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temozolomide

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https://www.readbyqxmd.com/read/28436750/emap-ii-sensitize-u87mg-and-glioma-stem-like-cells-to-temozolomide-via-induction-of-autophagy-mediated-cell-death-and-g2-m-arrest
#1
Qi Yu, Libo Liu, Ping Wang, Yilong Yao, Yixue Xue, Yunhui Liu
Despite the fact that temozolomide (TMZ) has been widely accepted as the key chemotherapeutic agent to prolong the survival of patients with glioblastoma, failure and recurrence cases can still be observed in clinics. Glioma stem-like cells (GSCs) are thought to be responsible for the drug resistance. In this study, we investigate whether endothelial monocyte-activating polypeptide-II (EMAP-II), a pro-inflammatory cytokine, can enhance TMZ cytotoxicity on U87MG and GSCs or not. As described in prior research, GSCs have been isolated from U87MG and maintained in the serum-free DMEM/F12 medium containing EGF, b-FGF, and B27...
April 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28436299/mgmt-gene-variants-temozolomide-myelotoxicity-and-glioma-risk-a-concise-literature-survey-including-an-illustrative-case
#2
Meric A Altinoz, Ilhan Elmaci, Fatih Han Bolukbasi, Cumhur Gokhan Ekmekci, Guven Yenmis, Ramazan Sari, Aydin Sav
Temozolomide may cause thrombocytopenia or neutropenia in 3-4% of glioblastoma patients, respectively. However, pancytopenia is rarely reported. MGMT (O6-methylguanine-DNA-methyltransferase) enzyme repairs temozolomide-induced DNA mutations and associates both with antitumour efficacy and myelosuppression. Many studies on the effects of MGMT gene-methylation on temozolomide's effects exist, but much fewer publications concerning MGMT variants were documented. A full sequencing of the MGMT gene was performed in a female glioblastoma patient, who developed pancytopenia following temozolomide treatment...
April 23, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28435646/osteosclerosis-secondary-to-metastatic-oligodendroglioma
#3
Patrick R Maloney, Vitor Nagai Yamaki, Ravi Kumar, Derek Johnson, Christopher Hunt, Mark E Jentoft, Michelle Clarke
This paper reviews a case of metastatic 1p/19q codeleted oligodendrioglioma causing diffuse osteosclerosis and pain. Primary central nervous system (CNS) tumors rarely metastasize outside the CNS, and metastatic oligodendroglioma is rarer still. The patient in this study had relief of pain after being treated with temozolomide. We discuss this rare presentation and potential treatment options, and review the literature in regards to metastatic oligodendrogliomas.
March 24, 2017: Rare Tumors
https://www.readbyqxmd.com/read/28432588/patterns-of-care-and-outcomes-of-multi-agent-versus-single-agent-chemotherapy-as-part-of-multimodal-management-of-low-grade-glioma
#4
Waqar Haque, Vivek Verma, E Brian Butler, Bin S Teh
For high-risk low-grade gliomas (LGGs), adjuvant radiotherapy (RT) with procarbazine/lomustine/vincristine (PCV) chemotherapy increases overall survival (OS) over RT alone. However, in practice, temozolomide (TMZ) is often used instead of PCV. Using the National Cancer Data Base (NCDB), we provide the first investigation of practice patterns and outcomes of chemoradiotherapy with single-agent chemotherapy (SAC, analogous to TMZ) or multi-agent chemotherapy (MAC, analogous to PCV) for LGG. Patients with high-risk Grade II LGGs were queried in the NCDB...
April 21, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28432280/small-molecules-targeting-histone-demethylase-genes-kdms-inhibit-growth-of-temozolomide-resistant-glioblastoma-cells
#5
Barbara Banelli, Antonio Daga, Alessandra Forlani, Giorgio Allemanni, Daniela Marubbi, Maria Pia Pistillo, Aldo Profumo, Massimo Romani
In glioblastoma several histone demethylase genes (KDM) are overexpressed compared to normal brain tissue and the development of Temozolomide (TMZ) resistance is accompanied by the transient further increased expression of KDM5A and other KDMs following a mechanism that we defined as "epigenetic resilience". We hypothesized that targeting KDMs may kill the cells that survive the cytotoxic therapy.We determined the effect of JIB 04 and CPI-455, two KDM inhibitors, on glioblastoma cells and found that both molecules are more effective against TMZ-resistant rather than native cells...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28432119/temozolomide-treatment-can-improve-overall-survival-in-aggressive-pituitary-tumors-and-pituitary-carcinomas
#6
Hélène Lasolle, Christine Cortet, Fréderic Castinetti, Lucie Cloix, Philippe Caron, Brigitte Delemer, Rachel Desailloud, Christel Jublanc, Christine Lebrun-Frenay, Jean-Louis Sadoul, Luc Taillandier, Marie Batisse-Lignier, Fabrice Bonnet, Nathalie Bourcigaux, Damien Bresson, Olivier Chabre, Philippe Chanson, Cyril Garcia, Magalie Haissaguerre, Yves Reznik, Sophie Borot, Chiara Villa, Alexandre Vasiljevic, Stephan Gaillard, Emmanuel Jouanneau, Guillaume Assié, Gérald Raverot
OBJECTIVES: Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. DESIGN: Multicenter retrospective study by members of the French Society of Endocrinology. METHODS: Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included...
June 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28430288/mesenchymal-proangiogenic-factor-ykl-40-related-to-glioblastomas-and-its-relationship-with-the-subventricular-zone
#7
Kelvin M Pińa Batista, Sayoa Alvarez de Eulate-Beramendi, Kenia Y Álvarez Reyes de Pińa, Pedro Reimunde Figueira, Adan Fernandez Canal, Josué M Avecillas Chasin, Ángela Meilan, Rodrigo Ugalde, Ivan Fernandez Vega
<i>Glioblastoma is the most common primary brain tumor. Despite multimodality therapy with aggressive microsurgical resection and adjuvant chemotherapy and radiotherapy, the median survival is below 15 months. Glioblastomas are heterogeneous tumors with high resistance to most chemotherapeutic drugs. According to reliable evidence, YKL-40, one of the best investigated chitinase-like protein, may facilitate invasion, migration and angiogenesis, and could be also responsible for temozolomide resistance in glioblastoma, thus conferring a dismal prognosis...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28430038/prognostic-implications-of-the-subcellular-localization-of-survivin-in-glioblastomas-treated-with-radiotherapy-plus-concomitant-and-adjuvant-temozolomide
#8
Taiichi Saito, Kazuhiko Sugiyama, Yukio Takeshima, Vishwa Jeet Amatya, Fumiyuki Yamasaki, Takeshi Takayasu, Ryo Nosaka, Yoshihiro Muragaki, Takakazu Kawamata, Kaoru Kurisu
OBJECTIVE Currently, the standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Various prognostic biomarkers for GBM have been described, including survivin expression. The aim of this study was to determine whether the subcellular localization of survivin correlates with GBM prognosis in patients who received the standard treatment protocol. METHODS The authors retrospectively examined the subcellular localization of survivin (nuclear, cytoplasmic, or both) using immunohistochemistry in 50 patients with GBM who had received the standard treatment...
April 21, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28429093/a-case-of-glioblastoma-resected-immediately-after-administering-bevacizumab-consideration-on-histopathological-findings-and-safety-of-surgery
#9
Yukina Tokuda, Ryota Tamura, Kentaro Ohara, Kazunari Yoshida, Hikaru Sasaki
Surgery after administering bevacizumab should be carefully considered particularly because of wound healing concerns. A 27-year-old man presented with multiple tumor recurrences after gross total removal of a left temporal oligodendroglioma (1p/19q-noncodeleted). Whole brain radiotherapy with concomitant temozolomide and bevacizumab was immediately prescribed; however, the patient's condition deteriorated because of brain herniation. Three days after administering bevacizumab, an emergency tumor removal with external decompression and a ventriculo-peritoneal shunt was performed...
April 20, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28427800/the-effect-of-optune%C3%A2-tumor-treating-fields-transducer-arrays-on-skin-radiation-dose-during-radiotherapy
#10
Edward Bender, Kevin Kozak, Steven Howard, Lori Hayes, John Bayouth, H Ian Robins
A Phase 3 clinical study demonstrated that the addition of 200kHz Tumor Treating Fields (TTF) to temozolomide in the post-radiation (RT) phase of therapy in newly diagnosed glioblastoma increases progression free and overall survival (resulting in FDA and European Union approval). Preclinical studies have demonstrated the ability of TTF to act as a radiosensitizer, suggesting concurrent TTF and RT may have clinical utility. The removal and replacement of TTF transducer arrays from the scalps of patients on a daily basis, i...
April 17, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28427200/idh1-r132h-mutation-regulates-glioma-chemosensitivity-through-nrf2-pathway
#11
Kaishu Li, Leping Ouyang, Mingliang He, Ming Luo, Wangqing Cai, Yalin Tu, Rongbiao Pi, Anmin Liu
PURPOSE: Numerous studies have reported that glioma patients with isocitrate dehydrogenase 1(IDH1) R132H mutation are sensitive to temozolomide treatment. However, the mechanism of IDH1 mutations on the chemosensitivity of glioma remains unclear. In this study, we investigated the role and the potential mechanism of Nrf2 in IDH1 R132H-mediated drug resistance. METHODS: Wild type IDH1 (R132H-WT) and mutant IDH1 (R132H) plasmids were constructed. Stable U87 cells and U251 cells overexpressing IDH1 were generated...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427088/a-phase-2-study-of-temozolomide-in-pretreated-metastatic-colorectal-cancer-with-mgmt-promoter-methylation
#12
M A Calegari, A Inno, S Monterisi, A Orlandi, D Santini, M Basso, A Cassano, M Martini, T Cenci, I de Pascalis, F Camarda, B Barbaro, L M Larocca, S Gori, G Tonini, C Barone
BACKGROUND: Presently, few options are available for refractory colorectal cancer (CRC). O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation is a frequent and early event in CRC tumourigenesis. This epigenetic silencing is a predictor of response to the alkylating drug temozolomide in glioblastoma. Preclinical evidences and some case reports showed temozolomide activity in CRC with MGMT silencing, but the available data from clinical trials are inconsistent. METHODS: This was a multicentre, phase 2 trial, planned according to a two-stage Simon's optimal design to investigate activity and safety of temozolomide in refractory CRC harbouring MGMT promoter methylation...
April 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28426279/combination-of-gemcitabine-and-docetaxel-regress-both-gastric-leiomyosarcoma-proliferation-and-invasion-in-an-imageable-patient-derived-orthotopic-xenograft-ipdox-model
#13
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Tasuku Kiyuna, Scott D Nelson, Sarah M Dry, Yunfeng Li, Tara A Russell, Arun S Singh, Bartosz Chmielowski, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
Gastric leiomyosarcoma is a recalcitrant cancer and chemotherapy strategy is controversial. The present study used a patient-derived orthotopic xenograft (PDOX) nude mouse model of gastric leiomyosarcoma to identify an effective therapeutic regimen in order to develop individualized precision medicine for this disease. A gastric leiomyosarcoma obtained from a patient was first grown in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP) in order to stably label the tumor stroma. The RFP-expressing tumor was then passaged orthotopically in the gastric wall of non-transgenic nude mice to establish an imageable PDOX (iPDOX) model...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28425987/biological-activity-of-tumor-treating-fields-in-preclinical-glioma-models
#14
Manuela Silginer, Michael Weller, Roger Stupp, Patrick Roth
Glioblastoma is the most common and aggressive form of intrinsic brain tumor with a very poor prognosis. Thus, novel therapeutic approaches are urgently needed. Tumor-treating fields (TTFields) may represent such a novel treatment option. The aim of this study was to investigate the effects of TTFields on glioma cells, as well as the functional characterization of the underlying mechanisms. Here, we assessed the anti-glioma activity of TTFields in several preclinical models. Applying TTFields resulted in the induction of cell death in a frequency- and intensity-dependent manner in long-term glioma cell lines, as well as glioma-initiating cells...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28425046/mir-198-enhances-temozolomide-sensitivity-in-glioblastoma-by-targeting-mgmt
#15
Er Nie, Xin Jin, Weining Wu, Tianfu Yu, Xu Zhou, Zhumei Shi, Junxia Zhang, Ning Liu, Yongping You
Glioblastoma is one of the most frequent and aggressive brain tumors. Accumulating evidence indicates that microRNAs are involved in glioma proliferation, invasion and drug resistance. Previous studies showed that miR-198 is downregulated in glioblastoma. However, the function of miR-198 in glioblastoma is still unclear. In this study, we report that miR-198 levels were greatly downregulated in glioblastoma specimens and decreased expression of miR-198 was associated with poor prognosis in patients with glioblastoma...
April 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28424876/extent-of-surgical-resection-and-adjuvant-temozolomide-improves-survival-in-pediatric-gbm-a-single-center-experience
#16
Subhash Gupta, Supriya Mallick, Rony Benson, K P Haresh, Pramod Kumar Julka, Goura Kishor Rath
BACKGROUND: Pediatric glioblastoma (pGBM) is an uncommon entity. The importance of concurrent and adjuvant temozolomide is not known in this subset of patients. METHODS: We retrospectively analyzed our database between 2000 and 2015. All patients were treated with maximally safe surgical resection. This was followed by a uniform treatment schedule of post-operative radiation with concurrent daily temozolomide at 75 mg/m(2). Radiation dose was 60 Gy in 30 fractions planned by 3-dimensional conformal radiotherapy...
April 19, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28424082/subventricular-zones-new-key-targets-for-glioblastoma-treatment
#17
J Khalifa, F Tensaouti, A Lusque, B Plas, J-A Lotterie, A Benouaich-Amiel, E Uro-Coste, V Lubrano, E Cohen-Jonathan Moyal
BACKGROUND: We aimed to identify subventricular zone (SVZ)-related prognostic factors of survival and patterns of recurrence among patients with glioblastoma. METHODS: Forty-three patients with primary diagnosed glioblastoma treated in our Cancer Center between 2006 and 2010 were identified. All patients received surgical resection, followed by temozolomide-based chemoradiation. Ipsilateral (iSVZ), contralateral (cSVZ) and bilateral (bSVZ) SVZs were retrospectively segmented and radiation dose-volume histograms were generated...
April 20, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28423611/the-stem-cell-cancer-stem-cell-marker-aldh1a3-regulates-the-expression-of-the-survival-factor-tissue-transglutaminase-in-mesenchymal-glioma-stem-cells
#18
Kelly E Sullivan, Kathy Rojas, Richard A Cerione, Ichiro Nakano, Kristin F Wilson
Tissue transglutaminase (tTG), a dual-function enzyme with GTP-binding and acyltransferase activities, has been implicated in the survival and chemotherapy resistance of aggressive cancer cells and cancer stem cells, including glioma stem cells (GSCs). Using a model system comprising two distinct subtypes of GSCs referred to as proneural (PN) and mesenchymal (MES), we find that the phenotypically aggressive and radiation therapy-resistant MES GSCs exclusively express tTG relative to PN GSCs. As such, the self-renewal, proliferation, and survival of these cells was sensitive to treatment with tTG inhibitors, with a benefit being observed when combined with the standard of care for high grade gliomas (i...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423558/biological-basis-and-clinical-study-of-glycogen-synthase-kinase-3%C3%AE-targeted-therapy-by-drug-repositioning-for-glioblastoma
#19
Takuya Furuta, Hemragul Sabit, Yu Dong, Katsuyoshi Miyashita, Masashi Kinoshita, Naoyuki Uchiyama, Yasuhiko Hayashi, Yutaka Hayashi, Toshinari Minamoto, Mitsutoshi Nakada
BACKGROUND: Glycogen synthase kinase (GSK)-3β has emerged as an appealing therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic effect of the current approved drugs against GBM via inhibition of GSK3β activity both, in experimental setting and in a clinical study for recurrent GBM patients by repositioning existent drugs in combination with temozolomide (TMZ). MATERIALS AND METHODS: Progression-free and overall survival rates were compared between patients with low or high expression of active GSK3β in the primary tumor...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423515/preclinical-therapeutic-efficacy-of-a-novel-blood-brain-barrier-penetrant-dual-pi3k-mtor-inhibitor-with-preferential-response-in-pi3k-pten-mutant-glioma
#20
Dimpy Koul, Shuzhen Wang, Shaofang Wu, Norihiko Saito, Siyuan Zheng, Feng Gao, Isha Kaul, Masaki Setoguchi, Kiyoshi Nakayama, Kumiko Koyama, Yoshinobu Shiose, Erik P Sulman, Yasuhide Hirota, W K Alfred Yung
Glioblastoma (GBM) is an ideal candidate disease for signal transduction targeted therapy because the majority of these tumors harbor genetic alterations that result in aberrant activation of growth factor signaling pathways. Loss of heterozygosity of chromosome 10, mutations in the tumor suppressor gene PTEN, and PI3K mutations are molecular hallmarks of GBM and indicate poor prognostic outcomes in many cancers. Consequently, inhibiting the PI3K pathway may provide therapeutic benefit in these cancers. PI3K inhibitors generally block proliferation rather than induce apoptosis...
March 28, 2017: Oncotarget
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