We have previously observed that HIV-1 replication is suppressed in uninflamed lung and increased during tuberculosis. In vitro THP-1 cell–derived macrophages inhibited HIV-1 replication after infection with Mycobacterium tuberculosis. Suppression of HIV-1 replication was associated with inhibition of the HIV-1 long terminal repeat (LTR) and induction of ISGF-3, a type I interferon (IFN)–specific transcription factor. Repression of the HIV-1 LTR required intact CCAAT/enhancer binding protein (C/EBP) sites. THP-1 cell–derived macrophages infected with M. tuberculosis, lipopolysaccharide, or IFN-β induced the 16-kD inhibitory C/EBPβ isoform and coincidentally repressed HIV-1 LTR transcription. C/EBPβ was the predominant C/EBP family member produced in THP-1 macrophages during HIV-1 LTR repression. In vivo, alveolar macrophages from uninflamed lung strongly expressed inhibitory 16-kD C/EBPβ, but pulmonary tuberculosis abolished inhibitory C/EBPβ expression and induced a novel C/EBP DNA binding protein. Therefore, in vitro, proinflammatory stimulation produces an IFN response inhibiting viral replication by induction of a C/EBPβ transcriptional repressor. THP-1 cell–derived macrophages stimulated with type I IFN are similar to alveolar macrophages in the uninflamed lung in vivo. In contrast, the cellular immune response in active pulmonary tuberculosis disrupts this innate immunity, switching C/EBP expression and allowing high level viral replication.

Purpose: To evaluate the efficacy and toxicity of a novel combination chemotherapeutic regimen including cisplatin with an oral anticancer agent, S-1 that consisted of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, for non-small-cell lung cancer (NSCLC) patients.Experimental Design: In this phase II trial, patients with locally advanced and metastatic NSCLC were treated with the oral administration of S-1 at 40 mg/m 2 twice a day for 21 consecutive days while cisplatin (60 mg/m 2 ) was administered intravenously on day 8. This schedule was repeated every 5 weeks.Results: Of 56 patients enrolled in the study, 55 patients were eligible and analyzed. The median number of cycles administered was 3 (range, 1-12 cycles). Among these 55 patients, one complete response and 25 partial responses were observed with an overall response rate of 47% (95% confidence interval, 34 -61%). The median survival time was 11 months and the 1-year survival rate was 45%. Hematologic toxicities of grades 3 and 4 included neutropenia (29%) and anemia (22%). No grade 4 nonhematologic toxicity was observed. Grade 3 toxicity included anorexia (13%), vomiting (7%), or diarrhea (7%).Conclusions: S-1 plus cisplatin combination chemotherapy showed a promising effectiveness with acceptable toxicity rates in patients with advanced NSCLC. These results warrant further investigations of this regimen including a randomized controlled trial for its use as a first line treatment for NSCLC.

Angiogenic cytokines, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiogenin, are candidates for the induction of pleural effusions because they have been implicated in the induction of neovascularization, vascular permeability, and hemorrhage both in the inflammatory process and in tumor progression. Thus, we hypothesized that these angiogenic factors in effusion might be involved in the clinical manifestation of malignant pleural disease. We measured the levels of VEGF, bFGF, and angiogenin in pleural effusions and sera from 40 patients. Pleural effusions due to malignancy (1,350 pg/ml) contained significantly higher levels of VEGF than effusions due to inflammatory diseases (102 pg/ml; p = 0.034). Furthermore, hemorrhagic effusions showed significantly higher VEGF levels (1,942 pg/ml) than non-hemorrhagic effusions (202 pg/ml; p = 0.016) in malignant patients. In contrast, neither bFGF nor angiogenin were correlated with any clinical manifestation of pleural effusion. Immunohistochemical study revealed that malignant cells in the pleura were stained with anti-VEGF antibody. Our data suggest that VEGF secreted from tumor cells may be involved in the accumulation of pleural effusion in malignancy, and that increased levels of VEGF may induce hemorrhagic effusion.