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Methotrexate-induced pneumonitis has been reported as an infrequent but potentially serious complication of therapy in a variety of malignant and benign conditions. Because inflammatory cell infiltration is concerned with the development of methotrexate-induced pneumoinitis, and because airway epithelial cells participate in the orchestration of lung inflammation, the authors determined whether methotrexate might stimulate airway epithelial cells (A549 cells) to release neutrophil, monocyte, and eosinophil chemotactic activities (NCA, MCA, and ECA). A549 cells released NCA, MCA, and ECA in a dose- and time-dependent manner in response to methotrexate. Partial characterization revealed the heterogeneity of NCA, MCA, and ECA. The release of chemo-tactic activity was blocked by lipoxygenase inhibitors and cycloheximide. NCA was inhibited by leukotriene (LT) B[SUB4] receptor antagonist, and anti-interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) antibodies. MCA was attenuated by LTB[SUB4] receptor antagonist, and anti-monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage CSF (GM-CSF) (antibodies. ECA was attenuated by LTB[SUB4] receptor antagonist, and anti-IL-8 and GM-CSF antibodies. The release of IL-8, G-CSF, MCP-1, GM-CSF, and LTB[SUB4] from A549 cells significantly increased in response to methotrexate. The mRNA expression of IL-8 and MCP-1 was augmented by methotrexate stimulation. These data suggest that type II epithelial cells may modulate inflammatory cell recruitment into the lung by releasing NCA, MCA, and ECA in response to methotrexate. [ABSTRACT FROM AUTHOR]

Demonstrates that human lung fibroblasts release chemotactic activity for neutrophils and monocytes in response to cyclophosphamide in a dose- and time-dependent manner. Indication that both neutrophil and monocyte activities were chemotactic; Suggestion that lung fibroblasts may modulate inflammatory cell recruitment into the lung by releasing neutrophil and monocyte in response to cyclophosphamide.

Examines whether human lung fibroblasts (HLF) may release mediators that are responsible for monocyte chemokinetic activity (MCA). Review of literature; Methodology of the study; Results.

Background: Optimal chemotherapeutic regimen in thymic carcinoma remains uncertain and the efficacy of second line chemotherapy has not been established either., Patients and Methods: We retrospectively evaluated the efficacy of an irinotecan plus cisplatin or carboplatin (IP) regimen as a salvage treatment for patients with unresectable thymic carcinoma that progressed after cisplatin, doxorubicin, vincristine and cyclophosphamide (ADOC) chemotherapy. Seven patients with histologically confirmed thymic carcinoma that was resistant to or who had relapsed after initial chemotherapy with ADOC were treated with IP. The treatment consisted of irinotecan (CPT-11, 60 mg/m2, days 1, 8 and 15) and cisplatin (80 mg/m2, day 1) or carboplatin (AUC 4) intravenously every 4 weeks, for at least 2 cycles., Result: Two patients achieved partial responses. Although another two patients showed a significant reduction of the primary thoracic lesion, the appearance of a new lesion was found in one and a metastatic lesion was unchanged in the other. Neutropenia over grade 3 was observed in all patients but none of the patients developed serious infections. There were no severe non-hematological toxicities, including diarrhea., Conclusion: We conclude that salvage chemotherapy may be useful in certain patients with thymic carcinoma and irinotecan may be a novel and alternative agent for relapsed thymic carcinoma.

Objective: Simplified sleep polysomnography was performed in 207 adult men to examine the relationship between the frequency of sleep-disordered breathing (SDB) and lifestyle-related illness., Methods: Each subject was checked for SDB using a simplified sleep polysomnograph (Auto-Set Portable; Teijin Limited, Tokyo, Japan). Apnea and hypopnea were detected with a nasal cannula type airflow sensor. Hypoxemia was checked with a percutaneous oxygen saturation (SpO2) monitor. We analyzed the relationships between SDB and body mass index (BMI) and hypertension, hyperlipidemia, liver dysfunction, fatty liver, and abnormal glucose metabolism., Results: Fifty-nine subjects (29%) showed SDB with apnea hypopnea index (AHI) over 15 times/h. The frequency of obesity (BMI > or = 25), hypertension, hypercholesterolemia, fasting blood glucose level, and HbA1c were significantly higher in patients with SDB than in normal individuals (AHI < 5 times/h). The frequencies of hypertension, hyperlipidemia, and abnormal glucose metabolism were compared between the obesity-free normal AHI group and the SDB group, and only that of hypertension was significantly different between the two groups., Conclusions: The present study revealed a high frequency of SDB among Japanese individuals. The results also suggest that as SDB becomes severe, it becomes more closely linked to the onset of lifestyle-related illnesses, such as hypertension, hypercholesterolemia and abnormal glucose metabolism.

The role of systemic chemotherapy and optimal regimen in thymic carcinoma remains uncertain. We evaluated the clinical responsiveness of ADOC (cisplatin, doxorubicin, vincristine, and cyclophosphamide) chemotherapy for advanced thymic carcinoma that have distant metastatic or unresectable lesions. From 1996 to 2000, we treated eight cases of thymic carcinoma. According to the classification by Masaoka et al., the clinical stage in one case was IVa, whereas the others were IVb. Histologic subtypes were as follows: four cases were squamous cell carcinoma, two cases were undifferentiated, and two were small-cell carcinoma. All patients received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously on day 1, 0.6 mg/m2 of vincristine intravenously on day 3, and 700 mg/m2 of cyclophosphamide intravenously on day 4, ADOC regimen, respectively, at 3- to 4-week intervals. Six patients obtained a partial response after ADOC chemotherapy and the overall clinical response rate was 75%. There were no life-threatening side effects noted. Cisplatin plus VP-16 chemotherapy (PVP) was performed in three cases before the ADOC regimen, but PVP chemotherapy did not show beneficial effects in two patients. Median survival time was 19 months. ADOC chemotherapy appears to have significant activity against thymic carcinoma.