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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/28099914/advances-in-epigenetic-glioblastoma-therapy
#2
Dong Hoon Lee, Hyun-Wook Ryu, Hye-Rim Won, So Hee Kwon
Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults despite contemporary gold-standard first-line treatment strategies. This type of tumor recurs in virtually all patients and no commonly accepted standard treatment exists for the recurrent disease. Therefore, advances in all scientific and clinical aspects of GBM are urgently needed. Epigenetic mechanisms are one of the major factors contributing to the pathogenesis of cancers, including glioblastoma. Epigenetic modulators that regulate gene expression by altering the epigenome and non-histone proteins are being exploited as therapeutic drug targets...
January 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098764/iqgap1-in-podosomes-invadosomes-is-involved-in-the-progression-of-glioblastoma-multiforme-depending-on-the-tumor-status
#3
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/28096196/craniospinal-irradiation-using-helical-tomotherapy-for-central-nervous-system-tumors
#4
Sanziana R I Schiopu, Gregor Habl, Matthias Häfner, Sonja Katayama, Klaus Herfarth, Juergen Debus, Florian Sterzing
The aim of this study was to describe early and late toxicity, survival and local control in 45 patients with primary brain tumors treated with helical tomotherapy craniospinal irradiation (HT-CSI). From 2006 to 2014, 45 patients with central nervous system malignancies were treated with HT-CSI. The most common tumors were medulloblastoma in 20 patients, ependymoma in 10 patients, intracranial germinoma (ICG) in 7 patients, and primitive neuroectodermal tumor in 4 patients. Hematological toxicity during treatment included leukopenia Grades 1-4 (6...
January 17, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28093680/the-international-diffuse-intrinsic-pontine-glioma-registry-an-infrastructure-to-accelerate-collaborative-research-for-an-orphan-disease
#5
Joshua Baugh, Ute Bartels, James Leach, Blaise Jones, Brooklyn Chaney, Katherine E Warren, Jenavieve Kirkendall, Renee Doughman, Cynthia Hawkins, Lili Miles, Christine Fuller, Tim Hassall, Eric Bouffet, Adam Lane, Darren Hargrave, Jacques Grill, Lindsey M Hoffman, Chris Jones, Alex Towbin, Sharon A Savage, Michelle Monje, Xiao-Nan Li, David S Ziegler, Sophie Veldhuijzen van Zanten, Christof M Kramm, Dannis G van Vuurden, Maryam Fouladi
Diffuse intrinsic pontine glioma (DIPG), a rare, often fatal childhood brain tumor, remains a major therapeutic challenge. In 2012, investigators, funded by the DIPG Collaborative (a philanthropic partnership among 29 private foundations), launched the International DIPG Registry (IDIPGR) to advance understanding of DIPG. Comprised of comprehensive deidentified but linked clinical, imaging, histopathological, and genomic repositories, the IDIPGR uses standardized case report forms for uniform data collection; serial imaging and histopathology are centrally reviewed by IDIPGR neuro-radiologists and neuro-pathologists, respectively...
January 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28091986/shift-of-microrna-profile-upon-glioma-cell-migration-using-patient-derived-spheroids-and-serum-free-conditions
#6
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/28088075/development-of-a-hypoxia-triggered-and-hypoxic-radiosensitized-liposome-as-a-doxorubicin-carrier-to-promote-synergetic-chemo-radio-therapy-for-glioma
#7
Hongmei Liu, Yandong Xie, Yafei Zhang, Yifan Cai, Baiyang Li, Honglin Mao, Yingguo Liu, Jun Lu, Longzhen Zhang, Rutong Yu
The treatment of malignant primary brain tumors is challenging. Concomitant radiochemotherapy has become the standard clinical treatment for malignant glioma, but there are two critical challenges to overcome in order to increase efficacy. First, glioma is known to have increased resistant to radiation due to its intra-tumoral hypoxia. In addition, the blood-brain barrier (BBB) restricts the distribution of the chemotherapeutic agent to the brain. Therefore, we developed a hypoxic radiosensitizer-prodrug liposome (MLP), in order to deliver DOX to the tumor and to overcome the above challenges, achieving a synergistic chemo-/radiotherapy treatment of malignant glioma...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28081463/analysis-of-the-results-of-recurrent-intracranial-meningiomas-treated-with-re-radiosurgery
#8
Moinay Kim, Do Hee Lee, Hyun Jung Kim Rn, Young Hyun Cho, Jeong Hoon Kim, Do Hoon Kwon
OBJECTS: Meningioma is the most common intracranial neoplasm, comprising approximately 30% of all primary intracranial tumors (Claus et al., 2005) [1]. Treatment options include observation, microsurgical resection, stereotactic radiosurgery (SRS), and whole brain radiation therapy (WBRT). Gamma knife radiosurgery (GKRS) is a very effective treatment for intracranial meningiomas; previous studies showed the tumor control rate at 5-10 years of follow-up as 84.3%-100% in all cases (Feigl et al...
December 29, 2016: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28079712/a-comprehensive-review-of-genomics-and-noncoding-rna-in-gliomas
#9
Ahmed Hassan, Jennifer Mosley, Sanjay Singh, Pascal Olivier Zinn
Glioblastoma (GBM) is the most malignant primary adult brain tumor. In spite of our greater understanding of the biology of GBMs, clinical outcome of GBM patients remains poor, as their median survival with best available treatment is 12 to 18 months. Recent efforts of The Cancer Genome Atlas (TCGA) have subgrouped patients into 4 molecular/transcriptional subgroups: proneural, neural, classical, and mesenchymal. Continuing efforts are underway to provide a comprehensive map of the heterogeneous makeup of GBM to include noncoding transcripts, genetic mutations, and their associations to clinical outcome...
January 11, 2017: Topics in Magnetic Resonance Imaging: TMRI
https://www.readbyqxmd.com/read/28079711/cell-signaling-pathways-in-brain-tumors
#10
Rebecca A Harrison, John F de Groot
Primary brain tumors, particularly glioblastoma, are associated with significant morbidity and are often recalcitrant to standard therapies. In recent years, brain tumors have been the focus of large-scale genomic sequencing efforts, providing unprecedented insight into the genomic aberrations and cellular signaling mechanisms that drive these cancers. Discoveries from these efforts have translated into novel diagnostic algorithms, biomarkers, and therapeutic strategies in Neuro-Oncology. However, the cellular mechanisms that drive brain tumors are heterogeneous and complex: applying this new knowledge to improve patient outcomes remains a challenge...
January 11, 2017: Topics in Magnetic Resonance Imaging: TMRI
https://www.readbyqxmd.com/read/28078450/genome-wide-methylation-profiles-in-primary-intracranial-germ-cell-tumors-indicate-a-primordial-germ-cell-origin-for-germinomas
#11
Shintaro Fukushima, Satoshi Yamashita, Hisato Kobayashi, Hirokazu Takami, Kohei Fukuoka, Taishi Nakamura, Kai Yamasaki, Yuko Matsushita, Hiromi Nakamura, Yasushi Totoki, Mamoru Kato, Tomonari Suzuki, Kazuhiko Mishima, Takaaki Yanagisawa, Akitake Mukasa, Nobuhito Saito, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga, Motoo Nagane, Toshihiko Iuchi, Koji Yoshimoto, Masahiro Mizoguchi, Kaoru Tamura, Keiichi Sakai, Kazuhiko Sugiyama, Mitsutoshi Nakada, Kiyotaka Yokogami, Hideo Takeshima, Yonehiro Kanemura, Masahide Matsuda, Akira Matsumura, Kazuhiko Kurozumi, Keisuke Ueki, Masahiro Nonaka, Akio Asai, Nobutaka Kawahara, Yuichi Hirose, Tatusya Takayama, Yoichi Nakazato, Yoshitaka Narita, Tatsuhiro Shibata, Masao Matsutani, Toshikazu Ushijima, Ryo Nishikawa, Koichi Ichimura
Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling...
January 11, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28077796/tumor-cell-migration-is-inhibited-by-a-novel-therapeutic-strategy-antagonizing-the-alpha-7-receptor
#12
Chris Pepper, Henry Tu, Paul Morrill, Sara Garcia-Rates, Chris Fegan, Susan Greenfield
A 14mer peptide (T14) derived from the C-terminus of acetylcholinesterase (AChE) selectively activates metastatic breast cancer cells via the alpha-7 nicotinic receptor (α7 nAChR). This naturally occurring peptide is also present in brain, is elevated in Alzheimer's disease, and is antagonised by a cyclized variant (NBP-14). Here we investigated the effects of NBP-14 in six different cancer cell lines, primary leukemia B-cells and normal B-cells. All cells tested expressed α7 nAChR, intracellular and extracellular T14...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28074323/changes-in-cerebral-metabolism-during-ketogenic-diet-in-patients-with-primary-brain-tumors-1-h-mrs-study
#13
Moran Artzi, Gilad Liberman, Nachum Vaisman, Felix Bokstein, Faina Vitinshtein, Orna Aizenstein, Dafna Ben Bashat
Normal brain cells depend on glucose metabolism, yet they have the flexibility to switch to the usage of ketone bodies during caloric restriction. In contrast, tumor cells lack genomic and metabolic flexibility and are largely dependent on glucose. Ketogenic-diet (KD) was suggested as a therapeutic option for malignant brain cancer. This study aimed to detect metabolic brain changes in patients with malignant brain gliomas on KD using proton magnetic-resonance-spectroscopy ((1)H-MRS). Fifty MR scans were performed longitudinally in nine patients: four patients with recurrent glioblastoma (GB) treated with KD in addition to bevacizumab; one patient with gliomatosis-cerebri treated with KD only; and four patients with recurrent GB who did not receive KD...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28074321/predictive-factors-of-early-distant-brain-failure-after-gamma-knife-radiosurgery-alone-in-patients-with-brain-metastases-of-non-small-cell-lung-cancer
#14
Young Cheol Na, Hyun Ho Jung, Hye Ryun Kim, Byoung Chul Cho, Jin Woo Chang, Yong Gou Park, Won Seok Chang
The objective of this study was to elucidate the predictive factors for early distant brain failure in patients with brain metastases of non-small-cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKRS) without previous whole-brain radiotherapy (WBRT) or surgery. We retrospectively reviewed clinical and imaging data of 459 patients with brain metastases of NSCLC who underwent GKRS from June 2008 to December 2013. The primary end-point was early distant brain failure, defined as the detection of newly developed metastatic lesions on magnetic resonance imaging (MRI) 3 months after GKRS...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28073783/podoplanin-expression-in-primary-brain-tumors-induces-platelet-aggregation-and-increases-risk-of-venous-thromboembolism
#15
Julia Riedl, Matthias Preusser, Pegah Mir Seyed Nazari, Florian Posch, Simon Panzer, Christine Marosi, Peter Birner, Johannes Thaler, Christine Brostjan, Daniela Lötsch, Walter Berger, Johannes A Hainfellner, Ingrid Pabinger, Cihan Ay
Venous thromboembolism (VTE) is common in patients with brain tumors, and underlying mechanisms are unclear. We hypothesized that podoplanin, a sialomucin-like glycoprotein, increases the risk of VTE in primary brain tumors via its ability to induce platelet aggregation. Immunohistochemical staining against podoplanin and intratumoral platelet aggregates was performed in brain tumor specimens of 213 patients (mostly high-grade gliomas [89%]) included in the Vienna Cancer and Thrombosis Study (CATS), a prospective observational cohort study of patients with newly diagnosed cancer or progressive disease aimed at identifying patients at risk of VTE...
January 10, 2017: Blood
https://www.readbyqxmd.com/read/28073578/prophylactic-cranial-irradiation-after-definitive-chemoradiotherapy-for-limited-stage-small-cell-lung-cancer-do-all-patients-benefit
#16
Ahsan S Farooqi, Emma B Holliday, Pamela K Allen, Xiong Wei, James D Cox, Ritsuko Komaki
PURPOSE: Prophylactic cranial irradiation (PCI) can improve overall survival (OS) and suppress brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete response to primary therapy. However, PCI can be toxic. We sought to identify characteristics of patients who may not benefit from PCI. METHODS: We identified 658 patients who received chemoradiotherapy at MD Anderson in 1986-2012; 364 received PCI and 294 did not. Median follow-up time was 21...
January 7, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28069040/anti-inflammatory-and-immune-regulatory-effects-of-acupuncture-after-craniotomy-study-protocol-for-a-parallel-group-randomized-controlled-trial
#17
Seung-Yeon Cho, Seung-Bo Yang, Hee Sup Shin, Seung Hwan Lee, Jun Seok Koh, Seungwon Kwon, Woo-Sang Jung, Sang-Kwan Moon, Jung-Mi Park, Chang-Nam Ko, Seong-Uk Park
BACKGROUND: Despite recent advances in the medical and surgical fields, complications such as infection, pneumonia, or brain swelling may occur after a craniotomy. In some patients, perioperative antibiotic prophylaxis causes adverse effects such as itching, rash, or digestive conditions. Certain patients still develop infections severe enough to require a repeat operation despite antibiotic prophylaxis. Acupuncture has been used to treat inflammatory conditions, and many basic and clinical studies have provided evidence of its anti-inflammatory and immune regulatory effects...
January 10, 2017: Trials
https://www.readbyqxmd.com/read/28069038/motility-of-glioblastoma-cells-is-driven-by-netrin-1-induced-gain-of-stemness
#18
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/28068482/metabolic-reprogramming-in-brain-tumors
#19
Sriram Venneti, Craig B Thompson
Next-generation sequencing has substantially enhanced our understanding of the genetics of primary brain tumors by uncovering several novel driver genetic alterations. How many of these genetic modifications contribute to the pathogenesis of brain tumors is not well understood. An exciting paradigm emerging in cancer biology is that oncogenes actively reprogram cellular metabolism to enable tumors to survive and proliferate. We discuss how some of these genetic alterations in brain tumors rewire metabolism...
December 21, 2016: Annual Review of Pathology
https://www.readbyqxmd.com/read/28068234/radiation-dose-dependent-hippocampal-atrophy-detected-with-longitudinal-volumetric-magnetic-resonance-imaging
#20
Tyler M Seibert, Roshan Karunamuni, Hauke Bartsch, Samar Kaifi, Anitha Priya Krishnan, Yoseph Dalia, Jeffrey Burkeen, Vyacheslav Murzin, Vitali Moiseenko, Joshua Kuperman, Nathan S White, James B Brewer, Nikdokht Farid, Carrie R McDonald, Jona A Hattangadi-Gluth
PURPOSE: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. METHODS AND MATERIALS: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors...
February 1, 2017: International Journal of Radiation Oncology, Biology, Physics
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