Distant metastases of solid tumors are usually associated with fatal outcome. Disseminated cancer cells are considered early indicators of metastasis. Their sensitive detection and quantification would be a valuable tool for staging of disease and as guidance for therapeutic decisions.
We established a highly sensitive and quantitative multimarker real-time RT-PCR assay for amplification of cancer-related genes MAGE-A1, -A2, -A3/6, -A4, -A10 and -A12 using SYBR green I to detect one single tumor cell in 2 mL of blood or bone marrow. The feasibility of the assay was tested in a large cohort of 177 patients with locally confined prostate carcinoma.
Analysis revealed frequent MAGE expression in venous blood and bilateral bone marrow samples (25.5% of all cases) and yielded the first quantitative profile of MAGE expression with a broad range of transcript concentrations for individual markers in the minimal systemic tumor load of patients with localized cancer.
Rare transcripts of different MAGE-A genes can be quantified in clinical samples of cancer patients by a sensitive multimarker real-time RT-PCR. Because of frequent expression of MAGE genes in various types of cancer the multimarker MAGE real-time RT-PCR may be generally useful for detection, quantification and characterization of the individual disseminated tumor load in cancer patients.
"Thus, the detection of these markers, which are highly specific to cellular malignancy, makes them potential markers for early diagnosis and prognosis, and even a target for immunotherapy. We used the real time RT-PCR assay, which detects even small amounts of MAGE-RNA [25,26]. In this case report, we further combined these highly prevalent tumor markers with this sensitive detection method using brush biopsy material for the early diagnosis of OSCC. "
[Show abstract][Hide abstract] ABSTRACT: The aim of this case report is to introduce the combined use of brush biopsy and measurement of MAGE-A expression in the diagnosis of oral squamous cell carcinoma (OSCC).
We report of a 49-year old male patient who was referred to our department with a persistent-suspicious looking leukoplakia. Brush biopsy and an incisional biopsy were performed following clinical diagnosis. Histopathological examination revealed no malignancy. Expression analysis of melanoma-associated antigens A (MAGE-A) using real time RT-PCR was applied to brush biopsy materials because of the high prevalence of MAGE-A determined previously in OSCC's. Results indicated significant MAGE-A3 and A4 expression pattern. Therefore, the lesion was excised completely and an early invasive carcinoma was identified.
These results emphasize the role of brush biopsy using a tumor marker with a high expression frequency combined with a high sensitive and high specific detection system in the early diagnosis of OSCC, particularly in widespread leukoplakias.
[Show abstract][Hide abstract] ABSTRACT: Delivery of tumor-associated Ag-derived peptides in a high immunogenic form represents one of the key issues for effective peptide-based cancer vaccine development. We report herein the ability of nonpathogenic filamentous bacteriophage fd virions to deliver HLA-A2-restricted MAGE-A10(254-262)- or MAGE-A3(271-279)-derived peptides and to elicit potent specific CTL responses in vitro and in vivo. Interestingly, human anti-MAGE-A3(271-279)-specific CTLs were able to kill human MAGE-A3(+) tumor cells, even if these cells naturally express a low amount of MAGE-A3(271-279) peptide-HLA epitope surface complexes and are usually not recognized by CTLs generated by conventional stimulation procedures. MAGE-A3(271-279)-specific/CD8(+) CTL clones were isolated from in vitro cultures, and their high avidity for Ag recognition was assessed. Moreover, in vivo tumor protection assay showed that vaccination of humanized HHD (HLA-A2.1(+)/H2-D(b+)) transgenic mice with phage particles expressing MAGE-A3(271-279)-derived peptides hampered tumor growth. Overall, these data indicate that engineered filamentous bacteriophage virions increase substantially the immunogenicity of delivered tumor-associated Ag-derived peptides, thus representing a novel powerful system for the development of effective peptide-based cancer vaccines.
The Journal of Immunology 04/2008; 180(6):3719-28. DOI:10.4049/jimmunol.180.6.3719 · 4.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prognosis of cancer patients is largely determined by the occurrence of distant metastases. In patients with primary tumors, this relapse is mainly due to clinically occult micrometastasis present in secondary organs at primary diagnosis but not detectable even with high resolution imaging procedures. Sensitive and specific immunocytochemical and molecular assays enable the detection and characterization of disseminated tumor cells (DTC) at the single cell level in bone marrow (BM) as the common homing site of DTC and circulating tumor cells (CTC) in peripheral blood. Because of the high variability of results in DTC and CTC detection, there is an urgent need for standardized methods. In this review, we will focus on BM and present currently available methods for the detection and characterization of DTC. Furthermore, we will discuss data on the biology of DTC and the clinical relevance of DTC detection. While the prognostic impact of DTC in BM has clearly been shown for primary breast cancer patients, less is known about the clinical relevance of DTC in patients with other carcinomas. Current findings suggest that DTC are capable to survive chemotherapy and persist in a dormant nonproliferating state over years. To what extent these DTC have stem cell properties is subject of ongoing investigations. Further characterization is required to understand the biology of DTC and to identify new targets for improved risk prevention and tailoring of therapy. Our review will focus on breast, colon, lung, and prostate cancer as the main tumor entities in Europe and the United States.
International Journal of Cancer 11/2008; 123(9):1991-2006. DOI:10.1002/ijc.23825 · 5.09 Impact Factor
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