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Zhongrun Qian, Sunhai Zhou, Zhiyi Zhou, Xi Yang, Shuanlin Que, Jin Lan, Yongming Qiu, Yingying Lin
Temozolomide (TMZ), as a kind of alkylating agent, is widely utilized for the treatment of glioblastoma (GBM). However, temozolomide resistance (TR) often develops quickly and results in tumor recurrence and poor outcome. Recent advances have demonstrated that miRNAs exert critical roles in chemoresistance. Downregulation of miR‑146b‑5p promotes glioma cell proliferation, reduces apoptosis, and correlates with poor survival of patients. Nonetheless, the function of miR‑146b‑5p in temozolomide resistance remains unclear...
September 19, 2017: Oncology Reports
Qi Liu, Yajun Xue, Qingshan Chen, Huairui Chen, Xiaofei Zhang, Leiping Wang, Cong Han, Shuanglin Que, Meiqing Lou, Jin Lan
Temozolomide (TMZ) is commonly used in glioblastoma (GBM) chemotherapy. However, a great challenge for TMZ treatment is the rapid development of resistance and subsequent tumor recurrence and poor outcome. In the present study we established TMZ-resistant GBM cells (U87-TR and U251-TR) and found that the expression of PomGnT1 was significantly upregulated in TMZ-resistant GBM cells compared with the TMZ-sensitive counterparts. Furthermore, overexpression of PomGnT1 in U87-MG and U251-MG cells led to increased IC50 values for TMZ and reduced apoptosis of cells...
September 19, 2017: Oncology Reports
Delphine Garnier, Brian Meehan, Thomas Kislinger, Paul Daniel, Ankit Sinha, Bassam Abdulkarim, Ichiro Nakano, Janusz Rak
Background: Glioblastoma (GBM) is almost invariably fatal due to failure of standard therapy. The relapse of GBM following surgery, radiation and systemic temozolomide (TMZ) is attributed to the ability of glioma stem cells (GSCs) to survive, evolve and repopulate the tumor mass, events on which therapy exerts a poorly understood influence. Methods: Here we explore the molecular and cellular evolution of TMZ resistance as it emerges in vivo (xenograft models) in a series of human GSCs with either proneural (PN) or mesenchymal (MES) molecular characteristics...
July 28, 2017: Neuro-oncology
Pierina Navarria, Federico Pessina, Stefano Tomatis, Riccardo Soffietti, Marco Grimaldi, Egesta Lopci, Arturo Chiti, Antonella Leonetti, Alessandra Casarotti, Marco Rossi, Luca Cozzi, Anna Maria Ascolese, Matteo Simonelli, Simona Marcheselli, Armando Santoro, Elena Clerici, Lorenzo Bello, Marta Scorsetti
BACKGROUND: The current standard of care for newly diagnosed glioblastoma (GBM) is surgical resection, followed by radiation therapy (RT) with concurrent and adjuvant temozolomide chemotherapy (TMZ-CHT). The patients outcome is still poor. In this study we evaluated hypofractionated radiation therapy (HFRT), instead of standard fractionated radiation therapy, with concomitant and adjuvant TMZ chemotherapy, in terms of safety and effectiveness. METHODS: Patients with newly diagnosed GBM, Karnofsky performance scale (KPS) ≥70, and tumor up to 10 cm underwent maximal feasible surgical resection were treated...
September 15, 2017: Oncotarget
Quentin Séry, Marion Rabé, Lisa Oliver, François M Vallette, Catherine Gratas
Temozolomide (TMZ) is the main chemotherapeutic agent used for treating newly diagnosed Glioblastoma Multiforme (GBM), the most frequent malignant brain tumors in adults. This alkylating agent induces DNA double strand breaks (DSBs) which in turn lead to apoptosis by activating the Bcl-2 controlled mitochondrial pathway. However, GBM invariably recur as tumors become resistant to TMZ. We investigated the implication of EGFR ligands in this resistance and we found that the pro Heparin Binding Epidermal Growth Factor (proHB-EGF) expression is linked to the early response to TMZ in human glioma cell lines...
September 29, 2017: Biochemical and Biophysical Research Communications
Kalpalata Tripathy, Bidyutprava Das, Ajit Kumar Singh, Aparajita Misra, Sanjib Misra, Sudhansu Sekhar Misra
INTRODUCTION: Glioblastoma Multiforme (GBM) is the most aggressive glial tumour with hallmark characteristics of rampant proliferation of glial cells along with high pleomorphism, necrosis, endothelial proliferation and high MIB-1 labeling index (cell proliferation marker). These tumours are managed by surgery followed by Radiotherapy (RT), Chemotherapy (CT) and adjuvant CT Temozolomide (TMZ). AIM: To evaluate Epidermal Growth Factor Receptor (EGFR) protein expression in GBM patients...
August 2017: Journal of Clinical and Diagnostic Research: JCDR
Sylvie Berthier, Josiane Arnaud, Pierre Champelovier, Edwige Col, Catherine Garrel, Cécile Cottet, Jean Boutonnat, François Laporte, Patrice Faure, Florence Hazane-Puch
Glioblastoma (GBM) is the most common type of primary tumor of the central nervous system with a poor prognosis, needing the development of new therapeutic drugs. Few studies focused on sodium selenite (SS) effects in cancer cells cultured as multicellular tumor spheroids (MCTS or 3D) closer to in vivo tumor. We investigated SS anticancer effects in three human GBM cell lines cultured in 3D: LN229, U87 (O(6)-methyguanine-DNA-methyltransferase (MGMT) negative) and T98G (MGMT positive). SS absorption was evaluated and the cytotoxicity of SS and temozolomide (TMZ), the standard drug used against GBM, were compared...
December 2017: Journal of Trace Elements in Medicine and Biology
Francesco Pasqualetti, Alessandra Gonnelli, Martina Cantarella, Durim Delishaj, Alessandro Molinari, Valerio Ortenzi, Francesco Carbone, Sabrina Montrone, Stefano Ursino, Sara Franceschi, Riccardo Morganti, Paola Orlandi, Teresa Di Desidero, Chiara Maria Mazzanti, Katia Zavaglia, Antonio Giuseppe Naccarato, Guido Bocci, Fabiola Paiar
Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults and, despite recent advances, the prognosis for this cancer remains dismal. The aims of this study were to test the influence of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms on progression free survival (PFS) and overall survival (OS) in GBM patients treated with radiotherapy (RT) and temozolomide (TMZ). Fifty GBM patients treated with upfront radio-chemotherapy (RT 60 Gy/30 sessions; TMZ 75 mg/m(2) during RT and 200 mg/m(2) days 1 → 5 every 28 days) were enrolled...
September 30, 2017: Investigational New Drugs
Feng Jin, Guang-Kui Han, Hao Zhang, Ran Zhang, Gen-Hua Li, Song Feng, Xian-Yun Qin, Ling-Sheng Kong, Quan-Min Nie, Hua-Rong Li, Lei Zhao
This study aims to determine the difference in the inhibitory effect of temozolomide (TMZ) on TJ905 glioma cells and stem cells. TJ905 cancer stem cells were isolated. Livin is a member of the inhibitor of apoptosis protein family. The TJ905 cells and cancer stem cells were transfected with a Livin-shRNA and negative-shRNA, respectively, and then treated with TMZ. At 48 h post-transfection, a cell counting kit 8 assay, flow cytometry, and real-time qPCR were performed to detect cell proliferation, the cell cycle, and the expression of the Caspase-3, -7, and -9 mRNAs, respectively...
2017: Frontiers in Neurology
Si-di Xie, Zi-Yang Chen, Hai Wang, Min-Yi He, Yun-Tao Lu, Bing-Xi Lei, He-Zhen Li, Ya-Wei Liu, Song-Tao Qi
OBJECTIVE: To investigate the role of microtubule-actin crosslinking factor 1 (MACF1) in the response of glioma cells to temozolomide (TMZ). METHODS: TMZ was applied to a human gliomablastoma cell line (U87) and changes in the protein expression and cellular localization were determined with Western blot, RT-PCR, and immunofluorescence. The responses of the cells with MACF1 expression knockdown by RNA interference to TMZ were assessed. TMZ-induced effects on MACF1 expression were also assessed by immunohistochemistry in a nude mouse model bearing human glioblastoma xenografts...
September 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Sani H Kizilbash, Shiv K Gupta, Kenneth Chang, Ryo Kawashima, Karen E Parrish, Brett L Carlson, Katrina K Bakken, Ann C Mladek, Mark A Schroeder, Paul A Decker, Gaspar J Kitange, Yuqiao Shen, Ying Feng, Andrew A Protter, William F Elmquist, Jann N Sarkaria
Poly (ADP-ribose) polymerase PARP inhibitors, including talazoparib (TAL), potentiate temozolomide (TMZ) efficacy in multiple tumor types, however TAL-mediated sensitization has not been evaluated in orthotopic glioblastoma (GBM) models. This study evaluates TAL ± TMZ in clinically relevant GBM models. TAL at 1-3 nmol/L sensitized T98G, U251 and GBM12 cells to TMZ, and enhanced DNA damage signaling and G2/M arrest in vitro. In vivo cyclical therapy with TAL (0.15 mg/kg twice daily) combined with low dose TMZ (5 mg/kg daily) was well tolerated...
September 25, 2017: Molecular Cancer Therapeutics
Heng Liao, Lijie Bi, Jun Wei, Xin Song
Cytostatic antineoplastic drugs are considered carcinogenic and mutagenic risk factors for health workers who are occupationally exposed to them; however, the molecular mechanisms underlying these effects remain to be elucidated. Therefore, the present study aimed to investigate the underlying mechanisms of antineoplastic drugs‑induced apoptosis of peripheral blood lymphocytes (PBLs) obtained from oncology nurses handling antineoplastic drugs. A microRNA (miRNA/miR) polymerase chain reaction (PCR) array was performed to analyze the expression levels of miRNAs in the PBLs from 3 trained nurses occupationally exposed to antineoplastic drugs...
September 22, 2017: Molecular Medicine Reports
Kwang-Yu Chang, Chih-Ta Huang, Tsung-I Hsu, Che-Chia Hsu, Jr-Jiun Liu, Cheng-Keng Chuang, Jan-Jong Hung, Wen-Chang Chang, Kelvin K Tsai, Jian-Ying Chuang
It has been suggested that stress stimuli from the microenvironment maintain a subset of tumor cells with stem-like properties, including drug resistance. Here, we investigate whether Sp1, a stress-responsive factor, regulates stemness gene expression and if its inhibition sensitizes cancer cells to chemotherapy. Hydrogen peroxide- and serum deprivation-induced stresses were performed in glioblastoma (GBM) cells and patient-derived cells, and the effect of the Sp1 inhibitor mithramycin A (MA) on these stress-induced stem cells and temozolomide (TMZ)-resistant cells was evaluated...
November 4, 2017: Biochemical and Biophysical Research Communications
Bin Jiang, Xueqing Lun, Xiaoguang Hao, Yihua Wang, Xin Yin, Dezhang Huang, Wei He, Zhigang Wang
BACKGROUND: Malignant glioma still has a poor prognosis and remains incurable. Although temozolomide (TMZ) has demonstrated antitumor activity, its use recently has been halted because of some patients' resistance to this drug. New treatments are desperately needed. An oncolytic virus (virotherapy) is being developed as a novel cancer therapy. We have previously reported that recombinant Vesicular Stomatitis Virus (VSV-ΔM51) and double deleted Vaccinia Virus (vvDD) infected and killed glioma cell lines in vitro and prolonged survival in animal glioma models...
September 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Lin Shi, Hongyuan Li, Yang Zhan
The present study evaluated the retinoic acid (RA) enhancement of temozolomide (TMZ) effects on the human glioma cells U251 and explored its underlying molecular mechanism. The cell growth was detected using the MTT assay and the cell cycle was assessed by flow cytometry. Cell apoptosis was analyzed by Annexin V/propidium iodide staining, and the cell morphology was evaluated using transmission electron microscopy (TEM). Additionally, reverse transcription-PCR and western blot analysis were applied to detect the mRNA and protein levels...
September 2017: Oncology Letters
Chung-Yin Lin, Rui-Jin Li, Chiung-Yin Huang, Kuo-Chen Wei, Pin-Yuan Chen
Convection-enhanced delivery (CED) is a promising technique for the delivery of drugs directly into the central nervous system (CNS) and, more specifically, the brain. CED can increase drug concentration within a brain tumor, thereby improving the therapeutic efficacy and limiting the systemic toxicity of tumoricidal agents. In this study, we evaluated a drug-liposome construct in vitro and in vivo using U87 tumor-bearing nude mice. Dipalmitoylphosphatidylcholine (DPPC)-based liposomes were designed to deliver a lipophilic temozolomide (TMZ) formulation (LipoTMZ)...
September 15, 2017: Journal of Drug Targeting
Natalia M Leguisamo, Helena C Gloria, Antonio N Kalil, Talita V Martins, Daniel B Azambuja, Lisiane B Meira, Jenifer Saffi
Colorectal cancer (CRC) is prevalent worldwide, and treatment often involves surgery and genotoxic chemotherapy. DNA repair mechanisms, such as base excision repair (BER) and mismatch repair (MMR), may not only influence tumour characteristics and prognosis but also dictate chemotherapy response. Defective MMR contributes to chemoresistance in colorectal cancer. Moreover, BER affects cellular survival by repairing genotoxic base damage in a process that itself can disrupt metabolism. In this study, we characterized BER and MMR gene expression in colorectal tumours and the association between this repair profile with patients' clinical and pathological features...
August 15, 2017: Oncotarget
Alexander S G Micko, Adelheid Wöhrer, Romana Höftberger, Greisa Vila, Christine Marosi, Engelbert Knosp, Stefan Wolfsberger
PURPOSE: Knowledge of biological behavior is crucial for clinical management of functioning pituitary macroadenomas. For recurrent cases unresponsive to standard treatment, temozolomide (TMZ) has been used as a therapeutic alternative. MGMT (O6-methyl-guanine-DNA methyltransferase) and MSH6 (mutS homolog 6) immunoexpression have been linked to the response to TMZ treatment and MGMT immunoexpression has been additionally linked to early recurrence of non-functioning pituitary adenomas...
September 12, 2017: Pituitary
Lixia Wang, Jingna Su, Zhe Zhao, Yingying Hou, Xuyuan Yin, Nana Zheng, Xiuxia Zhou, Jingzhe Yan, Jun Xia, Zhiwei Wang
Emerging evidence has demonstrated that microRNAs (miRNA) play a critical role in chemotherapy-induced epithelial-mesenchymal transition (EMT) in glioma. However, the underlying mechanism of chemotherapy-triggered EMT has not been fully understood. In the current study, we determined the role of miR-26b in regulation of EMT in stable temozolomide (TMZ)-resistant (TR) glioma cells, which have displayed mesenchymal features. Our results illustrated that miR-26b was significantly downregulated in TR cells. Moreover, ectopic expression of miR-26b by its mimics reversed the phenotype of EMT in TR cells...
October 18, 2017: Cell Cycle
Anna Angelousi, Gregory Kaltsas, Anna Koumarianou, Martin O Weickert, Ashley Grossman
The majority of neuroendocrine tumours (NETs) are well-differentiated tumours that follow an indolent course, in contrast to a minority of poorly differentiated neuroendocrine carcinomas (NECs) which exhibit an aggressive course and assocaited with an overall short survival. Although surgery is the only curative treatment for NETs it is not always feasible,necessitating the application of other therapies including chemotherapy. Streptozotocin (STZ)-based regimens have long been used for advanced or metastatic well-to-moderately differentiated (G1-G2) NETs, especially those originating from the pancreas (pNETs)...
September 11, 2017: Reviews in Endocrine & Metabolic Disorders
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