Signal Transduction Protein Array Analysis Links LRRK2 to Ste20 Kinases and PKC Zeta That Modulate Neuronal Plasticity

Abstract Growing evidence has suggested that inflammatory responses promote the progression of saccular intracranial aneurysms (IAs). However, a biomarker predicting the progression has yet to be established. This study aimed to identify novel molecules upregulated during the progression using a previously established rat aneurysm model. In this model, aneurysms are induced at the surgically created common carotid artery (CCA) bifurcation. Based on sequential morphological data, the observation periods after the surgical manipulations were defined as the growing phase (on the 10th day) or the stable phase (on the 30th day). Total cell lysates from the CCA with or without an aneurysm lesion were prepared to perform protein array analysis. The protein array analysis revealed that the matricellular protein cellular communication network factor 1 (CCN1) is induced in lesions during the growing phase. Immunohistochemistry corroborated the significant upregulation of CCN1 in the growing phase compared with the stable phase. Simultaneously with the induction of CCN1, significant increases in the number of CD68-positive macrophages, myeloperoxidase-positive cells, and proliferating smooth muscle cells in lesions were observed. Immunohistochemistry of human IA specimens reproduced the induction of CCN1 in some lesions. These findings imply a potential role of CCN1 as a marker predicting the progression of saccular aneurysms.

Download Full-text

Nonparametric, Distance-Based, Supervised Protein Array Analysis

Informatics In Proteomics ◽

10.1201/9781420027624.ch12 ◽

2005 ◽

pp. 255-266

Author(s):

Zhen Zhang ◽

Nicole White ◽

Mei-Fen Yeh ◽

Jeanne Kowalski

Keyword(s):

Protein Array ◽

Array Analysis ◽

Protein Array Analysis

Download Full-text

Azide-tagged sphingolipids for the proteome-wide identification of C16-ceramide-binding proteins

Chemical Communications ◽

10.1039/c8cc05691a ◽

2018 ◽

Vol 54 (97) ◽

pp. 13742-13745

Author(s):

Janine Schulte-Zweckel ◽

Tabea Schneidewind ◽

Jose Luis Abad ◽

Andreas Brockmeyer ◽

Petra Janning ◽

...

Keyword(s):

Binding Proteins ◽

Protein Array ◽

Proteomic Profiling ◽

Array Analysis ◽

Protein Array Analysis

Unknown ceramide-binding proteins can be identified by combining azide-tagged sphingolipids with MS-based proteomic profiling and protein array analysis.

Download Full-text

Development of INSOL‐tag for proteome‐wide protein handling and its application in protein array analysis

Genes to Cells ◽

10.1111/gtc.12735 ◽

2019 ◽

Vol 25 (1) ◽

pp. 41-53

Author(s):

Eriko Fukuda ◽

Masatoshi Mori ◽

Hiroshi Shiku ◽

Yoshihiro Miyahara ◽

Yoshifumi Kawamura ◽

...

Keyword(s):

Protein Array ◽

Array Analysis ◽

Protein Array Analysis

Download Full-text

Echinaceaand anti-inflammatory cytokine responses: Results of a gene and protein array analysis

Pharmaceutical Biology ◽

10.1080/13880200902839525 ◽

2009 ◽

Vol 47 (6) ◽

pp. 500-508 ◽

Cited By ~ 6

Author(s):

M. Altamirano-Dimas ◽

M. Sharma ◽

J.B. Hudson

Keyword(s):

Inflammatory Cytokine ◽

Protein Array ◽

Array Analysis ◽

Cytokine Responses ◽

Anti Inflammatory ◽

Protein Array Analysis ◽

Anti Inflammatory Cytokine

Download Full-text

Protein array analysis of oligomerization-induced changes in alpha-synuclein protein–protein interactions points to an interference with Cdc42 effector proteins

Neuroscience ◽

10.1016/j.neuroscience.2008.02.049 ◽

2008 ◽

Vol 154 (4) ◽

pp. 1450-1457 ◽

Cited By ~ 19

Author(s):

C. Schnack ◽

K.M. Danzer ◽

B. Hengerer ◽

F. Gillardon

Keyword(s):

Protein Interactions ◽

Alpha Synuclein ◽

Effector Proteins ◽

Protein Array ◽

Protein Protein Interactions ◽

Array Analysis ◽

Protein Array Analysis ◽

Induced Changes

Download Full-text

Therapeutic Efficacy and Safety of Lenvatinib for Unresectable Hepatocellular Carcinoma Beyond Progression with Sorafenib

10.1101/2020.01.03.893800 ◽

2020 ◽

Author(s):

Tetsu Tomonari ◽

Yasushi Sato ◽

Hironori Tanaka ◽

Takahiro Tanaka ◽

Yasuteru Fujino ◽

...

Keyword(s):

Signal Transduction ◽

Signal Transduction Pathways ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

First Line ◽

Array Analysis ◽

Third Line ◽

Protein Array Analysis ◽

Third Line Treatment

AbstractBackground & AimsThe efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line treatment of LEN, investigated the sensitivity of SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and their signal transduction pathway by protein array analysis.MethodsWe retrospectively enrolled 57 unresectable HCC patients. Radiologic responses in 53 patients were evaluated by modified Response Evaluation Criteria in Solid Tumors. Active signal transduction pathways in cells were identified by protein array analysis, including 1205 proteins.ResultsPatients comprised 34 tyrosine kinase inhibitor (TKI)-naive (first-line), nine SOR-intolerant (second-line), and ten resistant to regorafenib (third-line). Objective response rates (ORRs) were 61.8% (21/34) in TKI-naive, 33.3% (3/9) in second-line, and 20.0% (2/10) in third-line groups. The overall survival (OS) and the progression free survival (PFS) in the first-line was significantly longer than those in third-line group (p<0.05). Patients with better liver functional reserve (Child score, ALBI grade) exhibited higher ORR and longer OS. LEN was well-tolerated as second/third-line treatment. The IC50 value of LEN against PLC/PRF5-R2 cells (30 μM) was significantly higher than that against PLC/PRF5 cells (6.4 μM). LEN inhibited significantly more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than PLC/PRF5-R2 cells.ConclusionsLEN was active and safe as a second/third-line treatment for unresectable HCC. LEN seems to be more effective for HCC patients with better hepatic reserve function or before TKI-resistance is acquired because of partial cross-resistance to SOR.

Download Full-text

Patterns of protein expression in infectious meningitis: A cerebrospinal fluid protein array analysis

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2005.03.009 ◽

2005 ◽

Vol 164 (1-2) ◽

pp. 134-139 ◽

Cited By ~ 34

Author(s):

Stefan Kastenbauer ◽

Barbara Angele ◽

Bernd Sporer ◽

Hans-Walter Pfister ◽

Uwe Koedel

Keyword(s):

Cerebrospinal Fluid ◽

Protein Expression ◽

Protein Array ◽

Array Analysis ◽

Protein Array Analysis ◽

Cerebrospinal Fluid Protein

Download Full-text

Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma beyond progression of sorafenib treatment: A real-world evidence and in vitro assessment with protein phosphorylation array.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.485 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 485-485

Author(s):

Yasushi Sato ◽

Tetsu Tomonari ◽

Hironori Tanaka ◽

Takahiro Tanaka ◽

Akihiro Hirao ◽

...

Keyword(s):

Signal Transduction ◽

Signal Transduction Pathways ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

Array Analysis ◽

Third Line ◽

Protein Array Analysis ◽

Third Line Treatment

485 Background: No information is available on the efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy. We evaluated the characteristics and the therapeutic efficacy and safety of LEN as a second- and third-line treatment as well as first- treatment for unresectable HCC patients in clinical settings. Moreover, to rationalize these clinical findings in vitro, we assessed the anti-tumor activity of LEN on SOR-resistant cell line and performed a comprehensive phosphorylated protein array analysis associated with 377 signal transduction pathways using SOR-resistant and parental HCC cells. Methods: We retrospectively enrolled 51 unresectable HCC patients. Radiologic responses in 41 patients were evaluated by modified RECIST. Active signal transduction pathways in the cells were identified by protein array analysis, including 1205 proteins. Results: The evaluated patients comprised 25 TKI-naive (first- line), 7 intolerant to SOR (second-line), and 9 patients resistant to regorafenib (third-line). The ORRs were 64% in first-line, 42.8% in second-line, and 22.2% in third-line groups (first-line vs. third-line p< 0.05). The OS in the first-line was significantly longer than that in third-line group ( p< 0.05). Patients with better liver functional reserve (Child score, ALBI grade) exhibited higher ORR and longer OS. LEN was well-tolerated in the second/third-line treatment. The IC50 value of LEN against PLC/PRF5-R2 (30 μM) was significantly higher than that against PLC/PRF5 (6.4 μM). LEN significantly inhibited more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than in PLC/PRF5-R2 cells. Conclusions: Our study indicates that LEN was active and safe in the second/third-line treatment for unresectable HCC. LEN seems more effective for HCC patients with better hepatic reserve function, or before TKI-resistance is acquired because of the partial cross-resistance to SOR.

Download Full-text