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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/29328445/the-effects-of-interleukin-2-and-rad-p53-as-a-treatment-for-glioblastoma
#2
Hai-Bo Qiao, Jia Li, Lian-Jie Lv, Ben-Jin Nie, Peng Lu, Feng Xue, Zhi-Ming Zhang
Interleukin 2 (IL-2) is an anti-cancer cytokine that stimulates T cell propagation, triggering innate and adaptive immunity. IL-2 has been used for cancer therapy and has achieved curative effects. Recombinant adenovirus p53 injection (rAd‑p53) is a gene therapeutic agent that may improve the prognosis of patients with glioblastoma (GBM). In the present study, the effect of combined IL‑2 and rAd‑p53 treatment was studied. The ability of IL‑2 to stimulate immunoregulation and the ability of p53 to induce apoptosis for GBM was researched in the GBM tumor model...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29309973/digital-pcr-quantification-of-serpina1-predicts-prognosis-in-high-grade-glioma
#3
Satoshi Ookawa, Masahiko Wanibuchi, Yuko Kataoka-Sasaki, Masanori Sasaki, Shinichi Oka, Shunya Ohtaki, Shouhei Noshiro, Katsuya Komatsu, Yukinori Akiyama, Takeshi Mikami, Nobuhiro Mikuni, Jeffery D Kocsis, Osamu Honmou
BACKGROUND: SERPINA1 plays an anti-inflammatory role in protecting tissues from proteolytic mechanisms. SERPINA1 is positive in gliomas by immunohistochemical analysis; however, the role of SERPINA1 including the relationship with prognosis has been uncertain. In recent years, digital polymerase chain reaction (PCR) has provided ultra-sensitive assessment of mRNA expression from formalin fixed paraffin embedded (FFPE) tissues. OBJECTIVE: In this study, we quantitatively determined the expression of SERPINA1 in high-grade gliomas (HGGs) using digital PCR and analyzed its relationship with prognosis...
January 5, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29308973/current-and-emerging-egfr-therapies-for-glioblastoma
#4
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/29303013/inhibition-of-plasma-kallikrein-kinin-system-to-alleviate-renal-injury-and-arthritis-symptoms-in-rats-with-adjuvant-induced-arthritis
#5
Jie Zhu, Hui Wang, Jingyu Chen, Wei Wei
BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Impairment of kidney functions in RA was observed. However, the mechanism of kidney injury of RA has not been clear. Plasma kallikrein-kinin system (KKS) was involved in inflammatory processes in kidney disease. AIM: This study aimed to explore the role of plasma KKS in immune reactions and kidney injury of RA. RESULTS: The paw of AA rats appeared to be swelling and redness, the arthritis index was significantly increased on the 18, 21 and 24 d after injection and secondary inflammation in multi-sites was observed...
January 5, 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29290950/human-fibulin-3-protein-variant-expresses-anti-cancer-effects-in-the-malignant-glioma-extracellular-compartment-in-intracranial-xenograft-models
#6
Yanyan Li, Yuan Hu, Chuanjin Liu, Qingyue Wang, Xiaoxiao Han, Yong Han, Xue-Shun Xie, Xiong-Hui Chen, Xiang Li, Eric R Siegel, Kambiz Afrasiabi, Mark E Linskey, You-Xin Zhou, Yi-Hong Zhou
Background: Decades of cytotoxic and more recently immunotherapy treatments for malignant glioma have had limited success due to dynamic intra-tumoral heterogeneity. The dynamic interplay of cancer cell subpopulations has been found to be under the control of proteins in the cancer microenvironment. EGF-containing fibulin-like extracellular matrix protein (EFEMP1) (also fibulin-3) has the multiple functions of suppressing cancer growth and angiogenesis, while promoting cancer cell invasion...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290619/-a-giant-cell-arteritis-revealing-a-goodpasture-s-syndrome
#7
Pascaline M Alix, Amélie Belloi, Émilie Berthoux, Frédérique Dijoud, Emmanuel Villar, Caroline Pariset
Goodpasture's syndrome is a triad of anti-glomerular basement membrane (anti-GBM) circulating antibodies, glomerulonephritis and pulmonary hemorrhage. We reported a 65-year-old woman with headaches, asthenia and weight loss. Giant cell arteritis was confirmed by temporal artery biopsy. The patient had associated renal condition with moderate acute renal failure, proteinuria and haematuria. Renal biopsy showed extracapillary glomerulonephritis and linear staining of immunoglobulins G along glomerular basement membrane...
December 28, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29289891/new-antiglioma-zwitterionic-pronucleotides-with-an-fdump-framework
#8
Agnieszka Szymanska-Michalak, Dariusz Wawrzyniak, Grzegorz Framski, Jacek Stawinski, Jan Barciszewski, Adam Kraszewski
We have designed and synthesized new 5-fluoro-2'-deoxyuridine 5'-phosphate pronucleotides which can function as potential agents against the glioblastoma multiforme tumor. Their anti-malignant potency has been tested against T98G, U-118 MG, U-87 MG gliomas, HeLa, and Caco-2 cancer cell lines, using MRC-5 healthy cells as a reference. Five of the sixteen compounds (4c, 4f-i) exhibited significant anticancer potency and high selectivity indices (SI 12-66). It is likely that these zwitterionic pronucleotides may function in a similar manner to zwitterionic phospholipids, by inducing cell membrane charge disorder, making the cell permeable to bioactive agents...
December 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29285298/andrographolide-suppresses-the-migratory-ability-of-human-glioblastoma-multiforme-cells-by-targeting-erk1-2-mediated-matrix-metalloproteinase-2-expression
#9
Shih-Liang Yang, Fu-Hsuan Kuo, Pei-Ni Chen, Yi-Hsien Hsieh, Nuo-Yi Yu, Wei-En Yang, Ming-Ju Hsieh, Shun-Fa Yang
Glioblastoma multiforme (GBM) can be a fatal tumor because of difficulties in treating the related metastasis. Andrographolide is the bioactive component of the Andrographis paniculata. Andrographolide possesses the anti-inflammatory activity and inhibits the growth of various cancers; however, its effect on GBM cancer motility remains largely unknown. In this study, we examined the antimetastatic properties of andrographolide in human GBM cells. Our results revealed that andrographolide inhibited the invasion and migration abilities of GBM8401 and U251 cells...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29275837/plasticity-and-heterogeneity-of-th17-in-immune-mediated-kidney-diseases
#10
REVIEW
Christian F Krebs, Ulf Panzer
Anti-neutrophil cytoplasmatic antibody (ANCA)-associated glomerulonephritis, anti-glomerular basement membrane (GBM) glomerulonephritis and lupus nephritis are the most common causes of rapid progressive glomerulonephritis (RPGN) in the Western world. These aggressive forms of autoimmune kidney diseases significantly contribute to end-stage renal disease and are associated with high morbidity and mortality. Moreover, patients show significant heterogeneity with respect to clinical outcome and response to therapy...
December 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29274334/targeting-of-egfr-increase-anti-cancer-effects-of-arsenic-trioxide-promising-treatment-for-glioblastoma-multiform
#11
Yashar Mesbahi, Ali Zekri, Shahin Ahmadian, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Glioblastoma multiform (GBM) accounts for the most common form of primary brain tumors with very limited survival rate. Drug resistance is the main challenges for good prognosis of GBM patients. Arsenic trioxide (ATO) as a multifunctional drug has been investigated for the treatment of several solid tumors. Amplification/overexpression of the epidermal growth factor receptor (EGFR) gene as a signature genetic abnormality of GBM tumors can be a chemoresistance mechanism. In this study, we use erlotinib as an EGFR inhibitor to increase the sensitivity of GBM cell lines to ATO treatment...
December 20, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29251531/micellar-formulations-of-crizotinib-and-dasatinib-in-the-management-of-glioblastoma-multiforme
#12
Khaled Greish, Anfal Jasim, Neha Parayath, Sara Abdelghany, Ali Alkhateeb, Sebastien Taurin, Hayley Nehoff
Glioblastoma multiforme (GBM) defies the currently practiced management of radiotherapy, chemotherapy and surgery and hence, it is associated with a high fatality rate with a median survival of 14.6 months. In our previous work investigating different tyrosine kinase inhibitors (TKIs), we established that a combination of Crizotinib and Dasatinib exerted the most potent effect on different GBM cell lines. In the current work, to improve targeted therapy at the site of the tumor and avoid systemic toxicity, we exploited the enhanced permeability and retention effect by designing micellar formulations of these two TKIs...
December 18, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29242629/immune-microenvironment-of-experimental-rat-c6-gliomas-resembles-human-glioblastomas
#13
Anna Gieryng, Dominika Pszczolkowska, Katarzyna Bocian, Michal Dabrowski, Wenson David Rajan, Michal Kloss, Jakub Mieczkowski, Bozena Kaminska
Glioblastoma (GBM) is the most aggressive primary brain tumor, with ineffective anti-tumor responses and a poor prognosis despite aggressive treatments. GBM immune microenvironment is heterogenous  and activation of specific immune populations in GBM is not fully characterized. Reliable animal models are critical for defining mechanisms of anti-tumor immunity. First we analyzed the immune subpopulations present in rat C6 gliomas. Using flow cytometry we determined kinetics of infiltration of myeloid cells and T lymphocytes into glioma-bearing brains...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29236891/high-expression-of-xiap-and-bcl-2-may-inhibit-programmed-cell-death-in-glioblastomas
#14
Daniela Pretti da Cunha Tirapelli, Isis Lacrose Lustosa, Sarah Bomfim Menezes, Indira Maynart Franco, Andressa Romualdo Rodrigues, Fernanda Maris Peria, Alexandre Magno da Nóbrega Marinho, Luciano Neder Serafini, Carlos Gilberto Carlotti, Luís Fernando Tirapelli
Glioblastoma (GBM) is the most malignant glioma and represents 29% of all brain tumors. Tumorigenesis is intimately connected with characteristics acquired in the physiologic pathway of cellular death. OBJECTIVE: In the present study, the expression of anti-apoptotic (XIAP and Bcl-2) and apoptotic (cytochrome C, caspase 9, APAF-1), caspase 3 and the Smac/DIABLO genes related to the apoptosis pathway were evaluated in 30 samples of glioblastoma. METHODS: The gene expression was evaluated in 30 glioblastomas (WHO grade IV) and compared to 10 white matter control samples with real-time PCR...
December 2017: Arquivos de Neuro-psiquiatria
https://www.readbyqxmd.com/read/29232556/mst4-phosphorylation-of-atg4b-regulates-autophagic-activity-tumorigenicity-and-radioresistance-in-glioblastoma
#15
Tianzhi Huang, Chung Kwon Kim, Angel A Alvarez, Rajendra P Pangeni, Xuechao Wan, Xiao Song, Taiping Shi, Yongyong Yang, Namratha Sastry, Craig M Horbinski, Songjian Lu, Roger Stupp, John A Kessler, Ryo Nishikawa, Ichiro Nakano, Erik P Sulman, Xinghua Lu, Charles David James, Xiao-Ming Yin, Bo Hu, Shi-Yuan Cheng
ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29221175/trpm8-is-required-for-survival-and-radioresistance-of-glioblastoma-cells
#16
Dominik Klumpp, Stephanie C Frank, Lukas Klumpp, Efe C Sezgin, Marita Eckert, Lena Edalat, Martin Bastmeyer, Daniel Zips, Peter Ruth, Stephan M Huber
TRPM8 is a Ca2+-permeable nonselective cation channel belonging to the melastatin sub-group of the transient receptor potential (TRP) family. TRPM8 is aberrantly overexpressed in a variety of tumor entities including glioblastoma multiforme where it reportedly contributes to tumor invasion. The present study aimed to disclose further functions of TRPM8 in glioma biology in particular upon cell injury by ionizing radiation. To this end, TCGA data base was queried to expose the TRPM8 mRNA abundance in human glioblastoma specimens and immunoblotting was performed to analyze the TRPM8 protein abundance in primary cultures of human glioblastoma...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218086/microrna-520d-5p-inhibits-human-glioma-cell-proliferation-and-induces-cell-cycle-arrest-by-directly-targeting-pttg1
#17
Tongle Zhi, Kuan Jiang, Xiupeng Xu, Tianfu Yu, Weining Wu, Er Nie, Xu Zhou, Xin Jin, Junxia Zhang, Yingyi Wang, Ning Liu
Glioma accounts for the majority of primary malignant brain tumors in adults and is highly aggressive. Although various therapeutic approaches have been applied, outcomes of glioma treatment remain poor. Acquiring a better understanding of the pathogenic mechanisms is essential to the design of effective therapeutic strategies. Previous studies have found that miR-520d-5p was negatively correlated with glioma grade, but its role and mechanism in glioma progression remain largely unknown. In the present study, we reported that miR-520d-5p directly targeted the Pituitary Tumor Transforming Gene 1 (PTTG1) and functioned as a tumor-suppressor in glioma...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29207684/recurrent-glioma-clinical-trial-checkmate-143-the-game-is-not-over-yet
#18
REVIEW
Anna C Filley, Mario Henriquez, Mahua Dey
Glioblastoma (GBM) is the most common, and aggressive, primary brain tumor in adults. With a median patient survival of less than two years, GBM represents one of the biggest therapeutic challenges of the modern era. Even with the best available treatment, recurrence rates are nearly 100% and therapeutic options at the time of relapse are extremely limited. Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody, has provided significant clinical benefits in the treatment of various advanced cancers and represented a promising therapy for primary and recurrent GBM...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29202377/quantifying-the-prognostic-significance-in-glioblastoma-of-seizure-history-at-initial-presentation-a-systematic-review-and-meta-analysis
#19
REVIEW
Victor M Lu, Toni R Jue, Kevin Phan, Kerrie L McDonald
The role of prognostic factors in the management of glioblastoma (GBM) is very important given the stasis in improving its clinical outcomes. Patients who initially present with a positive seizure history at diagnosis have anecdotally experienced superior survival outcomes. The aim of this review was to perform a systematic review and meta-analysis to quantify the potential prognostic significance of positive seizure history in GBM patients. A search strategy was performed using the PRISMA guidelines for article identification, screening, eligibility and inclusion...
December 1, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29196443/modelling-glioblastoma-tumour-host-cell-interactions-using-adult-brain-organotypic-slice-co-culture
#20
Maria Angeles Marques-Torrejon, Ester Gangoso, Steven M Pollard
Glioblastoma (GBM) is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as GBM stem cells (GSCs). Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human)...
December 1, 2017: Disease Models & Mechanisms
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