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https://www.readbyqxmd.com/read/28089821/the-role-of-stat3-in-glioblastoma-progression-through-dual-influences-on-tumor-cells-and-the-immune-microenvironment
#1
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/28076790/the-anti-warburg-effect-elicited-by-the-camp-pgc1%C3%AE-pathway-drives-differentiation-of-glioblastoma-cells-into-astrocytes
#2
Fan Xing, Yizhao Luan, Jing Cai, Sihan Wu, Jialuo Mai, Jiayu Gu, Haipeng Zhang, Kai Li, Yuan Lin, Xiao Xiao, Jiankai Liang, Yuan Li, Wenli Chen, Yaqian Tan, Longxiang Sheng, Bingzheng Lu, Wanjun Lu, Mingshi Gao, Pengxin Qiu, Xingwen Su, Wei Yin, Jun Hu, Zhongping Chen, Ke Sai, Jing Wang, Furong Chen, Yinsheng Chen, Shida Zhu, Dongbing Liu, Shiyuan Cheng, Zhi Xie, Wenbo Zhu, Guangmei Yan
Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that specifically directed GBM differentiation into astroglia. Transcriptomic and proteomic analyses revealed that oxidative phosphorylation and mitochondrial biogenesis are involved in induced differentiation of GBM...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076333/surgical-debulking-promotes-recruitment-of-macrophages-and-triggers-glioblastoma-phagocytosis-in-combination-with-cd47-blocking-immunotherapy
#3
Huaiyang Zhu, Lina Leiss, Ning Yang, Cecilie B Rygh, Siddhartha S Mitra, Samuel H Cheshier, Irving L Weissman, Bin Huang, Hrvoje Miletic, Rolf Bjerkvig, Per Ø Enger, Xingang Li, Jian Wang
Surgical resection is a standard component of treatment in the clinical management of patients with glioblastoma multiforme (GBM). However, experimental therapies are rarely investigated in the context of tumor debulking in preclinical models. Here, a surgical debulking GBM xenograft model was developed in nude rats, and was used in combination with CD47 blocking immunotherapy, a novel treatment strategy that triggers phagocytosis of tumor cells by macrophages in diverse cancer types including GBM. Orthotopic patient-derived xenograft tumors expressing CD47 were resected at 4 weeks after implantation and immediately thereafter treated with anti-CD47 or control antibodies injected into the cavity...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28070598/advanced-mri-assessment-to-predict-benefit-of-anti-programmed-cell-death-1-protein-immunotherapy-response-in-patients-with-recurrent-glioblastoma
#4
Lei Qin, Xiang Li, Amanda Stroiney, Jinrong Qu, Jeffrey Helgager, David A Reardon, Geoffrey S Young
INTRODUCTION: We describe the imaging findings encountered in GBM patients receiving immune checkpoint blockade and assess the potential of quantitative MRI biomarkers to differentiate patients who derive therapeutic benefit from those who do not. METHODS: A retrospective analysis was performed on longitudinal MRIs obtained on recurrent GBM patients enrolled on clinical trials. Among 10 patients with analyzable data, bidirectional diameters were measured on contrast enhanced T1 (pGd-T1WI) and volumes of interest (VOI) representing measurable abnormality suggestive of tumor were selected on pGdT1WI (pGdT1 VOI), FLAIR-T2WI (FLAIR VOI), and ADC maps...
January 9, 2017: Neuroradiology
https://www.readbyqxmd.com/read/28059653/sulforaphane-suppresses-the-growth-of-glioblastoma-cells-glioblastoma-stem-cell-like-spheroids-and-tumor-xenografts-through-multiple-cell-signaling-pathways
#5
Khadijeh Bijangi-Vishehsaraei, M Reza Saadatzadeh, Haiyan Wang, Angie Nguyen, Malgorzata M Kamocka, Wenjing Cai, Aaron A Cohen-Gadol, Stacey L Halum, Jann N Sarkaria, Karen E Pollok, Ahmad R Safa
OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM...
January 6, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28054986/d-l-sulforaphane-induces-ros-dependent-apoptosis-in-human-gliomablastoma-cells-by-inactivating-stat3-signaling-pathway
#6
Ziwei Miao, Fei Yu, Yahao Ren, Jun Yang
d,l-Sulforaphane (SFN), a synthetic analogue of broccoli-derived isomer l-SFN, exerts cytotoxic effects on multiple tumor cell types through different mechanisms and is more potent than the l-isomer at inhibiting cancer growth. However, the means by which SFN impairs glioblastoma (GBM) cells remains poorly understood. In this study, we investigated the anti-cancer effect of SFN in GBM cells and determined the underlying molecular mechanisms. Cell viability assays, flow cytometry, immunofluorescence, and Western blot results revealed that SFN could induced apoptosis of GBM cells in a dose- and time-dependent manner, via up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2...
January 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28034905/absence-of-cytomegalovirus-in-glioblastoma-and-other-high-grade-gliomas-by-real-time-pcr-immunohistochemistry-and-in-situ-hybridization
#7
Matthias Holdhoff, Gunes Guner, Fausto J Rodriguez, Jessica L Hicks, Qizhi Zheng, Michael S Forman, Xiaobu Ye, Stuart A Grossman, Alan K Meeker, Christopher M Heaphy, Charles G Eberhart, Angelo M De Marzo, Ravit Arav-Boger
PURPOSE: Reports of cytomegalovirus (CMV) detection in high-grade gliomas (HGG)/glioblastoma (GBM) have been conflicting. We undertook a comprehensive approach to determine presence or absence of CMV in tissue, plasma and serum of HGG patients. EXPERIMENTAL DESIGN: In a retrospective arm, 25 fresh frozen tissues from GBM patients were tested for CMV by real-time PCR. Tissue microarrays from 70 HGG patients were tested by immunohistochemistry (IHC) and 20 formalin-fixed paraffin-embedded (FFPE) GBM tissues by IHC and chromogenic in situ hybridization (CISH), targeting CMV-encoded IE1/2 and pp65...
December 29, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28032512/anti-proliferative-study-and-isolation-of-ochnaflavone-from-the-ethyl-acetate-soluble-fraction-of-ochna-kibbiensis-hutch-dalziel
#8
Abdullahi M Ismail, Aliyu M Musa, Tajuddeen Nasir, Mohammed G Magaji, Yusuf A Jega, Iliya Ibrahim
Anti-proliferative activity of the ethyl acetate fractions of Ochna schweinfurthiana F. Hoffm. and Ochna kibbiensis Hutch. and Dalziel methanol leaf extracts were investigated against glioblastoma multiforme (GBM U-1242 MG) cell line. O. kibbiensis significantly (p < 0.001) and dose dependently (IC50 = 25.74 μg/mL) reduced cell count. At 125 μg/mL, O. kibbiensis extract reduced cell count by about 92% compared to the untreated control. On the other hand, at 125 μg/mL, O. schweinfurthiana extract reduced cell count only by 20%, indicating a much weaker activity (IC50 = 823...
December 29, 2016: Natural Product Research
https://www.readbyqxmd.com/read/28025034/ccl2-ccr2-signaling-pathway-in-glioblastoma-multiforme
#9
REVIEW
Alireza Vakilian, Hossein Khorramdelazad, Parisa Heidari, Zahra Sheikh Rezaei, Gholamhossein Hassanshahi
Glioblastoma multiform (GBM) is described as one of the most frequent primary brain tumors. These types of malignancies constitute only 15% of all primary brain tumors. Despite, extensive developments on effective therapeutic methods during the 20th century as well as the first decade of the present century (21st), the median survival rate for patients suffering from GBM is only approximately 15 months, even in response to multi-modal therapy. numerous types of reticuloendothelial system cells such as macrophages and microglial cells occupied within both GBM and also normal surrounding tissues...
December 24, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/28011470/advances-in-experimental-targeted-therapy-and-immunotherapy-for-patients-with-glioblastoma-multiforme
#10
REVIEW
Jiri Polivka, Jiri Polivka, Lubos Holubec, Tereza Kubikova, Vladimir Priban, Ondrej Hes, Kristyna Pivovarcikova, Inka Treskova
Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28004272/rice-bran-protein-hydrolysates-attenuate-diabetic-nephropathy-in-diabetic-animal-model
#11
Kampeebhorn Boonloh, Eun Soo Lee, Hong Min Kim, Mi Hye Kwon, You Mi Kim, Patchareewan Pannangpetch, Bunkerd Kongyingyoes, Upa Kukongviriyapan, Supawan Thawornchinsombut, Eun Young Lee, Veerapol Kukongviriyapan, Choon Hee Chung
INTRODUCTION: Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells. METHODS: Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks...
December 21, 2016: European Journal of Nutrition
https://www.readbyqxmd.com/read/28003545/anti-pd-1-antitumor-immunity-is-enhanced-by-local-and-abrogated-by-systemic-chemotherapy-in-gbm
#12
Dimitrios Mathios, Jennifer E Kim, Antonella Mangraviti, Jillian Phallen, Chul-Kee Park, Christopher M Jackson, Tomas Garzon-Muvdi, Eileen Kim, Debebe Theodros, Magdalena Polanczyk, Allison M Martin, Ian Suk, Xiaobu Ye, Betty Tyler, Chetan Bettegowda, Henry Brem, Drew M Pardoll, Michael Lim
The immunosuppressive effects of chemotherapy present a challenge for designing effective cancer immunotherapy strategies. We hypothesized that although systemic chemotherapy (SC) exhibits negative immunologic effects, local chemotherapy (LC) can potentiate an antitumor immune response. We show that LC combined with anti-programmed cell death protein 1 (PD-1) facilitates an antitumor immune response and improves survival (P < 0.001) in glioblastoma. LC-treated mice had increased infiltration of tumor-associated dendritic cells and clonal expansion of antigen-specific T effector cells...
December 21, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27998729/in%C3%A2-vivo-imaging-of-inflamed-glomeruli-reveals-dynamics-of-neutrophil-extracellular-trap-formation-in-glomerular-capillaries
#13
Clare L V Westhorpe, James E Bayard, Kim M O'Sullivan, Pam Hall, Qiang Cheng, A Richard Kitching, Michael J Hickey
Neutrophil extracellular traps (NETs) have been documented in glomeruli of patients with glomerulonephritis. However, the dynamics of NET formation in the glomerulus and their functional contribution to acute glomerular injury are poorly understood. Herein, we used in vivo multiphoton microscopy to investigate NET formation in the acutely inflamed glomerulus. Glomerular inflammation was induced using an antibody against the glomerular basement membrane. After induction of glomerular inflammation, multiphoton microscopy revealed that approximately 20% of glomeruli contained structures composed of extracellular DNA within the capillaries...
December 17, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27994064/a-novel-nfia-nf%C3%AE%C2%BAb-feed-forward-loop-contributes-to-glioblastoma-cell-survival
#14
JunSung Lee, Edlira Hoxha, Hae-Ri Song
BACKGROUND: The nuclear factor I-A (NFIA) transcription factor promotes glioma growth and inhibits apoptosis in glioblastoma (GBM) cells. Here we report that the NFIA pro-survival effect in GBM is mediated in part via a novel NFIA-nuclear factor-kappaB (NFκB) p65 feed-forward loop. METHODS: We examined effects of gain- and loss-of-function manipulations of NFIA and NFκB p65 on each other's transcription, cell growth, apoptosis and sensitivity to chemotherapy in patient-derived GBM cells and established GBM cell lines...
December 18, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27993946/anaplastic-lymphoma-kinase-expression-and-gene-alterations-in-glioblastoma-correlations-with-clinical-outcome
#15
George Karagkounis, George Stranjalis, Theodore Argyrakos, Varvara Pantelaion, Konstantinos Mastoris, Dimitra Rontogianni, Spyridon Komaitis, Theodosis Kalamatianos, Damianos Sakas, Dina Tiniakos
AIMS: To study anaplastic lymphoma kinase (ALK) protein expression and possible underlying gene alterations in glioblastoma (GBM), correlating them with clinical outcome. METHODS: We studied ALK immunohistochemical expression and fluorescent in situ hybridisation (FISH)-detected ALK gene alterations in 51 GBMs (46 isocitrate dehydrogenase-1 (IDH1)(R132H)-negative and 5 IDH-mutant (IDH1(R132H)-positive)). We compared two anti-ALK antibodies and immunohistochemical detection systems (5Α4/Nichirei Biosciences, D5F3/Ventana)...
December 19, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27990624/vascular-mimicry-in-glioblastoma-following-anti-angiogenic-and-anti-20-hete-therapies
#16
Kartik Angara, Mohammad H Rashid, Adarsh Shankar, Roxan Ara, Asm Iskander, Thaiz F Borin, Meenu Jain, Bhagelu R Achyut, Ali S Arbab
Glioblastoma (GBM) is one hypervascular and hypoxic tumor known among solid tumors. Antiangiogenic therapeutics (AATs) have been tested as an adjuvant to normalize blood vessels and control abnormal vasculature. Evidence of relapse exemplified in the progressive tumor growth following AAT reflects development of resistance to AATs. Here, we identified that GBM following AAT (Vatalanib) acquired an alternate mechanism to support tumor growth, called vascular mimicry (VM). We observed that Vatalanib induced VM vessels are positive for periodic acid-Schiff (PAS) matrix but devoid of any endothelium on the inner side and lined by tumor cells on the outer-side...
December 19, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27981771/goodpasture-disease-as-a-consequence-of-melioidosis
#17
D Mackintosh, M Mantha, K Oliver
We describe a case of anti-glomerular basement membrane (GBM) antibody-mediated disease in association with concomitant Burkholderia pseudomallei (melioidosis) bacteraemia. The temporal profile of the illness and initial absence of circulating anti-GBM antibodies, in light of the subsequent definitive histological diagnosis of anti-GBM disease, makes this case interesting and unusual. Additionally, there have been no prior case reports suggesting melioidosis as a cause of biopsy-proven glomerulonephritis.
December 2016: Internal Medicine Journal
https://www.readbyqxmd.com/read/27976583/enhanced-antiglioma-efficacy-of-ultrahigh-loading-capacity-paclitaxel-prodrug-conjugate-self-assembled-targeted-nanoparticles
#18
Yan Jiang, Xiuzhen Wang, Xin Liu, Wei Lv, Hongjuan Zhang, Mingwan Zhang, Xinrui Li, Hongliang Xin, Qunwei Xu
Glioblastoma multiforme (GBM) presents one of the most lethal brain tumor with a dismal prognosis. And nanodrug delivery system (nano-DDS) have raised a lot of concern, while the conventional nanoformulations addressed many limitations, especially the low drug loading capacity and poor stability in vivo. Herein, we proposed PTX prodrug (PTX-SS-C18) conjugate self-assembled nanoparticles (PSNPs) functionalized with Pep-1, glioma homing peptide, to overcome the blood brain tumor barrier (BBTB) via interleukin 13 receptor α2 (IL-13Rα2)-mediated endocytosis for targeting GMB...
December 23, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27956075/natural-product-htp-screening-for-attenuation-of-cytokine-induced-neutrophil-chemo-attractants-cincs-and-no2-in-lps-ifn%C3%AE-activated-glioma-cells
#19
Elizabeth A Mazzio, David Bauer, Patricia Mendonca, Equar Taka, Karam F A Soliman
Chronic and acute central nervous system (CNS) inflammation are contributors toward neurological injury associated with head trauma, stroke, infection, Parkinsons or Alzheimers disease. CNS inflammatory illnesses can also contribute toward risk of developing glioblastoma multiforme (GBM). With growing public interest in complementary and alternative medicines (CAMs), we conduct a high throughput (HTP) screening of >1400 natural herbs, plants and over the counter (OTC) products for anti-inflammatory effects on lipopolysaccharide (LPS)/interferon gamma (IFNγ) activated C6 glioma cells...
January 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27941331/interleukin-17ra-promotes-humoral-responses-and-glomerular-injury-in-experimental-rapidly-progressive-glomerulonephritis
#20
Joanna R Ghali, Kim M O'Sullivan, Peter J Eggenhuizen, Stephen R Holdsworth, A Richard Kitching
BACKGROUND/AIMS: Interleukin (IL)-17A and IL-17F are proinflammatory cytokines, which signal through a receptor complex consisting of IL-17RA and IL-17RC subunits. We sought to define the role of IL-17RA expression by leukocytes and stromal cells in nephritogenic immunity and injury in experimental glomerulonephritis. METHODS: Glomerulonephritis was induced in wild-type and IL-17RA-deficient (IL-17RA-/-) mice by sheep anti-mouse glomerular basement membrane globulin...
December 10, 2016: Nephron
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