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https://www.readbyqxmd.com/read/28069687/adaptive-resistance-of-melanoma-cells-to-raf-inhibition-via-reversible-induction-of-a-slowly-dividing-de-differentiated-state
#1
Mohammad Fallahi-Sichani, Verena Becker, Benjamin Izar, Gregory J Baker, Jia-Ren Lin, Sarah A Boswell, Parin Shah, Asaf Rotem, Levi A Garraway, Peter K Sorger
Treatment of BRAF-mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live-cell imaging, single-cell analysis, and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest, and the remainder adapt to drug. Drug-adapted cells up-regulate markers of the neural crest (e.g., NGFR), a melanocyte precursor, and grow slowly...
January 9, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28013393/ngf-anti-vegf-combined-exposure-protects-rcs-retinal-cells-and-photoreceptors-that-underwent-a-local-worsening-of-inflammation
#2
Maria Luisa Rocco, Bijorn Omar Balzamino, Graziana Esposito, Carla Petrella, Luigi Aloe, Alessandra Micera
PURPOSE: Our previous study highlighted the potential nerve growth factor (NGF) effect on damaged photoreceptors from a rat model of spontaneous Retinitis Pigmentosa (RP). Herein, we tested the combined NGF/anti-vascular endothelial growth factor (αVEGF) effect on cultured retinal cells isolated from Royal College of Surgeons (RCS) rats receiving an intravitreal VEGF injection (iv-VEGF) to exacerbate retinal inflammation/neovascularization. METHODS: RCS (n = 75) rats were equally grouped as untreated (n = 25), iv-saline (single saline intravitreal injection; n = 25) and iv-VEGF (single VEGF intravitreal injection; n = 25)...
December 24, 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/27987372/six1-maintains-tumor-basal-cells-via-tgf-%C3%AE-pathway-and-associates-with-poor-prognosis-in-esophageal-cancer
#3
Takao Nishimura, Masashi Tamaoki, Rie Komatsuzaki, Naohide Oue, Hirokazu Taniguchi, Masayuki Komatsu, Kazuhiko Aoyagi, Keiko Minashi, Fumiko Chiwaki, Hisashi Shinohara, Yuji Tachimori, Wataru Yasui, Manabu Muto, Teruhiko Yoshida, Yoshiharu Sakai, Hiroki Sasaki
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. Although improvement in both surgical techniques and neoadjuvant chemotherapy has been achieved, the 5-year survival rate of locally advanced tumors was, at best, still 55%. Therefore, elucidation of mechanisms of the malignancy is eagerly awaited. Epithelial-mesenchymal transition (EMT) by transforming growth factor-beta (TGF-β) has been reported to have critical biological roles for cancer cell stemness, whereas little is known about it in ESCC...
December 17, 2016: Cancer Science
https://www.readbyqxmd.com/read/27927008/microrna-296-5p-promotes-invasiveness-through-downregulation-of-nerve-growth-factor-receptor-and-caspase-8
#4
Hong Lee, Chang Hoon Shin, Hye Ree Kim, Kyung Hee Choi, Hyeon Ho Kim
Glioblastomas (GBM) are very difficult to treat and their aggressiveness is one of the main reasons for this as well as for the frequent recurrences. MicroRNAs posttranscriptionally regulate their target genes through interaction between their seed sequence and 3'UTR of the target mRNAs. We previously reported that miR-296-3p is regulated by neurofibromatosis 2 (NF2) and enhances the invasiveness of GBM cells via SOCS2/STAT3. In this study, we investigated whether miR-296-5p, which originates from the same precursor miRNA as miR-296-3p, can increase the invasiveness of GBM cells...
December 8, 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27906583/isolation-of-bovine-skin-derived-precursor-cells-and-their-developmental-potential-after-nuclear-transfer
#5
Jiajia Xiao, Qiaoqiao Li, Pengxiang Qu, Zihan Zhang, Shaohui Pan, Yongsheng Wang, Yong Zhang
Nuclei from less differentiated stem cells yield high cloning efficiency. However, pluripotent stem cells are rather difficult to obtain from bovines. Skin-derived precursor (SKPs) cells exhibit a certain degree of pluripotency, which has been shown to enhance the efficiency of nuclear transfer (NT) in pigs. In this study, bovine SKPs were isolated and characterized. Results showed that bovine SKPs expressed nestin, fibronectin, vimentin, pluripotency-related genes, and characteristic neural crest markers, such as NGFR, PAX3, SOX9, SNAI2, and OCT4...
November 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27834852/tonsil-derived-mesenchymal-stem-cells-differentiate-into-a-schwann-cell-phenotype-and-promote-peripheral-nerve-regeneration
#6
Namhee Jung, Saeyoung Park, Yoonyoung Choi, Joo-Won Park, Young Bin Hong, Hyun Ho Choi Park, Yeonsil Yu, Geon Kwak, Han Su Kim, Kyung-Ha Ryu, Jae Kwang Kim, Inho Jo, Byung-Ok Choi, Sung-Chul Jung
Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs...
November 9, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27805868/ovariectomy-alters-gene-expression-of-the-hippocampal-formation-in-middle-aged-rats
#7
Miklós Sárvári, Imre Kalló, Erik Hrabovszky, Norbert Solymosi, Zsolt Liposits
Ovarian hormones regulate the transcriptome of the hippocampus and modulate its functions. During menopause this complex signaling declines, leading to impaired learning and memory. This study was undertaken to clarify the effects of long-term, surgical ovariectomy (OVX) on the rat hippocampal transcriptome. At age of 13 months, intact control and ovariectomized groups were formed. All animals were sacrificed 5 weeks after gonadectomy, hippocampal formations were dissected and processed for transcriptome analysis...
November 2, 2016: Endocrinology
https://www.readbyqxmd.com/read/27804051/receptor-mediated-toxicity-of-human-amylin-fragment-aggregated-by-short-and-long-term-incubations-with-copper-ions
#8
Giuseppe Caruso, Donatella A Distefano, Paolo Parlascino, Claudia G Fresta, Giuseppe Lazzarino, Susan M Lunte, Vincenzo G Nicoletti
Human amylin (hA1-37) is a polypeptide hormone secreted in conjunction with insulin from the pancreatic β-cells involved in the pathogenesis of type 2 diabetes mellitus (T2DM). The shorter fragment hA17-29 than full-length peptide is capable to form amyloids "in vitro". Here, we monitored the time course of hA17-29 β-amyloid fibril and oligomer formation [without and with copper(II)], cellular toxicity of different amyloid aggregates, and involvement of specific receptors (receptor for advanced glycation end-products, RAGE; low-affinity nerve growth factor receptor, p75-NGFR) in aggregate toxicity...
November 1, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27781424/update-on-the-integrated-histopathological-and-genetic-classification-of-medulloblastoma-a-practical-diagnostic-guideline
#9
Torsten Pietsch, Christine Haberler
The revised WHO classification of tumors of the CNS 2016 has introduced the concept of the integrated diagnosis. The definition of medulloblastoma entities now requires a combination of the traditional histological information with additional molecular/genetic features. For definition of the histopathological component of the medulloblastoma diagnosis, the tumors should be assigned to one of the four entities classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma...
November 2016: Clinical Neuropathology
https://www.readbyqxmd.com/read/27775873/generation-and-characterization-of-mice-bearing-null-alleles-of-nradd-nrh2
#10
Nicolas Unsain, Genevieve Dorval, Jae Hyung Sheen, Philip A Barker
The Neurotrophin receptor associated death domain gene (Nradd/Nrh2/Plaidd) is a type I transmembrane protein with a unique and short N-terminal extracellular domain and a transmembrane and intracellular domain that bears high similarity to the p75 neurotrophin receptor (p75NTR/Ngfr). Initial studies suggested that NRADD regulates neurotrophin signaling but very little is known about its physiological roles. We have generated and characterized NRADD conditional and germ-line null mouse lines. These mice are viable and fertile and dońt show evident abnormalities...
December 2016: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/27727393/remote-ischemic-preconditioning-protects-retinal-photoreceptors-evidence-from-a-rat-model-of-light-induced-photoreceptor-degeneration
#11
Alice Brandli, Daniel M Johnstone, Jonathan Stone
Purpose: To test whether remote ischemic preconditioning (RIP) is protective to photoreceptors, in a light damage model, and to identify mechanisms involved. Methods: A pressure cuff was used to induce ischemia (2 × 5 minutes) in one hind limb of 4- to 6-month-old albino Sprague-Dawley rats raised in dim, cyclic light (12 hours 5 lux, 12 hours dark). Immediately following the ischemia, rats were exposed to bright continuous light (1000 lux) for 24 hours. After 7-day survival in dim, cyclic light conditions, retinal function was assessed using the flash electroretinogram (ERG) and retinal structure was examined for photoreceptor survival and death, as well as for stress...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27683113/esm1-mediates-ngfr-induced-invasion-and-metastasis-in-murine-oral-squamous-cell-carcinoma
#12
Chen Chen, June Ho Shin, Joshua T Eggold, Man Ki Chung, Luhua H Zhang, Jeremy Lee, John B Sunwoo
Oral squamous cell carcinoma (OSCC) is a highly invasive and metastatic malignancy. The nerve growth factor receptor (NGFR) has been observed to be expressed on a subset of cells in OSCC, and NGFR+ cells have greater tumor-initiating capacity in vivo. Further, inhibition of NGFR reduces tumor growth, indicating a functional role of this receptor; however, the mechanisms by which NGFR confers enhanced tumor formation are not known. Here, we used an established murine model of OSCC and gene expression array analysis to identify ESM1 as a downstream target gene of NGFR, critical for tumor invasion and metastasis...
September 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27577679/nerve-growth-factor-ngf-mediated-regulation-of-p75-ntr-expression-contributes-to-chemotherapeutic-resistance-in-triple-negative-breast-cancer-cells
#13
Reka Chakravarthy, Katarzyna Mnich, Adrienne M Gorman
Triple negative breast cancer [TNBC] cells are reported to secrete the neurotrophin nerve growth factor [NGF] and express its receptors, p75 neurotrophin receptor [p75(NTR)] and TrkA, leading to NGF-activated pro-survival autocrine signaling. This provides a rationale for NGF as a potential therapeutic target for TNBC. Here we show that exposure of TNBC cells to NGF leads to increased levels of p75(NTR), which was diminished by NGF-neutralizing antibody or NGF inhibitors [Ro 08-2750 and Y1086]. NGF-mediated increase in p75(NTR) levels were partly due to increased transcription and partly due to inhibition of proteolytic processing of p75(NTR)...
September 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27559294/characterization-of-gene-expression-patterns-among-artificially-developed-cancer-stem-cells-using-spherical-self-organizing-map
#14
Akimasa Seno, Tomonari Kasai, Masashi Ikeda, Arun Vaidyanath, Junko Masuda, Akifumi Mizutani, Hiroshi Murakami, Tetsuya Ishikawa, Masaharu Seno
We performed gene expression microarray analysis coupled with spherical self-organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors (OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC-specific genes (POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7...
2016: Cancer Informatics
https://www.readbyqxmd.com/read/27485826/genome-wide-association-study-of-aggressive-behaviour-in-chicken
#15
Zhenhui Li, Ming Zheng, Bahareldin Ali Abdalla, Zhe Zhang, Zhenqiang Xu, Qiao Ye, Haiping Xu, Wei Luo, Qinghua Nie, Xiquan Zhang
In the poultry industry, aggressive behaviour is a large animal welfare issue all over the world. To date, little is known about the underlying genetics of the aggressive behaviour. Here, we performed a genome-wide association study (GWAS) to explore the genetic mechanism associated with aggressive behaviour in chickens. The GWAS results showed that a total of 33 SNPs were associated with aggressive behaviour traits (P < 4.6E-6). rs312463697 on chromosome 4 was significantly associated with aggression (P = 2...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27325642/cd271-expression-on-patient-melanoma-cells-is-unstable-and-unlinked-to-tumorigenicity
#16
Samantha E Boyle, Clare G Fedele, Vincent Corbin, Elisha Wybacz, Pacman Szeto, Jeremy Lewin, Richard J Young, Annie Wong, Robert Fuller, John Spillane, David Speakman, Simon Donahoe, Miklos Pohl, David Gyorki, Michael A Henderson, Ricky W Johnstone, Anthony T Papenfuss, Mark Shackleton
The stability of markers that identify cancer cells that propagate disease is important to the outcomes of targeted therapy strategies. In human melanoma, conflicting data exist as to whether hierarchical expression of CD271/p75/NGFR (nerve growth factor receptor) marks cells with enriched tumorigenicity, which would compel their specific targeting in therapy. To test whether these discrepancies relate to differences among groups in assay approaches, we undertook side-by-side testing of published methods of patient-derived melanoma xenografting (PDX), including comparisons of tissue digestion procedures or coinjected Matrigel formulations...
July 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27282385/nerve-growth-factor-receptor-negates-the-tumor-suppressor-p53-as-a-feedback-regulator
#17
Xiang Zhou, Qian Hao, Peng Liao, Shiwen Luo, Minhong Zhang, Guohui Hu, Hongbing Liu, Yiwei Zhang, Bo Cao, Melody Baddoo, Erik K Flemington, Shelya X Zeng, Hua Lu
Cancer develops and progresses often by inactivating p53. Here, we unveil nerve growth factor receptor (NGFR, p75NTR or CD271) as a novel p53 inactivator. p53 activates NGFR transcription, whereas NGFR inactivates p53 by promoting its MDM2-mediated ubiquitin-dependent proteolysis and by directly binding to its central DNA binding domain and preventing its DNA-binding activity. Inversely, NGFR ablation activates p53, consequently inducing apoptosis, attenuating survival, and reducing clonogenic capability of cancer cells, as well as sensitizing human cancer cells to chemotherapeutic agents that induce p53 and suppressing mouse xenograft tumor growth...
June 10, 2016: ELife
https://www.readbyqxmd.com/read/27248788/mesenchymal-stem-cells-from-human-extra-ocular-muscle-harbor-neuroectodermal-differentiation-potential
#18
Darilang Mawrie, Atul Kumar, Damaris Magdalene, Jina Bhattacharyya, Bithiah Grace Jaganathan
Mesenchymal stem cells (MSC) have been proposed as suitable candidates for cell therapy for neurological disorderssince they exhibit good neuronal differentiation capacity. However, for better therapeutic outcomes, it is necessary to isolate MSC from a suitable tissue sourcethat posses high neuronal differentiation. In this context, we isolated MSC from extra ocular muscle (EOM) tissue and tested the in vitro neuronal differentiation potential. In the current study, EOM tissue derived MSC were characterized and compared with bone marrow derived MSC...
2016: PloS One
https://www.readbyqxmd.com/read/27153397/mechanisms-and-disease-associations-of-haplotype-dependent-allele-specific-dna-methylation
#19
Catherine Do, Charles F Lang, John Lin, Huferesh Darbary, Izabela Krupska, Aulona Gaba, Lynn Petukhova, Jean-Paul Vonsattel, Mary P Gallagher, Robin S Goland, Raphael A Clynes, Andrew Dwork, John G Kral, Catherine Monk, Angela M Christiano, Benjamin Tycko
Haplotype-dependent allele-specific methylation (hap-ASM) can impact disease susceptibility, but maps of this phenomenon using stringent criteria in disease-relevant tissues remain sparse. Here we apply array-based and Methyl-Seq approaches to multiple human tissues and cell types, including brain, purified neurons and glia, T lymphocytes, and placenta, and identify 795 hap-ASM differentially methylated regions (DMRs) and 3,082 strong methylation quantitative trait loci (mQTLs), most not previously reported...
May 5, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27146030/endometrial-mesenchymal-stem-stromal-cells-their-fibroblast-progeny-in-endometriosis-and-more
#20
Caroline E Gargett, Shanti Gurung
No abstract text is available yet for this article.
June 2016: Biology of Reproduction
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