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https://www.readbyqxmd.com/read/28731079/a-polymeric-temozolomide-nanocomposite-against-orthotopic-glioblastoma-xenograft-tumor-specific-homing-directed-by-nestin
#1
Suma Prabhu, Jayant Sastri Goda, Srinivas Mutalik, Bhabani Shankar Mohanty, Pradip Chaudhari, Sharada Rai, Nayanabhirama Udupa, Bola Sadashiva Satish Rao
The development of effective therapeutic strategies for glioblastoma faces challenges such as modulating the blood brain barrier (BBB) for drug influx and selectively targeting tumor cells. Nanocarrier drug delivery strategies are functionalized to enhance vascular permeability. We engineered superparamagnetic iron oxide nanoparticle (SPION) based polymeric nanocomposites (84.37 ± 12.37 nm / 101.56 ± 7.42 nm) embedding temozolomide (TMZ) targeted against glioblastoma by tagging an antibody against nestin, a stem cell marker, and transferrin / polysorbate-80 to permeate the BBB...
July 21, 2017: Nanoscale
https://www.readbyqxmd.com/read/28726172/combined-treatment-for-non-small-cell-lung-cancer-and-breast-cancer-patients-with-brain-metastases-with-whole-brain-radiotherapy-and-temozolomide-a-systematic-review-and-meta-analysis
#2
REVIEW
Jingru Tian, Yien Luo, Juanjuan Xiang, Jingqun Tang
Brain metastasis is the leading cause of death among advanced non-small cell lung cancer (NSCLC) and breast cancer patients. The standard treatment for brain metastases is radiotherapy. The combination of radiotherapy and chemotherapy has been tested. However, the management of brain metastases has yet to be successful. Here, we aimed to determine the efficacy and safety of whole brain radiotherapy (WBRT) alone or in combination with temozolomide (TMZ) in NSCLC and breast cancer patients with brain metastases...
July 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28718668/olea-europaea-leaf-extract-improves-the-efficacy-of-temozolomide-therapy-by-inducing-mgmt-methylation-and-reducing-p53-expression-un-glioblastoma
#3
Gulcin Tezcan, Berrin Tunca, Hilal Demirci, Ahmet Bekar, Mevlut Ozgur Taskapilioglu, Hasan Kocaeli, Unal Egeli, Gulsah Cecener, Sahsine Tolunay, Ozgur Vatan
Unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter leads to Temozolomide (TMZ) resistance in most of the glioblastoma multiforme (GBM) patients. We previously investigated the synergistic effect of Olea europaea leaf extract (OLE) on TMZ cytotoxicity through modulating microRNA expression. To date, knowledge about the effect of OLE on MGMT methylation is insufficient. The aim of the current study was to evaluate the potential modulating effect of OLE on the TMZ response of GBM tumors through MGMT methylation...
July 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28717885/risk-of-severe-acute-liver-injury-among-patients-with-brain-cancer-treated-with-temozolomide-a-nested-case-control-study-using-the-healthcore-integrated-research-database
#4
Vibha C A Desai, Scott C Quinlan, Anne C Deitz, Jinghua He, Crystal N Holick, Stephan Lanes
Temozolomide (TMZ) is used to treat adult patients with glioblastoma multiforme (GBM). Cases of hepatotoxicity have been reported among patients using TMZ. The objective of the study was to assess the relation, if any, between exposure to TMZ and serious acute liver injury (SALI). We used the HealthCore Integrated Research Database to perform a case-control study nested within a retrospective cohort of adult patients aged 18-100 years with at least two diagnoses of brain cancer anytime between 2006 and 2014...
July 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28717400/treatment-of-nras-mutated-advanced-or-metastatic-melanoma-rationale-current-trials-and-evidence-to-date
#5
REVIEW
Amélie Boespflug, Julie Caramel, Stephane Dalle, Luc Thomas
The disease course of BRAF (v-raf murine sarcoma viral oncogene homolog B1)-mutant melanoma has been drastically improved by the arrival of targeted therapies. NRAS (neuroblastoma RAS viral oncogene homolog)-mutated melanoma represents 15-25% of all metastatic melanoma patients. It currently does not have an approved targeted therapy. Metastatic patients receive immune-based therapies as first-line treatments, then cytotoxic chemotherapy like carboplatin/paclitaxel (C/P), dacarbazine (DTIC) or temozolomide (TMZ) as a second-line treatment...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28716484/the-anti-tumor-activity-of-the-stat3-inhibitor-stx-0119-occurs-via-promotion-of-tumor-infiltrating-lymphocyte-accumulation-in-temozolomide-resistant-glioblastoma-cell-line
#6
Yasuto Akiyama, Chizu Nonomura, Tadashi Ashizawa, Akira Iizuka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Akira Asai, Mamoru Ito, Yoshio Kiyohara, Ken Yamaguchi
STAT3 is considered to be a key molecule to mediating tumor-induced immunosuppression in various manners at tumor sites, by acting through immune-regulatory cytokines derived from the tumor cells. Specific anti-STAT3 inhibitors have been developed using nude mouse models transplanted with human tumor cells. However, mouse systems cannot accurately represent the human immune response induced by STAT3 inhibitors, and more humanized therapeutic model based on human immune cells and tumors are needed. In the present study, an immune-deficient NOG mouse with the deletion of both MHC-class I and class II genes, an MHC-double knockout mouse (dKO-NOG), was developed and used to establish humanized immunotherapeutic model...
July 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28714520/genomic-profiling-of-long-non-coding-rna-and-mrna-expression-associated-with-acquired-temozolomide-resistance-in-glioblastoma-cells
#7
Huijun Zeng, Ningbo Xu, Yanting Liu, Boyang Liu, Zhao Yang, Zhao Fu, Changlin Lian, Hongbo Guo
Temozolomide (TMZ) is an alkylating chemotherapeutic agent widely used in anti-glioma treatment. However, acquired TMZ resistance represents a major clinical challenge that leads to tumor relapse or progress. This study investigated the genomic profiles including long non-coding RNA (lncRNA) and mRNA expression associated with acquired TMZ resistance in glioblastoma (GBM) cells in vitro. The TMZ-resistant (TR) of GBM sub-cell lines were established through repetitive exposure to increasing TMZ concentrations in vitro...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28714013/glioblastoma-entities-express-subtle-differences-in-molecular-composition-and-response-to-treatment
#8
Joana Balça-Silva, Diana Matias, Anália Do Carmo, Luiz Gustavo Dubois, Ana Cristina Gonçalves, Henrique Girão, Nathalie Henriques Silva Canedo, Ana Helena Correia, Jorge Marcondes De Souza, Ana Bela Sarmento-Ribeiro, Maria Celeste Lopes, Vivaldo Moura-Neto
Glioblastoma (GBM) is a grade IV astrocytoma. GBM patients show resistance to chemotherapy such as temozolomide (TMZ), the gold standard treatment. In order to simulate the molecular mechanisms behind the different chemotherapeutic responses in GBM patients we compared the cellular heterogeneity and chemotherapeutic resistance mechanisms in different GBM cell lines. We isolated and characterized a human GBM cell line obtained from a GBM patient, named GBM11. We studied the GBM11 behaviour when treated with Tamoxifen (TMX) that, among other functions, is a protein kinase C (PKC) inhibitor, alone and in combination with TMZ in comparison with the responses of U87 and U118 human GBM cell lines...
July 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713019/glioma-sensitive-or-chemoresistant-to-temozolomide-differentially-modulate-macrophage-protumor-activities
#9
Juliana H Azambuja, Elita F da Silveira, Taíse R de Carvalho, Pathise S Oliveira, Simone Pacheco, Carlus T do Couto, Fátima T Beira, Francieli M Stefanello, Rosélia M Spanevello, Elizandra Braganhol
BACKGROUND: Glioblastomas are the most devastating brain tumor characterized by chemoresistance development and poor prognosis. Macrophages are a component of tumor microenvironment related to glioma malignancy. The relation among inflammation, innate immunity and cancer is accepted; however, molecular and cellular mechanisms mediating this relation and chemoresistance remain unresolved. OBJECTIVE: Here we evaluated whether glioma sensitive or resistant to temozolomide (TMZ) modulate macrophage polarization and inflammatory pathways associated...
July 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28708601/synergistic-and-targeted-therapy-with-a-procaspase-3-activator-and-temozolomide-extends-survival-in-glioma-rodent-models-and-is-feasible-for-the-treatment-of-canine-malignant-glioma-patients
#10
Avadhut D Joshi, Rachel C Botham, Lisa J Schlein, Howard S Roth, Antonella Mangraviti, Alexandra Borodovsky, Betty Tyler, Steve Joslyn, Jayme S Looper, Michael Podell, Timothy M Fan, Paul J Hergenrother, Gregory J Riggins
PURPOSE: Glioblastoma is a deadly brain cancer with a median survival time of ~15 months. Ionizing radiation plus the DNA alkylator temozolomide (TMZ) is the current standard therapy. PAC-1, a procaspase-3 activating small molecule, is blood-brain barrier penetrant and has previously demonstrated ability to synergize with diverse pro-apoptotic chemotherapeutics. We studied if PAC-1 could enhance the activity of TMZ, and whether addition of PAC-1 to standard treatment would be feasible in spontaneous canine malignant gliomas...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708230/short-course-radiotherapy-concomitant-with-temozolomide-in-gbm-patients-a-phase-ii-study
#11
Laura Fariselli, Lucia Cuppini, Paola Gaviani, Marcello Marchetti, Valentina Pinzi, Ida Milanesi, Giorgia Simonetti, Irene Tramacere, Francesco DiMeco, Andrea Salmaggi, Antonio Silvani
PURPOSE: Despite recent advances, the prognosis of glioblastoma (GBM) remains poor. The aim of this study was to assess the efficacy and tolerability of multiple daily fraction radiotherapy performed with multiple temozolomide (TMZ) administrations in newly diagnosed patients with GBM. METHODS: This trial was a prospective, open-label, monocentric, nonrandomized, single arm, phase II study. The primary endpoint was the proportion of progression-free patients at 12 months, and the secondary endpoints were overall survival (OS) and toxicity...
July 8, 2017: Tumori
https://www.readbyqxmd.com/read/28706148/expression-differences-of-programmed-death-ligand-1-in-de-novo-and-recurrent-glioblastoma-multiforme
#12
Sabrina Heynckes, Annette Gaebelein, Gerrit Haaker, Jürgen Grauvogel, Pamela Franco, Irina Mader, Maria Stella Carro, Marco Prinz, Daniel Delev, Oliver Schnell, Dieter Henrik Heiland
The biology of recurrent glioblastoma multiforme (GBM) is a dynamic process influenced by selection pressure induced by different antitumoural therapies. The poor clinical outcome of tumours in the recurrent stage necessitates the development of effective therapeutic strategies. Checkpoint-inhibition (PD1/PD-L1 Inhibition) is a hallmark of immunotherapy being investigated in ongoing clinical trials. The purpose of this study was to analyse the PD-L1 expression in de-novo and recurrent glioblastoma multiforme and to explore associated genetic alterations and clinical traits...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704425/in-vitro-nuclear-magnetic-resonance-spectroscopy-metabolic-biomarkers-for-the-combination-of-temozolomide-with-pi3k-inhibition-in-paediatric-glioblastoma-cells
#13
Nada M S Al-Saffar, Alice Agliano, Lynley V Marshall, L Elizabeth Jackson, Geetha Balarajah, Jasmin Sidhu, Paul A Clarke, Chris Jones, Paul Workman, Andrew D J Pearson, Martin O Leach
Recent experimental data showed that the PI3K pathway contributes to resistance to temozolomide (TMZ) in paediatric glioblastoma and that this effect is reversed by combination treatment of TMZ with a PI3K inhibitor. Our aim is to assess whether this combination results in metabolic changes that are detectable by nuclear magnetic resonance (NMR) spectroscopy, potentially providing metabolic biomarkers for PI3K inhibition and TMZ combination treatment. Using two genetically distinct paediatric glioblastoma cell lines, SF188 and KNS42, in vitro 1H-NMR analysis following treatment with the dual pan-Class I PI3K/mTOR inhibitor PI-103 resulted in a decrease in lactate and phosphocholine (PC) levels (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28700357/are-three-weeks-hypofractionated-radiation-therapy-hfrt-comparable-to-six-weeks-for-newly-diagnosed-glioblastoma-patients-results-of-a-phase-ii-study
#14
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...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698441/-combination-therapy-with-radiation-temozolomide-and-bevacizumab-after-partial-tumor-removal-in-glioblastoma-patients-with-low-performance-status
#15
Junzo Nakao, Eiichi Ishikawa, Masahide Matsuda, Tetsuya Yamamoto, Shingo Takano, Akira Matsumura
INTRODUCTION: It is unclear whether or not bevacizumab(Bev)has a curative ability in newly diagnosed glioblastoma(GBM) patients with low Karnofsky performance status(KPS). MATERIALS AND METHODS: Four of 14 patients with newly diagnosed GBM received combination therapy with extended local radiation, temozolomide(TMZ), and Bev after partialremovalor biopsy of the tumor. RESULTS: The average patient age was 77.2 years(range 67-85)and the male-to-female ratio was 1:3...
June 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28693171/temozolomide-induces-autophagy-in-primary-and-established-glioblastoma-cells-in-an-egfr-independent-manner
#16
Silvia Würstle, Fabian Schneider, Florian Ringel, Jens Gempt, Friederike Lämmer, Claire Delbridge, Wei Wu, Jürgen Schlegel
Despite major contributions to the current molecular understanding of autophagy, a recycling process for intracellular components to maintain homeostatic balance, relatively little is known about the interacting networks. To address this issue, the current study investigated the role of autophagy in primary and established glioblastoma multiforme (GBM) cells and its interplay with the epidermal growth factor receptor (EGFR) and the standard chemotherapeutic agent temozolomide (TMZ). TMZ treatment leads to an upregulation of autophagy, predominantly in primary GBM cells...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28683436/effects-of-trimetazidine-on-pdcd4-nf-%C3%AE%C2%BAb-tnf-%C3%AE-pathway-in-coronary-microembolization
#17
Qiang Su, Lang Li, Jinmin Zhao, Yuhan Sun, Huafeng Yang
BACKGROUND/AIMS: The local inflammatory response caused by coronary microembolization (CME) is the primary cause of progressive cardiac dysfunction. The PDCD4/NF-κB/TNF-α signaling pathway plays a significant role in CME-induced myocardial Inflammation. Trimetazidine (TMZ) reduces myocardial injury, caused by percutaneous coronary intervention, through relieving the CME-induced myocardial systolic dysfunction. Therefore, the present study investigated the role of TMZ pre-treatment in the protection of myocardium after CME and PDCD4/NF-κB/TNF-α in mini pigs...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28682902/long-term-outcomes-of-concomitant-chemoradiotherapy-with-temozolomide-for-newly-diagnosed-glioblastoma-patients-a-single-center-analysis
#18
Tae Hoon Roh, Hun Ho Park, Seok-Gu Kang, Ju Hyung Moon, Eui Hyun Kim, Chang-Ki Hong, Sung Soo Ahn, Hye Jin Choi, Jaeho Cho, Se Hoon Kim, Seung Koo Lee, Dong Seok Kim, Sun Ho Kim, Chang-Ok Suh, Kyu Sung Lee, Jong Hee Chang
The present study analyzed outcomes of surgery followed by concomitant chemoradiotherapy (CCRT) with temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM) at a single institution. Outcomes were retrospectively reviewed in 252 consecutive patients with newly diagnosed GBM who underwent surgery followed by CCRT with TMZ at the authors' institution between 2005 and 2013. At initial operation, 126 (50.0%), 55 (21.8%), 45 (17.9%), and 26 (10.3%) patients underwent gross total resection (GTR), subtotal resection, partial resection (PR), and biopsy, respectively...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28679777/efficacy-of-onalespib-a-long-acting-second-generation-hsp90-inhibitor-as-a-single-agent-and-in-combination-with-temozolomide-against-malignant-gliomas
#19
Alessandro Canella, Alessandra M Welker, Ji Young Yoo, Jihong Xu, Fazly S Abbas, Divya Kesanakurti, Prabhakaran Nagarajan, Christine E Beattie, Erik P Sulman, Joseph L Liu, Joy Gumin, Frederick F Lang, Metin Gurcan, Balveen Kaur, Deepa Sampath, Vinay K Puduvalli
HSP90, a highly conserved molecular chaperone that regulates the function of several oncogenic client proteins is altered in glioblastoma. However, HSP90 inhibitors currently in clinical trials are short-acting, have unacceptable toxicities or are unable to cross the blood brain barrier (BBB). We examined the efficacy of onalespib, a potent, long-acting novel HSP90 inhibitor as a single agent and in combination with temozolomide (TMZ) against gliomas invitro and invivo<br /><br />Experimental Design: The effect of onalespib on HSP90, its client proteins, and on the biology of glioma cell lines and patient-derived glioma-initiating cells (GSC) was determined...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28675067/postoperative-neoadjuvant-temozolomide-before-radiotherapy-versus-standard-radiotherapy-in-patients-60-years-or-younger-with-anaplastic-astrocytoma-or-glioblastoma-a-randomized-trial
#20
Annika Malmström, Hans Skovgaard Poulsen, Bjørn Henning Grønberg, Giuseppe Stragliotto, Steinbjørn Hansen, Thomas Asklund, Birgitta Holmlund, Małgorzata Łysiak, Joseph Dowsett, Bjarne Winther Kristensen, Peter Söderkvist, Johan Rosell, Roger Henriksson
INTRODUCTION: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ. PATIENTS AND METHODS: Patients, after surgery for GBM or AA, age ≤60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200 mg/m(2) days 1-5 every 28 days, followed by RT 60 Gy in 30 fractions or RT only...
July 4, 2017: Acta Oncologica
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