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https://www.readbyqxmd.com/read/29334602/high-dose-metformin-plus-temozolomide-shows-increased-anti-tumor-effects-in-glioblastoma-in-vitro-and-in-vivo-compared-with-monotherapy
#1
Jung Eun Lee, Ji Hee Lim, Yong Kil Hong, Seung Ho Yang
Purpose: The purpose of the study is to investigate the efficacy of combined treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in vitro and in vivo. Materials and Methods: We investigated the efficacy of combined treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM orthotopic mice model was established by inoculation of 5x105 U87 cells and treated with metformin, TMZ, and the combination for 4 weeks. Western blotting and immunofluorescence of tumor specimens were analyzed to investigate AMP-activated protein kinase (AMPK) and AKT pathway...
January 10, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29333126/impact-on-radiation-dose-and-volume-v57-gy-of-the-brain-on-recurrence-and-survival-of-patients-with-glioblastoma-multiformae
#2
Igor Stojkovski, Valentina Krstevska, Snezhana Smichkoska
Background: The aim of the study was to analyze impact of irradiated brain volume V57 Gy (volume receiving 57 Gy and more) on time to progression and survival of patients with glioblastoma. Patients and methods: Dosimetric analysis of treatment plan data has been performed on 70 patients with glioblastoma, treated with postoperative radiochemotherapy with temozolomide, followed by adjuvant temozolomide. Patients were treated with 2 different methods of definition of treatment volumes and prescription of radiation dose...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29333122/metformin-enhanced-in-vitro-radiosensitivity-associates-with-g2-m-cell-cycle-arrest-and-elevated-adenosine-5-monophosphate-activated-protein-kinase-levels-in-glioblastoma
#3
Sebastian Adeberg, Denise Bernhardt, Semi B Harrabi, Nils H Nicolay, Juliane Hörner-Rieber, Laila König, Michael Repka, Angela Mohr, Amir Abdollahi, Klaus-Josef Weber, Juergen Debus, Stefan Rieken
Background: It is hypothesized that metabolism plays a strong role in cancer cell regulation. We have recently demonstrated improved progression-free survival in patients with glioblastoma who received metformin as an antidiabetic substance during chemoradiation. Although metformin is well-established in clinical use the influence of metformin in glioblastoma is far from being understood especially in combination with other treatment modalities such as radiation and temozolomide. Materials and Methods: In this study, we examined the influence of metformin in combinations with radiation and temozolomide on cell survival (clonogenic survival), cell cycle (routine flow cytometric analysis, FACScan), and phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho-AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29333019/modulated-radiotherapy-with-concurrent-and-adjuvant-temozolomide-for-anaplastic-gliomas-indian-single-center-data
#4
Tejinder Kataria, Trinanjan Basu, Deepak Gupta, Shikha Goyal, Shahida Nasreen, Shyam S Bisht, Ashu Abhishek, Susovan Banerjee, Kushal Narang, Ajaya N Jha, Ishani Mohapatra, Jayesh A Modi
Objective: To evaluate early clinical outcome for anaplastic gliomas (AG) treated in the era of modulated radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ) in an Indian setting. Materials and Methods: Fifty-three patients with AGs treated with modulated RT and concurrent (95%) and adjuvant TMZ (90%) were analyzed. About 80% of patients had Karnofsky performance status (KPS) at least 90 with 30% seizure at presentation. Postoperative magnetic resonance imaging was available in 65% cases and RT dose was 60 Gy in 30 fractions...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29333005/prognostic-factors-and-survival-outcomes-of-intracranial-ependymoma-treated-with-multimodality-approach
#5
Kunhi Parambath Haresh, Ajeet Kumar Gandhi, Supriya Mallick, Rony Benson, Subhash Gupta, Daya Nand Sharma, Pramod Kumar Julka, Goura Kisor Rath
Objectives: We aimed to analyze treatment outcomes of intracranial ependymoma (ICE) treated at our institute with multimodality approach. Materials and Methods: Demography, treatment details, and survival data of 40 patients (2005-2012) were collected in a predesigned pro forma. Kaplan Meier method was used to analyze disease-free survival (DFS) and the impact of prognostic factors was determined using univariate analysis (log-rank test). Multivariate analysis was performed using Cox-proportional hazard model...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29332604/the-effect-of-an-adenosine-a2a-agonist-on-intra-tumoral-concentrations-of-temozolomide-in-patients-with-recurrent-glioblastoma
#6
Sadhana Jackson, Jon Weingart, Edjah K Nduom, Thura T Harfi, Richard T George, Dorothea McAreavey, Xiaobu Ye, Nicole M Anders, Cody Peer, William D Figg, Mark Gilbert, Michelle A Rudek, Stuart A Grossman
BACKGROUND: The blood-brain barrier (BBB) severely limits the entry of systemically administered drugs including chemotherapy to the brain. In rodents, regadenoson activation of adenosine A2A receptors causes transient BBB disruption and increased drug concentrations in normal brain. This study was conducted to evaluate if activation of A2A receptors would increase intra-tumoral temozolomide concentrations in patients with glioblastoma. METHODS: Patients scheduled for a clinically indicated surgery for recurrent glioblastoma were eligible...
January 15, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29331023/temozolomide-analog-pmx-465-downregulates-mgmt-expression-in-hct116-colorectal-carcinoma-cells
#7
Zhikuan Yang, Danping Wei, Feifei Liu, Jing Liu, Xiaoming Wu, Malcolm F G Stevens, Tracey D Bradshaw, Ying Luo, Jihong Zhang
The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by inherent or the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in a significant proportion of tumors. We have found that TMZ analog C8-methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against the colorectal carcinoma HCT116 cells which are MGMT-overexpressing and mismatch repair (MMR)-deficient. In this study, we found that PMX 465 could downregulate the expression of MGMT in HCT116 cells at the protein and mRNA levels...
January 13, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29330865/a-case-of-radiation-induced-osteosarcoma-of-the-skull-presenting-as-a-cutaneous-epidermotropic-tumour-with-a-short-latent-period
#8
E Rashidghamat, E Calonje
Radiation induced sarcoma is an unusual but well documented tumor. The frequency of radiation induced sarcoma of the head and neck region has been reported as 0.143%. In the literature the median interval between irradiation and development of sarcoma is 11 years. Cases of RIS with a short latent period i.e. less than four years are rare. We report a case of a 34 year-old female who developed an osteosarcoma of the scalp, over a previous craniotomy scar, three years after excision of a frontal anaplastic oligodendroglioma which had been followed by a course of 6 weeks radiotherapy (58 Gy) and 6 cycles of Temozolomide...
January 13, 2018: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/29330228/treatment-of-aggressive-pituitary-tumours-and-carcinomas-results-of-a-european-society-of-endocrinology-ese-survey-2016
#9
Ann I McCormack, Olaf Dekkers, Stephan Petersenn, Vera Popovic, Jacqueline Trouillas, Gerald Raverot, Pia Burman
OBJECTIVE: To collect outcome data in a large cohort of patients with aggressive pituitary tumours (APT)/carcinomas (PC), and specifically report effects of temozolomide (TMZ) treatment. DESIGN: Electronic survey to ESE members Dec 2015-Nov 2016. RESULTS: Reports on 165 patients (40 PC, 125 APT) were obtained. Median age at diagnosis was 43 (range 4-79) years. 69% of the tumours were clinically functioning, and the most frequent immunohistochemical subtype were corticotroph tumours (45%)...
January 12, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29319131/temozolomide-therapy-for-aggressive-pituitary-crooke-s-cells-corticotropinoma-causing-cushing-s-disease-a-case-report-with-literature-review
#10
Aleksandra Gilis-Januszewska, Małgorzata Wilusz, Jacek Pantofliński, Renata Turek-Jabrocka, Grzegorz Sokołowski, Anna Sowa-Staszczak, Łukasz Kluczyński, Dorota Pach, Grzegorz Zieliński, Alicja Hubalewska-Dydejczyk
AbstractContext: Aggressive pituitary tumours causing Cushing's Disease are very rare, difficult to treat, and usually resistant to conventional therapy. There is growing evidence for the use of temozolomide (TZM), an alkylating chemotherapeutic agent, as first line chemotherapy in tumours resistant to repeated neurosurgery, radiotherapy and adrenalectomy. OBJECTIVE: To present the response to TMZ in a rare case of an aggressive pituitary tumour in the course of Cushing's Disease and to review the literature referring to similar cases...
January 10, 2018: Endokrynologia Polska
https://www.readbyqxmd.com/read/29318507/mid-term-prognosis-of-non-functioning-pituitary-adenomas-with-high-proliferative-potential-really-an-aggressive-variant
#11
Yoshikazu Ogawa, Hidefumi Jokura, Kuniyasu Niizuma, Teiji Tominaga
Pituitary adenomas with high proliferation rate and rapid growth are well known, but the clinical characteristics, prognosis, and treatment algorithm remain unclear. The clinical characteristics and mid-term prognosis of patients with non-functioning pituitary adenomas with high proliferative potential were retrospectively investigated. This study identified 53 patients with Ki-67 labeling index of > 3% among 845 patients with non-functioning pituitary adenoma (6.3%) initially treated by surgery. Prophylactic treatment was not applied for patients with residual tumor, but salvage treatment was performed if tumor progression was identified within the follow-up period...
January 9, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29315292/phase-i-study-of-sorafenib-combined-with-radiation-therapy-and-temozolomide-as-first-line-treatment-of-high-grade-glioma
#12
A F Hottinger, A Ben Aissa, V Espeli, D Squiban, N Dunkel, M I Vargas, T Hundsberger, N Mach, K Schaller, D C Weber, A Bodmer, P-Y Dietrich
This corrects the article DOI: 10.1038/bjc.2014.209.
January 9, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29313954/phase-1-2-trial-of-temsirolimus-and-sorafenib-in-the-treatment-of-patients-with-recurrent-glioblastoma-north-central-cancer-treatment-group-study-alliance-n0572
#13
David Schiff, Kurt A Jaeckle, S Keith Anderson, Evanthia Galanis, Caterina Giannini, Jan C Buckner, Phillip Stella, Patrick J Flynn, Bradley J Erickson, John F Schwerkoske, Vesna Kaluza, Erin Twohy, Janet Dancey, John Wright, Jann N Sarkaria
BACKGROUND: Mitogen-activated protein kinase (MAPK) activation and mammalian target of rapamycin (mTOR)-dependent signaling are hallmarks of glioblastoma. In the current study, the authors conducted a phase 1/2 study of sorafenib (an inhibitor of Raf kinase and vascular endothelial growth factor receptor 2 [VEGFR-2]) and the mTOR inhibitor temsirolimus in patients with recurrent glioblastoma. METHODS: Patients with recurrent glioblastoma who developed disease progression after surgery or radiotherapy plus temozolomide and with ≤2 prior chemotherapy regimens were eligible...
January 3, 2018: Cancer
https://www.readbyqxmd.com/read/29313231/relationship-between-hedgehog-signaling-pathway-and-drug-resistance-of-poorly-differentiated-gliomas
#14
S A Cherepanov, N F Grinenko, O M Antonova, P B Kurapov, I I Shepeleva, V P Chekhonin
The effects of Hedgehog signaling inhibitor (cyclopamine) and activator (Shh) on drug resistance of U251-MG human glioma cells and human astrocyte culture to cisplatin, temozolomide, and doxorubicin were studied. Cyclopamine and Shh modified the drug resistance of U251-MG cells but not of human astrocytes. Experiments with cyclopamine, Shh, and chemical drugs can contribute to detection of the mechanisms of signaling effects on the drug resistance processes, while the experimental data can serve as one of the criteria for choosing individual chemotherapy for patients...
January 8, 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29308973/current-and-emerging-egfr-therapies-for-glioblastoma
#15
Stefan Alexandru Artene, Cristian Tuţă, Alexandra Dragoi, Oana Alexandru, Purcaru Stefana Oana, Daniela Elise Tache, Maria Mihaela Dănciulescu, Mihai Virgil Boldeanu, Cristian Adrian Siloşi, Anica Dricu
Glioblastomas (GBM) are the most lethal and hard to treat malignancies in clinical practice. The standard of care for treating GBM involving surgery and adjuvant radiotherapy and concomitant temozolomide (TMZ) has remained virtually unchanged in the past decade. Molecular targeted therapies against cancer-specific structures have reported mediocre results in the treatment of GBM, due to multiple factors such as the presence of the blood brain barrier (BBB) or a vast array of molecular alterations which greatly hinder the action of the most therapeutic agents...
January 8, 2018: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/29306018/aldehyde-dehydrogenase-1a3-aldh1a3-is-regulated-by-autophagy-in-human-glioblastoma-cells
#16
Wei Wu, Johannes Schecker, Sylvia Würstle, Fabian Schneider, Martin Schönfelder, Jürgen Schlegel
Aldehyde dehydrogenase is a polymorphic enzyme, which responsible for the oxidation of aldehydes. It has been shown that ALDH1A3 is expressed in human glioblastomas and that its expression correlates with a worse prognosis. In our present study ALDH1A3 expression was associated with resistance against Temozolomide (TMZ) treatment and sensitivity could be re-established in ALDH1A3 knockout cells. TMZ treatment at high concentrations diminished ALDH1A3 protein and this downregulation made the tumor cells more sensitive to chemotherapy...
January 3, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29301329/differential-characterization-of-temozolomide-resistant-human-glioma-cells
#17
Sheng-Wei Lai, Bor-Ren Huang, Yu-Shu Liu, Hsiao-Yun Lin, Chun-Chuan Chen, Cheng-Fang Tsai, Dah-Yuu Lu, Chingju Lin
Glioblastoma multiforme (GBM) is the most common type of primary and malignant tumor occurring in the adult central nervous system. Temozolomide (TMZ) has been considered to be one of the most effective chemotherapeutic agents to prolong the survival of patients with glioblastoma. Many glioma cells develop drug-resistance against TMZ that is mediated by increasing O-6-methylguanine-DNA methyltransferase (MGMT) levels. The expression of connexin 43 was increased in the resistant U251 subline compared with the parental U251 cells...
January 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29299820/malignant-transformation-in-non-functioning-pituitary-adenomas-pituitary-carcinoma
#18
REVIEW
Nèle Lenders, Ann McCormack
Non-functioning pituitary carcinomas (NFPC) are defined as tumours of adenophyseal origin with craniospinal or systemic dissemination, with the absence of a hormonal hypersecretion syndrome. These are a histologically heterogenous group of tumours, comprising gonadotroph, null cell, "silent" tumours of corticotroph, somatotroph or lactotroph cell lineages as well as plurihormonal Pit-1 tumours. NFPC are exceedingly rare, and hence few cases have been described. This review has identified 38 patients with NFPC reported in the literature...
January 3, 2018: Pituitary
https://www.readbyqxmd.com/read/29298660/adjuvant-stereotactic-fractionated-radiotherapy-to-the-resection-cavity-in-recurrent-glioblastoma-the-gliocave-study-noa-17-aro-2016-3-dktk-rog-trial
#19
Christoph Straube, Hagen Scherb, Jens Gempt, Jan Kirschke, Claus Zimmer, Friederike Schmidt-Graf, Bernhard Meyer, Stephanie E Combs
BACKGROUND: Glioblastoma relapses in the vast majority of cases within 1 year. Maximum safe resection of the recurrent glioblastoma can be offered in some cases. Re-irradiation has been established for the treatment of recurrent glioblastoma, too. In both cases, adjuvant treatment, mostly using temozolomide, can improve PFS and OS after these interventions. However, combining gross tumor resection and adjuvant re-radiotherapy to the resection cavity has not been tested so far. METHODS/DESIGN: In the multicenter two-armed randomized Phase II GlioCave Study, fractionated stereotactic radiotherapy to the resection cavity, after gross tumor resection of recurrent glioblastoma, will be compared to observation...
January 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29296224/dormant-glioblastoma-cells-acquire-stem-cell-characteristics-and-are-differentially-affected-by-temozolomide-and-at101-treatment
#20
Vivian Adamski, Annika Hempelmann, Charlotte Flüh, Ralph Lucius, Michael Synowitz, Kirsten Hattermann, Janka Held-Feindt
Cellular dormancy is defined as a state in which cells enter quiescence driven by intrinsic or extrinsic factors, and striking parallels exist between the concept of cellular dormancy in malignancies and the cancer stem cell theory. We showed now that the proven dormancy markers insulin-like growth factor-binding protein 5, ephrin receptor A5 and histone cluster 1 H2B family member K were expressed in human glioblastomas in situ, were located in single tumor cells, and could be co-stained with each other and with the stem cell markers krüppel-like factor 4, octamer binding transcription factor 4 and sex determining region Y-box 2...
December 8, 2017: Oncotarget
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