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https://www.readbyqxmd.com/read/28220388/real-world-evidence-for-the-antianginal-efficacy-of-trimetazidine-from%C3%A2-the%C3%A2-russian-observational-choice-2-study
#1
Maria Glezer
INTRODUCTION: The guidelines recommend a beta-blocker or calcium channel blocker as the first-line medication for angina, supplemented by other agents for additional symptoms. One such agent is trimetazidine (TMZ), which has been shown to reduce the frequency of anginal episodes and improve exercise performance without affecting haemodynamic parameters. However, extensive real-world evidence for its efficacy in combination with first-line therapies has been lacking. METHODS: The aim of this large-scale, Russian, multicentre, 6-month, open-label, prospective observational study was to assess the effect of adding TMZ modified release 35 mg bid to background antianginal therapy in the real-world clinical setting...
February 20, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28217019/-99m-tc-tetrofosmin-uptake-correlates-with-the-sensitivity-of-glioblastoma-cell-lines-to-temozolomide
#2
George A Alexiou, Xanthi Xourgia, Paraskevi Gerogianni, Evrysthenis Vartholomatos, John A Kalef-Ezra, Andreas D Fotopoulos, Athanasios P Kyritsis
(99m)Tc-tetrofosmin ((99m)Tc-TF) is a single-photon emission computed tomography tracer that has been used for brain tumor imaging. The aim of the study was to assess if (99m)Tc-TF uptake by glioblastoma cells correlates with their response to temozolomide (TMZ). We investigated the correlation of TMZ antitumor effect with the (99m)Tc-TF uptake in two glioblastoma cell lines. The U251MG cell line is sensitive to TMZ, whereas T98G is resistant. Viability and proliferation of the cells were examined by trypan blue exclusion assay and xCELLigence system...
January 2017: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28212543/metabotropic-glutamate-receptors-as-a-new-therapeutic-target-for-malignant-gliomas
#3
REVIEW
Mery Stefani Leivas Pereira, Fábio Klamt, Chairini Cássia Thomé, Paulo Valdeci Worm, Diogo Losch de Oliveira
Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209108/acute-temozolomide-induced-liver-injury%C3%A2-mixed-type-hepatocellular-and-cholestatic-toxicity
#4
C Aygun, A Y Altınok, A Çakır, A F Agan, Y Balaban
Temozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. His laboratory analysis showed alanine aminotransferase(ALT) : 632 IU/L (normal range 0-40) ; aspartate aminotransferase(AST) : 554 IU/L (normal range 5-34) ; alkaline phosphatase(ALP) : 1143 IU/L (normal range 40-150) ; γ-glutamyl transpeptidase(GGT) : 514 IU/L (normal range 9-64 IU/L) ; total bilirubin : 15...
September 2016: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/28208677/targeting-protein-kinase-ck2-evaluating-cx-4945-potential-for-gl261-glioblastoma-therapy-in-immunocompetent-mice
#5
Laura Ferrer-Font, Lucia Villamañan, Nuria Arias-Ramos, Jordi Vilardell, Maria Plana, Maria Ruzzene, Lorenzo A Pinna, Emilio Itarte, Carles Arús, Ana Paula Candiota
Glioblastoma (GBM) causes poor survival in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment but resistance always ensues. Protein kinase CK2 (CK2) contributes to tumour development and proliferation in cancer, and it is overexpressed in human GBM. Accordingly, targeting CK2 in GBM may benefit patients. Our goal has been to evaluate whether CK2 inhibitors (iCK2s) could increase survival in an immunocompetent preclinical GBM model. Cultured GL261 cells were treated with different iCK2s including CX-4945, and target effects evaluated in vitro...
February 12, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28207276/hydrophobic-nanoparticles-reduce-the-%C3%AE-sheet-content-of-sevi-amyloid-fibrils-and-inhibit-sevi-enhanced-hiv-infectivity
#6
Daniel A Sheik, Jeffrey M Chamberlain, Lauren R Brooks, Melissa L Clark, Young Hun Kim, Geoffray Leriche, Clifford P Kubiak, Stephen Dewhurst, Jerry Yang
Semen-Derived Enhancer of Virus Infection (SEVI) fibrils are naturally abundant amyloid aggregates found in semen that facilitate viral attachment and internalization of HIV in cells, thereby increasing the probability of infection. Mature SEVI fibrils are comprised of aggregated peptides exhibiting high β-sheet secondary structural characteristics. Herein, we show that polymers containing hydrophobic side chains can interact with SEVI and reduce its β-sheet content by ~45% compared to the β-sheet content of SEVI in the presence of polymers with hydrophilic side chains, as estimated by Polarization Modulation-Infrared Reflectance Absorption Spectroscopy Measurements...
February 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28202508/chemosensitivity-of-idh1-mutant-gliomas-due-to-an-impairment-in-parp1-mediated-dna-repair
#7
Yanxin Lu, Jakub Kwintkiewicz, Yang Liu, Katherine Tech, Lauren N Frady, Yu-Ting Su, Wendy Bautista, Seog In Moon, Jeffrey MacDonald, Matthew G Edwend, Mark R Gilbert, Chunzhang Yang, Jing Wu
Mutations in isocitrate dehydrogenase (IDH) are the most prevalent genetic abnormalities in lower grade gliomas. The presence of these mutations in glioma is prognostic for better clinical outcomes with longer patient survival. In the present study, we found that defects in oxidative metabolism and 2-HG production confer chemosensitization in IDH1-mutated glioma cells. In addition, temozolomide (TMZ) treatment induced greater DNA damage and apoptotic changes in mutant glioma cells. The PARP1-associated DNA repair pathway was extensively compromised in mutant cells due to decreased NAD+ availability...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28199863/analysis-of-chemopredictive-assay-for-targeting-cancer-stem-cells-in-glioblastoma-patients
#8
Candace M Howard, Jagan Valluri, Anthony Alberico, Terrence Julien, Rida Mazagri, Robert Marsh, Hoyt Alastair, Antonio Cortese, Michael Griswold, Wanmei Wang, Krista Denning, Linda Brown, Pier Paolo Claudio
INTRODUCTION: The prognosis of glioblastoma (GBM) treated with standard-of-care maximal surgical resection and concurrent adjuvant temozolomide (TMZ)/radiotherapy remains very poor (less than 15 months). GBMs have been found to contain a small population of cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. The highly invasive nature of high-grade gliomas and their inherent resistance to therapy lead to very high rates of recurrence. For these reasons, not all patients with similar diagnoses respond to the same chemotherapy, schedule, or dose...
February 12, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28197654/temozolomide-during-radiotherapy-of-glioblastoma-multiforme-daily-administration-improves-survival
#9
Silke Birgit Nachbichler, Gabi Schupp, Hendrik Ballhausen, Maximilian Niyazi, Claus Belka
BACKGROUND: Temozolomide-(TMZ)-based chemoradiotherapy defines the current gold standard for the treatment of newly diagnosed glioblastoma. Data regarding the influence of TMZ dose density during chemoradiotherapy are currently not available. We retrospectively compared outcomes in patients receiving no TMZ, TMZ during radiotherapy on radiotherapy days only, and TMZ constantly 7 days a week. PATIENTS AND METHODS: From 2002-2012, a total of 432 patients with newly diagnosed glioblastoma received radiotherapy in our department: 118 patients had radiotherapy alone, 210 had chemoradiotherapy with TMZ (75 mg/m(2)) daily (7/7), and 104 with TMZ only on radiotherapy days (5/7)...
February 14, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28197649/dose-response-relationship-of-temozolomide-determined-by-the-pig-a-comet-and-micronucleus-assay
#10
M Guérard, G Johnson, S Dertinger, G Duran-Pacheco, J Funk, A Zeller
Temozolomide (TMZ), a monofunctional alkylating agent, was selected as a model compound to determine its quantitative genotoxic dose-response relationship in different tissues (blood, liver, and jejunum) and endpoints [Pig-a-, comet-, and micronucleus assay (MNT)] in male rats. TMZ was administered p.o. over 5 consecutive days (day 1-5), followed by a treatment-free period of 50 days (day 6-56) and a final administration prior to necropsy (day 57-59). TMZ showed a dose-dependent increase in DNA damage in all interrogated endpoints...
February 15, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28193190/enhanced-expression-of-vastatin-inhibits-angiogenesis-and-prolongs-survival-in-murine-orthotopic-glioblastoma-model
#11
Yi Li, Jun Li, Yat Ming Woo, Zan Shen, Hong Yao, Yijun Cai, Marie Chia-Mi Lin, Wai Sang Poon
BACKGROUND: Antiangiogenic therapies are considered promising for the treatment of glioblastoma (GB). The non-collagenous C-terminal globular NC1 domain of type VIII collagen a1 chain, Vastatin, is an endogenous antiangiogenic polypeptide. Sustained enhanced expression of Vastatin was shown to inhibit tumour growth and metastasis in murine hepatocellular carcinoma models. In this study, we further explored the efficacy of Vastatin in the treatment of GB xenografts. METHOD: Treatment of Vastatin was carried out using a nanopolymer gene vector PEI600-CyD-Folate (H1)...
February 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28192785/temozolomide-with-or-without-radiotherapy-in-patients-with-newly-diagnosed-glioblastoma-multiforme-a-meta-analysis
#12
Enshan Feng, Changbai Sui, Tongxin Wang, Gaoling Sun
BACKGROUND/AIM: The current meta-analysis evaluated the survival outcomes of newly diagnosed glioblastoma patients treated with radiotherapy (RT) alone and with RT + temozolomide (TMZ). METHODS: Relevant studies were identified by an extensive literature search in Medline, Current Contents and Cochrane databases by 2 independent reviewers using the terms "glioblastoma multiforme/glioblastoma, TMZ, radiation therapy/RT and survival." RESULTS: Results revealed a median survival of 13...
February 14, 2017: European Neurology
https://www.readbyqxmd.com/read/28187000/malat1-is-a-prognostic-factor-in-glioblastoma-multiforme-and-induces-chemoresistance-to-temozolomide-through-suppressing-mir-203-and-promoting-thymidylate-synthase-expression
#13
Wei Chen, Xin-Ke Xu, Jun-Liang Li, Kuan-Kei Kong, Hui Li, Cheng Chen, Jing He, Fangyu Wang, Ping Li, Xiao-Song Ge, Fang-Cheng Li
Glioblastoma multiforme (GBM) is the most malignant brain tumor with limited therapeutic options. Temozolomide (TMZ) is a novel cytotoxic agent used as first-line chemotherapy for GBM, however, some individual cells can't be isolated for surgical resection and show treatment-resistance, thus inducing poor prognosis. By using the HiSeq sequencing and bioinformatics methods, we identified lncRNAs showing different expression levels in TMZ-resistant and non-resistant patients. RT-qPCR was then performed in tissues and serum samples, and lncRNA MALAT1 was finally identified to show considerable discriminating potential to identify responding patients from non-responding patients...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185110/foxm1-mediated-rfc5-expression-promotes-temozolomide-resistance
#14
Wan-Xin Peng, Xiu Han, Chun-Li Zhang, Lu Ge, Feng-Yi Du, Jie Jin, Ai-Hua Gong
Although methylguanine-DNA-methyltransferase (MGMT) plays an important role in resistance to temozolomide (TMZ) in glioma, 40% of gliomas with MGMT inactivation are still resistant to TMZ. The underlying mechanism is not clear. Here, we report that forkhead box M1 (FoxM1) transcriptionally activates the expression of DNA repair gene replication factor C5 (RFC5) to promote TMZ resistance in glioma cells independent of MGMT activation. We showed that RFC5 expression is positively correlated with FoxM1 expression in human glioma cells and FoxM1 is able to transcriptionally activate RFC expression by interaction with the RFC5 promoter...
February 9, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28181188/atorvastatin-promotes-cytotoxicity-and-reduces-migration-and-proliferation-of-human-a172-glioma-cells
#15
Karen A Oliveira, Tharine Dal-Cim, Flávia G Lopes, Fabiana K Ludka, Cláudia B Nedel, Carla I Tasca
Malignant gliomas have resistance mechanisms to chemotherapy that enable tumor invasiveness and aggressiveness. Alternative therapies in cancer treatment, as statins, have been suggested to decrease proliferation, inhibit cell migration, and induce cell death. The aim of this study was to evaluate the effect of atorvastatin (ATOR) on cell viability, migration, proliferation, apoptosis, and autophagy in A172 human glioma cells. Temozolomide (TMZ), a chemotherapic used to glioma treatment, was tested as a comparison to cytotoxic effects on gliomas...
February 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28178660/plk1-inhibition-enhances-temozolomide-efficacy-in-idh1-mutant-gliomas
#16
Robert F Koncar, Zhengtao Chu, Lindsey E Romick-Rosendale, Susanne I Wells, Timothy A Chan, Xiaoyang Qi, El Mustapha Bahassi
Despite multimodal therapy with radiation and the DNA alkylating agent temozolomide (TMZ), malignant gliomas remain incurable. Up to 90% of grades II-III gliomas contain a single mutant isocitrate dehydrogenase 1 (IDH1) allele. IDH1 mutant-mediated transformation is associated with TMZ resistance; however, there is no clinically available means of sensitizing IDH1 mutant tumors to TMZ. In this study we sought to identify a targetable mechanism of TMZ resistance in IDH1 mutant tumors to enhance TMZ efficacy...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177664/trimetazidine-potentiates-the-antiepileptic-activity-and-ameliorates-the-metabolic-changes-associated-with-pentylentetrazole-kindling-in-rats-treated-with-valproic-acid
#17
Amina Ahmed Sedky, Osama Mahmod Elserafy, Olfat A Hassan, Hala Salah Abdel Kawy, Amany Hasanin, Mona Hussein Raafat
Oxidative stress is implicated in epileptogenesis as well as in the metabolic changes associated with increased risk of atherosclerotic vascular disease in epilepsy. The present work investigated the impact of the antioxidants trimetazidine (TMZ) on the antiepileptic activity of valproic acid (VAP) and on the metabolic and histological changes in hippocampal, aortic and hepatic tissues associated with epilepsy and/or VPA. Rats were divided into: Non-Pentylentetrazole (PTZ) group; subdivided into: control and VPA treated groups, PTZ-treated group subdivided into: PTZ, PTZ/VPA, PTZ/TMZ, PTZ/VPA+TMZ groups...
January 29, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28176936/add-on-bevacizumab-can-prevent-early-clinical-deterioration-and-prolong-survival-in-newly-diagnosed-partially-resected-glioblastoma-patients-with-a-poor-performance-status
#18
Nobuhiro Hata, Koji Yoshimoto, Ryusuke Hatae, Daisuke Kuga, Yojiro Akagi, Yuhei Sangatsuda, Satoshi O Suzuki, Tadahisa Shono, Masahiro Mizoguchi, Koji Iihara
PURPOSE: The AVAglio trial established the beneficial effect of add-on bevacizumab (BEV) for the treatment of newly diagnosed glioblastomas (nd-GBMs) that led to the approval of BEV for the treatment of these patients in Japan. However, the rationality of using BEV as a first-line treatment for nd-GBMs remains controversial. The purpose of this study was to analyze the outcomes of a case series of nd-GBM patients. PATIENTS AND METHODS: The outcomes of 69 nd-GBM patients treated after 2006 were retrospectively analyzed...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28176884/impact-of-including-peritumoral-edema-in-radiotherapy-target-volume-on-patterns-of-failure-in-glioblastoma-following-temozolomide-based-chemoradiotherapy
#19
Seo Hee Choi, Jun Won Kim, Jee Suk Chang, Jae Ho Cho, Se Hoon Kim, Jong Hee Chang, Chang-Ok Suh
We assessed the impact of including peritumoral edema in radiotherapy volumes on recurrence patterns among glioblastoma multiforme (GBM) patients treated with standard chemoradiotherapy (CRT). We analyzed 167 patients with histologically confirmed GBM who received temozolomide (TMZ)-based CRT between May 2006 and November 2012. The study cohort was divided into edema (+) (n = 130) and edema (-) (n = 37) groups, according to whether the entire peritumoral edema was included. At a median follow-up of 20 months (range, 2-99 months), 118 patients (71%) experienced progression/recurrence (infield: 69%; marginal: 26%; outfield: 16%; CSF seeding: 12%)...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28175496/141%C3%A2-phase-i-trial-of-genetically-modified-hematopoietic-progenitor-cells-facilitate-bone-marrow-chemoprotection-and-enabling-tmz-o6bg-dose-escalation-resulting-in-improved-survival
#20
Andrew E Sloan, Hua Fung, Jane Reese, Lisa R Rogers, Christopher Murphay, Hillard Lazrus, Boro Dropulic, Stan L Gerson
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
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