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https://www.readbyqxmd.com/read/28212543/metabotropic-glutamate-receptors-as-a-new-therapeutic-target-for-malignant-gliomas
#1
REVIEW
Mery Stefani Leivas Pereira, Fábio Klamt, Chairini Cássia Thomé, Paulo Valdeci Worm, Diogo Losch de Oliveira
Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211108/evaluation-of-the-quality-and-health-literacy-demand-of-online-renal-diet-information
#2
K Lambert, J Mullan, K Mansfield, A Koukomous, L Mesiti
BACKGROUND: Dietary modification is critical in the self-management of chronic kidney disease. The present study describes the accuracy, quality and health literacy demand of renal diet information for adults with kidney disease obtained from the Internet and YouTube (www.youtube.com). METHODS: A comprehensive content analysis was undertaken in April and July 2015 of 254 eligible websites and 161 YouTube videos. The accuracy of the renal diet information was evaluated by comparing the key messages with relevant evidence-based guidelines for the dietary management of people with kidney disease...
February 16, 2017: Journal of Human Nutrition and Dietetics: the Official Journal of the British Dietetic Association
https://www.readbyqxmd.com/read/28195901/prognostic-molecular-and-imaging-biomarkers-in-primary-glioblastoma
#3
Edit Bosnyák, Sharon K Michelhaugh, Neil V Klinger, David O Kamson, Geoffrey R Barger, Sandeep Mittal, Csaba Juhász
PURPOSE: Several molecular glioma markers (including isocitrate dehydrogenase 1 [IDH1] mutation, amplification of the epidermal growth factor receptor [EGFR], and methylation of the O6-methylguanine-DNA methyltransferase [MGMT] promoter) have been associated with glioblastoma survival. In this study, we examined the association between tumoral amino acid uptake, molecular markers, and overall survival in patients with IDH1 wild-type (primary) glioblastoma. PATIENTS AND METHODS: Twenty-one patients with newly diagnosed IDH1 wild-type glioblastomas underwent presurgical MRI and PET scanning with alpha[C-11]-L-methyl-tryptophan (AMT)...
February 14, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28193626/autologous-heat-shock-protein-peptide-vaccination-for-newly-diagnosed-glioblastoma-impact-of-peripheral-pd-l1-expression-on-response-to-therapy
#4
Orin Bloch, Michael Lim, Michael E Sughrue, Ricardo J Komotar, John M Abrahams, Donald M O'Rourke, Anthony D'Ambrosio, Jeffrey N Bruce, Andrew T Parsa
PURPOSE: Standard therapy for newly diagnosed glioblastoma (GBM) is surgical resection, followed by concurrent radiotherapy and temozolomide chemotherapy. In this phase 2 clinical trial, the addition of an autologous heat shock protein vaccine to standard therapy was evaluated. Tumor-induced immunosuppression, mediated by expression of PD-L1 on tumor and circulating immune cells, may impact the efficacy of vaccination. Expression of PD-L1 on peripheral myeloid cells was evaluated for the first time as a predictor of survival...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28188088/high-dose-neural-stem-cell-radiation-may-not-improve-survival-in-glioblastoma
#5
R Achari, M Arunsingh, R K Badgami, A Saha, S Chatterjee, R K Shrimali, I Mallick, B Arun
AIMS: To evaluate the effect of radiotherapy dose-volume parameters of neural stem cell (NSC) compartment on progression-free survival (PFS) and overall survival after post-resection chemoradiation in newly diagnosed glioblastoma. MATERIALS AND METHODS: Sixty-one patients with unifocal glioblastoma were included. Ipsilateral (NSC_Ipsi), contralateral (NSC_Contra) and combined NSC (NSC_Combined) were contoured on radiotherapy planning computerised tomography datasets...
February 8, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28185110/foxm1-mediated-rfc5-expression-promotes-temozolomide-resistance
#6
Wan-Xin Peng, Xiu Han, Chun-Li Zhang, Lu Ge, Feng-Yi Du, Jie Jin, Ai-Hua Gong
Although methylguanine-DNA-methyltransferase (MGMT) plays an important role in resistance to temozolomide (TMZ) in glioma, 40% of gliomas with MGMT inactivation are still resistant to TMZ. The underlying mechanism is not clear. Here, we report that forkhead box M1 (FoxM1) transcriptionally activates the expression of DNA repair gene replication factor C5 (RFC5) to promote TMZ resistance in glioma cells independent of MGMT activation. We showed that RFC5 expression is positively correlated with FoxM1 expression in human glioma cells and FoxM1 is able to transcriptionally activate RFC expression by interaction with the RFC5 promoter...
February 9, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28177192/dna-targeted-inhibition-of-mgmt
#7
Nathan William Luedtke, Theodor Marsoner, Olivia Schmidt, Therese Trimer
The cationic porphyrin 5,10,15,20-tetrakis (diisopropyl-guanidine)-21H,23H-porphine "DIGPor" selectively binds to DNA containing O6-methylguanine (O6-MeG) and inhibits the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). The O6-MeG selectivity and MGMT inhibitory activity of DIGPor was improved by incorporating ZnII into the porphyrin. The resulting metal complex "Zn-DIGPor" potentiated the activity of the DNA alkylating drug temozolomide in an MGMT-expressing cell line. To the best of our knowledge, these results provide the first examples of DNA-targeted MGMT inhibition...
February 8, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28176884/impact-of-including-peritumoral-edema-in-radiotherapy-target-volume-on-patterns-of-failure-in-glioblastoma-following-temozolomide-based-chemoradiotherapy
#8
Seo Hee Choi, Jun Won Kim, Jee Suk Chang, Jae Ho Cho, Se Hoon Kim, Jong Hee Chang, Chang-Ok Suh
We assessed the impact of including peritumoral edema in radiotherapy volumes on recurrence patterns among glioblastoma multiforme (GBM) patients treated with standard chemoradiotherapy (CRT). We analyzed 167 patients with histologically confirmed GBM who received temozolomide (TMZ)-based CRT between May 2006 and November 2012. The study cohort was divided into edema (+) (n = 130) and edema (-) (n = 37) groups, according to whether the entire peritumoral edema was included. At a median follow-up of 20 months (range, 2-99 months), 118 patients (71%) experienced progression/recurrence (infield: 69%; marginal: 26%; outfield: 16%; CSF seeding: 12%)...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28168370/volume-of-high-risk-intratumoral-subregions-at-multi-parametric-mr-imaging-predicts-overall-survival-and-complements-molecular-analysis-of-glioblastoma
#9
Yi Cui, Shangjie Ren, Khin Khin Tha, Jia Wu, Hiroki Shirato, Ruijiang Li
OBJECTIVE: To develop and validate a volume-based, quantitative imaging marker by integrating multi-parametric MR images for predicting glioblastoma survival, and to investigate its relationship and synergy with molecular characteristics. METHODS: We retrospectively analysed 108 patients with primary glioblastoma. The discovery cohort consisted of 62 patients from the cancer genome atlas (TCGA). Another 46 patients comprising 30 from TCGA and 16 internally were used for independent validation...
February 6, 2017: European Radiology
https://www.readbyqxmd.com/read/28161760/incidence-survival-pathology-and-genetics-of-adult-latino-americans-with-glioblastoma
#10
Maryam Shabihkhani, Donatello Telesca, Masoud Movassaghi, Yalda B Naeini, Kourosh M Naeini, Seyed Amin Hojat, Diviya Gupta, Gregory M Lucey, Michael Ontiveros, Michael W Wang, Lauren S Hanna, Desiree E Sanchez, Sergey Mareninov, Negar Khanlou, Harry V Vinters, Marvin Bergsneider, Phioanh Leia Nghiemphu, Albert Lai, Linda M Liau, Timothy F Cloughesy, William H Yong
: Latino Americans are a rapidly growing ethnic group in the United States but studies of glioblastoma in this population are limited. We have evaluated characteristics of 21,184 glioblastoma patients from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. This SEER data from 2001 to 2011 draws from 28% of the U.S. POPULATION: Latinos have a lower incidence of GBM and present slightly younger than non-Latino Whites. Cubans present at an older age than other Latino sub-populations...
February 4, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28159862/temozolomide-in-the-era-of-precision-medicine
#11
REVIEW
Anish Thomas, Mamoru Tanaka, Jane Trepel, William C Reinhold, Vinodh N Rajapakse, Yves Pommier
In the January 1, 2017, issue of Cancer Research, Nagel and colleagues demonstrate the value of assays that determine the DNA repair capacity of cancers in predicting response to temozolomide. Using a fluorescence-based multiplex flow cytometric host cell reactivation assay that provides simultaneous readout of DNA repair capacity across multiple pathways, they show that the multivariate drug response models derived from cell line data were applicable to patient-derived xenograft models of glioblastoma. In this commentary, we first outline the mechanism of activity and current clinical application of temozolomide, which, until now, has been largely limited to glioblastoma...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28152515/o-6-methylguanine-dna-methyltransferase-expression-is-associated-with-pituitary-adenoma-tumor-recurrence-a-systematic-meta-analysis
#12
Congxin Dai, Bowen Sun, Xiaohai Liu, Xinjie Bao, Ming Feng, Yong Yao, Junji Wei, Kan Deng, Chengxian Yang, Xueyuan Li, Wenbin Ma, Renzhi Wang
O-6-methylguanine-DNA methyltransferase (MGMT) reportedly counteracts the cytotoxic effects of the alkylating agent temozolomide. MGMT expression is often low in aggressive pituitary adenomas (PAs) and recurrent PAs. However, because these associations are controversial, we performed this meta-analysis to clarify the involvement of MGMT in the prognosis and clinicopathology of PA. We searched for relevant studies in electronic databases (MEDLINE, the Cochrane Library Database, EMBASE, CINAHL, Web of Science and the Chinese Biomedical Database (CBD)) and calculated/pooled the odds ratios (ORs) or standard mean differences (SMDs) with 95% confidence intervals (95% CIs)...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28148826/prognostic-relevance-of-tumor-purity-and-tert-promoter-mutations-on-mgmt-promoter-methylation-in-glioblastoma
#13
Eva Schulze Heuling, Felix Knab, Josefine Radke, Eskil Eskilsson, Emmanuel Martinez-Ledesma, Arend Koch, Marcus Czabanka, Christoph Dieterich, Roel G Verhaak, Christoph Harms, Philipp Euskirchen
: Promoter methylation status of O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme, is a critical biomarker in glioblastoma multiforme (GBM) as treatment decisions and clinical trial inclusion rely on its accurate assessment. However, interpretation of results is complicated by poor inter-assay reproducibility as well as weak a correlation between methylation status and expression levels of MGMT. The present study systematically investigates the influence of tumor purity on tissue subjected to MGMT analysis...
February 1, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28147335/promoter-methylation-of-mcam-er%C3%AE-and-er%C3%AE-in-serum-of-early-stage-prostate-cancer-patients
#14
Mariana Brait, Mithu Banerjee, Leonel Maldonado, Akira Ooki, Myriam Loyo, Elisa Guida, Evgeny Izumchenko, Leslie Mangold, Elizabeth Humphreys, Eli Rosenbaum, Alan Partin, David Sidransky, Mohammad Obaidul Hoque
BACKGROUND: Prostate cancer (PC) is the second most common cancer among men worldwide. Currently, the most common non-invasive approach for screening and risk assessment of PC is measuring the level of serum prostate-specific antigen (PSA). However, the sensitivity of PSA is 42.8 % and specificity is 41.1%. As a result, the serum PSA test leads to numerous unneeded biopsies. Therefore, a rigorous search for biomarkers for early detection of PC is ongoing. In this study, we aim to assess a panel of epigenetic markers in an intend to develop an early detection test for PC...
28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28147244/the-pi3k-inhibitor-gdc-0941-enhances-radiosensitization-and-reduces-chemoresistance-to-temozolomide-in-gbm-cell-lines
#15
Fei Shi, Hongchuan Guo, Rong Zhang, Hongyu Liu, Liangliang Wu, Qiyan Wu, Jialin Liu, Tianyi Liu, Qiuhang Zhang
Glioblastoma multiforme (GBM) is among the most lethal of all human tumors. It is the most frequently occurring malignant primary brain tumor in adults. The current standard of care (SOC) for GBM is initial surgical resection followed by treatment with a combination of temozolomide (TMZ) and ionizing radiation (IR). However, GBM has a dismal prognosis, and survivors have compromised quality of life owing to the adverse effects of radiation. GBM is characterized by overt activity of the phosphoinositide 3-kinase (PI3K) signaling pathway...
January 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28144153/fbln4-as-candidate-gene-associated-with-long-term-and-short-term-survival-with-primary-glioblastoma
#16
Fubin Li, Yiping Li, Kewei Zhang, Ye Li, Ping He, Yujia Liu, Hongyan Yuan, Honghua Lu, Jinxiang Liu, Songtian Che, Zhenju Li, Li Bie
BACKGROUND: Glioblastoma multiforme (GBM) is the most common malignant and lethal type of primary central nervous system tumor in humans. In spite of its high lethality, a small percentage of patients have a relatively good prognosis, with median survival times of 36 months or longer. The identification of clinical subsets of GBM associated with distinct molecular genetic profiles has made it possible to design therapies tailored to treat individual patients. METHODS: We compared microarray data sets from long-term survivors (LTSs) and short-term survivors (STSs) to screen for prognostic biomarkers in GBM patients using the WebArrayDB platform...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28143714/chloroethylating-nitrosoureas-in-cancer-therapy-dna-damage-repair-and-cell-death-signaling
#17
REVIEW
Teodora Nikolova, Wynand P Roos, Oliver H Krämer, Herwig M Strik, Bernd Kaina
Chloroethylating nitrosoureas (CNU), such as lomustine, nimustine, semustine, carmustine and fotemustine are used for the treatment of malignant gliomas, brain metastases of different origin, melanomas and Hodgkin disease. They alkylate the DNA bases and give rise to the formation of monoadducts and subsequently interstrand crosslinks (ICL). ICL are critical cytotoxic DNA lesions that link the DNA strands covalently and block DNA replication and transcription. As a result, S phase progression is inhibited and cells are triggered to undergo apoptosis and necrosis, which both contribute to the effectiveness of CNU-based cancer therapy...
January 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28135856/promoter-hypermethylation-and-its-impact-on-expression-of-mgmt-gene-in-the-git-malignant-patients-of-kashmiri-origin
#18
Arif Akbar Bhat, Hilal Ahmad Wani, Shiekh Ishaq, Ajaz Ahmad Waza, Rawoof Ahmad Malik, Iram Shabir, Showkat Jeelani, Showkat Kadla, Waseem Qureshie, Akbar Masood, Sabhiya Majid
Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Gastrointestinal tract (GIT) cancer is a major medical and economic burden worldwide. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumor suppressor genes. Although a number of cancer-associated genes have been found to be hypermethylated in GIT cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown...
January 31, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28110959/patterns-of-failure-for-patients-with-glioblastoma-following-o-2-18-f-fluoroethyl-l-tyrosine-pet-and-mri-guided-radiotherapy
#19
Michael Lundemann, Junia Cardoso Costa, Ian Law, Svend Aage Engelholm, Aida Muhic, Hans Skovgaard Poulsen, Per Munck Af Rosenschold
BACKGROUND AND PURPOSE: To evaluate the patterns of failure following clinical introduction of amino-acid O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET)-PET-guided target definition for radiotherapy (RT) of glioblastoma patients. MATERIALS AND METHODS: The first 66 consecutive patients with confirmed histology, scanned using FET-PET/CT and MRI were selected for evaluation. Chemo-radiotherapy was delivered to a volume based on both MRI and FET-PET (PETvol). The volume of recurrence (RV) was defined on MRI data collected at the time of progression according to RANO criteria...
January 19, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28110346/prognostic-value-of-molecular-and-imaging-biomarkers-in-patients-with-supratentorial-glioma
#20
Egesta Lopci, Marco Riva, Laura Olivari, Fabio Raneri, Riccardo Soffietti, Arnoldo Piccardo, Alberto Bizzi, Pierina Navarria, Anna Maria Ascolese, Roberta Rudà, Bethania Fernandes, Federico Pessina, Marco Grimaldi, Matteo Simonelli, Marco Rossi, Tommaso Alfieri, Paolo Andrea Zucali, Marta Scorsetti, Lorenzo Bello, Arturo Chiti
PURPOSE: We evaluated the relationship between (11)C-methionine PET ((11)C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. METHODS: A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative (11)C-METH PET were analysed. Semiquantitative evaluation of the (11)C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV)...
January 21, 2017: European Journal of Nuclear Medicine and Molecular Imaging
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