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  1. Article ; Online: Exploring the Interactions of Oncolytic Viral Therapy and Immunotherapy of Anti-CTLA-4 for Malignant Melanoma Mice Model.

    Yu, Jui-Ling / Jang, Sophia R-J / Liu, Kwei-Yan

    Cells

    2023  Volume 12, Issue 3

    Abstract: Oncolytic ability to direct target and lyse tumor cells makes oncolytic virus therapy (OVT) a promising approach to treating cancer. Despite its therapeutic potential to stimulate anti-tumor immune responses, it also has immunosuppressive effects. The ... ...

    Abstract Oncolytic ability to direct target and lyse tumor cells makes oncolytic virus therapy (OVT) a promising approach to treating cancer. Despite its therapeutic potential to stimulate anti-tumor immune responses, it also has immunosuppressive effects. The efficacy of OVTs as monotherapies can be enhanced by appropriate adjuvant therapy such as anti-CTLA-4. In this paper, we propose a mathematical model to explore the interactions of combined therapy of oncolytic viruses and a checkpoint inhibitor, anti-CTLA-4. The model incorporates both the susceptible and infected tumor populations, natural killer cell population, virus population, tumor-specific immune populations, virus-specific immune populations, tumor suppressive cytokine IFN-g, and the effect of immune checkpoint inhibitor CTLA-4. In particular, we distinguish the tumor-specific immune abilities of CD8
    MeSH term(s) Animals ; Mice ; Cytokines ; Disease Models, Animal ; Immunotherapy/methods ; Melanoma/therapy ; Oncolytic Virotherapy/methods ; Melanoma, Cutaneous Malignant
    Chemical Substances Cytokines ; Ctla4 protein, mouse
    Language English
    Publishing date 2023-02-03
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12030507
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Modification of Epigenetic Histone Acetylation in Hepatocellular Carcinoma.

    Liu, Kwei-Yan / Wang, Li-Ting / Hsu, Shih-Hsien

    Cancers

    2018  Volume 10, Issue 1

    Abstract: Cells respond to various environmental factors such as nutrients, food intake, and drugs or toxins by undergoing dynamic epigenetic changes. An imbalance in dynamic epigenetic changes is one of the major causes of disease, oncogenic activities, and ... ...

    Abstract Cells respond to various environmental factors such as nutrients, food intake, and drugs or toxins by undergoing dynamic epigenetic changes. An imbalance in dynamic epigenetic changes is one of the major causes of disease, oncogenic activities, and immunosuppressive effects. The aryl hydrocarbon receptor (AHR) is a unique cellular chemical sensor present in most organs, and its dysregulation has been demonstrated in multiple stages of tumor progression in humans and experimental models; however, the effects of the pathogenic mechanisms of AHR on epigenetic regulation remain unclear. Apart from proto-oncogene activation, epigenetic repressions of tumor suppressor genes are involved in tumor initiation, procession, and metastasis. Reverse epigenetic repression of the tumor suppressor genes by epigenetic enzyme activity inhibition and epigenetic enzyme level manipulation is a potential path for tumor therapy. Current evidence and our recent work on deacetylation of histones on tumor-suppressive genes suggest that histone deacetylase (HDAC) is involved in tumor formation and progression, and treating hepatocellular carcinoma with HDAC inhibitors can, at least partially, repress tumor proliferation and transformation by recusing the expression of tumor-suppressive genes such as
    Language English
    Publishing date 2018-01-03
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers10010008
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  3. Article: Homeobox Genes and Hepatocellular Carcinoma.

    Liu, Kwei-Yan / Wang, Li-Ting / Hsu, Shih-Hsien / Wang, Shen-Nien

    Cancers

    2019  Volume 11, Issue 5

    Abstract: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer, and is the third leading cause of cancer-related deaths each year. It involves a multi-step progression and is strongly associated with chronic inflammation induced by the intake of ... ...

    Abstract Hepatocellular carcinoma (HCC) is the sixth most common type of cancer, and is the third leading cause of cancer-related deaths each year. It involves a multi-step progression and is strongly associated with chronic inflammation induced by the intake of environmental toxins and/or viral infections (i.e., hepatitis B and C viruses). Although several genetic dysregulations are considered to be involved in disease progression, the detailed regulatory mechanisms are not well defined. Homeobox genes that encode transcription factors with homeodomains control cell growth, differentiation, and morphogenesis in embryonic development. Recently, more aberrant expressions of Homeobox genes were found in a wide variety of human cancer, including HCC. In this review, we summarize the currently available evidence related to the role of Homeobox genes in the development of HCC. The objective is to determine the roles of this conserved transcription factor family and its potential use as a therapeutic target in future investigations.
    Language English
    Publishing date 2019-05-03
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers11050621
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Multidimensional Analysis of Lung Lymph Nodes in a Mouse Model of Allergic Lung Inflammation following

    Liu, Kwei-Yan / Gao, Yajing / Xiao, Wenfeng / Fu, Jinrong / Huang, Saihua / Han, Xiao / Hsu, Shih-Hsien / Xiao, Xiaojun / Huang, Shau-Ku / Zhou, Yufeng

    Environmental health perspectives

    2023  Volume 131, Issue 3, Page(s) 37014

    Abstract: Background: Ambient particulate matter with an aerodynamic diameter of : Objectives: We aimed to explore the impact of environmental : Methods: PM: Results: Mice exposed to : Discussion: These findings suggest that ... ...

    Abstract Background: Ambient particulate matter with an aerodynamic diameter of
    Objectives: We aimed to explore the impact of environmental
    Methods: PM
    Results: Mice exposed to
    Discussion: These findings suggest that the
    MeSH term(s) Mice ; Animals ; Interleukin-4 ; Lung/pathology ; Hypersensitivity/genetics ; Hypersensitivity/pathology ; Disease Models, Animal ; Pneumonia/chemically induced ; Allergens/toxicity ; Lymph Nodes/pathology ; Pyroglyphidae ; Pyrenes
    Chemical Substances Interleukin-4 (207137-56-2) ; Allergens ; Pyrenes
    Language English
    Publishing date 2023-03-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195189-0
    ISSN 1552-9924 ; 0091-6765 ; 1078-0475
    ISSN (online) 1552-9924
    ISSN 0091-6765 ; 1078-0475
    DOI 10.1289/EHP11580
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 1360: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 379: Show issues

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  5. Article ; Online: Phosphorylation of intestine-specific homeobox by ERK1 modulates oncogenic activity and sorafenib resistance.

    Wang, Li-Ting / Liu, Kwei-Yan / Chiou, Shyh-Shin / Huang, Shau-Ku / Hsu, Shih-Hsien / Wang, Shen-Nien

    Cancer letters

    2021  Volume 520, Page(s) 160–171

    Abstract: Nuclear translocation regulated by phosphorylation is a key step in providing activated mitogen-activated protein kinases (MAPKs) access to their nuclear targets; however, the mechanisms linking MAPK-induced nuclear translocation and target gene ... ...

    Abstract Nuclear translocation regulated by phosphorylation is a key step in providing activated mitogen-activated protein kinases (MAPKs) access to their nuclear targets; however, the mechanisms linking MAPK-induced nuclear translocation and target gene expression mediating oncologic activity remain obscure. Here, we show that the MAPK extracellular signal-regulated kinase (ERK) 1, but not ERK2, phosphorylated intestine-specific homeobox (ISX), leading to its nuclear translocation and downstream oncogenic signaling. Mechanistically, ERK1 phosphorylated serine 183 of ISX, facilitating its nuclear translocation and downstream target gene expression. In contrast, dominant-negative ERK1 expression in hepatoma cells inhibited the nuclear translocation of ISX and the expression of downstream genes involved in cell proliferation, malignant transformation, and epithelial-mesenchymal transition in vitro and in vivo. An activating mutation in ISX (S183D) exhibited a constitutive nuclear localization and resistance to sorafenib. Additionally, in 576 paired clinical hepatocellular carcinoma (HCC) samples and adjacent normal tissues, ERK1 and ISX were co-expressed in a tumor-specific manner at mRNA and protein levels, while their mRNA levels showed significant correlation with survival duration, tumor size, number, and stage. These results highlight the significance of ERK1/ISX signaling in HCC progression and its potential as a prognostic and therapeutic target in HCC.
    MeSH term(s) Animals ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm/drug effects ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Homeodomain Proteins/genetics ; Humans ; Intestines/metabolism ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Male ; Mice ; Mitogen-Activated Protein Kinase 3/genetics ; Phosphorylation ; Signal Transduction/drug effects ; Sorafenib/pharmacology ; Transcription Factors/genetics
    Chemical Substances Homeodomain Proteins ; Isx protein, human ; Transcription Factors ; Sorafenib (9ZOQ3TZI87) ; MAPK3 protein, human (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24)
    Language English
    Publishing date 2021-07-12
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2021.07.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1177: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Aryl hydrocarbon receptor promotes lipid droplet biogenesis and metabolic shift in respiratory Club cells.

    Wang, Hsueh-Chun / Liu, Kwei-Yan / Wang, Li-Ting / Hsu, Shih-Hsien / Wang, Shao-Chun / Huang, Shau-Ku

    Human cell

    2021  Volume 34, Issue 3, Page(s) 785–799

    Abstract: Club cells are critical in maintaining airway integrity via, in part, secretion of immunomodulatory Club cell 10 kd protein (CC10) and xenobiotic detoxification. Aryl hydrocarbon receptor (AhR) is important in xenobiotic metabolism, but its role in Club ... ...

    Abstract Club cells are critical in maintaining airway integrity via, in part, secretion of immunomodulatory Club cell 10 kd protein (CC10) and xenobiotic detoxification. Aryl hydrocarbon receptor (AhR) is important in xenobiotic metabolism, but its role in Club cell function is unclear. To this end, an AhR ligand, 6-formylindolo[3,2-b]carbazole (FICZ, 10 nM) was found to induce, in a ligand and AhR-dependent manner, endoplasmic reticulum stress, phospholipid remodeling, free fatty acid and triglyceride synthesis, leading to perilipin 2-dependent lipid droplet (LD) biogenesis in a Club cell-like cell line, NL20. The increase in LDs was due, in part, to the blockade of adipose triglyceride lipase to LDs, while perilipin 5 facilitated LDs-mitochondria connection, leading to the breakdown of LDs via mitochondrial β-oxidation and acetyl-coA generation. In FICZ-treated cells, increased CC10 secretion and its intracellular association with LDs were noted. Administration of low (0.28 ng), medium (1.42 ng), and high (7.10 ng) doses of FICZ in C57BL/6 mice significantly enhanced lipopolysaccharide (LPS, 0.1 μg)-induced airway inflammation, mucin secretion, pro-inflammatory cytokines and CC10 in the bronchoalveolar lavage fluids, as compared to those seen in mice receiving LPS alone, suggesting the importance of AhR signaling in controlling the metabolic homeostasis and functions of Club cells.
    MeSH term(s) Animals ; Carbazoles/pharmacology ; Cell Line ; Epithelial Cells/metabolism ; Humans ; Inactivation, Metabolic ; Ligands ; Lipid Droplets/metabolism ; Mice, Inbred C57BL ; Mitochondria/metabolism ; Perilipin-1/pharmacology ; Receptors, Aryl Hydrocarbon/physiology ; Respiratory System/cytology ; Signal Transduction/physiology ; Uteroglobin/metabolism ; Xenobiotics/metabolism ; Mice
    Chemical Substances 6-formylindolo(3,2-b)carbazole ; Carbazoles ; Ligands ; Perilipin-1 ; Receptors, Aryl Hydrocarbon ; Scgb1a1 protein, mouse ; Xenobiotics ; Uteroglobin (9060-09-7)
    Language English
    Publishing date 2021-03-08
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1149134-6
    ISSN 1749-0774 ; 0914-7470
    ISSN (online) 1749-0774
    ISSN 0914-7470
    DOI 10.1007/s13577-021-00491-6
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3676: Show issues Location:
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  7. Article ; Online: Aryl hydrocarbon receptor-kynurenine axis promotes oncogenic activity in BCP-ALL.

    Wang, Li-Ting / Liu, Kwei-Yan / Wang, Shen-Nien / Lin, Ming-Hong / Liao, Yu-Mei / Lin, Pei-Chin / Huang, Shau-Ku / Hsu, Shih-Hsien / Chiou, Shyh-Shin

    Cell biology and toxicology

    2022  Volume 39, Issue 4, Page(s) 1471–1487

    Abstract: B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the most common childhood cancer, originates from lymphoid precursor cells in bone marrow committed to the B-cell lineage. Environmental factors and genetic abnormalities disturb the normal ... ...

    Abstract B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the most common childhood cancer, originates from lymphoid precursor cells in bone marrow committed to the B-cell lineage. Environmental factors and genetic abnormalities disturb the normal maturation of these precursor cells, promoting the formation of leukemia cells and suppressing normal hematopoiesis. The underlying mechanisms of progression are unclear, but BCP-ALL incidence seems to be increasing in parallel with the adoption of modern lifestyles. This study hypothesized that air pollution and haze are risk factors for BCP-ALL progression. The current study revealed that indeno(1,2,3-cd)pyrene (IP), a major component of polycyclic aromatic hydrocarbons (PAHs) in air, promotes oncogenic activities (proliferation, transformation, and disease relapse) in vitro and in vivo. Mechanistically, IP treatment activated the aryl hydrocarbon receptor (AHR)-indoleamine-2,3-dioxygenase (IDOs) axis, thereby enhancing tryptophan metabolism and kynurenine (KYN) level and consequent promoting the KYN-AHR feedback loop. IP treatment decreased the time to disease relapse and increased the BCP-ALL cell count in an orthotopic xenograft mouse model. Additionally, in 50 clinical BCP-ALL samples, AHR and IDO were co-expressed in a disease-specific manner at mRNA and protein levels, while their mRNA levels showed a significant correlation with disease-free survival duration. These results indicated that PAH/IP exposure promotes BCP-ALL disease progression.
    MeSH term(s) Humans ; Mice ; Animals ; Kynurenine/metabolism ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Neoplasms ; Polycyclic Aromatic Hydrocarbons
    Chemical Substances Kynurenine (343-65-7) ; Receptors, Aryl Hydrocarbon ; Polycyclic Aromatic Hydrocarbons
    Language English
    Publishing date 2022-06-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 48824-0
    ISSN 1573-6822 ; 0742-2091
    ISSN (online) 1573-6822
    ISSN 0742-2091
    DOI 10.1007/s10565-022-09734-0
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    Zs.B 3024: Show issues Location:
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  8. Article: Aryl Hydrocarbon Receptor is Essential in the Control of Lung Club Cell Homeostasis.

    Liu, Kwei-Yan / Wang, Li-Ting / Wang, Hsueh-Chun / Wang, Shen-Nien / Tseng, Li-Wen / Chai, Chee-Yin / Chiou, Shyh-Shin / Huang, Shau-Ku / Hsu, Shih-Hsien

    Journal of inflammation research

    2021  Volume 14, Page(s) 299–311

    Abstract: Background: Club cells play an important role in maintaining lung homeostasis and aryl hydrocarbon receptor (AhR) is known to be important in xenobiotic metabolism, but its role in regulating club cells is currently unknown.: Methods: To this end, ... ...

    Abstract Background: Club cells play an important role in maintaining lung homeostasis and aryl hydrocarbon receptor (AhR) is known to be important in xenobiotic metabolism, but its role in regulating club cells is currently unknown.
    Methods: To this end, mice with club cell-specific AhR deficiency were generated and evaluated in a model of antigen (ovalbumin, OVA)-induced airway inflammation for the number of infiltrating inflammatory cells, the levels of cytokines and CC10 and Notch signaling by standard methods.
    Results: After OVA sensitization and challenge,
    Conclusion: Under the condition of pulmonary inflammation, AhR is critical in controlling lung club cell homeostasis via targeting Notch1 signaling and the generation of anti-inflammatory mediators.
    Language English
    Publishing date 2021-02-05
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2494878-0
    ISSN 1178-7031
    ISSN 1178-7031
    DOI 10.2147/JIR.S284800
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  9. Article ; Online: WLS/wntless is essential in controlling dendritic cell homeostasis via a WNT signaling-independent mechanism.

    Wang, Li-Ting / Lin, Ming-Hong / Liu, Kwei-Yan / Chiou, Shyh-Shin / Wang, Shen-Nien / Chai, Chee-Yin / Tseng, Li-Wen / Chiou, Hsin-Ying Clair / Wang, Hsueh-Chun / Yokoyama, Kazunari K / Hsu, Shih-Hsien / Huang, Shau-Ku

    Autophagy

    2021  Volume 17, Issue 12, Page(s) 4202–4217

    Abstract: We propose that beyond its role in WNT secretion, WLS/GPR177 (wntless, WNT ligand secretion mediator) acts as an essential regulator controlling protein glycosylation, endoplasmic reticulum (ER) homeostasis, and dendritic cell (DC)-mediated immunity. WLS ...

    Abstract We propose that beyond its role in WNT secretion, WLS/GPR177 (wntless, WNT ligand secretion mediator) acts as an essential regulator controlling protein glycosylation, endoplasmic reticulum (ER) homeostasis, and dendritic cell (DC)-mediated immunity. WLS deficiency in bone marrow-derived DCs (BMDCs) resulted in poor growth and an inability to mount cytokine and T-cell responses
    MeSH term(s) Animals ; Autophagy/physiology ; Dendritic Cells ; Endoplasmic Reticulum Stress ; Homeostasis ; Mice ; Wnt Signaling Pathway
    Language English
    Publishing date 2021-04-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2021.1907516
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6741: Show issues Location:
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  10. Article ; Online: PCAF-mediated acetylation of ISX recruits BRD4 to promote epithelial-mesenchymal transition.

    Wang, Li-Ting / Liu, Kwei-Yan / Jeng, Wen-Yih / Chiang, Cheng-Ming / Chai, Chee-Yin / Chiou, Shyh-Shin / Huang, Ming-Shyang / Yokoyama, Kazunari K / Wang, Shen-Nien / Huang, Shau-Ku / Hsu, Shih-Hsien

    EMBO reports

    2020  Volume 21, Issue 2, Page(s) e48795

    Abstract: Epigenetic regulation is important for cancer progression; however, the underlying mechanisms, particularly those involving protein acetylation, remain to be fully understood. Here, we show that p300/CBP-associated factor (PCAF)-dependent acetylation of ... ...

    Abstract Epigenetic regulation is important for cancer progression; however, the underlying mechanisms, particularly those involving protein acetylation, remain to be fully understood. Here, we show that p300/CBP-associated factor (PCAF)-dependent acetylation of the transcription factor intestine-specific homeobox (ISX) regulates epithelial-mesenchymal transition (EMT) and promotes cancer metastasis. Mechanistically, PCAF acetylation of ISX at lysine 69 promotes the interaction with acetylated bromodomain-containing protein 4 (BRD4) at lysine 332 in tumor cells, and the translocation of the resulting complex into the nucleus. There, it binds to promoters of EMT genes, where acetylation of histone 3 at lysines 9, 14, and 18 initiates chromatin remodeling and subsequent transcriptional activation. Ectopic ISX expression enhances EMT marker expression, including TWIST1, Snail1, and VEGF, induces cancer metastasis, but suppresses E-cadherin expression. In lung cancer, ectopic expression of PCAF-ISX-BRD4 axis components correlates with clinical metastatic features and poor prognosis. These results suggest that the PCAF-ISX-BRD4 axis mediates EMT signaling and regulates tumor initiation and metastasis.
    MeSH term(s) Acetylation ; Epigenesis, Genetic ; Epithelial-Mesenchymal Transition/genetics ; Genes, Homeobox ; Humans ; Neoplasms ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; p300-CBP Transcription Factors/metabolism
    Chemical Substances Nuclear Proteins ; Transcription Factors ; p300-CBP Transcription Factors (EC 2.3.1.48)
    Language English
    Publishing date 2020-01-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.201948795
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5433: Show issues Location:
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    Zs.MG 41: Show issues

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