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https://www.readbyqxmd.com/read/28109176/oncogenic-roles-of-smarcb1-ini1-and-its-deficient-tumors
#1
Kenichi Kohashi, Yoshinao Oda
SMARCB1/INI1 is one of the core subunit proteins of the ATP-dependent SWI/SNF chromatin remodeling complex, and is identified as a potent and bona fide tumor suppressor. Interactions have been demonstrated between SMARCB1/INI1 and key proteins in various pathways related to tumor proliferation and progression: the p16-RB pathway, WNT signaling pathway, sonic hedgehog signaling pathway and Polycomb pathway. Initially, no detectable SMARCB1/INI1 protein expression was found in malignant rhabdoid tumor cells, whereas all other kinds of tumor cells and non-tumorous tissue showed SMARCB1/INI1 protein expression...
January 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28104793/rab23-s-genetic-structure-function-and-related-diseases-a-review
#2
Li-Qiang Zheng, Su-Min Chi, Cheng-Xin Li
Rab23, has been proven to play a role in membrane trafficking and protein transport in eukaryotic cells. Rab23 is also a negative regulator of the Sonic hedgehog signaling pathway in an indirect way. The nonsense mutation and loss of protein of Rab23 has been associated with neural tube defect in mice and aberrant expression in various diseases in human such as neural system,breast, visceral and cutaneous tumor. In addition, Rab23 may play joint  roles in autophagosome formation during anti-infection process against  Group A streptococcus...
January 19, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28100636/centriole-splitting-caused-by-loss-of-the-centrosomal-linker-protein-c-nap1-reduces-centriolar-satellite-density-and-impedes-centrosome-amplification
#3
Anne-Marie Flanagan, Elena Stavenschi, Shivakumar Basavaraju, David Gaboriau, David A Hoey, Ciaran G Morrison
Duplication of the centrosomes is a tightly regulated process. Abnormal centrosome numbers can impair cell division and cause changes in how cells migrate. Duplicated centrosomes are held together by a proteinaceous linker made up of rootletin filaments anchored to the centrioles by C-NAP1. This linker is removed in a NEK2A kinase-dependent manner as mitosis begins. To explore C-NAP1 activities in regulating centrosome activities, we used genome editing to ablate it. C-NAP1 null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with re-expression of C-NAP1 rescuing both these phenotypes...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28099273/making-the-most-of-hypomethylating-agents-in-myelodysplastic-syndrome
#4
Geetika Bhatt, William Blum
PURPOSE OF REVIEW: Hypomethylating agents (HMA) are the preferred therapy for patients with higher risk myelodysplastic syndromes (MDS) and an alternative therapeutic strategy for older patients with acute myeloid leukemia. These agents have improved both survival and quality of life, but results overall remain poor. The purpose of this review is to highlight recent developments in clinical research with HMA in MDS/acute myeloid leukemia over the last year. RECENT FINDINGS: Combination of HMA with B-cell lymphoma-2 inhibitors, hedgehog inhibitors, and a variety of other agents are underway, as are further studies with reformulated HMA that have more favorable pharmacokinetics (including oral bioavailability)...
January 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28098912/microrna-9-limits-hepatic-fibrosis-by-suppressing-the-activation-and-proliferation-of-hepatic-stellate-cells-by-directly-targeting-mrp1-abcc1
#5
Jie Sun, Huanying Zhang, Liying Li, Lianfeng Yu, Lifang Fu
Liver fibrosis is a chronic liver disease characterized by the proliferation and activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix (ECM). Research suggests that microRNAs (miRNAs) are a new type of regulator of liver fibrosis. In the present study, we investigated the role of microRNA-9 (miR-9) in the process of liver fibrosis, as well as the underlying mechanism of action. Downregulated levels of miR-9 were found in fibrotic liver tissues and activated HSCs as detected by qRT-PCR; whereas, expression of multidrug resistance‑associated protein 1 (MRP1/ABCC1) was upregulated in the fibrotic liver tissues and activated HSCs...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098170/targeting-the-pi3k-akt-pathway-via-gli1-inhibition-enhanced-the-drug-sensitivity-of-acute-myeloid-leukemia-cells
#6
Hui Liang, Qi-Li Zheng, Peng Fang, Jian Zhang, Tuo Zhang, Wei Liu, Min Guo, Christopher L Robinson, Shui-Bing Chen, Xiao-Ping Chen, Fang-Ping Chen, Hui Zeng
Combination targeted therapy is commonly used to treat acute myeloid leukemia (AML) patients, particularly in refractory/relapse (RR) population. However, concerns have been raised regarding the safety and patient tolerance of combination chemotherapy. It is critical to choose the appropriate treatment for precision therapy. We performed genome-wide RNA profiling using RNA-Seq to compare the RR group and the complete remission (CR) group (a total of 42 adult AML patients). The Hedgehog (Hh) and PI3K/AKT pathways were upregulated in the RR population, which was further confirmed by western blot and/or qPCR...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28091959/genetic-variation-in-mitochondrial-genes-of-the-tick-haemaphysalis-flava-collected-from-wild-hedgehogs-in-china
#7
Zhong-Bo Li, Tian-Yin Cheng, Xing-Li Xu, Lu-Lin Song, Guo-Hua Liu
The tick Haemaphysalis flava (Acari: Ixodidae) is an important ectoparasite, which causes direct damage to their hosts and also acts as a vector of various infectious disease agents in China. Despite its significance, the epidemiology, genetics and biology of H. flava has not been studied in detail. In the present study, the genetic variation in three mitochondrial (mt) DNA regions, namely cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 and 4 (nad1 and nad4), was examined in H. flava ticks collected from wild hedgehogs in China...
January 16, 2017: Experimental & Applied Acarology
https://www.readbyqxmd.com/read/28089430/high-variability-of-expression-profiles-of-homeologous-genes-for-wnt-hh-notch-and-hippo-signaling-pathways-in-xenopus-laevis
#8
Tatsuo Michiue, Takayoshi Yamamoto, Yuuri Yasuoka, Toshiyasu Goto, Takafumi Ikeda, Kei Nagura, Takuya Nakayama, Masanori Taira, Tsutomu Kinoshita
Cell signaling pathways, such as Wnt, Hedgehog (Hh), Notch, and Hippo, are essential for embryogenesis, organogenesis, and tissue homeostasis. In this study, we analyzed 415 genes involved in these pathways in the allotetraploid frog, Xenopus laevis. Most genes are retained in two subgenomes called L and S (193 homeologous gene pairs and 29 singletons). This conservation rate of homeologs is much higher than that of all genes in the X. laevis genome (86.9% vs 60.2%). Among singletons, 24 genes are retained in the L subgenome, a rate similar to the average for all genes (82...
January 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28088536/targeting-sonic-hedgehog-signaling-in-neurological-disorders
#9
REVIEW
Sita Sharan Patel, Sunil Tomar, Diksha Sharma, Neeraj Mahindroo, Malairaman Udayabanu
Sonic hedgehog (Shh) signaling influences neurogenesis and neural patterning during the development of central nervous system. Dysregulation of Shh signaling in brain leads to neurological disorders like autism spectrum disorder, depression, dementia, stroke, Parkinson's diseases, Huntington's disease, locomotor deficit, epilepsy, demyelinating disease, neuropathies as well as brain tumors. The synthesis, processing and transport of Shh ligand as well as the localization of its receptors and signal transduction in the central nervous system has been carefully reviewed...
January 11, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28077784/identification-and-characterization-of-hpv-independent-cervical-cancers
#10
Carolyn E Banister, Changlong Liu, Lucia Pirisi, Kim E Creek, Phillip J Buckhaults
BACKGROUND: Human papillomavirus (HPV) initiates cervical cancer, and continuous expression of HPV oncogenes E6 and E7 is thought to be necessary to maintain malignant growth. Current therapies target proliferating cells, rather than specific pathways, and most experimental therapies specifically target E6/E7. We investigated the presence and expression of HPV in cervical cancer, to correlate HPV oncogene expression with clinical and molecular features of these tumors that may be relevant to new targeted therapies...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077677/pharmacological-rescue-of-diabetic-skeletal-stem-cell-niches
#11
Ruth Tevlin, Eun Young Seo, Owen Marecic, Adrian McArdle, Xinming Tong, Bryan Zimdahl, Andrey Malkovskiy, Rahul Sinha, Gunsagar Gulati, Xiyan Li, Taylor Wearda, Rachel Morganti, Michael Lopez, Ryan C Ransom, Christopher R Duldulao, Melanie Rodrigues, Allison Nguyen, Michael Januszyk, Zeshaan Maan, Kevin Paik, Kshemendra-Senarath Yapa, Jayakumar Rajadas, Derrick C Wan, Geoffrey C Gurtner, Michael Snyder, Philip A Beachy, Fan Yang, Stuart B Goodman, Irving L Weissman, Charles K F Chan, Michael T Longaker
Diabetes mellitus (DM) is a metabolic disease frequently associated with impaired bone healing. Despite its increasing prevalence worldwide, the molecular etiology of DM-linked skeletal complications remains poorly defined. Using advanced stem cell characterization techniques, we analyzed intrinsic and extrinsic determinants of mouse skeletal stem cell (mSSC) function to identify specific mSSC niche-related abnormalities that could impair skeletal repair in diabetic (Db) mice. We discovered that high serum concentrations of tumor necrosis factor-α directly repressed the expression of Indian hedgehog (Ihh) in mSSCs and in their downstream skeletogenic progenitors in Db mice...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077400/differential-expression-of-hedgehog-and-snail-in-cutaneous-fibrosing-disorders-implications-for-targeted-inhibition
#12
Amrita Goyal, Katy R Linskey, Jonathan Kay, Lyn M Duncan, Rosalynn M Nazarian
OBJECTIVES: To examine Hedgehog signaling in cutaneous fibrosing disorders for which effective approved therapies are lacking, expand our knowledge of pathophysiology, and explore the rationale for targeted inhibition. METHODS: Stain intensity and percentage of cells staining for Sonic hedgehog (Shh), Indian hedgehog (Ihh), Patched (Ptch), glycogen synthase kinase 3 β (GSK3-β), β-catenin, and Snail were evaluated in human skin biopsy specimens of keloid, hypertrophic scar (Hscar), scleroderma, nephrogenic systemic fibrosis (NSF), scar, and normal skin using a tissue microarray...
December 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28073938/sonic-hedgehog-guides-axons-via-zipcode-binding-protein-1-mediated-local-translation
#13
Lea Lepelletier, Sébastien D Langlois, Christopher B Kent, Kristy Welshhans, Steves Morin, Gary J Bassell, Patricia T Yam, Frédéric Charron
: Sonic hedgehog (Shh) attracts spinal cord commissural axons toward the floorplate. How Shh elicits changes in the growth cone cytoskeleton that drive growth cone turning is unknown. We find that the turning of rat commissural axons up a Shh gradient requires protein synthesis. In particular, Shh stimulation increases β-actin protein at the growth cone, even when the cell bodies have been removed. Thus Shh induces the local translation of β-actin at the growth cone. We hypothesised that this requires zipcode binding protein 1 (ZBP1), an mRNA binding protein that transports β-actin mRNA and releases it for local translation upon phosphorylation...
January 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28073840/fda-approval-summary-sonidegib-for-locally-advanced-basal-cell-carcinoma
#14
Denise Casey, Suzanne Demko, Stacy Shord, Hong Zhao, Huanyu Chen, Kun He, Alexander Putman, Whitney S Helms, Patricia Keegan, Richard Pazdur
On July 24, 2015, the U. S. Food and Drug Administration (FDA) approved sonidegib (ODOMZO®, Novartis) for treatment of patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiation therapy. The approval was based on data from one randomized, double-blind, non-comparative trial of two doses of sonidegib administered to 230 hedgehog inhibitor-naïve patients with metastatic basal cell carcinoma (mBCC, n=36) or laBCC (n=194). Patients were randomized 2:1 to receive sonidegib 800 mg (n=151) or 200 mg (n=79) daily...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28069742/islet1-dependent-%C3%AE-catenin-hedgehog-signaling-is-required-for-outgrowth-of-the-lower-jaw
#15
Feixue Li, Guoquan Fu, Ying Liu, Xiaoping Miao, Yan Li, Xueqin Yang, Xiaoyun Zhang, Dongliang Yu, Lin Gan, Mengsheng Qiu, Yiping Chen, Ze Zhang, Zunyi Zhang
Mandibular patterning information initially resides in the epithelium during development. However, how transcriptional regulation of epithelial-derived signaling controls morphogenesis of the mandible remains elusive. Using Shh(Cre) to target the mandibular epithelium, we ablated transcription factor Islet1, resulting in a distally truncated mandible via unbalanced cell apoptosis and decreased cell proliferation in the distal mesenchyme. Loss of Islet1 caused a lack of cartilage at the distal tip, leading to the two growing mandibular elements to be fused surrounding the rostral process of Meckels cartilage...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28068223/hepatocyte-taz-wwtr1-promotes-inflammation-and-fibrosis-in-nonalcoholic-steatohepatitis
#16
Xiaobo Wang, Ze Zheng, Jorge Matias Caviglia, Kathleen E Corey, Tina M Herfel, Bishuang Cai, Ricard Masia, Raymond T Chung, Jay H Lefkowitch, Robert F Schwabe, Ira Tabas
Nonalcoholic steatohepatitis (NASH) is a leading cause of liver disease worldwide. However, the molecular basis of how benign steatosis progresses to NASH is incompletely understood, which has limited the identification of therapeutic targets. Here we show that the transcription regulator TAZ (WWTR1) is markedly higher in hepatocytes in human and murine NASH liver than in normal or steatotic liver. Most importantly, silencing of hepatocyte TAZ in murine models of NASH prevented or reversed hepatic inflammation, hepatocyte death, and fibrosis, but not steatosis...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28068221/devilish-effects-of-taz-in-nonalcoholic-steatohepatitis
#17
Scott L Friedman, Youngmin A Lee
Nonalcoholic steatohepatitis leads to cirrhosis and cancer in a rising number of patients with metabolic syndrome. In this issue of Cell Metabolism, Wang et al. (2016) identify the transcriptional co-activator Taz as a driver of inflammation and fibrosis through the induction of Indian hedgehog in hepatocytes, which stimulates fibrogenesis by hepatic stellate cells.
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28067220/bi-and-uniciliated-ependymal-cells-define-continuous-floor-plate-derived-tanycytic-territories
#18
Zaman Mirzadeh, Yael Kusne, Maria Duran-Moreno, Elaine Cabrales, Sara Gil-Perotin, Christian Ortiz, Bin Chen, Jose Manuel Garcia-Verdugo, Nader Sanai, Arturo Alvarez-Buylla
Multiciliated ependymal (E1) cells line the brain ventricles and are essential for brain homeostasis. We previously identified in the lateral ventricles a rare ependymal subpopulation (E2) with only two cilia and unique basal bodies. Here we show that E2 cells form a distinct biciliated epithelium extending along the ventral third into the fourth ventricle. In the third ventricle floor, apical profiles with only primary cilia define an additional uniciliated (E3) epithelium. E2 and E3 cells' ultrastructure, marker expression and basal processes indicate that they correspond to subtypes of tanycytes...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28063021/hepatotoxicity-with-vismodegib-an-md-anderson-cancer-center-and-research-on-adverse-drug-events-and-reports-project
#19
Beatrice J Edwards, Dennis W Raisch, Smita S Saraykar, Ming Sun, Josh A Hammel, Hai T Tran, Nathaniel Wehr, Rasha Arabyat, Dennis P West
BACKGROUND: On 30 January 2012, the US FDA approved vismodegib (Erivedge(®), Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma. OBJECTIVE: Our objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers. METHODS: FAERS was searched for reports dated 1 January 2009 through 31 December 2015 using terms including hedgehog pathway and vismodegib and hepatic-related terms such as liver, jaundice, and hepatitis, among others...
January 6, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28061797/natural-compounds-targeting-major-cell-signaling-pathways-a-novel-paradigm-for-osteosarcoma-therapy
#20
REVIEW
Pablo Angulo, Gaurav Kaushik, Dharmalingam Subramaniam, Prasad Dandawate, Kathleen Neville, Katherine Chastain, Shrikant Anant
Osteosarcoma is the most common primary bone cancer affecting children and adolescents worldwide. Despite an incidence of three cases per million annually, it accounts for an inordinate amount of morbidity and mortality. While the use of chemotherapy (cisplatin, doxorubicin, and methotrexate) in the last century initially resulted in marginal improvement in survival over surgery alone, survival has not improved further in the past four decades. Patients with metastatic osteosarcoma have an especially poor prognosis, with only 30% overall survival...
January 7, 2017: Journal of Hematology & Oncology
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