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temozolomide

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https://www.readbyqxmd.com/read/28538211/the-oxido-metabolic-driver-atf4-enhances-temozolamide-chemo-resistance-in-human-gliomas
#1
Daishi Chen, Manfred Rauh, Michael Buchfelder, Ilker Y Eyupoglu, Nicolai Savaskan
Malignant gliomas are devastating neoplasia with limited curative treatment options. Temozolomide (TMZ, Temcat®, Temodal® or Temodar®) is a first-line treatment for malignant gliomas but the development of drug resistance remains a major concern. Activating transcription factor 4 (ATF4) is a critical oxido-metabolic regulator in gliomas, and its role in the pathogenesis of TMZ-resistance remains elusive. We investigated the effect of TMZ on human glioma cells under conditions of enhanced ATF4 expression (ATF4OE) and ATF4 knock down (ATF4KD)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537897/mek-inhibitors-cobimetinib-and-trametinib-regressed-a-gemcitabine-resistant-pancreatic-cancer-patient-derived-orthotopic-xenograft-pdox
#2
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Tasuku Kiyuna, Thinzar M Lwin, Ho Kyoung Hwang, Jonathan C Delong, Bryan M Clary, Michael Bouvet, Michiaki Unno, Robert M Hoffman
A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534151/opening-the-ventricle-during-surgery-diminishes-survival-among-patients-with-newly-diagnosed-glioblastoma-treated-with-carmustine-wafers-a-multi-center-retrospective-study
#3
Yukihiko Sonoda, Ichiyo Shibahara, Ken-Ichiro Matsuda, Ryuta Saito, Tomoyuki Kawataki, Masaya Oda, Yuichi Sato, Hirokazu Sadahiro, Sadahiro Nomura, Toshio Sasajima, Takaaki Beppu, Masayuki Kanamori, Kaori Sakurada, Toshihiro Kumabe, Teiji Tominaga, Hiroyuki Kinouchi, Hiroaki Shimizu, Kuniaki Ogasawara, Michiyasu Suzuki
Carmustine wafers (CW) were approved in Japan for newly diagnosed and recurrent malignant gliomas during 2013. The ventricle is often opened during surgery to achieve maximum resection. While not generally recommended in such situations, CW might be safely achieved by occluding an opened ventricle using gelform or collagen sheets. However, whether CW implantation actually confers a survival benefit for patients who undergo surgery with an open ventricle to treat glioblastoma remains unclear. Clinical, imaging, and survival data were collected in this multicenter retrospective study of 122 consecutive patients with newly diagnosed glioblastoma to determine adverse events and efficacy...
May 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28533574/in-vitro-radiosensitizing-effects-of-temozolomide-on-u87mg-cell-lines-of-human-glioblastoma-multiforme
#4
Samira Borhani, Hossein Mozdarani, Somayyeh Babalui, Mohsen Bakhshandeh, Hassan Nosrati
BACKGROUND: Glioma is the most common primary brain tumor with poor prognosis. Temozolomide (TMZ) has been used with irradiation (IR) to treat gliomas. The aim of the present study was to evaluate the cytotoxic and radiosensitizing effect of TMZ when combined with high-dose and high-dose rate of gamma irradiation in vitro. METHODS: Two 'U87MG' cell lines and skin fibroblast were cultured and assigned to five groups for 24, 48, and 72 hours. The groups were namely, TMZ group (2000 μM/L), IR group (5 Gy), TMZ plus IR group, control group, and control solvent group...
May 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28533487/autophagy-related-gene-expression-is-an-independent-prognostic-indicator-of-glioma
#5
Huixue Zhang, Xiaoyan Lu, Ning Wang, Jianjian Wang, Yuze Cao, Tianfeng Wang, Xueling Zhou, Yang Jiao, Lei Yang, Xiaokun Wang, Lin Cong, Jianlong Li, Jie Li, He-Ping Ma, Yonghui Pan, Shangwei Ning, Lihua Wang
In this study, we identified 74 differentially expressed autophagy-related genes in glioma patients. Analysis using a Cox proportional hazard regression model showed that MAPK8IP1 and SH3GLB1, two autophagy-related genes, were associated with the prognostic signature for glioma. Glioma patients from the CGGA batches 1 and 2, GSE4412 and TCGA datasets could be divided into high- and low-risk groups with different survival times based on levels of MAPK8IP1 and SH3GLB1 expression. The autophagy-related signature was an independent predictor of survival outcomes in glioma patients...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28530704/upregulation-of-cyp17a1-by-sp1-mediated-dna-demethylation-confers-temozolomide-resistance-through-dhea-mediated-protection-in-glioma
#6
J-Y Chuang, W-L Lo, C-Y Ko, S-Y Chou, R-M Chen, K-Y Chang, J-J Hung, W-C Su, W-C Chang, T-I Hsu
Steroidogenesis-mediated production of neurosteroids is important for brain homeostasis. Cytochrome P450 17A1 (CYP17A1), which converts pregnenolone to dehydroepiandrosterone (DHEA) in endocrine organs and the brain, is required for prostate cancer progression and acquired chemotherapeutic resistance. However, whether CYP17A1-mediated DHEA synthesis is involved in brain tumor malignancy, especially in glioma, the most prevalent brain tumor, is unknown. To investigate the role of CYP17A1 in glioma, we determined that CYP17A1 expression is significantly increased in gliomas, which secrete more DHEA than normal astrocytes...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28529591/antitumor-activity-of-7-o-succinyl-macrolactin-a-tromethamine-salt-in-the-mouse-glioma-model
#7
Jun Jin, Suh Hee Choi, Jung Eun Lee, Jin-Deok Joo, Jung Ho Han, Su-Young Park, Chae-Yong Kim
Chemoradiotherapy with temozolomide is the current standard treatment option for patients with glioblastoma. However, the majority of patients with glioblastoma survive for <2 years. Therefore, it is necessary to develop more effective therapeutic strategies for the treatment of glioblastoma. 7-O-succinyl macrolactin A tromethamine salt (SMA salt), a macrolactin compound, is known to possess an antiangiogenic activity. The present study investigated the antitumor effects of SMA salt in the treatment of glioblastoma by evaluating in vitro and in vivo antitumor effects of SMA salt in an experimental glioblastoma model...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28527010/glioblastoma-multiforme-gbm-in-the-elderly-initial-treatment-strategy-and-overall-survival
#8
Scott M Glaser, Michael J Dohopolski, Goundappa K Balasubramani, John C Flickinger, Sushil Beriwal
The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status...
May 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28526577/changes-in-tumor-cell-heterogeneity-after-chemotherapy-treatment-in-a-xenograft-model-of-glioblastoma
#9
Alessandra M Welker, Brian D Jaros, Min An, Christine E Beattie
Glioblastoma (GBM) is a highly aggressive brain cancer with limited treatments and poor patient survival. GBM tumors are heterogeneous containing a complex mixture of dividing cells, differentiated cells, and cancer stem cells. It is unclear, however, how these different cell populations contribute to tumor growth or whether they exhibit differential responses to chemotherapy. Here we set out to address these questions using a zebrafish xenograft transplant model (Welker et al., 2016). We found that a small population of differentiated vimentin-positive tumor cells, but a majority of Sox2-positive putative cancer stem cells, were dividing during tumor growth...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28524900/tumor-treating-fields-nursing-implications-for-an-emerging-technology%C3%A2
#10
Alice Chang
Tumor-treating fields (TTFields) are a new technology used for cancer treatment consisting of battery-powered, insulated electromagnetic transducers that are placed on the scalp. This wearable, adhesive device is a certified physician-prescribed therapy for patients with glioblastoma multiforme, a type of primary brain cancer. TTFields are being used concomitantly with temozolomide (Temodar®) in patients with newly diagnosed glioblastoma and as a monotherapy in patients with recurrent glioblastoma after radiation therapy and chemotherapy...
June 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28524099/metabolomics-of-therapy-response-in-preclinical-glioblastoma-a-multi-slice-mrsi-based-volumetric-analysis-for-noninvasive-assessment-of-temozolomide-treatment
#11
Nuria Arias-Ramos, Laura Ferrer-Font, Silvia Lope-Piedrafita, Victor Mocioiu, Margarida Julià-Sapé, Martí Pumarola, Carles Arús, Ana Paula Candiota
Glioblastoma (GBM) is the most common aggressive primary brain tumor in adults, with a short survival time even after aggressive therapy. Non-invasive surrogate biomarkers of therapy response may be relevant for improving patient survival. Previous work produced such biomarkers in preclinical GBM using semi-supervised source extraction and single-slice Magnetic Resonance Spectroscopic Imaging (MRSI). Nevertheless, GBMs are heterogeneous and single-slice studies could prevent obtaining relevant information. The purpose of this work was to evaluate whether a multi-slice MRSI approach, acquiring consecutive grids across the tumor, is feasible for preclinical models and may produce additional insight into therapy response...
May 18, 2017: Metabolites
https://www.readbyqxmd.com/read/28522381/a-survival-analysis-with-identification-of-prognostic-factors-in-a-series-of-110-patients-with-newly-diagnosed-glioblastoma-pre-and-post-introduction-of-the-stupp-regimen-a-single-center-observational-study
#12
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 in GBM is based on maximal safe resection followed by Stupp protocol. Survival outcomes in cancer can vary in different population groups and outcomes can be conditioned by several factors. In Serbia Temozolomide has been introduced as adjuvant therapy only in 2011. The aims of this study are to confirm the efficacy and safety of Stupp protocol on both OS and PFS and evaluate the influence of the prognostic factors in one of the largest series of patients with GBM, treated over a 2-year period...
May 15, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28522280/primary-spinal-glioma-in-children-results-from-a-referral-pediatric-institution-in-shanghai
#13
J Khalil, Z Chuanying, Z Qing, Y Belkacémi, J Mawei
PURPOSE: Primary spinal cord glioma is a rare entity especially in children; accounting for less than 10% of all central nervous system tumors. Low grade is the most reported subtype. Treatment modalities have largely evolved; large improvements have been made in the surgical field but also in both of radiotherapy and chemotherapy. Nevertheless, the optimal treatment is yet to be defined. MATERIAL AND METHODS: A chart review of 11 pediatric patients with a diagnosis of low grade spinal cord glioma at Xhinhua hospital in Shanghai was conducted...
May 15, 2017: Cancer Radiothérapie: Journal de la Société Française de Radiothérapie Oncologique
https://www.readbyqxmd.com/read/28520445/telodendrimers-for-physical-encapsulation-and-covalent-linking-of-individual-or-combined-therapeutics
#14
Ashok Kakkar, Jason Choi, Alexandre Moquin, Enzo Bomal, Li Na, Dusica Maysinger
New therapeutics for glioblastoma multiforme and our ability to deliver them using efficient nanocarriers, constitute topical areas of research. We report a comparative study of temozolomide and quercetin in the treatment of glioblastoma (GBM) in 3D, and their incorporation into micelles obtained from synthetically articulated architectural copolymers, and a commercially available linear polymer poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA). A versatile synthetic methodology to telodendrimers which can be easily adapted to the needs of other therapeutic interventions, is presented...
May 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28516344/defining-optimal-cutoff-value-of-mgmt-promoter-methylation-by-roc-analysis-for-clinical-setting-in-glioblastoma-patients
#15
Guoqiang Yuan, Liang Niu, Yinian Zhang, Xiaoqing Wang, Kejun Ma, Hang Yin, Junqiang Dai, Wangning Zhou, Yawen Pan
Resistance to temozolomide (TMZ) chemotherapy poses a significant challenge in the treatment of glioblastoma (GBM). Hypermethylation in O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is thought to play a critical role in this resistance. Pyrosequencing (PSQ) has been shown to be accurate and robust for MGMT promoter methylation testing. The unresolved issue is the determination of a cut-off value for dichotomization of quantitative MGMT PSQ results into "MGMT methylated" and "MGMT unmethylated" patient subgroups as a basis for further treatment decisions...
May 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28516286/establishment-of-a-tumor-sphere-cell-line-from-a-metastatic-brain-neuroendocrine-tumor
#16
Ryoichi Iwata, Masato Maruyama, Tomoki Ito, Yosuke Nakano, Yonehiro Kanemura, Taro Koike, Souichi Oe, Kunikazu Yoshimura, Masahiro Nonaka, Shosaku Nomura, Tetsuo Sugimoto, Hisao Yamada, Akio Asai
Neuroendocrine tumors are rare, and little is known about the existence of cancer stem cells in this disease. Identification of the tumorigenic population will contribute to the development of effective therapies targeting neuroendocrine tumors. Surgically resected brain metastases from a primary neuroendocrine tumor of unknown origin were dissociated and cultured in serum-free neurosphere medium. Stem cell properties, including self-renewal, differentiation potential, and stem cell marker expression, were examined...
May 17, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28514722/the-interventional-effect-of-new-drugs-combined-with-the-stupp-protocol-on-glioblastoma-a-network-meta-analysis
#17
Mei Li, Xiangqi Song, Jun Zhu, Aijun Fu, Jianmin Li, Tong Chen
OBJECTIVE: New therapeutic agents in combination with the standard Stupp protocol (a protocol about the temozolomide combined with radiotherapy treatment with glioblastoma was research by Stupp R in 2005) were assessed to evaluate whether they were superior to the Stupp protocol alone, to determine the optimum treatment regimen for patients with newly diagnosed glioblastoma. PATIENTS AND METHODS: We implemented a search strategy to identify studies in the following databases: PubMed, Cochrane Library, EMBASE, CNKI, CBM, Wanfang, and VIP, and assessed the quality of extracted data from the trials included...
May 11, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28512247/targetable-t-type-calcium-channels-drive-glioblastoma
#18
Ying Zhang, Nichola Cruickshanks, Fang Yuan, Baomin Wang, Mary Pahuski, Julia Wulfkuhle, Isela Gallagher, Alexander F Koeppel, Sarah Hatef, Christopher Papanicolas, Jeongwu Lee, Eli E Bar, David Schiff, Stephen Turner, Emanuel F Petricoin, Lloyd S Gray, Roger Abounader
Glioblastoma stem-like cells (GSC) promote tumor initiation, progression and therapeutic resistance. Here we show how GSC can be targeted by the FDA approved drug mibefradil which inhibits the T-type calcium channel Cav3.2. This calcium channel was highly expressed in human GBM specimens and enriched in GSC. Analyses of the TCGA and REMBRANDT databases confirmed upregulation of Cav3.2 in a subset of tumors and showed that overexpression associated with worse prognosis. Mibefradil treatment or RNAi-mediated attenuation of Cav3...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28510787/a-phase-ii-trial-of-arsenic-trioxide-and-temozolomide-in-combination-with-radiation-therapy-for-patients-with-malignant-gliomas
#19
Priya Kumthekar, Sean Grimm, James Chandler, Minesh Mehta, Maryanne Marymont, Robert Levy, Kenji Muro, Irene Helenowski, Katie McCarthy, Leanne Fountas, Jeffrey Raizer
Standard treatment for GBM is radiation (RT) and temozolomide (TMZ). Arsenic trioxide (ATO) is synergistic with RT based on several mechanisms of action previously identified, however not tested herein. The MTD of ATO, RT and TMZ was determined in a Phase I trial. We now present the combined Phase I/II data. Patients with newly diagnosed malignant gliomas were eligible for treatment. Patients were treated with RT (60 GY), TMZ (75 mg/m(2) daily × 42 days) and ATO 0.20 mg/kg daily in week 1 then twice a week ×5 weeks, after completing RT they were treated with TMZ 5/28 for up to 12 months...
May 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28504721/tumour-exosomes-from-cells-harbouring-ptprz1-met-fusion-contribute-to-a-malignant-phenotype-and-temozolomide-chemoresistance-in-glioblastoma
#20
A-L Zeng, W Yan, Y-W Liu, Z Wang, Q Hu, E Nie, X Zhou, R Li, X-F Wang, T Jiang, Y-P You
Exosomes are carriers of pro-tumorigenic factors that participate in glioblastoma (GBM) progression, and many fusion genes are strong driver mutations in neoplasia and are involved in tumorigenesis. However, the ability of fusion genes to be transduced by exosomes is unknown. We characterized exosomes from GBM cells harbouring and not harbouring PTPRZ1-MET fusion (ZM fusion). We also determined the effect of the exosomes from ZM fusion cells (ZM exosomes) on pro-oncogenic secretions and showed that ZM exosomes are internalized by the recipient cells...
May 15, 2017: Oncogene
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