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https://www.readbyqxmd.com/read/28429876/iodine-131-meta-iodobenzylguanidine-therapy-for-patients-with-newly-diagnosed-high-risk-neuroblastoma
#1
REVIEW
Kathelijne Cjm Kraal, Elvira C van Dalen, Godelieve Am Tytgat, Berthe Lf Van Eck-Smit
BACKGROUND: Patients with newly diagnosed high-risk (HR) neuroblastoma (NBL) still have a poor outcome, despite multi-modality intensive therapy. This poor outcome necessitates the search for new therapies, such as treatment with (131)I-meta-iodobenzylguanidine ((131)I-MIBG). OBJECTIVES: To assess the efficacy and adverse effects of (131)I-MIBG therapy in patients with newly diagnosed HR NBL. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library 2016, Issue 3), MEDLINE (PubMed) (1945 to 25 April 2016) and Embase (Ovid) (1980 to 25 April 2016)...
April 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28429653/clinical-development-of-fenretinide-as-an-antineoplastic-drug-pharmacology-perspectives
#2
Jason P Cooper, C Patrick Reynolds, Hwangeui Cho, Min H Kang
Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved <10 µmol/L concentrations in patients. To improve bioavailability of 4-HPR, new oral powder (LYM-X-SORB®, LXS) and intravenous lipid emulsion (ILE) formulations are being tested in early-phase clinical trials...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28429453/tolcapone-induces-oxidative-stress-leading-to-apoptosis-and-inhibition-of-tumor-growth-in-neuroblastoma
#3
Tyler Maser, Maria Rich, David Hayes, Ping Zhao, Abhinav B Nagulapally, Jeffrey Bond, Giselle Saulnier Sholler
Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and other catecholamines by O-methylation. Tolcapone, a drug commonly used in the treatment of Parkinson's disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells. In this study, we demonstrate that Tolcapone kills neuroblastoma (NB) cells in preclinical models by inhibition of COMT. Treating four established NB cells lines (SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90) and two primary NB cell lines with Tolcapone for 48 h decreased cell viability in a dose-dependent manner, with IncuCyte imaging and Western blotting indicating that cell death was due to caspase-3-mediated apoptosis...
April 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28426994/silica-nanoparticles-induced-intrinsic-apoptosis-in-neuroblastoma-sh-sy5y-cells-via-cytc-apaf-1-pathway
#4
Yanyan Yang, Yongbo Yu, Jiahui Wang, Yanbo Li, Yang Li, Jia Wei, Tong Zheng, Minghua Jin, Zhiwei Sun
The present study was to investigate effects of Silica nanoparticles (SiNPs) on nervous system and explore potential mechanisms in human neuroblastoma cells (SH-SY5Y). Cytotoxicity was detected by cell viability and Lactate dehydrogenase (LDH) release. Flow cytometry analysis was applied to assess mitochondrial membrane potential (MMP) loss, intracellular Ca(2+) and apoptosis. To clarify the mechanism of SiNPs-induced apoptosis, intrinsic apoptosis-related proteins were detected. Our results showed that SiNPs caused cytotoxicity, cell membrane damage and Ca(2+) increase in a dose-dependent manner in SH-SY5Y cells...
January 30, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28426528/comparative-analysis-of-multicolor-flow-cytometry-and-immunohistochemistry-for-the-detection-of-disseminated-tumor-cells
#5
Eszter Szánthó, Bettina Kárai, Gergely Ivády, Judit Bedekovics, István Szegedi, Miklós Petrás, György Ujj, Anikó Ujfalusi, Csongor Kiss, János Kappelmayer, Zsuzsanna Hevessy
Disseminating cells of a primary solid tumor may represent the origin of metastases and relapses. We aimed at comparing the diagnostic efficacy of multicolor flow cytometry (MFC) and morphology/immunohistochemistry (IHC) in the detection of disseminated tumor cells in the bone marrow (BM) and body fluids of patients with solid tumors, and in pediatric neuroblastoma cases. We investigated 72 samples retrospecively from 50 patients by MFC. Morphology/IHC data were available in 48 cases. In the first cohort, 36 samples derived from 34 patients with various forms of suspected and proven solid tumors and in the second cohort, 36 samples of 16 children with suspected and proven neuroblastoma were analyzed at diagnosis or during follow-up in a 4-color setting by MFC, and the results were compared with those obtained by IHC...
April 19, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28425916/combined-alk-and-mdm2-inhibition-increases-antitumor-activity-and-overcomes-resistance-in-human-alk-mutant-neuroblastoma-cell-lines-and-xenograft-models
#6
Hui Qin Wang, Ensar Halilovic, Xiaoyan Li, Jinsheng Liang, Yichen Cao, Daniel P Rakiec, David A Ruddy, Sebastien Jeay, Jens U Wuerthner, Noelito Timple, Shailaja Kasibhatla, Nanxin Li, Juliet A Williams, William R Sellers, Alan Huang, Fang Li
The efficacy of ALK inhibitors in patients with ALK-mutant neuroblastoma is limited, highlighting the need to improve their effectiveness in these patients. To this end we sought to develop a combination strategy to enhance the antitumor activity of ALK inhibitor monotherapy in human neuroblastoma cell lines and xenograft models expressing activated ALK. Herein, we report that combined inhibition of ALK and MDM2 induced a complementary set of anti-proliferative and pro-apoptotic proteins. Consequently, this combination treatment synergistically inhibited proliferation of TP53 wild-type neuroblastoma cells harboring ALK amplification or mutations in vitro, and resulted in complete and durable responses in neuroblastoma xenografts derived from these cells...
April 20, 2017: ELife
https://www.readbyqxmd.com/read/28423674/a-single-center-clinical-analysis-of-children-with-high-risk-neuroblastoma
#7
Xiangdong Tian, Yanna Cao, Jingfu Wang, Jie Yan, Yao Tian, Zhongyuan Li, Huijuan Wang, Xiaofeng Duan, Yan Jin, Qiang Zhao
The current multidisciplinary treatment for patients with high-risk neuroblastoma (NB) is the common census. However, protocols and opinions are different in different regions and institutions. We aimed to assess the protocol formulated by Chinese Children's Cancer Group study in 2009, and the impact of surgery extent was highlightly evaluated. METHODS: This study enrolled patients with high-risk neuroblastoma between 2009 and 2014 in Department of Pediatric Oncology of Tianjin Medical University Cancer Institute and Hospital...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423619/cdca2-promotes-lung-adenocarcinoma-cell-proliferation-and-predicts-poor-survival-in-lung-adenocarcinoma-patients
#8
Run Shi, Chunrong Zhang, Yaqin Wu, Xin Wang, Qi Sun, Jing Sun, Wenjie Xia, Gaochao Dong, Anpeng Wang, Feng Jiang, Lin Xu
Cell division cycle associated 2(CDCA2) is overexpressed in neuroblastoma and oral squamous cell carcinoma, and its overexpression positively correlates to tumor progression. However, the biological and clinical significance of CDCA2 in lung adenocarcinoma(LAC) has never been investigated. We determined the expression profile and clinical significance of CDCA2 using The Cancer Genome Atlas(TCGA) and tissue microarray(TMA). Furthermore, we explored the biological function of CDCA2 both in vitro and in vivo. A great upregulation of CDCA2 was observed in LAC tissues compared with adjacent normal tissues...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423360/tiam1-variants-improve-clinical-outcome-in-neuroblastoma
#9
Elena Sanmartín, Yania Yáñez, Victoria Fornés-Ferrer, José L Zugaza, Adela Cañete, Victoria Castel, Jaime Font de Mora
Identification of tumor driver mutations is crucial for improving clinical outcome using a personalized approach to the treatment of cancer. Neuroblastoma is a tumor of the peripheral sympathetic nervous system for which only a few driver alterations have been described including MYCN amplification and ALK mutations. We assessed 106 primary neuroblastoma tumors by next generation sequencing using a customized amplicon-based gene panel. Our results reveal that genetic variants in TIAM1 gene associate with better clinical outcome, suggesting a role for these TIAM1 variants in preventing progression of this disease...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422997/promoter-hypermethylation-as-a-mechanism-for-lamin-a-c-silencing-in-a-subset-of-neuroblastoma-cells
#10
Ines Rauschert, Fabian Aldunate, Jens Preussner, Miguel Arocena-Sutz, Vanina Peraza, Mario Looso, Juan C Benech, Ruben Agrelo
Nuclear lamins support the nuclear envelope and provide anchorage sites for chromatin. They are involved in DNA synthesis, transcription, and replication. It has previously been reported that the lack of Lamin A/C expression in lymphoma and leukaemia is due to CpG island promoter hypermethylation. Here, we provide evidence that Lamin A/C is silenced via this mechanism in a subset of neuroblastoma cells. Moreover, Lamin A/C expression can be restored with a demethylating agent. Importantly, Lamin A/C reintroduction reduced cell growth kinetics and impaired migration, invasion, and anchorage-independent cell growth...
2017: PloS One
https://www.readbyqxmd.com/read/28422555/improved-local-control-by-extensive-surgery-in-high-risk-neuroblastoma-may-be-dependent-on-adjuvant-radiotherapy
#11
Jakob Stenman, Nikolas Herold, Pär-Johan Svensson, Per Kogner
No abstract text is available yet for this article.
April 19, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28421738/targeting-the-nrf2-amyloid-beta-liaison-in-alzheimer-s-disease-a-rational-approach
#12
Elena Simoni, Melania M Serafini, Roberta Caporaso, Chiara Marchetti, Marco Racchi, Anna Minarini, Manuela Bartolini, Cristina Lanni, Michela Rosini
Amyloid is a prominent feature of Alzheimer's disease (AD). Yet, a linear linkage between amyloid-β peptide (Aβ) and the disease onset and progression has recently been questioned. In this context, the crucial partnership between Aβ and Nrf2 pathways is acquiring paramount importance, offering prospects for deciphering the Aβ-centered disease network. Here, we report on a new class of anti-aggregating agents rationally designed to simultaneously activate transcription-based antioxidant responses, whose lead 1 showed interesting properties in a preliminary investigation...
April 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28420370/neuroprotective-effect-of-demethoxycurcumin-a-natural-derivative-of-curcumin-on-rotenone-induced-neurotoxicity-in-sh-sy-5y-neuroblastoma-cells
#13
Muthu Ramkumar, Srinivasagam Rajasankar, Veerappan Venkatesh Gobi, Chinnasamy Dhanalakshmi, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Ameer Kalandar, Ranganathan Chidambaram
BACKGROUND: Mitochondrial dysfunction and oxidative stress are the main toxic events leading to dopaminergic neuronal death in Parkinson's disease (PD) and identified as vital objective for therapeutic intercession. This study investigated the neuro-protective effects of the demethoxycurcumin (DMC), a derivative of curcumin against rotenone induced neurotoxicity. METHODS: SH-SY5Y neuroblastoma cells are divided into four experimental groups: untreated cells, cells incubated with rotenone (100 nM), cells treated with DMC (50 nM) + rotenone (100 nM) and DMC alone treated...
April 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28420320/pediatric-non-vestibular-schwannoma
#14
Cory Broehm, Alyaa Al-Ibraheemi, Karen J Fritchie
While the clinicopathologic features of pediatric vestibular schwannomas, often in the context of neurofibromatosis type 2 (NF2), have been well studied, there is less data regarding the characteristics of pediatric non-vestibular schwannomas (NVS). Additionally, the rate of loss of SMARCB1/INI1 expression in this population has not been systematically evaluated. Our institutional archives were searched for cases of NVS arising in patients 18 years or younger. Clinicopathologic features including SMARCB1/INI1 status were assessed for each case...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28420318/advancing-clinicopathologic-diagnosis-of-high-risk-neuroblastoma-using-computerized-image-analysis-and-proteomic-profiling
#15
M Khalid Khan Niazi, Jonathan H Chung, Katherine J Heaton-Johnson, Daniel Martinez, Raquel Castellanos, Meredith S Irwin, Stephen R Master, Bruce R Pawel, Metin N Gurcan, Daniel A Weiser
A subset of patients with neuroblastoma are at extremely high risk for treatment failure, though they are not identifiable at diagnosis and therefore have the highest mortality with conventional treatment approaches. Despite tremendous understanding of clinical and biological features that correlate with prognosis, neuroblastoma at ultra-high risk for treatment failure remains a diagnostic challenge. As a first step towards improving prognostic risk stratification within the high-risk group of patients, we determined the feasibility of using computerized image analysis and proteomic profiling on single slides from diagnostic tissue specimens...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28419087/novel-targeted-therapy-for-neuroblastoma-silencing-the-mxd3-gene-using-sirna
#16
Connie Duong, Sakiko Yoshida, Cathy Chen, Gustavo Barisone, Elva Diaz, Yueju Li, Laurel Beckett, Jong Chung, Reuben Antony, Jan Nolta, Nitin Nitin, Noriko Satake
BACKGROUND: Neuroblastoma is the second most common extracranial cancer in children. Current therapies for neuroblastoma, which use a combination of chemotherapy drugs, have limitations for high-risk subtypes and can cause significant long-term adverse effects in young patients. Therefore, a new therapy is needed. In this study, we investigated the transcription factor MXD3 as a potential therapeutic target in neuroblastoma. METHODS: MXD3 expression was analyzed in five neuroblastoma cell lines by immunocytochemistry and quantitative real time reverse transcription PCR and in 18 primary patient tumor samples by immunohistochemistry...
April 18, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28417423/evaluation-of-the-expression-of-amyloid-precursor-protein-and-the-ratio-of-secreted-amyloid-beta-42-to-amyloid-beta-40-in-sh-sy5y-cells-stably-transfected-with-wild-type-single-mutant-and-double-mutant-forms-of-the-app-gene-for-the-study-of-alzheimer-s-disease
#17
Aslina Pahrudin Arrozi, Siti Nur Syazwani Shukri, Wan Zurinah Wan Ngah, Yasmin Anum Mohd Yusof, Mohd Hanafi Ahmad Damanhuri, Suzana Makpol
Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models in neurodegenerative research, and their use has advanced the understanding of the pathology of neurodegeneration over the past few decades. In Alzheimer's disease (AD), several pathogenic mutations have been described, all of which cause elevated levels of pathological hallmarks such as amyloid-beta (Aβ). Although the genetics of Alzheimer's disease is well known, familial AD only accounts for a small number of cases in the population, with the rest being sporadic AD, which contains no known mutations...
April 17, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28415761/yap-promotes-tumorigenesis-and-cisplatin-resistance-in-neuroblastoma
#18
Chao Yang, Juan Tan, Jun Zhu, Shan Wang, Guanghui Wei
The transcriptional co-activator Yes-associated protein (YAP) is essential for Hippo pathway-driven tumorigenesis in various cancers. However, the expression and function of YAP in neuroblastoma remains elusive. Here, we show that YAP was highly expressed in Neuroblastoma (NB) and expression levels correlated with advanced tumor staging. Knockdown of YAP significantly impaired neuroblastoma proliferation, tumorigenesis, and invasion in vitro. Injection of the YAP inhibitor, Peptide 17, dramatically prevented neuroblastoma subcutaneous tumor growth by efficiently downregulating YAP expression in tumors...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415610/the-tubulin-inhibitor-mg-2477-induces-autophagy-regulated-cell-death-ros-accumulation-and-activation-of-foxo3-in-neuroblastoma
#19
Judith Hagenbuchner, Lorena Lungkofler, Ursula Kiechl-Kohlendorfer, Giampietro Viola, Maria Grazia Ferlin, Michael J Ausserlechner, Petra Obexer
Neuroblastoma is the most frequent extra-cranial solid tumor in children with still high mortality in stage M. Here we studied the tubulin-inhibitor MG-2477 as a possible therapeutic agent for neuroblastoma therapy and uncovered that MG-2477 induces death in neuroblastoma cells independent of PKB-activation status and stage. MG-2477 triggers within 30 minutes extensive autophagosome-formation that finally leads to cell death associated with mitotic catastrophe. Autophagy is critical for MG-2477-induced death and is regulated by the BH3-only protein PMAIP1/NOXA which sequesters the anti-apoptotic BCL2-protein BCLXL and thereby displaces and activates the autophagy-regulator BECN1/beclin1...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413806/ryanodine-and-ip3-receptor-mediated-calcium-signaling-play-a-pivotal-role-in-neurological-infrared-laser-modulation
#20
Gleb P Tolstykh, Cory A Olsovsky, Bennett L Ibey, Hope T Beier
Pulsed infrared (IR) laser energy has been shown to modulate neurological activity through both stimulation and inhibition of action potentials. While the mechanism(s) behind this phenomenon is (are) not completely understood, certain hypotheses suggest that the rise in temperature from IR exposure could activate temperature- or pressure-sensitive ion channels or create pores in the cellular outer membrane, allowing an influx of typically plasma-membrane-impermeant ions. Studies using fluorescent intensity-based calcium ion ([Formula: see text]) sensitive dyes show changes in [Formula: see text] levels after various IR stimulation parameters, which suggests that [Formula: see text] may originate from the external solution...
April 2017: Neurophotonics
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