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Long Chen, Yifeng Jiang, Zhen Du
Although previous studies have demonstrated that dental pulp stem cells (DPSCs) from mature and immature teeth exhibit potential for multi-directional differentiation, the molecular and biological difference between the DPSCs from mature and immature permanent teeth has not been fully investigated. In the present study, 500 differentially expressed genes from dental pulp cells (DPCs) in mature and immature permanent teeth were obtained from the Gene Expression Omnibus online database. Based on bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery, these genes were divided into a number of subgroups associated with immunity, inflammation and cell signaling...
April 2018: Experimental and Therapeutic Medicine
Weiwei Qian, Xiaochuan Kong, Tao Zhang, Dengdian Wang, Jin Song, Yuan Li, Xiaoting Li, Hao Geng, Jie Min, Qi Kong, Jie Liu, Zhiqi Liu, Daming Wang, Zhiqiang Zhang, Dexin Yu, Caiyun Zhong
Cancer stem cells (CSCs) are essentially responsible for tumor initiation, growth, progression, metastasis and recurrence, and cigarette smoke (CS) is closely involved in the occurrence and development of kidney cancer. However, the effect of CS on renal CSCs has not been elucidated yet. In the present study, tumorsphere formation assay was used to enrich renal CSCs from 786-O and ACHN cells. We illustrated that CS effectively promoted renal CSCs stemness by enhancing tumorsphere formation, increasing the expression of renal CSCs markers (CD133, CD44, ALDHA1, Oct4, and Nanog) and elevating CD133+ cell population...
March 13, 2018: Oncogenesis
Dario Presutti, Manuela Ceccarelli, Laura Micheli, Giuliana Papoff, Simonetta Santini, Simone Samperna, Cristiana Lalli, Lorena Zentilin, Giovina Ruberti, Felice Tirone
Medulloblastoma (MB), the tumor of the cerebellum, is the most frequent brain cancer in childhood and a major cause of pediatric mortality. Based on gene profiling, four MB subgroups have been identified, i.e., Wnt or Sonic Hedgehog (Shh) types, and subgroup 3 or 4. The Shh-type MB has been shown to arise from the cerebellar precursors of granule neurons (GCPs), where a hyperactivation of the Shh pathway leads to their neoplastic transformation. We have previously shown that the gene Tis21 (PC3/Btg2) inhibits the proliferation and promotes the differentiation and migration of GCPs...
2018: PloS One
Tomohiro Katagiri, Minoru Kobayashi, Michio Yoshimura, Akiyo Morinibu, Satoshi Itasaka, Masahiro Hiraoka, Hiroshi Harada
Hypoxic and stroma-rich microenvironments, characteristic features of pancreatic cancers, are strongly associated with a poor prognosis. However, whether and how hypoxia increases stromal compartments remain largely unknown. Here, we investigated the potential importance of a master regulator of the cellular adaptive response to hypoxia, hypoxia-inducible factor-1 (HIF-1), in the formation of stroma-rich microenvironments of pancreatic tumors. We found that pancreatic cancer cells secreted more Sonic hedgehog protein (SHH) under hypoxia by upregulating its expression and efficiency of secretion in a HIF-1-dependent manner...
February 13, 2018: Oncotarget
Xin Shi, Shengcai Wei, Kevin J Simms, Devan N Cumpston, Thomas J Ewing, Ping Zhang
Activation and reprogramming of hematopoietic stem/progenitor cells play a critical role in the granulopoietic response to bacterial infection. Our current study determined the significance of Sonic hedgehog (SHH) signaling in the regulation of hematopoietic precursor cell activity during the host defense response to systemic bacterial infection. Bacteremia was induced in male Balb/c mice via intravenous injection (i.v.) of Escherichia coli (5 × 107 CFUs/mouse). Control mice received i.v. saline. SHH protein level in bone marrow cell (BMC) lysates was markedly increased at both 24 and 48 h of bacteremia...
2018: Frontiers in Immunology
Kelsey H Elliott, Grethel Millington, Samantha A Brugmann
BACKGROUND: Submandibular glands (SMGs) are specialized epithelial structures which generate saliva necessary for mastication and digestion. Loss of SMGs can lead to inflammation, oral lesions, fungal infections, problems with chewing/swallowing, and tooth decay. Understanding the development of the SMG is important for developing therapeutic options for patients with impaired SMG function. Recent studies have suggested Sonic hedgehog (Shh) signaling in the epithelium plays an integral role in SMG development; however, the mechanism by which Shh influences gland development remains nebulous...
March 13, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
I-Li Tan, Alexandre Wojcinski, Harikrishna Rallapalli, Zhimin Lao, Reeti M Sanghrajka, Daniel Stephen, Eugenia Volkova, Andrey Korshunov, Marc Remke, Michael D Taylor, Daniel H Turnbull, Alexandra L Joyner
The main cell of origin of the Sonic hedgehog (SHH) subgroup of medulloblastoma (MB) is granule cell precursors (GCPs), a SHH-dependent transient amplifying population in the developing cerebellum. SHH-MBs can be further subdivided based on molecular and clinical parameters, as well as location because SHH-MBs occur preferentially in the lateral cerebellum (hemispheres). Our analysis of adult patient data suggests that tumors with Smoothened ( SMO ) mutations form more specifically in the hemispheres than those with Patched 1 ( PTCH1 ) mutations...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Karolina Nemes, Michael C Frühwald
Malignant Rhabdoid Tumor (MRT) is a rare and highly aggressive malignancy primarily affecting infants and young children. The most common anatomic locations are the central nervous system (AT/RT), the kidneys (RTK) and other soft tissues (eMRT). The genetic origin of this disease is linked to mutations in SMARCB1, a gene encoding a core subunit of the SWI/SNF chromatin-remodeling complex. Areas covered: Conventional multimodal treatment may offer a significant survival benefit to certain patients. It remains to be determined, however, which patients will prove resistant to chemotherapy and need novel therapeutic approaches...
March 12, 2018: Expert Opinion on Therapeutic Targets
Felipe de Oliveira, José Alberto Landeiro, Igor de Castro
Background: Medulloblastoma is an embryonal neoplasm and accounts for 1% of all adult intracranial tumors. It is associated with many familiar cancer syndromes, but there is no known cause for medulloblastoma. Many studies have documented differences between childhood and adult medulloblastomas in terms of location, proliferation, and apoptotic indices. There are four histological groups - classic and the variant forms (desmoplastic/nodular, anaplasic, and large cell). There are four major subgroups according to molecular configuration: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4 with differences between them according to prognostic outcomes...
2018: Surgical Neurology International
Li Yang, Qing-Hua Zou, Yan Zhang, Yin Shi, Chun-Rong Hu, Cai-Xia Hui, Xiao-Fei Liu, Yong-Fei Fang
Rheumatoid arthritis (RA) patients may suffer from comorbid neuropsychiatric symptoms including mild cognitive impairment (MCI). Although comorbidity of MCI is common, there are currently no validated plasma biomarkers to aid MCI diagnosis. This study screened plasma from patients with RA with and without comorbid MCI to identify potential biomarkers useful in the differential diagnosis of comorbid MCI. Plasma samples were collected from patients with RA without comorbid MCI, with comorbid MCI, and from healthy controls...
March 10, 2018: Clinical Rheumatology
Miki Iwasaki, Junpei Kuroda, Koichi Kawakami, Hironori Wada
Bone is a connective tissue composed of many cell types, including osteoblasts. How bones acquire their unique size and shape during development remains poorly understood. Herein we investigated the molecular and cellular mechanisms of bone morphogenesis in the zebrafish scale by using transgenic lines to enable visualization of specific types of osteoblasts. We demonstrate that the zebrafish scale contains three distinct types of osteoblasts: (i) a monolayer of central osteoblasts along the inner surface of scales; (ii) marginal osteoblasts elongated along the scale edge; and (iii) submarginal osteoblasts located between the central and marginal osteoblast populations...
March 7, 2018: Developmental Biology
Marie-Amélie Farreny, Eric Agius, Sophie Bel-Vialar, Nathalie Escalas, Nagham Khouri-Farah, Chadi Soukkarieh, Cathy Danesin, Fabienne Pituello, Philippe Cochard, Cathy Soula
BACKGROUND: Most oligodendrocytes of the spinal cord originate from ventral progenitor cells of the pMN domain, characterized by expression of the transcription factor Olig2. A minority of oligodendrocytes is also recognized to emerge from dorsal progenitors during fetal development. The prevailing view is that generation of ventral oligodendrocytes depends on Sonic hedgehog (Shh) while dorsal oligodendrocytes develop under the influence of Fibroblast Growth Factors (FGFs). RESULTS: Using the well-established model of the chicken embryo, we show that ventral spinal progenitor cells activate FGF signaling at the onset of oligodendrocyte precursor cell (OPC) generation...
March 8, 2018: Neural Development
Carolyn M Dancevic, Yann Gibert, Joachim Berger, Adam D Smith, Clifford Liongue, Nicole Stupka, Alister C Ward, Daniel R McCulloch
The ADAMTS5 metzincin, a secreted zinc-dependent metalloproteinase, modulates the extracellular matrix (ECM) during limb morphogenesis and other developmental processes. Here, the role of ADAMTS5 was investigated by knockdown of zebrafish adamts5 during embryogenesis. This revealed impaired Sonic Hedgehog (Shh) signaling during somite patterning and early myogenesis. Notably, synergistic regulation of myod expression by ADAMTS5 and Shh during somite differentiation was observed. These roles were not dependent upon the catalytic activity of ADAMTS5...
March 7, 2018: International Journal of Molecular Sciences
Gregorio J Petrirena, Julien Masliah-Planchon, Quentin Sala, Bertrand Pourroy, Didier Frappaz, Emeline Tabouret, Thomas Graillon, Jean-Claude Gentet, Olivier Delattre, Olivier Chinot, Laetitia Padovani
Background: Response to targeting and non-targeting agents is variable and molecular information remains poorly described in patients with recurrent sonic-hedgehog-driven medulloblastoma (SHH-MB). Materials and Methods: Clinical and PET/CT findings during treatment with successive hedgehog antagonists and temozolomide monotherapies are described in a heavily pre-treated patient with recurrent extraneural metastases from PTCH1 mutated/ wild type smoothened ( SMO ) CNS SHH-MB...
February 9, 2018: Oncotarget
Mahmoud Hashemi Tabar, Mohammad Reza Tabandeh, Eskandar Moghimipour, Dian Dayer, Ata A Ghadiri, Elham Allah Bakhshi, Mahmoud Orazizadeh, Mohammad Ali Ghafari
Pancreatic and duodenal homeobox 1 (Pdx1) and Sonic hedgehog (Shh) are the key regulators of beta-cell function. In vitro experiments have shown that there is significant cooperation between Pdx1 and Shh with regard to the production and maintenance of insulin-producing cells (IPCs). In this study, the combined effect of Pdx1 overexpression and Shh manipulation on the function of adipose tissue-derived IPCs was determined. A eukaryotic expression vector ( Pdx1- pCDNA3.1(+)) was constructed and transfected into a Chinese hamster ovary (CHO) cell line...
March 2018: FEBS Open Bio
Gang Chen, Ming Yan, Rong Rong Li, Wan Tao Chen
OBJECTIVE: To investigate the Sonic Hedgehog (SHH) signalling molecules and activated leukocyte cell adhesion molecule (ALCAM) expression in the mechanisms regulating invasion and metastasis in oral squamous cell carcinoma (OSCC). METHODS: The expressions of SHH signalling molecules Gli family zinc finger 1/2 (Gli1/Gli2), as well as ALCAM expression, was analysed in 101 OSCC patients by immunohistochemistry. The potential relationship between Gli1/Gli2 and ALCAM in regard to invasion and metastasis were studied by western blot, invasion and wound-healing assays...
2018: Chinese Journal of Dental Research
Chiachen Chen, Mary B Breslin, Michael S Lan
Neuroendocrine (NE) lung tumors account for 20% of total lung cancer cases and represent a subset of aggressive tumors with metastatic potential. High-risk NE lung cancer patients display disseminated disease, N-myc expression/amplification, and poorly differentiated tumors. In this study, we investigate the molecular mechanisms underlying a zinc-finger transcription factor, INSM1 in NE lung cancer. Our study revealed that INSM1 crosstalk with the Shh-PI3K/AKT-N-myc/Ascl1-MEK/ERK1/2 transcriptional network in NE lung cancer...
March 1, 2018: Cellular Signalling
Xiuqin Ye, Wei Hong, Binwei Hao, Gongyong Peng, Lingmei Huang, Zhuxiang Zhao, Yumin Zhou, Mengning Zheng, Chenglong Li, Chunxiao Liang, Erkang Yi, Jinding Pu, Bing Li, Pixin Ran
BACKGROUND: The contribution of airway remodeling in chronic obstructive pulmonary disease (COPD) has been well documented, with airway smooth muscle cell proliferation and migration playing a role in the remodeling process. Here, we aimed to verify the effects of fine particulate matter (PM2.5) on human bronchial smooth muscle cell (HBSMC) migration and to explore the underlying signaling pathways. METHODS: HBSMC apoptosis, proliferation and migration were measured using flow cytometry, cell counting and transwell migration assays, respectively...
March 2, 2018: Respiratory Research
Sivan Gershanov, Helen Toledano, Shalom Michowiz, Orit Barinfeld, Albert Pinhasov, Nitza Goldenberg-Cohen, Mali Salmon-Divon
Purpose: Medulloblastoma (MB), the most common malignant brain tumor in children, is divided into four tumor subgroups: wingless-type (WNT), sonic hedgehog (SHH), Group 3, and Group 4. Ideally, clinical practice and treatment design should be subgroup specific. While WNT and SHH subgroups have well-defined biomarkers, distinguishing Group 3 from Group 4 is not straightforward. MicroRNAs (miRNAs), which regulate posttranscriptional gene expression, are involved in MB tumorigenesis. However, the miRNA-messenger RNA (mRNA) regulatory network in MB is far from being fully understood...
2018: Cancer Management and Research
Ammad Ahmad Farooqi, Sumbul Khalid, Aamir Ahmad
Genomic and proteomic studies have helped improve our understanding of the underlying mechanism(s) of cancer development and progression. Mutations, overexpressed oncogenes, inactivated/downregulated tumor suppressors, loss of apoptosis, and dysregulated signal transduction cascades are some of the well-studied areas of research. Resveratrol has gained considerable attention in the last two decades because of its pleiotropic anticancer activities. In this review, we have summarized the regulation of WNT, SHH (sonic hedgehog)/GLI (glioma-associated oncogene homolog), TGFβ1 (transforming growth factor beta 1)/SMAD, NOTCH, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), STAT (signal transducer and activator of transcription), and microRNAs by resveratrol in different cancers...
February 26, 2018: International Journal of Molecular Sciences
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