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https://www.readbyqxmd.com/read/29145972/cancer-immunotherapy-getting-brainy-visualizing-the-distinctive-cns-metastatic-niche-to-illuminate-therapeutic-resistance
#1
Mark Owyong, Niloufar Hosseini-Nassab, Gizem Efe, Alexander Honkala, Renske J E van den Bijgaart, Vicki Plaks, Bryan Ronain Smith
The advent of cancer immunotherapy (CIT) and its success in treating primary and metastatic cancer may offer substantially improved outcomes for patients. Despite recent advancements, many malignancies remain resistant to CIT, among which are brain metastases, a particularly virulent disease with no apparent cure. The immunologically unique niche of the brain has prompted compelling new questions in immuno-oncology such as the effects of tissue-specific differences in immune response, heterogeneity between primary tumors and distant metastases, and the role of spatiotemporal dynamics in shaping an effective anti-tumor immune response...
November 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29138567/resveratrol-ameliorates-chronic-unpredictable-mild-stress-induced-depression-like-behavior-involvement-of-the-hpa-axis-inflammatory-markers-bdnf-and-wnt-%C3%AE-catenin-pathway-in-rats
#2
Xin-Hua Yang, Su-Qi Song, Yun Xu
Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES), a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS), after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29137378/trastuzumab-distribution-in-an-in-vivo-and-in-vitro-model-of-brain-metastases-of-breast-cancer
#3
Tori B Terrell-Hall, Mohamed Ismail Nounou, Fatema El-Amrawy, Jessica I G Griffith, Paul R Lockman
Background: Drug and antibody delivery to brain metastases has been highly debated in the literature. The blood-tumor barrier (BTB) is more permeable than the blood-brain barrier (BBB), and has shown to have highly functioning efflux transporters and barrier properties, which limits delivery of targeted therapies. Methods: We characterized the permeability of (125)I-trastuzumab in an in-vivo, and fluorescent trastuzumab-Rhodamine123 (t-Rho123) in a novel microfluidic in-vitro, BBB and BTB brain metastases of breast cancer model...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133572/drug-repositioning-meets-precision-in-glioblastoma
#4
Wolfgang Wick, Tobias Kessler
Glioblastoma has a gigantic unmet medical need. Molecular knowledge has evolved substantially, including data on clonal selection with progression. Past trials for all-comers may have produced false negative results. Molecular precision at progression needs workup of new tissue and revisiting drugs with focus on brain tumor penetration may yield surprises.
November 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29133392/closed-loop-control-of-targeted-ultrasound-drug-delivery-across-the-blood-brain-tumor-barriers-in-a-rat-glioma-model
#5
Tao Sun, Yongzhi Zhang, Chanikarn Power, Phillip M Alexander, Jonathan T Sutton, Muna Aryal, Natalia Vykhodtseva, Eric L Miller, Nathan J McDannold
Cavitation-facilitated microbubble-mediated focused ultrasound therapy is a promising method of drug delivery across the blood-brain barrier (BBB) for treating many neurological disorders. Unlike ultrasound thermal therapies, during which magnetic resonance thermometry can serve as a reliable treatment control modality, real-time control of modulated BBB disruption with undetectable vascular damage remains a challenge. Here a closed-loop cavitation controlling paradigm that sustains stable cavitation while suppressing inertial cavitation behavior was designed and validated using a dual-transducer system operating at the clinically relevant ultrasound frequency of 274...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29125233/in-vivo-imaging-xenograft-models-for-the-evaluation-of-anti-brain-tumor-efficacy-of-targeted-drugs
#6
Kenji Kita, Sachiko Arai, Akihiro Nishiyama, Hirokazu Taniguchi, Koji Fukuda, Rong Wang, Tadaaki Yamada, Shinji Takeuchi, Shoichiro Tange, Atsushi Tajima, Mitsutoshi Nakada, Kazuo Yasumoto, Yoshiharu Motoo, Takashi Murakami, Seiji Yano
Molecular-targeted drugs are generally effective against tumors containing driver oncogenes, such as EGFR, ALK, and NTRK1. However, patients harboring these oncogenes frequently experience a progression of brain metastases during treatment. Here, we present an in vivo imaging model for brain tumors using human cancer cell lines, including the EGFR-L858R/T790M-positive H1975 lung adenocarcinoma cells, the NUGC4 hepatocyte growth factor (HGF)-dependent gastric cancer cells, and the KM12SM colorectal cancer cells containing the TPM3-NTRK1 gene fusion...
November 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29116485/prevalence-risk-factors-and-response-to-treatment-for-hypersomnia-of-central-origin-in-survivors-of-childhood-brain-tumors
#7
Raja B Khan, Thomas E Merchant, Zsila S Sadighi, Mercedes S Bello, Zhaohua Lu, April Sykes, Merrill S Wise, Valerie M Crabtree, Jennifer Zabrowski, Andrea Simmons, Mary E Clark, Belinda N Mandrell
Daytime sleepiness is recognized in childhood brain tumor survivors. Our objective was to determine prevalence, risk factors for PSG/MLST proven hypersomnia/narcolepsy, and response to stimulants in childhood brain tumor survivors. Standard PSG/MSLT criteria were used to diagnose hypersomnia/narcolepsy. Medical records of brain tumor survivors having undergone a PSG/MSLT were reviewed for the diagnostic code of hypersomnia/narcolepsy. Survivors with hypersomnia/narcolepsy were matched with 2-3 survivors without reported hypersomnia/narcolepsy by age at tumor diagnosis, gender, and time from tumor diagnosis...
November 8, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29114278/profiling-cognitive-deficits-in-intra-axial-and-extra-axial-tumors-using-addenbrooke-s-cognitive-examination-as-a-screening-tool-an-indian-experience
#8
Sandhya Cherkil, Dilip Panikar, Deepak Kuttikkattu Soman
Background: Tumors of the brain, whether intra- or extra-axial, results in cognitive deficits. The aim of the present study was to profile cognitive deficits using Addenbrooke's Cognitive Examination-Malayalam (ACE-M) as a screen and to determine the sensitivity and specificity of the same. Methods: Seventy-four drug naïve patients diagnosed to have brain tumors were assessed for cognitive functioning using ACE-M before surgery. Results: Patients with high-grade intra-axial tumors showed a significant association on the cognitive domains of registration (0...
October 2017: Asian Journal of Neurosurgery
https://www.readbyqxmd.com/read/29107216/pharmacological-effects-and-potential-therapeutic-targets-of-dt-13
#9
REVIEW
Ghulam Jilany Khan, Mohsin Rizwan, Muhammad Abbas, Muhammad Naveed, Yu Boyang, Muhammad Ahsan Naeem, Sara Khan, Shengtao Yuan, Mirza Muhammad Faran Ashraf Baig, Li Sun
DT-13 is an isolated compound from Dwarf lillytruf tuber and currently among active research drugs by National Natural Science foundation of China for its several potential effects. The drug has been reported for its multiple pharmacological actions however no thorough review studies are available on it. Our present study is highlighting the pros and cons of DT-13 focusing on its potential pharmacological actions, therapeutic utilization and further exploration for novel targets. The drug possesses very low toxicity profile, quick onset and long duration of action with slow elimination that combinely makes it favorable for the clinical studies...
October 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29105885/emp-induced-bbb-disruption-enhances-drug-delivery-to-glioma-and-increases-treatment-efficacy-in-rats
#10
Kangchu Li, Keying Zhang, Shenglong Xu, Xiaowu Wang, Yongchun Zhou, Yan Zhou, Peng Gao, Jiajin Lin, Guirong Ding, Guozhen Guo
Chemotherapy on gliomas is not satisfactorily efficient because the presence of blood-brain barriers (BBB) leads to inadequate exposure of tumor cells to administered drugs. In order to facilitate chemotherapeutics to penetrate BBB and increase the treatment efficacy of gliomas, electromagnetic pulse (EMP) was applied and the 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU) lomustine concentration in tumor tissue, tumor size, tumor apoptosis, and side effects were measured in glioma-bearing rat model. The results showed that EMP exposure could enhance the delivery of CCNU to tumor tissue, facilitate tumor apoptosis, and inhibit tumor growth without obvious side effects...
November 6, 2017: Bioelectromagnetics
https://www.readbyqxmd.com/read/29100430/novel-naprt-specific-antibody-identifies-small-cell-lung-cancer-and-neuronal-cancers-as-promising-clinical-indications-for-a-nampt-inhibitor-niacin-co-administration-strategy
#11
Jonathan Cole, Marie-Christine Guiot, Michel Gravel, Cynthia Bernier, Gordon C Shore, Anne Roulston
Tumor cells are particularly dependent on NAD(+) due to higher rates of metabolism, DNA synthesis and repair. Nicotinamide phosphoribosyltransferase inhibitors (NAMPTis) inhibit NAD(+) biosynthesis and represent promising new anti-cancer agents. However, clinical efficacy has been limited by toxicities demonstrating the need for drug combinations to broaden the therapeutic index. One potential combination involves niacin/NAMPTi co-administration. Niacin can rescue NAD(+) biosynthesis through a parallel pathway that depends on nicotinic acid phosphoribosyltransferase (NAPRT) expression...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100012/targeting-glioma-stem-cell-derived-pericytes-disrupts-the-blood-tumor-barrier-and-improves-chemotherapeutic-efficacy
#12
Wenchao Zhou, Cong Chen, Yu Shi, Qiulian Wu, Ryan C Gimple, Xiaoguang Fang, Zhi Huang, Kui Zhai, Susan Q Ke, Yi-Fang Ping, Hua Feng, Jeremy N Rich, Jennifer S Yu, Shideng Bao, Xiu-Wu Bian
The blood-tumor barrier (BTB) is a major obstacle for drug delivery to malignant brain tumors such as glioblastoma (GBM). Disrupting the BTB is therefore highly desirable but complicated by the need to maintain the normal blood-brain barrier (BBB). Here we show that targeting glioma stem cell (GSC)-derived pericytes specifically disrupts the BTB and enhances drug effusion into brain tumors. We found that pericyte coverage of tumor vasculature is inversely correlated with GBM patient survival after chemotherapy...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29099956/recycling-drug-screen-repurposes-hydroxyurea-as-a-sensitizer-of-glioblastomas-to-temozolomide-targeting-de-novo-dna-synthesis-irrespective-of-molecular-subtype
#13
Jian Teng, Seyedali Hejazi, Lotte Hiddingh, Litia Carvalho, Mark de Gooijer, Hiroaki Wakimoto, Marco Barazas, Marie Tannous, Andrew S Chi, David P Noske, Pieter Wesseling, Thomas Wurdinger, Tracy T Batchelor, Bakhos A Tannous
Background: Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor. Standard-of-care treatment involves maximal surgical resection of the tumor followed by radiation and chemotherapy (temozolomide; TMZ). The five-year survival rate of patients with GBM is <10%, a colossal failure that has been partially attributed to intrinsic and/or acquired resistance to TMZ through MGMT (O6-methylguanine DNA methyltransferase) promoter methylation status in the tumor...
November 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29097918/gd-3-asparagine-anionic-linear-globular-dendrimer-second-generation-g2-complexes-novel-nanobiohybrid-theranostics
#14
Nasim Hashempour Alamdari, Mahmood Alaei-Beirami, Seyed Ataollah Sadat Shandiz, Hadi Hejazinia, Rahimeh Rasouli, Mostafa Saffari, Seyed Esmaeil Sadat Ebrahimi, Artin Assadi, Mehdi Shafiee Ardestani
Designing a unique theranostic biocompatible, biodegradable, and cost-effective agent which is easy to be synthesized as a biohybrid material was the aim of this study. In this matter, asparagine attached to anionic linear globular dendrimer G2 (as a biocompatible, biodegradable, and cost-effective agent which is negatively charged nanosized and water soluble polymer that outweighs other traditionally used dendrimers) and finally contrast agent (Gd(3+)) was loaded (which made complexes) in synthesized asparagine-dendrimer...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29088958/a-systematic-review-of-perioperative-seizure-prophylaxis-during-brain-tumor-resection-the-case-for-a-multicenter-randomized-clinical-trial
#15
Vyshak Chandra, Andrew K Rock, Charles Opalak, Joel M Stary, Adam P Sima, Matthew Carr, Rafael A Vega, William C Broaddus
OBJECTIVE The majority of neurosurgeons administer antiepileptic drugs (AEDs) prophylactically for supratentorial tumor resection without clear evidence to support this practice. The putative benefit of perioperative seizure prophylaxis must be weighed against the risks of adverse effects and drug interactions in patients without a history of seizures. Consequently, the authors conducted a systematic review of prospective randomized controlled trials (RCTs) that have evaluated the efficacy of perioperative seizure prophylaxis among patients without a history of seizures...
November 2017: Neurosurgical Focus
https://www.readbyqxmd.com/read/29083341/a-case-of-refractary-epilepsy-and-related-pain-due-to-dysmenorrhea-solved-with-loading-dose-of-lacosamide-clinical-and-neurophysiological-correlates
#16
Nicolino Marchitto, Umberto Ceratti, Serenella Dalmaso, Gianfranco Raimondi
 In most cases, the etiology of epilepsy is unknown, although some individuals may develop epilepsy as a result of certain brain injuries, following a stroke, a brain tumor or because of drugs and alcohol. Even some rare genetic mutations may be related to the onset of the condition. Seizures are the result of excessive and abnormal activity of neurons in the cerebral cortex. In this case report we show a clinical case of refractory epilepsy due to pain related to uncontrolled dysmenorrhea. The patient, 43 yrs old, had a history of epilepsy of 20 years and ovarian cancer...
October 23, 2017: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/29080702/glioblastoma-and-chemoresistance-to-alkylating-agents-involvement-of-apoptosis-autophagy-and-unfolded-protein-response
#17
REVIEW
Sabine Hombach-Klonisch, Maryam Mehrpour, Shahla Shojaei, Craig Harlos, Marshall Pitz, Ahmed Hamai, Krzysztof Siemianowicz, Wirginia Likus, Emilia Wiechec, Brian D Toyota, Reyhane Hoshyar, Amir Seyfoori, Zahra Sepehri, Sudharsana R Ande, Forough Khadem, Mohsen Akbari, Adrienne M Gorman, Afshin Samali, Thomas Klonisch, Saeid Ghavami
Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB...
November 8, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29076412/efficacy-duration-and-timing-of-withdrawal-of-prophylactic-treatment-with-antiepileptic-drugs-in-neurosurgical-conditions
#18
Daniel R Calnan, Erin D'Agostino, Matthew R Reynolds, Kimon Bekelis
Seizure control is a critical component of care in many neurosurgical conditions. The development of seizures in patients without a previously identified seizure disorder occurs in a significant proportion of traumatic brain injury, subarachnoid hemorrhage, and brain tumor patients. In this literature review and synthesis, we will discuss the incidence of seizures in selected conditions, indications and evidence for the initiation of antiepileptic drugs (AEDs), suggested duration of usage for AEDs, and current AED guidelines by the American Academy of Neurology (AAN), Congress of Neurological Surgeons (CNS), American Academy of Neurological Surgeons (AANS) and international committees...
October 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29074604/prospective-feasibility-trial-for-genomics-informed-treatment-in-recurrent-and-progressive-glioblastoma
#19
Sara A Byron, Nhan L Tran, Rebecca F Halperin, Joanna J Phillips, John G Kuhn, John F de Groot, Howard Colman, Keith L Ligon, Patrick Y Wen, Timothy F Cloughesy, Ingo K Mellinghoff, Nicholas Butowski, Jennie Taylor, Jennifer L Clarke, Susan M Chang, Mitchel S Berger, Annette M Molinaro, Gerald M Maggiora, Sen Peng, Sara Nasser, Winnie S Liang, Jeffrey M Trent, Michael E Berens, John D Carpten, David Wesley Craig, Michael D Prados
PURPOSE: Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generation sequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma. METHODS: We conducted a prospective genomics-informed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome-sequencing and tumor RNA-sequencing was performed to identify molecular targets for potential matched therapy...
October 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29074439/gemcitabine-and-glioblastoma-challenges-and-current-perspectives
#20
REVIEW
Chiara Bastiancich, Guillaume Bastiat, Frederic Lagarce
Gemcitabine is a nucleoside analog currently used for the treatment of various solid tumors as a single agent or in combination with other chemotherapeutic drugs. Its use against highly aggressive brain tumors (glioblastoma) has been evaluated in preclinical and clinical trials leading to controversial results. Gemcitabine can inhibit DNA chain elongation, is a potent radiosensitizer and it can enhance antitumor immune activity, but it also presents some drawbacks (e.g., short half-life, side effects, chemoresistance)...
October 23, 2017: Drug Discovery Today
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