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https://www.readbyqxmd.com/read/28648712/emerging-strategies-for-delivering-antiangiogenic-therapies-to-primary-and-metastatic-brain-tumors
#1
Vasileios Askoxylakis, Costas D Arvanitis, Christina S F Wong, Gino B Ferraro, Rakesh K Jain
Five-years survival rates have not increased appreciably for patients with primary and metastatic brain tumors. Nearly 17,000 patients die from primary brain tumors, whereas approximately 200,000 cases are diagnosed with brain metastasis every year in the US alone. At the same time, with improved control of systemic disease, the incidence of brain metastasis is increasing. Thus novel approaches for improving the treatment outcome for these uniformly fatal diseases are needed urgently. In the review, we summarize the challenges in the treatment of these diseases using antiangiogenic therapies alone or in combination with radio-, chemo- and immuno-therapies...
June 22, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28623325/fluorescence-lifetime-imaging-microscopy-a-novel-diagnostic-tool-for-metastatic-cell-detection-in-the-cerebrospinal-fluid-of-children-with-medulloblastoma
#2
Sivan Gershanov, Shalom Michowiz, Helen Toledano, Gilad Yahav, Orit Barinfeld, Avraham Hirshberg, Haim Ben-Zvi, Gabriel Mircus, Mali Salmon-Divon, Dror Fixler, Nitza Goldenberg-Cohen
In pediatric brain tumours, dissemination of malignant cells within the central nervous system confers poor prognosis and determines treatment intensity, but is often undetectable by imaging or cytology. This study describes the use of fluorescence lifetime (FLT) imaging microscopy (FLIM), a novel diagnostic tool, for detection of metastatic spread. The study group included 15 children with medulloblastoma and 2 with atypical teratoid/rhabdoid tumour. Cells extracted from the tumour and the cerebrospinal fluid (CSF) 2 weeks postoperatively and repeatedly during chemo/radiotherapy were subjected to nuclear staining followed by FLT measurement and cytological study...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28614736/nanoparticle-mediated-knockdown-of-dna-repair-sensitizes-cells-to-radiotherapy-and-extends-survival-in-a-genetic-mouse-model-of-glioblastoma
#3
Forrest M Kievit, Kui Wang, Tatsuya Ozawa, Aria W Tarudji, John R Silber, Eric C Holland, Richard G Ellenbogen, Miqin Zhang
Glioblastoma (GBM) remains incurable, and recurrent tumors that rarely respond to standard-of-care radiation and chemo-therapies. Therefore, strategies that enhance the effects of these therapies should provide significant benefits to GBM patients. We have developed a nanoparticle delivery vehicle that can stably bind and protect nucleic acids for specific delivery into brain tumor cells. These nanoparticles can deliver therapeutic siRNAs to sensitize GBM cells to radiotherapy and improve GBM treatment via systemic administration...
June 11, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28602756/antrodia-cinnamomea-sensitizes-radio-chemo-therapy-of-cancer-stem-like-cells-by-modulating-microrna-expression
#4
Yu-Kai Su, Ping-Hsiao Shih, Wei-Hwa Lee, Oluwaseun Adebayo Bamodu, Alexander T H Wu, Chun-Chih Huang, Yew-Min Tzeng, Michael Hsiao, Chi-Tai Yeh, Chien-Min Lin
ETHNOPHARMACOLOGICAL RELEVANCE: The discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention...
June 8, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28587121/chemotherapeutic-drugs-dna-damage-and-repair-in-glioblastoma
#5
REVIEW
Laura Annovazzi, Marta Mellai, Davide Schiffer
Despite improvements in therapeutic strategies, glioblastoma (GB) remains one of the most lethal cancers. The presence of the blood-brain barrier, the infiltrative nature of the tumor and several resistance mechanisms account for the failure of current treatments. Distinct DNA repair pathways can neutralize the cytotoxicity of chemo- and radio-therapeutic agents, driving resistance and tumor relapse. It seems that a subpopulation of stem-like cells, indicated as glioma stem cells (GSCs), is responsible for tumor initiation, maintenance and recurrence and they appear to be more resistant owing to their enhanced DNA repair capacity...
May 26, 2017: Cancers
https://www.readbyqxmd.com/read/28566437/local-dna-repair-inhibition-for-sustained-radiosensitization-in-high-grade-gliomas
#6
Amanda R King, Christopher D Corso, Evan M Chen, Eric Song, Paul Bongiorni, Zhe Chen, Ranjini K Sundaram, Ranjit S Bindra, W Mark Saltzman
High-grade gliomas such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) are characterized by an aggressive phenotype with nearly universal local disease progression despite multimodal treatment, which typically includes chemotherapy, radiation therapy (RT), and possibly surgery. Radiosensitizers that have improved the effects of RT for extracranial tumors have been ineffective for the treatment of GBM and DIPG, in part due to poor blood brain barrier penetration and rapid intracranial clearance of small molecules...
May 31, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28551545/cytotoxicity-of-temozolomide-on-human-glioblastoma-cells-is-enhanced-by-the-concomitant-exposure-to-an-extremely-low-frequency-electromagnetic-field-100hz-100g
#7
Zeinab Akbarnejad, Hossein Eskandary, Luciana Dini, Cristian Vergallo, Seyed Noureddin Nematollahi-Mahani, Alireza Farsinejad, Maryam Fekri Soofi Abadi, Meysam Ahmadi
Glioblastoma multiforme (GBM) is the most malignant brain cancer that causes high mortality in humans. It responds poorly to the most common cancer treatments, such as surgery, chemo- and radiation therapy. Temozolomide (TMZ) is an alkylating agent that has been widely used to treat GBM; resistance to this drug is often found. One unexplored possibility for overcoming this resistance is a treatment based on concomitant exposure to electromagnetic fields (EMF) and TMZ. Indeed, many evidences show that EMF affects cancer cells and drug performance...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28536567/the-repurposing-of-anti-psychotic-drugs-quetiapine-and-olanzapine-as-anti-cryptococcus-drugs
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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...
August 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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