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https://www.readbyqxmd.com/read/29225516/hedgehog-gli1-signaling-pathway-regulates-mgmt-expression-and-chemoresistance-to-temozolomide-in-human-glioblastoma
#1
Ke Wang, Dongjiang Chen, Zhouqi Qian, Daming Cui, Liang Gao, Meiqing Lou
Background: Chemoresistance of glioblastoma (GBM) is a feature of this devastating disease. This study is to determine the relationship between Hedgehog (HH)/Gli1 signaling pathway and chemoresistance to temozolomide (TMZ) in human GBM. Methods: We analyzed Gli1 nuclear staining and O6-methylguanine DNA methyltransferase (MGMT) expression in 48 cases of primary GBM tissues by immunohistochemistry. Quantitative PCR, western blot, methylation-specific PCR, cell proliferation and apoptosis assay were used to investigate changes of MGMT expression and chemosensitivity to TMZ after manipulating HH/Gli1 signaling activity in A172 and U251 GBM cell lines...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29222038/hdac6-inhibition-induces-glioma-stem-cells-differentiation-and-enhances-cellular-radiation-sensitivity-through-the-shh-gli1-signaling-pathway
#2
Wei Yang, Yingying Liu, Ruoling Gao, Hongquan Yu, Ting Sun
The existence of small numbers of stem-like cells, called glioma stem cells (GSCs), in human glioblastoma multiforme (GBM) is responsible for recurrence due to resistance to radiotherapy and chemotherapy. Inhibition of histone deacetylase 6 (HDAC6) enhanced radiosensitivity of cancer cells. However, the effect of inhibiting HDAC6 on stemness and radioresistance of GSCs and its molecular mechanism are largely unknown. In the present study, we found that HDAC6 was upregulated in GSCs comparing to non-stem tumor cells...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29221447/disruption-of-postnatal-folliculogenesis-and-development-of-ovarian-tumor-in-a-mouse-model-with-aberrant-transforming-growth-factor-beta-signaling
#3
Yang Gao, Xin Fang, David F Vincent, David W Threadgill, Laurent Bartholin, Qinglei Li
BACKGROUND: Transforming growth factor beta (TGFB) superfamily signaling is implicated in the development of sex cord-stromal tumors, a category of poorly defined gonadal tumors. The aim of this study was to determine potential effects of dysregulated TGFB signaling in the ovary using Cre recombinase driven by growth differentiation factor 9 (Gdf9) promoter known to be expressed in oocytes. METHODS: A mouse model containing constitutively active TGFBR1 (TGFBR1CA) using Gdf9-iCre (termed TGFBR1-CAG9Cre) was generated...
December 8, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29218101/delta-notch-like-epidermal-growth-factor-related-receptor-dner-orchestrates-stemness-and-cancer-progression-in-prostate-cancer
#4
Lijun Wang, Qi Wu, Shan Zhu, Zhiyu Li, Jingping Yuan, Dehua Yu, Zhiliang Xu, Juanjuan Li, Shengrong Sun, Changhua Wang
DNER, Delta/Notch-like epidermal growth factor (EGF)-related receptor, is a neuron-specific transmembrane protein carrying extracellular EGF-like repeats. The function of DNER in prostate cancer has not been evaluated. Here, we showed that the upregulation of DNER is observed in various cancers, including prostate cancer. Knockdown of DNER in PC-3 cells inhibited cell proliferation, migration and invasion as well as tumorigenesis in PC-3 xenografts. DNER knockdown specifically inhibited cell growth in spheroids...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29215700/novel-smoothened-antagonists-as-anti-neoplastic-agents-for-the-treatment-of-osteosarcoma
#5
Giulia Bernardini, Michela Geminiani, Silvia Gambassi, Maurizio Orlandini, Elena Petricci, Barbara Marzocchi, Marcella Laschi, Maurizio Taddei, Fabrizio Manetti, Annalisa Santucci
Osteosarcoma (OS) is an ultra-rare highly malignant tumor of the skeletal system affecting mainly children and young adults and it is characterized by an extremely aggressive clinical course. OS patients are currently treated with chemotherapy and complete surgical resection of cancer tissue. However, resistance to chemotherapy and the recurrence of disease, as pulmonary metastasis, remain the two greatest challenges in the management and treatment of this tumour. For these reasons, it is of primary interest to find alternative therapeutic strategies for OS...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29211850/sonic-hedgehog-and-wnt-signaling-promote-adrenal-gland-regeneration-in-male-mice
#6
Isabella Finco, Antonio M Lerario, Gary D Hammer
The atrophy and hypofunction of the adrenal cortex following long-term pharmacologic glucocorticoid therapy are a major health problem necessitating chronic glucocorticoid replacement that often prolongs the ultimate return of endogenous adrenocortical function. Underlying this functional recovery is anatomic regeneration, the cellular and molecular mechanisms of which are poorly understood. Investigating the lineage contribution of cortical Shh+ progenitor cells and the SHH-responsive capsular Gli1+ cells to the regenerating adrenal cortex, we observed a spatially and temporally bimodal contribution of both cell types to adrenocortical regeneration following cessation of glucocorticoid treatment...
December 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/29208033/evaluating-the-oxysterol-combination-of-22-s-hydroxycholesterol-and-20-s-hydroxycholesterol-in-periodontal-regeneration-using-periodontal-ligament-stem-cells-and-alveolar-bone-healing-models
#7
Jin-Sun Lee, EunJi Kim, Seonggu Han, Kyung Lhi Kang, Jung Sun Heo
BACKGROUND: Oxysterols, oxygenated by-products of cholesterol biosynthesis, play roles in various physiological and pathological systems. However, the effects of oxysterols on periodontal regeneration are unknown. This study investigated the effects of the specific oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on the regeneration of periodontal tissues using in-vitro periodontal ligament stem cells (PDLSCs) and in-vivo models of alveolar bone defect...
December 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29203771/alu-dependent-rna-editing-of-gli1-promotes-malignant-regeneration-in-multiple-myeloma
#8
Elisa Lazzari, Phoebe K Mondala, Nathaniel Delos Santos, Amber C Miller, Gabriel Pineda, Qingfei Jiang, Heather Leu, Shawn A Ali, Anusha-Preethi Ganesan, Christina N Wu, Caitlin Costello, Mark Minden, Raffaella Chiaramonte, A Keith Stewart, Leslie A Crews, Catriona H M Jamieson
Despite novel therapies, relapse of multiple myeloma (MM) is virtually inevitable. Amplification of chromosome 1q, which harbors the inflammation-responsive RNA editase adenosine deaminase acting on RNA (ADAR)1 gene, occurs in 30-50% of MM patients and portends a poor prognosis. Since adenosine-to-inosine RNA editing has recently emerged as a driver of cancer progression, genomic amplification combined with inflammatory cytokine activation of ADAR1 could stimulate MM progression and therapeutic resistance. Here, we report that high ADAR1 RNA expression correlates with reduced patient survival rates in the MMRF CoMMpass data set...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29200875/rkip-reduction-enhances-radioresistance-by-activating-the-shh-signaling-pathway-in-non-small-cell-lung-cancer
#9
Shi-Yang Xie, Guang Li, Chong Han, Yang-Yang Yu, Nan Li
Non-small-cell lung cancer (NSCLC) is exceptionally deadly because the tumors lack sensitive early-stage diagnostic biomarkers and are resistant to radiation and chemotherapy. Here, we investigated the role and mechanism of Raf kinase inhibitory protein (RKIP) in NSCLC radioresistance. The clinical data showed that the RKIP expression level was generally lower in radioresistant NSCLC tissues than in radiosensitive tissues. Reduced RKIP expression was related to NSCLC radioresistance and poor prognosis. In vitro experiments showed that RKIP knockdown increased radioresistance and metastatic ability in NSCLC cell lines...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29190924/pttg1-cooperated-with-gli1-leads-to-epithelial-mesenchymal-transition-in-esophageal-squamous-cell-cancer
#10
Wang Feng, Xuan Xiaoyan, Li Shenglei, Liu Hongtao, Jiang Guozhong
Pituitary tumor-transforming gene-1 (PTTG1) could acquire its metastasis-promoting effects via inducing epithelial-mesenchymal transition (EMT). However, its role and mechanism in EMT in esophageal squamous cell cancer (ESCC) had not been clearly elucidated. Here, we demonstrated that PTTG1 was overexpressed in ESCC cell lines and tissues especially those with lymph node metastasis. Down regulation of PTTG1 levels dampened the ESCC cells invasion, migration, proliferation ability and colony formation in vitro and inhibited the growth of mouse xenograft model of ESCC cells in vivo...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29189160/role-of-glioma-associated-gli1-oncogene-in-carcinogenesis-and-cancer-targeted-therapy
#11
Jie Wu, Dingxin Di, Chen Zhao, Yingyi Liu, Hongxia Chen, Yan Gong, Xianda Zhao, Honglei Chen
Glioma-associated oncogenes (GLIs) are zinc finger protein family members and downstream regulatory factors of the classic Hedgehog (Hh) signaling pathway. GLI proteins influence the growth and development of organisms and aid in tissue repair. However, aberrant expression of the GLI family member GLI1 promotes carcinogenesis by inducing epithelial-mesenchymal transition (EMT), angiogenesis, and other signaling pathways. Overexpression of GLI1 is thought to be an indicator of poor prognosis as well as a potential therapeutic target for cancers...
November 29, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29187450/oral-squamous-cell-carcinoma-derived-sonic-hedgehog-promotes-angiogenesis
#12
Hiromasa Kuroda, Naito Kurio, Tsuyoshi Shimo, Kenichi Matsumoto, Masanori Masui, Kiyofumi Takabatake, Tatsuo Okui, Soichiro Ibaragi, Yuki Kunisada, Kyoichi Obata, Norie Yoshioka, Koji Kishimoto, Hitoshi Nagatsuka, Akira Sasaki
BACKGROUND: Sonic hedgehog (SHH) signaling is related to the pathogenesis of oral squamous cell carcinoma (OSCC), but its role in OSCC is not yet well understood. In this study, we analyzed the role of SHH signaling in OSCC. MATERIALS AND METHODS: We examined the expression pattern of SHH and its signal proteins in clinically resected OSCC samples by immunohistochemistry. We also evaluated the function of SHH signaling using the hedgehog signaling inhibitor cyclopamine in vivo and in vitro by proliferation, migration and angiogenesis analyses...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29164577/mir-150-alleviates-emt-and-cell-invasion-of-colorectal-cancer-through-targeting-gli1
#13
H Fan, X Liu, W-W Zheng, Z-H Zhuang, C-D Wang
OBJECTIVE: Epithelial-mesenchymal transition (EMT) is related to colorectal cancer invasion and metastasis. Glioma-associated oncogene homolog 1 (Gli1) abnormal expression is associated with EMT, invasion, and metastasis in various cancers. MiR-150 is found downregulated in colorectal cancer pathogenesis. Bioinformatics analysis shows the complementary targeted relationship between miR-150 and the 3'-UTR of Gli1 mRNA. This study explores the role of miR-150 in regulating Gli1 expression, colorectal cancer cell EMT, and invasion...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29162857/temporal-expression-pattern-of-genes-during-the-period-of-sex-differentiation-in-human-embryonic-gonads
#14
Linn S Mamsen, Emil H Ernst, Rehannah Borup, Agnete Larsen, Rasmus H Olesen, Erik Ernst, Richard A Anderson, Stine G Kristensen, Claus Y Andersen
The precise timing and sequence of changes in expression of key genes and proteins during human sex-differentiation and onset of steroidogenesis was evaluated by whole-genome expression in 67 first trimester human embryonic and fetal ovaries and testis and confirmed by qPCR and immunohistochemistry (IHC). SRY/SOX9 expression initiated in testis around day 40 pc, followed by initiation of AMH and steroidogenic genes required for androgen production at day 53 pc. In ovaries, gene expression of RSPO1, LIN28, FOXL2, WNT2B, and ETV5, were significantly higher than in testis, whereas GLI1 was significantly higher in testis than ovaries...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138054/keratinocyte-sonic-hedgehog-up-regulation-drives-the-development-of-giant-congenital-nevi-via-paracrine-endothelin-1-secretion
#15
Arash Chitsazan, Blake Ferguson, Rehan Villani, Herlina Y Handoko, Pamela Mukhopadhyay, Brian Gabrielli, Wolter J Mooi, H Peter Soyer, Duncan Lambie, Kiarash Khosrotehrani, Grant Morahan, Graeme J Walker
Giant congenital nevi are associated with clinical complications such as neurocutaneous melanosis and melanoma. Virtually nothing is known about why some individuals develop these lesions. We previously identified the sonic hedgehog (Shh) pathway regulator Cdon as a candidate nevus modifier gene. Here we validate this by studying Cdon knockout mice, and go on to establishment the mechanism by which Shh exacerbates nevogenesis. Cdon knockout mice develop blue nevi without the need for somatic melanocyte oncogenic mutation...
November 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29137400/downregulation-of-the-sonic-hedgehog-gli-pathway-transcriptional-target-neogenin-1-is-associated-with-basal-cell-carcinoma-aggressiveness
#16
Bárbara S Casas, Christelle Adolphe, Pablo Lois, Nelson Navarrete, Natalia Solís, Eva Bustamante, Patricio Gac, Patricio Cabané, Ivan Gallegos, Brandon J Wainwright, Verónica Palma
Basal Cell Carcinoma (BCC) is one of the most diagnosed cancers worldwide. It develops due to an unrestrained Sonic Hedgehog (SHH) signaling activity in basal cells of the skin. Certain subtypes of BCC are more aggressive than others, although the molecular basis of this phenomenon remains unknown. We have previously reported that Neogenin-1 (NEO1) is a downstream target gene of the SHH/GLI pathway in neural tissue. Given that SHH participates in epidermal homeostasis, here we analyzed the epidermal expression of NEO1 in order to identify whether it plays a role in adult epidermis or BCC...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29127258/homozygous-mutation-in-cep19-a-gene-mutated-in-morbid-obesity-in-bardet-biedl-syndrome-with-predominant-postaxial-polydactyly
#17
Esra Yıldız Bölükbaşı, Sara Mumtaz, Muhammad Afzal, Ute Woehlbier, Sajid Malik, Aslıhan Tolun
BACKGROUND: Bardet-Biedl syndrome (BBS) is a ciliopathy with extensive phenotypic variability and genetic heterogeneity. We aimed to discover the gene mutated in a consanguineous kindred with multiple cases of a BBS phenotype. METHODS: SNP genotype data were used for linkage analysis and exome sequencing to identify mutations. Modelling and in silico analysis were performed to predict mutation severity. RESULTS: Patients had postaxial polydactyly plus variable other clinical features including rod-cone dystrophy, obesity, intellectual disability, renal malformation, developmental delay, dental anomalies, speech disorder and enlarged fatty liver...
November 10, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29125483/the-targeted-regulation-of-gli1-by-mir-361-to-inhibit-epithelia-mesenchymal-transition-and-invasion-of-esophageal-carcinoma-cells
#18
Pingping Lin, Qingsong Pang, Ping Wang, Xiying Lv, Lanfang Liu, Aike Li
Epithelia-mesenchymal transition (EMT) is critical for invasion and metastasis of esophageal carcinoma. Gli1, a transcriptional factor in Hedgehog pathway, is correlated with EMT, invasion and metastasis of tumors. However, its role in esophageal cancer is still unknown. Bioinformatics analysis revealed relationship between microRNA (miR)-361 and 3'-UTR of Gli1 gene. This study thus investigated the role of miR-361 and Gli1 in invasion and metastasis of esophageal cancer. Both tumor and adjacent tissues were collected from 58 esophageal cancer patients to test the expressions of miR-361 and Gli1, the relationship of which was confirmed by dual-luciferase reporter gene assay...
November 3, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29122585/strong-sonic-hedgehog-signaling-in-the-mouse-ventral-spinal-cord-is-not-required-for-oligodendrocyte-precursor-cell-opc-generation-but-is-necessary-for-correct-timing-of-its-generation
#19
Hirokazu Hashimoto, Wen Jiang, Takeshi Yoshimura, Kyeong-Hye Moon, Jinwoong Bok, Kazuhiro Ikenaka
In the mouse neural tube, sonic hedgehog (Shh) secreted from the floor plate (FP) and the notochord (NC) regulates ventral patterning of the neural tube, and later is essential for the generation of oligodendrocyte precursor cells (OPCs). During early development, the NC is adjacent to the neural tube and induces ventral domains in it, including the FP. In the later stage of development, during gliogenesis in the spinal cord, the pMN domain receives strong Shh signaling input. While this is considered to be essential for the generation of OPCs, the actual role of this strong input in OPC generation remains unclear...
November 6, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29113369/prognostic-role-of-gli1-expression-in-breast-cancer-a-meta-analysis
#20
Bilan Wang, Ting Yu, Yuzhu Hu, Mengmeng Xiang, Haoning Peng, Yunzhu Lin, Lu Han, Lingli Zhang
Glioma-associated oncogene 1 (Gli1) is a critical transcriptional factor of Sonic hedgehog pathway which has been proved to participate in the initiation and progression of tumor in mammalians. However, its clinical value in breast cancer remains unknown. Thus, a meta-analysis was performed to clarify the association of Gli1 over-expression, clinic-pathological characteristics, molecular subtypes and prognosis in breast cancer. According to included criteria, 13 eligible studies containing 2816 patients all around the world were selected in this study...
October 6, 2017: Oncotarget
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