Detection of mRNAs of GA733 Genes by RT-PCR in Exfoliated Cells of Pleural and Peritoneal Effusions and Its Clinical Values

Zhang, Kun‐He; Cao, Feng; Fu, Qubo; Zhu, Jiang; Jiang, Chen; Lv, Nonghua

doi:10.2169/internalmedicine.46.0199

Cited by 7 publications

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“…Noteworthy, higher sEpCAM levels were found only in 39% of patients with tumor cells in ascites. This is by far lower than EpCAM gene expression rates described for tumor cells of malignant effusions [ 25 ] and for cell surface protein studies using microfluidic chips [ 28 ]. This may implicate that many tumor cells in ascites have probably lost EpCAM expression because they underwent epithelial to mesenchymal transition (EMT, such as MDA231 cells) and tumor cell types releasing only low amounts of sEpCAM into their microenvironment.…”

Section: Discussionmentioning

confidence: 82%

“…However, most EpCAM-targeting agents did not hold promise [ 23 ] and further studies on predictive biomarkers are necessary to privilege the right patient collectives for EpCAM-targeted therapies [ 24 ]. EpCAM gene expression has been observed in cancer cells of approximately 75% of patients with malignant ascites [ 25 ] and therefore, the EpCAM-targeting antibody catumaxomab was approved in 2009 by the European Union for the intraperitoneal treatment of patients suffering from malignant ascites. Catumaxomab is a trifunctional antibody binding to EpCAM on epithelial-like tumor cells and CD3+ T cells and can activate with its Fc part monocytes and NK cells.…”

Section: Introductionmentioning

confidence: 99%

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Soluble EpCAM levels in ascites correlate with positive cytology and neutralize catumaxomab activity in vitro

et al. 2015

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BackgroundEpCAM is highly expressed on membrane of epithelial tumor cells and has been detected as soluble/secreted (sEpCAM) in serum of cancer patients. In this study we established an ELISA for in vitro diagnostics to measure sEpCAM concentrations in ascites. Moreover, we evaluated the influence of sEpCAM levels on catumaxomab (antibody) - dependent cellular cytotoxicity (ADCC).MethodsAscites specimens from cancer patients with positive (C+, n = 49) and negative (C-, n = 22) cytology and ascites of patients with liver cirrhosis (LC, n = 31) were collected. All cell-free plasma samples were analyzed for sEpCAM levels with a sandwich ELISA system established and validated by a human recombinant EpCAM standard for measurements in ascites as biological matrix. In addition, we evaluated effects of different sEpCAM concentrations on catumaxomab-dependent cell-mediated cytotoxicity (ADCC) with human peripheral blood mononuclear cells (PBMNCs) and human tumor cells.ResultsOur ELISA showed a high specificity for secreted EpCAM as determined by control HEK293FT cell lines stably expressing intracellular (EpICD), extracellular (EpEX) and the full-length protein (EpCAM) as fusion proteins. The lower limit of quantification was 200 pg/mL and the linear quantification range up to 5,000 pg/mL in ascites as biological matrix. Significant levels of sEpCAM were found in 39% of C+, 14% of C- and 13% of LC ascites samples. Higher concentrations of sEpCAM were detectable in C+ (mean: 1,015 pg/mL) than in C- (mean: 449 pg/mL; p = 0.04) or LC (mean: 326 pg/mL; p = 0.01). Soluble EpCAM concentration of 1 ng/mL significantly inhibited ADCC of PBMNCs on EpCAM overexpressing target cells.ConclusionElevated concentrations of sEpCAM can be found in a subgroup of C+ and also in a small group of C- patients. We consider that sEpCAM levels in different tumor entities and individual patients should be evaluated prior to applying anti-EpCAM antibody-based cancer therapies, since sEpCAM neutralizes catumaxomab activity, making therapy less efficient.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1371-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Soluble EpCAM levels in ascites correlate with positive cytology and neutralize catumaxomab activity in vitro

et al. 2015

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Current applications of molecular testing on body cavity fluids

Gomes

Schmitt

2020

Diagnostic Cytopathology

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IntroductionEffusion cytology has a high sensitivity for the diagnosis of malignancy and provides abundant material for molecular testing. Effusion draining is a minimally invasive procedure with few complications.Materials and methodsWe performed a review of publications regarding the use of molecular testing in serous effusions.ResultsIn diagnostics, BAP‐1 IHC and CDKN2A FISH are powerful tools for the diagnosis of malignant mesothelioma. FISH, PCR, and EBER‐ISH work well in lymphomas. RT‐PCR may enhance the diagnosis of secondary epithelial malignancies. In theranostics, molecular testing on serous effusions is widely reported for the detection of alterations in genes related to lung carcinomas, such as EGFR, ALK, ROS1, and BRAF. PD‐L1 expression testing by immunohistochemistry (IHC) also seems to be viable in this type of sample. HER2 FISH and IHC provide actionable results in the context of breast malignancies. Results in serous effusions seem to be equivalent to tissue biopsies for most applications and across different molecular techniques. The most interesting technology is next‐generation sequencing (NGS), given its ability to sequence multiple genes on a single sample and the decreasing costs that have closely followed increasing throughputs. Cell‐free DNA from effusion supernatants might be the most promising area for future research, showing superiority to serum and even to cell‐block samples in limited studies.ConclusionsMolecular tests are viable in serous effusion specimens when sufficient material is available. Given the rising importance of molecular testing we expect this to be an active field of research in the near future.

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Unraveling the multifaceted role of EpCAM in colorectal cancer: an integrated review of its function and interplay with non-coding RNAs

Jiang,

Wang,

Liang

et al. 2023

Med Oncol

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Detection of mRNAs of GA733 Genes by RT-PCR in Exfoliated Cells of Pleural and Peritoneal Effusions and Its Clinical Values

Abstract: Objective

Cited by 7 publications

References 20 publications

Soluble EpCAM levels in ascites correlate with positive cytology and neutralize catumaxomab activity in vitro

Soluble EpCAM levels in ascites correlate with positive cytology and neutralize catumaxomab activity in vitro

Current applications of molecular testing on body cavity fluids

Unraveling the multifaceted role of EpCAM in colorectal cancer: an integrated review of its function and interplay with non-coding RNAs

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