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Growth factors in brain

Ramon Andrade De Mello, Carles Escriu, Pedro Castelo-Branco, Paloma Lucena Cabral, Giannis Mountzios, Gilberto de Lima Lopes, Pedro Madureira
Introduction: Tyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced non-small-cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection. Materials And Methods: We performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC...
February 20, 2018: Oncotarget
Ke-Wei Tian, Yuan-Yuan Zhang, Hong Jiang, Shu Han
The placenta has emerged as an attractive source of mesenchymal stem cells (MSCs) because of the absence of ethical issues, non-invasive access, and abundant yield. However, inflammatory cell invasion into grafts negatively impacts the survival and efficacy of transplanted cells. Previous studies have shown that synthetic C16 peptide can competitively block the transmigration of leukocytes into the central nerve system, while angiopoietin-1 (Ang-1) can inhibit inflammation-induced blood vessel leakage and inflammatory cell infiltration in rats with experimental allergic encephalomyelitis (EAE)...
March 15, 2018: Scientific Reports
Fernanda Ramos-Gomes, Julia Bode, Alyona Sukhanova, Svetlana V Bozrova, Mara Saccomano, Miso Mitkovski, Julia Eva Krueger, Anja K Wege, Walter Stuehmer, Pavel S Samokhvalov, Daniel Baty, Patrick Chames, Igor Nabiev, Frauke Alves
Early detection of malignant tumours and, especially, micrometastases and disseminated tumour cells is still a challenge. In order to implement highly sensitive diagnostic tools we demonstrate the use of nanoprobes engineered from nanobodies (single-domain antibodies, sdAbs) and fluorescent quantum dots (QDs) for single- and two-photon detection and imaging of human micrometastases and disseminated tumour cells in ex vivo biological samples of breast and pancreatic metastatic tumour mouse models expressing human epidermal growth factor receptor 2 (HER2) or carcinoembryonic antigen (CEA)...
March 15, 2018: Scientific Reports
Yukari Yoshida, Yukihiko Sejimo, Masashi Kurachi, Yasuki Ishizaki, Takashi Nakano, Akihisa Takahashi
X-ray irradiation (X-irradiation) induces disruption of the blood-brain barrier (BBB). However, the mechanisms underlying the permeability changes are unclear. Therefore, in the present study, we examined the cellular and molecular changes produced by X-irradiation of the brain. Male ICR mice were irradiated locally on their head, posterior to the bregma, except for the eyes, with a single dose of 60 Gy. BBB permeability was assessed using Evans blue dye. We also examined vascular endothelial growth factor (VEGF) expression, microglial morphology, and the expression of the tight junction protein claudin-5 from 0...
March 12, 2018: Neurochemistry International
Clara Barneo-Caragol, Eduardo Martínez-Morillo, Susana Rodríguez-González, Paloma Lequerica-Fernández, Ignacio Vega-Naredo, Francisco V Álvarez Menéndez
BACKGROUND: Preeclampsia (PE) is considered a specific vascular disease in which endothelial dysfunction may be the crucial factor of its pathogenesis. It has been suggested that strontium (Sr) may play a role in the pathophysiology of PE. Our group established in a previous study the serum levels of Sr in healthy pregnancies, and the main aim of the present study was to evaluate Sr concentrations and oxidative status in preeclamptic women. METHODS: The study population included women with early-onset PE (E-PE, n = 39), late-onset PE (L-PE, n = 67) and serial samples from a subset of preeclamptic women (PE-ss, n = 20)...
May 2018: Journal of Trace Elements in Medicine and Biology
Xiaoyan Cui, Zhenqiang Fu, Menghan Wang, Xiaofei Nan, Boai Zhang
OBJECTIVES: Along with their lipid-lowering effect, statins have been reported to have neuroprotective function in both in vivo and in vitro models of neurodegenerative diseases. We conducted this study in order to uncover the he neuroprotective effect of the lipophilic statin pitavastatin (PTV) and investigate the underlying molecular mechanisms using primary cultured cerebral neurons exposed to oxygen-glucose deprivation (OGD). METHODS: The primary cultured cerebral neurons were randomly assigned into four groups: the control group, the pitavastatin treatment group, the OGD group and the OGD + pitavastatin treatment group...
March 16, 2018: Neurological Research
Carmen J Zamora-Sánchez, Aylin Del Moral-Morales, Ana M Hernández-Vega, Valeria Hansberg-Pastor, Ivan Salido-Guadarrama, Mauricio Rodríguez-Dorantes, Ignacio Camacho-Arroyo
Glioblastomas (GBM) are the most frequent and aggressive brain tumors. In these malignancies, progesterone (P4) promotes proliferation, migration, and invasion. The P4 metabolite allopregnanolone (3α-THP) similarly promotes cell proliferation in the U87 human GBM cell line. Here, we evaluated global changes in gene expression of U87 cells treated with 3α-THP, P4, and the 5α-reductase inhibitor, finasteride (F). 3α-THP modified the expression of 137 genes, while F changed 90. Besides, both steroids regulated the expression of 69 genes...
March 15, 2018: International Journal of Molecular Sciences
Ana E López-Pérez, Kulmira Nurgali, Raquel Abalo
Beyond their well-known role in embryonic development of the central and peripheral nervous system, neurotrophins, particularly nerve growth factor and brain-derived neurotrophic factor, exert an essential role in pain production and sensitization. This has mainly been studied within the framework of somatic pain, and even antibodies (tanezumab and fasinumab) have recently been developed for their use in chronic somatic painful conditions, such as osteoarthritis or low back pain. However, data suggest that neurotrophins also exert an important role in the occurrence of visceral pain and visceral sensitization...
April 2018: Behavioural Pharmacology
Yanchun Ma, Kun Chen, Zhenhua Yang, Ming Guan
Lung cancer is the most common type of malignancy to metastasize to the brain, with the median survival time of patients being 6-11 months. In the present study, the aim was to compare the actionable gene mutation profiles of primary lung adenocarcinoma (LC) samples and LC brain metastasis (LCBM) samples through targeted sequencing. Next generation sequencing (NGS) of 13 formalin-fixed, paraffin-embedded LC samples and 15 LCBM samples was performed using a customized OncoAim™ cancer panel and OncoAim™ RNA fusion panel on the MiSeq platform...
April 2018: Oncology Letters
Nathália Kersting, Bárbara Kunzler Souza, Igor Araujo Vieira, Rafael Pereira Dos Santos, Danielly Brufatto Olguins, Lauro José Gregianin, André Tesainer Brunetto, Algemir Lunardi Brunetto, Rafael Roesler, Caroline Brunetto de Farias, Gilberto Schwartsmann
OBJECTIVE: Ewing sarcoma (ES) is a type of childhood cancer probably arising from stem mesenchymal or neural crest cells. The epidermal growth factor receptor (EGFR) acts as a driver oncogene in many types of solid tumors. However, its involvement in ES remains poorly understood. METHODS: Human SK-ES-1 and RD-ES ES cells were treated with EGF, the EGFR inhibitor tyrphostin (AG1478), or phosphoinositide 3-kinase (PI3K) or extracellular-regulated kinase (ERK)/mitogen-activated kinase (MAPK) inhibitors...
March 14, 2018: Oncology
Yicai Xiao, Gaofeng Li, Yujie Chen, Yuchun Zuo, Kauthar Rashid, Tibiao He, Hua Feng, John H Zhang, Fei Liu
Iatrogenic brain injury inevitably occurs in neurosurgical operations, leading to brain edema, ischemia, intracranial hematoma, and other postoperative complications, eventually worsening neurological outcomes of patients. If apoptotic cells are not rapidly eliminated by phagocytic engulfment, they may communicate with surrounding cells to undergo secondary necrosis and releasing toxic signals. Recent studies have shown that milk fat globule-epidermal growth factor-8 (MFGE8), which promotes phagocytosis and inhibits inflammation, is an endogenous protective factor in response to brain infarction, Alzheimer's disease, subarachnoid hemorrhage, and prion disease...
2018: Frontiers in Neurology
Alan H Nagahara, Bayard R Wilson, Iryna Ivasyk, Imre Kovacs, Saytam Rawalji, John R Bringas, Phillip J Pivirotto, Waldy San Sebastian, Lluis Samaranch, Krystof S Bankiewicz, Mark H Tuszynski
Brain-derived neurotrophic factor (BDNF) gene delivery to the entorhinal cortex is a candidate for treatment of Alzheimer's disease (AD) to reduce neurodegeneration that is associated with memory loss. Accurate targeting of the entorhinal cortex in AD is complex due to the deep and atrophic state of this brain region. Using MRI-guided methods with convection-enhanced delivery, we were able to accurately and consistently target AAV2-BDNF delivery to the entorhinal cortex of non-human primates; 86 ± 3% of transduced cells in the targeted regions co-localized with the neuronal marker NeuN...
March 13, 2018: Gene Therapy
George Inana, Christopher Murat, Weijun An, Xiang Yao, Ian R Harris, Jing Cao
BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly characterized by retinal pigment epithelium (RPE) degeneration with accumulation of abnormal intracellular deposits (lipofuscin) and photoreceptor death. RPE is vital for the retina and integrity of photoreceptors through its phagocytic function which is closely linked to formation of lipofuscin through daily phagocytosis of discarded photoreceptor outer segments (POS). Although phagocytosis has been implicated in AMD, it has not been directly shown to be altered in AMD...
March 13, 2018: Journal of Translational Medicine
Liu-Lin Xiong, Yu Zou, Yu Shi, Piao Zhang, Rong-Ping Zhang, Xie-Jie Dai, Bin Liu, Ting-Hua Wang
The aim of the present study was to determine the effect of implanted neural stem cells (NSCs) on the functional recovery of tree shrews (TSs) subjected to hemi‑sectioned spinal cord injury (hSCI), and to investigate the possible mechanism involved. NSCs (passage 2), derived from the hippocampus of TSs (embryonic day 20), were labeled with Hoechst 33342 and transplanted intraspinally into the hSC of TSs at thoracic level 10 in the acute (immediately after injury) and chronic (day 9 post‑injury) stages...
March 9, 2018: International Journal of Molecular Medicine
Lili Zhang, Zhaomin Fan, Yuechen Han, Lei Xu, Wenwen Liu, Xiaohui Bai, Meijuan Zhou, Jianfeng Li, Haibo Wang
Valproic acid (VPA), a medication primarily used to treat epilepsy and bipolar disorder, has been applied to the repair of central and peripheral nervous system injury. The present study investigated the effect of VPA on functional recovery, survival of facial motor neurons (FMNs), and expression of proteins in rats after facial nerve trunk transection by functional measurement, Nissl staining, TUNEL, immunofluorescence, and Western blot. Following facial nerve injury, all rats in group VPA showed a better functional recovery, which was significant at the given time, compared with group NS...
March 12, 2018: Journal of Molecular Neuroscience: MN
Na Wang, Renkai Wang, Ruoqing Wang, Songlin Chen
The Chinese tongue sole (Cynoglossus semilaevis) is a typical female heterogamete species that exhibits female-biased sexual size dimorphism, which has severely hindered the sustainable development of the species in aquaculture. In the present study, four important somatotropic and reproductive tissues including brain, pituitary, liver, and gonad from 15 females and 15 males were used for transcriptome analysis via RNA-seq. A mean of 37,533,991 high-quality clean reads was obtained from each library and 806, 1482, 818, and 14,695 differentially expressed genes in female and male were identified from the brain, pituitary, liver, and gonad, respectively (fold change ≥ 2 and q < 0...
March 12, 2018: Functional & Integrative Genomics
Anthony M Rossi, Vilaiwan M Fernandes
Various regions of the developing brain coordinate their construction so that the correct types and numbers of cells are generated to build a functional network. We previously discovered that wrapping glia in the Drosophila visual system are essential for coordinating retinal and lamina development. We showed that wrapping glia, which ensheath photoreceptor axons, respond to an epidermal growth factor cue from photoreceptors by secreting insulins. Wrapping glial insulins activate the mitogen-activated protein kinase (MAPK) pathway downstream of insulin receptor in lamina precursors to induce neuronal differentiation...
2018: Journal of Experimental Neuroscience
Marie Duhamel, Mélanie Rose, Franck Rodet, Adriana-Nathalia Murgoci, Lea Zografidou, Anne Régnier-Vigouroux, Fabien Vanden Abeele, Firas Kobeissy, Serge Nataf, Laurent Pays, Maxence Wisztorski, Dasa Cizkova, Isabelle Fournier, Michel Salzet
High grade gliomas are the most common brain tumors in adult. These tumors are characterized by a high infiltration in microglial cells and macrophages. The immunosuppressive tumor environment is known to orient immune cells towards a pro-tumoral and anti-inflammatory phenotype. Therefore, the current challenge for cancer therapy is to find a way to reorient macrophages toward an anti-tumoral phenotype. Previously, we demonstrated that macrophages secreted anti-tumoral factors when they were invalidated for the proprotein converstase 1/3 (PC1/3) and treated with LPS...
March 12, 2018: Molecular & Cellular Proteomics: MCP
Camila Dalmolin, Daniela Volcan Almeida, Marcio Azevedo Figueiredo, Luis Fernando Marins
The brain is a highly demanding organ in terms of energy requirements, and precise regulatory mechanisms must operate to ensure adequate energy delivery to maintain normal neuronal activity. Of the energy-promoting substrates present in the circulation, glucose is preferred by the brain, and as with all other substrates, its utilization depends on the presence of humoral factors such as hormones including growth hormone (GH). Glucose enters the cells though specific transport proteins. Among all transporter families and subtypes described to date, the most studied ones are the glucose transporters (GLUTs)...
March 9, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Takehiko Kaneko
SanBio Co., Ltd. is developing regenerative medicine, SB623. SB623 secretes neurotrophic and growth factors, and can possibly show benefit in repair of the damaged brain after stroke. An open-label, single-arm phase I/IIa clinical study was conducted with 18 chronic ischemic stroke patients in the United States to evaluate the safety and clinical outcomes of surgical transplantation of SB623. Clinical evaluation for a one year follow-up period showed significant improvements with all mean scores on the European Stroke Scale, the National Institute of Health Stroke Scale, and on the basis of fugl-Meyer Assessment...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
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