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Brad Stone

Publications and source records attributed to Brad Stone.

11 recordsLinked to original sources
PubMed2006

Immunoediting of cancers may lead to epithelial to mesenchymal transition.

Tumors evade both natural and pharmacologically induced (e.g., vaccines) immunity by a variety of mechanisms, including induction of tolerance and immunoediting. Immunoediting results in reshaping the immunogenicity of the tumor, which can be accompanied by loss of Ag expression and MHC molecules. In this study, we evaluated immunoediting in the neu-transgenic mouse model of breast cancer. A tumor cell line that retained expression of rat neu was generated from a spontaneous tumor of the neu-transgenic mouse and, when injected into the non-transgenic parental FVB/N mouse, resulted in the development of a strong immune response, initial rejection, and ultimately the emergence of neu Ag-loss variants. Morphologic and microarray data revealed that the immunoedited tumor cells underwent epithelial to mesenchymal transition accompanied by an up-regulation of invasion factors and increased invasiveness characteristic of mesenchymal tumor cells. These results suggest that immunoediting of tumor results in cellular reprogramming may be accompanied by alterations in tumor characteristics including increased invasive potential. Understanding the mechanisms by which tumors are immunoedited will likely lead to a better understanding of how tumors evade immune detection.

Animals↗
PubMed2006

Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection.

Biomarkers for early detection of epithelial ovarian cancer (EOC) are urgently needed. Patients can generate antibodies to tumor-associated antigens (TAAs). We tested multiplex detection of antibodies to candidate ovarian TAAs and statistical modeling for discrimination of sera of EOC patients and controls. Binding of serum antibody of women with EOC or healthy controls to candidate TAA-coated microspheres was assayed in parallel. A Bayesian model/variable selection approach using Markov Chain Monte Carlo computations was applied to these data, and serum CA125 values, to determine the best predictive model. The selected model was subjected to area under the receiver-operator curve (AUC) analysis. The best model generated an AUC of 0.86 [95% confidence interval (95% CI), 0.78-0.90] for discrimination between sera of EOC patients and healthy patients using antibody specific to p53, NY-CO-8, and HOXB7. Inclusion of CA125 in the model provided an AUC of 0.89 (95% CI, 0.84-0.92) compared with an AUC of 0.83 (95% CI, 0.81-0.85) using CA125 alone. However, using TAA responses alone, the model discriminated between independent sera of women with nonmalignant gynecologic conditions and those with advanced-stage or early-stage EOC with AUCs of 0.71 (95% CI, 0.67-0.76) and 0.70 (95% CI, 0.48-0.75), respectively. Serum antibody to p53 and HOXB7 is positively associated with EOC, whereas NY-CO-8-specific antibody shows negative association. Bayesian modeling of these TAA-specific serum antibody responses exhibits similar discrimination of patients with early-stage and advanced-stage EOC from women with nonmalignant gynecologic conditions and may be complementary to CA125.

Antibodies, Neoplasm↗
PubMed2006

Identification of autoantibodies elicited in a patient with prostate cancer presenting as dermatomyositis.

OBJECTIVES: Dermatomyositis is an uncommon autoimmune disease distinguished by proximal muscle weakness and a characteristic skin rash. Dermatomyositis has also frequently been associated with malignancy, typically heralding the diagnosis of ovarian, lung, gastric, or colorectal cancer. We report an unusual case of prostate adenocarcinoma preceded by a diagnosis of dermatomyositis. We hypothesized that in this particular patient, proteins produced by the neoplastic prostatic tissue, which might be normally expressed in muscle tissue, were immunologically recognized as autoantigens. METHODS: Serum from this patient was used to screen a cDNA lambda phage expression library from normal prostate tissue for prostate protein-specific IgG. RESULTS: We identified several immunoreactive plaques encoding known autoantigens, and several encoding known muscle-related proteins, including aldolase C, eukaryotic translation elongation factor 1 alpha 1, transgelin, and acetyl-coenzyme A acyltransferase 1. IgG specific for these proteins were not specifically recognized in sera from other patients with prostate cancer compared with male control blood donors, and were not specifically recognized in a small panel of sera from patients with breast or ovarian cancer and dermatomyositis. CONCLUSIONS: Our results demonstrate that this patient with prostate cancer presenting as dermatomyositis had autoantibodies to specific proteins, possibly associated with his autoimmune myopathy. Moreover, given this patient's history and the multiple treatment options for prostate cancer, the identification of dermatomyositis in men should prompt an evaluation to exclude a concurrent diagnosis of prostate cancer.

Adenocarcinoma↗
PubMed2003

Serologic analysis of ovarian tumor antigens reveals a bias toward antigens encoded on 17q.

We utilized SEREX immunoscreening to identify a set of novel tumor antigens that are associated with human serous ovarian cancer and may prove useful for the early detection and treatment of this disease. Extensive screening with a panel of sera from 25 late-stage ovarian cancer patients against 3 independent cDNA libraries identified a set of 9 antigens that were immunogenic in more than 1 patient and not in a panel of 20-45 normal female serum donors. These antigens include p53, NY-ESO-1, UBQLN1, HOXB6, TOP2A, putative helicase-RUVBL (RUVBL), HMBA-inducible (HEXIM1), DDX5 and HDCMA. Ten of 25 ovarian cancer patients (40%) expressed serum IgG to at least 1 of these antigens, while 14% (4/25) had antibodies to 2 or more antigens. Unexpectedly, 4 antigens identified in this screen, DDX5, HEXIM1, TOP2A and HOXB6, are encoded within a region of 17q that also includes the genes for HER2/neu, Homeobox-B7 and BRCA1. Real-time RT-PCR analysis showed that mRNA for HER2/neu and 3 SEREX-defined antigens, TOP2A, HOXB6 and DDX5, was more abundant in ovarian tumors than most normal tissues, including normal and benign ovarian tissues, suggesting that elevated expression of genes encoded within this region of chromosome 17 is a common event in ovarian tumors. Thus, these abnormal expression patterns combined with the endogenous immune response suggests that these antigens represent potential targets for immunotherapy.

Antigens, Neoplasm↗
PubMed2002

Beyond the light.

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Elective Surgical Procedures↗