Treatment outcomes in patients with extranodal marginal zone B-cell lymphoma of the lung.

OBJECTIVES: To evaluate clinical presentations, treatment modalities, and outcomes of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma by stage strata. METHODS: We retrospectively reviewed 51 patients diagnosed with pulmonary MALT lymphoma between January 2003 and December 2015. To compare treatment modalities and outcomes, we stratified the patients into low-stage (IE/IIE) and high-stage (IIIE/IVE) groups using modified Ann Arbor staging. Progression-free survival was estimated using Kaplan-Meier curves, and differences were compared using the log-rank test. A hazard ratio of progression by stage strata, adjusted for other clinical variables, was determined using a Cox adjusted proportional hazards model. RESULTS: The majority of patients had stage IE disease (76.5%; 39 of 51). With advancing stage, patients were more likely to have respiratory and B symptoms and higher International Prognostic Index scores. The most common treatment modality was surgical resection in low-stage patients (33 of 43) and chemotherapy in high-stage patients (7 of 8). At a median follow-up of 40.7 months, progression-free survival was longer for low-stage patients (median, 40.7 months vs 24.9 months; P < .001), and high-stage patients were 9.2 times more likely to progress (hazard ratio, 9.24; 95% confidence interval, 1.93-44.36). Among 30 patients with surgically resected stage IE disease, 8 with central lesions were treated via lobectomy and 22 with peripheral lesions were treated via lobectomy (n = 8) or limited resection (n = 14). One of these patients, with a central lesion, experienced disease recurrence. CONCLUSIONS: Our findings suggest that the clinical course of low-stage pulmonary MALT lymphoma, for which the mainstay of treatment is surgical resection, might be indolent.

3-Dimensional micropillar drug screening identifies FGFR2-IIIC overexpression as a potential target in metastatic giant cell tumor.

We established two patient derived tumor cells (PDCs) from right and left pulmonary metastatic lesions respectively of a patient with giant cell tumor. At that time, patient-derived tumor cells from right and left surgical specimens were collected and cultured. High-throughput screening (HTS) for 24 drugs was conducted with a micropillar/microwell chip platform using giant cell tumor PDCs. Using 6 doses per drug in 6 replicates for giant cell tumor PDCs, the dose response curves and corresponding IC50 values were calculated from the scanned images using the S+ Chip Analyzer. A sensitive response was more significantly achieved for AZD4547 (FGFR2 inhibitor) in giant cell tumor PDCs originated from the right pulmonary nodule under the micropillar/microwell chip platform using 3D culture. This sensitivity was consistent with the target expression patterns of giant cell tumor PDCs (FGFR2-IIIC mRNA expression in giant cell tumor PDCs originated from the right pulmonary nodule was increased significantly as compared to those originated from left). However, in a conventional 2D cultured MTT assay, there was no difference for IC50 values of AZD4547 between giant cell tumor PDCs originated from right and left pulmonary nodules. An HTS platform based on 3D culture on micropillar/microwell chips and PDC models could be applied as a useful preclinical tool to evaluate the intrapatient tumor/response heterogeneity. This platform based on 3D culture might reflect far better the relation between the tumor-biology and the matched targeted agent as compared to a conventional 2D cultured MTT assay.

Anti-inflammatory activities of Dangyuja (Citrus grandis Osbeck) in concanavalin A stimulated murine splenocytes and 12-O-tetradecanoylphorbol-13-acetate-induced murine skin edema.

Dangyuja (Citrus grandis Osbeck), a citrus cultivated in southern Korea, has been used in traditional medicine for its anti-inflammatory effect. In this study, we investigated the anti-inflammatory potential of extract of Citrus grandis Osbeck (ECGO). In in vitro assays, ECGO treatment of concanavalin A (10µg/ml, for 24h) stimulated splenocytes showed significant reduction in CD44/CD62L+ T cell population and a marked decrease in the production of inflammatory cytokines IL-2, IFN-γ and IL-4. Interestingly, in vivo assays of ECGO topical treatment (100µg/20µl/ear) significantly mitigated the TPA (4µg/20µl/ear) induced edema induction and Myeloperoxidase activity. Anti-inflammatory potential of ECGO were further evidenced through its potent decrease in expression of inducible nitric oxide, cyclooxygenase-2, IL-1ß and TNF-α and suppressed homing of CD3+ T cells and F4/80+ macrophages to site of inflammation. This study emphasizes the possibility of developing ECGO as an alternative natural topical agent to combat inflammatory diseases.