Inflammation is a significant component of chronic neurodegenerative diseases. Cyclooxygenase-2 (COX-2) is expressed in activated microglial cells and appears to be an important source of prostaglandins during inflammatory conditions. To investigate the effect of curcumin on COX-2 gene expression in microglial cells, we treated lipopolysaccharide (LPS)-challenged BV2 microglial cells with various concentrations of curcumin. Curcumin significantly inhibited LPS-mediated induction of COX-2 expression in both mRNA and protein levels in a concentration-dependent manner. COX-2 enzyme activity was also inhibited in accordance with mRNA and protein levels. Furthermore, curcumin markedly inhibited LPS-induced nuclear factor kB (NF-kB) and activator protein 1 (AP-1) DNA bindings. These data suggest that curcumin suppresses LPS-induced COX-2 gene expression by inhibiting NF-k B and AP-1 DNA bindings in BV2 microglial cells.

Objectives: Anti-angiogenic agents are reported to exert clinical activity on epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancers. We evaluated the clinical outcomes of nintedanib and docetaxel in refractory NSCLC according to EGFR mutation status during the Korean nintedanib named patient program. Methods: Docetaxel was administered either 75 or 37.5 mg/m² on D1, D8 q every 3 weeks for 4–6 cycles plus nintedanib 200 mg orally twice daily until disease progression or unacceptable toxicity. Results: Sixty-two patients were enrolled for study. Twenty-eight patients with activating EGFR mutations progressed after EGFR-tyrosine kinase inhibitors (TKI) therapy and 25 out of 28 patients showing progression after platinum doublet chemotherapy were enrolled. The objective response rate was 29% and median PFS and OS were 3.9 months and 11.7 months. Based on the EGFR mutation status, the objective response rate was 39.3 vs. 21.9% (EGFR mut(+) vs. EGFR mut(–), p = 0.142) and median PFS was 6.5 vs. 3.3 months (EGFR mut(+) vs. EGFR mut(–), p = 0.009). No treatment-related deaths were reported. The most frequent drug-related adverse events (AE) were neutropenia (53.2%) and diarrhea (37.1%). Treatment in 12 patients (19.3%) was permanently discontinued due to AEs without disease progression. Conclusions: Our data indicated that nintedanib-docetaxel combination could be considered to be effective treatment in EGFR TKI-resistant EGFR mutant NSCLC.

Purpose: The purpose of this study was to examine the impact of different approaches stratified on risk based on chromosome 13 deletion and serum beta-2 microglobulin (MG) level would lead to survival benefit in patients with newly-diagnosed multiple myeloma. Patients and Methods: At diagnosis, fresh marrow samples for FISH and serum for beta-2 MG were sent to central laboratory and reviewed. Patients who had chromosome 13 deletion and high beta-2 MG (>2.5 mg/L) were considered to have high-risk disease. Patients without chromosome 13 deletion and low beta-2 MG were classified as low-risk group. Intermediate-risk group had to have either one of these two risk factors. After VAD induction chemotherapy, autologous stem cell transplantation conditioned with MEL200 was performed in patients at high- and intermediate-risk. DECP consolidation chemotherapy was added for high-risk patients. Patients who achieved CR after VAD in low-risk did not receive any further treatment. Results: As of Jun 2004, 50 patients were registered from 10 centers. Median age was 58 (range, 39–68) years old. Chromosome 13 deletion was detected in 18 patients (36%) and beta-2 MG was elevated in 39 patients (78%). Thirteen patients were classified as high-risk, 31 patients as intermediate-risk and 6 patients as low-risk. After median follow-up of 9 months, progression-free and overall survival at 1-year were 56% and 76%, respectively. To date, no statistically significant differences in survival were observed between risk groups (figure 1). Conclusion: In this study, risk-based approach in patients with multiple myeloma appeared to be feasible. Study accrual is ongoing and updated results will be presented. Figure Figure

14066 Background: Gemcitabine has been the standard regimen for advanced pancreatic cancer, but the effect on the response rate and survival is still disappointing. 5-fluorouracil(5-FU) and cisplatin are synergistic with gemcitabine as well as with each other. This study is aimed to determine the efficacy and safety of combination chemotherapy with gemcitabine, 5-FU and cisplatin for advanced pancreatic cancer. Methods: Patients(pt) with recurred or advanced pancreatic cancer were entered into this study, who had histologically proven adenocarcinoma, no prior radiotherapy, measurable lesion (≥2cm), ECOG performance scale (PS) 0–2, age 18–70, adequate bone marrow, cardiac and renal function, ALT ≤ 3× normal, and total bilirubin ≤ 2mg/dL.The pt were treated every 3weeks with gemcitabine 800 mg/m2, at 10mg/m2/min on days 1 and 8, 5-FU 1g/m2/24 hour continuous infusion from day 1 through 3 for 72 hours (extended to 4 days later in 12 pt due to lack of toxicity), and cisplatin 60 mg/m2 on day 2, 24 hours after the start of gemcitabine. Concurrent chemo-radiotherapy with gemcitabine 250 mg/m2/week was given to the pt with response of stable disease or better after 4 cycles of chemotherapy, if PS ≤1 and age ≤ 65. Results: Characteristics of 25 eligible pt; 17 male/ 8 female, PS 0,1 in 20 pt, 2 in 4 pt, Stage III in 3 pt, IV in 22, age 40–69 (median 62). Five pt had prior 5-FU-based chemotherapy. A total of 109 cycles were given (median 4; 1–10 cycles/person). Response by WHO criteria: 3 PR (14.3%; 95% confidence interval: 0 - 29.6%), 11 SD (52.4%) and 7 PD in 21 assessable pt. The median time to progression was 230 days (48+-478+) and median survival was 322 days (70+-757+). WHO grade ≥3 toxicity: neutropenia 19.3% (/cycle), thrombocytopenia 28.4%, mucositis 1.8%, and nausea and vomiting 5.6%. The clinical benefit response and correlation of tumor response with CA-19–9 level will be detailed on presentation. Conclusions: The chemotherapy with gemcitabine, 5-FU and cisplatin for advanced pancreatic cancer is safe, active and may have better survival benefit than gemcitabine alone. Based on these results, a nationwide phase III trial comparing with gemcitabine alone has been started. No significant financial relationships to disclose.