Novel Carcinoembryonic-Antigen-(CEA)-Specific Pretargeting System to Assess Tumor Cell Viability after Irradiation of Colorectal Cancer Cells

Meller, B.; Rave-Fränck, Margarete; Breunig, Christian; Schirmer, Markus; Baehre, M.; Nadrowitz, Roger; Liersch, Torsten; Meller, J.

doi:10.1007/s00066-010-2191-5

Cited by 9 publications

(7 citation statements)

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“…According to our data, the overall detection rate of the DLC1 methylation in CRC patients was paralel to that of CEA and CA19-9. However, we found no correlation between DLC1 methylation and elevated levels of CEA or CA19-9 [28][29][30] 1. Wu , which demonstrated that DNA methylation and conventional tumor markers could serve as complementary diagnosis markers.…”

Section: Discussioncontrasting

confidence: 82%

Detection and clinical significance of DLC1 gene methylation in serum DNA from colorectal cancer patients

Zou

Tang

et al. 2011

Chin. J. Cancer Res.

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Objective: Deleted in liver cancer 1 (DLC1) is a new candidate tumor suppressor gene, whose down-regulation or even silence will result from promoter hypermethylation in various human cancers including colorectal cancer (CRC). The aim of this study is to evaluate the diagnostic role of DLC1 gene methylation in the serum DNA from CRC patients.Methods: This study enrolled 85 CRC patients and 45 patients with benign colorectal diseases. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status of DLC1 gene in serum DNA. The combination of DLC1 methylation and conventional tumor markers was further analyzed.Results: Hypermethylation of DLC1 was detected in 42.4% (36/85) of CRC serums, while seldom in the benign controls (8.9%, 4/45) (P<0.001). The aberrant DLC1 methylation in serum DNA was not associated with patients' clinicopathological features and elevated CEA/CA19-9 levels. Furthermore, the combinational analysis of CEA, CA19-9 and DLC1 methylation showed a higher sensitivity and no reduced diagnostic specificity than CEA and CA19-9 combination for CRC diagnosis. Conclusion:The serum DLC1 methylation may be a promising biomarker for the early detection of CRC, which will further increase the diagnostic efficiency in combination with CEA and CA19-9.

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Section: Discussioncontrasting

confidence: 82%

Detection and clinical significance of DLC1 gene methylation in serum DNA from colorectal cancer patients

Zou

Tang

et al. 2011

Chin. J. Cancer Res.

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“…Data were half-life-corrected, and percentage uptake of applied activity was calculated. Since differences in treatment resulted in altered proliferation, the calculated uptake was correlated to the determined cell count in each particular culture flask and normalised to 10 6 cells as already described [ 26 , 27 ].…”

Section: Methodsmentioning

confidence: 99%

Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy

et al. 2015

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BackgroundProstate-specific membrane antigen (PSMA) is a promising target for diagnostics and therapy of prostate carcinoma (PCa). Based on the hypothesis that PSMA expression can be modulated by variations in androgen deprivation therapy (ADT), we investigated the binding of a PSMA-directed radiopharmaceutical in vitro in order to get an insight of the interactions between altered premedication and PSMA expression before repetitive PSMA-directed PET/CT for therapy response and targeted therapy implementation.MethodsThe human castration-resistant PCa cell line VCaP (CRPC) was treated with either 1 nmol/L testosterone (T) over 20 passages yielding the androgen-sensitive cell line (revCRPC) or with 5 μmol/L abiraterone acetate (AA) generating the abiraterone-tolerant subtype CRPCAA. In these cell lines, T and AA were varied by either supply or withdrawal of T and AA. PSMA expression of the three cell culture models was detected by Western blot and immunohistochemical staining. For quantitative measurement of tracer uptake, 0.3 nmol/L 68Ga-labelled PSMA-HBED-CC peptide (100–300 kBq/ml) was added to different treated parallel cultures (n = 9 each). Time-dependent uptake per 106 cells of each culture was calculated and evaluated. PSMA mRNA expression was investigated by qPCR.ResultsPSMA expression increased dependently on intensified ADT in all three basic cell lines. 68Ga-PSMA-HBED-CC uptake almost doubled during 3 h in all cell lines (p < 0.01). Compared to the basic cells, pre-incubation with abiraterone for 48 h resulted in a significant increased uptake in CRPC (p < 0.001). In revCRPC, 48-h AA pre-incubation resulted in an eightfold higher uptake after 3 h (p < 0.001). Additional withdrawal of external testosterone increased the uptake up to tenfold (p < 0.01). The increase of PSMA expression upon ADT and AA treatments was confirmed by qPCR and Western blot data. Furthermore, in CRPCAA, 48-h AA withdrawal increased the uptake up to fivefold (p < 0.01).ConclusionsThe investigated three PCa cell culture subtypes represent a serial preclinical model of androgen deprivation therapy as a proxy for clinical situations with differing basal PSMA expression. The uptake of PSMA-binding tracers could be stimulated by therapeutic effective short-term variation in premedication in all stages of ADT response. These complex interactions have to be considered in the interpretation of diagnostic imaging using PSMA ligands as well as in the optimal timing of PSMA-based therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0145-8) contains supplementary material, which is available to authorized users.

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“…Fluorescence-based, laparoscopic imaging, using antibodies targeting antigens found on tumour cells, has already shown considerable potential (Mahmood, 2010; Tiernan et al , 2012). In non-invasive imaging, iodine-124 labelled antibodies to CEA have been administered to enhance PET cancer scanning (Schoffelen et al , 2010; Boerman and Oyen, 2011; Carrasquillo et al , 2011; Meller et al , 2011; O'Donoghue et al , 2011; Schoffelen et al , 2012), and CEA antibodies have been conjugated to iron oxide nanoparticles to improve MRI imaging (Vigour et al , 2010). In therapeutic applications, radioisotope antibodies, usually directed towards CEA or TAG-72, have been used to deliver tumour selective radiotherapy (Meredith et al , 1996; Meyer et al , 2009; de Jong et al , 2011) and have been shown to be particularly effective in small-volume disease (Koppe et al , 2005; Barbet et al , 2012).…”

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confidence: 99%

Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting

et al. 2013

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Background:Colorectal cancer-specific biomarkers have been used as molecular targets for fluorescent intra-operative imaging, targeted PET/MRI, and selective cytotoxic drug delivery yet the selection of biomarkers used is rarely evidence-based. We evaluated sensitivities and specificites of four of the most commonly used markers: carcinoembryonic antigen (CEA), tumour-associated glycoprotein-72 (TAG-72), folate receptor-α (FRα) and Epithelial growth factor receptor (EGFR).Methods:Marker expression was evaluated semi-quantitatively in matched mucosal and colorectal cancer tissues from 280 patients using immunohistochemistry (scores of 0–15). Matched positive and negative lymph nodes from 18 patients were also examined.Results:Markers were more highly expressed in tumour tissue than in matched normal tissue in 98.8%, 79.0%, 37.1% and 32.8% of cases for CEA, TAG-72, FRα and EGFR, respectively. Carcinoembryonic antigen showed the greatest differential expression, with tumours scoring a mean of 10.8 points higher than normal tissues (95% CI 10.31–11.21, P<0.001). Similarly, CEA showed the greatest differential expression between positive and negative lymph nodes. Receiver operating characteristic analyses showed CEA to have the best sensitivity (93.7%) and specificity (96.1%) for colorectal cancer detection.Conclusion:Carcinoembryonic antigen has the greatest potential to allow highly specific tumour imaging and drug delivery; future translational research should aim to exploit this.

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Novel Carcinoembryonic-Antigen-(CEA)-Specific Pretargeting System to Assess Tumor Cell Viability after Irradiation of Colorectal Cancer Cells

Abstract: This novel pretargeting system allows the quantitative analysis of CEA-expressing colorectal cancer cells and represents a promising tool for evaluation of tumor cell viability after irradiation.

Cited by 9 publications

References 41 publications

Detection and clinical significance of DLC1 gene methylation in serum DNA from colorectal cancer patients

Detection and clinical significance of DLC1 gene methylation in serum DNA from colorectal cancer patients

Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy

Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting

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