Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2018-07-03
    Description: Adult stem cells maintain tissue homeostasis. This unique capability largely depends on the stem cell niche, a specialized microenvironment, which preserves stem cell identity through physical contacts and secreted factors. In many cancers, latent tumor cell niches are thought to house stem cells and aid tumor initiation. However, in developing tissue and cancer it is unclear how the niche is established. The well-characterized germline stem cells (GSCs) and niches in the Drosophila melanogaster ovary provide an excellent model to address this fundamental issue. As such, we conducted a small-scale RNAi screen of 560 individually expressed UAS-RNAi lines with targets implicated in female fertility. RNAi was expressed in the soma of larval gonads, and screening for reduced egg production and abnormal ovarian morphology was performed in adults. Twenty candidates that affect ovarian development were identified and subsequently knocked down in the soma only during niche formation. Feminization factors (Transformer, Sex lethal, and Virilizer), a histone methyltransferase (Enhancer of Zeste), a transcriptional machinery component (Enhancer of yellow 1), a chromatin remodeling complex member (Enhancer of yellow 3) and a chromosome passenger complex constituent (Incenp) were identified as potentially functioning in the control of niche size. The identification of these molecules highlights specific molecular events that are critical for niche formation and will provide a basis for future studies to fully understand the mechanisms of GSC recruitment and maintenance.
    Electronic ISSN: 2160-1836
    Topics: Biology
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2018-09-12
    Description: A major limitation of targeted cancer therapy is the rapid emergence of drug resistance, which often arises through mutations at or downstream of the drug target or through intrinsic resistance of subpopulations of tumor cells. Medulloblastoma (MB), the most common pediatric brain tumor, is no exception, and MBs that are driven by sonic hedgehog (SHH) signaling are particularly aggressive and drug-resistant. To find new drug targets and therapeutics for MB that may be less susceptible to common resistance mechanisms, we used a developmental phosphoproteomics approach in murine granule neuron precursors (GNPs), the developmental cell of origin of MB. The protein kinase CK2 emerged as a driver of hundreds of phosphorylation events during the proliferative, MB-like stage of GNP growth, including the phosphorylation of three of the eight proteins commonly amplified in MB. CK2 was critical to the stabilization and activity of the transcription factor GLI2, a late downstream effector in SHH signaling. CK2 inhibitors decreased the viability of primary SHH-type MB patient cells in culture and blocked the growth of murine MB tumors that were resistant to currently available Hh inhibitors, thereby extending the survival of tumor-bearing mice. Because of structural interactions, one CK2 inhibitor (CX-4945) inhibited both wild-type and mutant CK2, indicating that this drug may avoid at least one common mode of acquired resistance. These findings suggest that CK2 inhibitors may be effective for treating patients with MB and show how phosphoproteomics may be used to gain insight into developmental biology and pathology.
    Print ISSN: 1945-0877
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2018-08-17
    Description: Shuang Li, Yong Suk Cho, Bing Wang, Shuangxi Li, and Jin Jiang Hedgehog (Hh) transduces signals by promoting cell surface accumulation and activation of the G-protein-coupled receptor (GPCR)-family protein Smoothened (Smo) in Drosophila , but the molecular mechanism underlying the regulation of Smo trafficking remains poorly understood. Here, we identified the Cul4–DDB1 E3 ubiquitin ligase complex as being essential for Smo ubiquitylation and cell surface clearance. We found that the C-terminal intracellular domain of Smo recruits Cul4–DDB1 through the β subunit of trimeric G protein (Gβ), and that Cul4–DDB1–Gβ promotes the ubiquitylation of both Smo and its binding partner G-protein-coupled-receptor kinase 2 (Gprk2) and induces the internalization and degradation of Smo. Hh dissociates Cul4–DDB1 from Smo by recruiting the catalytic subunit of protein kinase A (PKA) to phosphorylate DDB1, which disrupts its interaction with Gβ. Inactivation of the Cul4–DDB1 complex resulted in elevated Smo cell surface expression, whereas an excessive amount of Cul4–DDB1 blocked Smo accumulation and attenuated Hh pathway activation. Taken together, our study identifies an E3 ubiquitin ligase complex targeting Smo for ubiquitylation and provides new insight into how Hh signaling regulates Smo trafficking and cell surface expression.
    Keywords: Ubiquitin
    Print ISSN: 0021-9533
    Electronic ISSN: 1477-9137
    Topics: Biology , Medicine
    Published by Company of Biologists
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2018-01-28
    Description: Introduction Thread embedding acupuncture (TEA) is a special type of acupuncture that inserts certain medical threads (eg, catgut or polydioxanone) into subcutaneous tissue or muscles at specific points. Although TEA has been widely used for the treatment of musculoskeletal pain in Korea, China and Taiwan, evidence regarding its efficacy is lacking. The aim of this protocol is to evaluate the effectiveness and safety of TEA in the treatment of musculoskeletal pain, by conducting a systematic review and meta-analysis. Methods and analysis The following 16 databases will be searched from their inception to 14 May 2017: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, three Chinese database (China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database and the Wanfang database) and eight Korean databases (Korean Medical Database, Korean Association of Medical Journal Editors, Korean Studies Information Service System, Korean National Assembly Digital Library, National Digital Science Library, Oriental Medicine Advanced Searching Integrated System, ’Database Periodical Information Academic and Korean Traditional Knowledge Portal'). The WHO International Clinical Trials Registry Platform will also be searched to retrieve the recently completed studies. All randomised controlled studies in which TEA was used on specific points for the treatment of musculoskeletal pain will be included and no restrictions on language will be applied. The risk of bias of each study will be evaluated by the Cochrane risk of bias tool. Mean difference or standardised mean difference for continuous data and risk ratio for dichotomous data will be calculated with 95% CIs using a random effects model or a fixed effects model. Additional subgroup and sensitivity analyses will be conducted according to a predefined protocol. Ethics and dissemination No ethical issues are predicted. The systematic review will be published in a peer-reviewed journal or conference presentation. These findings will summarise the current evidence of TEA for the treatment of musculoskeletal pain and may provide guidance for clinicians and patients to select TEA for musculoskeletal pain. PROSPERO registration number CRD42015019046.
    Keywords: Open access, Anaesthesia
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2018-03-06
    Description: High-grade glioma (HGG) is highly angiogenic, but antiangiogenic therapy has transient clinical benefit in only a fraction of patients. Vascular regulators of these heterogeneous responses remain undetermined. We found up-regulation of Sox7 and down-regulation of Sox17 in tumor endothelial cells (tECs) in mouse HGG. Sox7 deletion suppressed VEGFR2 expression, vascular abnormality, hypoxia-driven invasion, regulatory T cell infiltration, and tumor growth. Conversely, Sox17 deletion exacerbated these phenotypes by up-regulating Sox7 in tECs. Anti-VEGFR2 antibody treatment delayed tumor growth by normalizing Sox17 -deficient abnormal vessels with high Sox7 levels but promoted it by regressing Sox7 -deficient vessels, recapitulating variable therapeutic responses to antiangiogenic therapy in HGG patients. Our findings establish that Sox7 promotes tumor growth via vessel abnormalization, and its level determines the therapeutic outcome of VEGFR2 inhibition in HGG. In 189 HGG patients, Sox7 expression was heterogeneous in tumor vessels, and high Sox7 levels correlated with poor survival, early recurrence, and impaired vascular function, emphasizing the clinical relevance of Sox7 in HGG.
    Keywords: Solid Tumors
    Print ISSN: 0022-1007
    Electronic ISSN: 1540-9538
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2018-03-06
    Description: Background: Targeted delivery of therapeutic agent meets with hurdle of finding target ligand or receptor those are expressed tumor cells in homogenous patterns but not on normal cells. Apoptosis is an event that is programmed in all cells exposed to specific stimuli and this phenotypic event does not vary in patient to patient. In attempt to overcome limitations of conventional targeted therapy, radiation-induced apoptosis-targeted chemotherapy (RIATC) was suggested in our previous study. Caspase-3 cleavable docetaxel prodrug is treated following local administration of low dose radiation in tumor site which induces apoptosis. After initial activation of the prodrug, in-situ amplification of prodrug from expressed caspase-3 boost further activation of the prodrug.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...