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  1. Artikel ; Online: Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB

    Soh, Hendrick / Venkatesan, Natarajan / Veena, Mysore S. / Ravichandran, Sandhiya / Zinabadi, Alborz / Basak, Saroj K. / Parvatiyar, Kislay / Srivastava, Meera / Liang, Li-Jung / Gjertson, David W. / Torres, Jorge Z. / Moatamed, Neda A. / Srivatsan, Eri S.

    Molecular and Cellular Biology. 2016 June 1, v. 36, no. 12 p.1776-1792

    2016  

    Abstract: We and others have shown that the cystatin E/M gene is inactivated in primary human tumors, pointing to its role as a tumor suppressor gene. However, the molecular mechanism of tumor suppression is not yet understood. Using plasmid-directed cystatin E/M ... ...

    Abstract We and others have shown that the cystatin E/M gene is inactivated in primary human tumors, pointing to its role as a tumor suppressor gene. However, the molecular mechanism of tumor suppression is not yet understood. Using plasmid-directed cystatin E/M gene overexpression, a lentivirus-mediated tetracycline-inducible vector system, and human papillomavirus 16 (HPV 16) E6 and E7 gene-immortalized normal human epidermal keratinocytes, we demonstrated intracellular and non-cell-autonomous apoptotic growth inhibition of tumor cell lines and that growth inhibition is associated with cytoplasmic retention of NF-κB. We further demonstrated decreased phosphorylation of IκB kinase (IKKβ) and IκBα in the presence of tumor necrosis factor alpha (TNF-α), confirming the role of cystatin E/M in the regulation of the NF-κB signaling pathway. Growth suppression of nude mouse xenograft tumors carrying a tetracycline-inducible vector system was observed with the addition of doxycycline in drinking water, confirming that the cystatin E/M gene is a tumor suppressor gene. Finally, immunohistochemical analyses of cervical carcinoma in situ and primary tumors have shown a statistically significant inverse relationship between the expression of cystatin E/M and cathepsin L and a direct relationship between the loss of cystatin E/M expression and nuclear expression of NF-κB. We therefore propose that the cystatin E/M suppressor gene plays an important role in the regulation of NF-κB.
    Schlagwörter Human papillomavirus type 16 ; apoptosis ; cathepsin L ; cell growth ; doxycycline ; gene overexpression ; growth retardation ; humans ; immunohistochemistry ; keratinocytes ; mice ; neoplasm cells ; phosphorylation ; suppressor genes ; tumor necrosis factor-alpha ; tumor suppressor genes ; uterine cervical neoplasms ; xenotransplantation
    Sprache Englisch
    Erscheinungsverlauf 2016-0601
    Umfang p. 1776-1792.
    Erscheinungsort Taylor & Francis
    Dokumenttyp Artikel ; Online
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.00878-15
    Datenquelle NAL Katalog (AGRICOLA)

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  2. Artikel ; Online: Reply to v.R. Bhatt et Al and m.C. Chamberlain.

    Welsh, James W / McGovern, Susan L / Wefel, Jeffrey S / Komaki, Ritsuko / Brown, Paul D / Soh, Hendrick E

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2013  Band 31, Heft 25, Seite(n) 3165–3166

    Mesh-Begriff(e) Antineoplastic Agents/therapeutic use ; Brain Neoplasms/secondary ; Brain Neoplasms/therapy ; Carcinoma, Non-Small-Cell Lung/secondary ; Carcinoma, Non-Small-Cell Lung/therapy ; Cranial Irradiation ; Female ; Humans ; Lung Neoplasms/pathology ; Male ; Mutation ; Quinazolines/therapeutic use ; Receptor, Epidermal Growth Factor/antagonists & inhibitors ; Receptor, Epidermal Growth Factor/genetics
    Chemische Substanzen Antineoplastic Agents ; Quinazolines ; Receptor, Epidermal Growth Factor (EC 2.7.10.1)
    Sprache Englisch
    Erscheinungsdatum 2013-09-01
    Erscheinungsland United States
    Dokumenttyp Comment ; Letter
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.2013.50.7160
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB.

    Soh, Hendrick / Venkatesan, Natarajan / Veena, Mysore S / Ravichandran, Sandhiya / Zinabadi, Alborz / Basak, Saroj K / Parvatiyar, Kislay / Srivastava, Meera / Liang, Li-Jung / Gjertson, David W / Torres, Jorge Z / Moatamed, Neda A / Srivatsan, Eri S

    Molecular and cellular biology

    2016  Band 36, Heft 12, Seite(n) 1776–1792

    Abstract: We and others have shown that the cystatin E/M gene is inactivated in primary human tumors, pointing to its role as a tumor suppressor gene. However, the molecular mechanism of tumor suppression is not yet understood. Using plasmid-directed cystatin E/M ... ...

    Abstract We and others have shown that the cystatin E/M gene is inactivated in primary human tumors, pointing to its role as a tumor suppressor gene. However, the molecular mechanism of tumor suppression is not yet understood. Using plasmid-directed cystatin E/M gene overexpression, a lentivirus-mediated tetracycline-inducible vector system, and human papillomavirus 16 (HPV 16) E6 and E7 gene-immortalized normal human epidermal keratinocytes, we demonstrated intracellular and non-cell-autonomous apoptotic growth inhibition of tumor cell lines and that growth inhibition is associated with cytoplasmic retention of NF-κB. We further demonstrated decreased phosphorylation of IκB kinase (IKKβ) and IκBα in the presence of tumor necrosis factor alpha (TNF-α), confirming the role of cystatin E/M in the regulation of the NF-κB signaling pathway. Growth suppression of nude mouse xenograft tumors carrying a tetracycline-inducible vector system was observed with the addition of doxycycline in drinking water, confirming that the cystatin E/M gene is a tumor suppressor gene. Finally, immunohistochemical analyses of cervical carcinoma in situ and primary tumors have shown a statistically significant inverse relationship between the expression of cystatin E/M and cathepsin L and a direct relationship between the loss of cystatin E/M expression and nuclear expression of NF-κB. We therefore propose that the cystatin E/M suppressor gene plays an important role in the regulation of NF-κB.
    Mesh-Begriff(e) Animals ; Cathepsin L/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cystatin M/genetics ; Cystatin M/metabolism ; Cytoplasm/metabolism ; Doxycycline/administration & dosage ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Vectors/pharmacology ; HeLa Cells ; Humans ; I-kappa B Proteins/metabolism ; Lentivirus/genetics ; Mice ; Mice, Nude ; NF-kappa B/metabolism ; Neoplasm Transplantation ; Phosphorylation ; Signal Transduction ; Tumor Necrosis Factor-alpha/metabolism ; Uterine Cervical Neoplasms/genetics ; Uterine Cervical Neoplasms/metabolism ; Uterine Cervical Neoplasms/pathology
    Chemische Substanzen CST6 protein, human ; Cystatin M ; I-kappa B Proteins ; NF-kappa B ; TNF protein, human ; Tumor Necrosis Factor-alpha ; CTSL protein, human (EC 3.4.22.15) ; Cathepsin L (EC 3.4.22.15) ; Doxycycline (N12000U13O)
    Sprache Englisch
    Erscheinungsdatum 2016-05-31
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.00878-15
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1666: Hefte anzeigen Standort:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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  4. Artikel ; Online: Combining radiation and immunotherapy: a new systemic therapy for solid tumors?

    Tang, Chad / Wang, Xiaohong / Soh, Hendrick / Seyedin, Steven / Cortez, Maria Angelica / Krishnan, Sunil / Massarelli, Erminia / Hong, David / Naing, Aung / Diab, Adi / Gomez, Daniel / Ye, Huiping / Heymach, John / Komaki, Ristuko / Allison, James P / Sharma, Padmanee / Welsh, James W

    Cancer immunology research

    2014  Band 2, Heft 9, Seite(n) 831–838

    Abstract: With the recent success of checkpoint inhibitors and other immunomodulating agents, there has been renewed interest in the combination of such agents with radiation. The biologic premise behind such a strategy is that the tumor-antigen release achieved ... ...

    Abstract With the recent success of checkpoint inhibitors and other immunomodulating agents, there has been renewed interest in the combination of such agents with radiation. The biologic premise behind such a strategy is that the tumor-antigen release achieved by localized radiation will promote specific tumor targeting by the adaptive immune system, which can be augmented further by systemic immune-stimulating agents. In this manner, clinicians hope to induce a phenomenon known as the abscopal effect, whereby localized radiation results in immune-mediated tumor regression in disease sites well outside of the radiation field. Herein, we present a comprehensive overview of the early clinical and preclinical evidence behind this approach.
    Mesh-Begriff(e) Animals ; Antigens, Neoplasm/immunology ; Combined Modality Therapy ; Humans ; Immune System ; Immunotherapy/methods ; Mice ; Neoplasms/therapy ; Radiotherapy
    Chemische Substanzen Antigens, Neoplasm
    Sprache Englisch
    Erscheinungsdatum 2014-09-03
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-14-0069
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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