Prostaglandin E2 (PGE2), which is a potent pro-inflammatory lipid mediator, is biosynthesized from arachidonic acid by cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Non-steroidal anti-inflammatory drugs (NSAIDs) are used clinically as COX inhibitors, but they have gastrointestinal and cardiovascular side-effects. Thus, the terminal enzyme mPGES-1 holds promise as the next therapeutic target. In this study, we found that the ellagitannins granatin A and granatin B isolated from pomegranate leaves, and geraniin, which is their structural analog, selectively suppressed mPGES-1 expression without affecting COX-2 in non-small cell lung carcinoma A549 cells. The ellagitannins also down-regulated tumor necrosis factor α, inducible nitric oxide synthase, and anti-apoptotic factor B-cell chronic lymphocytic leukemia/lymphoma 2, and induced A549 cells to undergo apoptosis. These findings indicate that the ellagitannins have anti-inflammatory and anti-carcinogenic effects, due to their specific suppression of mPGES-1. Abbreviations: Bcl-2: B-cell chronic lymphocytic leukemia/lymphoma 2; COX: cyclooxygenase; CRE: cAMP response element; DHHDP: dehydrohexahydroxydiphenoyl; Et2O: diethyl ether; EtOAc: ethyl acetate; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; iNOS: inducible nitric oxide synthase; mPGES-1: microsomal prostaglandin E synthase-1; n-BuOH: water-saturated n-butanol; NSAIDs: non-steroidal anti-inflammatory drugs; NF-κB: nuclear factor-κB; PG: prostaglandin; TNF: tumor necrosis factor; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling

OBJECTIVE: Brain tumor patients with KPS of 60 to 30 after the initial treatment are not able to spend independent life at home. The goal of this study is to return these patients to their home with minimal family support by delivering intensive rehabilitation to them. Seventy-five brain patients were evaluated every 10 days from the beginning to the end of rehabilitation treatment, according to clinical scales of Functional Independence Measure (FIM) of 1–7 points depending on the degree of independence. The rehabilitation effect was judged by the degree of improvement of 11 out of 13 motor FIM items, excluding stair climbing and bathing movements. When more than half number of the 11 motor FIM items requiring physical assistance (4 points or less) improved up to non-assistance (5 points or more), it was judged as a significant effect. In addition, when all 11 items present with 6 points (independence possible) or more and all 5 of FIM recognition items are 5 points or more (understand the domestic rules), it was judged that the patients acquired independent living ability. RESULTS: 1. Of the 75 patients, 54 (72%) showed a significant effect, and 38 of them (50.7% of the total) aquired independence at home. The acquisition-rate of independent living ability by tumor was 44.7% for 38 malignant gliomas, 53.8% for 13 metastatic tumors, 50% for 14 meningiomas, and 71.4% for 7 vascular tumors, and there was no significant difference between them. 2. The median time to reach the maximum rehabilitation effect was 35 days. CONCLUSION: Intensive rehabilitation for brain tumor patients with KPS of 60 to 30 is effective and should be incorporated into the palliative treatments in the brain tumor treatment guidelines.