Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Leukocyte Elastase/metabolism , Antibodies, Monoclonal, Humanized , Breast Neoplasms/enzymology , Clinical Trials as Topic , Female , Humans , Neoplasm Metastasis , Receptor, ErbB-2 , TrastuzumabABSTRACT
BACKGROUND: We prospectively tested whether circulating tumor cells could be detected in peripheral blood of patients with thyroid tumors by a reverse transcription-polymerase chain reaction (RT-PCR) to detect carcinoembryonic antigen (CEA) messenger RNA (mRNA). METHODS: We assayed for CEA mRNA by RT-PCR in peripheral blood sampled before and 2 to 3 weeks after curative surgery for thyroid tumors in 121 patients. Blood samples from 7 patients with chronic thyroiditis and 7 healthy subjects served as controls. RESULTS: No control samples were positive for CEA mRNA by RT-PCR. Of 121 preoperative samples from patients with thyroid tumor, 6 were positive (5.0%). Preoperative frequencies of CEA mRNA positivity in benign tumor, papillary carcinoma, follicular variant papillary carcinoma, minimally invasive follicular carcinoma, and widely invasive follicular carcinoma were 0%, 0%, 0%, 44.4% (4/9), and 50.0% (2/4), respectively. Among positive patients only one, who had widely invasive follicular carcinoma, remained positive after surgery. CONCLUSIONS: RT-PCR detection of tumor cells in preoperative blood often can distinguish malignant from benign follicular thyroid tumors.
Subject(s)
Adenoma/metabolism , Carcinoembryonic Antigen/metabolism , Carcinoma/metabolism , Goiter, Nodular/metabolism , Neoplastic Cells, Circulating/metabolism , Thyroid Neoplasms/metabolism , Adenoma/diagnosis , Adult , Carcinoembryonic Antigen/genetics , Carcinoma/diagnosis , Case-Control Studies , Diagnosis, Differential , Follow-Up Studies , Goiter, Nodular/diagnosis , Humans , Middle Aged , Prospective Studies , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Thyroid Neoplasms/diagnosisABSTRACT
BACKGROUND: In 100 consecutive patients with node-negative breast cancer who underwent curative surgery, we prospectively tested whether detection of circulating tumor cells in peripheral blood by means of reverse transcription-polymerase chain reaction for carcinoembryonic antigen (CEA) messenger RNA (mRNA) could predict patient outcomes. METHODS: We performed reverse transcription-polymerase chain reaction in blood samples taken before surgery and in repeat samples taken 2 to 3 weeks after surgery. Univariate and multivariate analyses of relapse-free survival were performed. RESULTS: Patients with CEA mRNA in preoperative samples had poorer survival rates than those who had no detectable CEA mRNA. The worst survival rate was seen in those with CEA mRNA in both pre- and postoperative samples. Stepwise multivariate analysis selected CEA mRNA expression pattern (P=.001; relative risk=0.69) and histologic tumor grade (P=.002; relative risk=1.35) as independent prognostic factors for disease-free survival. CONCLUSIONS: Molecular detection of CEA mRNA in both pre- and postoperative blood samples is an independent, negative prognostic factor in patients with node-negative breast cancer undergoing curative surgery.
Subject(s)
Biomarkers, Tumor/immunology , Breast Neoplasms/immunology , Carcinoembryonic Antigen/immunology , Carcinoma, Ductal, Breast/immunology , Neoplastic Cells, Circulating/immunology , Adult , Aged , Biomarkers, Tumor/blood , Breast Neoplasms/blood , Breast Neoplasms/surgery , Carcinoembryonic Antigen/blood , Carcinoembryonic Antigen/genetics , Carcinoma, Ductal, Breast/blood , Carcinoma, Ductal, Breast/surgery , Female , Humans , Lymphatic Metastasis , Mastectomy/methods , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction/methods , Treatment OutcomeABSTRACT
Altered peptide ligands (APL) induce T cell responses different from those induced by the original agonistic peptide. As shown for CD4(+) T cells, partial agonists induce partial T cell activation without proliferation because of lower affinities and higher off rates to TCR than those of agonists. To determine whether overexpression of partially agonistic TCR ligands on antigen-presenting cells provides high-avidity TCR ligands, we generated L cell transfectants expressing various numbers of HLA-DR4 covalently linked with APL derived from a streptococcal peptide and observed responses of the cognate T cells. Some overexpressed HLA-DR4/partially agonistic APL complexes induced T cell proliferation in a density-dependent manner. However, tyrosine phosphorylation of zeta-associated protein-70 (ZAP-70) and linker for activation of T cells and kinase activity of ZAP-70 were not detectable. T cell proliferation stimulated with L cell transfectants was sensitive to the PKC inhibitor Gö6976, but to a lesser extent to Gö6983, suggesting the involvement of mu isotype of PKC (PKCmu). In vitro kinase assays revealed that PKCmu activity was up-regulated only in T cells stimulated with L cell transfectants that induced T cell proliferation. Our data suggest the presence of a unique signaling pathway coupling TCR ligation with T cell proliferation associated with PKCmu activation and impaired ZAP-70 activation.