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temozolomide

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https://www.readbyqxmd.com/read/29779087/down-regulation-of-mdr1-by-ad-dkk3-via-akt-nf%C3%AE%C2%BAb-pathways-augments-the-anti-tumor-effect-of-temozolomide-in-glioblastoma-cells-and-a-murine-xenograft-model
#1
Toshitaka Fujihara, Yoshifumi Mizobuchi, Kohei Nakajima, Teruyoshi Kageji, Kazuhito Matsuzaki, Keiko T Kitazato, Ryotaro Otsuka, Keijiro Hara, Hideo Mure, Toshiyuki Okazaki, Kazuyuki Kuwayama, Shinji Nagahiro, Yasushi Takagi
BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1...
May 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29777945/patterns-of-care-and-outcomes-of-chemoradiation-versus-radiation-alone-for-mgmt-promoter-unmethylated-glioblastoma
#2
Anna Lee, Nikita Malakhov, Niki Sheth, Arthur Wang, Peter Han, David Schreiber
OBJECTIVE: The recommended treatment for O6 -methylguanine-DNA methyltransferase (MGMT) promoter unmethylated glioblastoma (GBM) is radiation therapy with concurrent/adjuvant temozolomide (TMZ). However, it is well known that the clinical benefit from TMZ is lower in these patients. We sought to analyze patterns of care and outcomes of chemoradiation versus radiation alone in this cohort using a large, hospital database. PATIENTS AND METHODS: Patients diagnosed with MGMT promoter unmethylated GBM from 2010 to 2012 who received radiation (RT) or chemoradiation (CRT) were identified in the National Cancer Database...
May 16, 2018: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29777137/enhanced-efficacy-of-combined-temozolomide-and-bromodomain-inhibitor-therapy-for-gliomas-using-targeted-nanoparticles
#3
Fred C Lam, Stephen W Morton, Jeffrey Wyckoff, Tu-Lan Vu Han, Mun Kyung Hwang, Amanda Maffa, Elena Balkanska-Sinclair, Michael B Yaffe, Scott R Floyd, Paula T Hammond
Effective treatment for glioblastoma (GBM) is limited by the presence of the blood-brain barrier (BBB) and rapid resistance to single agent therapies. To address these issues, we developed a transferrin-functionalized nanoparticle (Tf-NP) that can deliver dual combination therapies. Using intravital imaging, we show the ability of Tf-NPs to traverse intact BBB in mice as well as achieve direct tumor binding in two intracranial orthotopic models of GBM. Treatment of tumor-bearing mice with Tf-NPs loaded with temozolomide and the bromodomain inhibitor JQ1 leads to increased DNA damage and apoptosis that correlates with a 1...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29776835/the-combination-of-mannitol-and-temozolomide-increases-the-effectiveness-of-stem-cell-treatment-in-a-chronic-stroke-model
#4
Chunggab Choi, Hye Min Kim, Jeeheun Shon, Jiae Park, Hyeong-Taek Kim, Suk Ho Kang, Seung-Hun Oh, Nam Keun Kim, Ok Joon Kim
BACKGROUND: The blood-brain barrier (BBB) presents a significant challenge to the therapeutic efficacy of stem cells in chronic stroke. Various methods have been developed to increase BBB permeability, but these are associated with adverse effects and are, therefore, not clinically applicable. We recently identified that combination drug treatment of mannitol and temozolomide improved BBB permeability in vitro. Here, we investigated whether this combination could increase the effectiveness of stem cell treatment in an animal model of chronic ischemic stroke...
May 15, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29775717/temozolomide-loaded-nano-lipid-based-chitosan-hydrogel-for-nose-to-brain-delivery-characterization-nasal-absorption-histopathology-and-cell-line-study
#5
Anam Khan, Mohd Aqil, Syed Sarim Imam, Abdul Ahad, Yasmin Sultana, Asgar Ali, Khalid Khan
The present study was designed to develop and optimize Temozolomide nano lipid chitosan gel delivery (TMZNLCHG) to target the brain through nasal route. The formulation was developed using chitosan as a gelling agent and Vit E: gelucire 44/14 blend as lipid. The formulations were evaluated for particle size, drug loading, morphology, drug release, nasal diffusion, cell line study, and histopathology study. The average particle size, PDI, %EE, loading, drug release, and % permeation were found to be 134 nm, 0...
May 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29774875/-clinical-efficacy-of-stereotactic-radiation-therapy-combined-with-temozolomide-on-recurrent-brain-glioma
#6
Huiping Zhao, Sha Liu, Chengchuan Jiang, Xiangjun Li, Sanyuan Tang
To investigate the clinical efficacy of stereotactic radiation therapy combined with temozolomide on recurrent glioma.
 Methods: A total of 36 patients with recurrent glioma were retrospectively analyzed and divided into a control group (n=12), who received stereotactic radiation therapy, and an experimental group (n=24), who received stereotactic radiation therapy plus temozolomide. The clinical efficacy and adverse reactions for the 2 groups were compared.
 Results: Total effective rate and local control rate for clinical treatment were 66...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29774132/natural-products-a-hope-for-glioblastoma-patients
#7
REVIEW
Raghupathy Vengoji, Muzafar A Macha, Surinder K Batra, Nicole A Shonka
Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29772755/temozolomide-enhances-triple-negative-breast-cancer-virotherapy-in-vitro
#8
Rodolfo Garza-Morales, Roxana Gonzalez-Ramos, Akiko Chiba, Roberto Montes de Oca-Luna, Lacey R McNally, Kelly M McMasters, Jorge G Gomez-Gutierrez
Triple-negative breast cancer (TNBC) is one of the most aggressive types of cancer, and treatment is limited to chemotherapy and radiation. Oncolytic virotherapy may be a promising approach to treat TNBC. However, oncolytic adenovirus (OAd)-based mono-therapeutic clinical trials have resulted in modest outcomes. The OAd potency could be increased by chemotherapy-induced autophagy, an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. In this study, the ability of alkylating agent temozolomide (TMZ)-induced autophagy to increase OAd replication and oncolysis in TNBC cells was evaluated...
May 17, 2018: Cancers
https://www.readbyqxmd.com/read/29765555/a-protein-folding-molecular-imaging-biosensor-monitors-the-effects-of-drugs-that-restore-mutant-p53-structure-and-its-downstream-function-in-glioblastoma-cells
#9
Ramasamy Paulmurugan, Rayhaneh Afjei, Thillai V Sekar, Husam A Babikir, Tarik F Massoud
Misfolding mutations in the DNA-binding domain of p53 alter its conformation, affecting the efficiency with which it binds to chromatin to regulate target gene expression and cell cycle checkpoint functions in many cancers, including glioblastoma. Small molecule drugs that recover misfolded p53 structure and function may improve chemotherapy by activating p53-mediated senescence. We constructed and optimized a split Renilla luciferase (RLUC) complementation molecular biosensor (NRLUC-p53-CRLUC) to determine small molecule-meditated folding changes in p53 protein...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765554/targeted-nanoparticle-delivery-of-therapeutic-antisense-micrornas-presensitizes-glioblastoma-cells-to-lower-effective-doses-of-temozolomide-in-vitro-and-in-a-mouse-model
#10
Meenakshi Malhotra, Thillai Veerapazham Sekar, Jeyarama S Ananta, Rammohan Devulapally, Rayhaneh Afjei, Husam A Babikir, Ramasamy Paulmurugan, Tarik F Massoud
Temozolomide (TMZ) chemotherapy for glioblastoma (GBM) is generally well tolerated at standard doses but it can cause side effects. GBMs overexpress microRNA-21 and microRNA-10b, two known oncomiRs that promote cancer development, progression and resistance to drug treatment. We hypothesized that systemic injection of antisense microRNAs (antagomiR-21 and antagomiR-10b) encapsulated in cRGD-tagged PEG-PLGA nanoparticles would result in high cellular delivery of intact functional antagomiRs, with consequent efficient therapeutic response and increased sensitivity of GBM cells to lower doses of TMZ...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765354/pituitary-directed-therapies-for-cushing-s-disease
#11
REVIEW
Fabienne Langlois, Jennifer Chu, Maria Fleseriu
Cushing's disease (CD) is caused by a pituitary corticotroph neuroendocrine tumor inducing uncontrolled hypercortisolism. Transsphenoidal surgery is the first-line treatment in most cases. Nonetheless, some patients will not achieve cure even in expert hands, others may not be surgical candidates and a significant percentage will experience recurrence. Many patients will thus require medical therapy to achieve disease control. Pharmacologic options to treat CD have increased in recent years, with an explosion in knowledge related to pathophysiology at the molecular level...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29763623/molecular-pathological-radiological-and-immune-profiling-of-non-brainstem-pediatric-high-grade-glioma-from-the-herby-phase-ii-randomized-trial
#12
Alan Mackay, Anna Burford, Valeria Molinari, David T W Jones, Elisa Izquierdo, Jurriaan Brouwer-Visser, Felice Giangaspero, Christine Haberler, Torsten Pietsch, Thomas S Jacques, Dominique Figarella-Branger, Daniel Rodriguez, Paul S Morgan, Pichai Raman, Angela J Waanders, Adam C Resnick, Maura Massimino, Maria Luisa Garrè, Helen Smith, David Capper, Stefan M Pfister, Thomas Würdinger, Rachel Tam, Josep Garcia, Meghna Das Thakur, Gilles Vassal, Jacques Grill, Tim Jaspan, Pascale Varlet, Chris Jones
The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8+ tumor-infiltrating lymphocytes, and longer survival with the addition of BEV...
May 14, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29761922/fm19g11-inhibits-o-6-methylguanine-dna-methyltransferase-expression-under-both-hypoxic-and-normoxic-conditions
#13
Chao-Guo You, Han-Song Sheng, Chao-Ran Xie, Nu Zhang, Xue-Sheng Zheng
FM19G11 is a small molecular agent that inhibits hypoxia-inducible factor-1-alpha (HIF-1α) and other signaling pathways. In this study, we characterized the modulating effects of FM19G11 on O6 -methylguanine DNA-methyltransferase (MGMT), the main regulator of temozolomide (TMZ) resistance in glioblastomas. This study included 2 MGMT-positive cell lines (GBM-XD and T98G). MGMT promoter methylation status, mRNA abundance, and protein levels were determined before and after FM19G11 treatment, and the roles of various signaling pathways were characterized...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29760590/evaluation-of-high-grade-astrocytoma-recurrence-patterns-after-radiotherapy-in-the-era-of-temozolomide-a-single-institution-experience
#14
Arno Lotar Cordova, Taynná Vernalha Rocha Almeida, Cintia Mara da Silva, Pedro Argolo Piedade, Cristiane Maria Almeida, Carlos Genesio Bezzera Lima, Carolina Dutra, Rafael Martins Ferreira, Marcelo Neves Linhares, Valeriy Denyak
Aim: Evaluating the recurrence patterns of high-grade astrocytomas in patients who were treated with radiotherapy (RT) plus temozolomide (TMZ). Background: The current literature suggests that reducing the margins added to the CTV does not significantly change the risk of recurrence and overall survival; thus, we decided to analyze our data and to examine the possibility of changing the adopted margins. Materials and methods: From February 2008 till September 2013, 55 patients were treated for high-grade astrocytomas, 20 patients who had been confirmed to have recurrence were selected for the present study...
May 2018: Reports of Practical Oncology and Radiotherapy
https://www.readbyqxmd.com/read/29759570/re-irradiation-as-salvage-treatment-in-recurrent-glioblastoma-a-comprehensive-literature-review-to-provide-practical-answers-to-frequently-asked-questions
#15
REVIEW
Silvia Scoccianti, Giulio Francolini, Giulio Alberto Carta, Daniela Greto, Beatrice Detti, Gabriele Simontacchi, Luca Visani, Muhammed Baki, Linda Poggesi, Pierluigi Bonomo, Monica Mangoni, Isacco Desideri, Stefania Pallotta, Lorenzo Livi
The primary aim of this review is to provide practical recommendations in terms of fractionation, dose, constraints and selection criteria to be used in the daily clinical routine. Based on the analysis of the literature reviewed, in order to keep the risk of severe side effects ≤3,5%, patients should be stratified according to the target volume. Thus, patients should be treated with different fractionation and total EQD2 (<12.5 ml: EQD2 < 65 Gy with radiosurgery; >12.5 ml and <35 ml: EQD2 < 50 Gy with hypofractionated stereotactic radiotherapy; >35 ml and <50 ml: EQD2 < 36 Gy with conventionally fractionated radiotherapy)...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29758196/temozolomide-combined-with-pd-1-antibody-therapy-for-mouse-orthotopic-glioma-model
#16
Bailing Dai, Na Qi, Junchao Li, Guilong Zhang
PURPOSE: Temozolomide (TMZ) is the most frequent adjuvant chemotherapy drug in gliomas. PDL1 expresses on various tumors, including gliomas, and anti-PD-1 antibodies have been approved for treating some tumors by FDA. This study was to evaluate the therapeutical potential of combined TMZ with anti-PD-1 antibody therapy for mouse orthotopic glioma model. METHODS: We performed C57BL/6 mouse orthotopic glioma model by stereotactic intracranial implantation of glioma cell line GL261, mice were randomly divided into four groups: (1) control group; (2) TMZ group; (3) anti-PD-1 antibody group; (4) TMZ combined with anti-PD-1 antibody group...
May 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29755901/emerging-cellular-therapies-for-glioblastoma-multiforme
#17
REVIEW
Paul J Choi, R Shane Tubbs, Rod J Oskouian
Glioblastoma multiforme (GBM) is the most common type of malignant primary brain cancer in adults. It is composed of highly malignant cells that display metastatic and angiogenic characteristics, making it resistant to current first-line chemotherapy with temozolomide, an alkylating agent. Despite many years of research, GBM remains poorly responsive to multiple available therapies, giving GBM patients, who receive the conventional combination of chemoradiotherapies and surgical resection, a dismal prognosis...
March 11, 2018: Curēus
https://www.readbyqxmd.com/read/29755294/inhibition-of-the-pi3k-but-not-the-mek-erk-pathway-sensitizes-human-glioma-cells-to-alkylating-drugs
#18
Bodo Haas, Veronika Klinger, Christina Keksel, Verena Bonigut, Daniela Kiefer, Julia Caspers, Julia Walther, Maria Wos-Maganga, Sandra Weickhardt, Gabriele Röhn, Marco Timmer, Roland Frötschl, Niels Eckstein
Background: Intrinsic chemoresistance of glioblastoma (GBM) is frequently owed to activation of the PI3K and MEK/ERK pathways. These signaling cascades are tightly interconnected however the quantitative contribution of both to intrinsic resistance is still not clear. Here, we aimed at determining the activation status of these pathways in human GBM biopsies and cells and investigating the quantitative impact of both pathways to chemoresistance. Methods: Receptor tyrosine kinase (RTK) pathways in temozolomide (TMZ) treatment naive or TMZ resistant human GBM biopsies and GBM cells were investigated by proteome profiling and immunoblotting of a subset of proteins...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29755109/regulated-intratumoral-expression-of-il-12-using-a-rheoswitch-therapeutic-system-%C3%A2-rts-%C3%A2-gene-switch-as-gene-therapy-for-the-treatment-of-glioma
#19
John A Barrett, Hongliang Cai, John Miao, Pranay D Khare, Paul Gonzalez, Jessica Dalsing-Hernandez, Geeta Sharma, Tim Chan, Laurence J N Cooper, Francois Lebel
The purpose of this study was to determine if localized delivery of IL-12 encoded by a replication-incompetent adenoviral vector engineered to express IL-12 via a RheoSwitch Therapeutic System® (RTS® ) gene switch (Ad-RTS-IL-12) administered intratumorally which is inducibly controlled by the oral activator veledimex is an effective approach for glioma therapy. Mice bearing 5-10-day-old intracranial GL-261 gliomas were intratumorally administered Ad-RTS-mIL-12 in which IL-12 protein expression is tightly controlled by the activator ligand, veledimex...
May 14, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29750673/quality-of-life-perception-cognitive-function-and-psychological-status-in-a-real-world-population-of-glioblastoma-patients-treated-with-radiotherapy-and-temozolomide-a-single-center-prospective-study
#20
Giuseppe Lombardi, Eleonora Bergo, Paola Del Bianco, Luisa Bellu, Ardi Pambuku, Mario Caccese, Leonardo Trentin, Vittorina Zagonel
BACKGROUND: Health-related quality of life (HRQoL), cognitive function, and psychological status represent an important focus during the treatment of glioblastoma patients. Nevertheless, few randomized, prospective clinical trials have analyzed these factors, and very little is known in the real-clinical world. We evaluated these characteristics in glioblastoma patients treated with standard first-line therapy outside clinical trials. PATIENTS AND METHODS: In total, 111 newly, histologically diagnosed glioblastoma patients treated at our oncology center with radiotherapy and temozolomide were prospectively enrolled...
May 10, 2018: American Journal of Clinical Oncology
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