Detection of MAGE-4 protein in sera of patients with head-and-neck squamous-cell carcinoma

The MAGE-4 gene, a member of the MAGE gene family, is expressed in various cancers, including head-and-neck squamous-cell carcinomas (HN-SCC), but is not expressed in any normal tissues except for the testis and placenta. The aim of this study was to determine whether serum MAGE-4 protein is a useful tumor marker for detection of HN-SCC. An enzyme-linked immunosorbent assay was used to measure serum level of MAGE-4 protein. The serum level of MAGE-4 in pre-operative HN-SCC patients was significantly higher than that in patients with non-malignant diseases (NMD) of the head and neck, volunteers undergoing cancer screening (VOL), or healthy donors (HD). When the cut-off level was determined at 1.15 ng/ml (mean plus 3 SD of HD), sera from 28 of 96 patients with HN-SCC (p < 0.0001 vs. the other groups), 7 of 82 patients with NMD, 2 of 92 with VOL, and 0 of 68 HD were positive for MAGE-4. Serum levels of MAGE-4 protein in all 7 HN-SCC patients whose sera were positive for MAGE-4 before operation decreased after operation, and, in one patient, a renewed rise in serum level was followed by recurrence. These results indicate that MAGE-4 protein is detectable in sera of a significant number of HN-SCC patients, and that serum MAGE-4 protein might be a useful tumor marker to monitor the recurrence of MAGE-4-positive HN-SCC. Int. J. Cancer, 70:287–290, 1997. © 1997 Wiley-Liss, Inc.     

An orally bioavailable small molecule antagonist of CRTH2, ramatroban (BAY u3405), inhibits prostaglandin D2-induced eosinophil migration in vitro

Ramatroban (Baynas, BAY u3405), a thromboxane A(2) (TxA(2)) antagonist marketed for allergic rhinitis, has been shown to partially attenuate prostaglandin (PG)D(2)-induced bronchial hyperresponsiveness in humans, as well as reduce antigen-induced early- and late-phase inflammatory responses in mice, guinea pigs, and rats. PGD(2) is known to induce eosinophilia following intranasal administration, and to induce eosinophil activation in vitro. In addition to the TxA(2) receptor, PGD(2) is known as a ligand for the PGD(2) receptor, and the newly identified G-protein-coupled chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). To fully characterize PGD(2)-mediated inflammatory responses relevant to eosinophil activation, further analysis of the mechanism of action of ramatroban has now been performed. PGD(2)-stimulated human eosinophil migration was shown to be mediated exclusively through activation of CRTH2, and surprisingly, these effects were completely inhibited by ramatroban. This is also the first report detailing an orally bioavailable small molecule CRTH2 antagonist. Our findings suggest that clinical efficacy of ramatroban may be in part mediated through its action on this Th2-, eosinophil-, and basophil-specific chemoattractant receptor.     

Human polymorphonuclear leukocyte activating factor isolated from Aleurites Fordii Hemsl. (Euphorbiaceae) seed

A human polymorphonuclear leukocyte (PMN) activating factor (AFH-S) was isolated from a tropical plant seed, Aleurites Fordii Hemsl. (AFH) in PBS. It is found that the AFH-S stimulate human PMNs and induced superoxide generation and chemotaxis. Superoxide generation was affected by the extracellular calcium ion or pretreatment with H-7 (PK-C inhibitor), but not by mepacrine (PLA2 inhibitor) or pertussis toxin (islet-activating protein: IAP). Furthermore, a lag time exists dose-dependently. In addition the cytosolic calcium was not increased by the stimulation with AFH-S. Thus, the receptor for AFH-S was suggested to be independent from Ni-like protein, PI-response, or PLA2-activation, and stimulate PMNs through activation of PK-C.     

Aspiration of Cerebrospinal Fluid Rhinorrhea as a Cause of Non-resolving Pneumonia

We herein report two cases of cerebrospinal fluid (CSF) rhinorrhea associated with lung infiltrates. One patient presented with symptomatic non-resolving pneumonia, while the other was asymptomatic. In both cases, the lung infiltrates completely resolved when CSF leakage had subsided. Pulmonary involvement in CSF rhinorrhea is under-recognized, and despite being the definitive treatment, surgery for CSF rhinorrhea is typically postponed due to the presence of lung infiltrates. However, meningitis is a serious complication due to a delay in surgical management. Physicians should be made aware that CSF rhinorrhea is a potential cause of intractable lung infiltrates.