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https://www.readbyqxmd.com/read/29779087/down-regulation-of-mdr1-by-ad-dkk3-via-akt-nf%C3%AE%C2%BAb-pathways-augments-the-anti-tumor-effect-of-temozolomide-in-glioblastoma-cells-and-a-murine-xenograft-model
#1
Toshitaka Fujihara, Yoshifumi Mizobuchi, Kohei Nakajima, Teruyoshi Kageji, Kazuhito Matsuzaki, Keiko T Kitazato, Ryotaro Otsuka, Keijiro Hara, Hideo Mure, Toshiyuki Okazaki, Kazuyuki Kuwayama, Shinji Nagahiro, Yasushi Takagi
BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1...
May 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29779041/the-potential-importance-of-myeloid-derived-suppressor-cells-mdscs-in-the-pathogenesis-of-alzheimer-s-disease
#2
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
The exact cause of Alzheimer's disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concurrently, it should prevent neuronal injuries induced by inflammation...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29778285/subcutaneous-tissue-metastasis-from-glioblastoma-multiforme-a-case-report-and-review-of-the-literature
#3
Natalia Frade Porto, Juan Delgado Fernández, María de Los Ángeles García Pallero, Juan Ramón Penanes Cuesta, Paloma Pulido Rivas, Ricardo Gil Simoes
Glioblastoma multiforme is the most common primary brain tumor, despite an aggressive clinical course, less than 2% of patients develop extraneural metastasis. We present a 72-year-old male diagnosed with a right temporal glioblastoma due to headache. He underwent total gross resection surgery and after that the patient was treated with adyuvant therapy. Five months after the patient returned with trigeminal neuralgia, and MRI showed an infratemporal cranial mass which infiltrates masticator space, the surrounding bone, the temporal muscle and superior cervical and parotid lymph nodes...
May 16, 2018: Neurocirugía
https://www.readbyqxmd.com/read/29777731/tumor-necrosis-factor-receptor-2-is-required-for-ischemic-preconditioning-mediated-neuroprotection-in-the-hippocampus-following-a-subsequent-longer-transient-cerebral-ischemia
#4
Jae-Chul Lee, Chan Woo Park, Myoung Cheol Shin, Jun Hwi Cho, Hyang-Ah Lee, Young-Myeong Kim, Joon Ha Park, Ji Hyeon Ahn, Jeong Hwi Cho, Hyun-Jin Tae, In Koo Hwang, Tae-Kyeong Lee, Moo-Ho Won, Il Jun Kang
Tumor Necrosis Factor-α (TNF-α) is a proinflammatory cytokine implicated in neuronal damage in response to cerebral ischemia. Ischemic preconditioning (IPC) provides neuroprotection against a subsequent severer or longer transient ischemia by ischemic tolerance. Here, we focused on the role of TNF-α in IPC-mediated neuroprotection against neuronal death following a subsequent longer transient cerebral ischemia (TCI). Gerbils used in this study were randomly assigned to eight groups; sham group, TCI operated group, IPC plus (+) sham group, IPC + TCI operated group, sham + etanercept (an inhibitor of TNF-a) group, TCI + etanercept group, IPC + sham + etanercept group, and IPC + TCI + etanercept group...
May 16, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29777685/thiamine-preserves-mitochondrial-function-in-a-rat-model-of-traumatic-brain-injury-preventing-inactivation-of-the-2-oxoglutarate-dehydrogenase-complex
#5
Garik V Mkrtchyan, Muammer Üçal, Andrea Müllebner, Sergiu Dumitrescu, Martina Kames, Rudolf Moldzio, Marek Molcanyi, Samuel Schaefer, Adelheid Weidinger, Ute Schaefer, Juergen Hescheler, Johanna Catharina Duvigneau, Heinz Redl, Victoria I Bunik, Andrey V Kozlov
BACKGROUND AND PURPOSE: Based on the fact that traumatic brain injury is associated with mitochondrial dysfunction we aimed at localization of mitochondrial defect and attempted to correct it by thiamine. EXPERIMENTAL APPROACH: Interventional controlled experimental animal study was used. Adult male Sprague-Dawley rats were subjected to lateral fluid percussion traumatic brain injury. Thiamine was administered 1 h prior to trauma; cortex was extracted for analysis 4 h and 3 d after trauma...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777576/glioblastoma-recurrence-correlates-with-nlgn3-levels
#6
Rui Liu, Xing-Ping Qin, Yang Zhuang, Ya Zhang, Hua-Bao Liao, Jun-Chun Tang, Meng-Xian Pan, Fei-Fei Zeng, Yang Lei, Rui-Xue Lei, Shu Wang, An-Chun Liu, Juan Chen, Zhi-Feng Zhang, Dan Zhao, Song-Lin Wu, Ren-Zhong Liu, Ze-Fen Wang, Qi Wan
Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin-3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain...
May 18, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29777137/enhanced-efficacy-of-combined-temozolomide-and-bromodomain-inhibitor-therapy-for-gliomas-using-targeted-nanoparticles
#7
Fred C Lam, Stephen W Morton, Jeffrey Wyckoff, Tu-Lan Vu Han, Mun Kyung Hwang, Amanda Maffa, Elena Balkanska-Sinclair, Michael B Yaffe, Scott R Floyd, Paula T Hammond
Effective treatment for glioblastoma (GBM) is limited by the presence of the blood-brain barrier (BBB) and rapid resistance to single agent therapies. To address these issues, we developed a transferrin-functionalized nanoparticle (Tf-NP) that can deliver dual combination therapies. Using intravital imaging, we show the ability of Tf-NPs to traverse intact BBB in mice as well as achieve direct tumor binding in two intracranial orthotopic models of GBM. Treatment of tumor-bearing mice with Tf-NPs loaded with temozolomide and the bromodomain inhibitor JQ1 leads to increased DNA damage and apoptosis that correlates with a 1...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29776650/signaling-pathway-deregulation-and-molecular-alterations-across-pediatric-medulloblastomas
#8
REVIEW
B Lhermitte, A F Blandin, A Coca, E Guerin, A Durand, N Entz-Werlé
Medulloblastomas (MBs) account for 15% of brain tumors in children under the age of 15. To date, the overall 5-year survival rate for all children is only around 60%. Recent advances in cancer genomics have led to a fundamental change in medulloblastoma classification and is evolving along with the genomic discoveries, allowing to regularly reclassify this disease. The previous molecular classification defined 4 groups (WNT-activated MB, SHH-activated MB and the groups 3 and 4 characterized partially by NMYC and MYC driven MBs)...
May 15, 2018: Neuro-Chirurgie
https://www.readbyqxmd.com/read/29775808/phase-ii-study-of-maintenance-pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-sclc
#9
Shirish M Gadgeel, Nathan A Pennell, Mary Jo Fidler, Balazs Halmos, Philip Bonomi, James Stevenson, Bryan Schneider, Ammar Sukari, Jaclyn Ventimiglia, Wei Chen, Cathy Galasso, Antoinette Wozniak, Julie Boerner, Gregory P Kalemkerian
PURPOSE: To assess the efficacy of maintenance pembrolizumab in extensive-stage small cell lung cancer (SCLC) patients, after treatment with platinum/etoposide. PATIENTS AND METHODS: Extensive-stage SCLC patients with a response or stable disease following induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg IV every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary endpoint of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary endpoint...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29775807/fir-efficacy-safety-and-biomarker-analysis-of-a-phase-ii-open-label-study-of-atezolizumab-in-pd-l1-selected-patients-with-non-small-cell-lung-cancer
#10
David R Spigel, Jamie E Chaft, Scott Gettinger, Bo H Chao, Luc Dirix, Peter Schmid, Laura Q M Chow, Rodney J Hicks, Larry Leon, Jill Fredrickson, Marcin Kowanetz, Alan Sandler, Roel Funke, Naiyer A Rizvi
INTRODUCTION: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. METHODS: Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases)...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29775768/canine-pet-dog-tumor-microsurgery-and-intratumoral-concentration-and-safety-of-metronomic-chlorambucil-for-spontaneous-glioma-a-phase-i-clinical-trial
#11
R Timothy Bentley, Stephanie A Thomovsky, Margaret A Miller, Deborah W Knapp, Aaron A Cohen-Gadol
INTRODUCTION: Metronomic (daily low-dose) chlorambucil requires further study before implementation in human glioma. OBJECTIVE: Investigate the distribution and safety of metronomic chlorambucil in naturally occurring canine glioma. METHODS: Eight client-owned (pet) dogs with newly diagnosed spontaneous glioma were prospectively enrolled. Chlorambucil was administered preoperatively at 4 mg/m2 q 24hr for ≥ 3 days, and continued postoperatively until death or dose-limiting adverse events...
May 15, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29775614/tumor-dependent-secretion-of-close-homolog-of-l1-results-in-elevation-of-its-circulating-level-in-mouse-model-for-human-lung-tumor
#12
Norihiro Kotani, Yui Ida, Takanari Nakano, Izumi Sato, Ryusuke Kuwahara, Arisa Yamaguchi, Masahiro Tomita, Koichi Honke, Takayuki Murakoshi
Close homolog of L1 (CHL1) and its truncated form mainly play crucial roles in mouse brain development and neural functions. Herein, we newly identified that truncated form of CHL1 is produced and released from lung tumor tissue in a mouse model expressing human EML4-ALK fusion gene. Both western blot and direct ELISA analysis revealed that mouse CHL1 level in serum (including serum extracellular vesicles) was significantly elevated in EML4-ALK transgenic mice. The correlation between the tumor size and the amount of CHL1 secretion could be examined in this study, and showed a significant positive correlation in a tumor size-dependent manner...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775613/suppression-of-nlrp3-inflammasome-attenuates-stress-induced-depression-like-behavior-in-nlgn3-deficient-mice
#13
Ze-Qun Li, Zhi-Yuan Yan, Bo-Jun Lan, Yi-Qun Dong, Ye Xiong
Depression, regulated by central nervous system (CNS), is a significant inflammatory disorder. Neuroligin3 (NLGN3) has been implicated in brain functions. In the study, a chronic unpredictable mild stress (CUMS) model in wild type (WT) or NLGN3-knockout (KO) mice was established to explore the role of NLGN3 in regulating depression and to reveal the underlying molecular mechanism. The results indicated that NLGN3-knockout markedly reversed the loss of body weight, the reduction of sucrose consumption, the decrease of immobile time in the forced swimming tests (FST) and tail suspension tests (TST) induced by CUMS paradigm...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775160/site-specific-expression-of-amine-oxidases-in-breast-cancer-metastases
#14
Yoon Jin Cha, Woo Hee Jung, Ja Seung Koo
We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 126 metastatic breast tumors (31 bone metastases (24.6%), 36 brain metastases (28.6%), 11 liver metastases (8.7%), and 48 lung metastases (38.1%)). Immunohistochemical staining for amine oxidase-related proteins (lysyl oxidase, diamine oxidase, and monoamine oxidase A and B) was performed. In metastatic breast cancer tissue, lysyl oxidase ( p = 0...
May 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29775109/outcomes-of-surgery-as-part-of-the-management-of-metastatic-non-small-cell-lung-cancer-a-surveillance-epidemiology-and-end-results-database-analysis
#15
Omar Abdel-Rahman
The role of local treatment in patients with oligometastatic non-small-cell lung cancer (NSCLC) is a subject of ongoing debate. This study assessed the survival impact of combined surgery to the primary tumor and metastatic disease in the management of metastatic NSCLC. Stage IV NSCLC patients at presentation, diagnosed from 2004 to 2013 were identified from the SEER (Surveillance, Epidemiology, and End Results) database. Propensity-matched analysis was performed considering baseline characteristics (age, gender, race, histology, TN stage, and site of metastases)...
April 21, 2018: Cancer Investigation
https://www.readbyqxmd.com/read/29775073/diffuse-gliomas-for-nonneuropathologists-the-new-integrated-molecular-diagnostics
#16
Sunhee C Lee
Diffuse gliomas comprise the bulk of "brain cancer" in adults. The recent update to the 4th edition of the World Health Organization's classification of tumors of the central nervous system reflects an unprecedented change in the landscape of the diagnosis and management of diffuse gliomas that will affect all those involved in the management and care of patients. Of the recently discovered gene alterations, mutations in the Krebs cycle enzymes isocitrate dehydrogenases (IDHs) 1 and 2 have fundamentally changed the way the gliomas are understood and classified...
May 18, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29774873/-application-of-intraoperative-mri-combined-with-neuronavigation-in-microsurgical-resection-for-insular-glioma
#17
Quanwei Zhou, Li Xia, Kejun He, Sheng Yan, Xiaoping Xu, Xixi Li, Zhengsong Huang, Nu Zhang
To evaluate the value of intraoperative magnetic resonance imaging (iMRI) combined with neuronavigation for the resection of insular gliomas.
 Methods: From August 2014 to October 2017 in the First Hospital Affiliated to Sun Yat-sen University, clinical data of 41 patients with insular glioma, who underwent the surgery assisted with 3.0T iMRI and neuronavigation, were analyzed retrospectively, and the resection extent, complications and prognosis were evaluated.
 Results: Subtotal tumor resection was achieved in 21 patients and partial resection was done in 20 after iMRI scanning...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29774871/-progression-of-basic-research-clinical-application-of-photodynamic-therapy-and-fluorescence-guided-surgery-in-glioma-treatment
#18
Xuegang Li, Hua Feng, Fei Li
The prognosis of glioma remains poor because of the infiltrative nature and the high local relapse rate. The current goals for patients with gliomas is maximal safe resection and adjuvant therapy. Tumor-specific photosensitizer, such as hematoporphyrin derivative (HpD) 5-aminolevulinic acid (5-ALA), can be selective up-taken and accumulated in tumor tissue. Light with appropriate wavelength can penetrate tumor tissue and excite the photosensitizer. The excited photosensitizer within glioma cells permits fluorescence visualization of tumor tissue during surgery and has been introduced in treatment of glioma as fluorescence-guided surgery (FGS)...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29774870/radiomics-in-gliomas-a-promising-assistance-for-glioma-clinical-research
#19
Yueshuang Leng, Xiaoyi Wang, Weihua Liao, Ya Cao
Gliomas are the most common brain primary tumors worldwide, which is the earliest sequenced cancer gene in the Cancer Genome Atlas (TCGA) project. The World Health Organization Classification Update of Central Nervous System (CNS) Tumors 2016 highlights that glioma is the first tumor classified based on both of the molecular markers and histology. Radiomics is an extraction approach for high-throughput data which collects the quantitative image information appearing. Combined imaging data with genomics and proteomics, radiomics show promising prediction for cancer diagnosis, treatment, and prognosis...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29774869/genetic-epidemiology-and-risk-factors-for-brain-tumors
#20
Xuejun Li, Hang Cao, Yanhong Liu
This report summarized current knowledge and findings relevant to environmental and genetic risk factors in brain tumors, with a particular focus on glioma. To date, the established risk factors for brain tumors are family history and ionizing radiation exposure; whereas there is an inverse association between tumors and other factors such as history of allergies, atopic conditions, chickenpox, and varicella zoster virus infection. To identify inherited genetic variants impacting susceptibility of brain tumors, large scale familial linkage-scan pedigree analysis, population-based candidate genes, and genome-wide association study were performed...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
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