PURPOSE Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748 ) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 q6w for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 q3w for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

BRAF V600E(+) PTC tended to have larger tumor volumes and higher expression of VEGF. The level of VEGF expression was closely correlated with tumor size, extrathyroidal invasion, and stage. The relatively high levels of VEGF expression may be related to poorer clinical outcomes and recurrences in BRAF V600E(+) PTC.

Fatty acid synthase (FASN) is highly expressed in breast carcinomas to support their continuous growth and proliferation, but has low expression level in normal tissues. Considerable interest has been developed in searching for novel FASN inhibitors as a therapeutic target for breast cancer. In present study, amentoflavone was isolated from Selaginella tamariscina, a traditional oriental medicine that has been used to treat cancer for many years, and was found to significantly inhibit the in vitro enzymatic activity of FASN at concentrations above 50 microM. Amentoflavone was also found to decrease fatty acid synthesis by the reduction of [(3)H]acetyl-CoA incorporation into lipids in FASN-overexpressed SK-BR-3 human breast cancer cells. Furthermore, this study showed that amentoflavone, at a concentration greater than 75 microM, increased the cleavage-activity of caspase-3 and poly (ADP-ribose) polymerase (PARP), and administration of pan-caspase inhibitor Z-VAD-FMK completely rescued the SK-BR-3 cells from PARP cleavages. The sequential internucleosomal DNA fragmentation in SK-BR-3 cells was observed at a concentration of 100 microM. A decrease in breast cancer cell growth was observed in SK-BR-3 cells at 12 and 24 h post treatment with 100 microM of amentoflavone, followed by a dramatic suppression after 48 h. The inhibition of cancer-growth by amentoflavone was dose-dependent, showing a slight reduction at 50 microM and significant reduction at concentrations of 75 and 100 microM. FASN-nonexpressed NIH-3T3 normal cell growth was not decreased by amentoflavone-treatment, both in time- and dose-dependent manners. These data provide evidence that amentoflavone isolated from S. tamariscina induced breast cancer apoptosis through blockade of fatty acid synthesis.

BackgroundExcessive catecholamine release in pheochromocytoma is known to cause transient reversible left ventricular (LV) dysfunction, such as in the case of pheochromocytoma-associated catecholamine cardiomyopathy. We investigated patterns of clinical presentation and incidence of LV dysfunction in patients with pheochromocytoma.MethodsFrom January 2004 to April 2011, consecutive patients with pheochromocytoma were retrospectively studied with clinical symptoms, serum catecholamine profiles, and radiologic findings. Patterns of electrocardiography and echocardiography were also analyzed.ResultsDuring the study period, a total of 36 patients (21 males, 49.8 ± 15.8 years, range 14-81 years) with pheochromocytoma were included. In the electrocardiographic examinations, normal findings were the most common findings (19, 52.8%). LV hypertrophy in 12 cases (33.3%), sinus tachycardia in 3 (8.3%), ischemic pattern in 1 (2.8%) and supraventricular tachycardia in 1 (2.8%). Echocardiographic exam was done in 29 patients (80.6%). Eighteen patients (62.1%) showed normal finding, 8 (27.6%) revealed concentric LV hypertrophy with normal LV systolic function, and 3 (10.3%) demonstrate LV systolic dysfunction (LV ejection fraction < 50%). Three showed transient LV dysfunction (2 with inverted Takotsubo-type cardiomyopathy and 1 with a diffuse hypokinesia pattern). Common presenting symptoms in the 3 cases were new onset chest discomfort and dyspnea which were not common in the other patients. Their echocardiographic abnormalities were normalized with conventional treatment within 3 days.ConclusionOut of total 36 patients with pheochromocytoma, 3 showed transient LV systolic dysfunction (catecholamine cardiomyopathy). Pheochromocytoma should be included as one of possible causes of transient LV systolic dysfunction.