In the growing field of tumor targeting, there is an urgent need to profile suitable molecular targets. In this study, CD44v6 and EGFR expression was quantified in samples of patients with head and neck squamous cell carcinoma (HNSCC) using a single-dose (SD) radioimmunoassay.
The SD radioimmunoassay using 125I-chimeric monoclonal antibody (cMAb) U36 and 125I-cMAb cetuximab was first validated and then applied to quantify the expression of their target antigen molecules, CD44v6 and EGFR, in patient samples. Results were compared to immunohistochemical staining.
The SD assay provided sensitive quantitative values of the molecular targets studied, generally agreeing with the immunohistochemistry (IHC) results. The results indicated that expression of CD44v6 (0.2-20 nmol/mug membrane) was generally higher than that of EGFR (0.6-2.3 nmol/microg membrane) in the tumor samples analyzed, which corresponded to an average of 700,000 and 90,000 antigen molecules per cell, respectively.
The SD radioimmunoassay is simple, reliable, and can be performed on a small amount (50 mg) of tissue. This assay could be a useful tool in the growing field of personalized cancer therapy, and can be used as a complement to IHC. In the tumors studied, CD44v6 was generally expressed at a higher level than EGFR, which might suggest that it could be more readily targeted by MAbs.
[Show abstract][Hide abstract] ABSTRACT: Regulatory T cells (Treg) are important regulators of anti-cancer immune responses, and an increase in Treg frequency was observed in the blood of cancer patients. Blood samples from 112 patients with head and neck squamous cell carcinoma antigen (HNSCC) were obtained at the time of tumour diagnosis, and lymphocyte subpopulations (CD3(+); CD3(-)CD16(+)CD56(+); CD4(+); CD8(+); CD19(+); CD4(+)CD45RA(+)) with emphasis on Treg counts (CD3(+)CD4(+)CD25(+)), complete blood count and tumour markers (squamous cell carcinoma [SCC]; CEA; alpha-1-antitrypsin [AAT]; Cyfra 21-1; C-reactive protein [CRP]) were analysed. The data were grouped according to TNM classification, and their significance for the course of the disease at an interval of 1 year after the end of the therapy was determined. The percentage of CD8(+) cells increased and the CD/D8 ratio decreased with tumour grade. The ratio of B lymphocytes decreased in patients with locoregional metastases (11.25%versus 9.22%). Treg (15.2%) and CD4(+) cells (45.3%) increased, while NK cells (11.8%) decreased in HNSCC patients compared to controls (9.0%, 38.1% and 15.8%, respectively). The data obtained at time of diagnosis were used to assess the significance of tumour markers (SCC, Cyfra 21-1 and AAT) for evaluation of prognosis. The erythrocyte counts (4.64 x 10(12)/l versus 4.45 x 10(12)/l) and haemoglobin levels (14.58 g/dl versus 14.05 g/dl) decreased, while Treg counts (8.91%versus 15.70%) increased in patients with early recurrence. Our results show that examination of these parameters could be helpful for prognostication in HNSCC patients and aid improvement of treatment strategy.
Journal of Cellular and Molecular Medicine 02/2009; 14(1-2):426-33. DOI:10.1111/j.1582-4934.2008.00650.x · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The up regulation of Phospho-Src family kinase oncogene has been correlated with reduced postoperative survival in various cancers but never in tongue cancer.
We analyzed phospho-Src family kinase in 39 tongue (mobile) cancer patients by immunohistochemistry, compared these results with similar analysis for TUNEL and c-erbB-2 and with both clinical tumor characteristics and patient survival probability rates.
Phospho-Src family kinase overexpression was found in most tongue cancer biopsies (62%), significantly correlating with tumors larger in size (P = 0.05), progression—lymph node metastasis (0.004) and stage (P = 0.05), and correlating with TUNEL (P = 0.01) and c-erbB-2 (P = 0.05) expression rates. At 60 months, survival probability for negative phospho-Src family kinase level (=0) patients was 67%, but 30% for positive phospho-Src family kinase level (>0) patients (P = 0.05).
Inverse correlation between phospho-Src family kinase and patient survival demonstrates the prognostic role of phospho-Src family kinase in tongue cancer. These findings suggest a novel link between phospho-Src family kinase and TUNEL and c-erbB-2 pathways, tilting the balance toward cell proliferation.
Journal of Cancer Research and Clinical Oncology 07/2009; 136(1):27-34. DOI:10.1007/s00432-009-0633-1 · 3.08 Impact Factor
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