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https://www.readbyqxmd.com/read/29045167/identification-of-a-novel-de-novo-heterozygous-deletion-in-the-sox10-gene-in-waardenburg-syndrome-type-ii-using-next-generation-sequencing
#1
Haonan Li, Peng Jin, Qian Hao, Wei Zhu, Xia Chen, Ping Wang
OBJECTIVES: Waardenburg syndrome (WS) is a rare autosomal dominant disorder associated with pigmentation abnormalities and sensorineural hearing loss. In this study, we investigated the genetic cause of WSII in a patient and evaluated the reliability of the targeted next-generation exome sequencing method for the genetic diagnosis of WS. METHODS: Clinical evaluations were conducted on the patient and targeted next-generation sequencing (NGS) was used to identify the candidate genes responsible for WSII...
October 18, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29044103/oct4-impedes-cell-fate-redirection-by-the-melanocyte-lineage-master-regulator-mitf-in-mouse-escs
#2
Danna Sheinboim, Itay Maza, Iris Dror, Shivang Parikh, Vladislav Krupalnik, Rachel E Bell, Asaf Zviran, Yusuke Suita, Ofir Hakim, Yael Mandel-Gutfreund, Mehdi Khaled, Jacob H Hanna, Carmit Levy
Ectopic expression of lineage master regulators induces transdifferentiation. Whether cell fate transitions can be induced during various developmental stages has not been systemically examined. Here we discover that amongst different developmental stages, mouse embryonic stem cells (mESCs) are resistant to cell fate conversion induced by the melanocyte lineage master regulator MITF. By generating a transgenic system we exhibit that in mESCs, the pluripotency master regulator Oct4, counteracts pro-differentiation induced by Mitf by physical interference with MITF transcriptional activity...
October 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/29042215/a-novel-stilbene-like-compound-that-inhibits-melanoma-growth-by-regulating-melanocyte-differentiation-and-proliferation
#3
Noah A Stueven, Nicholas M Schlaeger, Aaron P Monte, Sheng-Ping L Hwang, Cheng-Chen Huang
Melanoma is the most aggressive form of skin cancer. Current challenges to melanoma therapy include the adverse effects from immunobiologics, resistance to drugs targeting the MAPK pathway, intricate interaction of many signal pathways, and cancer heterogeneity. Thus combinational therapy with drugs targeting multiple signaling pathways becomes a new promising therapy. Here, we report a family of stilbene-like compounds called A11 that can inhibit melanoma growth in both melanoma-forming zebrafish embryos and mouse melanoma cells...
October 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29029422/serine-207-phosphorylated-lysyl-trna-synthetase-predicts-disease-free-survival-of-non-small-cell-lung-carcinoma
#4
Suliman Boulos, Min Chul Park, Marian Zeibak, Shen Yun Foo, Yoon Kyung Jeon, Young Tae Kim, Alex Motzik, Sagi Tshori, Tamar Hamburger, Sunghoon Kim, Hovav Nechushtan, Ehud Razin
It has been shown that various tRNA synthetases exhibit non-canonical activities unrelated to their original role in translation. We have previously described a signal transduction pathway in which serine 207 phosphorylated lysyl-tRNA synthetase (P-s207 LysRS) is released from the cytoplasmic multi-tRNA synthetase complex (MSC) into the nucleus, where it activates the transcription factor MITF in stimulated cultured mast cells and cardiomyocytes. Here we describe a similar transformation of LysRS due to EGFR signaling activation in human lung cancer...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028954/1-benzyl-indole-3-carbinol-is-a-highly-potent-new-small-molecule-inhibitor-of-wnt-%C3%AE-catenin-signaling-in-melanoma-cells-that-coordinately-inhibits-cell-proliferation-and-disrupts-expression-of-microphthalmia-associated-transcription-factor-isoform-m
#5
Aishwarya Kundu, Michelle G Khouri, Sheila Aryana, Gary L Firestone
1-Benzyl-indole-3-carbinol (1-benzyl-I3C), a synthetic analogue of the crucifer derived natural phytochemical I3C, displayed significantly wider sensitivity and anti-proliferative potency in melanoma cells than the natural compound. Unlike I3C, which targets mainly oncogenic BRAF-expressing cells, 1-benzyl I3C effectively inhibited proliferation of melanoma cells with a more extensive range of mutational profiles, including those expressing wild type BRAF. In both cultured melanoma cell lines and in vivo in melanoma cell-derived tumor xenografts, 1-benzyl-I3C disrupted canonical Wnt/β-catenin signaling that resulted in the down regulation of β-catenin protein levels with a concomitant increase in levels of the β-catenin destruction complex components GSK3β and Axin...
September 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29022913/mbd2-upregulates-mir-301a-5p-to-induce-kidney-cell-apoptosis-during-vancomycin-induced-aki
#6
Juan Wang, Huiling Li, Shuangfa Qiu, Zheng Dong, Xudong Xiang, Dongshan Zhang
Despite DNA methylation occurred in acute kidney injury (AKI), how it influenced progression of AKI remains unclear. Methyl-CpG-binding domain protein 2 (MBD2), a protein readers of methylation, was used to analyze the impact of DNA methylation on vancomycin (VAN)-induced AKI. Here, in cultured human kidney tubular epithelial cells (HK-2), we show that knockdown of MBD2 by siRNA attenuated VAN-induced apoptosis, caspase activity, and the expression of BAX and cleaved caspase 3. Interestingly, knockdown of MBD2 by siRNA was associated with the suppression of miR-301a-5p...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28993145/an-inhibitory-mechanism-of-action-of-a-novel-syringic-acid-derivative-on-%C3%AE-melanocyte-stimulating-hormone-%C3%AE-msh-induced-melanogenesis
#7
Yoon Ju Jeong, Jae-Young Lee, Jino Park, Soo Nam Park
AIMS: To report the effects of a novel syringic-acid derivative, (R)-ethyl-2-acetamido-3-(4-hydroxy-3,5-dimethoxybenzoylthio)propanoate (EABTO), on melanin synthesis and to identify its mechanism of action in B16F1 melanoma cells. METHODS: The effects of EABTO on melanin synthesis in B16F1 cells and human epidermal melanocytes and the influence on cell-free tyrosinase activity were evaluated. EABTO-induced cellular signaling cascades were studied by western blotting...
October 6, 2017: Life Sciences
https://www.readbyqxmd.com/read/28990013/primary-oral-melanoma-a-clinicopathologic-review-and-case-presentation
#8
Mayara Santos de Castro, Bruno Saulo de Assis Reis, Denismar Alves Nogueira, Marina Lara de Carli, João Adolfo Costa Hanemann, Alessandro Antônio Costa Pereira, Oslei Paes de Almeida, Felipe Fornias Sperandio
OBJECTIVE: The purpose of this manuscript is to present a clinicopathologic review of the literature concerning all the detailed cases of primary oral melanoma (OM) that were confirmed by immunohistochemistry. In addition, a pertinent case presentation is addressed. DATA SOURCES: An extensive electronic search of the literature was performed using PubMed/Medline from 1953 to 2017. Relevant articles were selected based on specific inclusion criteria. Statistical analyses were conducted by the Shapiro-Wilk, Fisher's exact, chi-square, and Z tests (α = ...
October 6, 2017: Quintessence International
https://www.readbyqxmd.com/read/28982372/detection-of-two-non-synonymous-snps-in-slc45a2-on-bta20-as-candidate-causal-mutations-for-oculocutaneous-albinism-in-braunvieh-cattle
#9
Sophie Rothammer, Elisabeth Kunz, Doris Seichter, Stefan Krebs, Martina Wassertheurer, Ruedi Fries, Gottfried Brem, Ivica Medugorac
BACKGROUND: Cases of albinism have been reported in several species including cattle. So far, research has identified many genes that are involved in this eye-catching phenotype. Thus, when two paternal Braunvieh half-sibs with oculocutaneous albinism were detected on a private farm, we were interested in knowing whether their phenotype was caused by an already known gene/mutation. RESULTS: Analysis of genotyping data (50K) of the two albino individuals, their mothers and five other relatives identified a 47...
October 5, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28981602/inhibition-of-collagenase-and-melanogenesis-by-ethanol-extracts-of-orostachys-japonicus-a-berger-possible-involvement-of-erk-and-akt-signaling-pathways-in-melanoma-cells
#10
Dai Sig Im, Jong-Min Lee, Jongsung Lee, Hye Jin Shin, Kyoung Tai No, See-Hyoung Park, Kiyoung Kim
Orostachys japonicus is an herb that contains several functional components and has traditionally been used to treat various diseases in Asia. In this study, bioactive components from different parts of the O. japonicus plant were investigated, and the contents of the functional components in ethanol extracts of O. japonicus cultivated in Korea and China were compared. The antioxidant effects of O. japonicus ethanol extracts were investigated using Raw 264.7 cells. It was found that 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity was significantly decreased in the cells treated with the extracts...
October 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28978095/melphalan-modifies-the-bone-microenvironment-by-enhancing-osteoclast-formation
#11
Ryan C Chai, Michelle M McDonald, Rachael L Terry, Nataša Kovačić, Jenny M Down, Jessica A Pettitt, Sindhu T Mohanty, Shruti Shah, Gholamreza Haffari, Jiake Xu, Matthew T Gillespie, Michael J Rogers, John T Price, Peter I Croucher, Julian M W Quinn
Melphalan is a cytotoxic chemotherapy used to treat patients with multiple myeloma (MM). Bone resorption by osteoclasts, by remodeling the bone surface, can reactivate dormant MM cells held in the endosteal niche to promote tumor development. Dormant MM cells can be reactivated after melphalan treatment; however, it is unclear whether melphalan treatment increases osteoclast formation to modify the endosteal niche. Melphalan treatment of mice for 14 days decreased bone volume and the endosteal bone surface, and this was associated with increases in osteoclast numbers...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977883/targeted-exome-sequencing-of-korean-triple-negative-breast-cancer-reveals-homozygous-deletions-associated-with-poor-prognosis-of-adjuvant-chemotherapy-treated-patients
#12
Hae Min Jeong, Ryong Nam Kim, Mi Jeong Kwon, Ensel Oh, Jinil Han, Se Kyung Lee, Jong-Sun Choi, Sara Park, Seok Jin Nam, Gyung Yup Gong, Jin Wu Nam, Doo Ho Choi, Hannah Lee, Byung-Ho Nam, Yoon-La Choi, Young Kee Shin
Triple-negative breast cancer is characterized by the absence of estrogen and progesterone receptors and human epidermal growth factor receptor 2, and is associated with a poorer outcome than other subtypes of breast cancer. Moreover, there are no accurate prognostic genes or effective therapeutic targets, thereby necessitating continued intensive investigation. This study analyzed the genetic mutation landscape in 70 patients with triple-negative breast cancer by targeted exome sequencing of tumor and matched normal samples...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977677/signaling-cascades-activated-by-uvb-in-human-melanocytes-lead-to-the-increased-expression-of-melanocyte-receptors-endothelin-b-receptor-and-c-kit-%C3%A2
#13
Shuko Terazawa, Genji Imokawa
A single exposure of normal human melanocytes (NHMs) to ultraviolet B (UVB) radiation induces a distinct increase in the expression of c-KIT and endothelin B receptor (EDNRB) and up-regulates the expression of microphthalmia-associated transcription factor (MITF). In this review, we clarify the signaling mechanisms by which UVB stimulates the expression of MITF in NHMs, thus leading to up-regulation of those two important melanogenic receptors. The increased expression of MITF in UVB-exposed NHMs is accompanied by a markedly stimulated and prolonged phosphorylation of p38/CREB...
October 4, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28976960/cancer-drug-addiction-is-relayed-by-an-erk2-dependent-phenotype-switch
#14
Xiangjun Kong, Thomas Kuilman, Aida Shahrabi, Julia Boshuizen, Kristel Kemper, Ji-Ying Song, Hans W M Niessen, Elisa A Rozeman, Marnix H Geukes Foppen, Christian U Blank, Daniel S Peeper
Observations from cultured cells, animal models and patients raise the possibility that the dependency of tumours on the therapeutic drugs to which they have acquired resistance represents a vulnerability with potential applications in cancer treatment. However, for this drug addiction trait to become of clinical interest, we must first define the mechanism that underlies it. We performed an unbiased CRISPR-Cas9 knockout screen on melanoma cells that were both resistant and addicted to inhibition of the serine/threonine-protein kinase BRAF, in order to functionally mine their genome for 'addiction genes'...
October 12, 2017: Nature
https://www.readbyqxmd.com/read/28943528/scopoletin-stimulates-melanogenesis-via-camp-pka-pathway-and-partially-p38-activation
#15
Dae-Sung Kim, Su-Bin Cha, Min-Cheol Park, Seol-A Park, Hye-Soo Kim, Won-Hong Woo, Yeun-Ja Mun
Scopoletin was recently shown to stimulate melanogenesis through cAMP-response element-binding protein (CREB) phosphorylation. In this study, we investigated the molecular events of melanogenesis-induced by scopoletin. After exposure to scopoletin, the protein levels of tyrosinase and tyrosianse related protein-1 (TRP-1) were significantly increased in B16F10 cells. The mRNA levels of tyrosinase and microphthalmia-associated transcription factor (MITF) were also enhanced by scopoletin. cAMP production and phosphorylation of p38 mitogen-activated protein kinase (MAPK) were increased by scopoletin treatment...
September 22, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28935865/melanoblast-development-coincides-with-the-late-emerging-cells-from-the-dorsal-neural-tube-in-turtle-trachemys-scripta
#16
Ritva Rice, Judith Cebra-Thomas, Maarja Haugas, Juha Partanen, David P C Rice, Scott F Gilbert
Ectothermal reptiles have internal pigmentation, which is not seen in endothermal birds and mammals. Here we show that the development of the dorsal neural tube-derived melanoblasts in turtle Trachemys scripta is regulated by similar mechanisms as in other amniotes, but significantly later in development, during the second phase of turtle trunk neural crest emigration. The development of melanoblasts coincided with a morphological change in the dorsal neural tube between stages mature G15 and G16. The melanoblasts delaminated and gathered in the carapacial staging area above the neural tube at G16, and differentiated into pigment-forming melanocytes during in vitro culture...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923400/mitf-suppression-improves-the-sensitivity-of-melanoma-cells-to-a-braf-inhibitor
#17
Satoshi Aida, Yukiko Sonobe, Hiromi Tanimura, Nobuhiro Oikawa, Munehiro Yuhki, Hiroshi Sakamoto, Takakazu Mizuno
Microphthalmia-associated transcription factor (MITF) is expressed in melanomas and has a critical role in melanocyte development and transformation. Because inhibition of MITF inhibits cell growth in melanoma, MITF is a potential therapeutic target molecule. Here, we report the identification of CH6868398, which has a novel chemical structure and suppresses MITF expression at the protein level in melanoma cells. CH6868398 showed cell growth inhibition activity against MITF-dependent melanoma cells both with and without BRAF mutation and also exhibited anti-tumor efficacy in a melanoma xenograft model...
September 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28919486/resveratrol-inhibits-proliferation-promotes-differentiation-and-melanogenesis-in-ht-144-melanoma-cells-through-inhibition-of-mek-erk-kinase-pathway
#18
Ming-Jun Lei, Yao Dong, Chun-Xia Sun, Xiang-Hong Zhang
The present study was aimed to investigate the effect of resveratrol on the viability of HT-144 melanoma cells and formation of melanin. MTT assay was used for analysis of cell viability and western blot for determination of phospho-Mek 1/2, phospho-Erk 1/2 (Tyr-204), Mitf, PBG-D and p-CREB-1 expression. MTT assay results showed that treatment of HT-144 cells with various doses of resveratrol led to a concentration dependent inhibition of proliferation. The antiproliferative activity was significant at 15 μM concentration of resveratrol after 24 h...
October 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28915638/oleoylethanolamide-inhibits-%C3%AE-melanocyte-stimulating-hormone-stimulated-melanogenesis-via-erk-akt-and-creb-signaling-pathways-in-b16-melanoma-cells
#19
Juan Zhou, Tong Ren, Ying Li, Anran Cheng, Wanyi Xie, Lanxi Xu, Lu Peng, Jinbin Lin, Lianxiang Lian, Yong Diao, Xin Jin, Lichao Yang
The present study aimed to examine the potential inhibitory activity of oleoylethanolamide (OEA) on α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis and the molecular mechanism(s) involved in the process in B16 mouse melanoma cells. Our data demonstrated that OEA markedly inhibited melanin synthesis and tyrosinase activity in α-MSH-stimulated B16 cells. In addition, the expression of melanogenesis-related proteins, such as melanocortin-1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1) and tyrosinase, was suppressed in a concentration-dependent manner by OEA...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28910630/fragment-and-conquer
#20
Vera Kozjak-Pavlovic, Suvagata Roy Chowdhury, Thomas Rudel
The replication vacuole of Legionella pneumophila makes contact with host mitochondria. In this issue of Cell Host & Microbe, Escoll et al. (2017) dissect the mechanisms of this interaction, the effect of the T4SS effector MitF on mitochondrial function, and the resultant metabolic reprogramming of infected cells to benefit the bacteria.
September 13, 2017: Cell Host & Microbe
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