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https://www.readbyqxmd.com/read/28817816/exosomes-derived-from-human-bone-marrow-mesenchymal-stem-cells-promote-tumor-growth-through-hedgehog-signaling-pathway
#1
Jin Qi, Yali Zhou, Zuoyi Jiao, Xu Wang, Yang Zhao, Yangbin Li, Huijuan Chen, Luxi Yang, Hongwen Zhu, Yumin Li
BACKGROUND/AIMS: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. METHODS: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28799948/anticancer-drugs-and-the-regulation-of-hedgehog-genes-gli1-and-ptch1-a-comparative-study-in-nonmelanoma-skin-cancer-cell-lines
#2
Uffe H Olesen, Sophie Bojesen, Julie Gehl, Merete Haedersdal
Nonmelanoma skin cancer is the most common cancer in humans, comprising mainly basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC proliferation is highly dependent on the Hedgehog signaling pathway. We aimed to investigate a panel of anticancer drugs with known activity against skin cancer for their therapeutic potential in localized, enhanced topical treatment of SCC and BCC. Cytotoxicity profiles for vismodegib, 5-fluorouracil (5-FU), methotrexate (MTX), cisplatin, bleomycin, and vorinostat were established in terms of half maximal inhibitory concentration values in a panel of immortalized keratinocytes (HaCaT), BCC (UWBCC1 and BCC77015), and SCC (A431 and SCC25) cell lines...
August 9, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28799057/expression-patterns-of-key-sonic-hedgehog-signaling-pathway-components-in-the-developing-and-adult-mouse-midbrain-and-in-the-mn9d-cell-line
#3
Melanie Feuerstein, Enaam Chleilat, Shokoufeh Khakipoor, Konstantinos Michailidis, Christian Ophoven, Eleni Roussa
The temporal dynamic expression of Sonic Hedgehog (SHH) and signaling during early midbrain dopaminergic (mDA) neuron development is one of the key players in establishing mDA progenitor diversity. However, whether SHH signaling is also required during later developmental stages and in mature mDA neurons is less understood. We study the expression of SHH receptors Ptch1 and Gas1 (growth arrest-specific 1) and of the transcription factors Gli1, Gli2 and Gli3 in mouse midbrain during embryonic development [embryonic day (E) 12...
August 11, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28794318/dysregulated-expression-of-mitf-in-subsets-of-hepatocellular-carcinoma-and-cholangiocarcinoma
#4
Nattakarn Nooron, Koji Ohba, Kazuhisa Takeda, Shigeki Shibahara, Anchalee Chiabchalard
Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array...
August 2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28794157/suppressor-of-fused-restraint-of-hedgehog-activity-level-is-critical-for-osteogenic-proliferation-and-differentiation-during-calvarial-bone-development
#5
Jianying Li, Ying Cui, Jie Xu, Qihui Wang, Xueqin Yang, Yan Li, Xiaoyun Zhang, Mengsheng Qiu, Ze Zhang, Zunyi Zhang
Hedgehog signaling plays crucial roles in the development of calvarial bone, relying on the activation of Gli transcription factors. However, the molecular mechanism of the role of regulated Gli protein level in osteogenic specification of mesenchyme still remains elusive. Here, we show by conditionally inactivating Suppressor of Fused (Sufu), a critical repressor of Hedgehog signaling, in Wnt1-Cre mediated cranial neural crest (CNC), or Dermo1-Cre mediated mesodermal lineages, that Sufu restraint of Hedgehog activity level is critical for differentiation of pre-osteogenic mesenchyme...
August 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28768932/efficient-synthesis-of-heterocyclic-flavonoids-with-hedgehog-signal-inhibitory-activity
#6
Midori A Arai, Takao Utsumi, Natsuki Yanase, Teruhisa Fujimatsu, Masami Ishibashi
The hedgehog (Hh) signaling pathway performs important roles in embryonic development and cellular proliferation and differentiation. However, in many cancer cells Hh signaling is aberrantly activated, which has provided a strong impetus for the development of Hh pathway inhibitors. To address this, we synthesized a series of heterocyclic flavonoids and evaluated their Hh signaling inhibitory activity on cancer cell lines using our cell-based assay system. Of the synthetic flavonoids, compounds 4a and g showed good inhibitory activity (IC50 was 16...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28768710/yap-taz-deletion-in-gli-cell-derived-myofibroblasts-attenuates-fibrosis
#7
Ming Liang, Michael Yu, Ruohan Xia, Ke Song, Jun Wang, Jinlong Luo, Guang Chen, Jizhong Cheng
In damaged kidneys, increased extracellular matrix (ECM) and tissue stiffness stimulate kidney fibrosis through incompletely characterized molecular mechanisms. The transcriptional coactivators yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) function as mechanosensors in cancer cells and have been implicated in the regulation of myofibroblasts in the kidney. We hypothesized that the development of kidney fibrosis depends on Yap-induced activation and proliferation of kidney fibroblasts...
August 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28759046/ezh2-mediated-upregulation-of-ros1-oncogene-promotes-oral-cancer-metastasis
#8
C-H Shih, Y-J Chang, W-C Huang, T-H Jang, H-J Kung, W-C Wang, M-H Yang, M-C Lin, S-F Huang, S-W Chou, E Chang, H Chiu, T-Y Shieh, Y-J Chen, L-H Wang, L Chen
Current anti-epidermal growth factor receptor (EGFR) therapy for oral cancer does not provide satisfactory efficacy due to drug resistance or reduced EGFR level. As an alternative candidate target for therapy, here we identified an oncogene, ROS1, as an important driver for oral squamous cell carcinoma (OSCC) metastasis. Among tumors from 188 oral cancer patients, upregulated ROS1 expression strongly correlated with metastasis to lung and lymph nodes. Mechanistic studies uncover that the activated ROS1 results from highly expressed ROS1 gene instead of gene rearrangement, a phenomenon distinct from other cancers...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28754906/kras-activation-and-over-expression-of-sirt1-bcl6-contributes-to-the-pathogenesis-of-endometriosis-and-progesterone-resistance
#9
Jung-Yoon Yoo, Tae Hoon Kim, Asgerally T Fazleabas, Wilder A Palomino, Soo Hyun Ahn, Chandrakant Tayade, David P Schammel, Steven L Young, Jae-Wook Jeong, Bruce A Lessey
Endometriosis is an inflammatory condition that is associated with progesterone resistance and cell proliferation, resulting in pain, infertility and pregnancy loss. We previously demonstrated phosphorylation of STAT3 in eutopic endometrium of infertile women with this disorder leading to over-expression of the oncogene BCL6 and stabilization of hypoxia-induced factor 1 alpha (HIF-1α). Here we report coordinated activation of KRAS and over-expression of Sirtuin 1 (SIRT1), a histone deacetylase and gene silencer, in the eutopic endometrium from women with endometriosis throughout the menstrual cycle...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747628/the-anti-cancer-effects-of-itraconazole-in-epithelial-ovarian-cancer
#10
Chel Hun Choi, Ji-Yoon Ryu, Young-Jae Cho, Hye-Kyung Jeon, Jung-Joo Choi, Kris Ylaya, Yoo-Young Lee, Tae-Joong Kim, Joon-Yong Chung, Stephen M Hewitt, Byoung-Gie Kim, Duk-Soo Bae, Jeong-Won Lee
We assessed the anti-proliferative activity of itraconazole using an EOC cell line (SKOV3ip1) and endothelial cell lines (HUVEC & SVEC4-10). We also examined angiogenesis (VEGFR2, p-ERK, p-PLCr1/2), hedgehog (Gli1, Ptch1, SMO), and mTOR (pS6K1) signaling pathways to determine the mechanism of action of itraconazole. Furthermore, we evaluated the synergistic effects of itraconazole and paclitaxel using orthotopic mouse models with established EOC cells (SKOV3ip1 or HeyA8) as well as patient-derived xenografts (PDXs)...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747625/the-regulation-of-hh-gli1-signaling-cascade-involves-gsk3%C3%AE-mediated-mechanism-in-estrogen-derived-endometrial-hyperplasia
#11
Jyoti Bala Kaushal, Pushplata Sankhwar, Suparna Kumari, Pooja Popli, Vinay Shukla, Mohd Kamil Hussain, Kanchan Hajela, Anila Dwivedi
The present study was undertaken to explore the functional involvement of Hh signaling and its regulatory mechanism in endometrial hyperplasia. Differential expression of Hh signaling molecules i.e., Ihh, Shh, Gli1 or Gsk3β was observed in endometrial hyperplasial (EH) cells as compared to normal endometrial cells. Estradiol induced the expression of Hh signaling molecules and attenuated the expression of Gsk3β whereas anti-estrogen (K1) or progestin (MPA) suppressed these effects in EH cells. Cyclopamine treatment or Gli1 siRNA knockdown suppressed the growth of EH cells and reduced the expression of proliferative markers...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28744817/knockdown-of-prmt1-suppresses-il-1%C3%AE-induced-cartilage-degradation-and-inflammatory-responses-in-human-chondrocytes-through-gli1-mediated-hedgehog-signaling-pathway
#12
Lei Xia, Hong-Xing Zhang, Mei-Li Xing, Yu-Ben Xu, Peng Li, Liang-Ku Huang, Jie Bai, Zhao Tian, Zan-Dong Zhao
Osteoarthritis (OA) is characterized by articular cartilage degradation and joint inflammation. The purpose of the present study is to elucidate the role of the specific function of PRMT1 in chondrocytes and its association with the pathophysiology of OA. We observed that the expression of PRMT1 was apparently upregulated in OA cartilage, as well as in chondrocytes stimulated with IL-1β. Additionally, knockdown of PRMT1 suppressed interleukin 1 beta (IL-1β)-induced extracellular matrix (ECM) metabolic imbalance by regulating the expression of MMP-13, ADAMTS-5, COL2A1, and ACAN...
July 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28738329/distinct-involvement-of-the-sonic-hedgehog-signaling-pathway-in-gastric-adenocarcinoma-of-fundic-gland-type-and-conventional-gastric-adenocarcinoma
#13
Yuzuru Tajima, Takashi Murakami, Tsuyoshi Saito, Takafumi Hiromoto, Yoichi Akazawa, Noriko Sasahara, Hiroyuki Mitomi, Takashi Yao, Sumio Watanabe
BACKGROUND/AIMS: Gastric adenocarcinoma of fundic gland type (GAFG), which is a rare variant of gastric cancer, is reportedly associated with both Wnt/β-catenin signaling activation and guanine nucleotide binding protein, alpha stimulating complex (GNAS) mutations. This study aimed to elucidate potential roles of the Sonic hedgehog (Shh) signaling pathway in GAFG. METHODS: We performed immunostaining for β-catenin and Shh signal-associated proteins, including Patched (Ptch), Smoothened (Smo), and Glioma-associated oncogene-1 (Gli1), and the direct sequencing of GNAS/BRAF/KRAS in 27 GAFGs, and compared them with 30 conventional gastric adenocarcinomas (CGAs)...
July 22, 2017: Digestion
https://www.readbyqxmd.com/read/28735864/identification-of-a-dyrk1a-mediated-phosphorylation-site-within-the-nuclear-localization-sequence-of-the-hedgehog-transcription-factor-gli1
#14
Ben K Ehe, David R Lamson, Michael Tarpley, Rob U Onyenwoke, Lee M Graves, Kevin P Williams
GLI1 is a key downstream transcription effector of the Hedgehog (Hh) signaling pathway that is involved in promoting cell growth, differentiation and tissue patterning in embryonic development. GLI1 over-activation and its nuclear localization has also been linked to the increased aggressiveness of a number of cancers. It has previously been demonstrated that DYRK1A (dual-specificity tyrosine-regulated kinase 1A) can phosphorylate GLI1 and promote GLI1 nuclear localization and its transcriptional activity. Utilizing recombinant human GLI1 and DYRK1A proteins and phospho-peptide mass spectrometry, we demonstrated that GLI1 is phosphorylated by DYRK1A at Ser408, a phospho-site that falls within the putative nuclear localization sequence (NLS) of GLI1, suggesting a possible mechanistic role in modulating its translocation...
July 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28735299/identification-of-the-first-dominant-mutation-of-lama5-gene-causing-a-complex-multisystem-syndrome-due-to-dysfunction-of-the-extracellular-matrix
#15
Simone Sampaolo, Filomena Napolitano, Alfonsina Tirozzi, Mafalda Giovanna Reccia, Luca Lombardi, Olimpia Farina, Adriano Barra, Ferdinando Cirillo, Mariarosa Anna Beatrice Melone, Fernando Gianfrancesco, Giuseppe Di Iorio, Teresa Esposito
BACKGROUND: The laminin alpha 5 gene (LAMA5) plays a master role in the maintenance and function of the extracellular matrix (ECM) in mammalian tissues, which is critical in developmental patterning, stem cell niches, cancer and genetic diseases. Its mutations have never been reported in human disease so far. The aim of this study was to associate the first mutation in LAMA5 gene to a novel multisystem syndrome. METHODS: A detailed characterisation of a three-generation family, including clinical, biochemical, instrumental and morphological analysis, together with genetics and expression (WES and RNAseq) studies, was performed...
July 22, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28734986/exogenous-hedgehog-antagonist-delays-but-does-not-prevent-fracture-healing-in-young-mice
#16
Xiaochen Liu, Jennifer A McKenzie, Clayton W Maschhoff, Michael J Gardner, Matthew J Silva
Fracture healing recapitulates many aspects of developmental osteogenesis. The hedgehog (Hh) signaling pathway, essential to skeletal development, is upregulated during fracture healing, although its importance is unclear. Our goal was to assess the functional importance of Hh signaling in endochondral fracture healing. We created closed, transverse diaphyseal femur fractures in mice, stabilized with an intramedullary pin, and administered a systemic Hh inhibitor or vehicle. Because Hh pathway activation is mediated by the receptor Smoothened (Smo), we used the Smo antagonist GDC-0449 (GDC, 50mg/kg, twice daily) to target the pathway...
July 19, 2017: Bone
https://www.readbyqxmd.com/read/28731043/gastroblastoma-harbors-a-recurrent-somatic-malat1-gli1-fusion-gene
#17
Rondell P Graham, Asha A Nair, Jaime I Davila, Long Jin, Jin Jen, William R Sukov, Tsung-Teh Wu, Henry D Appelman, Jorge Torres-Mora, Kyle D Perry, Lizhi Zhang, Sara M Kloft-Nelson, Ryan A Knudson, Patricia T Greipp, Andrew L Folpe
Gastroblastoma is a rare distinctive biphasic tumor of the stomach. The molecular biology of gastroblastoma has not been studied, and no affirmative diagnostic markers have been developed. We retrieved two gastroblastomas from the consultation practices of the authors and performed transcriptome sequencing on formalin-fixed paraffin-embedded tissue. Recurrent predicted fusion genes were validated at genomic and RNA levels. The presence of the fusion gene was confirmed on two additional paraffin-embedded cases of gastroblastoma...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28726779/maml1-acts-cooperatively-with-gli-proteins-to-regulate-sonic-hedgehog-signaling-pathway
#18
Roberta Quaranta, Maria Pelullo, Sabrina Zema, Francesca Nardozza, Saula Checquolo, Dieter Matthias Lauer, Francesca Bufalieri, Rocco Palermo, Maria Pia Felli, Alessandra Vacca, Claudio Talora, Lucia Di Marcotullio, Isabella Screpanti, Diana Bellavia
Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule cell progenitors (GCPs) and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma. The effects of Shh pathway are mediated by the Gli family of transcription factors, which controls the expression of a number of target genes, including Gli1. Here, we identify Mastermind-like 1 (Maml1) as a novel regulator of the Shh signaling since it interacts with Gli proteins, working as a potent transcriptional coactivator...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28722677/prognostic-role-of-gli1-expression-in-breast-cancer-a-meta-analysis
#19
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...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28720477/nanoquinacrine-caused-apoptosis-in-oral-cancer-stem-cells-by-disrupting-the-interaction-between-gli1-and-%C3%AE-catenin-through-activation-of-gsk3%C3%AE
#20
Anmada Nayak, Sumit Siddharth, Sarita Das, Deepika Nayak, Chinmayee Sethy, Chanakya Nath Kundu
Presences of cancer stem cells (CSCs) in a bulk of cancer cells are responsible for tumor relapse, metastasis and drug resistance in oral cancer. Due to high drug efflux, DNA repair and self-renewable capacity of CSCs, the conventional chemotherapeutic agents are unable to kill the CSCs. CSCs utilizes Hedgehog (HH-GLI), WNT-β catenin signalling for its growth and development. GSK3β negatively regulates both the pathways in CSCs. Here, we have shown that a nano-formulated bioactive small molecule inhibitor Quinacrine (NQC) caused apoptosis in oral cancer stem cells (OCSCs; isolated from different oral cancer cells and oral cancer patient derived primary cells) by down regulating WNT-β catenin and HH-GLI components through activation of GSK3β...
September 1, 2017: Toxicology and Applied Pharmacology
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