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https://www.readbyqxmd.com/read/28342984/hdac4-and-hdac6-sustain-dna-double-strand-break-repair-and-stem-like-phenotype-by-promoting-radioresistance-in-glioblastoma-cells
#1
Francesco Marampon, Francesca Megiorni, Simona Camero, Clara Crescioli, Heather P McDowell, Roberta Sferra, Antonella Vetuschi, Simona Pompili, Luca Ventura, Francesca De Felice, Vincenzo Tombolini, Carlo Dominici, Roberto Maggio, Claudio Festuccia, Giovanni Luca Gravina
The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investigated. We found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. Retrospective clinical data analysis demonstrated that high-intensity HDAC4 and/or HDAC6 immunostaining was predictive of poor clinical outcome. In vitro experiments revealed that short hairpin RNA-mediated silencing of HDAC4 or HDAC6 radiosensitized U87MG and U251MG GBM cell lines by promoting DNA double-strand break (DSBs) accumulation and by affecting DSBs repair molecular machinery...
March 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28340412/discovery-of-2-substituted-1h-benzo-d-immidazole-4-carboxamide-derivatives-as-novel-poly-adp-ribose-polymerase-1-inhibitors-with-in%C3%A2-vivo-anti-tumor-activity
#2
Jie Zhou, Ming Ji, Zhixiang Zhu, Ran Cao, Xiaoguang Chen, Bailing Xu
Novel 1H-benzo[d]immidazole-4-carboxamide derivatives bearing five-membered or six-membered N-heterocyclic moieties at the 2-position were designed and synthesized as PARP-1 inhibitors. Structure-activity relationships were conducted and led to a number of potent PARP-1 inhibitors having IC50 values in the single or double digit nanomolar level. Some potent PARP-1 inhibitors also had similar inhibitory activities against PARP-2. Among all the synthesized compounds, compound 10a and 11e displayed strong potentiation effects on temozolomide (TMZ) in MX-1 cells (PF50 = 7...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340188/commentary-on-phase-iii-randomized-study-of-radiation-and-temozolomide-versus-radiation-and-nitrosourea-therapy-for-anaplastic-astrocytoma-results-of-nrg-oncology-rtog-9813
#3
https://www.readbyqxmd.com/read/28336956/preclinical-development-of-a-humanized-neutralizing-antibody-targeting-hgf
#4
Hyori Kim, Sung Hee Hong, Jung Yong Kim, In-Chull Kim, Young-Whan Park, Song-Jae Lee, Seong-Won Song, Jung Ju Kim, Gunwoo Park, Tae Min Kim, Yun-Hee Kim, Jong Bae Park, Junho Chung, In-Hoo Kim
Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336375/tumortropic-adipose-derived-stem-cells-carrying-smart-nanotherapeutics-for-targeted-delivery-and-dual-modality-therapy-of-orthotopic-glioblastoma
#5
Wen-Chia Huang, I-Lin Lu, Wen-Hsuan Chiang, Yi-Wen Lin, Yuan-Chung Tsai, Hsin-Hung Chen, Chien-Wen Chang, Chi-Shiun Chiang, Hsin-Cheng Chiu
Chemotherapy is typically used to treat malignant brain tumors, especially for the tumors in surgically inaccessible areas. However, owing to the existence of blood-brain barrier (BBB), the tumor accumulation and therapeutic efficacy of clinical therapeutics is still of great concerns. To this end, we present herein a prominent therapeutic strategy adopting adipose-derived stem cells (ADSCs) capable of carrying nanotherapeutic payloads selectively toward brain tumors for thermo/chemotherapy. The nanoparticle (NP) payload was obtained from co-assembly of poly(γ-glutamic acid-co-distearyl γ-glutamate) with poly(lactic-co-glycolic acid), paclitaxel (PTX), and oleic acid-coated superparamagnetic iron oxide NPs in aqueous solution...
March 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28332226/mir-223-pax6-axis-regulates-glioblastoma-stem-cell-proliferation-and-the-chemo-resistance-to-tmz-via-regulating-pi3k-akt-pathway
#6
Bai-Sheng Huang, Qi-Zhi Luo, Yang Han, Dong Huang, Qing-Ping Tang, Li-Xiang Wu
Chemotherapy is a standard strategy for glioma, while chemoresistance remains a major therapeutic challenge in current clinical practice. Our present study was aimed to determine whether inhibition of the miR-223/ paired box 6 (PAX6) pathway could increase the sensitivity of glioma to Temozolomide. An elevated level of miR-223 was observed in glioma tissues. Exogenous miR-223 promoted cell survival when exposed to Temozolomide (TMZ), while miR-223 inhibition could reverse this process. The RNA and protein levels of PAX6 were significantly decreased by exogenous miR-223, and the 3'-untranslated region of PAX6 was shown to be a target of miR-223...
March 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28332000/neutrophil-lymphocyte-ratio-dynamics-during-concurrent-chemo-radiotherapy-for-glioblastoma-is-an-independent-predictor-for-overall-survival
#7
Matthew Mason, Catherine Maurice, Mairead G McNamara, Minh Thi Tieu, Zarnie Lwin, Barbara-Ann Millar, Cynthia Menard, Normand Laperriere, Michael Milosevic, Eshetu G Atenafu, Warren Mason, Caroline Chung
Elevated neutrophil-lymphocyte ratio (NLR) may predict worse outcomes in cancer, including glioblastoma (GBM). This study assessed whether change in NLR during focal radiotherapy and concomitant temozolomide (RT-TMZ) provides further prognostic information. This was a retrospective review of patients treated with RT-TMZ for histologically confirmed GBM from January 2004 to September 2010. Variables assessed included age, ECOG performance status (PS), dexamethasone use and extent of surgery. Hematological results were collected at baseline, during and 4 weeks post RT-TMZ...
March 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28328619/evaluation-of-o6-methylguanine-dna-methyltransferase-as-a-predicting-factor-of-response-to-temozolomide-based-chemotherapy-in-well-differentiated-metastatic-pancreatic-neuroendocrine-tumors
#8
Paul Girot, Clotilde Dumars, Jean-François Mosnier, Léa Muzellec, Hélène Senellart, Fanny Foubert, François-Xavier Caroli-Bosc, Estelle Cauchin, Nicolas Regenet, Tamara Matysiak-Budnik, Yann Touchefeu
OBJECTIVE: Temozolomide (TMZ) is an alkylating agent frequently used in well-differentiated metastatic pancreatic neuroendocrine tumors (PNETs) with very variable responses. O-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme whose loss of expression has been suggested to be predictive of response to TMZ in various human tumors. We evaluated the predictive value of MGMT status, assessed by immunohistochemistry (IHC) and methylation-specific PCR (MS-PCR), in well-differentiated metastatic PNETs treated by a TMZ-based chemotherapy...
March 21, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28324304/management-of-elderly-patients-with-glioblastoma
#9
REVIEW
Patrick Roth, Dorothee Gramatzki, Michael Weller
PURPOSE OF REVIEW: Glioblastoma represents one of the major challenges in neurooncology and approximately half of the patients are 60 years or older. We summarize the particular situation of elderly glioblastoma patients with a focus on therapeutic considerations. RECENT FINDINGS: Favorable molecular markers such as mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes are virtually absent in glioblastomas in elderly patients. Treatment options are similar to the situation in young patients and comprise surgical resection, radiation therapy, and alkylating chemotherapy...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28320338/the-allosteric-akt-inhibitor-mk2206-shows-a-synergistic-interaction-with-chemotherapy-and-radiotherapy-in-glioblastoma-spheroid-cultures
#10
Ravi S Narayan, Carlos A Fedrigo, Eelke Brands, Rogier Dik, Lukas J A Stalpers, Brigitta G Baumert, Ben J Slotman, Bart A Westerman, Godefridus J Peters, Peter Sminia
BACKGROUND: Glioblastoma multiforme (GBM) is the most common, invasive and deadly primary type of malignant brain tumor. The Phosphatidylinositol-3-Kinase/AKT (PI3K/AKT) pathway is highly active in GBM and has been associated with increased survival and resistance to therapy. The aim of this study is to investigate the effects of AKT inhibition in combination with the current standard of care which consists of irradiation and temozolomide (TMZ) on human malignant glioma cells growing adherent and as multicellular spheroids in vitro...
March 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#11
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/28315063/the-effect-of-regadenoson-on-the-integrity-of-the-human-blood-brain-barrier-a-pilot-study
#12
Sadhana Jackson, Richard T George, Martin A Lodge, Anna Piotrowski, Richard L Wahl, Sachin K Gujar, Stuart A Grossman
Regadenoson is an FDA approved adenosine receptor agonist which increases blood-brain barrier (BBB) permeability in rodents. Regadenoson is used clinically for pharmacologic cardiac stress testing using SPECT or CT imaging agents that do not cross an intact BBB. This study was conducted to determine if standard doses of regadenoson transiently disrupt the human BBB allowing higher concentrations of systemically administered imaging agents to enter the brain. Patients without known intracranial disease undergoing clinically indicated pharmacologic cardiac stress tests were eligible for this study...
March 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28314386/veliparib-in-combination-with-radiotherapy-for-the-treatment-of-mgmt-unmethylated-glioblastoma
#13
Toni Rose Jue, Kyoko Nozue, Ashleigh J Lester, Swapna Joshi, Lisette B W Schroder, Shane P Whittaker, Sheri Nixdorf, Robert W Rapkins, Mustafa Khasraw, Kerrie L McDonald
BACKGROUND: The O (6) -methylguanine methyltransferase (MGMT) gene is frequently unmethylated in patients with glioblastoma (GBM), rendering them non-responsive to the standard treatment regime of surgery followed by concurrent radiotherapy (RT) and temozolomide. Here, we investigate the efficacy of adding a PARP inhibitor, veliparib, to radiotherapy to treat MGMT unmethylated GBM. METHODS: The inhibition of PARP with veliparib (ABT-888), a potent and orally bioavailable inhibitor in combination with RT was tested on a panel of patient derived cell lines (PDCLs) and patient-derived xenografts (PDX) models generated from GBM patients with MGMT unmethylated tumors...
March 17, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28302331/novel-recursive-partitioning-analysis-classification-for-newly-diagnosed-glioblastoma-a-multi-institutional-study-highlighting-the-mgmt-promoter-methylation-and-idh1-gene-mutation-status
#14
Chan Woo Wee, Eunji Kim, Nalee Kim, In Ah Kim, Tae Min Kim, Yu Jung Kim, Chul-Kee Park, Jin Wook Kim, Chae-Yong Kim, Seung Hong Choi, Jae Hyoung Kim, Sung-Hye Park, Gheeyoung Choe, Soon-Tae Lee, Jong Hee Chang, Se Hoon Kim, Chang-Ok Suh, Il Han Kim
BACKGROUND AND PURPOSE: To refine the recursive partitioning analysis (RPA) classification for glioblastoma incorporating the MGMT methylation and IDH1 mutation status. METHODS AND MATERIALS: Three-hundred forty patients were treated with radiotherapy plus concurrent and adjuvant temozolomide in three tertiary-referral hospitals. MGMT methylation and IDH1 mutation status were available in all patients. Methylation of the MGMT (MGMTmeth) and mutation of IDH1 (IDH1mut) were observed in 42...
March 13, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28301347/outcomes-for-anaplastic-glioma-treated-with-radiation-therapy-with-or-without-concurrent-temozolomide
#15
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/28299344/advances-in-immunotherapy-for-glioblastoma-multiforme
#16
REVIEW
Boyuan Huang, Hongbo Zhang, Lijuan Gu, Bainxin Ye, Zhihong Jian, Creed Stary, Xiaoxing Xiong
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients with GBM have poor outcomes, even with the current gold-standard first-line treatment: maximal safe resection combined with radiotherapy and temozolomide chemotherapy. Accumulating evidence suggests that advances in antigen-specific cancer vaccines and immune checkpoint blockade in other advanced tumors may provide an appealing promise for immunotherapy in glioma. The future of therapy for GBM will likely incorporate a combinatorial, personalized approach, including current conventional treatments, active immunotherapeutics, plus agents targeting immunosuppressive checkpoints...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28298550/limited-role-for-extended-maintenance-temozolomide-for-newly-diagnosed-glioblastoma
#17
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/28298017/transtentorial-dissemination-of-optic-nerve-glioblastoma-case-report
#18
Panagiotis Mastorakos, Michael A Hays, James P Caruso, Ching-Jen Chen, Dale Ding, Davis G Taylor, M Beatriz Lopes, Mark E Shaffrey
Optic nerve glioblastoma is a rare entity that usually presents with rapidly progressive vision loss, which eventually results in blindness and, ultimately, death. As with malignant gliomas in other anatomical locations, local recurrence is common. Isolated rapid changes in vision, atypical neuroimaging findings, and the rarity of optic nerve glioblastoma may render diagnosis challenging and, thus, delay treatment. The authors present a case of optic nerve glioblastoma that was treated with subtotal resection followed by adjuvant radiation therapy and temozolomide...
February 17, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28297578/%C3%AE-elemene-selectively-inhibits-the-proliferation-of-glioma-stem-like-cells-through-the-downregulation-of-notch1
#19
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/28296618/short-course-radiation-plus-temozolomide-in-elderly-patients-with-glioblastoma
#20
James R Perry, Normand Laperriere, Christopher J O'Callaghan, Alba A Brandes, Johan Menten, Claire Phillips, Michael Fay, Ryo Nishikawa, J Gregory Cairncross, Wilson Roa, David Osoba, John P Rossiter, Arjun Sahgal, Hal Hirte, Florence Laigle-Donadey, Enrico Franceschi, Olivier Chinot, Vassilis Golfinopoulos, Laura Fariselli, Antje Wick, Loic Feuvret, Michael Back, Michael Tills, Chad Winch, Brigitta G Baumert, Wolfgang Wick, Keyue Ding, Warren P Mason
Background Glioblastoma is associated with a poor prognosis in the elderly. Survival has been shown to increase among patients 70 years of age or younger when temozolomide chemotherapy is added to standard radiotherapy (60 Gy over a period of 6 weeks). In elderly patients, more convenient shorter courses of radiotherapy are commonly used, but the benefit of adding temozolomide to a shorter course of radiotherapy is unknown. Methods We conducted a trial involving patients 65 years of age or older with newly diagnosed glioblastoma...
March 16, 2017: New England Journal of Medicine
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