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https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#1
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28301347/outcomes-for-anaplastic-glioma-treated-with-radiation-therapy-with-or-without-concurrent-temozolomide
#2
Emory McTyre, John T Lucas, Corbin Helis, Michael Farris, Michael Soike, Ryan Mott, Adrian W Laxton, Stephen B Tatter, Glenn J Lesser, Roy E Strowd, Hui-Wen Lo, Waldemar Debinski, Michael D Chan
OBJECTIVES: Postoperative management of anaplastic glioma remains without a clear standard of care-in this study we report outcomes for patients treated with radiotherapy (RT) with and without temozolomide (TMZ). MATERIALS AND METHODS: We identified 71 consecutive patients with World Health Organization grade III glioma treated with either RT alone or with concurrent TMZ (RT+TMZ), between 2000 and 2013. Tumor histology was anaplastic astrocytoma in 42 patients, anaplastic oligodendroglioma in 25 patients, and anaplastic oligoastrocytoma in 4 patients...
March 15, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28298550/limited-role-for-extended-maintenance-temozolomide-for-newly-diagnosed-glioblastoma
#3
Dorothee Gramatzki, Philipp Kickingereder, Bettina Hentschel, Jörg Felsberg, Ulrich Herrlinger, Gabriele Schackert, Jörg-Christian Tonn, Manfred Westphal, Michael Sabel, Uwe Schlegel, Wolfgang Wick, Torsten Pietsch, Guido Reifenberger, Markus Loeffler, Martin Bendszus, Michael Weller
OBJECTIVE: To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles. METHODS: The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression...
March 15, 2017: Neurology
https://www.readbyqxmd.com/read/28297578/%C3%AE-elemene-selectively-inhibits-the-proliferation-of-glioma-stem-like-cells-through-the-downregulation-of-notch1
#4
Hai-Bin Feng, Jing Wang, Hao-Ran Jiang, Xin Mei, Yi-Ying Zhao, Fu-Rong Chen, Yue Qu, Ke Sai, Cheng-Cheng Guo, Qun-Ying Yang, Zong-Ping Zhang, Zhong-Ping Chen
Glioma is the most frequent primary central nervous system tumor. Although the current first-line medicine, temozolomide (TMZ), promotes patient survival, drug resistance develops easily. Thus, it is important to investigate novel therapeutic reagents to solidify the treatment effect. β-Elemene (bELE) is a compound from a Chinese herb whose anticancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem-like cells (GSLCs) has not yet been reported. We studied both the in vitro and the in vivo inhibitory effect of bELE and TMZ in GSLCs and parental cells and their combined effects...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28293765/rutin-increases-the-cytotoxicity-of-temozolomide-in-glioblastoma-via-autophagy-inhibition
#5
Pingde Zhang, Stella Sun, Ning Li, Amy Suk Wai Ho, Karrie Mei Yee Kiang, Xiaoqin Zhang, Yin Stephen Cheng, Ming Wai Poon, Derek Lee, Jenny Kan Suen Pu, Gilberto Ka Kit Leung
The chemotherapeutic agent temozolomide (TMZ) is widely used in the treatment of glioblastoma multiforme (GBM). Rutin, a citrus flavonoid ecglycoside found in edible plants, has neuroprotective and anticancer activities. This study aimed to investigate the efficacy and the underlying mechanisms of rutin used in combination with TMZ in GBM. In vitro cell viability assay demonstrated that rutin alone had generally low cytotoxic effect, but it enhanced the efficacy of TMZ in a dose-dependent manner. Subcutaneous and orthotopic xenograft studies also showed that tumor volumes were significantly lower in mice receiving combined TMZ/Rutin treatment as compared to TMZ or rutin alone treatment...
March 14, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28292827/the-glycoside-oleandrin-reduces-glioma-growth-with-direct-and-indirect-effects-on-tumor-cells
#6
Stefano Garofalo, Alfonso Grimaldi, Giuseppina Chece, Alessandra Porzia, Stefania Morrone, Fabrizio Mainiero, Giuseppina D'Alessandro, Vincenzo Esposito, Barbara Cortese, Silvia Di Angelantonio, Flavia Trettel, Cristina Limatola
Oleandrin is a glycoside that inhibits the ubiquitous enzyme Na(+)-K(+)-ATPase. In addition to its known effects on cardiac muscle, recent in vitro and in vivo evidence highlighted potential for anticancer properties of this compound. In this paper we evaluated for the first time the effect of oleandrin on brain tumors. To this aim mice were transplanted with human or murine glioma and analyzed for tumor progression upon oleandrin treatment. In both systems, oleandrin impaired glioma development, reduced tumor size, and inhibited cell proliferation...
March 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28291643/successful-treatment-of-pituitary-carcinoma-with-concurrent-radiation-temozolomide-and-bevacizumab-after-resection
#7
Waseem Touma, Spencer Hoostal, Richard A Peterson, Andres Wiernik, Karen S SantaCruz, Emil Lou
The optimal treatment of pituitary carcinomas (PC) is unknown. Treatment includes surgical resection, radiation, and more recently, temozolomide (TMZ). Pituitary adenomas have relatively high expression of vascular endothelial growth factor; therefore, bevacizumab, an antiangiogenic agent, has been used in a small number of aggressive or malignant pituitary tumors after recurrence. However, it has not been administered concurrently with other chemotherapeutic agents or combined with radiation therapy in PC...
March 11, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28290002/plasma-and-cerebrospinal-fluid-pharmacokinetics-of-select-chemotherapeutic-agents-following-intranasal-delivery-in-a-non-human-primate-model
#8
James C League-Pascual, Cynthia M Lester-McCully, Shaefali Shandilya, Lukas Ronner, Louis Rodgers, Rafael Cruz, Cody J Peer, William D Figg, Katherine E Warren
The blood-brain barrier (BBB) limits entry of most chemotherapeutic agents into the CNS, resulting in inadequate exposure within CNS tumor tissue. Intranasal administration is a proposed means of delivery that can bypass the BBB, potentially resulting in more effective chemotherapeutic exposure at the tumor site. The objective of this study was to evaluate the feasibility and pharmacokinetics (plasma and CSF) of intranasal delivery using select chemotherapeutic agents in a non-human primate (NHP) model. Three chemotherapeutic agents with known differences in CNS penetration were selected for intranasal administration in a NHP model to determine proof of principle of CNS delivery, assess tolerability and feasibility, and to evaluate whether certain drug characteristics were associated with increased CNS exposure...
March 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28288921/therapy-for-recurrent-high-grade-gliomas-results-of-a-prospective-multicenter-study-on-health-related-quality-of-life
#9
Linda Stöckelmaier, Mirjam Renovanz, Jochem König, Katrin Nickel, Anne-Katrin Hickmann, Regine Mayer-Steinacker, Minou Nadji-Ohl, Oliver Ganslandt, Lars Bullinger, Christian Rainer Wirtz, Jan Coburger
OBJECTIVE: To assess impact of therapy on patients' health-related quality of life (HRQoL) in recurrent high-grade glioma (HGG) in an unselected cohort. METHODS: In this prospective multicenter study, we analyzed EORTC QLQ-C30 and BN20 questionnaires of 92 patients within one year after diagnosis of tumor recurrence of a HGG and respective treatment. We evaluated the influence of re-radiation, second and third-line chemotherapies and number of recurrent surgeries on sum scores for functioning, symptoms and total score as well as on sub scores for functioning and neurological symptoms using multivariate mixed models and descriptive statistics...
March 10, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28288919/a-case-of-therapy-related-acute-myeloid-leukemia-associated-with-adjuvant-temozolomide-chemotherapy-for-anaplastic-astrocytoma
#10
Kenzo Kosugi, Katsuya Saito, Wataru Takahashi, Yukina Tokuda, Hideyuki Tomita
BACKGROUND: Temozolomide (TMZ) is now standard adjuvant therapy in combination with radiotherapy for patients with newly diagnosed malignant glioma. Treatment-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) associated with TMZ chemotherapy for patients with glioma is quite a rare complication. CASE DESCRIPTION: A 43-year-old man with an anaplastic astrocytoma received radiation therapy synchronized with ranimustine (MCNU) and adjuvant TMZ chemotherapy for 15 cycles...
March 10, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28286975/single-vs-combination-immunotherapeutic-strategies-for-glioma
#11
Mayuri Chandran, Marianela Candolfi, Diana Shah, Yohei Mineharu, Vivek Yadav, Carl Koschmann, Antonela S Asad, Pedro R Lowenstein, Maria G Castro
Malignant gliomas are highly invasive tumors, associated with a dismal survival rate despite standard of care, which includes surgical resection, radiotherapy and chemotherapy with temozolomide (TMZ). Precision immunotherapies or combinations of immunotherapies that target unique tumor-specific features may substantially improve upon existing treatments. Areas covered: Clinical trials of single immunotherapies have shown therapeutic potential in high-grade glioma patients, and emerging preclinical studies indicate that combinations of immunotherapies may be more effective than monotherapies...
March 13, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28282906/gsk3%C3%AE-and-vdac-involvement-in-er-stress-and-apoptosis-modulation-during-orthotopic-liver-transplantation
#12
Mohamed Amine Zaouali, Arnau Panisello, Alexandre Lopez, Carlos Castro, Emma Folch, Teresa Carbonell, Anabela Rolo, Carlos Marques Palmeira, Agustin Garcia-Gil, René Adam, Joan Roselló-Catafau
We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia-reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured...
March 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28272232/continuous-dose-intense-temozolomide-and-cisplatin-in-recurrent-glioblastoma-patients
#13
Yu Wang, Xiangyi Kong, Yi Guo, Renzhi Wang, Wenbin Ma
In glioblastoma multiforme (GBM), both temozolomide (TMZ) and cisplatin are very active at various toxic levels. Previous studies demonstrated that cisplatin with the standard regimen of TMZ is active in patients suffering from recurrent GBM, generating a moderate level of toxicity. Also, continuous dose-intense TMZ is a helpful therapy for patients with recurrent GBM. We have conducted a research to evaluate the security and effectiveness of cisplatin with constant dose-intense TMZ for reduplicative GBM. The time to progression (TTP) and progression-free survival (PFS) at 6 months (PFS-6) was the major end point...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28270035/bmi-1-promotes-self-renewal-of-radio-and-temozolomide-tmz-resistant-breast-cancer-cells
#14
Yanfang Yan, Ying Wang, Pengxin Zhao, Weiyuan Ma, Zhigang Hu, Kaili Zhang
Breast cancer is a hormone-dependent malignancy and is the most prevalent cause of cancer-related mortality among females. Radiation therapy and chemotherapy are common treatments of breast cancer. However, tumor relapse and metastasis following therapy are major clinical challenges. The importance of B-lymphoma Moloney murine leukemia virus insertion region-1 (BMI-1) was implicated in cell proliferation, stem cell maintenance, and tumor initiation. We established radio- and temozolomide (TMZ)-resistant (IRC-R) MCF-7 and MDA-MB-231 cell lines to investigate the mechanism involved in therapeutic resistance...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28261829/trimetazidine-has-protective-effects-on-spermatogenesis-in-a-streptozotocin-induced-diabetic-rat-model
#15
M F Ozcan, E R Hekimoglu, K Ener, M Namuslu, R Altintas, H T Celik, Z Akbulut, S Altinova
The aim of this study was to investigate the protective effects of trimetazidine (TMZ), as an antioxidant agent, on streptozotocin (STZ)-induced diabetic rats. A total of 50 male Sprague Dawley rats were randomly classified into five groups as follows: Group 1 (control), Group 2 (STZ-induced diabetic rats), Group 3 (STZ-induced diabetic rats treated orally with 1 cc/day isotonic saline), Group 4 (diabetic rats treated orally with 10 mg/kg/day TMZ) and Group 5 (diabetic rats treated orally with 20 mg/kg/day TMZ)...
March 6, 2017: Andrologia
https://www.readbyqxmd.com/read/28260965/enhancement-of-temozolomide-stability-by-loading-in-chitosan-carboxylated-polylactide-based-nanoparticles
#16
Antonio Di Martino, Pavel Kucharczyk, Zdenka Capakova, Petr Humpolicek, Vladimir Sedlarik
In the presented work, amphiphilic nanoparticles based on chitosan and carboxy-enriched polylactic acid have been prepared to improve the stability of the pro-drug temozolomide in physiological media by encapsulation. The carrier, with a diameter in the range of 150-180 nm, was able to accommodate up to 800 μg of temozolomide per mg of polymer. The obtained formulation showed good stability in physiological condition and preparation media up to 1 month. Temozolomide loaded inside the carrier exhibited greater stability than the free drug, in particular in simulated physiological solution at pH 7...
2017: Journal of Nanoparticle Research: An Interdisciplinary Forum for Nanoscale Science and Technology
https://www.readbyqxmd.com/read/28260024/foxo3a-induces-temozolomide-resistance-in-glioblastoma-cells-via-the-regulation-of-%C3%AE-catenin-nuclear-accumulation
#17
Ke Xu, Zhenhao Zhang, Hua Pei, Huamin Wang, Liang Li, Qianfeng Xia
Glioblastoma multiforme (GBM), the most common malignant brain tumor, is currently treated with temozolomide (TMZ), but GBM often exhibits resistance to TMZ. Although several mechanisms underlying GBM resistance to TMZ have been identified, these mechanisms are yet to fully explain how GBM gains resistance to TMZ. Our previous work has shown that FoxO3a, a member of the FoxO subfamily of transcription factors, promotes glioma cell proliferation and invasion. In this study, we sought to determine whether FoxO3a participates in TMZ resistance in GBM cells...
February 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259296/critical-review-of-the-addition-of-tumor-treating-fields-ttfields-to-the-existing-standard-of-care-for-newly-diagnosed-glioblastoma-patients
#18
REVIEW
M Mehta, P Wen, R Nishikawa, D Reardon, K Peters
Since 2005, the standard of care for patients with newly diagnosed glioblastoma (GBM) has consisted of maximal resection followed by radiotherapy plus daily temozolomide (TMZ), followed by maintenance TMZ. In patients selected for clinical trials, median overall survival (OS) and progression-free survival (PFS) with this regimen is 15-17 months and 6-7 months, respectively. There have been various, largely unsuccessful attempts to improve on this standard of care. With the FDA approval of the tumor-treating fields (TTFields) device, Optune, for recurrent GBM (2011), and the more recent EF-14 interim trial results and approval for newly diagnosed GBM patients, several questions have arisen...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28256321/trimetazidine-in-conditions-other-than-coronary-disease-old-drug-new-tricks
#19
REVIEW
Hai Zou, Xing-Xing Zhu, Ya-Hui Ding, Qin-Yang Jin, Lin-Yan Qian, Dong-Sheng Huang, Xue-Jiang Cen
Trimetazidine (TMZ) has traditionally been used as an anti-ischemic drug for coronary artery disease by selectively inhibiting the mitochondrial long-chain 3-ketoacyl-CoA thiolase. Recently, new applications for this therapy have been investigated. This article reviews alternative uses for TMZ in non-coronary artery diseases, such as non-ischemic cardiomyopathy, sepsis, myocardial dysfunction induced by anti-cancer drugs, diabetic cardiomyopathy and contrast-induced nephropathy.
May 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28248861/clinical-effect-of-trimetazidine-on-prevention-of-contrast-induced-nephropathy-in-patients-with-renal-insufficiency-an-updated-systematic-review-and-meta-analysis
#20
Ziliang Ye, Haili Lu, Qiang Su, Wenqin Guo, Weiran Dai, Hongqing Li, Huafeng Yang, Lang Li
BACKGROUND: With the continuous development of cardiac interventional medicine, the incidence of contrast-induced nephropathy (CIN) is increasing every year, which is a serious threat to people's physical and mental health. Trimetazidine (TMZ) is a type of anti-ischemic drug developed in recent years, which can significantly reduce the incidence of CIN. At present, a systematic review and meta-analysis was conducted to evaluate the clinical effect of TMZ on prevention of CIN in patients with renal insufficiency...
March 2017: Medicine (Baltimore)
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