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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/28536931/guanosine-promotes-cytotoxicity-via-adenosine-receptors-and-induces-apoptosis-in-temozolomide-treated-a172-glioma-cells
#2
Karen A Oliveira, Tharine A Dal-Cim, Flávia G Lopes, Cláudia B Nedel, Carla Inês Tasca
Gliomas are a malignant tumor group whose patients have survival rates around 12 months. Among the treatments are the alkylating agents as temozolomide (TMZ), although gliomas have shown multiple resistance mechanisms for chemotherapy. Guanosine (GUO) is an endogenous nucleoside involved in extracellular signaling that presents neuroprotective effects and also shows the effect of inducing differentiation in cancer cells. The chemotherapy allied to adjuvant drugs are being suggested as a novel approach in gliomas treatment...
May 23, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28533574/in-vitro-radiosensitizing-effects-of-temozolomide-on-u87mg-cell-lines-of-human-glioblastoma-multiforme
#3
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/28532702/trimetazidine-in-the-prevention-of-contrast-induced-nephropathy-in-chronic-kidney-disease
#4
Tarek A Ibrahim, Ramzy H El-Mawardy, Ahmed S El-Serafy, Ehab M El-Fekky
BACKGROUND: Contrast induced nephropathy (CIN) may be defined as Acute Renal Failure (ARF) that occurs within 24-72h of exposure to intra-venous or intra-arterial iodinated contrast media that cannot be attributed to other causes. CIN occurs in up to 5% of hospitalized patients with normal renal function prior to injection of contrast media. It occurs more frequently in patients with renal impairment particularly if associated with diabetic nephropathy. Among all procedures utilizing contrast agents for either diagnostic or therapeutic purposes, coronary angiography and percutaneous coronary interventions are associated with the highest rates of CIN...
February 10, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28530704/upregulation-of-cyp17a1-by-sp1-mediated-dna-demethylation-confers-temozolomide-resistance-through-dhea-mediated-protection-in-glioma
#5
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/28527010/glioblastoma-multiforme-gbm-in-the-elderly-initial-treatment-strategy-and-overall-survival
#6
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
#7
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/28516344/defining-optimal-cutoff-value-of-mgmt-promoter-methylation-by-roc-analysis-for-clinical-setting-in-glioblastoma-patients
#8
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/28512247/targetable-t-type-calcium-channels-drive-glioblastoma
#9
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
#10
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/28501897/mir-181b-modulates-chemosensitivity-of-glioblastoma-multiforme-cells-to-temozolomide-by-targeting-the-epidermal-growth-factor-receptor
#11
Yunxiang Chen, Rui Li, Minhong Pan, Zhumei Shi, Wei Yan, Ning Liu, Yongping You, Junxia Zhang, Xiefeng Wang
Temozolomide (TMZ) is a promising chemotherapeutic agent to treat Glioblastoma multiforme (GBM). However, resistance to TMZ develops quickly with a high frequency. The mechanisms underlying GBM cells' resistance to TMZ are not fully understood. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs. Recently, miRNAs have been discovered to play important roles in drug resistance. A previous study showed that miR-181b in involved in glioma tumorigenesis...
May 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28500786/dovitinib-enhances-temozolomide-efficacy-in-glioblastoma-cells
#12
Thatchawan Thanasupawat, Suchitra Natarajan, Amy Rommel, Aleksandra Glogowska, Hugo Bergen, Jerry Krcek, Marshall Pitz, Jason Beiko, Sherry Krawitz, Inder M Verma, Saeid Ghavami, Thomas Klonisch, Sabine Hombach-Klonisch
The multikinase inhibitor and FDA-approved drug Dovitinib (Dov) crosses the blood-brain-barrier and was recently used as single drug application in clinical trials for GB patients with recurrent disease. The Dov-mediated molecular mechanisms in GB cells are unknown. We used GB patient cells and cell lines to show that Dov downregulated the stem cell protein Lin28 and its target High Mobility Group protein A2 (HMGA2). The Dov-induced reduction in pSTAT3(Tyr705) phosphorylation demonstrated that Dov negatively affects the STAT3-LIN28-Let-7-HMGA2 regulatory axis in GB cells...
May 13, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28494176/comparative-analysis-of-the-effects-of-a-sphingosine-kinase-inhibitor-to-temozolomide-and-radiation-treatment-on-glioblastoma-cell-lines
#13
Liliana R Oancea-Castillo, Carmen Klein, Amir Abdollahi, Klaus-Josef Weber, Anne Régnier-Vigouroux, Ivana Dokic
Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28480325/the-sequence-of-delta24-rgd-and-tmz-administration-in-malignant-glioma-affects-the-role-of-cd8-t-cell-anti-tumor-activity
#14
Anne Kleijn, Wouter van den Bossche, Erik S Haefner, Zineb Belcaid, Chantal Burghoorn-Maas, Jenneke J Kloezeman, Suzan D Pas, Sieger Leenstra, Reno Debets, Jeroen de Vrij, Clemens M F Dirven, Martine L M Lamfers
The conditionally replicating oncolytic adenovirus Delta24-RGD (Ad) is currently under investigation in clinical trials for glioblastoma, including in combination with temozolomide (TMZ), the standard chemotherapy for this tumor. Previously, we showed that the efficacy of Delta24-RGD in a murine model is primarily dependent on the virus-induced anti-tumor immune response. As observed with most chemotherapies, TMZ has pronounced immune-modulating effects. Here, we studied the combined effects of these treatments in a murine glioma model...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28477008/combination-therapy-with-micellarized-cyclopamine-and-temozolomide-attenuate-glioblastoma-growth-through-gli1-down-regulation
#15
Yu-Jie Liu, Ying-Cong Ma, Wen-Jie Zhang, Zhen-Zhen Yang, De-Sheng Liang, Zhi-Fu Wu, Xian-Rong Qi
Glioblastoma multiforme (GBM) is the most common and deadly brain cancer, characterized by its aggressive proliferation to adjacent tissue and high recurrence rate. We studied the efficacy and related mechanisms of the combination of cyclopamine (Cyp, a Sonic-hedgehog pathway (Shh) inhibitor) and temozolomide (TMZ, the clinically most used chemotherapeutic agent) in anti-GBM treatment. The micellarized Cyp (MCyp) showed better performance than Cyp solution in inhibiting GBM cells proliferation (3.77-fold against U87 MG cells and 3...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28475720/developing-an-algorithm-for-optimizing-care-of-elderly-patients-with-glioblastoma
#16
Patrick M Flanigan, Arman Jahangiri, Ruby Kuang, Albert Truong, Sarah Choi, Alvin Chou, Annette M Molinaro, Michael W McDermott, Mitchel S Berger, Manish K Aghi
BACKGROUND: Elderly patients with glioblastoma have an especially poor prognosis; optimizing their medical and surgical care remains of paramount importance. OBJECTIVE: To investigate patient and treatment characteristics of elderly vs nonelderly patients and develop an algorithm to predict elderly patients' survival. METHODS: Retrospective analysis of 554 patients (mean age = 60.8; 42.0% female) undergoing first glioblastoma resection or biopsy at our institution (2005-2011)...
May 5, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28474573/corilagin-induces-high-levels-of-apoptosis-in-the-temozolomide-resistant-t98g-glioma-cell-line
#17
Roberta Milani, Eleonora Brognara, Enrica Fabbri, Alessia Finotti, Monica Borgatti, Ilaria Lampronti, Giovanni Marzaro, Adriana Chilin, Kenneth Ka-Ho Lee, Stanton Hon-Lung Kok, Chung-Hin Chui, Roberto Gambari
Glioblastoma multiforme (GBM), a malignant tumor of the central nervous system, has a high mortality rate; no curativetreatment is presently available and the most commonly used chemiotherapeutic drug, the alkylating agent temozolomide (TMZ), is only able to increase life expectancy and is often associated with drugresistance. Therefore, an urgent need does exist for novel drugs aimed at treating gliomas. In the present study we obtained three major results using corliagin: (a) demonstrate that it inhibits the growth of U251 glioma cells through activation of the apoptotic pathway; (b) demonstrate that it is also active on temozolomideresistant T98G glioma cells; (c) demonstrate that when used in combination with temozolomide on T98G glioma cells a higher level of pro-apototic and antiproliferative effects are observed...
May 4, 2017: Oncology Research
https://www.readbyqxmd.com/read/28472509/multicenter-phase-ii-study-of-temozolomide-and-myeloablative-chemotherapy-with-autologous-stem-cell-transplant-for-newly-diagnosed-anaplastic-oligodendroglioma
#18
Alissa A Thomas, Lauren E Abrey, Robert Terziev, Jeffrey Raizer, Nina L Martinez, Peter Forsyth, Nina Paleologos, Matthew Matasar, Craig S Sauter, Craig Moskowitz, Stephen D Nimer, Lisa M DeAngelis, Thomas Kaley, Sean Grimm, David N Louis, J Gregory Cairncross, Katherine S Panageas, Samuel Briggs, Geraldine Faivre, Nimish A Mohile, Jayesh Mehta, Philip Jonsson, Debyani Chakravarty, Jianjiong Gao, Nikolaus Schultz, Cameron W Brennan, Jason T Huse, Antonio Omuro
Background: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytomas (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 (200mg/m2 X5/28-day). Responding patients were eligible for HDC (thiotepa 250mg/m2/day X3 days then busulfan 3...
May 2, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28470120/cell-intrinsic-bmal1-dependent-circadian-regulation-of-temozolomide-sensitivity-in-glioblastoma
#19
Emily A Slat, Jasmin Sponagel, Luciano Marpegan, Tatiana Simon, Najla Kfoury, Albert Kim, Andrea Binz, Erik D Herzog, Joshua B Rubin
The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1...
April 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28467795/survival-benefit-of-glioblastoma-patients-after-fda-approval-of-temozolomide-concomitant-with-radiation-and-bevacizumab-a-population-based-study
#20
Ping Zhu, Xianglin L Du, Guangrong Lu, Jay-Jiguang Zhu
Few population-based analyses have investigated survival change in glioblastoma multiforme (GBM) patients treated with concomitant radiotherapy-temozolomide (RT-TMZ) and adjuvant temozolomide (TMZ) and then bevacizumab (BEV) after Food and Drug Administration (FDA) approval, respectively. We aimed to explore the effects on survival with RT-TMZ, adjuvant TMZ and BEV in general GBM population based on the Surveillance, Epidemiology, and End Results (SEER) and Texas Cancer Registry (TCR) databases. A total of 28933 GBM patients from SEER (N = 24578) and TCR (N = 4355) between January 2000 and December 2013 were included...
April 12, 2017: Oncotarget
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