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https://www.readbyqxmd.com/read/28536567/the-repurposing-of-anti-psychotic-drugs-quetiapine-and-olanzapine-as-anti-cryptococcus-drugs
#1
Adepemi O Ogundeji, Carolina H Pohl, Olihile M Sebolai
The management of cryptococcal infections is often difficult. This can, in part, be attributed to the fungistatic nature of fluconazole, which may result in cells disseminating to give rise to pathogen-emergent psychosis following brain inflammation. This chance at treatment failure has necessitated the current study wherein the antimicrobial quality of anti-psychotic drugs viz. quetiapine and olanzapine, was assessed. The response of test strains toward quetiapine or olanzapine alone and in combined therapy with fluconazole or amphotericn B was measured...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28536277/3d-mathematical-modeling-of-glioblastoma-suggests-that-transdifferentiated-vascular-endothelial-cells-mediate-resistance-to-current-standard-of-care-therapy
#2
Huaming Yan, Mónica Romero-López, Lesly I Benitez, Kaijun Di, Hermann B Frieboes, Christopher C W Hughes, Daniela A Bota, John S Lowengrub
Glioblastoma (GBM), the most aggressive brain tumor in human patients, is decidedly heterogeneous and highly vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and promoting resistance to therapy. Recently, crosstalk between GSC and vascular endothelial cells has been shown to significantly promote GSC self-renewal and tumor progression. Further, GSC also transdifferentiate into bona-fide vascular endothelial cells (GEC), which inherit mutations present in GSC and are resistant to traditional anti-angiogenic therapies...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28529554/novel-drugs-in-pediatric-gliomas
#3
Dongli Zhang, Xiaoming Liu, Conghai Fan, Jiao Chen
Astrocytomas (gliomas) are the most common primary brain tumors among adults and second most frequent neoplasm among children. New ideas and novel approaches are being explored world over with aim to devise better management strategeies for this deadly pathological state. We searched the electronic database PubMed for pre-clinical as well as clinical controlled trials reporting importance of various therapeutic drugs against gliomas. It was observed clearly that this approach of using therapeutic drugs is clearly evolving and has been observed to be promising future therapeutic avenue against gliomas...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28509337/impact-of-induction-chemotherapy-hyperfractionated-accelerated-radiotherapy-and-high-dose-thiotepa-on-brain-volume-loss-and-functional-status-of-children-with-primitive-neuroectodermal-tumour
#4
Elwira Szychot, Kiran Seunarine, Kshitij Mankad, Steffi Thust, Chris Clark, Mark N Gaze, Antony Michalski
BACKGROUND: The introduction of aggressive chemo-radiotherapy regimens has improved overall survival in children with primitive neuroectodermal tumours (PNET). However, these combinations may result in neurotoxicity. Previously reported magnetic resonance imaging abnormalities in children receiving intensive sequential chemotherapy, hyperfractionated accelerated radiotherapy (HART) and high-dose thiotepa prompted us to investigate the degree of brain volume loss and patients' functional status after therapy...
May 16, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28483841/trem2-deficiency-impairs-chemotaxis-and-microglial-responses-to-neuronal-injury
#5
Fargol Mazaheri, Nicolas Snaidero, Gernot Kleinberger, Charlotte Madore, Anna Daria, Georg Werner, Susanne Krasemann, Anja Capell, Dietrich Trümbach, Wolfgang Wurst, Bettina Brunner, Sebastian Bultmann, Sabina Tahirovic, Martin Kerschensteiner, Thomas Misgeld, Oleg Butovsky, Christian Haass
Sequence variations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to an increased risk for neurodegenerative disorders such as Alzheimer's disease and frontotemporal lobar degeneration. In the brain, TREM2 is predominantly expressed in microglia. Several disease-associated TREM2 variants result in a loss of function by reducing microglial phagocytosis, impairing lipid sensing, preventing binding of lipoproteins and affecting shielding of amyloid plaques. We here investigate the consequences of TREM2 loss of function on the microglia transcriptome...
May 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28454069/cns-bioavailability-and-radiation-protection-of-normal-hippocampal-neurogenesis-by-a-lipophilic-mn-porphyrin-based-superoxide-dismutase-mimic-mntnbuoe-2-pyp-5
#6
David Leu, Ivan Spasojevic, Huy Nguyen, Brian Deng, Artak Tovmasyan, Tin Weitner, Romulo S Sampaio, Ines Batinic-Haberle, Ting-Ting Huang
Although radiation therapy can be effective against cancer, potential damage to normal tissues limits the amount that can be safely administered. In central nervous system (CNS), radiation damage to normal tissues is presented, in part, as suppressed hippocampal neurogenesis and impaired cognitive functions. Mn porphyrin (MnP)-based redox active drugs have demonstrated differential effects on cancer and normal tissues in experimental animals that lead to protection of normal tissues and radio- and chemo-sensitization of cancers...
April 22, 2017: Redox Biology
https://www.readbyqxmd.com/read/28450700/sensitization-of-glioblastoma-tumor-micro-environment-to-chemo-and-immunotherapy-by-galectin-1-intranasal-knock-down-strategy
#7
Matthias Van Woensel, Thomas Mathivet, Nathalie Wauthoz, Rémi Rosière, Abhishek D Garg, Patrizia Agostinis, Véronique Mathieu, Robert Kiss, Florence Lefranc, Louis Boon, Jochen Belmans, Stefaan W Van Gool, Holger Gerhardt, Karim Amighi, Steven De Vleeschouwer
In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435518/sparc-overexpression-alters-microrna-expression-profiles-involved-in-tumor-progression
#8
Bhavesh K Ahir, Nasya M Elias, Sajani S Lakka
Medulloblastoma is the most common malignant brain tumor in children. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in multiple processes in various cancers. Previously, we reported that SPARC expression significantly impairs medulloblastoma tumor growth in vitro and in vivo and also alters chemo sensitivity. MicroRNAs are a class of post-transcriptional gene regulators with critical functions in tumor progression. In addition, microRNA (miRNA) expression changes are also involved in chemo-resistance...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28429473/surgery-for-limited-stage-small-cell-lung-cancer
#9
REVIEW
Hayley Barnes, Katharine See, Stephen Barnett, Renée Manser
BACKGROUND: Current treatment guidelines for limited-stage small-cell lung cancer (SCLC) recommend concomitant platinum-based chemo-radiotherapy plus prophylactic cranial irradiation, based on the premise that SCLC disseminates early, and is chemosensitive. However, although there is usually a favourable initial response, relapse is common and the cure rate for limited-stage SCLC remains relatively poor. Some recent clinical practice guidelines have recommended surgery for stage 1 (limited) SCLC followed by adjuvant chemotherapy, but this recommendation is largely based on the findings of observational studies...
April 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28427529/primary-central-nervous-system-lymphoma
#10
REVIEW
Giovanni Citterio, Michele Reni, Gemma Gatta, Andrés José Maria Ferreri
Primary CNS lymphomas (PCNSL) represent a subgroup of malignancies with specific characteristics, aggressive course, and unsatisfactory outcome in contrast with other lymphomas comparable for tumour burden and/or histological type. Despite a high chemo- and radiosensitivity, remissions are frequently shortlasting, mainly because the blood brain-barrier limits the access of many drugs to the CNS. Moreover, survivor patients are at high risk of developing severe treatment-related toxicity, mainly disabling neurotoxicity, raising the question of how to balance therapy intensification with side-effects control...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28424411/migration-pattern-actin-cytoskeleton-organization-and-response-to-pi3k-mtor-and-hsp90-inhibition-of-glioblastoma-cells-with-different-invasive-capacities
#11
Simon Memmel, Dmitri Sisario, Caren Zöller, Vanessa Fiedler, Astrid Katzer, Robin Heiden, Nicholas Becker, Lorenz Eing, Fábio L R Ferreira, Heiko Zimmermann, Markus Sauer, Michael Flentje, Vladimir L Sukhorukov, Cholpon S Djuzenova
High invasiveness and resistance to chemo- and radiotherapy of glioblastoma multiforme (GBM) make it the most lethal brain tumor. Therefore, new treatment strategies for preventing migration and invasion of GBM cells are needed. Using two different migration assays, Western blotting, conventional and super-resolution (dSTORM) fluorescence microscopy we examine the effects of the dual PI3K/mTOR-inhibitor PI-103 alone and in combination with the Hsp90 inhibitor NVP-AUY922 and/or irradiation on the migration, expression of marker proteins, focal adhesions and F-actin cytoskeleton in two GBM cell lines (DK-MG and SNB19) markedly differing in their invasive capacity...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419303/tumor-microtubes-convey-resistance-to-surgical-lesions-and-chemotherapy-in-gliomas
#12
Sophie Weil, Matthias Osswald, Gergely Solecki, Julia Grosch, Erik Jung, Dieter Lemke, Miriam Ratliff, Daniel Hänggi, Wolfgang Wick, Frank Winkler
Background: Primary and adaptive resistance against chemo- and radiotherapy, and local recurrence after surgery limit the benefits from these standard treatments in glioma patients. Recently we found that glioma cells can extend ultra-long membrane protrusions, "tumor microtubes" (TMs), for brain invasion, proliferation, and interconnection of single cells to a syncytium that is resistant to radiotherapy. We wondered whether TMs also convey resistance to the other two standard treatment modalities...
April 17, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28418837/rapamycin-promotes-differentiation-increasing-%C3%AE-iii-tubulin-neun-and-neurod-while-suppressing-nestin-expression-in-glioblastoma-cells
#13
Michela Ferrucci, Francesca Biagioni, Paola Lenzi, Stefano Gambardella, Rosangela Ferese, Maria Teresa Calierno, Alessandra Falleni, Alfonso Grimaldi, Alessandro Frati, Vincenzo Esposito, Cristina Limatola, Francesco Fornai
Glioblastoma cells feature mammalian target of rapamycin (mTOR) up-regulation which relates to a variety of effects such as: lower survival, higher infiltration, high stemness and radio- and chemo-resistance. Recently, it was demonstrated that mTOR may produce a gene shift leading to altered protein expression. Therefore, in the present study we administered different doses of the mTOR inhibitor rapamycin to explore whether the transcription of specific genes are modified. By using a variety of methods we demonstrate that rapamycin stimulates gene transcription related to neuronal differentiation while inhibiting stemness related genes such as nestin...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412744/mitochondrial-vdac1-based-peptides-attacking-oncogenic-properties-in-glioblastoma
#14
Anna Shteinfer-Kuzmine, Tasleem Arif, Yakov Krelin, Shambhoo Sharan Tripathi, Avijit Paul, Varda Shoshan-Barmatz
Glioblastoma multiforme (GBM), a primary brain malignancy characterized by high morbidity, invasiveness, proliferation, relapse and mortality, is resistant to chemo- and radiotherapies and lacks effective treatment. GBM tumors undergo metabolic reprograming and develop anti-apoptotic defenses. We targeted GBM with a peptide derived from the mitochondrial protein voltage-dependent anion channel 1 (VDAC1), a key component of cell energy, metabolism and apoptosis regulation. VDAC1-based cell-penetrating peptides perturbed cell energy and metabolic homeostasis and induced apoptosis in several GBM and GBM-derived stem cell lines...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28336375/tumortropic-adipose-derived-stem-cells-carrying-smart-nanotherapeutics-for-targeted-delivery-and-dual-modality-therapy-of-orthotopic-glioblastoma
#15
Wen-Chia Huang, I-Lin Lu, Wen-Hsuan Chiang, Yi-Wen Lin, Yuan-Chung Tsai, Hsin-Hung Chen, Chien-Wen Chang, Chi-Shiun Chiang, Hsin-Cheng Chiu
Chemotherapy is typically used to treat malignant brain tumors, especially for the tumors in surgically inaccessible areas. However, owing to the existence of blood-brain barrier (BBB), the tumor accumulation and therapeutic efficacy of clinical therapeutics is still of great concerns. To this end, we present herein a prominent therapeutic strategy adopting adipose-derived stem cells (ADSCs) capable of carrying nanotherapeutic payloads selectively toward brain tumors for thermo/chemotherapy. The nanoparticle (NP) payload was obtained from co-assembly of poly(γ-glutamic acid-co-distearyl γ-glutamate) with poly(lactic-co-glycolic acid), paclitaxel (PTX), and oleic acid-coated superparamagnetic iron oxide NPs in aqueous solution...
March 21, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28302031/hif1a-is-overexpressed-in-medulloblastoma-and-its-inhibition-reduces-proliferation-and-increases-epas1-and-atg16l1-methylation
#16
Gustavo Alencastro Veiga Cruzeiro, Maristella Bergamo Dos Reis, Vanessa Silva Silveira, Régia Caroline Peixoto Lira, Carlos Gilberto Carlotti, Luciano Neder, Ricardo Santos Oliveira, José Andres Yunes, Silvia Regina Brandalise, Simone Aguiar, Agda Karina Eterovic, Luiz Gonzaga Tone, Carlos Alberto Scrideli, Elvis Terci Valera
BACKGROUND: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxia-related genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions...
March 15, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28273854/overexpression-of-transforming-acidic-coiled-coil%C3%A2-containing-protein-3-reflects-malignant-characteristics-and-poor-prognosis-of-glioma
#17
Ying Sun, Yu Tian, Guang-Zhi Wang, Shi-Hong Zhao, Bo Han, Yong-Li Li, Chuan-Lu Jiang
Gliomas are malignant primary brain tumors with poor prognosis. Recently, research was indicative of a tight connection between tumor malignancy and genetic alterations. Here, we propose an oncogenic implication of transforming acidic coiled-coil-containing protein 3 (TACC3) in gliomas. By comprehensively analyzing the Chinese glioma genome atlas (CGGA) and publicly available data, we demonstrated that TACC3 were overexpressed along with glioma grade and served as an independent negative prognostic biomarker for glioma patients...
March 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28241049/expression-of-cd133-and-cd44-in-glioblastoma-stem-cells-correlates-with-cell-proliferation-phenotype-stability-and-intra-tumor-heterogeneity
#18
Daniel V Brown, Gulay Filiz, Paul M Daniel, Frédéric Hollande, Sebastian Dworkin, Stephanie Amiridis, Nicole Kountouri, Wayne Ng, Andrew P Morokoff, Theo Mantamadiotis
Glioblastoma (GBM) is a heterogeneous tumor of the brain with a poor prognosis due to recurrence and drug resistance following therapy. Genome-wide profiling has revealed the existence of distinct GBM molecular subtypes that respond differently to aggressive therapies. Despite this, molecular subtype does not predict recurrence or drug resistance and overall survival is similar across subtypes. One of the key features contributing to tumor recurrence and resistance to therapy is proposed to be an underlying subpopulation of resistant glioma stem cells (GSC)...
2017: PloS One
https://www.readbyqxmd.com/read/28169355/enhancement-of-5-aminolevulinic-acid-based-fluorescence-detection-of-side-population-defined-glioma-stem-cells-by-iron-chelation
#19
Wenqian Wang, Kouichi Tabu, Yuichiro Hagiya, Yuta Sugiyama, Yasuhiro Kokubu, Yoshitaka Murota, Shun-Ichiro Ogura, Tetsuya Taga
Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28157626/evaluation-of-18-f-atri-as-pet-tracer-for-in-vivo-imaging-of-atr-in-mouse-models-of-brain-cancer
#20
Giuseppe Carlucci, Brandon Carney, Ahmad Sadique, Axel Vansteene, Jun Tang, Thomas Reiner
RATIONALE: Ataxia telangiectasia and Rad3-related (ATR) threonine serine kinase is one of the key elements in orchestrating the DNA damage response (DDR). As such, inhibition of ATR can amplify the effects of chemo- and radiation-therapy, and several ATR inhibitors (ATRi) have already undergone clinical testing in cancer. For more accurate patient selection, monitoring and staging, real-time in vivo imaging of ATR could be invaluable; the development of appropriate imaging agents has remained a major challenge...
May 2017: Nuclear Medicine and Biology
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