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Cancer: Brain Cancers

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Total 538 results found since Jan 2013.

ERK1 and ERK2 present functional redundancy in tetrapods despite higher evolution rate of ERK1
Conclusions: ERK isoforms appeared by a single gene duplication at the onset of vertebrate evolution at least 400 Mya. Our results demonstrate that tetrapods can live by expressing either one or both ERK isoforms, supporting the notion that ERK1/2 act interchangeably. Substrate recognition sites and catalytic cleft are nearly invariant in all vertebrate ERKs further suggesting functional redundancy. We suggest that future ERK research should shift towards understanding the role and regulation of total ERK quantity, especially in light of newly described erk2 gene amplification identified in tumors.
Source: BMC Evolutionary Biology - September 3, 2015 Category: Molecular Biology Authors: Roser BuscàRichard ChristenMatthew LovernAlexander CliffordJia-Xing YueGreg GossJacques PouysségurPhilippe Lenormand Source Type: research

Cytotoxic and genotoxic effects mediated by M2 muscarinic receptor activation in human glioblastoma cells
In conclusion, in addition to a cytostatic effect previously described, in the present study we have better characterized the mechanisms causing the cytotoxic effects and the apoptotic cell death in glioblastoma cells after M2 receptor activation. These data allow to consider this receptor a new interesting therapeutic tool for the glioblastoma treatment.
Source: Neurochemistry International - October 10, 2015 Category: Neuroscience Source Type: research

Strategies to target drugs to gliomas and CNS metastases of solid tumors
Abstract The treatment for central nervous system metastases of solid tumors and gliomas is limited as the blood–brain barrier (BBB) is an obstacle to systemic therapy. Here, we review the physiochemical properties of the BBB and both current and new drug strategies to penetrate brain tumors. We focus on targeting receptor- or carrier-mediated transport mechanisms over the BBB used by drug conjugates, nanoparticles, polymer-based nanocarriers, siRNA, and antibodies.
Source: Journal of Neurology - October 17, 2015 Category: Neurology Source Type: research

Inhibition of KIF14 Suppresses Tumor Cell Growth and Promotes Apoptosis in Human Glioblastoma
Conclusions: The upregulation of KIF14 in astrocytoma is associated with disease severity, and suppression of KIF14 inhibits cell proliferation and induces apoptosis through a mechanism involving the inactivation of AKT signaling, suggesting that KIF14 plays an important role in astrocytoma tumorigenesis and could be a promising molecular target for anticancer therapy.Cell Physiol Biochem 2015;37:1659-1670
Source: Cellular Physiology and Biochemistry - November 5, 2015 Category: Cytology Source Type: research

Porphyromonas gingivalis initiates a mesenchymal‐like transition through ZEB1 in gingival epithelial cells
This article is protected by copyright. All rights reserved.
Source: Cellular Microbiology - December 7, 2015 Category: Microbiology Authors: Maryta N. Sztukowska, Akintunde Ojo, Saira Ahmed, Anne L. Carenbauer, Qian Wang, Brain Shumway, Howard F. Jenkinson, Huizhi Wang, Douglas S. Darling, Richard J. Lamont Tags: Research article Source Type: research

Abstract A02: Identification of distinct BUB1B-sensitive and -resistant subtypes of glioblastoma with prognostic value
Glioblastoma multiforme is the most aggressive and common form of brain cancer in adults. The combined analysis of functional genetics with glioblastoma (GBM) network modeling identified BUB1B, a critical mitotic spindle checkpoint player, as a new requirement of glioblastoma tumors to suppress lethal consequences of altered kinetochore (KT) (1). Here, we further collected GBM stem-like cells (GSCs) including both BUB1B-sensitive and -resistant isolates, and performed whole-transcriptome sequencing that capture gene expression levels of each GSC. Based on the expression signature associated with BUB1B-sensitiveness from GS...
Source: Cancer Research - December 9, 2015 Category: Cancer & Oncology Authors: Lee, E., Paddison, P. J., Zhu, J. Tags: Computational Genomics and Evolutionary Dynamics Source Type: research

Abstract B12: GABP selectively binds and activates the mutant TERT promoter across multiple cancer types
Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, fundamental steps in the initiation of human cancer. Multiple cancer types, including up to 83% of glioblastomas (GBM), harbor highly recurrent mutations in the TERT promoter specific to two nucleotide positions. The common mutation sites, G228A and G250A, may create de-novo ETS family transcription factor binding sites, but the precise mechanism of how these mutations confer increased TERT expression has been elusive. Here, we demonstrate the de-novo ETS motif to be critical for mutant ...
Source: Cancer Research - December 9, 2015 Category: Cancer & Oncology Authors: Bell, R. J. A., Rube, H. T., Kreig, A., Mancini, A., Fouse, S. F., Nagarajan, R. P., Choi, S., Hong, C., He, D., Pekmezci, M., Wiencke, J. K., Wrensch, M. R., Chang, S. M., Walsh, K. M., Myong, S., Song, J. S., Costello, J. F. Tags: Mutational Landscape in Brain Tumors Source Type: research

Abstract B26: MAPK-interacting kinase inhibition sensitizes glioblastoma and glioma stem cells to arsenic trioxide
In this study, we sought to determine the mechanisms by which MNK signaling regulates arsenic trioxide responses in GBM and glioma stem cells.GBM cell lines were treated with ATO in the presence or absence of MNK inhibitors or siRNA against MNK isoforms. Western blots of treated samples were analyzed with antibodies against phosphorylated eIF4E, the key downstream effector of the MNKs. Following treatment with ATO and MNK inhibitors, proliferation rate and apoptosis were determined by WST-1 assay and Annexin V-FITC/PI staining. GBM cell lines were grown under stem cell conditions and subjected to qPCR and flow cytometry to...
Source: Cancer Research - December 9, 2015 Category: Cancer & Oncology Authors: Bell, J. B., Eckerdt, F., Arslan, A. D., Iqbal, A., Alvarez, A. A., Cheng, S.-Y., Nakano, I., Platanias, L. C. Tags: Preclinical Therapeutics/Trials/Models Source Type: research

A Zbtb7a proto‐oncogene as a novel target for miR‐125a
In our previous study, we showed that miR‐125a directly targeted a WT1 oncogene, which was overexpressed in leukemia and various kinds of solid tumors including lung, breast, gastric, and colon cancers, and brain tumors and was deeply involved in leukemogenesis and tumorigenesis and that miR‐125a knockout mice overexpressed WT1 and developed myeloproliferative disease. It had been also reported that miR‐125a is downregulated in leukemia and various types of solid tumors such as lung cancers, suggesting its tumor suppressor function. Therefore, it is important to elucidate what is target(s) of miR‐125a for understan...
Source: Molecular Carcinogenesis - December 29, 2015 Category: Molecular Biology Authors: Nozomi Hojo, Naoya Tatsumi, Nahoko Moriguchi, Akihide Matsumura, Soyoko Morimoto, Jun Nakata, Fumihiro Fujiki, Sumiyuki Nishida, Hiroko Nakajima, Akihiro Tsuboi, Yoshihiro Oka, Naoki Hosen, Seiji Hayashi, Haruo Sugiyama, Yusuke Oji Tags: Research Article Source Type: research

Abstract C26: Development of selective MELK kinase inhibitors for breast cancer treatment
In this study, we are reporting development of a series of selective MELK kinase inhibitors. Synthesized compounds exert excellent selectivity and potency in MELK inhibition in a low nanomolar range. Therapeutic effect of the compounds was investigated in the panel of breast cancer cell lines with different genetic background as well as with different MELK kinase levels; it was shown that for some cell lines compounds induced cell death with nanomolar ED50 values. The compound's effect on the proliferation and in the colony formation assay was also investigated. Taken altogether, the presented data supports our rationale o...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kowalczyk, P., Węgrzyn, P., Prokopowicz, M., Knop, M., Mazur, K., Dziedzic, K., Gluza, K., Knop, M., Dziedzic, K., Mazur, K., Radzimierski, A., Commandeur, C., Zawadzka, M., Bloudoff, K., Vaillancourt, F., Larsen, N., Wang, J., Reynolds, D., Ito, D Tags: Cancer Stem Cells: Poster Presentations - Proffered Abstracts Source Type: research

Abstract C195: A Wee1 inhibitor analog of AZD1775 demonstrates synergy with cisplatin with reduced single-agent toxicity in medulloblastoma
Medulloblastoma is the most common primary brain tumor in children. Current treatment for medulloblastoma includes surgical resection, radiation and cytotoxic chemotherapy. Although this approach has improved survival rates, the high doses of chemotherapy required to circumvent drug resistance mechanisms and result in clinical efficacy often give rise to lasting neurocognitive defects, stunted growth, deafness, and even secondary tumors. Therefore, synergistic drug combinations that maintain clinical efficacy, but allow dose reductions of cytotoxic agents limiting their adverse effects would be an attractive approach for p...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Matheson, C. J., Venkataraman, S., Amani, V., Harris, P., Backos, D. S., Foreman, N. K., Vibhakar, R., Reigan, P. Tags: Therapeutic Agents: Small Molecule Kinase Inhibitors: Poster Presentations - Proffered Abstracts Source Type: research

Up-Regulation of microRNA-183 Promotes Cell Proliferation and Invasion in Glioma By Directly Targeting NEFL.
This study revealed that miR-183 promotes glioma cell proliferation by targeting NEFL, and also demonstrated that miR-183 could be a potential target for GBM treatment. PMID: 26879754 [PubMed - as supplied by publisher]
Source: Cellular and Molecular Neurobiology - February 15, 2016 Category: Cytology Authors: Wang ZY, Xiong J, Zhang SS, Wang JJ, Gong ZJ, Dai MH Tags: Cell Mol Neurobiol Source Type: research

Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme.
Authors: Bien-Möller S, Lange S, Holm T, Böhm A, Paland H, Küpper J, Herzog S, Weitmann K, Havemann C, Vogelgesang S, Marx S, Hoffmann W, Schroeder HW, Rauch BH Abstract A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P1-S1P5) and S1P metabolizing enzymes in human GBM (n = 117) compared to healt...
Source: Oncotarget - February 19, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Combined inhibition of vascular endothelial growth factor receptor signaling with temozolomide enhances cytotoxicity against human glioblastoma cells via downregulation of Neuropilin-1
Abstract Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor with grave prognosis. Despite the growing understanding of the complex signaling networks responsible for the initiation and progression of GBM, many experimental therapies have fallen short of their treatment goals. In the present study, we investigated the novel molecular mechanisms responsible for synergistic action of temozolomide (TMZ) and anti-VEGF therapy in GBM cells. We tested the combined effects of TMZ and VEGF blockade in four human GBM cell lines: TMZ-sensitive U251-MG and U373-MG cells, and TMZ-resist...
Source: Journal of Neuro-Oncology - March 7, 2016 Category: Cancer & Oncology Source Type: research

Abstract A68: Penfluridol suppresses triple-negative breast cancer metastasis to brain by inhibiting integrin signaling
Breast cancer is the second leading cause of cancer related deaths in US. Breast tumor metastasis to brain is major cause of deaths. Brain metastasis of triple negative breast cancer cells (TNBC) is highly resistant to current therapies and is a cause of reduced survival rates in patients. In current study, we evaluated penfluridol, a first generation, highly potent antipsychotic drug against three different highly aggressive TNBC cell line. The IC50 of penfluridol was around 6 µM in 4T1, MDA-MB-231 and HCC-1806, breast cancer cells respectively. Our result showed that the expression of integrinβ4, integrin&alph...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Ranjan, A., Gupta, P., Srivastava, S. K. Tags: Other Topics: Poster Presentations - Proffered Abstracts Source Type: research