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Brain tumor drug

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https://www.readbyqxmd.com/read/29791136/precisely-striking-tumor-without-adjacent-normal-tissue-damage-via-mitochondria-templated-accumulation
#1
Zhao-Yu Ma, Kai Han, Xinxin Dai, Heyou Han
Ignored damage in adjacent normal tissue is fatal especially in some specific tumor therapy such as brain tumor, but it remains a great challenge to conquer it due to random drug diffusion and tumor complexity. Herein, we show the hyperthermia in mitochondria, an interparticle plasmonic coupling effect activated nanoevent, selectively strikes tumor tissue without damaging adjacent normal tissue. Spherical gold nanoparticles with a mitochondria-targeting moiety, triphenyl phosphonium, preferentially accumulated inside tumor mitochondria and reached the threshold to activate interparticle plasmonic coupling effect among gold nanoparticles, realizing selective light-thermal conversion and mitochondrial dysfunction in tumor, whereas little hyperthermia and mitochondrial dysfunction were observed in adjacent normal tissue...
May 23, 2018: ACS Nano
https://www.readbyqxmd.com/read/29790744/myristic-acid-modified-da7r-peptide-for-whole-process-glioma-targeted-drug-delivery
#2
Man Ying, Songli Wang, Mingfei Zhang, Ruifeng Wang, Hangchang Zhu, Huitong Ruan, Danni Ran, Zhilan Chai, Xiaoyi Wang, Weiyue Lu
Clinical treatment of aggressive glioma has been a great challenge, mainly due to the complexity of glioma microenvironment and the existence of blood-brain tumor barrier (BBTB)/blood-brain barrier (BBB), which severely hamper the effective accumulation of most therapeutic agents in glioma region. Additionally, vasculogenic mimicry (VM), angiogenesis and glioma stem cells (GSC) in malignant glioma also lead to the failure of clinical therapy. To address the aforementioned issues, a whole-process glioma targeted drug delivery strategy was proposed...
May 23, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29790738/design-and-development-of-polysaccharide-doxorubicin-peptide-bioconjugates-for-dual-synergistic-effects-of-integrin-targeted-and-cell-penetrating-peptides-for-cancer-chemotherapy
#3
Alexandra A P Mansur, Sandhra Maria Carvalho, Zelia Ines Portela Lobato, Maria de Fátima Leite, Armando da Silva Cunha, Herman S Mansur
Polymer-drug conjugation is an attractive approach for target delivering insoluble and highly toxic drugs to tumor sites to overcome the side-effects caused by cancer chemotherapy. In this study we designed and synthesized novel polymer-drug-peptide conjugates for improved specificity on targeting cancer cells. Chemically modified polysaccharide, carboxymethylcellulose (CMC), was conjugated with doxorubicin (DOX) anticancer drug by amide bonds and dually biofunctionalized with integrin-target receptor tripeptide (RGD) and L-arginine (R) as cell-penetrating amino acid for synergistic targeting and enhancing internalization by cancer cells...
May 23, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29789530/efficient-blood-brain-barrier-opening-in-primates-with-neuronavigation-guided-ultrasound-and-real-time-acoustic-mapping
#4
Shih-Ying Wu, Christian Aurup, Carlos Sierra Sanchez, Julien Grondin, Wenlan Zheng, Hermes Kamimura, Vincent P Ferrera, Elisa E Konofagou
Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29783757/a-repurposed-drug-for-brain-cancer-enhanced-atovaquone-amorphous-solid-dispersion-by-combining-a-spontaneously-emulsifying-component-with-a-polymer-carrier
#5
Hiroyuki Takabe, Zachary N Warnken, Yajie Zhang, Daniel A Davis, Hugh D C Smyth, John G Kuhn, Steve Weitman, Robert O Williams Iii
Glioblastoma multiforme (GBM) is the most common and lethal central nervous system tumor. Recently, atovaquone has shown inhibition of signal transducer and activator transcription 3, a promising target for GBM therapy. However, it is currently unable to achieve therapeutic drug concentrations in the brain with the currently reported and marketed formulations. The present study sought to explore the efficacy of atovaquone against GBM as well as develop a formulation of atovaquone that would improve oral bioavailability, resulting in higher amounts of drug delivered to the brain...
May 19, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29782307/cutaneous-manifestations-of-tuberous-sclerosis
#6
Mirjana Bakić, Marina Ratković, Branka Gledović, Balsa Vujović, Danilo Radunović, Vera Babić, Vladimir Prelević
Dear Editor, Tuberous sclerosis (TS) is an autosomal dominant multisystem disease, which occurs due to genetically determined hyperplasia of ectodermal and mesodermal cells. Clinical manifestations present on the skin and in the nervous system, kidneys, heart, and other organs. Recent studies estimate the incidence of TS at 1/6000 to 1/10,000 live births, and a prevalence in the general population of approximately 1 in 20,000 (1). There are two different genetic loci responsible for TS: 9q34 (TSC1-hamartin) and 16p13...
April 2018: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/29781781/gene-expression-microarray-analysis-reveals-prognostic-markers-of-survival-in-high-grade-astrocytomas
#7
Jun Yang, Ziming Hou, Changjiang Wang, Hao Wang, Hongbing Zhang
OBJECTIVE: High grade astrocytoma (HGA) as an aggressive brain tumor, is always correlated with poor prognosis. In this paper, we aimed to explore the genetic prognostic biomarkers for HGA. METHODS: The genome-wide expression profile of 26 brain tumor samples obtained from 26 patients with HGA was downloaded from Gene Expression Omnibus. The risk genes for prognosis of HGA were identified and verified by the data in TCGA database. Protein-protein interaction (PPI) network of risk factor genes was constructed and significant module was screened...
May 21, 2018: Neurological Research
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
#8
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/29777137/enhanced-efficacy-of-combined-temozolomide-and-bromodomain-inhibitor-therapy-for-gliomas-using-targeted-nanoparticles
#9
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/29774132/natural-products-a-hope-for-glioblastoma-patients
#10
REVIEW
Raghupathy Vengoji, Muzafar A Macha, Surinder K Batra, Nicole A Shonka
Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774098/establishment-of-primary-cell-culture-and-an-intracranial-xenograft-model-of-pediatric-ependymoma-a-prospect-for-therapy-development-and-understanding-of-tumor-biology
#11
Lorena Favaro Pavon, Tatiana Tais Sibov, Silvia Regina Caminada de Toledo, Daniela Mara de Oliveira, Francisco Romero Cabral, Jean Gabriel de Souza, Pamela Boufleur, Luciana C Marti, Jackeline Moraes Malheiros, Edgar Ferreira da Cruz, Fernando F Paiva, Suzana M F Malheiros, Manoel A de Paiva Neto, Alberto Tannús, Sérgio Mascarenhas de Oliveira, Nasjla Saba Silva, Andrea Maria Cappellano, Antonio Sérgio Petrilli, Ana Marisa Chudzinski-Tavassi, Sérgio Cavalheiro
Background: Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29769307/orally-bioavailable-and-blood-brain-barrier-penetrating-atm-inhibitor-az32-radiosensitizes-intracranial-gliomas-in-mice
#12
Jeremy Karlin, Jasmine Allen, Syed F Ahmad, Gareth Hughes, Victoria Sheridan, Rajesh Odedra, Paul Farrington, Elaine B Cadogan, Lucy C Riches, Antonio Garcia-Trinidad, Andrew G Thomason, Bhavika Patel, Jennifer Vincent, Alan Lau, Kurt G Pike, Thomas A Hunt, Amrita Sule, Nicholas C K Valerie, Laura Biddlestone-Thorpe, Jenna Kahn, Jason M Beckta, Nitai Mukhopadhyay, Bernard Barlaam, Sebastien L Degorce, Jason Kettle, Nicola Colclough, Joanne Wilson, Aaron Smith, Ian P Barrett, Li Zheng, Tianwei Zhang, Yingchun Wang, Kan Chen, Martin Pass, Stephen T Durant, Kristoffer Valerie
Inhibition of ataxia-telangiectasia mutated (ATM) during radiotherapy of glioblastoma multiforme (GBM) may improve tumor control by short-circuiting the response to radiation-induced DNA damage. A major impediment for clinical implementation is that current inhibitors have limited CNS bioavailability, thus, the goal was to identify ATM inhibitors (ATMi) with improved CNS penetration. Drug screens and refinement of lead compounds identified AZ31 and AZ32. The compounds were then tested in vivo for efficacy and impact on tumor and healthy brain...
May 16, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29765540/could-a-plant-derived-protein-potentiate-the-anticancer-effects-of-a-stem-cell-in-brain-cancer
#13
Camila Ramalho Bonturi, Helena Motaln, Mariana Cristina Cabral Silva, Bruno Ramos Salu, Marlon Vilela de Brito, Luciana de Andrade Luz Cost, Heron Fernandes Vieira Torquato, Natalia Neto Dos Santos Nunes, Edgar Julian Paredes-Gamero, Tamara Lah Turnšek, Maria Luiza Vilela Oliva
Glioblastoma is the most aggressive brain tumor with poor overall survival bellow 2 years. The natural compounds with anti-cancer properties, are thus gaining attention for possible adjuvant GBM treatment. In various cancer models Enterolobium contortisiliquum Trypsin Inhibitor (EcTI) proved to have anti-cancer effects. Here, we investigated the EcTI effects on GBM U87 cells and on mesenchymal stem cells (MSC) compared to their direct coculture (MSC/U87). MSC are present in tumor stroma, modulating GBM cells phenotype, and also represent potential drug delivery vehicle due to their tumor tropism...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29761249/targeting-glioblastoma-derived-pericytes-improves-chemotherapeutic-outcome
#14
REVIEW
Daniel A P Guerra, Ana E Paiva, Isadora F G Sena, Patrick O Azevedo, Walison N Silva, Akiva Mintz, Alexander Birbrair
Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood-brain barrier limits the arrival of several promising anti-glioblastoma drugs, and restricts the design of efficient therapies. Recently, by using state-of-the-art technologies, including thymidine kinase targeting system in combination with glioblastoma xenograft mouse models, it was revealed that targeting glioblastoma-derived pericytes improves chemotherapy efficiency. Strikingly, ibrutinib treatment enhances chemotherapeutic effectiveness, by targeting pericytes, improving blood-brain barrier permeability, and prolonging survival...
May 14, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29758196/temozolomide-combined-with-pd-1-antibody-therapy-for-mouse-orthotopic-glioma-model
#15
Bailing Dai, Na Qi, Junchao Li, Guilong Zhang
PURPOSE: Temozolomide (TMZ) is the most frequent adjuvant chemotherapy drug in gliomas. PDL1 expresses on various tumors, including gliomas, and anti-PD-1 antibodies have been approved for treating some tumors by FDA. This study was to evaluate the therapeutical potential of combined TMZ with anti-PD-1 antibody therapy for mouse orthotopic glioma model. METHODS: We performed C57BL/6 mouse orthotopic glioma model by stereotactic intracranial implantation of glioma cell line GL261, mice were randomly divided into four groups: (1) control group; (2) TMZ group; (3) anti-PD-1 antibody group; (4) TMZ combined with anti-PD-1 antibody group...
May 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29757276/fluorescence-molecular-tomography-for-in-vivo-imaging-of-glioblastoma-xenografts
#16
Jorge A Benitez, Ciro Zanca, Jianhui Ma, Webster K Cavenee, Frank B Furnari
Tumorigenicity is the capability of cancer cells to form a tumor mass. A widely used approach to determine if the cells are tumorigenic is by injecting immunodeficient mice subcutaneously with cancer cells and measuring the tumor mass after it becomes visible and palpable. Orthotopic injections of cancer cells aim to introduce the xenograft in the microenvironment that most closely resembles the tissue of origin of the tumor being studied. Brain cancer research requires intracranial injection of cancer cells to allow the tumor formation and analysis in the unique microenvironment of the brain...
April 26, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29751640/drug-delivery-nanosystems-for-the-localized-treatment-of-glioblastoma-multiforme
#17
REVIEW
L Nam, C Coll, L C S Erthal, C de la Torre, D Serrano, R Martínez-Máñez, M J Santos-Martínez, E Ruiz-Hernández
Glioblastoma multiforme is one of the most prevalent and malignant forms of central nervous system tumors. The treatment of glioblastoma remains a great challenge due to its location in the intracranial space and the presence of the blood⁻brain tumor barrier. There is an urgent need to develop novel therapy approaches for this tumor, to improve the clinical outcomes, and to reduce the rate of recurrence and adverse effects associated with present options. The formulation of therapeutic agents in nanostructures is one of the most promising approaches to treat glioblastoma due to the increased availability at the target site, and the possibility to co-deliver a range of drugs and diagnostic agents...
May 11, 2018: Materials
https://www.readbyqxmd.com/read/29750582/a-cytotoxic-three-dimensional-spheroid-high-throughput-assay-using-patient-derived-glioma-stem-cells
#18
Victor Quereda, Shurong Hou, Franck Madoux, Louis Scampavia, Timothy P Spicer, Derek Duckett
Glioblastoma (GBM) is the most aggressive primary brain cancer with an average survival time after diagnosis of only 12-14 months, with few (<5%) long-term survivors. A growing body of work suggests that GBMs contain a small population of glioma stem cells (GSCs) that are thought to be major contributors to treatment resistance and disease relapse. Identifying compounds that modulate GSC proliferation would provide highly valuable molecular probes of GSC-directed signaling. However, targeting GSCs pharmacologically has been challenging...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29750281/an-orthotopic-glioblastoma-animal-model-suitable-for-high-throughput-screenings
#19
Linda Pudelko, Steven Edwards, Mirela Balan, Daniel Nyqvist, Jonathan Al-Saadi, Johannes Dittmer, Ingrid Almlöf, Thomas Helleday, Lars Bräutigam
Background: Glioblastoma (GBM) is an aggressive form of brain cancer with poor prognosis. Although murine animal models have given valuable insights into the GBM disease biology, they cannot be used in high-throughput screens to identify and profile novel therapies. The only vertebrate model suitable for large-scale screens, the zebrafish, has proven to faithfully recapitulate biology and pathology of human malignancies and clinically relevant orthotopic zebrafish models have been developed...
May 10, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29749579/in-vivo-detection-of-acute-intracellular-acidification-in-glioblastoma-multiforme-following-a-single-dose-of-cariporide
#20
Mohammed Albatany, Alex Li, Susan Meakin, Robert Bartha
Glioblastoma is an aggressive brain cancer that is very difficult to treat. Clinically, it is important to be able to distinguish aggressive from non-aggressive brain tumors. Previous studies have shown that some drugs can induce a rapid change in intracellular pH that could help to identify aggressive cancer. The sodium proton exchanger (NHE1) plays a significant role in maintaining pH balance in the tumor microenvironment. Cariporide is a sodium proton exchange inhibitor that is well tolerated by humans in cardiac applications...
May 10, 2018: International Journal of Clinical Oncology
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