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https://www.readbyqxmd.com/read/29225516/hedgehog-gli1-signaling-pathway-regulates-mgmt-expression-and-chemoresistance-to-temozolomide-in-human-glioblastoma
#1
Ke Wang, Dongjiang Chen, Zhouqi Qian, Daming Cui, Liang Gao, Meiqing Lou
Background: Chemoresistance of glioblastoma (GBM) is a feature of this devastating disease. This study is to determine the relationship between Hedgehog (HH)/Gli1 signaling pathway and chemoresistance to temozolomide (TMZ) in human GBM. Methods: We analyzed Gli1 nuclear staining and O6-methylguanine DNA methyltransferase (MGMT) expression in 48 cases of primary GBM tissues by immunohistochemistry. Quantitative PCR, western blot, methylation-specific PCR, cell proliferation and apoptosis assay were used to investigate changes of MGMT expression and chemosensitivity to TMZ after manipulating HH/Gli1 signaling activity in A172 and U251 GBM cell lines...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29221202/ezh2-alteration-driven-by-microrna-524-5p-and-microrna-324-5p-promotes-cell-proliferation-and-temozolomide-resistance-in-glioma
#2
Tongle Zhi, Tianfu Yu, Minhong Pan, Er Nie, Weining Wu, Xiefeng Wang, Ning Liu, Yongping You, Yingyi Wang, Junxia Zhang
Recent data have been shown that EZH2 is a critical oncogene via the repression of tumor suppressor genes in human cancers. In our study, we performed a genome-wide miRNA screen with a bioinformatics analysis to identify EZH2 specific miRNAs. Of these miRNAs, miR-524-5p and miR-324-5p were decreased in glioma tissues, and confered poor prognosis for glioma patients. Upregulation of miR-524-5p and miR-324-5p reduced glioma cell proliferation and increased temozolomide (TMZ) chemosensitivity by targeting EZH2...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212499/radiotherapy-plus-temozolomide-in-elderly-patients-with-glioblastoma-a-real-life-report
#3
J Biau, E Chautard, E De Schlichting, G Dupic, B Pereira, A Fogli, M Müller-Barthélémy, P Dalloz, T Khalil, A F Dillies, X Durando, C Godfraind, P Verrelle
BACKGROUND: The optimization of the management for elderly glioblastoma patients is crucial given the demographics of aging in many countries. We report the outcomes for a "real-life" patient cohort (i.e. unselected) comprising consecutive glioblastoma patients aged 70 years or more, treated with different radiotherapy +/- temozolomide regimens. METHODS: From 2003 to 2016, 104 patients ≥ 70 years of age, consecutively treated by radiotherapy for glioblastoma, were included in this study...
December 6, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/29208287/development-of-temozolomide-coated-nano-zinc-oxide-for-reversing-the-resistance-of-malignant-glioma-stem-cells
#4
Meiguang Zheng, Shengwen Wang, Zhenghao Liu, Lin Xie, Yuefei Deng
Recently most of the researchers have turned their interest towards plant mediated synthesis of metal nanoparticles to avoid several environmental toxicants. In this manuscript, we have discussed the ecofriendly syntheses of zinc oxide nanoparticles (ZnO NPs) were achieved using Glycyrrhiza glabra (G. glabra) seed aqueous extract. The green synthesized ZnO NPs were characterized using analytical techniques like XRD, TEM, particle size histogram and Zeta potential. From the results, it was found that the green synthesized ZnO NPs were around 35nm in size with irregular spherical shape...
February 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29202181/targeted-nanocomplex-carrying-sirna-against-malat1-sensitizes-glioblastoma-to-temozolomide
#5
Sang-Soo Kim, Joe B Harford, Manish Moghe, Antonina Rait, Kathleen F Pirollo, Esther H Chang
Intrinsic therapeutic resistance especially in cancer stem cells (CSCs) together with extensive tumor cell infiltration and restricted permeation of the blood-brain barrier (BBB) by drugs may all contribute to the treatment failure in patients with glioblastoma multiforme (GBM). Accumulating evidence suggests that long non-coding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a role in tumor cell infiltration and therapeutic resistance of GBM. Using our tumor-targeted nanocomplex, we have modulated the expression of MALAT1 and investigated its impact on GBM cells...
November 30, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29199725/rechallenge-temozolomide-in-glioma-a-case-series-from-india
#6
V M Patil, R Tonse, R Kothari, A Chandrasekaran, N Pande, S Epari, T Gupta, R Jalali
INTRODUCTION: Temozolomide (TMZ) is an integral part of upfront treatment of high-grade gliomas. It is administered postsurgery as concurrent therapy with radiation and subsequently as adjuvant chemotherapy for 6-12 cycles. It is unknown whether rechallenge of salvage TMZ in previously treated high-grade glioma has any efficacy. MATERIAL AND METHODS: Patients treated with salvage rechallenged TMZ between January 2015 and August 2016 were included for this retrospective analysis...
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29190898/trimedazidine-alleviates-pulmonary-artery-banding-induced-acute-right-heart-dysfunction-and-activates-pras40-in-rats
#7
Yunshan Cao, Jiyang Song, Shutong Shen, Heling Fu, Xiang Li, Ying Xu, Aqian Wang, Xinli Li, Min Zhang
The molecular mechanism underlying acute right heart failure (RHF) is poorly understood. We used pulmonary artery banding (PAB) to induce acute RHF characterized by a rapid rise of right ventricular pressure, and then a decrease in right ventricular pressure along with a decrease in blood pressure right after banding. We found higher brain natriuretic peptide (BNP) and beta-myosin heavy chain (βMHC) levels and lower alpha-myosin heavy chain (αMHC) levels in RHF rats than sham-operated rats. Hemodynamic indexes in rats with acute RHF were slightly improved by trimedazidine TMZ, a key inhibitor of fatty acid (FA) oxidation...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29188211/response-of-leptomeningeal-dissemination-of-anaplastic-glioma-to-temozolomide-experience-of-two-cases
#8
Jin Woo Bae, Eun Kyung Hong, Ho-Shin Gwak
The incidence of leptomeningeal dissemination (LMD) of anaplastic glioma has been increasing. LMD can be observed at the time of initial presentation or the time of recurrence. As a result of both rarity and unusual presentation, a standard therapy has not yet been suggested. In contrast to leptomeningeal carcinomatosis for systemic solid cancers, a relatively prolonged survival is observed in some patients with LMD of anaplastic gliomas. Treatment modalities include whole craniospinal irradiation, intra-cerebrospinal fluid (CSF) chemotherapy, and systemic chemotherapy...
October 2017: Brain Tumor Research and Treatment
https://www.readbyqxmd.com/read/29181405/review-of-natural-product-derived-compounds-as-potent-antiglioblastoma-drugs
#9
REVIEW
Moon Nyeo Park, Hyo Sook Song, Myungsun Kim, Min-Jung Lee, Whisung Cho, Hyun-Jin Lee, Cho-Hyun Hwang, Soojong Kim, Yechae Hwang, Beomku Kang, Bonglee Kim
Common care for glioblastoma multiforme (GBM) is a surgical resection followed by radiotherapy and temozolomide- (TMZ-) based chemotherapy. Unfortunately, these therapies remain inadequate involving severe mortality and recurrence. Recently, new approaches discovering combinations of multiple inhibitors have been proposed along with the identification of key driver mutations that are specific to each patient. To date, this approach is still limited by the lack of effective therapy. Hopefully, novel compounds derived from natural products are suggested as potential solutions...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29168083/analysis-of-the-cancer-genome-atlas-tcga-database-identifies-an-inverse-relationship-between-interleukin-13-receptor-%C3%AE-1-and-%C3%AE-2-gene-expression-and-poor-prognosis-and-drug-resistance-in-subjects-with-glioblastoma-multiforme
#10
Jing Han, Raj K Puri
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. A variety of targeted agents are being tested in the clinic including cancer vaccines, immunotoxins, antibodies and T cell immunotherapy for GBM. We have previously reported that IL-13 receptor subunits α1 and α2 of IL-13R complex are overexpressed in GBM. We are investigating the significance of IL-13Rα1 and α2 expression in GBM tumors. In order to elucidate a possible relationship between IL-13Rα1 and α2 expression with severity and prognoses of subjects with GBM, we analyzed gene expression (by microarray) and clinical data available at the public The Cancer Genome Atlas (TCGA) database (Currently known as Global Data Commons)...
November 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29164620/repair-gene-mgmt-is-controlled-by-sp1-and-upregulated-by-glucocorticoids-but-not-by-temozolomide-and-radiation
#11
Dorthe Aasland, Thomas R Reich, Maja T Tomicic, Olivier J Switzeny, Bernd Kaina, Markus Christmann
Therapy of malignant glioma relies on treatment with the O(6) -methylating agent temozolomide (TMZ) concomitant with ionizing radiation followed by adjuvant TMZ. For the treatment of recurrences DNA chloroethylating drugs are also used. The main killing lesion induced by these drugs is O(6) -alkylguanine. Since this damage is repaired by O(6) -methylguanine-DNA methyltransferase (MGMT), the repair enzyme represents the most important factor of drug resistance, limiting the therapy of malignant high-grade gliomas...
November 22, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29163847/a-relative-increase-in-circulating-platelets-following-chemoradiation-predicts-for-poor-survival-of-patients-with-glioblastoma
#12
Keeratikarn Boonyawan, Kenneth R Hess, Jie Yang, Lihong Long, Qianghu Wang, Ravesanker Ezhilarasan, Alessandra Auia, Kristin D Alfaro-Munoz, John F de Groot, Krishna P Bhat, Erik P Sulman
Background: Thrombocytosis is triggered by and promotes tumor growth. The relationship between the change in circulating platelets after chemoradiation therapy (CRT) or adjuvant temozolomide (TMZ) and survival in glioblastoma remains unclear. We hypothesized that an increase in platelets after these treatments would be predictive of a shorter survival. Methods: We retrospectively reviewed data on 122 patients with newly diagnosed, pathologically proven glioblastoma who had been treated with surgery, followed by CRT and adjuvant TMZ, from 2007 to 2016...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163773/tumor-response-of-temozolomide-in-combination-with-morphine-in-a-xenograft-model-of-human-glioblastoma
#13
Anna Lisa Iorio, Martina da Ros, Lorenzo Genitori, Maurizio Lucchesi, Fabiana Colelli, Giacomo Signorino, Francesco Cardile, Giacomo Laffi, Maurizio de Martino, Claudio Pisano, Iacopo Sardi
Despite multimodal treatments comprising, radiation therapy (RT) and chemotherapy with temozolomide (TMZ), the prognosis of glioblastoma multiforme (GBM) remains dismal and consolidated therapy yields a median survival of 14.6 months. Blood Brain Barrier (BBB) mediated chemoresistance and high dose related toxicity make necessary the development of new therapeutic approach to sensitize GBM to TMZ. The aim of the present study was to investigate the potential of the treatment morphine plus TMZ metronmic doses (1,77 and 0,9 mg/kg) in GBM therapy...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29162646/nkg2d-dependent-anti-tumor-effects-of-chemotherapy-and-radiotherapy-against-glioblastoma
#14
Tobias Weiss, Hannah Schneider, Manuela Silginer, Alexander Steinle, Martin N Pruschy, Bojan Polic, Michael Weller, Patrick Roth
PURPOSE: NKG2D is a potent activating immune cell receptor and glioma cells express the cognate ligands (NKG2DL). These ligands are inducible by cellular stress and temozolomide (TMZ) or irradiation (IR), the standard treatment of glioblastoma, could affect their expression. However, a role of NKG2DL for the efficacy of TMZ and IR has never been addressed. EXPERIMENTAL DESIGN: We assessed the effect of TMZ and IR on NKG2DL in vitro and in vivo in a variety of murine and human glioblastoma models including glioma-initiating cells and a cohort of paired glioblastoma samples from patients before and after therapy...
November 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29162480/dual-targeting-immunoliposomes-using-angiopep-2-and-cd133-antibody-for-glioblastoma-stem-cells
#15
Jung Seok Kim, Dae Hwan Shin, Jin-Seok Kim
Glioblastoma stem cells (GSCs), which are identified as subpopulation of CD133(+)/ALDH1(+), are known to show resistance to the most of chemotherapy and radiation therapy, leading to the recurrence of tumor in glioblastoma multiforme (GBM) patients. Also, delivery of temozolomide (TMZ), a mainline treatment of GBM, to the GBM site is hampered by various barriers including the blood-brain barrier (BBB). A dual-targeting immunoliposome encapsulating TMZ (Dual-LP-TMZ) was developed by using angiopep-2 (An2) and anti-CD133 monoclonal antibody (CD133 mAb) for BBB transcytosis and specific delivery to GSCs, respectively...
November 18, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29162448/intracellular-cholesterol-level-regulates-sensitivity-of-glioblastoma-cells-against-temozolomide-induced-cell-death-by-modulation-of-caspase-8-activation-via-death-receptor-5-accumulation-and-activation-in-the-plasma-membrane-lipid-raft
#16
Yutaro Yamamoto, Arata Tomiyama, Nobuyoshi Sasaki, Hideki Yamaguchi, Takuya Shirakihara, Katsuhiko Nakashima, Kosuke Kumagai, Satoru Takeuchi, Terushige Toyooka, Kojiro Wada, Yoshitaka Narita, Koichi Ichimura, Ryuichi Sakai, Hiroki Namba, Kentaro Mori
Development of resistance against temozolomide (TMZ) in glioblastoma (GBM) after continuous treatment with TMZ is one of the critical problems in clinical GBM therapy. Intracellular cholesterol regulates cancer cell biology, but whether intracellular cholesterol is involved in TMZ resistance of GBM cells remains unclear. The involvement of intracellular cholesterol in acquired resistance against TMZ in GBM cells was investigated. Intracellular cholesterol levels were measured in human U251 MG cells with acquired TMZ resistance (U251-R cells) and TMZ-sensitive control U251 MG cells (U251-Con cells), and found that the intracellular cholesterol level was significantly lower in U251-R cells than in U251-Con cells...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29162424/injectable-hydrogels-for-localized-chemo-and-radio-therapy-in-brain-tumors
#17
Pilar de la Puente, Nicole Fettig, Micah J Luderer, Abbey Jin, Shruti Shah, Barbara Muz, Vaishali Kapoor, Sreekrishna M Goddu, Noha Nabil Salama, Christina Tsien, Dinesh Thotala, Kooresh Shoghi, Buck Rogers, Abdel Kareem Azab
PURPOSE: Overall survival of patients with newly diagnosed glioblastoma (GBM) remains dismal at 16 months with state-of-the-art treatment that includes surgical resection, radiation and chemotherapy. GBM tumors are highly heterogeneous and mechanisms for overcoming tumor resistance have not yet fully been elucidated. An injectable chitosan hydrogel capable of releasing chemotherapy (Temozolomide, TMZ) while retaining radioactive isotopes agents (Iodine, (131)I) was used as a vehicle for localized radiation and chemotherapy, within the surgical cavity...
November 18, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29159183/patients-affected-by-unmethylated-o-6-methylguanine-dna-methyltransferase-glioblastoma-undergoing-radiochemotherapy-may-benefit-from-moderately-dose-escalated-radiotherapy
#18
Paolo Tini, Valerio Nardone, Pierpaolo Pastina, Giuseppe Battaglia, Clelia Miracco, Lucio Sebaste, Giovanni Rubino, Alfonso Cerase, Luigi Pirtoli
Purpose: To compare the therapeutic results of two radiotherapy (RT) dose schedules in combined temozolomide- (TMZ-) RT treatment in newly diagnosed glioblastoma (GB), according to the O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status. Material and Method: Patients received either standard (60 Gy) or moderately escalated dose (70 Gy) radiotherapy (RT) with concomitant and adjuvant TMZ between June 2006 and October 2013. We retrospectively evaluated the therapeutic effectiveness of RT schedules in terms of Overall Survival (OS) and Progression-Disease Free Survival (PDFS) analyzing the MGMT methylation status...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29152101/functional-network-analysis-of-gene-phenotype-connectivity-associated-with-temozolomide
#19
Jia Shi, Bo Dong, Peng Zhou, Wei Guan, Ya Peng
Rationale: Glioma has a poor survival rate in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for treating glioma, but TMZ treatment consistently leads to high resistance. Aim: To investigate the underlying mechanisms of TMZ action with new therapeutic regimens in glioma. Methods and results: The biological effects of TMZ mainly depend on the three following DNA repair systems: methylguanine methyltransferase (MGMT), mismatch repair (MMR) and base excision repair (BER)...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151909/bkm120-sensitizes-c6-glioma-cells-to-temozolomide-via-suppression-of-the-pi3k-akt-nf-%C3%AE%C2%BAb-mgmt-signaling-pathway
#20
Mao Li, Ruo Fei Liang, Xiang Wang, Qing Mao, Yan Hui Liu
Glioblastoma is the most common type of malignant intracranial tumor in adults. Temozolomide (TMZ), as the first-line chemotherapy agent used in patients with glioblastoma, has demonstrated different effects in patients due to the expression of O6-methylguanine-DNA methyltransferase (MGMT) which is able to repair the DNA lesions induced by TMZ. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is over-activated in glioblastoma and has been revealed to be potentially implicated in resistance to TMZ...
December 2017: Oncology Letters
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