CEA ELISA Kit

Elevated levels of the carcinoembryonic antigen (CEA; CEACAM5) in the serum of colorectal cancer (CRC) patients represent a clinical biomarker that correlates with disease recurrence. However, a mechanistic role for soluble CEA (sCEA) in tumor progression and metastasis remains to be established. In our study, we report that sCEA acts as a paracrine factor, activating human fibroblasts by signaling through both the STAT3 and AKT1-mTORC1 pathways, promoting their transition to a cancer-associated fibroblast (CaF) phenotype. sCEA-activated fibroblasts express and secrete higher levels of fibronectin, including cellular EDA(+)-fibronectin (Fn-EDA) that selectively promote the implantation and adherence of CEA-expressing cancer cells. Immunohistochemical analyses of liver tissues derived from CRC patients with elevated levels of sCEA reveal that the expression of cellular Fn-EDA co-registers with CEA-expressing liver metastases. Taken together, these findings indicate a direct role for sCEA as a human fibroblast activation factor, in priming target tissues for the engraftment of CEA-expressing cancer cells, through the differentiation of tissue-resident fibroblasts, resulting in a local change in composition of the extracellular matrix.

This trial determined the pharmacokinetics, dosimetry, and dose-limiting toxicity of Y-90-hMN-14 IgG (humanized anticarcinoembryonic antigen [CEA, or CEACAM5] monoclonal antibody; labetuzumab), combined with doxorubicin and peripheral blood stem cell (PBSC) support in advanced medullary thyroid cancer (MTC) patients. Methods: Fifteen patients received an infusion of In-111-hMN-14 IgG. One to 2 wk later, 14 patients received 90Y-hMN-14 IgG, starting at 740 MBq/m(2), followed 24 h later with a fixed intravenous bolus dose of doxorubicin (60 Mg/m(2)). Preharvested PBSCs were reinfused when the Y-90 activity in the body was <= 111 MBq/m(2). Results: The mean red marrow dose estimated for the 90Y-hMN-14 IgG was 1.65 +/- 0.59 mGy/MBq (n = 11), with normal organs ranging from similar to 2.3 to 4.4 mGy/MBq. Eighty percent of all known lesions (125/156), including 78 of 79 bone and 16 putatively occult lesions, were targeted. The average radiation dose to the tumor was 15.1 +/- 10.8 mGy/ MBq (55.8 39.8 cGy/mCi) Y-90-hMN-4 IgG (n = 29 tumors in 8 patients), with a majority of the lesions receiving > 2,000 cGy at an administered dose of <= 1,480 MBq/m(2). The average tumor-to-red marrow, tumor-to-liver, tumor-to-lungs, and tumor-to-kidneys ratios were 15.0 +/- 11.0, 5.1 +/- 3.6, 6.9 +/- 6.1 and 9.0 +/- 8.7, respectively. Cardiopulmonary toxicity was dose limiting at 1,850 MBq/m(2). Minor responses were noted in 2 patients and 1 patient had a partial response (68% reduction in local and hepatic metastatic disease). Conclusion: This treatment combination was well tolerated with complete recovery of blood counts and reversible nonhematologic toxicities at the maximum tolerated dose of 1,480 MBq/m(2). Evidence of antitumor response in these patients with advanced cancer was modest, but encouraging; this type of treatment may be more successful if applied to more limited, earlier-stage disease.