LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 23

Search options

  1. Article ; Online: Differential Diagnosis of the Swollen Red Eyelid.

    Carlisle, Robert Thomas / Digiovanni, John

    American family physician

    2015  Volume 92, Issue 2, Page(s) 106–112

    Abstract: The swollen red eyelid is a common presentation in primary care. An understanding of the anatomy of the orbital region can guide care. Factors that guide diagnosis and urgency of care include acute vs. subacute onset of symptoms, presence or absence of ... ...

    Abstract The swollen red eyelid is a common presentation in primary care. An understanding of the anatomy of the orbital region can guide care. Factors that guide diagnosis and urgency of care include acute vs. subacute onset of symptoms, presence or absence of pain, identifiable mass within the eyelid vs. diffuse lid swelling, and identification of vision change or ophthalmoplegia. Superficial skin processes presenting with swollen red eyelid include vesicles of herpes zoster ophthalmicus; erythematous irritation of contact dermatitis; raised, dry plaques of atopic dermatitis; and skin changes of malignancies, such as basal or squamous cell carcinoma. A well-defined mass at the lid margin is often a hordeolum or stye. A mass within the midportion of the lid is commonly a chalazion. Preseptal and orbital cellulitis are important to identify, treat, and differentiate from each other. Orbital cellulitis is more often marked by changes in ability of extraocular movements and vision as opposed to preseptal cellulitis where these characteristics are classically normal. Less commonly, autoimmune processes of the orbit or ocular tumors with mass effect can create an initial impression of a swollen eyelid.
    MeSH term(s) Diagnosis, Differential ; Edema/etiology ; Eyelid Diseases/complications ; Eyelid Diseases/diagnosis ; Eyelids/anatomy & histology ; Eyelids/pathology ; Humans
    Language English
    Publishing date 2015-07-15
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 412694-4
    ISSN 1532-0650 ; 0002-838X ; 0572-3612
    ISSN (online) 1532-0650
    ISSN 0002-838X ; 0572-3612
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.B 848: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article: Role of stat3 in skin carcinogenesis: insights gained from relevant mouse models.

    Macias, Everardo / Rao, Dharanija / Digiovanni, John

    Journal of skin cancer

    2013  Volume 2013, Page(s) 684050

    Abstract: Signal transducer and activator of transcription 3 (Stat3) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat3 plays critical roles in various biological activities including ... ...

    Abstract Signal transducer and activator of transcription 3 (Stat3) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat3 plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat3-deficient mice have revealed that Stat3 plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat3-deficient mouse models has demonstrated that Stat3 is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat3 (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat3 in skin tumor progression. Studies using similar Stat3-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat3 in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat3 is an attractive target for skin cancer prevention and treatment.
    Language English
    Publishing date 2013-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2581531-3
    ISSN 2090-2913 ; 2090-2905
    ISSN (online) 2090-2913
    ISSN 2090-2905
    DOI 10.1155/2013/684050
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Attenuation of psoriasis-like skin lesion in a mouse model by topical treatment with indirubin and its derivative E804.

    Miyoshi, Ken / Takaishi, Mikiro / Digiovanni, John / Sano, Shigetoshi

    Journal of dermatological science

    2011  Volume 65, Issue 1, Page(s) 70–72

    MeSH term(s) Animals ; Breast Neoplasms/metabolism ; Cell Proliferation ; Female ; Humans ; Indoles/pharmacology ; Indoles/therapeutic use ; Keratinocytes/cytology ; Male ; Mice ; Prostatic Neoplasms/metabolism ; Psoriasis/drug therapy ; Sequence Analysis, DNA ; Signal Transduction ; Skin/drug effects ; Up-Regulation
    Chemical Substances Indirubin E804 ; Indoles ; indirubin (V86L8P74GI)
    Language English
    Publishing date 2011-10-08
    Publishing country Netherlands
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 1024446-3
    ISSN 1873-569X ; 0923-1811
    ISSN (online) 1873-569X
    ISSN 0923-1811
    DOI 10.1016/j.jdermsci.2011.10.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2870: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Protein tyrosine phosphatases, TC-PTP, SHP1, and SHP2, cooperate in rapid dephosphorylation of Stat3 in keratinocytes following UVB irradiation.

    Kim, Dae Joon / Tremblay, Michel L / Digiovanni, John

    PloS one

    2010  Volume 5, Issue 4, Page(s) e10290

    Abstract: Stat3 is initially dephosphorylated in murine keratinocytes in response to UVB irradiation. Treatment with Na(3)VO(4) desensitized keratinocytes to UVB-induced apoptosis with the recovery of phosphorylated Stat3 protein levels, implying that a protein ... ...

    Abstract Stat3 is initially dephosphorylated in murine keratinocytes in response to UVB irradiation. Treatment with Na(3)VO(4) desensitized keratinocytes to UVB-induced apoptosis with the recovery of phosphorylated Stat3 protein levels, implying that a protein tyrosine phosphatase (PTP) is involved in this mechanism. In the current work, we report that three PTPs including TC45 (the nuclear form of TC-PTP), SHP1, and SHP2 are involved in this rapid dephosphorylation of Stat3 in keratinocytes induced by UVB irradiation. Dephosphorylation of Stat3 was increased rapidly after UVB irradiation of cultured keratinocytes. Knockdown of TC-PTP, SHP1, or SHP2 using RNAi showed that these PTPs are likely responsible for most of the rapid Stat3 dephosphorylation observed following UVB irradiation. The level of phosphorylated Stat3 was significantly higher in keratinocytes transfected with TC-PTP, SHP1, or SHP2 siRNA in the presence or absence of UVB compared with keratinocytes transfected with control siRNA. TC45 was mainly localized in the cytoplasm of keratinocytes and translocated from cytoplasm to nucleus upon UVB irradiation. Stat3 dephosphorylation was associated with nuclear translocation of TC45. Further studies revealed that knockdown of all three phosphatases, using RNAi, prevented the rapid dephosphorylation of Stat3 following UVB irradiation. In mouse epidermis, the level of phosphorylated Stat3 was initially decreased, followed by a significant increase at later time points after UVB exposure. The levels of Stat3 target genes, such as cyclin D1 and c-Myc, followed the changes in activated Stat3 in response to UVB irradiation. Collectively, these results suggest that three phosphatases, TC45, SHP1, and SHP2, are primarily responsible for UVB-mediated Stat3 dephosphorylation and may serve as part of an initial protective mechanism against UV skin carcinogenesis.
    MeSH term(s) Animals ; Apoptosis/radiation effects ; Cells, Cultured ; Keratinocytes/metabolism ; Keratinocytes/radiation effects ; Mice ; Phosphorylation/radiation effects ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/physiology ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/radiation effects ; Protein Tyrosine Phosphatase, Non-Receptor Type 2/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 2/physiology ; Protein Tyrosine Phosphatase, Non-Receptor Type 2/radiation effects ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/physiology ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/radiation effects ; Protein Tyrosine Phosphatases, Non-Receptor/genetics ; Protein Tyrosine Phosphatases, Non-Receptor/physiology ; Protein Tyrosine Phosphatases, Non-Receptor/radiation effects ; RNA, Small Interfering/pharmacology ; STAT3 Transcription Factor/metabolism ; STAT3 Transcription Factor/radiation effects ; Ultraviolet Rays/adverse effects
    Chemical Substances RNA, Small Interfering ; STAT3 Transcription Factor ; Stat3 protein, mouse ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48) ; Protein Tyrosine Phosphatase, Non-Receptor Type 2 (EC 3.1.3.48) ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 (EC 3.1.3.48) ; Protein Tyrosine Phosphatases, Non-Receptor (EC 3.1.3.48) ; Ptpn11 protein, mouse (EC 3.1.3.48) ; Ptpn2 protein, mouse (EC 3.1.3.48) ; Ptpn6 protein, mouse (EC 3.1.3.48)
    Language English
    Publishing date 2010-04-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0010290
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Growth factor signaling pathways as targets for prevention of epithelial carcinogenesis.

    Rho, Okkyung / Kim, Dae Joon / Kiguchi, Karou / Digiovanni, John

    Molecular carcinogenesis

    2010  Volume 50, Issue 4, Page(s) 264–279

    Abstract: Growth factor receptor (GFR) signaling controls epithelial cell growth by responding to various endogenous or exogenous stimuli and subsequently activating downstream signaling pathways including Stat3, PI3K/Akt/mTOR, MAPK, and c-Src. Environmental ... ...

    Abstract Growth factor receptor (GFR) signaling controls epithelial cell growth by responding to various endogenous or exogenous stimuli and subsequently activating downstream signaling pathways including Stat3, PI3K/Akt/mTOR, MAPK, and c-Src. Environmental chemical toxicants and UVB irradiation cause enhanced and prolonged activation of GFR signaling and downstream pathways that contributes to epithelial cancer development including skin cancer. Recent studies, especially those with tissue-specific transgenic mouse models, have demonstrated that GFRs and their downstream signaling pathways contribute to all three stages of epithelial carcinogenesis by regulating a wide variety of biological functions including proliferation, apoptosis, angiogenesis, cell adhesion, and migration. Inhibiting these signaling pathways early in the carcinogenic process results in reduced cell proliferation and survival, leading to decreased tumor formation. Collectively, these studies suggest that GFR signaling and subsequent downstream signaling pathways are potential targets for the prevention of epithelial cancers including skin cancer.
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/drug effects ; Cell Transformation, Neoplastic/metabolism ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Humans ; Models, Biological ; Receptor, IGF Type 1/metabolism ; Receptors, Growth Factor/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology
    Chemical Substances Antineoplastic Agents ; Receptors, Growth Factor ; Receptor, IGF Type 1 (EC 2.7.10.1)
    Language English
    Publishing date 2010-07-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1004029-8
    ISSN 1098-2744 ; 0899-1987
    ISSN (online) 1098-2744
    ISSN 0899-1987
    DOI 10.1002/mc.20665
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2664: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Imiquimod attenuates the growth of UVB-induced SCC in mice through Th1/Th17 cells.

    Yokogawa, Maki / Takaishi, Mikiro / Nakajima, Kimiko / Kamijima, Reiko / Digiovanni, John / Sano, Shigetoshi

    Molecular carcinogenesis

    2012  Volume 52, Issue 10, Page(s) 760–769

    Abstract: Imiquimod (IMQ), a Toll-like receptor (TLR) 7/8 agonist, has been used to treat various skin neoplasms, including genital warts, actinic keratoses, and superficial basal cell carcinomas. Although IMQ has been recognized to activate both innate and ... ...

    Abstract Imiquimod (IMQ), a Toll-like receptor (TLR) 7/8 agonist, has been used to treat various skin neoplasms, including genital warts, actinic keratoses, and superficial basal cell carcinomas. Although IMQ has been recognized to activate both innate and adaptive immunity, the underlying mechanism(s) by which IMQ exerts its anti-tumor activity in vivo remains largely unknown. In this study, we took advantage of skin cancer-prone mice to characterize the effects of IMQ on ultraviolet irradiation (UV)-induced de novo carcinogenesis. Transgenic mice with keratinocytes expressing constitutively activated Stat3 (K5.Stat3C mice) developed squamous cell carcinomas (SCC in situ) as early as after 14 wk of UVB irradiation, while wild-type mice required much higher doses of UVB with more than 25 wk of UVB irradiation to produce SCC. Topical treatment of K5.Stat3C mice with IMQ attenuated UVB-induced epidermal dysplasia (SCC in situ). In addition, SCC growth due to increased total irradiation doses was significantly attenuated by IMQ treatment. Topical IMQ treatment induced T cell and plasmacytoid dendritic cell infiltrates at the tumor sites, where levels of IL-12/23p40, IL-12p35, IL-23p19, IL-17A, and IFN-γ mRNAs were up-regulated. Immunohistochemistry revealed T cell infiltrates consisting of T1, Th17, and CD8(+) T cells. We speculate that topical IMQ treatment attenuates the de novo growth of UVB-induced SCC through activation of Th17/Th1 cells and cytotoxic T lymphocytes.
    MeSH term(s) Administration, Topical ; Aminoquinolines/administration & dosage ; Aminoquinolines/pharmacology ; Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacology ; Blotting, Western ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/pathology ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/etiology ; Carcinoma, Squamous Cell/pathology ; Cell Transformation, Neoplastic/drug effects ; Cell Transformation, Neoplastic/pathology ; Cytokines/genetics ; Cytokines/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Dendritic Cells/pathology ; Epidermis/immunology ; Epidermis/metabolism ; Epidermis/pathology ; Imiquimod ; Immunoenzyme Techniques ; Keratinocytes/drug effects ; Keratinocytes/immunology ; Keratinocytes/metabolism ; Mice ; Mice, Transgenic ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; STAT3 Transcription Factor/physiology ; Skin Neoplasms/drug therapy ; Skin Neoplasms/etiology ; Skin Neoplasms/pathology ; Th1 Cells/drug effects ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Th17 Cells/drug effects ; Th17 Cells/immunology ; Th17 Cells/metabolism ; Ultraviolet Rays/adverse effects
    Chemical Substances Aminoquinolines ; Antineoplastic Agents ; Cytokines ; RNA, Messenger ; STAT3 Transcription Factor ; Imiquimod (P1QW714R7M)
    Language English
    Publishing date 2012-03-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1004029-8
    ISSN 1098-2744 ; 0899-1987
    ISSN (online) 1098-2744
    ISSN 0899-1987
    DOI 10.1002/mc.21901
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2664: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Silencing of ribonucleotide reductase subunit M1 potentiates the antitumor activity of gemcitabine in resistant cancer cells.

    Wonganan, Piyanuch / Chung, Woon-Gye / Zhu, Saijie / Kiguchi, Kaoru / Digiovanni, John / Cui, Zhengrong

    Cancer biology & therapy

    2012  Volume 13, Issue 10, Page(s) 908–914

    Abstract: Gemcitabine is a deoxycytidine analog used for the treatment of a wide range of solid tumors. Its efficacy is however often reduced due to the development of resistance. Ribonucleotide reductase M1 subunit (RRM1) is a key determinant of gemcitabine ... ...

    Abstract Gemcitabine is a deoxycytidine analog used for the treatment of a wide range of solid tumors. Its efficacy is however often reduced due to the development of resistance. Ribonucleotide reductase M1 subunit (RRM1) is a key determinant of gemcitabine resistance, and tumor cells that overexpress RRM1 are resistant to the cytotoxicity of gemcitabine. In the present study, we showed that RRM1-specific small interfering RNA (siRNA), when complexed with polyethylenimine, effectively downregulated the expression of RRM1 protein in mouse tumor cells that overexpress RRM1, both in vitro and in vivo. More importantly, systemic administration of the RRM1-specific siRNA significantly inhibited the growth of RRM1-overexpressing tumors in mice and sensitized the tumors to gemcitabine treatment. These findings suggest that silencing RRM1 expression using siRNA could potentially be an effective strategy to overcome gemcitabine resistance.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Mice ; Neoplasms/genetics ; Neoplasms/metabolism ; RNA Interference ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Ribonucleoside Diphosphate Reductase ; Tumor Suppressor Proteins/genetics
    Chemical Substances Antineoplastic Agents ; RNA, Small Interfering ; Tumor Suppressor Proteins ; Deoxycytidine (0W860991D6) ; gemcitabine (B76N6SBZ8R) ; RRM1 protein, human (EC 1.17.4.1) ; Ribonucleoside Diphosphate Reductase (EC 1.17.4.1)
    Language English
    Publishing date 2012-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2146305-0
    ISSN 1555-8576 ; 1538-4047
    ISSN (online) 1555-8576
    ISSN 1538-4047
    DOI 10.4161/cbt.20843
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5887: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article: Signal transducer and activator of transcription 3 (Stat3) in epithelial carcinogenesis.

    Kim, Dae Joon / Chan, Keith S / Sano, Shigetoshi / Digiovanni, John

    Molecular carcinogenesis

    2007  Volume 46, Issue 8, Page(s) 725–731

    Abstract: Signal transducer and activator of transcription 3 (Stat3) is one of a family of cytoplasmic proteins that participate in normal cellular responses to cytokines and growth factors as transcription factors. Stat3 modulates various physiological functions ... ...

    Abstract Signal transducer and activator of transcription 3 (Stat3) is one of a family of cytoplasmic proteins that participate in normal cellular responses to cytokines and growth factors as transcription factors. Stat3 modulates various physiological functions including cell survival, cell-cycle regulation, and angiogenesis through regulation of gene expression, and its constitutive activation is associated with a number of human epithelial cancers. Recent studies with skin-specific gain and loss of Stat3 function transgenic mice have shown that Stat3 plays critical roles in skin carcinogenesis. Multistage skin carcinogenesis bioassays performed with these transgenic mice clearly demonstrate that Stat3 is required for both tumor initiation and promotion through regulation of genes involved in survival and proliferation, respectively. Stat3 also plays a role in malignant progression of skin tumors by regulating genes that are involved in angiogenesis and invasion. Further studies have revealed that Stat3 plays a critical role in epidermal cell proliferation and survival following exposure to ultraviolet B (UVB) irradiation. In addition, Stat3 is constitutively active in UVB-induced skin tumors from both mice and humans. Collectively, these studies suggest that Stat3 may be a potential target for both the prevention and treatment of human epithelial cancers including skin cancer.
    MeSH term(s) Animals ; Cell Transformation, Neoplastic ; Epidermis/drug effects ; Epidermis/metabolism ; Epidermis/pathology ; Humans ; Neoplasms, Glandular and Epithelial/etiology ; Neoplasms, Glandular and Epithelial/metabolism ; Neoplasms, Radiation-Induced/etiology ; Neoplasms, Radiation-Induced/metabolism ; STAT3 Transcription Factor/metabolism ; Skin Neoplasms/etiology ; Skin Neoplasms/metabolism ; Ultraviolet Rays
    Chemical Substances STAT3 Transcription Factor
    Language English
    Publishing date 2007-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1004029-8
    ISSN 1098-2744 ; 0899-1987
    ISSN (online) 1098-2744
    ISSN 0899-1987
    DOI 10.1002/mc.20342
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2664: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article: Activation of epidermal akt by diverse mouse skin tumor promoters.

    Lu, Jerry / Rho, Okkyung / Wilker, Erik / Beltran, Linda / Digiovanni, John

    Molecular cancer research : MCR

    2007  Volume 5, Issue 12, Page(s) 1342–1352

    Abstract: Akt is a serine/threonine kinase involved in a variety of cellular responses, including cell proliferation and cell survival. Recent studies from our laboratory suggest that Akt signaling may play an important role in skin tumor promotion. To explore ... ...

    Abstract Akt is a serine/threonine kinase involved in a variety of cellular responses, including cell proliferation and cell survival. Recent studies from our laboratory suggest that Akt signaling may play an important role in skin tumor promotion. To explore this premise, we examined epidermal Akt activation and signaling in response to chemically diverse skin tumor promoters. Mice received single or multiple applications of 12-O-tetradecanoylphorbol-13-acetate (TPA), okadaic acid, or chrysarobin. All three tumor promoters were able to activate epidermal Akt as early as 1 h after treatment. Activation of Akt following tumor promoter treatment led to enhanced downstream signaling, including hyperphosphorylation of glycogen synthase kinase-3beta and Bad. Structure activity studies with phorbol ester analogues revealed that the magnitude of activation paralleled tumor-promoting activity. In cultured primary keratinocytes, TPA treatment also led to activation of Akt. Activation of the epidermal growth factor receptor (EGFR) seemed to underlie the ability of TPA to activate Akt as both PD153035, an inhibitor of EGFR, and GW2974, a dual-specific inhibitor of both EGFR and erbB2, were able to effectively reduce TPA-induced Akt phosphorylation as well as TPA-stimulated EGFR and erbB2 tyrosine phosphorylation in a dose-dependent manner. Furthermore, inhibition of protein kinase C (PKC) activity blocked TPA-stimulated heparin-binding EGF production and EGFR transactivation. Inhibition of PKC also led to a decreased association of Akt with the PP2A catalytic subunit, leading to increased Akt phosphorylation. However, combination of EGFR inhibitor and PKC inhibitor completely abrogated TPA-induced activation of Akt. Collectively, the current results support the hypothesis that elevated Akt activity and subsequent activation of downstream signaling pathways contribute significantly to skin tumor promotion. In addition, signaling through the EGFR via EGFR homodimers or EGFR/erbB2 heterodimers may be the primary event leading to Akt activation during tumor promotion in mouse skin.
    MeSH term(s) Animals ; Anthracenes/pharmacology ; Anticoagulants/metabolism ; Anticoagulants/pharmacology ; Carcinogens/pharmacology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Enzyme Activation/drug effects ; Enzyme Inhibitors/pharmacology ; Epidermis/drug effects ; Epidermis/enzymology ; Epidermis/pathology ; Female ; Heparin/metabolism ; Heparin/pharmacology ; Indoles/pharmacology ; Keratinocytes/drug effects ; Keratinocytes/enzymology ; Keratinocytes/pathology ; Maleimides/pharmacology ; Mice ; Mice, Inbred ICR ; Okadaic Acid/pharmacology ; Phosphorylation/drug effects ; Protein Kinase C/antagonists & inhibitors ; Protein Kinase C/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Receptor, Epidermal Growth Factor/metabolism ; Skin Neoplasms/chemically induced ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology ; Tetradecanoylphorbol Acetate/pharmacology
    Chemical Substances Anthracenes ; Anticoagulants ; Carcinogens ; Enzyme Inhibitors ; Indoles ; Maleimides ; Okadaic Acid (1W21G5Q4N2) ; chrysarobin (6307EF51M1) ; Heparin (9005-49-6) ; Receptor, Epidermal Growth Factor (EC 2.7.10.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Protein Kinase C (EC 2.7.11.13) ; bisindolylmaleimide I (L79H6N0V6C) ; Tetradecanoylphorbol Acetate (NI40JAQ945)
    Language English
    Publishing date 2007-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2098788-2
    ISSN 1557-3125 ; 1541-7786
    ISSN (online) 1557-3125
    ISSN 1541-7786
    DOI 10.1158/1541-7786.MCR-07-0115
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5744: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: Cathepsin K is involved in development of psoriasis-like skin lesions through TLR-dependent Th17 activation.

    Hirai, Toshitake / Kanda, Takashi / Sato, Kenji / Takaishi, Mikiro / Nakajima, Kimiko / Yamamoto, Mayuko / Kamijima, Reiko / Digiovanni, John / Sano, Shigetoshi

    Journal of immunology (Baltimore, Md. : 1950)

    2013  Volume 190, Issue 9, Page(s) 4805–4811

    Abstract: Cathepsins (CTSs) are lysosomal cysteine proteases that play an important role in the turnover of intracellular proteins and extracellular proteins, such as the degradation of extracellular matrices and the processing of antigenic proteins. A CTS ... ...

    Abstract Cathepsins (CTSs) are lysosomal cysteine proteases that play an important role in the turnover of intracellular proteins and extracellular proteins, such as the degradation of extracellular matrices and the processing of antigenic proteins. A CTS inhibitor, NC-2300, not only suppresses bone erosion by inhibition of cathepsin K (CTSK), but also ameliorates paw swelling at inflamed joints in adjuvant-induced arthritis in rats. It has been demonstrated that the amelioration of joint inflammation by NC-2300 is mediated by the downregulation of cytokine expression in dendritic cells, which are essential for Th17 activation. In this work, we studied the role for CTSs in the pathogenesis of psoriasis-like lesion in K5.Stat3C mice, a mouse model of psoriasis, in which Th17 contributes to lesion development similar to psoriasis. Psoriatic lesions expressed increased levels of Ctsk and Ctss mRNA compared with uninvolved skin and normal control skin. Similarly, the epidermis and dermis in K5.Stat3C mice demonstrated increased CTSK activities, which were sensitive to NC-2300. Topical treatment with NC-2300 significantly ameliorated 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like lesions in K5.Stat3C mice, and downregulated the expression of IL-12, IL-23, and Th17 cytokines. In vitro experiments revealed that TLR7 activation of bone marrow-derived myeloid dendritic cells led to increase in IL-23 at mRNA and protein levels, which were downregulated by NC-2300. These results suggest that CTSK plays a role in development of psoriatic lesions through TLR7-dependent Th17 polarization.
    MeSH term(s) Animals ; Bone Marrow/immunology ; Bone Marrow/metabolism ; Bone Marrow/pathology ; Cathepsin K/genetics ; Cathepsin K/immunology ; Cathepsin K/metabolism ; Dermis/enzymology ; Dermis/immunology ; Dermis/pathology ; Down-Regulation ; Epidermis/enzymology ; Epidermis/immunology ; Epidermis/pathology ; Female ; Humans ; Interleukin-12/genetics ; Interleukin-12/immunology ; Interleukin-12/metabolism ; Interleukin-23/genetics ; Interleukin-23/immunology ; Interleukin-23/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Myeloid Cells/pathology ; Psoriasis/enzymology ; Psoriasis/genetics ; Psoriasis/immunology ; Psoriasis/pathology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Th17 Cells/enzymology ; Th17 Cells/immunology ; Th17 Cells/pathology ; Toll-Like Receptor 7/genetics ; Toll-Like Receptor 7/immunology ; Toll-Like Receptor 7/metabolism ; Toll-Like Receptor 8/genetics ; Toll-Like Receptor 8/immunology ; Toll-Like Receptor 8/metabolism
    Chemical Substances Interleukin-23 ; RNA, Messenger ; Toll-Like Receptor 7 ; Toll-Like Receptor 8 ; Interleukin-12 (187348-17-0) ; Cathepsin K (EC 3.4.22.38)
    Language English
    Publishing date 2013-05-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1200901
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.37: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 28: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top