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temozolomide

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https://www.readbyqxmd.com/read/28822335/specificity-protein-1-modulated-superoxide-dismutase-2-enhances-temozolomide-resistance-in-glioblastoma-which-is-independent-of-o-6-methylguanine-dna-methyltransferase
#1
Kwang-Yu Chang, Tsung-I Hsu, Che-Chia Hsu, Shan-Yin Tsai, Jr-Jiun Liu, Shao-Wen Chou, Ming-Sheng Liu, Jing-Ping Liou, Chiung-Yuan Ko, Kai-Yun Chen, Jan-Jong Hung, Wen-Chang Chang, Cheng-Keng Chuang, Tzu-Jen Kao, Jian-Ying Chuang
Acquisition of temozolomide (TMZ) resistance is a major factor leading to the failure of glioblastoma (GBM) treatment. The exact mechanism by which GBM evades TMZ toxicity is not always related to the expression of the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT), and so remains unclear. In this study, TMZ-resistant variants derived from MGMT-negative GBM clinical samples and cell lines were studied, revealing there to be increased specificity protein 1 (Sp1) expression associated with reduced reactive oxygen species (ROS) accumulation following TMZ treatment...
August 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28821714/gadd45a-plays-a-protective-role-against-temozolomide-treatment-in-glioblastoma-cells
#2
Hsiao-Han Wang, Tsuey-Yu Chang, Wei-Chen Lin, Kuo-Chen Wei, Jyh-Wei Shin
Glioblastoma multiforme (GBM) is one of the most aggressive cancers. Despite recent advances in multimodal therapies, high-grade glioma remains fatal. Temozolomide (TMZ) is an alkylating agent used worldwide for the clinical treatment of GBM; however, the innate and acquired resistance of GBM limits its application. Here, we found that TMZ inhibited the proliferation and induced the G2/M arrest of GBM cells. Therefore, we performed microarrays to identify the cell cycle- and apoptosis-related genes affected by TMZ...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817826/the-safety-and-efficacy-of-the-s1-temozolomide-regimen-in-patients-with-metastatic-neuroendocrine-tumors
#3
Jiuda Zhao, Hong Zhao, Yihebali Chi
<br><br>Purpose Both capecitabine alone and capecitabine in combination with temozolomide have activities against neuroendocrine tumors (NETs). However, the role of S-1 in NETs is still unknown. We performed a study to evaluate the safety and efficacy of the S-1 plus temozolomide (STEM) regimen in patients with locally advanced or metastatic NETs. Methods A retrospective review was conducted in 20 patients with locally advanced or metastatic NETs treated with the STEM regimen. Of the patients, 15 (75...
August 17, 2017: Neuroendocrinology
https://www.readbyqxmd.com/read/28812310/gliosarcoma-arising-from-oligodendroglioma-idh-mutant-and-1p-19q-codeleted
#4
Takayuki Yasuda, Masayuki Nitta, Takashi Komori, Tatsuya Kobayashi, Kenta Masui, Takashi Maruyama, Tatsuo Sawada, Yoshihiro Muragaki, Takakazu Kawamata
Herein, we present a rare case of gliosarcoma arising from oligodendroglioma, isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted. A 36-year-old man presented with a non-enhanced calcified abnormal lesion on the right frontal lobe. The patient underwent subtotal surgical resection, PAV chemotherapy (procarbazine, nimustine (ACNU) and vincristine), and fractionated radiotherapy with 50 Gy. The pathological diagnosis was oligodendroglioma, IDH mutant and 1p/19q codeleted, World Health Organization 2016 grade II...
August 15, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28808777/phase-ii-study-of-bi-weekly-temozolomide-plus-bevacizumab-for-adult-patients-with-recurrent-glioblastoma
#5
Michael A Badruddoja, Marjorie Pazzi, Abhay Sanan, Kurt Schroeder, Kevin Kuzma, Thomas Norton, Thomas Scully, Daruka Mahadevan, Michael Malek Ahmadi
PURPOSE: Bevacizumab is an active anti-angiogenic agent in the treatment of recurrent glioblastoma. Temozolomide can prolong survival in patients with newly diagnosed glioblastoma. At recurrence, alternate dosing of temozolomide has shown to further deplete methyl-guanine-methyltransferase (MGMT) conferring added activity for patients who have progressed on the standard dosing regimen. In this study, bevacizumab plus biweekly temozolomide was evaluated for efficacy in adult patients with recurrent glioblastoma...
August 14, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28807361/challenges-to-treating-older-glioblastoma-patients-the-influence-of-clinical-and-tumour-characteristics-on-survival-outcomes
#6
C F Lorimer, C Hanna, F Saran, A Chalmers, J Brock
AIMS: There is now evidence to support giving single-agent chemotherapy, radiotherapy or hypofractionated concurrent chemoradiotherapy to older patients with glioblastoma (GBM). However, the clinical basis on which treatment decisions are made is under-researched and not standardised. This retrospective, multicentre study assessed whether pre-morbid characteristics or tumour imaging features could predict for overall survival in a cohort of older patients with GBM. MATERIALS AND METHODS: Patients aged > 70 years, diagnosed with GBM at three neuro-oncology centres from 2010 to 2015 were retrospectively analysed...
August 11, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28806010/blastomycosis-and-histoplasmosis-in-a-patient-with-glioblastoma-receiving-temozolomide
#7
Aiham H Jbeli, John Yu
Malignant glioblastoma multiform (GBM) is the most common primary malignancy of the brain in the U.S. Temozolomide (TMZ) is the cornerstone of management along with surgical resection and radiotherapy. Because of the reduction in the CD4+ lymphocyte count as a side effect of TMZ use, this patient population is under risk for opportunistic infections like Pneumocystis jiroveci. A male patient with newly diagnosed glioblastoma multiform presented with non-productive cough and chest pain. Before presentation, the patient received the standard therapy including surgical resection, radiation and TMZ...
October 2016: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28805815/aav-mediated-direct-in-vivo-crispr-screen-identifies-functional-suppressors-in-glioblastoma
#8
Ryan D Chow, Christopher D Guzman, Guangchuan Wang, Florian Schmidt, Mark W Youngblood, Lupeng Ye, Youssef Errami, Matthew B Dong, Michael A Martinez, Sensen Zhang, Paul Renauer, Kaya Bilguvar, Murat Gunel, Phillip A Sharp, Feng Zhang, Randall J Platt, Sidi Chen
A causative understanding of genetic factors that regulate glioblastoma pathogenesis is of central importance. Here we developed an adeno-associated virus-mediated, autochthonous genetic CRISPR screen in glioblastoma. Stereotaxic delivery of a virus library targeting genes commonly mutated in human cancers into the brains of conditional-Cas9 mice resulted in tumors that recapitulate human glioblastoma. Capture sequencing revealed diverse mutational profiles across tumors. The mutation frequencies in mice correlated with those in two independent patient cohorts...
August 14, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28801914/blockade-of-transforming-growth-factor-%C3%AE-signaling-enhances-oncolytic-herpes-simplex-virus-efficacy-in-patient-derived-recurrent-glioblastoma-models
#9
Shinichi Esaki, Fares Nigim, Esther Moon, Samantha Luk, Juri Kiyokawa, William Curry, Daniel P Cahill, Andrew S Chi, A John Iafrate, Robert L Martuza, Samuel D Rabkin, Hiroaki Wakimoto
Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis...
August 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28801587/temozolomide-arrests-glioma-growth-and-normalizes-intratumoral-extracellular-ph
#10
Jyotsna U Rao, Daniel Coman, John J Walsh, Meser M Ali, Yuegao Huang, Fahmeed Hyder
Gliomas maintain an acidic extracellular pH (pHe), which promotes tumor growth and builds resistance to therapy. Given evidence that acidic pHe beyond the tumor core indicates infiltration, we hypothesized that imaging the intratumoral pHe in relation to the peritumoral pHe can provide a novel readout of therapeutic influence on the tumor microenvironment. We used Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), which utilizes chemical shifts of non-exchangeable protons from macrocyclic chelates (e...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801186/interim-results-from-the-catnon-trial-eortc-study-26053-22054-of-treatment-with-concurrent-and-adjuvant-temozolomide-for-1p-19q-non-co-deleted-anaplastic-glioma-a-phase-3-randomised-open-label-intergroup-study
#11
Martin J van den Bent, Brigitta Baumert, Sara C Erridge, Michael A Vogelbaum, Anna K Nowak, Marc Sanson, Alba Ariela Brandes, Paul M Clement, Jean Francais Baurain, Warren P Mason, Helen Wheeler, Olivier L Chinot, Sanjeev Gill, Matthew Griffin, David G Brachman, Walter Taal, Roberta Rudà, Michael Weller, Catherine McBain, Jaap Reijneveld, Roelien H Enting, Damien C Weber, Thierry Lesimple, Susan Clenton, Anja Gijtenbeek, Sarah Pascoe, Ulrich Herrlinger, Peter Hau, Frederic Dhermain, Irene van Heuvel, Roger Stupp, Ken Aldape, Robert B Jenkins, Hendrikus Jan Dubbink, Winand N M Dinjens, Pieter Wesseling, Sarah Nuyens, Vassilis Golfinopoulos, Thierry Gorlia, Wolfgang Wick, Johan M Kros
BACKGROUND: The role of temozolomide chemotherapy in newly diagnosed 1p/19q non-co-deleted anaplastic gliomas, which are associated with lower sensitivity to chemotherapy and worse prognosis than 1p/19q co-deleted tumours, is unclear. We assessed the use of radiotherapy with concurrent and adjuvant temozolomide in adults with non-co-deleted anaplastic gliomas. METHODS: This was a phase 3, randomised, open-label study with a 2 × 2 factorial design. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with WHO performance status scores of 0-2...
August 8, 2017: Lancet
https://www.readbyqxmd.com/read/28800752/a-type-i-combi-targeting-approach-for-the-design-of-molecules-with-enhanced-potency-against-brca1-2-mutant-and-o6-methylguanine-dna-methyltransferase-mgmt-expressing-tumour-cells
#12
Zhor Senhaji Mouhri, Elliot Goodfellow, Bertrand Jean-Claude
BACKGROUND: Mutations of the DNA repair proteins BRCA1/2 are synthetically lethal with the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), which when inhibited, leads to cell death due to the absence of compensatory DNA repair mechanism. The potency of PARP inhibitors has now been clinically proven. However, disappointingly, acquired resistance mediated by the reactivation of wild type BRCA1/2 has been reported. In order to improve their efficacy, trials are ongoing to explore their combinations with temozolomide (TMZ)...
August 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28798282/feasibility-and-safety-of-extended-adjuvant-temozolomide-beyond-six-cycles-for-patients-with-glioblastoma
#13
S Yp Hsieh, D Tm Chan, M Km Kam, H Hf Loong, W K Tsang, D Mc Poon, S Cp Ng, W S Poon
INTRODUCTION: Temozolomide is the first chemotherapeutic agent proven effective for patients with newly diagnosed glioblastoma. The drug is well tolerated for its low toxicity. The current standard practice is concomitant chemoradiotherapy for 6 weeks followed by 6 cycles of adjuvant temozolomide. Some Caucasian studies have suggested that patients might benefit from extended adjuvant cycles of temozolomide (>6 cycles) to lengthen both progression-free survival and overall survival...
August 11, 2017: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
https://www.readbyqxmd.com/read/28797029/successful-use-of-equine-anti-thymocyte-globulin-atgam-for-fulminant-myocarditis-secondary-to-nivolumab-therapy
#14
Rebecca Y Tay, Elizabeth Blackley, Catriona McLean, Maggie Moore, Peter Bergin, Sanjeev Gill, Andrew Haydon
BACKGROUND: Immune-mediated myocarditis is an uncommon adverse effect of immune checkpoint inhibition and is associated with a high rate of mortality. METHODS: In this reported case, a 64-year-old woman with right temporo-parietal glioblastoma IDH-WT was treated with nivolumab, temozolomide and radiation therapy on a clinical trial. She developed malignant arrhythmias secondary to histologically confirmed severe immune-mediated myocarditis. She was treated with equine anti-thymocyte globulin (ATGAM) due to development of malignant arrhythmias refractory to high-dose corticosteroids...
August 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28796248/upregulation-of-dact2-suppresses-proliferation-and-enhances-apoptosis-of-glioma-cell-via-inactivation-of-yap-signaling-pathway
#15
Ying Tan, Qiu-Meng Li, Ning Huang, Si Cheng, Guan-Jian Zhao, Hong Chen, Song Chen, Zhao-Hua Tang, Wen-Qian Zhang, Qin Huang, Yuan Cheng
DACT2, one of the Dact gene family members, was shown to function as a tumor suppressor. However, its function in gliomas remains largely unknown. In this study, we investigated the role of DACT2, underlying molecular mechanisms and its clinical significance in glioma patients. Downexpression of DACT2 in gliomas compared with adjacent normal brain tissues was correlated with glioma grade and poor survival. Cox regression analysis revealed that the DACT2 is an independent prognostic indicator for glioma patients...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28791594/melanocortin-receptor-4-and-glioblastoma-cells-effects-of-the-selective-antagonist-ml00253764-alone-and-in-combination-with-temozolomide-in-vitro-and-in-vivo
#16
Francesca Vaglini, Carla Pardini, Teresa Di Desidero, Paola Orlandi, Francesco Pasqualetti, Alessandra Ottani, Simone Pacini, Daniela Giuliani, Salvatore Guarini, Guido Bocci
Currently, no description of melanocortin receptor-4 (MC4R) expression or activity is available in human cancer cells, including glioblastoma (GBM). The aim of this study is to evaluate the presence of MC4Rs in GBM cells and the selective inhibition of their activity through the MC4R antagonist ML00253764 alone and in association with temozolomide in vitro and in vivo. MC4R genotyping and gene expression were performed on human GBM cells (U-87 and U-118) with real-time PCR. MC4R western blotting, immunohistochemistry, and immunofluorescence were obtained in both cell lines and in human tissues...
August 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28791452/long-term-daily-temozolomide-with-dose-dependent-efficacy-in-mgmt-promotor-methylation-negative-recurrent-high-grade-astrocytoma
#17
Zhengqiu Zhou, Tracy A Howard, John L Villano
Temozolomide (TMZ) for malignant gliomas is traditionally dosed in 5 out of a 28-day cycle, however alternative regimens exist, including dose-dense. Continuous daily dosing is available, but the acceptable dose and duration of therapy is unknown. We document a 40-year-old male with recurrent anaplastic astrocytoma, IDH mutant and MGMT promotor methylation negative, who has well-tolerated continuous daily TMZ for 20 months at 100 mg per day for nearly the length of this period. A trial at 80 mg per day demonstrated disease progression with response upon return to 100 mg per day...
August 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28790487/developing-therapies-for-brain-tumors-the-impact-of-the-johns-hopkins-hunterian-neurosurgical-research-laboratory
#18
Henry Brem, Eric W Sankey, Ann Liu, Antonella Mangraviti, Betty M Tyler
The Johns Hopkins Hunterian Neurosurgical Laboratory at the Johns Hopkins University School of Medicine was created in 1904 by Harvey Cushing and William Halsted and has had a long history of fostering surgical training, encouraging basis science research, and facilitating translational application. Over the past 30 years, the laboratory has addressed the paucity of brain tumor therapies. Pre-clinical work from the laboratory led to the development of carmustine wafers with initial US Food and Drug Administration (FDA) approval in 1996...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28777020/direct-medical-costs-of-treatment-in-newly-diagnosed-high-grade-glioma-among-commercially-insured-us-patients
#19
Shan Jiang, Kala Hill, Dipen Patel, A Reginald Waldeck, Marc Botteman, Abdalla Aly, Andrew D Norden
AIM: This analysis assessed the direct medical costs of newly-diagnosed, temozolomide (TMZ)-treated glioblastoma (GBM) from the perspective of a US commercial setting. MATERIALS AND METHODS: The analysis included subjects identified from the IMS PharMetrics LifeLink Plus™ claims database from January 1, 2008 to August 31, 2014 who were ≥18 years of age, had ≥1 malignant brain cancer diagnosis, had brain surgery ≤90 days prior to TMZ initiation, had TMZ treatment, and were continuously enrolled for ≥12 months pre-diagnosis and ≥1 month post-diagnosis...
August 16, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28776671/%C3%AE-asarone-inhibited-cell-growth-and-promoted-autophagy-via-p53-bcl-2-bclin-1-and-p53-ampk-mtor-pathways-in-human-glioma-u251-cells
#20
Nanbu Wang, Qinxin Zhang, Laiyu Luo, Baile Ning, Yongqi Fang
Glioma is the most common type of primary brain tumor and has an undesirable prognosis. Autophagy plays an important role in cancer therapy, but it's effect is still not definite. P53 is an important tumor suppressor gene and protein that is closely to autophagy. Our aim was to study the effect of β-asarone on inhibiting cell proliferation in human glioma U251 cells and to detect the effect of the inhibition on autophagy through the P53 signal pathway. For cell growth, the cells were divided into four groups: the model, β-asarone, temozolomide (TMZ) and co-administration groups...
August 4, 2017: Journal of Cellular Physiology
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