Characterization and clinical validation of MCM2 and TOP2A monoclonal antibodies in the BD ProEx™ C assay: An immunoassay which detects aberrant S-phase induction in cervical tissue.

Background: The Papanicolaou (Pap) screen has been successful in reducing cervical cancer; but exhibits low sensitivity when detecting cervical dysplasia. Use of molecular biomarkers in Pap tests may improve diagnostic accuracy.

Design: Monoclonal antibodies to Minichromosome Maintenance Protein 2 (MCM2) and DNA Topoisomerase II α (TOP2A) were selected for use in IHC based on their ability to differentiate normal from diseased cervical tissues in tissue microarrays.

Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence.

Objective: To determine the utility of novel combinations of biomarkers, using both a one-step and two-step assay format, to distinguish serum of early ovarian cancer patients from that of healthy controls and to discern the utility of these biomarkers in a monitoring capacity.

Methods: For ovarian cancer detection, HE4, Glycodelin, MMP7, SLPI, Plau-R, MUC1, Inhibin A, PAI-1, and CA125 were evaluated in a cohort of 200 women with ovarian cancer and 396 healthy age-matched controls. Each biomarker was assessed by serum-based immunoassays utilizing novel monoclonal antibody pairs or commercial kits.

Exisulind-induced apoptosis in a non-small cell lung cancer orthotopic lung tumor model augments docetaxel treatment and contributes to increased survival.

We reported previously a significant increase in survival of nude rats harboring orthotopic A549 human non-small cell lung cancer tumors after treatment with a combination of exisulind (Sulindac Sulfone) and docetaxel (D. C. Chan, Clin.

Pro-apoptotic actions of exisulind and CP461 in SW480 colon tumor cells involve beta-catenin and cyclin D1 down-regulation.

Exisulind and its analogues are inhibitors of cyclic GMP phosphodiesterases (PDEs) that have been shown to activate and induce protein kinase G, resulting in the induction of apoptosis in colon cancer cells. These drugs also reduce beta-catenin protein levels and decrease cyclin D1 mRNA levels in SW480 cells. Herein we report on studies pertaining to exisulind regulation of beta-catenin levels and activity in colon tumor cells.

Exisulind in combination with docetaxel inhibits growth and metastasis of human lung cancer and prolongs survival in athymic nude rats with orthotopic lung tumors.

Docetaxel, a semisynthetic taxane, improves the survival of stage IIIB and IV non-small cell lung cancer patients. However, the 5-year survival remains poor, and few patients experience a complete remission. In this report, we evaluated the effects of exisulind, a novel proapoptotic agent that is a sulfone metabolite of sulindac, in combination with docetaxel on the growth of the human non-small cell lung cancer cell line A549 in vitro and in vivo.

Preclinical and clinical studies of docetaxel and exisulind in the treatment of human lung cancer.

Lung cancer is the leading cause of cancer death in the United States. The majority of patients with non-small cell lung cancers present with inoperable disease because of the presence of metastases to regional lymph nodes or other metastatic sites. About one third of patients have stage IV disease with metastases to distant organs at the time of diagnosis.

Centrosome amplification drives chromosomal instability in breast tumor development.

Earlier studies of invasive breast tumors have shown that 60-80% are aneuploid and approximately 80% exhibit amplified centrosomes. In this study, we investigated the relationship of centrosome amplification with aneuploidy, chromosomal instability, p53 mutation, and loss of differentiation in human breast tumors. Twenty invasive breast tumors and seven normal breast tissues were analyzed by fluorescence in situ hybridization with centromeric probes to chromosomes 3, 7, and 17.