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https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#1
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27894350/gant61-a-gli-inhibitor-sensitizes-glioma-cells-to-the-temozolomide-treatment
#2
Jianlong Li, Jinquan Cai, Shihong Zhao, Kun Yao, Ying Sun, Yongli Li, Lingchao Chen, Ruiyan Li, Xiuwei Zhai, Junhe Zhang, Chuanlu Jiang
BACKGROUND: The aim of this study was to investigate the effect of downregulating Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes of temozolomide (TMZ)-induced effects and explore the molecular mechanisms. METHODS: The cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone and in combination with TMZ in human glioma cell lines. The mRNA and protein expression alterations were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively...
November 28, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27893811/the-inhibition-of-microrna-128-on-igf-1-activating-mtor-signaling-involves-in-temozolomide-induced-glioma-cell-apoptotic-death
#3
Peng-Hsu Chen, Chia-Hsiung Cheng, Chwen-Ming Shih, Kuo-Hao Ho, Cheng-Wei Lin, Chin-Cheng Lee, Ann-Jeng Liu, Cheng-Kuei Chang, Ku-Chung Chen
Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade primary glioma in adults. Micro (mi)RNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagenesis. However, no studies have reported relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated miRNA profiles and its molecular mechanisms underlying the induction of glioma cell death...
2016: PloS One
https://www.readbyqxmd.com/read/27893419/silver-nanoparticles-enhance-the-sensitivity-of-temozolomide-on-human-glioma-cells
#4
Ping Liang, Hongming Shi, Weiguo Zhu, Qunfeng Gui, Ya Xu, Jianfeng Meng, Xiaoyuan Guo, Zhuang Gong, Huaqun Chen
Glioblastoma multiforme (GBM) continues to be associated with a dismal prognosis despite aggressive treatment. Significant efforts are being made to develop new nanotechnology-based therapeutic and diagnostic agents. Nanoparticles can act directly on cancer cells or as drug carriers to enhance the cancer therapeutic effect. In this study, we investigated the effect of silver nanoparticles (AgNPs) on human glioma U251 cells and its role in the combinational use with Temozolomide (TMZ), an imidazotetrazine derivative of the alkylating agent dacarbazine, against glioma cells...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27878252/temozolomide-inhibits-cellular-growth-and-motility-via-targeting-erk-signaling-in-glioma-c6-cells
#5
Yingge Wang, Shan Gao, Weiguang Wang, Jingyan Liang
Temozolomide (TMZ) is an alkylating agent used for the treatment of aggressive forms of brain tumor based on its antitumor actions. However, the exact effect on cancer and the underlying anticancer molecular mechanism of TMZ remain to be elucidated. In the present study, the effects of TMZ on the growth and motility of glioma C6 cells were investigated. MTT and Transwell assays were used to detect cellular growth and motility. The results showed that TMZ inhibited the proliferation, migration and invasion of the glioma C6 cells in vitro, western blot analysis determined that the phosphorylation of extracellular signal‑regulated protein kinase (ERK)1/2 was decreased in the TMZ‑treated cells, compared with the untreated control cells...
November 23, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27865821/the-effects-of-tumor-treating-fields-and-temozolomide-in-mgmt-expressing-and-non-expressing-patient-derived-glioblastoma-cells
#6
Paul A Clark, Jordan T Gaal, Joslyn K Strebe, Cheri A Pasch, Dustin A Deming, John S Kuo, H Ian Robins
A recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the addition of tumor treating fields (TTFields) to temozolomide (TMZ) after combined radiation/TMZ significantly increased survival and progression free survival. Preliminary data suggested benefit with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient-derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant: 12...
November 16, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27855650/trimetazidine-attenuates-pressure-overload-induced-early-cardiac-energy-dysfunction-via-regulation-of-neuropeptide-y-system-in-a-rat-model-of-abdominal-aortic-constriction
#7
Ailan Chen, Wanglin Li, Xinyu Chen, Yuechun Shen, Wenjun Dai, Qi Dong, Xinchun Li, Caiwen Ou, Minsheng Chen
BACKGROUND: Metabolism remodeling has been recognized as an early event following cardiac pressure overload. However, its temporal association with ventricular hypertrophy has not been confirmed. Moreover, whether trimetazidine could favorably affect this process also needs to be determined. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine on myocardial metabolism remodeling...
November 17, 2016: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/27845901/refractory-pituitary-adenoma-a-novel-classification-for-pituitary-tumors
#8
Congxin Dai, Ming Feng, Xiaohai Liu, Sihai Ma, Bowen Sun, Xinjie Bao, Yong Yao, Kan Deng, Yu Wang, Bing Xing, Wei Lian, Dingrong Zhong, Wenbin Ma, Renzhi Wang
Pituitary adenomas are classified as typical or atypical, invasive or noninvasive, and aggressive or nonaggressive based on pathological features, radiological findings, and clinical behavior. Only pituitary tumors with cerebrospinal and/or systemic metastasis are considered malignant carcinomas. However, some pituitary adenomas with high Ki-67 indexes exhibit aggressive behaviors, such as rapid growth, early and frequent recurrence, and resistance to conventional treatment, even in the absence of metastasis...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27837435/exosomal-mir-221-targets-dnm3-to-induce-tumor-progression-and-temozolomide-resistance-in-glioma
#9
Jian-Kai Yang, Ji-Peng Yang, Jing Tong, Shi-Yuan Jing, Bo Fan, Feng Wang, Guo-Zhu Sun, Bao-Hua Jiao
MicroRNA is an important regulator of glioblastoma. This study aims at validating microRNA-221 (miR-221) as a biomarker for glioblastoma, and understanding how miR-221 regulates glioblastoma progression. Using clinical samples, miR-221 expression was analyzed by quantitative reverse-transcriptase PCR (qPCR). SHG-44 cells were treated with anti-miR-221 or U87MG-derived exosomes followed by monitoring changes in cell viability, migration and temozolomide (TMZ) resistance. Bioinformatics approach was used to identify targets of miR-221...
November 11, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27832326/silencing-of-histone-deacetylase-2-suppresses-malignancy-for-proliferation-migration-and-invasion-of-glioblastoma-cells-and-enhances-temozolomide-sensitivity
#10
Zhiqiang Zhang, Yunmin Wang, Jiehan Chen, Qijia Tan, Caijun Xie, Cong Li, Wengang Zhan, Mei Wang
Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in glioblastoma multiforme (GBM) are not well known. Our present study investigated the expression of class I HDACs (HDAC1, 2, 3, 8) in GBM U87, A172, U251, and LN229 cells and compared their levels with that in primary normal human astrocytes (NHA) cells. It showed that HDAC2 expression is significantly up-regulated in GBM cells. Silencing of HDAC2 via its specific siRNAs can suppress the in vitro proliferation, migration, and invasion of GBM U87 and A172 cells...
November 10, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27828691/long-term-complete-remission-of-crooke-s-corticotropinoma-after-temozolomide-treatment
#11
Maria Kurowska, Jerzy S Tarach, Joanna Malicka, Grzegorz Zieliński, Maria Maksymowicz, Piotr Denew
INTRODUCTION: Crooke's corticotropinomas are the unique cause of Cushing's disease. The majority of them are aggressive macroadenomas, refractory to conventional therapy, with a high recurrence rate. The aim of the study was the presentation, in relation to data from the literature, of a case of a patient with ACTH-dependent Cushing's syndrome caused by recurrent Crooke's cells corticotropinoma, who achieved 33-month complete remission after treatment with temozolomide (TMZ). CASE REPORT: A 54-year-old man was diagnosed with Cushing's disease five years earlier on the basis of a typical clinical picture and hormonal tests...
2016: Endokrynologia Polska
https://www.readbyqxmd.com/read/27821033/acute-temozolomide-induced-liver-injury-mixed-type-hepatocellular-and-cholestatic-toxicity
#12
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...
July 2016: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/27803779/the-effect-of-oral-and-intraurethral-trimetazidine-use-on-urethral-healing
#13
Ali Ayyildiz, Sema Nur Ayyildiz, Erdal Benli, Havva Erdem, Selma Cirrik, Tevfik Noyan, R Cankon Germiyanoglu, Abdullah Çirakoglu
OBJECTIVES: We aimed to study the effect of trimetazidine (TMZ) on urethral wound repair. MATERIALS AND METHODS: A total of 52 male rats were used; 8 groups were formed: 1-week and 3-week control (C1, C3), sham (S1, S3), oral (OT1, OT3), and intraurethral TMZ (IUT1, IUT3) groups. Serum and urine total antioxidant capacity (TAC), total oxidant capacity (TOC), and 8-hydroxy-deoxy-guanosine (8-OHdG) were studied. Hematoxyline-Eosin was used for the histopathological study...
September 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27793847/dna-repair-capacity-in-multiple-pathways-predicts-chemoresistance-in-glioblastoma-multiforme
#14
Zachary D Nagel, Gaspar J Kitange, Shiv K Gupta, Brian A Joughin, Isaac A Chaim, Patrizia Mazzucato, Douglas A Lauffenburger, Jann N Sarkaria, Leona D Samson
Cancer cells can resist the effects of DNA-damaging therapeutic agents via utilization of DNA repair pathways, suggesting that DNA repair capacity (DRC) measurements in cancer cells could be used to identify patients most likely to respond to treatment. However, the limitations of available technologies have so far precluded adoption of this approach in the clinic. We recently developed fluorescence-based multiplexed host cell reactivation (FM-HCR) assays to measure DRC in multiple pathways. Here we apply a mathematical model that uses DRC in multiple pathways to predict cellular resistance to killing by DNA-damaging agents...
October 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27792996/microrna-101-reverses-temozolomide-resistance-by-inhibition-of-gsk3%C3%AE-in-glioblastoma
#15
Tian Tian, Ma Mingyi, Xia Qiu, Yang Qiu
Glioblastoma multiforme (GBM) is a chemotherapy-resistant brain tumor with limited treatment options. Temozolomide (TMZ), an alkylating agent, is a front-line chemotherapeutic drug currently employed in GBM. Although it is currently the most promising chemotherapy for GBM, resistance to TMZ is also common and accounts for many treatment failures. Therefore, understanding the underlying mechanisms that generate resistance is essential to develop more effective chemotherapies. Here, we show that microRNA-101 (miR-101) was significantly downregulated in TMZ-resistant GBM cells and human specimens...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27791206/metformin-treatment-reduces-temozolomide-resistance-of-glioblastoma-cells
#16
Seung Ho Yang, Shenglan Li, Guangrong Lu, Haipeng Xue, Dong H Kim, Jay-Jiguang Zhu, Ying Liu
It has been reported that metformin acts synergistically with temozolomide (TMZ) to inhibit proliferation of glioma cells including glioblastoma multiforme (GBM). However, the molecular mechanism underlying how metformin exerts its anti-cancer effects remains elusive. We used a combined experimental and bioinformatics approach to identify genes and complex regulatory/signal transduction networks that are involved in restoring TMZ sensitivity of GBM cells after metformin treatment. First, we established TMZ resistant GBM cell lines and found that the resistant cells regained TMZ sensitivity after metformin treatment...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27783227/the-simulation-of-uv-spectroscopy-and-electronic-analysis-of-temozolomide-and-dacarbazine-chemical-decomposition-to-their-metabolites
#17
M Hossein Khalilian, Saber Mirzaei, Avat Arman Taherpour
The electronic features of anti-tumor agent, temozolomide, and its degradation products (MTIC and metabolite AIC) have been traced by means of UV absorption spectroscopy in vacuo and aqueous media. For comparison, electronic spectra of related structures and drugs (e.g., dacarbazine) were also investigated. These investigations were carried out using time-dependent density functional theory (TD-DFT) method while the conductor like screening model (COSMO) were applied for the inclusion of solvent effects in electronic spectra...
November 2016: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/27777210/-rita-combined-with-temozolomide-inhibits-the-proliferation-of-human-glioblastoma-u87-cells
#18
Xiao-Yan He, Xiao-Li Feng, Xin-Pei Song, Huan-Chao Zeng, Zhong-Xu Cao, Wei-Wei Xiao, Bao Zhang, Qing-Hua Wu
OBJECTIVE: To observe the effect of RITA, a small molecule that targets p53, combined with temozolomide (TMZ) on proliferation, colony formation and apoptosis of human glioblastoma U87 cells and explore the underlying mechanism. METHODS: Cultured U87 cells were treated with RITA (1, 5, 10, 20 µmol/L), TMZ, or RITA+TMZ (half dose) for 24, 48 or 72 h. MTS assay were used to detect the cell proliferation, and the cell proliferation rate and inhibitory rate were calculated...
October 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27777151/management-of-patients-with-primary-intramedullary-spinal-cord-glioblastoma
#19
Bedjan Behmanesh, Matthias Setzer, Juergen Konczalla, Patrick Harter, Johanna Quick-Weller, Lioba Imoehl, Kea Franz, Florian Gessler, Volker Seifert, Gerhard Marquardt
BACKGROUND: Primary intramedullary spinal cord glioblastoma are very rare tumors of the spinal cord. They imply a very poor prognosis since complete surgical resection is not possible due to the infiltrative growth of these tumors. The aim of this study is to present our data achieved with an aggressive multimodality treatment. METHODS: We retrospectively reviewed our clinical database. All patients with histologically proven intramedullary spinal cord glioblastoma treated in our department were included in this study...
October 21, 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27770280/comparative-effectiveness-of-radiotherapy-with-vs-without-temozolomide-in-older-patients-with-glioblastoma
#20
Nils D Arvold, Matthew Cefalu, Yun Wang, Corwin Zigler, Deborah Schrag, Francesca Dominici
It is unknown whether the addition of temozolomide (TMZ) to radiotherapy (RT) is associated with improved overall survival (OS) among older glioblastoma patients. We performed a retrospective cohort SEER-Medicare analysis of 1652 patients aged ≥65 years with glioblastoma who received ≥10 fractions of RT from 2005 to 2009, or from 1995 to 1999 before TMZ was available. Three cohorts were assembled based on diagnosis year and treatment initiated within 60 days of diagnosis: (1) 2005-2009 and TMZ/RT, (2) 2005-2009 and RT only, or (3) 1995-1999 and RT only...
October 21, 2016: Journal of Neuro-oncology
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