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https://www.readbyqxmd.com/read/28301521/lysosomal-adaptation-how-cells-respond-to-lysosomotropic-compounds
#1
Shuyan Lu, Tae Sung, Nianwei Lin, Robert T Abraham, Bart A Jessen
Lysosomes are acidic organelles essential for degradation and cellular homoeostasis and recently lysosomes have been shown as signaling hub to respond to the intra and extracellular changes (e.g. amino acid availability). Compounds including pharmaceutical drugs that are basic and lipophilic will become sequestered inside lysosomes (lysosomotropic). How cells respond to the lysosomal stress associated with lysosomotropism is not well characterized. Our goal is to assess the lysosomal changes and identify the signaling pathways that involve in the lysosomal changes...
2017: PloS One
https://www.readbyqxmd.com/read/28292562/a-quantitative-analysis-of-multilineage-differentiating-stress-enduring-muse-cells-in-human-adipose-tissue-and-efficacy-of-melanocytes-induction
#2
Takeshi Yamauchi, Kenshi Yamasaki, Kenichiro Tsuchiyama, Saaya Koike, Setsuya Aiba
We have shown previously that multilineage-differentiating stress-enduring (Muse) cells in neonatal fibroblasts can differentiate into functional melanocytes. In this study, we quantitate Muse cells in adipose-mesenchymal stem cells (adipose-MSCs) of human subcutaneous tissue obtained from 11 subjects of various ages, and measured efficacy of melanocytes induction from Adipose-MSC-derived Muse cells (hASC-Muse cells). There was a statistically significant negative correlation between the age of donors and the numbers of adipose-MSCs recovered per g fat as well as the percentage of SSEA3+ cells in the adipose-MSC populations, but isolated hASC-Muse cells showed pluripotency and growth curves equally regardless the age of donors...
March 6, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28283772/identification-genetic-testing-and-management-of-hereditary-melanoma
#3
Sancy A Leachman, Olivia M Lucero, Jone E Sampson, Pamela Cassidy, William Bruno, Paola Queirolo, Paola Ghiorzo
Several distinct melanoma syndromes have been defined, and genetic tests are available for the associated causative genes. Guidelines for melanoma genetic testing have been published as an informal "rule of twos and threes," but these guidelines apply to CDKN2A testing and are not intended for the more recently described non-CDKN2A melanoma syndromes. In order to develop an approach for the full spectrum of hereditary melanoma patients, we have separated melanoma syndromes into two types: "melanoma dominant" and "melanoma subordinate...
March 10, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28283753/cosmetic-applications-of-glucitol-core-containing-gallotannins-from-a-proprietary-phenolic-enriched-red-maple-acer-rubrum-leaves-extract-inhibition-of-melanogenesis-via-down-regulation-of-tyrosinase-and-melanogenic-gene-expression-in-b16f10-melanoma-cells
#4
Hang Ma, Jialin Xu, Nicholas A DaSilva, Ling Wang, Zhengxi Wei, Liangran Guo, Shelby L Johnson, Wei Lu, Jun Xu, Qiong Gu, Navindra P Seeram
The red maple (Acer rubrum) is a rich source of phenolic compounds which possess galloyl groups attached to different positions of a 1,5-anhydro-D-glucitol core. While these glucitol-core containing gallotannins (GCGs) have reported anti-oxidant and anti-glycative effects, they have not yet been evaluated for their cosmetic applications. Herein, the anti-tyrosinase and anti-melanogenic effects of a proprietary phenolic-enriched red maple leaves extract [Maplifa(™); contains ca. 45% ginnalin A (GA) along with other GCGs] were investigated using enzyme and cellular assays...
March 10, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28282952/a%C3%A2-frameshift%C3%A2-mutation%C3%A2-in%C3%A2-kit%C3%A2-is%C3%A2-associated%C3%A2-with%C3%A2-white%C3%A2-spotting%C3%A2-in%C3%A2-the%C3%A2-arabian%C3%A2-camel
#5
Heather Holl, Ramiro Isaza, Yasmin Mohamoud, Ayeda Ahmed, Faisal Almathen, Cherifi Youcef, Semir Gaouar, Douglas F Antczak, Samantha Brooks
While the typical Arabian camel is characterized by a single colored coat, there are rare populations with white spotting patterns. White spotting coat patterns are found in virtually all domesticated species, but are rare in wild species. Theories suggest that white spotting is linked to the domestication process, and is occasionally associated with health disorders. Though mutations have been found in a diverse array of species, fewer than 30 genes have been associated with spotting patterns, thus providing a key set of candidate genes for the Arabian camel...
March 9, 2017: Genes
https://www.readbyqxmd.com/read/28276104/identification-of-novel-nf-%C3%A4-b-transcriptional-targets-in-tnf%C3%AE-treated-hela-and-hepg2-cells
#6
Fei Zhou, Xinhui Xu, Danyang Wang, Jian Wu, Jinke Wang
Identification of target genes of NF-ĸB is critical for deeply understanding its biological functions. Here we identified five novel NF-ĸB target genes. Firstly, we found that 20 NF-ĸB potential target genes (PTGs) identified by ChIP-Seq and Genechip assay were enriched into the KEGG term of Pathways in cancer, 16 of them were enriched into the KEGG pathways of Small cell lung cancer, Chronic myeloid leukemia, Basal cell carcinoma, Pancreatic cancer, and Colorectal cancer. Among these PTGs, there are many documented NF-ĸB target genes...
March 8, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28273108/structure-based-mutational-analysis-of-icat-residues-mediating-negative-regulation-of-%C3%AE-catenin-co-transcriptional-activity
#7
Mélanie J Domingues, Juan Martinez-Sanz, Laura Papon, Lionel Larue, Liliane Mouawad, Jacky Bonaventure
ICAT (Inhibitor of β-CAtenin and TCF) is a small acidic protein that negatively regulates β-catenin co-transcriptional activity by competing with TCF/LEF factors in their binding to β-catenin superhelical core. In melanoma cells, ICAT competes with LEF1 to negatively regulate the M-MITF and NEDD9 target genes. The structure of ICAT consists of two domains: the 3-helix bundle N-terminal domain binds to β-catenin Armadillo (Arm) repeats 10-12 and the C-terminal tail binds to Arm repeats 5-9. To elucidate the structural mechanisms governing ICAT/β-catenin interactions in melanoma cells, three ICAT residues Y15, K19 and V22 in the N-terminal domain, contacting hydrophobic β-catenin residue F660, were mutated and interaction was assessed by immunoprecipitation...
2017: PloS One
https://www.readbyqxmd.com/read/28263292/the-master-role-of-microphthalmia-associated-transcription-factor-in-melanocyte-and-melanoma-biology
#8
Akinori Kawakami, David E Fisher
Certain transcription factors have vital roles in lineage development, including specification of cell types and control of differentiation. Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes to promote melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis, including genes encoding proteins involved in apoptosis (eg, BCL2) and the cell cycle (eg, CDK2)...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28259754/mc1r-signaling-intracellular-partners-and-pathophysiological-implications
#9
REVIEW
Cecilia Herraiz, Jose C Garcia-Borron, Celia Jiménez-Cervantes, Conchi Olivares
The melanocortin-1 receptor (MC1R) preferentially expressed in melanocytes is best known as a key regulator of the synthesis of epidermal melanin pigments. Its paracrine stimulation by keratinocyte-derived melanocortins also activates DNA repair pathways and antioxidant defenses to build a complex, multifaceted photoprotective response. Many MC1R actions rely on cAMP-dependent activation of two transcription factors, MITF and PGC1α, but pleiotropic MC1R signaling also involves activation of mitogen-activated kinases and AKT...
March 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28258518/adrenocortical-carcinoma-arising-in-an-adrenal-rest-a-case-report-and-review-of-the-literature
#10
Kristine M Cornejo, Henrietta A Afari, Peter M Sadow
Carcinomas arising from embryonic adrenal rests are rare with only a handful of reported cases. We report a case of an adrenocortical carcinoma arising from an adrenal rest located between the bladder and prostate in a 51 year-old man. The patient presented following a year of rectal pain and constipation. Computed tomography (CT) scan revealed a 9 cm pelvic mass that appeared to arise from the soft tissue between the bladder and prostate, with displacement of the organs and narrowing of the rectal lumen, suspected to be a sarcoma...
March 3, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28256796/human-limbal-neurospheres-prevent-photoreceptor-cell-death-in-a-rat-model-of-retinal-degeneration
#11
Samuel McLenachan, Dan Zhang, Erwei Hao, Ling Zhang, Shang-Chih Chen, Fred K Chen
BACKGROUND: The culture of retinal progenitors from an accessible adult stem cell source such as the limbus could provide a useful autologous source of retinal cell therapies. The human corneoscleral limbus contains multipotent stem cells that can be cultured as floating neurospheres. Previous work in rodents has demonstrated neuronal and photoreceptor differentiation from limbal neurosphere cultures. Here, we have examined undifferentiated cultured adult human limbal neurospheres as donor cells for retinal cell therapies by transplantation into a rat model of retinal degeneration...
March 3, 2017: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/28249010/tfap2-paralogs-regulate-melanocyte-differentiation-in-parallel-with-mitf
#12
Hannah E Seberg, Eric Van Otterloo, Stacie K Loftus, Huan Liu, Greg Bonde, Ramakrishna Sompallae, Derek E Gildea, Juan F Santana, J Robert Manak, William J Pavan, Trevor Williams, Robert A Cornell
Mutations in the gene encoding transcription factor TFAP2A result in pigmentation anomalies in model organisms and premature hair graying in humans. However, the pleiotropic functions of TFAP2A and its redundantly-acting paralogs have made the precise contribution of TFAP2-type activity to melanocyte differentiation unclear. Defining this contribution may help to explain why TFAP2A expression is reduced in advanced-stage melanoma compared to benign nevi. To identify genes with TFAP2A-dependent expression in melanocytes, we profile zebrafish tissue and mouse melanocytes deficient in Tfap2a, and find that expression of a small subset of genes underlying pigmentation phenotypes is TFAP2A-dependent, including Dct, Mc1r, Mlph, and Pmel...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28248716/intraepithelial-melanoma-in-the-stomach-after-treatment-with-immune-checkpoint-blockade-therapy
#13
Elina Shustef, Carlos A Torres-Cabala, Jonathan L Curry, Michael T Tetzlaff, Priyadharsini Nagarajan, Doina Ivan, Victor G Prieto, Phyu P Aung
Melanoma is the most common tumor to metastasize to the gastrointestinal tract, commonly affecting the small intestine, colon, and anorectum. Primary mucosal melanoma can arise in any gastrointestinal site, most frequently affecting anorectal mucosa. Melanoma involving the gastric mucosa, specifically, is exceedingly rare and carries a poor prognosis with a median survival of 5 months. The presence of atypical melanocytes exclusively within gastric epithelium has not been previously described. We report a case of a 52-year-old man with widespread BRAFV600E mutant metastatic melanoma who was referred to our institution for immune checkpoint antibody-blockade therapy...
February 23, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28241436/gomisin-n-inhibits-melanogenesis-through-regulating-the-pi3k-akt-and-mapk-erk-signaling-pathways-in-melanocytes
#14
Jae Kyoung Chae, Lalita Subedi, Minsun Jeong, Yong Un Park, Chul Young Kim, Hakwon Kim, Sun Yeou Kim
Gomisin N, one of the lignan compounds found in Schisandra chinensis has been shown to possess anti-oxidative, anti-tumorigenic, and anti-inflammatory activities in various studies. Here we report, for the first time, the anti-melenogenic efficacy of Gomisin N in mammalian cells as well as in zebrafish embryos. Gomisin N significantly reduced the melanin content without cellular toxicity. Although it was not capable of modulating the catalytic activity of mushroom tyrosinase in vitro, Gomisin N downregulated the expression levels of key proteins that function in melanogenesis...
February 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28236341/ednrb-mutations-cause-waardenburg-syndrome-type-ii-in-the-heterozygous-state
#15
Sarah Issa, Nadege Bondurand, Emmanuelle Faubert, Sylvain Poisson, Laure Lecerf, Patrick Nitschke, Naima Deggouj, Natalie Loundon, Laurence Jonard, Albert David, Yves Sznajer, Patricia Blanchet, Sandrine Marlin, Veronique Pingault
Waardenburg syndrome (WS) is a genetic disorder characterized by sensorineural hearing loss and pigmentation anomalies. The clinical definition of four WS types is based on additional features due to defects in structures mostly arising from the neural crest, with type I and type II being the most frequent. While type I is tightly associated to PAX3 mutations, WS type II (WS2) remains partly enigmatic with mutations in known genes (MITF, SOX10) accounting for only 30% of the cases. We performed exome sequencing in a WS2 index case and identified a heterozygous missense variation in EDNRB...
February 24, 2017: Human Mutation
https://www.readbyqxmd.com/read/28217548/polygonum-multiflorum-root-extract-as-a-potential-candidate-for-treatment-of-early-graying-hair
#16
Nguyen Dinh Thang, Pham Ngoc Diep, Pham Thi Huong Lien, Le Thi Lien
Despite Polygonum multiflorum (PM) has been experiencely used as a drug to treat early graying hair phenomenon in Asian countries for a long time, there is limited study examined the real biological effects of PM on hair graying in vitro and in vivo. In this study, we investigated the effects of PM root extract (PM-RE) on melanin synthesis in human melanoma SKMEL-28 cells and embryos/larvae of wild-type strain AB zebrafish. We also preliminary revealed the molecular mechanism of early hair graying phenomenon in both in vitro and in vivo models...
January 2017: Journal of Advanced Pharmaceutical Technology & Research
https://www.readbyqxmd.com/read/28210865/the-impact-of-melanoma-genetics-on-treatment-response-and-resistance-in-clinical-and-experimental-studies
#17
M Kunz, M Hölzel
Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations...
February 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28208226/a-rare-case-of-tfe-related-pigmented-renal-tumor-with-overlapping-features-between-melanotic-xp11-translocation-renal-cancer-and-xp11-renal-cell-carcinoma-with-melanotic-features
#18
Leonardo Cardili, Gregório Wrublevsky Pereira, Cristiano Ribeiro Viana
In recent years, an increasing number of TFE3 rearrangement-associated tumors with melanotic features have been reported as primary neoplasm in different anatomical sites, including the kidney. Melanotic Xp11 translocation renal cancer (MXTRC) and Xp11 renal cell carcinoma with melanotic features (XRCCM) have been proposed to be main categories for pigmented lesions in the microophthalmia-associated transcription factor (MiTF/TFE3) family of renal tumors that may show variable degrees of melanocytic differentiation...
February 16, 2017: Pathology International
https://www.readbyqxmd.com/read/28196297/targeting-invasive-properties-of-melanoma-cells
#19
REVIEW
Imanol Arozarena, Claudia Wellbrock
Melanoma is a skin cancer notorious for its metastatic potential. As an initial step of the metastatic cascade melanoma cells part from the primary tumour and invade the surrounding tissue, which is crucial for their dissemination and the formation of distant secondary tumours. Over the last two decades our understanding of both, general and melanoma specific mechanisms of invasion has significantly improved, but to date no efficient therapeutic strategy tackling the invasive properties of melanoma cells has reached the clinic...
February 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28182633/characterizing-the-coding-region-determinant-binding-protein-crd-bp-microphthalmia-associated-transcription-factor-mitf-mrna-interaction
#20
Gerrit van Rensburg, Sebastian Mackedenski, Chow H Lee
Coding region determinant-binding protein (CRD-BP) binds to the 3'-UTR of microphthalmia-associated transcription factor (MITF) mRNA to prevent its targeted degradation by miR-340. Here, we aim to further understand the molecular interaction between CRD-BP and MITF RNA. Using point mutation in the GXXG motif of each KH domains, we showed that all four KH domains of CRD-BP are important for their physical association with MITF RNA. We mapped the CRD-BP-binding site in the 3'-UTR of MITF RNA from nts 1330-1740 and showed that the 49-nt fragment 1621-1669 is the minimal size MITF RNA for binding...
2017: PloS One
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