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The epidermal growth factor receptor (EGFR) variant type III (variously called EGFRvIII, de2-7 EGFR or ∆ ∆ ∆ ∆EGFR) has an in-frame deletion of the extracellular domain and is found in numerous types of human tumors. Since EGFRvIII has been reported to be tumorspecific and has oncogenic potential, it is being investigated as a potential therapeutic target. Because the cell-specific expression of EGFRvIII in lung has not been well documented, we examined the expression of EGFRvIII in 76 non-small cell lung cancers (NSCLCs) and 10 non-neoplastic lung tissues by immunohistochemistry using a new monoclonal antibody specific for this variant receptor. We found a higher incidence (30 of 76, 39%) of enhanced EGFRvIII expression in NSCLC than previously described. Interestingly, the presence of EGFRvIII was also observed in several normal tissue components of lung (e.g., normal bronchial epithelium). Given the high prevalence of EGFRvIII in NSCLC, a newly he epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of several human tumors, including those of the brain, breast, lung and head and neck, and is being actively studied as a target for therapy.1-6) Overexpression of the EGFR in multiple human tumors has been extensively documented, and it has become increasingly apparent that alterations within the EGFR gene may be as important as overexpression for oncogenic effect. 7,8) Several different types of alterations that result in aberrant protein products have been identified. [9][10][11] The most common variant, EGFRvIII (also referred to as ∆EGFR, or de2-7 EGFR), is characterized by an inframe deletion of exons 2-7 of the coding sequence, which has been found to be generated by gene rearrangement or aberrant mRNA splicing. [12][13][14][15] This deletion removes 267 amino acids from the extracellular domain of the normal EGFR, creating a unique epitope at the fusion junction. A number of functional differences between EGFRvIII and EGFR have been characterized. [15][16][17][18] Although EGFRvIII fails to bind EGF, the tyrosine kinase in the intracellular portion is constitutively activated, so that the receptor undergoes tyrosine (Tyr) autophosphorylation. 13,16,19,20) We have previously shown that overexpression of EGFRvIII in NIH3T3 cells causes a highly transformed phenotype as a result of the ligand-independent activation of the receptor kinase.16) Furthermore, we have demonstrated the frequent expression of EGFRvIII in a variety of human tumors with or without EGFR amplification, suggesting that EGFRvIII confers a growth advantage upon tumor cells in vivo. [21][22][23][24][25][26] EGFRvIII has also been shown to be an extremely attractive target for anticancer therapy.15) In a rodent model, vaccination with a peptide corresponding to the alteration present in EGFRvIII could both prevent tumor formation and induce the regression of tumors expressing this receptor.27) More recently, it has been shown that systemic treatment of mice bearing tumors expressing EGFRvIII with monoclonal antibodi...

Intestinal intraepithelial T lymphocytes (i-IELs) show features different from those of conventional T cells and play specific roles in the mucosal immunity. To investigate whether human bronchial intraepithelial T lymphocytes (IELs) are a distinct entity, we examined T cells in human bronchial xenografts transplanted on mice with severe combined immune deficiency (SCID). We transplanted human bronchi subcutaneously into mice with SCID, resected the xenografts after various incubation periods (7-174 d), and examined them for CD3(+), CD4(+), CD8(+), and CD45(+) cells by immunohistochemistry. The number of CD3(+) cells in the lamina propria decreased significantly in the first month (from 308.7 +/- 60.2 to 70.9 +/- 49. 4/mm(2); P < 0.05), and xenografts more than 5 mo of age had scant T cells in the lamina propria (5.2 +/- 2.0/mm(2)). However, there was no significant difference between the number of CD3(+) IELs in freshly isolated bronchi and in xenografts maintained for more than 5 mo. In freshly isolated bronchi, the number of CD4(+) IELs was significantly lower than that of CD8(+) cells (2.35 +/- 0.62 versus 4.56 +/- 1.32/mm basement membrane; P < 0.01). After transplantation, the mean CD4-to-CD8 ratio of all xenografts was significantly higher than that of freshly isolated bronchi (5.2 +/- 0.9 versus 0.6 +/- 0.2; P < 0.005). The IELs were positive for CD45, which is specific for human leukocytes, and they were eliminated by irradiation before the transplantation. Almost all IELs (99.5%) in the xenografts expressed alphabeta T-cell receptor, and 35.8% of IELs expressed alpha(e)beta7 integrin. Bronchial epithelial cells in the xenografts expressed interleukin (IL)-7, stem cell factor, intercellular adhesion molecule (ICAM)-1, and human leukocyte antigen-DR (HLA-DR). We conclude that in the SCID-Hu chimera model, human bronchial IELs survive for more than 5 mo, unlike the T cells in the lamina propria, and we suggest that human bronchial IELs may be stimulated by bronchial epithelial cells expressing IL-7, stem cell factor, ICAM-1, and HLA-DR.

We present 3 cases of rapidly progressive interstitial pneumonia (RPIP) associated with clinically amyopathic dermatomyositis (C-ADM) that were treated with two courses of direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP). Despite initial treatment with high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine, the lung disease and hypoxemia deteriorated in all the patients. After PMX-DHP treatment, the PaO2/FiO2 ratio and serum LDH and KL-6 were improved, the abnormal shadows in chest high-resolution computed tomography (HRCT) scans gradually decreased, and, finally, all patients survived. These findings indicate that PMX-DHP treatment could be effective in the management of RPIP in patients with C-ADM in combination with conventional therapy.