Structural and Functional Impact of Posttranslational Modification of Glypican-3 on Liver Carcinogenesis

Schepers, Emily; Glaser, Kathryn; Zwolshen, Harrison M; Hartman, Stephen J.; Bondoc, Alexander

doi:10.1158/0008-5472.can-22-3895

Cited by 16 publications

(7 citation statements)

References 96 publications

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“…To evaluate the selectivity of the VSCLIA, seven other cancer biomarkers, including CEA, NSE, PSA, CA125, CA199, FER, and GPC3 were selected for cross-reaction tests. All of these biomarkers are macromolecules with complex antigen epitopes existing in cancer patients, which might induce cross-reactions with VNAR in real serum detection, especially GPC3, a cell-surface glycoprotein that is frequently overexpressed in HCC like AFP . Under the optimal conditions, AFP was replaced by other biomarkers for the test of VSCLIA.…”

Section: Resultsmentioning

confidence: 99%

Development of Shark Single Domain Antibodies Specific for Human α-Fetoprotein and the Multimerization Strategy in Serum Detection

Wang,

Xie,

et al. 2024

Anal. Chem.

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Sensitive detection of cancer biomarkers can contribute to the timely diagnosis and treatment of diseases. In this study, the whitespotted bamboo sharks were immunized with human α-fetoprotein (AFP), and a phage-displayed variable new antigen receptor (VNAR) single domain antibody library was constructed. Then four unique VNARs (VNAR1, VNAR11, VNAR21, and VNAR25) against AFP were isolated from the library by biopanning for the first time. All of the sequences belong to type II of VNAR, and the VNAR11 was much different from the rest of the three sequences. Then VNAR1 and VNAR11 were selected to fuse with the C4-binding protein α chain (C4bpα) sequence and efficiently expressed in the Escherichia coli system. Furthermore, a VNAR-C4bpαmediated sandwich chemiluminescence immunoassay (VSCLIA) was developed for the detection of AFP in human serum samples. After optimization, the VSCLIA showed a limit of detection of 0.74 ng/mL with good selectivity and accuracy. Moreover, the results of clinical serum samples detected by the VSCLIA were confirmed by an automatic immunoanalyzer in the hospital, indicating its practical application in actual samples. In conclusion, the novel antibody element VNAR exhibits great potential for immunodiagnosis, and this study also provides a new direction and experimental basis for AFP detection.

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Section: Resultsmentioning

confidence: 99%

Development of Shark Single Domain Antibodies Specific for Human α-Fetoprotein and the Multimerization Strategy in Serum Detection

Wang,

Xie,

et al. 2024

Anal. Chem.

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“…5H ). Finally, elevated GPC3 expression occurs in hepatocellular carcinomas with limited expression found on healthy tissues ( 35 ). A single 8 mg/kg i.v.…”

Section: Resultsmentioning

confidence: 99%

Design and Evaluation of ZD06519, a Novel Camptothecin Payload for Antibody Drug Conjugates

Petersen,

Brant,

Lasalle

et al. 2024

Molecular Cancer Therapeutics

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In recent years, the field of antibody drug conjugates (ADCs) has seen a resurgence, largely driven by the clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present the development of a novel camptothecin ZD06519 (FD1), which has been specifically designed for its application as an ADC payload. A panel of camptothecin analogs with different substituents at the C-7 and C-10 positions of the camptothecin core were prepared and tested in vitro. Selected compounds spanning a range of potency and hydrophilicity were elaborated into drug-linkers, conjugated to trastuzumab, and evaluated in vitro and in vivo. ZD06519 was selected based on its favourable properties as a free molecule and as an antibody conjugate, which include moderate free payload potency (~1 nM), low hydrophobicity, strong bystander activity, robust plasma stability, and high-monomeric ADC content. When conjugated to different antibodies using a clinically validated MC-GGFG-based linker, ZD06519 demonstrated impressive efficacy in multiple CDX models and noteworthy tolerability in healthy mice, rats, and non-human primates.

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“…is a tumor fetal proteoglycan anchored to the cell membrane and is commonly detected in fetal liver but not in healthy adult liver. [ 41 , 42 ] To predict the diagnostic value of serum GPC3 in patients with HCC, a meta-analysis by Yang et al showed an association between GPC3 expression and HCC patient. [ 43 ] Another study pointed to GPC3 as a potential novel therapeutic target for osteosarcoma [ 44 ] ; Yu et al [ 45 ] found that the expression of GPC3 protein was significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

WGCNA combined with machine learning to find potential biomarkers of liver cancer

Lv,

Hou,

Zhang

et al. 2023

Medicine

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The incidence of hepatocellular carcinoma (HCC) has been increasing in recent years. With the development of various detection technologies, machine learning is an effective method to screen disease characteristic genes. In this study, weighted gene co-expression network analysis (WGCNA) and machine learning are combined to find potential biomarkers of liver cancer, which provides a new idea for future prediction, prevention, and personalized treatment. In this study, the “limma” software package was used. P < .05 and log2 |fold-change| > 1 is the standard screening differential genes, and then the module genes obtained by WGCNA analysis are crossed to obtain the key module genes. Gene Ontology and Kyoto Gene and Genome Encyclopedia analysis was performed on key module genes, and 3 machine learning methods including lasso, support vector machine-recursive feature elimination, and RandomForest were used to screen feature genes. Finally, the validation set was used to verify the feature genes, the GeneMANIA (http://www.genemania.org) database was used to perform protein–protein interaction networks analysis on the feature genes, and the SPIED3 database was used to find potential small molecule drugs. In this study, 187 genes associated with HCC were screened by using the “limma” software package and WGCNA. After that, 6 feature genes (AADAT, APOF, GPC3, LPA, MASP1, and NAT2) were selected by RandomForest, Absolute Shrinkage and Selection Operator, and support vector machine-recursive feature elimination machine learning algorithms. These genes are also significantly different on the external dataset and follow the same trend as the training set. Finally, our findings may provide new insights into targets for diagnosis, prevention, and treatment of HCC. AADAT, APOF, GPC3, LPA, MASP1, and NAT2 may be potential genes for the prediction, prevention, and treatment of liver cancer in the future.

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Structural and Functional Impact of Posttranslational Modification of Glypican-3 on Liver Carcinogenesis

Cited by 16 publications

References 96 publications

Development of Shark Single Domain Antibodies Specific for Human α-Fetoprotein and the Multimerization Strategy in Serum Detection

Development of Shark Single Domain Antibodies Specific for Human α-Fetoprotein and the Multimerization Strategy in Serum Detection

Design and Evaluation of ZD06519, a Novel Camptothecin Payload for Antibody Drug Conjugates

WGCNA combined with machine learning to find potential biomarkers of liver cancer

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