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Andre T Baron

Publications and source records attributed to Andre T Baron.

5 recordsLinked to original sources
PubMed2005

Serum soluble epidermal growth factor receptor concentrations decrease in postmenopausal metastatic breast cancer patients treated with letrozole.

Previous studies have implicated estrogen as a regulator of epidermal growth factor receptor (EGFR) expression in breast tumors. We therefore speculated that estrogen might modulate serologic soluble EGFR (sEGFR) concentrations in breast cancer patients. Accordingly, we measured serum sEGFR concentrations in postmenopausal women with metastatic breast cancer (MBC) treated with letrozole, an aromatase inhibitor that blocks estrogen synthesis. Serum specimens were obtained prior to and following 1 and 3 months of letrozole therapy. We report that sEGFR concentrations do not differ between MBC patients prior to letrozole treatment and age- and postmenopause-matched healthy women (P = 0.468). In contrast, however, sEGFR concentrations decreased significantly in 76% of MBC patients after both 1 month (P = 0.006) and 3 months (P = 0.003) of letrozole therapy versus pretreatment concentrations. Within the limitations of this study, we found no evidence for an association between pretreatment sEGFR concentrations or decreased treatment sEGFR concentrations and either progression-free or overall survival. Nonetheless, we conclude that future prospective studies are warranted to determine if baseline and/or longitudinal serum sEGFR concentrations may be useful for predicting disease progression and survival, and/or for monitoring responsiveness to aromatase inhibitors or other endocrine therapies in breast cancer patients.

Antineoplastic Agents↗
PubMed2005

Soluble epidermal growth factor receptor (sEGFR) [corrected] and cancer antigen 125 (CA125) as screening and diagnostic tests for epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecologic cancers in the United States. Because women who are diagnosed with early stage disease have a better prognosis than women diagnosed with late stage disease, early detection represents a potentially practical approach to reduce the mortality associated with EOC. Unfortunately, no single screening test has proven to be effective for this purpose, and a valid and feasible screening program to detect early stage EOC in the general population has not yet been devised. Consequently, research has focused on coupling two or more screening modalities to improve program validity and feasibility. Serum cancer antigen 125 (CA125) and a soluble isoform of the epidermal growth factor receptor (p110 sEGFR) have been studied individually as biomarkers of ovarian cancer. In this study, we compare serum CA125 levels and sEGFR concentrations in women with EOC to women with benign gynecologic conditions of ovarian and non-ovarian origin. We show that serum sEGFR concentrations are lower in patients with EOC than in women with benign gynecologic conditions, whereas serum CA125 levels are higher in patients to EOC compared with women with benign gynecologic conditions. These data also reveal that age and serum sEGFR concentrations modify the association between CA125 levels and EOC versus benign gynecologic disease. Hence, age- and sEGFR-dependent CA125 cutoff thresholds improve the ability of CA125 to discern EOC patients from women with benign ovarian tumors and non-ovarian gynecologic conditions. Our analyses show that parallel testing with fixed sEGFR and CA125 cutoff thresholds optimizes sensitivity to detect EOC, whereas serial testing with age- and sEGFR-dependent CA125 cutoff thresholds optimizes test specificity, and overall accuracy to discern patients with EOC from women with benign ovarian and non-ovarian gynecologic conditions. The combined use of serologic sEGFR and CA125, thus, has improved utility for screening and diagnosing EOC, which may increase the positive predictive value of a multimodal screening program that incorporates these biomarkers to detect and subsequently differentiate benign from malignant ovarian tumors.

Adult↗
PubMed2003

Soluble epidermal growth factor receptor (sEGFR/sErbB1) as a potential risk, screening, and diagnostic serum biomarker of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies in the United States, for which risk assessment, screening, and diagnostic tests are needed. We have shown previously that women with stage III/IV EOC have lower serum p110 sEGFR/sErbB1 (Soluble Epidermal Growth Factor Receptor) concentrations than healthy women. Here, we show that serum p110 sEGFR/sErbB1 is the product of a 3-kb EGFR/ERBB1 alternate transcript. We report that serum sEGFR concentrations in stage I/II and stage III/IV EOC patients are significantly lower than in healthy women, and that serum sEGFR concentrations are not associated with disease stage or tumor grade. Logistic regression models show that: (a) lower serum sEGFR concentrations are associated significantly with a greater risk of EOC; (b) the risk associated with lower serum sEGFR concentrations is reduced by older age or menopause; and (c) age- or menopausal status-specific cutoff values for sEGFR concentration are appropriate. Receiver operating characteristic curves indicate that: (a) serum sEGFR concentrations are more effective in discerning stage III/IV than stage I/II EOC cases from healthy women; and (b) sEGFR concentrations have an 89% probability of correctly discerning EOC patients from healthy women when accounting for effect modification by age. By maintaining a test specificity of approximately 95% across strata of age or menopausal status with appropriate cutoff values, we observe that sEGFR concentrations are most useful for detecting stage I/II (sensitivity: 64-67%) and stage III/IV (sensitivity: 75-81%) EOC in young, premenopausal women. We conclude that serum sEGFR concentrations warrant additional investigation in the risk assessment, early detection, and/or diagnosis of EOC.

Adult↗
PubMed2002

Generation and characterization of polyclonal antibodies specific for human p110 sEGFR.

The EGFR/ERBB family of receptor tyrosine kinases mediates intracellular signal transduction pathways important in the regulation of cell growth, differentiation, and transformation. We previously have reported the cloning and expression of a 3 kb alternative EGFR transcript which encodes a 110 kDa form of the receptor (p110 sEGFR). This receptor isoform is identical to the extracellular region of the full-length 170 kDa EGFR through amino acid 603; in addition, p110 sEGFR contains 78 unique carboxy-terminal amino acids. Here, we report the generation and characterization of polyclonal antisera specific for the unique carboxy-terminal sequence of p110 sEGFR. Polyclonal antisera were generated by immunizing rabbits with synthetic peptides corresponding to peptides contained within the unique carboxy-terminal sequence of p110 sEGFR. Immunoglobulin fractions from antisera which tested positive for immune reactivity to these peptides by ELISA were affinity-purified by protein G and peptide-based chromatography. This affinity-purified immunoglobulin fraction specifically recognizes p110 sEGFR by ELISA, immunoprecipitation, immunoblot analysis, and immunocytochemical methods. No cross-reactivity with full-length p170 EGFR is observed using any of these detection methods. These new polyclonal antibodies will be useful in determining the expression, localization, and function of p110 sEGFR, and importantly will allow us to distinguish between the expression of this receptor isoform and p170 EGFR.

Animals↗