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  • 1
    Online Resource
    Online Resource
    Rockefeller University Press ; 2015
    In:  Journal of Cell Biology Vol. 211, No. 2 ( 2015-10-26), p. 469-484
    In: Journal of Cell Biology, Rockefeller University Press, Vol. 211, No. 2 ( 2015-10-26), p. 469-484
    Abstract: Stem cell niches provide localized signaling molecules to promote stem cell fate and to suppress differentiation. The Drosophila melanogaster ovarian niche is established by several types of stromal cells, including terminal filament cells, cap cells, and escort cells (ECs). Here, we show that, in addition to its well-known function as a niche factor expressed in cap cells, the Drosophila transforming growth factor β molecule Decapentaplegic (Dpp) is expressed at a low level in ECs to maintain a pool of partially differentiated germline cells that may dedifferentiate to replenish germline stem cells upon their depletion under normal and stress conditions. Our study further reveals that the Dpp level in ECs is modulated by Hedgehog (Hh) ligands, which originate from both cap cells and ECs. We also demonstrate that Hh signaling exerts its function by suppressing Janus kinase/signal transducer activity, which promotes Dpp expression in ECs. Collectively, our data suggest a complex interplay of niche-associated signals that controls the development of a stem cell lineage.
    Type of Medium: Online Resource
    ISSN: 0021-9525 , 1540-8140
    RVK:
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 2015
    detail.hit.zdb_id: 1421310-2
    SSG: 12
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  • 2
    In: Developmental Biology, Elsevier BV, Vol. 276, No. 1 ( 2004-12), p. 89-100
    Type of Medium: Online Resource
    ISSN: 0012-1606
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2004
    detail.hit.zdb_id: 1463203-2
    SSG: 12
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  • 3
    In: Cell, Elsevier BV, Vol. 108, No. 6 ( 2002-03), p. 837-847
    Type of Medium: Online Resource
    ISSN: 0092-8674
    RVK:
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2002
    detail.hit.zdb_id: 187009-9
    detail.hit.zdb_id: 2001951-8
    SSG: 12
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  • 4
    In: Cancers, MDPI AG, Vol. 13, No. 17 ( 2021-09-06), p. 4486-
    Abstract: Metastasis is the main cause of mortality in breast cancer patients. There is an unmet need to develop therapies that can impede metastatic spread. Precision oncology has shown great promise for the treatment of cancers, as the therapeutic approach is tailored to a specific group of patients who are likely to benefit from the treatment, rather than the traditional approach of “one size fits all”. CD82, also known as KAI1, a glycoprotein belonging to the tetraspanin family and an established metastasis suppressor, could potentially be exploited to hinder metastases in breast cancer. This review explores the prospect of targeting CD82 as an innovative therapeutic approach in precision medicine for breast cancer patients, with the goal of preventing cancer progression and metastasis. Such an approach would entail the selection of a subset of breast cancer patients with low levels of CD82, and instituting an appropriate treatment scheme tailored towards restoring the levels of CD82 in this group of patients. Proposed precision treatment regimens include current modalities of treating breast cancer, in combination with either clinically approved drugs that could restore the levels of CD82, CD82 peptide mimics or non-coding RNA-based therapeutics.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 5
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 7, No. 9 ( 2008-09-01), p. 2672-2680
    Abstract: Inappropriate activation of JAK/STAT signaling occurs with high frequency in human cancers and is associated with cancer cell survival and proliferation. Therefore, the development of pharmacologic STAT signaling inhibitors has therapeutic potential in the treatment of human cancers. Here, we report 2-[(3,5-bis-trifluoromethyl-phenyl)-hydroxy-methyl]-1-(4-nitro-phenylamino)-6-phenyl-1,2,4a,7a-tetrahydro-pyrrolo[3,4-b] -pyridine-5,7-dione (AUH-6-96) as a novel small-molecule inhibitor of JAK/STAT signaling that we initially identified through a cell-based high-throughput screening using cultured Drosophila cells. Treatment of Drosophila cells with AUH-6-96 resulted in a reduction of Unpaired-induced transcriptional activity and tyrosine phosphorylation of STAT92E, the sole Drosophila STAT homologue. In human cancer cell lines, AUH-6-96 inhibited both constitutive and interleukin-6-induced STAT3 phosphorylation. Specifically, in Hodgkin lymphoma L540 cells, treatment with AUH-6-96 resulted in reduced levels of tyrosine phosphorylated STAT3 and of the STAT3 downstream target gene SOCS3 in a dose- and time-dependent manner. In addition, AUH-6-96-treated L540 cells showed decreased expression of persistently activated JAK3, suggesting that AUH-6-96 inhibits the JAK/STAT pathway signaling in L540 cells by affecting JAK3 activity and subsequently blocking STAT3 signaling. Importantly, AUH-6-96 selectively affected cell viability only of cancer cells harboring aberrant JAK/STAT signaling. In support of the specificity of AUH-6-96 for inhibition of JAK/STAT signaling, treatment with AUH-6-96 decreased cancer cell survival by inducing programmed cell death by down-regulating the expression of STAT3 downstream target antiapoptotic genes, such as Bcl-xL. In summary, this study shows that AUH-6-96 is a novel small-molecule inhibitor of JAK/STAT signaling and may have therapeutic potential in the treatment of human cancers harboring aberrant JAK/STAT signaling. [Mol Cancer Ther 2008;7(9):2672–80]
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 6
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 24, No. 13 ( 2020-07), p. 7427-7438
    Abstract: Gain‐ or loss‐of‐function mutations in Janus kinase 3 (JAK3) contribute to the pathogenesis of various haematopoietic malignancies and immune disorders, suggesting that aberrant JAK3 signalling is an attractive therapeutic target to treat these disorders. In this study, we performed structure‐based computational database screening using the 3D structure of the JAK3 kinase domain and the National Cancer Institute diversity set and identified tubulosine as a novel JAK3 inhibitor. Tubulosine directly blocked the catalytic activity of JAK3 by selective interacting with the JAK3 kinase domain. Consistently, tubulosine potently inhibited persistently activated and interleukin‐2‐dependent JAK3, and JAK3‐mediated downstream targets. Importantly, it did not affect the activity of other JAK family members, particularly prolactin‐induced JAK2/signal transducer and activator of transcription 5 and interferon alpha‐induced JAK1‐TYK2/STAT1. Tubulosine specifically decreased survival and proliferation of cancer cells, in which persistently active JAK3 is expressed, by inducing apoptotic and necrotic/autophagic cell death without affecting other oncogenic signalling. Collectively, tubulosine is a potential small‐molecule compound that selectively inhibits JAK3 activity, suggesting that it may serve as a promising therapeutic candidate for treating disorders caused by aberrant activation of JAK3 signalling.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2076114-4
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  • 7
    Online Resource
    Online Resource
    Bentham Science Publishers Ltd. ; 2018
    In:  Current Medicinal Chemistry Vol. 25, No. 12 ( 2018-04-19), p. 1409-1419
    In: Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 25, No. 12 ( 2018-04-19), p. 1409-1419
    Abstract: As nanomaterials possess attractive physicochemical properties, immense research efforts have been channeled towards their development for biological and biomedical applications. In particular, zinc nanomaterials (nZnOs) have shown great potential for use in in the medical and pharmaceutical fields, and as tools for novel antimicrobial treatment, thereby capitalizing on their unique antimicrobial effects. Methods: We conducted a literature search using databases to retrieve the relevant articles related to the synthesis, properties and current applications of nZnOs in the diagnosis and treatment of diseases. A total of 86 publications were selected for inclusion in this review. Results: Besides studies on the properties and the methodology for the synthesis of nZnOs, many studies have focused on the application of nZnOs as delivery agents, biosensors and antimicrobial agents, as well as in bioimaging. Conclusion: This review gives an overview of the current development of nZnOs for their potential use as theranostic agents. However, more comprehensive studies are needed to better assess the valuable contributions and the safety of nZnOs in nanomedicine.
    Type of Medium: Online Resource
    ISSN: 0929-8673
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2018
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    Bentham Science Publishers Ltd. ; 2021
    In:  Current Medicinal Chemistry Vol. 28, No. 25 ( 2021-08-16), p. 5137-5151
    In: Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 28, No. 25 ( 2021-08-16), p. 5137-5151
    Abstract: Breast cancer is the most common malignant tumor in women worldwide. Traditional ways of treatment, including radiotherapy and endocrine therapy, for breast cancer have inevitable side effects. In recent decades, targeted therapies for breast cancer have rapidly advanced and shown a promising future. The JAK/STAT signaling pathway has been shown to play important roles in tumorigenesis, maintenance and metastasis of breast cancer. Hence, many small molecule inhibitors of JAK and STAT proteins have been developed. These inhibitors exhibit potent inhibitory effects on breast cancer in both cellular and animal models, and even some of them have already been in clinical trials. This review article discussed the JAK/STAT signal transduction pathway in the pathogenesis of breast cancer, and the potential for the application of JAK/STAT inhibitors in breast cancer treatment.
    Type of Medium: Online Resource
    ISSN: 0929-8673
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2021
    SSG: 15,3
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  • 9
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 47-47
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 47-47
    Abstract: Gastric cancer still ranks among the top ten most common cancer in the world, despite a declining trend in incidence. The multifunctional protein Y Box Binding Protein-1 (YB-1) is known to regulate transcription, translation, DNA repair and cellular response to drug treatment. This study evaluated the correlation between YB-1 protein expression levels with clinico-pathological characteristics in the intestinal type of gastric cancer, which was further validated with in vitro experimentation. Tissue microarrays (TMAs) were constructed from specimens obtained from 167 patients diagnosed with intestinal gastric cancer. Immunohistochemical analysis of the YB-1 protein was performed on the TMAs . The intensity of YB-1 staining in the intestinal type of gastric cancer was scored as absent to strong staining and the percentage of YB-1 immunostained cells was determined. YB-1 immunoreactivity was based on the weighted average intensity (WAI) for each specimen, which was calculated as the sum of percentages of stained cells for each intensity divided by the total percentage of stained cells. siRNA-mediated silencing of the YB-1 gene in MKN7 intestinal gastric cancer cells was verified by RT-PCR. Cell migration and invasion assays were carried out using commercially available kits. YB-1 immunostaining was present in all the cancer tissue samples examined. The YB-1 protein was observed to be predominantly expressed in the cytoplasm of the gastric cancer cells. Univariate analysis revealed that YB-1 immunohistochemical expression was significantly correlated with lymph node status and perforation. However, multivariate analysis showed that only YB-1 protein expression is an independent predictor of lymph node spread. Down-regulation of the YB-1 gene expression in MKN7 cells significantly inhibited cell migration and invasion, processes which are important in the metastatic cascade. The findings suggest that YB-1 expression is associated with metastasis in the intestinal type of gastric cancer and is a potential prognostic biomarker and therapeutic target in this subtype of gastric cancer. Citation Format: TianTian Guo, Yingnan Yu, George Wai-Cheong Yip, Gyeong Hun Baeg, Aye Aye Thike, Puay-Hoon Tan, Ken Matsumoto, Boon Huat Bay. Y-box binding protein 1 is correlated with lymph node metastasis in intestinal type of gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 47. doi:10.1158/1538-7445.AM2014-47
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 10
    Online Resource
    Online Resource
    Elsevier BV ; 2018
    In:  Redox Biology Vol. 15 ( 2018-05), p. 125-134
    In: Redox Biology, Elsevier BV, Vol. 15 ( 2018-05), p. 125-134
    Type of Medium: Online Resource
    ISSN: 2213-2317
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2701011-9
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