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The ErbB receptors, such as ErbB-1 and ErbB-2, have been intensely pursued as targets for cancer therapeutics. Although initially efficacious in a subset of patients, drugs targeting these receptors led invariably to resistance, which is often associated with reactivation of the ErbB-3-PI3K-Akt signaling. This may be overcome by an ErbB-3 ligand that abrogates receptor-mediated signaling. Toward this end, we have generated a mouse monoclonal antibody, MP-RM-1, against the extracellular domain (ECD) of ErbB-3 receptor. Assessment of human tumor cell lines, as well as early passage tumor cells revealed that MP-RM-1 effectively inhibited both NRG-1β-dependent and -independent ErbB-3 activation. The antagonizing effect of MP-RM-1 was of non-competitive type, as binding of [125I]-labeled NRG-1β to ErbB-3 was not influenced by the antibody. MP-RM-1 treatment led, in most instances, to decreased ErbB-3 expression. In addition, MP-RM-1 was able to inhibit the colony formation ability of tumor cells and tumor growth in two human tumor xenograft nude mouse models. Treatment with the antibody was associated with a decreased ErbB-3 and Akt phosphorylation and ErbB-3 expression in the excised tumor tissue. Collectively, these results indicate that MP-RM-1 has the potential to interfere with signaling by ErbB-3 and reinforce the notion that ErbB-3 could be a key target in cancer-drug design. [ABSTRACT FROM AUTHOR]

Objectives: Differential diagnosis of pancreatic cancer versus chronic pancreatitis may be difficult. The aim of this study is to determine whether a group of tumor-associated antigens could differentiate between the two pathologies. Methods: CA 19-9, TAG-72, CAR-3, and a newly discovered antigen termed "90K" were determined in the serum and in the pancreatic juice of 19 patients with pancreatic cancer, 20 patients with chronic pancreatitis, and seven controls with lithiasis of extrapancreatic bile ducts. Results: The serum antigen levels of all three markers except 90K were significantly higher in pancreatic cancer than in chronic pancreatitis. High correlations were found between serum CA 19-9 and both TAG-72 and CAR-3. 90K did not correlate with other markers. In pancreatic juice, only 90K values were significantly higher in chronic pancreatitis than in pancreatic cancer, and only 90K and CA 19-9 were significantly correlated. At the stepwise discriminant analysis, serum CA 19-9 and pancreatic juice 90K had independent diagnostic roles. Used in combination, they correctly identified 84.2% of pancreatic cancer and 90% of chronic pancreatitis. Conclusions: These data suggest that pancreatic juice 90K and serum CA 19-9 can discriminate between chronic pancreatitis and pancreatic cancer. The data further support the complementary use of tumor-associated antigens along with other diagnostic tools. [ABSTRACT FROM AUTHOR]

A dose-finding study was undertaken to determine the maximum-tolerated dose, and the recommended dose of docetaxel in combination with 12-h timed (22:00-10:00) flat infusion of 5-fluorouracil (5-FU) in metastatic breast cancer patients. This schedule seems to reduce the occurrence of stomatitis of the docetaxel and infusional 5-FU regimen. [ABSTRACT FROM AUTHOR]