Distribution and molecular characterization of a cell-surface and a cytoplasmic antigen detectable in human melanoma cells with monoclonal antibodies

The monoclonal antibodies 225.28S and 465.12 to human melanoma-associated antigens have been tested with a large variety of surgically removed skin lesions and malignant tumors as well as with a panel of cultured cell lines in serological and immunochemical assays. The antibody 225.28S reacts with a plasma membrane antigen while the antibody 465.12 detects a cytoplasmic antigen. Both antibodies fail to react with melanocytes from normal skin as well as benign skin lesions but react with nevi, melanoma cells and some skin carcinomas. Analysis with surgically removed tumors and cultured human cell lines indicated that the plasma membrane antigen is restricted to skin lesions whereas the cytoplasmic antigen is synthesized by tumor cells of various histologcal origins. The plasma membrane antigen is composed of two glyco-polypeptides of 280,000 and > 440,000 daltons, while the cytoplasmic antigen consists of 4 glycopolypeptides of 94,000, 75,000, 70,000 and 25,000 daltons. None of these components are bridged by disulfide bonds. The cytoplasmic antigen was readily detected in the spent culture medium of melanoma cell lines in the form of a major 94,000 dalton and a minor 72,000 dalton structure, while the plasma membrane antigen was detectable only after vastly increasing the sensitivity of the assay system.     

STUDIES ON THE PATHOGENESIS OF FEVER : XX. SUPPRESSION AND REGENERATION OF PYROGEN-PRODUCING CAPACITY OF EXUDATE GRANULOCYTES

Suppression of the pyrogen-producing capacity of exudate granulocytes results from incubation of the cells in plasma, serum, or Ringer's solution. When transferred in this state and incubated in isotonic NaCl, the cells release much less pyrogen than untreated exudate cells. The suppressive effect is reversible and appears to involve the cellular uptake of calcium ions. In contrast, regeneration of pyrogen-producing capacity in depleted exudate cells occurs only when the cells are incubated in serum. The process resembles activation and requires the cellular synthesis of protein.     

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

Metastasis via the lymphatics is a major risk factor in squamous cell carcinoma of the oral cavity (OSCC). We sought to determine whether the presence of metastasis in the regional lymph node could be predicted by a gene expression signature of the primary tumor. A total of 18 OSCCs were characterized for gene expression by hybridizing RNA to Affymetrix U133A gene chips. Genes with differential expression were identified using a permutation technique and verified by quantitative RT-PCR and immunohistochemistry. A predictive rule was built using a support vector machine, and the accuracy of the rule was evaluated using crossvalidation on the original data set and prediction of an independent set of four patients. Metastatic primary tumors could be differentiated from nonmetastatic primary tumors by a signature gene set of 116 genes. This signature gene set correctly predicted the four independent patients as well as associating five lymph node metastases from the original patient set with the metastatic primary tumor group. We concluded that lymph node metastasis could be predicted by gene expression profiles of primary oral cavity squamous cell carcinomas. The presence of a gene expression signature for lymph node metastasis indicates that clinical testing to assess risk for lymph node metastasis should be possible.