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https://www.readbyqxmd.com/read/28100038/trim8-regulates-stemness-in-glioblastoma-through-pias3-stat3
#1
Changming Zhang, Subhas Mukherjee, Carol Tucker-Burden, James L Ross, Monica J Chau, Jun Kong, Daniel J Brat
Glioblastoma (GBM) is the most malignant form of primary brain tumor and GBM stem-like cells (GSCs) contribute to the rapid growth, therapeutic resistance and clinical recurrence of these fatal tumors. STAT3 signaling supports the maintenance and proliferation of GSCs, yet regulatory mechanisms are not completely understood. Here we report that tri-partite motif containing protein 8 (TRIM8) activates STAT3 signaling to maintain stemness and self-renewing capabilities of GSCs. TRIM8 (also known as "glioblastoma expressed ring finger protein") is expressed equally in GBM and normal brain tissues, despite its hemizygous deletion in the large majority of GBMs, and its expression is highly correlated with stem cell markers...
January 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28098764/iqgap1-in-podosomes-invadosomes-is-involved-in-the-progression-of-glioblastoma-multiforme-depending-on-the-tumor-status
#2
Deborah Rotoli, Natalia Dolores Pérez-Rodríguez, Manuel Morales, María Del Carmen Maeso, Julio Ávila, Ali Mobasheri, Pablo Martín-Vasallo
Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28091986/shift-of-microrna-profile-upon-glioma-cell-migration-using-patient-derived-spheroids-and-serum-free-conditions
#3
Sune Munthe, Bo Halle, Henning B Boldt, Helle Christiansen, Steffen Schmidt, Vivek Kaimal, Jessica Xu, Sonya Zabludoff, Jan Mollenhauer, Frantz R Poulsen, Bjarne W Kristensen
Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery. Another major reason is tumor cells having a so-called cancer stem cell phenotype being therefore resistant towards traditional chemo- and radiotherapy. A group of novel molecular targets are microRNAs (miRNAs). MiRNAs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. The aim of this study was to identify differentially expressed miRNAs in migrating GBM cells using serum-free stem cell conditions...
January 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28089821/the-role-of-stat3-in-glioblastoma-progression-through-dual-influences-on-tumor-cells-and-the-immune-microenvironment
#4
Nakho Chang, Sun Hee Ahn, Doo-Sik Kong, Hye Won Lee, Do-Hyun Nam
Glioblastoma multiforme (GBM) is the most aggressive form of cancer that begins within the brain; generally, the patient has a dismal prognosis and limited therapeutic options. Signal transducer and activator of transcription 3 (STAT3) is a critical mediator of tumorigenesis, tumor progression, and suppression of anti-tumor immunity in GBM. In a high percentage of GBM cells and tumor microenvironments, persistent activation of STAT3 induces cell proliferation, anti-apoptosis, glioma stem cell maintenance, tumor invasion, angiogenesis, and immune evasion...
January 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28087635/rb-controls-growth-survival-and-neuronal-migration-in-human-cerebral-organoids
#5
Takeshi Matsui, Vanesa Nieto-Estévez, Sergii Kyrychenko, Jay W Schneider, Jenny Hsieh
Retinoblastoma (RB) is a tumor suppressor gene which regulates cell cycle entry to S phase via E2F transcription factors. Using knockout (KO) mice, it has been described that Rb plays a role in cell migration and differentiation in developing and adult brain as well as apoptosis. In addition, the RB family is required for the self-renewal and survival of human embryonic stem cells (ESCs). However, little is known about the role of this gene in human brain development. Here, we investigated the role of RB in cerebral organoids from human ESCs deficient for RB...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28081224/resveratrol-impairs-glioma-stem-cells-proliferation-and-motility-by-modulating-the-wnt-signaling-pathway
#6
Chiara Cilibrasi, Gabriele Riva, Gabriele Romano, Massimiliano Cadamuro, Riccardo Bazzoni, Valentina Butta, Laura Paoletta, Leda Dalprà, Mario Strazzabosco, Marialuisa Lavitrano, Roberto Giovannoni, Angela Bentivegna
Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12-15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be the real driving force of tumor initiation, progression and relapse. Therefore, better therapeutic strategies GSCs-targeted are needed. Resveratrol is a polyphenolic phytoalexin found in fruits and vegetables displaying pleiotropic health benefits...
2017: PloS One
https://www.readbyqxmd.com/read/28069364/compact-mri-for-the-detection-of-teratoma-development-following-intrathecal-human-embryonic-stem-cell-injection-in-nod-scid-mice
#7
Yuval Ramot, Yael S Schiffenbauer, Netanel Amouyal, Nathan Ezov, Michal Steiner, Michal Izrael, Neta Lavon, Arik Hasson, Michel Revel, Abraham Nyska
Stem cells are emerging as a promising new treatment modality for a variety of central nervous system disorders. However, their use is hampered by the potential for the development of teratomas and other tumors. Therefore, there is a crucial need for the development of methods for detecting teratomas in preclinical safety studies. The aim of the current study is to assess the ability of a compact Magnetic Resonance Imaging (MRI) system to detect teratoma formation in mice. Five NOD-SCID mice were injected intrathecally with human embryonic stem cells (hESCs), with two mice serving as controls...
January 6, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28069038/motility-of-glioblastoma-cells-is-driven-by-netrin-1-induced-gain-of-stemness
#8
Irene Ylivinkka, Harri Sihto, Olli Tynninen, Yizhou Hu, Aki Laakso, Riku Kivisaari, Pirjo Laakkonen, Jorma Keski-Oja, Marko Hyytiäinen
BACKGROUND: Glioblastoma is an untreatable brain cancer. The tumors contain a population of stem-like cells which are highly invasive and resistant to therapies. These cells are the main reason for the lethality of glioblastoma. Extracellular guidance molecule netrin-1 promotes the invasiveness and survival of various cancer cell types. We have previously found that netrin-1 activates Notch signaling, and Notch signaling associates with cell stemness. Therefore, we have here investigated the effects of netrin-1 on glioblastoma pathogenesis and glioblastoma cell stemness...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28066899/a-role-for-the-histone-h2a-deubiquitinase-mysm1-in-maintenance-of-cd8-t-cells
#9
Michael Förster, Rupinder K Boora, Jessica C Petrov, Nassima Fodil, Isabella Albanese, Jamie Kim, Philippe Gros, Anastasia Nijnik
Several previous studies outlined the importance of the histone H2A deubiquitinase (H2A-DUB) MYSM1 in the regulation of stem cell quiescence and hematopoiesis. In this study we investigated the role of MYSM1 in T cell development. Using mouse models that allow conditional Mysm1 ablation at late stages of thymic development, we found that MYSM1 is intricately involved in the maintenance, activation, and survival of CD8+ T cells. Mysm1 ablation resulted in a 2-fold reduction in CD8+ T cell numbers, and also led to a hyperactivated CD8+ T cell state accompanied by impaired proliferation and increased proinflammatory cytokine production after ex vivo stimulation...
January 9, 2017: Immunology
https://www.readbyqxmd.com/read/28063758/acidic-ph-with-coordinated-reduction-of-basic-fibroblast-growth-factor-maintains-the-glioblastoma-stem-cell-like-phenotype-in%C3%A2-vitro
#10
Elizabeth M Haley, Samantha G Tilson, Ursula L Triantafillu, Justin W Magrath, Yonghyun Kim
Glioblastoma stem cells (GSCs) are a unique subpopulation of cells within glioblastoma multiforme (GBM) brain tumors that possess the ability to self-renew and differentiate into bulk tumor cells. GSCs are resistant to currently available treatments and are the likely culprit behind tumor relapse in GBM patients. However, GSCs are currently inaccessible to the larger scientific community because obtaining a sufficient number of GSCs remains technically challenging and cost-prohibitive. Thus, the objective of this study was to develop a more efficient GSC culture strategy that results in a higher cell yield of GSCs at a lower cost...
January 4, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28062709/trifluoperazine-a-well-known-antipsychotic-inhibits-glioblastoma-invasion-by-binding-to-calmodulin-and-disinhibiting-calcium-release-channel-ip3r
#11
Seokmin Kang, Jinpyo Hong, Jung Moo Lee, Hyo Eun Moon, Borami Jeon, Jungil Choi, Nal Ae Yoon, Sun Ha Paek, Eun Joo Roh, C Justin Lee, Sang Soo Kang
Calcium (Ca(2+)) signaling is an important signaling process, implicated in cancer cell proliferation and motility of the deadly glioblastomas that aggressively invade neighboring brain tissue. We have previously demonstrated that caffeine blocks glioblastoma invasion and extends survival by inhibiting Ca(2+) release channel inositol 1,4,5-trisphosphate receptor (IP3R) subtype 3. Trifluoperazine (TFP) is an FDA-approved antipsychotic drug for schizophrenia. Interestingly, TFP has been recently reported to show a strong anticancer effect on lung cancer, hepatocellular carcinoma, and T-cell lymphoma...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28055976/cd133-in-brain-tumor-the-prognostic-factor
#12
Bin Li, Cian M McCrudden, Hiu Fung Yuen, Xinping Xi, Peng Lyu, Kwok Wah Chan, Shu Dong Zhang, Hang Fai Kwok
CD133 has been shown to be an important stem cell factor that promotes glioma progression. However, the mechanism for CD133-mediated glioma progression has yet to be fully elucidated. In this study, we found that CD133 mRNA expression was a prognostic marker in three independent glioma patient cohorts, corroborating a putative role for CD133 in glioma progression. Importantly, we found that CD133 expression in glioma was highly correlated with the expression of HOX gene stem cell factors (HOXA5, HOXA7, HOXA10, HOXC4 and HOXC6)...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28040710/rest-represses-mir-124-and-mir-203-to-regulate-distinct-oncogenic-properties-of-glioblastoma-stem-cells
#13
Anantha L Marisetty, Sanjay K Singh, Tran N Nguyen, Cristian Coarfa, Bin Liu, Sadhan Majumder
BACKGROUND: Glioblastoma (GBM) is one of the most common, aggressive, and invasive human brain tumors. There are few reliable mechanism-based therapeutic approaches for GBM patients. The transcriptional repressor RE1 silencing transcriptional factor (REST) regulates the oncogenic properties of a class of GBM stem-like cells (high-REST [HR]-GSCs) in humans. However, it has been unclear whether REST represses specific targets to regulate specific oncogenic functions or represses all targets with overlapping functions in GSCs...
December 31, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/28040478/cathepsin-k-cleavage-of-sdf-1%C3%AE-inhibits-its-chemotactic-activity-towards-glioblastoma-stem-like-cells
#14
Vashendriya V V Hira, Urška Verbovšek, Barbara Breznik, Matic Srdič, Marko Novinec, Hala Kakar, Jill Wormer, Britt Van der Swaan, Brigita Lenarčič, Luiz Juliano, Shwetal Mehta, Cornelis J F Van Noorden, Tamara T Lah
Glioblastoma (GBM) is the most aggressive primary brain tumor with poor patient survival that is at least partly caused by malignant and therapy-resistant glioma stem-like cells (GSLCs) that are protected in GSLC niches. Previously, we have shown that the chemo-attractant stromal-derived factor-1α (SDF-1α), its C-X-C receptor type 4 (CXCR4) and the cysteine protease cathepsin K (CatK) are localized in GSLC niches in glioblastoma. Here, we investigated whether SDF-1α is a niche factor that through its interactions with CXCR4 and/or its second receptor CXCR7 on GSLCs facilitates their homing to niches...
December 28, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28039611/alternative-new-mesenchymal-stem-cell-source-exerts-tumor-tropism-through-alcam-and-n-cadherin-via-regulation-of-microrna-192-and-218
#15
Ran Kim, Sang In Park, Chang Youn Lee, Jihyun Lee, Pilseog Kim, Sekyung Oh, Hojin Lee, Min Young Lee, Jongmin Kim, Yong-An Chung, Ki-Chul Hwang, Lee-So Maeng, Woochul Chang
Gliomas are the most common type of malignant primary brain tumors. Some treatments of gliomas exist, but they are rarely curative. Mesenchymal stem cells (MSCs) are emerging as potential modes of targeted cancer therapy owing to their capacity for homing toward tumor sites. It has been proposed that MSCs derived from various sources, such as bone marrow, adipose tissue and umbilical cord blood, can be used as cell-based therapy for brain tumors. Here, MSCs obtained from the synovial fluid of osteoarthritis or rheumatoid arthritis patients were investigated as therapeutic candidates...
December 30, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28038463/setmar-isoforms-in-glioblastoma-a-matter-of-protein-stability
#16
Audrey Dussaussois-Montagne, Jérôme Jaillet, Laetitia Babin, Pierre Verrelle, Lucie Karayan-Tapon, Sylvaine Renault, Cécilia Rousselot-Denis, Ilyess Zemmoura, Corinne Augé-Gouillou
Glioblastomas (GBMs) are the most frequent and the most aggressive brain tumors, known for their chemo- and radio-resistance, making them often incurable. We also know that SETMAR is a protein involved in chromatin dynamics and genome plasticity, of which overexpression confers chemo- and radio-resistance to some tumors. The relationships between SETMAR and GBM have never been explored. To fill this gap, we define the SETMAR status of 44 resected tumors and of GBM derived cells, at both the mRNA and the protein levels...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035316/primary-pediatric-mid-brain-lymphoma-report-of-a-rare-pediatric-tumor-in-a-rare-location
#17
Rony Benson, Supriya Mallick, Suvendu Purkait, Vaishali Suri, K P Haresh, Subhash Gupta, Dayanand Sharma, Pramod Kumar Julka, Goura Kishore Rath
Primary central nervous system lymphoma (PCNSL) is a rare disease in pediatric age group. A thirteen-year-old male child presented with complaints of headache for six months, vomiting and diplopia for three days. Magnetic resonance imaging of the brain showed a single lesion of 1.7 cm × 1.6 cm × 1.6 cm in the mid brain and tectum. He underwent a gross total resection of the tumor. The histopathological evaluation revealed B cell high grade non Hodgkin lymphoma. The patient was treated with High dose methotrexate and cranio spinal radiation...
December 16, 2016: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/28030635/expression-and-prognostic-value-of-oct-4-in-astrocytic-brain-tumors
#18
Jeanette Krogh Petersen, Per Jensen, Mia Dahl Sørensen, Bjarne Winther Kristensen
BACKGROUND: Glioblastomas are the most frequent type of malignant primary brain tumor with a median overall survival less than 15 months. Therapy resistance of glioblastomas has been attributed to the presence of tumor initiating stem-like cells (TSCs). TSC-related markers have therefore been suggested to have promising potentials as prognostic markers in gliomas. METHODOLOGY/PRINCIPAL FINDINGS: The aim of the present study was to investigate the expression and prognostic impact of the TSC-related marker Oct-4 in astrocytic brain tumors of increasing grade...
2016: PloS One
https://www.readbyqxmd.com/read/28019637/recent-advances-in-targeted-therapy-for-glioma
#19
Lin Lin, Jinquan Cai, Chuanlu Jiang
Gliomas are the most common primary malignant brain tumors,which have a universally fatal outcome. Current standard treatment for glioma patients is surgical removal followed by radiotherapy and adjuvant chemotherapy. Due to therapeutic resistance and tumor recurrence, efforts are ongoing to identify the molecules that are fundamental to regulate the tumor progression and provide additional methods for individual treatment of glioma patients. By studying the initiation and maintenance of glioma, studies focused on the targets of tyrosine kinase receptors including EGFR, PDGFR and other crucial signal pathways such as PI3K/AKT and RAS/RAF/MAPK pathway...
December 23, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28011620/wnt5a-drives-an-invasive-phenotype-in-human-glioblastoma-stem-like-cells
#20
Elena Binda, Alberto Visioli, Fabrizio Giani, Nadia Trivieri, Orazio Palumbo, Silvia Restelli, Fabio Dezi, Tommaso Mazza, Caterina Fusilli, Federico Legnani, Massimo Carella, Francesco DiMeco, Rohit Duggal, Angelo Luigi Vescovi
Brain invasion by glioblastoma (hGBM) determines prognosis, recurrence and lethality in patients, but no master factor coordinating the invasive properties of GBM has been identified. Here we report evidence favouring such a role for the non-canonical WNT family member Wnt5a. We found the most invasive gliomas to be characterized by Wnt5a overexpression, which correlated with poor prognosis and also discriminated infiltrating mesenchymal GBM from poorly motile proneural and classical GBM. Indeed, Wnt5a overexpression associated with tumor-promoting stem-like characteristics (TPC) in defining the character of highly-infiltrating mesenchymal GBM cells (Wnt5aHigh)...
December 23, 2016: Cancer Research
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