Pseudomonas sp. BCNU 106 still has some underlying growth limitation in solvents. Therefore, efficient mass cultivation methods are needed to pursue its applications in biotechnology. Pseudomonas sp. BCNU 106 was cultured in a medium supplemented with 0·05 mol l-1 glycerol and cell survival was monitored during its cultivation in the presence of 1% (v/v) toluene. Exogenously supplemented glycerol provided more protection against damage caused by toluene stress and conferred higher solvent tolerance of Pseudomonas sp...
August 2017: Letters in Applied Microbiology
Steffi Urbschat, Christoph Sippl, Jana Engelhardt, Kai Kammers, Joachim Oertel, Ralf Ketter
BACKGROUND: To assess the influence of molecular markers with potential prognostic value to groups of patients with newly diagnosed glioblastoma patients were examined: group A with 36 patients (surgical resection plus standard combined chemoradiotherapy) and group B with 36 patients (surgical resection, standard combined chemoradiotherapy plus carmustine wafer implantation). Our aim was to determine chromosomal alterations, methylation status of MGMT, p15, and p16 (CDKN2A) in order to analyse the influence on patient survival time as well as radio- and chemotherapy responses...
2017: Molecular Cytogenetics
Bonaventura Casanova, Isidro Jarque, Francisco Gascón, Juan Carlos Hernández-Boluda, Francisco Pérez-Miralles, Javier de la Rubia, Carmen Alcalá, Jaime Sanz, Javier Mallada, Angeles Cervelló, Arantxa Navarré, María Carcelén-Gadea, Isabel Boscá, Sara Gil-Perotin, Carlos Solano, Miguel Angel Sanz, Francisco Coret
The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin...
July 2017: Neurological Sciences
Johann Klein, Tareq A Juratli, Yordan Radev, Dirk Daubner, Silke Soucek, Gabriele Schackert, Dietmar Krex
OBJECTIVE: To assess the safety and effectiveness of bis-chloroethylnitrosourea (BCNU) wafers in elderly patients with recurrent glioblastoma (GBM). METHODS: Patients with recurrent GBM operated on between 2007 and 2014 were divided into 3 groups: >65 years with BCNU wafer implantation, >65 years without BCNU wafer implantation, and ≤65 years with BCNU wafer implantation. We compared survival and complications. RESULTS: A total of 79 patients were identified: 24 in the older BCNU group (median age 68...
2017: Oncology
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