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https://www.readbyqxmd.com/read/28440814/depletion-of-adult-neurogenesis-using-the-chemotherapy-drug-temozolomide-in-mice-induces-behavioural-and-biological-changes-relevant-to-depression
#1
M Egeland, C Guinaudie, A Du Preez, K Musaelyan, P A Zunszain, C Fernandes, C M Pariante, S Thuret
Numerous studies have examined links between postnatal neurogenesis and depression using a range of experimental methods to deplete neurogenesis. The antimitotic drug temozolomide (TMZ) has previously been used successfully as an experimental tool in animals to deplete adult neurogenesis and is used regularly on human patients as a standard chemotherapy for brain cancer. In this study, we wanted to evaluate whether TMZ as a model for chemotherapy treatment could affect parameters related to depression in an animal model...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28436750/emap-ii-sensitize-u87mg-and-glioma-stem-like-cells-to-temozolomide-via-induction-of-autophagy-mediated-cell-death-and-g2-m-arrest
#2
Qi Yu, Libo Liu, Ping Wang, Yilong Yao, Yixue Xue, Yunhui Liu
Despite the fact that temozolomide (TMZ) has been widely accepted as the key chemotherapeutic agent to prolong the survival of patients with glioblastoma, failure and recurrence cases can still be observed in clinics. Glioma stem-like cells (GSCs) are thought to be responsible for the drug resistance. In this study, we investigate whether endothelial monocyte-activating polypeptide-II (EMAP-II), a pro-inflammatory cytokine, can enhance TMZ cytotoxicity on U87MG and GSCs or not. As described in prior research, GSCs have been isolated from U87MG and maintained in the serum-free DMEM/F12 medium containing EGF, b-FGF, and B27...
April 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28432588/patterns-of-care-and-outcomes-of-multi-agent-versus-single-agent-chemotherapy-as-part-of-multimodal-management-of-low-grade-glioma
#3
Waqar Haque, Vivek Verma, E Brian Butler, Bin S Teh
For high-risk low-grade gliomas (LGGs), adjuvant radiotherapy (RT) with procarbazine/lomustine/vincristine (PCV) chemotherapy increases overall survival (OS) over RT alone. However, in practice, temozolomide (TMZ) is often used instead of PCV. Using the National Cancer Data Base (NCDB), we provide the first investigation of practice patterns and outcomes of chemoradiotherapy with single-agent chemotherapy (SAC, analogous to TMZ) or multi-agent chemotherapy (MAC, analogous to PCV) for LGG. Patients with high-risk Grade II LGGs were queried in the NCDB...
April 21, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28432280/small-molecules-targeting-histone-demethylase-genes-kdms-inhibit-growth-of-temozolomide-resistant-glioblastoma-cells
#4
Barbara Banelli, Antonio Daga, Alessandra Forlani, Giorgio Allemanni, Daniela Marubbi, Maria Pia Pistillo, Aldo Profumo, Massimo Romani
In glioblastoma several histone demethylase genes (KDM) are overexpressed compared to normal brain tissue and the development of Temozolomide (TMZ) resistance is accompanied by the transient further increased expression of KDM5A and other KDMs following a mechanism that we defined as "epigenetic resilience". We hypothesized that targeting KDMs may kill the cells that survive the cytotoxic therapy.We determined the effect of JIB 04 and CPI-455, two KDM inhibitors, on glioblastoma cells and found that both molecules are more effective against TMZ-resistant rather than native cells...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28432119/temozolomide-treatment-can-improve-overall-survival-in-aggressive-pituitary-tumors-and-pituitary-carcinomas
#5
Hélène Lasolle, Christine Cortet, Fréderic Castinetti, Lucie Cloix, Philippe Caron, Brigitte Delemer, Rachel Desailloud, Christel Jublanc, Christine Lebrun-Frenay, Jean-Louis Sadoul, Luc Taillandier, Marie Batisse-Lignier, Fabrice Bonnet, Nathalie Bourcigaux, Damien Bresson, Olivier Chabre, Philippe Chanson, Cyril Garcia, Magalie Haissaguerre, Yves Reznik, Sophie Borot, Chiara Villa, Alexandre Vasiljevic, Stephan Gaillard, Emmanuel Jouanneau, Guillaume Assié, Gérald Raverot
OBJECTIVES: Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. DESIGN: Multicenter retrospective study by members of the French Society of Endocrinology. METHODS: Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included...
June 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28430038/prognostic-implications-of-the-subcellular-localization-of-survivin-in-glioblastomas-treated-with-radiotherapy-plus-concomitant-and-adjuvant-temozolomide
#6
Taiichi Saito, Kazuhiko Sugiyama, Yukio Takeshima, Vishwa Jeet Amatya, Fumiyuki Yamasaki, Takeshi Takayasu, Ryo Nosaka, Yoshihiro Muragaki, Takakazu Kawamata, Kaoru Kurisu
OBJECTIVE Currently, the standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Various prognostic biomarkers for GBM have been described, including survivin expression. The aim of this study was to determine whether the subcellular localization of survivin correlates with GBM prognosis in patients who received the standard treatment protocol. METHODS The authors retrospectively examined the subcellular localization of survivin (nuclear, cytoplasmic, or both) using immunohistochemistry in 50 patients with GBM who had received the standard treatment...
April 21, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28425987/biological-activity-of-tumor-treating-fields-in-preclinical-glioma-models
#7
Manuela Silginer, Michael Weller, Roger Stupp, Patrick Roth
Glioblastoma is the most common and aggressive form of intrinsic brain tumor with a very poor prognosis. Thus, novel therapeutic approaches are urgently needed. Tumor-treating fields (TTFields) may represent such a novel treatment option. The aim of this study was to investigate the effects of TTFields on glioma cells, as well as the functional characterization of the underlying mechanisms. Here, we assessed the anti-glioma activity of TTFields in several preclinical models. Applying TTFields resulted in the induction of cell death in a frequency- and intensity-dependent manner in long-term glioma cell lines, as well as glioma-initiating cells...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28423558/biological-basis-and-clinical-study-of-glycogen-synthase-kinase-3%C3%AE-targeted-therapy-by-drug-repositioning-for-glioblastoma
#8
Takuya Furuta, Hemragul Sabit, Yu Dong, Katsuyoshi Miyashita, Masashi Kinoshita, Naoyuki Uchiyama, Yasuhiko Hayashi, Yutaka Hayashi, Toshinari Minamoto, Mitsutoshi Nakada
BACKGROUND: Glycogen synthase kinase (GSK)-3β has emerged as an appealing therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic effect of the current approved drugs against GBM via inhibition of GSK3β activity both, in experimental setting and in a clinical study for recurrent GBM patients by repositioning existent drugs in combination with temozolomide (TMZ). MATERIALS AND METHODS: Progression-free and overall survival rates were compared between patients with low or high expression of active GSK3β in the primary tumor...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415586/promoting-oligodendroglial-oriented-differentiation-of-glioma-stem-cell-a-repurposing-of-quetiapine-for-the-treatment-of-malignant-glioma
#9
Yun Wang, Nanxin Huang, Hongli Li, Shubao Liu, Xianjun Chen, Shichang Yu, Nan Wu, Xiu-Wu Bian, Hai-Ying Shen, Chengren Li, Lan Xiao
As a major contributor of chemotherapy resistance and malignant recurrence, glioma stem cells (GSCs) have been proposed as a target for the treatment of gliomas. To evaluate the therapeutic potential of quetiapine (QUE), an atypical antipsychotic, for the treatment of malignant glioma, we established mouse models with GSCs-initiated orthotopic xenograft gliomas and subcutaneous xenograft tumors, using GSCs purified from glioblastoma cell line GL261. We investigated antitumor effects of QUE on xenograft gliomas and its underlying mechanisms on GSCs...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415451/the-sustained-delivery-of-temozolomide-from-electrospun-pcl-diol-b-pu-gold-nanocompsite-nanofibers-to-treat-glioblastoma-tumors
#10
Mohammad Irani, Gity Mir Mohamad Sadeghi, Ismaeil Haririan
In the present study, the PCL-Diol-b-PU/Au nanocompsite nanofibers were fabricated via electrospinning process during two different stages to load an anticancer temozolomide (TMZ) drug into the nanofibers. The first stage was the incorporation of Au nanoparticles into the nanofibers and the second stage was coating the gold nanoparticles on the surface of PCL-Diol-b-PU/Au composite nanofibers. The prepared nanofibrous formulations were characterized using FTIR, SEM and TEM analysis. Box-Behnken-design was used to investigate the influence of electrospinning parameters including solution concentration, applied voltage to tip-collector distance ratio and collector speed on the morphology and fiber diameter of PCL-Diol-b-PU/Au nanofibers...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28411277/long-term-survival-in-glioblastoma-with-cytomegalovirus-pp65-targeted-vaccination
#11
Kristen A Batich, Elizabeth A Reap, Gary E Archer, Luis Sanchez-Perez, Smita K Nair, Robert J Schmittling, Pam Norberg, Weihua Xie, James E Herndon, Patrick Healy, Roger E McLendon, Allan H Friedman, Henry S Friedman, Darell Bigner, Gordana Vlahovic, Duane A Mitchell, John H Sampson
Purpose: Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can extend survival and, in a separate study, that dose-intensified temozolomide (DI-TMZ) and adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) potentiate tumor-specific immune responses in patients with glioblastoma. Here, we evaluated pp65-specific cellular responses following DI-TMZ with pp65-DCs and determined the effects on long-term progression-free survival (PFS) and overall survival (OS)...
April 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28410193/metabolic-targeting-of-egfrviii-pdk1-axis-in-temozolomide-resistant-glioblastoma
#12
Kiran K Velpula, Maheedhara R Guda, Kamlesh Sahu, Jack Tuszynski, Swapna Asuthkar, Sarah E Bach, Justin D Lathia, Andrew J Tsung
Glioblastomas are characterized by amplification of EGFR. Approximately half of tumors with EGFR over-expression also express a constitutively active ligand independent EGFR variant III (EGFRvIII). While current treatments emphasize surgery followed by radiation and chemotherapy with Temozolomide (TMZ), acquired chemoresistance is a universal feature of recurrent GBMs. To mimic the GBM resistant state, we generated an in vitro TMZ resistant model and demonstrated that dichloroacetate (DCA), a metabolic inhibitor of pyruvate dehydrogenase kinase 1 (PDK1), reverses the Warburg effect...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409559/correlations-of-mgmt-genetic-polymorphisms-with-temozolomide-resistance-and-prognosis-of-patients-with-malignant-gliomas-a-population-based-study-in-china
#13
H-W Wang, Z-K Xu, Y Song, Y-G Liu
This study aims to investigate the associations of O(6)-methylguanine-DNA methyltransferase (MGMT) genetic polymorphisms (Leu84Phe and Ile143Val) with temozolomide (TMZ) resistance and prognosis of patients with malignant gliomas. A total of 212 patients diagnosed with malignant gliomas were enrolled in this study as the case group. All of these patients took oral TMZ and were assigned into the TMZ-sensitive (complete response+partial response) and the TMZ-resistant (stable disease+progressive disease) groups based on the clinical response after chemotherapy...
April 14, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28409498/differential-pro-apoptotic-effects-of-synthetic-4-thiazolidinone-derivative-les-3288-doxorubicin-and-temozolomide-in-human-glioma-u251-cells
#14
Lesya I Коbylinska, Olga Yu Klyuchivska, Iryna I Grytsyna, Natalia Finiuk, Rostyslav R Panchuk, Marina O Starykovych, Lilya Lehka, Roman B Lesyk, Borys S Zіmenkovsky, Rostyslav S Stoika
AIM: To compare various pro-apoptotic effects of synthetic 4-thiazolidinone derivative (Les-3288), doxorubicin (Dox) and temozolomide (TMZ) in the treatment of human glioma U251 cells to improve treatment outcomes of glioblastoma and avoid anticancer drug resistance. METHODS: The cytotoxic effects of drugs used in human glioma U251 cells were measured by cell viability and proliferation assay (MTT), Trypan blue exclusion test, and Western-blot analysis of the apoptosis-related proteins...
April 14, 2017: Croatian Medical Journal
https://www.readbyqxmd.com/read/28408249/temozolomide-does-not-influence-the-transcription-or-activity-of-matrix-metalloproteinases-9-and-2-in-glioma-cell-lines
#15
Yuta Suzuki, Kouki Fujioka, Keiichi Ikeda, Yuichi Murayama, Yoshinobu Manome
Glioblastoma multiforme (GBM) is a treatment-resistant malignancy with poor prognosis. Temozolomide (TMZ) is widely used as a first-line drug for GBM. Although this improves patient prognosis, it does not completely eradicate the tumour. Even after total surgical resection, GBM can exhibit uncontrollable invasiveness at the tumour margins owing to activation of matrix metalloproteinases (MMPs) such as MMP-2 and -9; these degrade collagen IV in the basement membrane, which normally prevents cancer invasion. TMZ induces DNA damage and activates transcription factors including c-jun, c-fos, nuclear factor-κβ, and early growth response protein-1, which have putative binding sites on the MMP-9 promoter...
April 10, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28403532/temozolomide-increases-mhc-i-expression-via-nf-%C3%AE%C2%BAb-signaling-in-glioma-stem-cells
#16
Dongyong Zhang, Bo Qiu, Yunjie Wang, Yanlei Guan, Luyang Zhang, Anhua Wu
Gliomas are the most common and primary tumors of the central nervous system in adults. Temozolomide (TMZ) is the main drug used to treat glioma, however, prognosis remains poor for most patients. Glioma stem cells (GSCs) are thought to enable glioma initiation and evasion from immune surveillance; their immunogenicity can be determined by expression of major histocompatibility complex (MHC)-I. The present study investigated the effect of TMZ on MHC-I expression in GSCs. Glioma spheres were cultured in serum-free medium containing epidermal growth factor, basic fibroblast growth factor, and B27; MHC-I expression was detected by immunocytochemistry, quantitative real-time PCR, and flow cytometry...
April 12, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28401486/dual-treatment-with-shikonin-and-temozolomide-reduces-glioblastoma-tumor-growth-migration-and-glial-to-mesenchymal-transition
#17
Diana Matias, Joana Balça-Silva, Luiz Gustavo Dubois, Bruno Pontes, Valéria Pereira Ferrer, Luciane Rosário, Anália do Carmo, Juliana Echevarria-Lima, Ana Bela Sarmento-Ribeiro, Maria Celeste Lopes, Vivaldo Moura-Neto
PURPOSE: Glioblastomas (GBM) comprise 17% of all primary brain tumors. These tumors are extremely aggressive due to their infiltrative capacity and chemoresistance, with glial-to-mesenchymal transition (GMT) proteins playing a prominent role in tumor invasion. One compound that has recently been used to reduce the expression of these proteins is shikonin (SHK), a naphthoquinone with anti-tumor properties. Temozolomide (TMZ), the most commonly used chemotherapeutic agent in GBM treatment, has so far not been studied in combination with SHK...
April 11, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28388894/juglone-induces-apoptosis-of-tumor-stem-like-cells-through-ros-p38-pathway-in-glioblastoma
#18
Jinfeng Wu, Haibo Zhang, Yang Xu, Jingwen Zhang, Wei Zhu, Yi Zhang, Liang Chen, Wei Hua, Ying Mao
BACKGROUND: Juglone is a natural pigment, which has cytotoxic effect against various human tumor cells. However, its cytotoxicity to glioma cells, especially to tumor stem-like cells (TSCs) has not been demonstrated. METHODS: TSCs of glioma were enriched from U87 and two primary cells (SHG62, and SHG66) using serum-free medium supplemented with growth factors, including bFGF, EGF and B27. After treatment of juglone with gradient concentrations (0, 10, 20, and 40 μM), the viability and apoptosis of TSCs were evaluated by WST-8 assay and flow cytometry...
April 7, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28380412/%C3%AE-asarone-promotes-temozolomide-s-entry-into-glioma-cells-and-decreases-the-expression-of-p-glycoprotein-and-mdr1
#19
Nanbu Wang, Qinxin Zhang, Baile Ning, Laiyu Luo, Yongqi Fang
Glioma is the most common primary brain tumor and has an undesirable prognosis due to the blood-brain barrier (BBB) and drug resistance. A thorough investigation of the changes in intracellular drug concentrations is important to observe therapeutic effects and cell resistance. P-glycoprotein (P-gp) is an essential protein of Multi-drug resistance 1 (MDR1). The over-expression of P-gp and MDR1 is associated with poor prognosis and drug-resistance in glioma. However, β-asarone can pass through the BBB easily and increase the drug concentration in the rat brain...
April 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28378865/mustard-inspired-delivery-shuttle-for-enhanced-blood-brain-barrier-penetration-and-effective-drug-delivery-in-glioma-therapy
#20
Nan Wang, Pei Sun, Mingming Lv, Gangsheng Tong, Xin Jin, Xinyuan Zhu
Effective penetration through the blood-brain barrier (BBB) remains a challenge for the treatment of many brain diseases. In this study, a small molecule, sinapic acid (SA), extracted from mustard, was selected as a novel bioinspired BBB-permeable ligand for efficient drug delivery in glioma treatment. SA was conjugated on the surface of zwitterionic polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-encapsulated bovine serum albumin (BSA)-based nanoparticles, yielding nBSA-SA. The PMPC shell serves as a protective layer to prolong the in vivo blood circulation time with a better chance to cross the BBB...
April 5, 2017: Biomaterials Science
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