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Article: Sialylated glycoproteins as biomarkers and drivers of progression in prostate cancer

Wen, Ru / Zhao, Hongjuan / Zhang, Dalin / Chiu, Chun-Lung / Brooks, James D.

Carbohydrate research. 2022 Sept., v. 519

2022

Abstract: Sialic acids have been implicated in cancer initiation, progression, and immune evasion in diverse human malignancies. Sialylation of terminal glycans on cell surface and secreted glycoproteins is a long-recognized feature of cancer cells. Recently, ... ...

Abstract	Sialic acids have been implicated in cancer initiation, progression, and immune evasion in diverse human malignancies. Sialylation of terminal glycans on cell surface and secreted glycoproteins is a long-recognized feature of cancer cells. Recently, immune checkpoint inhibitor immunotherapy has tremendously improved the outcomes of patients with various cancers. However, available immunotherapy approaches have had limited efficacy in metastatic castration-resistant prostate cancer. Sialic acid modified glycoproteins in prostate cancers and their interaction with Siglec receptors on tumor infiltrating immune cells might underlie immunosuppressive signaling in prostate cancer. Here, we summarize the function of sialic acids and relevant glycosynthetic enzymes in cancer initiation and progression. We also discuss the possible uses of sialic acids as biomarkers in prostate cancer and the potential methods for targeting Siglec-sialic acid interactions for prostate cancer treatment.
Keywords	biomarkers ; cancer therapy ; glycoproteins ; humans ; immune evasion ; immunosuppression ; immunotherapy ; metastasis ; polysaccharides ; prostatic neoplasms ; research ; sialic acid
Language	English
Dates of publication	2022-09
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1435-7
ISSN	1873-426X ; 0008-6215
ISSN (online)	1873-426X
ISSN	0008-6215
DOI	10.1016/j.carres.2022.108598
Database	NAL-Catalogue (AGRICOLA)

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Article: The Role of MARCKS in Metastasis and Treatment Resistance of Solid Tumors.

Chiu, Chun-Lung / Zhao, Hongjuan / Chen, Ching-Hsien / Wu, Reen / Brooks, James D

Cancers

2022 Volume 14, Issue 19

Abstract: The myristoylated alanine-rich C-kinase substrate (MARCKS) is a membrane-associated protein kinase C (PKC) substrate ubiquitously expressed in eukaryotic cells. MARCKS plays important roles in multiple cellular processes, including cell adhesion and ... ...

Abstract	The myristoylated alanine-rich C-kinase substrate (MARCKS) is a membrane-associated protein kinase C (PKC) substrate ubiquitously expressed in eukaryotic cells. MARCKS plays important roles in multiple cellular processes, including cell adhesion and motility, mucin secretion, exocytosis, and inflammatory response. Aberrant MARCKS signaling has been observed in the development and progression of multiple cancer types. In addition, MARCKS facilitates cancer metastasis through modulating cancer cell migration and invasion. Moreover, MARCKS contributes to treatment resistance, likely by promoting cancer stem cell renewal as well as immunosuppression. In this review, we describe MARCKS protein structure, cellular localization, and biological functions. We then discuss the role of MARCKS in cancer metastasis as well as its mechanisms of action in solid tumors. Finally, we review recent advances in targeting MARCKS as a new therapeutic strategy in cancer management.
Language	English
Publishing date	2022-10-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14194925
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Article ; Online: Sialylated glycoproteins as biomarkers and drivers of progression in prostate cancer.

Wen, Ru / Zhao, Hongjuan / Zhang, Dalin / Chiu, Chun-Lung / Brooks, James D

Carbohydrate research

2022 Volume 519, Page(s) 108598

Abstract	Sialic acids have been implicated in cancer initiation, progression, and immune evasion in diverse human malignancies. Sialylation of terminal glycans on cell surface and secreted glycoproteins is a long-recognized feature of cancer cells. Recently, immune checkpoint inhibitor immunotherapy has tremendously improved the outcomes of patients with various cancers. However, available immunotherapy approaches have had limited efficacy in metastatic castration-resistant prostate cancer. Sialic acid modified glycoproteins in prostate cancers and their interaction with Siglec receptors on tumor infiltrating immune cells might underlie immunosuppressive signaling in prostate cancer. Here, we summarize the function of sialic acids and relevant glycosynthetic enzymes in cancer initiation and progression. We also discuss the possible uses of sialic acids as biomarkers in prostate cancer and the potential methods for targeting Siglec-sialic acid interactions for prostate cancer treatment.
MeSH term(s)	Biomarkers ; Glycoproteins/metabolism ; Humans ; Immunologic Factors ; Male ; N-Acetylneuraminic Acid/metabolism ; Prostatic Neoplasms ; Sialic Acid Binding Immunoglobulin-like Lectins/metabolism ; Sialic Acids
Chemical Substances	Biomarkers ; Glycoproteins ; Immunologic Factors ; Sialic Acid Binding Immunoglobulin-like Lectins ; Sialic Acids ; N-Acetylneuraminic Acid (GZP2782OP0)
Language	English
Publishing date	2022-06-01
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1435-7
ISSN	1873-426X ; 0008-6215
ISSN (online)	1873-426X
ISSN	0008-6215
DOI	10.1016/j.carres.2022.108598
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Article ; Online: C-terminal tensin-like (

Chiu, Chun-Lung / Hong, Shiao-Ya / Tan, Ying / Lee, Yuh-Ru Julie / Shih, Yi-Ping / Tepper, Clifford G / Lo, Su Hao

Genes & diseases

2022 Volume 10, Issue 3, Page(s) 643–646

Language	English
Publishing date	2022-06-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2821806-1
ISSN	2352-3042 ; 2352-3042
ISSN (online)	2352-3042
ISSN	2352-3042
DOI	10.1016/j.gendis.2022.05.035
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Article ; Online: NUSAP1 Binds ILF2 to Modulate R-Loop Accumulation and DNA Damage in Prostate Cancer.

Chiu, Chun-Lung / Li, Caiyun G / Verschueren, Erik / Wen, Ru M / Zhang, Dalin / Gordon, Catherine A / Zhao, Hongjuan / Giaccia, Amato J / Brooks, James D

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: Increased expression of NUSAP1 has been identified as a robust prognostic biomarker in prostate cancer and other malignancies. We have previously shown that NUSAP1 is positively regulated by E2F1 and promotes cancer invasion and metastasis. To further ... ...

Abstract	Increased expression of NUSAP1 has been identified as a robust prognostic biomarker in prostate cancer and other malignancies. We have previously shown that NUSAP1 is positively regulated by E2F1 and promotes cancer invasion and metastasis. To further understand the biological function of NUSAP1, we used affinity purification and mass spectrometry proteomic analysis to identify NUSAP1 interactors. We identified 85 unique proteins in the NUSAP1 interactome, including ILF2, DHX9, and other RNA-binding proteins. Using proteomic approaches, we uncovered a function for NUSAP1 in maintaining R-loops and in DNA damage response through its interaction with ILF2. Co-immunoprecipitation and colocalization using confocal microscopy verified the interactions of NUSAP1 with ILF2 and DHX9, and RNA/DNA hybrids. We showed that the microtubule and charged helical domains of NUSAP1 were necessary for the protein-protein interactions. Depletion of ILF2 alone further increased camptothecin-induced R-loop accumulation and DNA damage, and NUSAP1 depletion abolished this effect. In human prostate adenocarcinoma,
MeSH term(s)	Humans ; Male ; DNA Damage ; Microtubule-Associated Proteins/metabolism ; Nuclear Factor 45 Protein/genetics ; Nuclear Factor 45 Protein/metabolism ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Proteomics ; R-Loop Structures
Chemical Substances	ILF2 protein, human ; Microtubule-Associated Proteins ; Nuclear Factor 45 Protein ; NUSAP1 protein, human
Language	English
Publishing date	2023-03-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24076258
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Article ; Online: Hyperactivity of Mek in TNS1 knockouts leads to potential treatments for cystic kidney diseases.

Wu, Zong-Ye / Chiu, Chun-Lung / Lo, Ethan / Lee, Yuh-Ru Julie / Yamada, Soichiro / Lo, Su Hao

Cell death & disease

2019 Volume 10, Issue 12, Page(s) 871

Abstract: Cystic kidney disease is the progressive development of multiple fluid-filled cysts that may severely compromise kidney functions and lead to renal failure. TNS1 (tensin-1) knockout mice develop cystic kidneys and die from renal failure. Here, we have ... ...

Abstract	Cystic kidney disease is the progressive development of multiple fluid-filled cysts that may severely compromise kidney functions and lead to renal failure. TNS1 (tensin-1) knockout mice develop cystic kidneys and die from renal failure. Here, we have established TNS1-knockout MDCK cells and applied 3D culture system to investigate the mechanism leading to cyst formation. Unlike wild-type MDCK cells, which form cysts with a single lumen, TNS1-knockout cysts contain multiple lumens and upregulated Mek/Erk activities. The multiple lumen phenotype and Mek/Erk hyperactivities are rescued by re-expression of wild-type TNS1 but not the TNS1 mutant lacking a fragment essential for its cell-cell junction localization. Furthermore, Mek inhibitor treatments restore the multiple lumens back to single lumen cysts. Mek/Erk hyperactivities are also detected in TNS1-knockout mouse kidneys. Treatment with the Mek inhibitor trametinib significantly reduces the levels of interstitial infiltrates, fibrosis and dilated tubules in TNS1-knockout kidneys. These studies establish a critical role of subcellular localization of TNS1 in suppressing Mek/Erk signaling and maintaining lumenogenesis, and provide potential therapeutic strategies by targeting the Mek/Erk pathway for cystic kidney diseases.
MeSH term(s)	Animals ; Cell Proliferation ; MAP Kinase Signaling System/physiology ; Mice ; Mice, Knockout ; Polycystic Kidney Diseases/metabolism ; Tensins/metabolism ; Transfection
Chemical Substances	TNS1 protein, human ; Tensins
Language	English
Publishing date	2019-11-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-019-2119-7
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Article ; Online: AZGP1 deficiency promotes angiogenesis in prostate cancer.

Wen, Ru M / Qiu, Zhengyuan / Marti, G Edward W / Peterson, Eric E / Marques, Fernando Jose Garcia / Bermudez, Abel / Wei, Yi / Nolley, Rosalie / Lam, Nathan / Polasko, Alex LaPat / Chiu, Chun-Lung / Zhang, Dalin / Cho, Sanghee / Karageorgos, Grigorios Marios / McDonough, Elizabeth / Chadwick, Chrystal / Ginty, Fiona / Jung, Kyeong Joo / Machiraju, Raghu /

Mallick, Parag / Crowley, Laura / Pollack, Jonathan R / Zhao, Hongjuan / Pitteri, Sharon J / Brooks, James D

Journal of translational medicine

2024 Volume 22, Issue 1, Page(s) 383

Abstract: Background: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has ... ...

Abstract	Background: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. Method: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1 Result: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1 Conclusion: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.
MeSH term(s)	Male ; Animals ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Humans ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Mice, Knockout ; Glycoproteins/metabolism ; Neoplasm Invasiveness ; Mice ; Gene Expression Regulation, Neoplastic ; Angiogenesis ; Zn-Alpha-2-Glycoprotein
Chemical Substances	AZGP1 protein, human ; Glycoproteins ; Zn-Alpha-2-Glycoprotein
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-024-05183-x
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Article ; Online: A novel predictor of cancer malignancy: up-regulation of myristoylated alanine-rich C kinase substrate phosphorylation in lung cancer.

Chen, Ching-Hsien / Chiu, Chun-Lung / Adler, Kenneth B / Wu, Reen

American journal of respiratory and critical care medicine

2014 Volume 189, Issue 8, Page(s) 1002–1004

MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma/metabolism ; Adenocarcinoma/mortality ; Aged ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma/metabolism ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/mortality ; Cohort Studies ; Female ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/mortality ; Male ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Middle Aged ; Myristoylated Alanine-Rich C Kinase Substrate ; Neoplasm Invasiveness ; Neoplasm Staging ; Phosphorylation ; Predictive Value of Tests ; Prognosis ; Sensitivity and Specificity ; Up-Regulation
Chemical Substances	Biomarkers, Tumor ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; Myristoylated Alanine-Rich C Kinase Substrate (125267-21-2)
Language	English
Publishing date	2014-04-14
Publishing country	United States
Document type	Letter
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.201401-0053LE
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Article ; Online: Erratum: "Polygonum multiflorum Decreases Airway Allergic Symptoms in a Murine Model of Asthma".

Lee, Chen-Chen / Lee, Yueh-Lun / Wang, Chien-N / Tsai, Hsing-Chuan / Chiu, Chun-Lung / Liu, Leroy F / Lin, Hung-Yun / Wu, Reen

The American journal of Chinese medicine

2017 Volume 45, Issue 5, Page(s) 1125

Language	English
Publishing date	2017-07-29
Publishing country	Singapore
Document type	Journal Article ; Published Erratum
ZDB-ID	193085-0
ISSN	1793-6853 ; 0090-2942 ; 0192-415X
ISSN (online)	1793-6853
ISSN	0090-2942 ; 0192-415X
DOI	10.1142/S0192415X17920033
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Article ; Online: Polygonum multiflorum Decreases Airway Allergic Symptoms in a Murine Model of Asthma.

Lee, Chen-Chen / Lee, Yueh-Lun / Wang, Chien-N / Tsai, Hsing-Chuan / Chiu, Chun-Lung / Liu, Leroy F / Lin, Hung-Yun / Wu, Reen

The American journal of Chinese medicine

2016 Volume 44, Issue 1, Page(s) 133–147

Abstract: The root of Polygonum multiflorum (also called He-Shou-Wu in Chinese) is a common herb and medicinal food in Asia used for its anti-aging properties. Our study investigated the therapeutic potential of an extract of the root of Polygonum multiflorum (PME) ...

Abstract	The root of Polygonum multiflorum (also called He-Shou-Wu in Chinese) is a common herb and medicinal food in Asia used for its anti-aging properties. Our study investigated the therapeutic potential of an extract of the root of Polygonum multiflorum (PME) in allergic asthma by using a mouse model. Feeding of 0.5 and 1 mg/mouse PME inhibited ovalbumin (OVA)-induced allergic asthma symptoms, including airway inflammation, mucus production, and airway hyper-responsiveness (AHR), in a dose-dependent manner. To discern PME's mechanism of action, we examined the profile and cytokine production of inflammatory cells in bronchial alveolar lavage fluid (BALF). We found that eosinophils, the main inflammatory cell infiltrate in the lung of OVA-immunized mice, significantly decreased after PME treatment. Th2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13, eotaxin, and the proinflammatory cytokine tumor necrosis factor (TNF)-[Formula: see text], decreased in PME-treated mice. Elevated mRNA expression of Th2 transcription factor GATA-3 in the lung tissue was also inhibited after oral feeding of PME in OVA-immunized mice. Thus, we conclude that PME produces anti-asthma activity through the inhibition of Th2 cell activation.
MeSH term(s)	Administration, Oral ; Animals ; Anti-Asthmatic Agents/pharmacology ; Asthma/drug therapy ; Asthma/metabolism ; Asthma/pathology ; Cytokines/metabolism ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Fallopia multiflora/chemistry ; Female ; GATA3 Transcription Factor/metabolism ; Inflammation Mediators/metabolism ; Lung/metabolism ; Mice, Inbred BALB C ; Mucus/metabolism ; Ovalbumin ; Phytotherapy ; Plant Extracts/administration & dosage ; Plant Extracts/pharmacology ; Plant Roots
Chemical Substances	Anti-Asthmatic Agents ; Cytokines ; GATA3 Transcription Factor ; Gata3 protein, mouse ; Inflammation Mediators ; Plant Extracts ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2016-02-16
Publishing country	Singapore
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	193085-0
ISSN	1793-6853 ; 0090-2942 ; 0192-415X
ISSN (online)	1793-6853
ISSN	0090-2942 ; 0192-415X
DOI	10.1142/S0192415X16500099
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