Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy.

PURPOSE: The purpose of this study was to elucidate the effect of decreased muscle mass on the toxicity and survival of patients with colon cancer treated with adjuvant chemotherapy after surgery. METHODS: We reviewed the data of 229 consecutive patients with stage III colon cancer who received adjuvant oxaliplatin, 5-fluorouracil, and leucovorin chemotherapy at a single center between 2003 and 2010. Baseline muscle mass was assessed by measuring the cross-sectional area of the psoas muscle at the level of the fourth lumbar vertebra on computed tomography images. Effects of muscle mass on toxicity of chemotherapy and survival were assessed. RESULTS: The median age of the 229 patients was 61 years (range, 28-80) and 134 (58.5 %) were men. The mean psoas muscle mass index (PI, psoas muscle area divided by height(2) [mm(2)/m(2)]) was 548.3. A 1 SD decrement in the PI was associated with an increase in all grade 3-4 toxicities in univariate (OR = 1.69, 95 % CI = 1.18-2.27) and multivariate (OR = 1.56, 95 % CI = 1.05-2.38) analyses. In univariate analysis, the PI was not associated with overall survival. However, multivariate analysis showed that a 1 SD decrement in the PI increased the hazard of overall mortality by 85 % (HR = 1.85, 95 % CI = 1.10-3.13). This effect of the PI on mortality was maintained in subgroup analyses, especially in older and obese patients. CONCLUSIONS: Decreased muscle mass was associated with increased risk of grade 3-4 toxicity and poor prognosis in patients with stage III colon cancer.

Blood pressure lowering effect of Korea ginseng derived ginseol K-g1.

We investigated the effect of Panax ginseng extract, which is rich in the ginsenoside protopanaxatriol (Ginseol K-g1), on blood pressure (BP). Adults over 20 years old with a systolic BP (SBP) between 120 and 159 mm Hg or a diastolic BP (DBP) between 80 and 99 mm Hg were included. At the end of an initial 2-week washout period, the patients were divided into three groups: the control group (placebo), the low-dose Ginseol K-g1 group (100 mg), and the high-dose Ginseol K-g1 (300 mg) group. The primary end point was the difference in seated SBP (seSBP) and seated DBP (seDBP) changes between the placebo and Ginseol K-g1 groups after 8 weeks of treatment. A total of 90 subjects participated in the study (mean age; 55.2 ± 11.8 years, 43 males). At week 8, levels of seSBP and seDBP were significantly decreased from baseline in the high-dose Ginseol K-g1 group (-3.1 mm Hg and -2.3 mm Hg, respectively, p < 0.05). In contrast, there was no significant decrease in seSBP or seDBP in the control or low-dose Ginseol K-g1 groups. No significant difference of seSBP and seDBP was identified among the three treatment groups at week 8. In patients who had a seSBP ≥ 130 mm Hg or an seDBP ≥ 85 mm Hg, the high dose of Ginseol K-g1 decreased the BP compared with the control group at week 4; however, there was no significant difference at week 8. The proportions of patients who experienced adverse events were comparable among the treatment groups. In conclusion, Ginseol K-g1 has a favorable effect on BP after 4 weeks of treatment, especially at a high dose. However, the effect is not maintained over 8 weeks. (Clinical trial registration information is available at http://www.clinicaltrials.gov , identifier: NCT01483430.).

Penta-O-galloyl-beta-D-glucose suppresses tumor growth via inhibition of angiogenesis and stimulation of apoptosis: roles of cyclooxygenase-2 and mitogen-activated protein kinase pathways.

Recent studies have revealed that 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) has anti-tumorigenic activity in vitro. In the present work, we evaluated the in vitro and in vivo antiangiogenic and antitumor activities of PGG and examined its molecular mechanisms. PGG significantly inhibited the proliferation and tube formation in basic fibroblast growth factor (bFGF)-treated human umbilical vein endothelial cells (HUVECs) at non-cytotoxic concentrations. PGG effectively disrupted the bFGF-induced neo-vascularization in chick chorioallantoic membrane (CAM) and in Matrigel plugs in the mice. When mice were intraperitoneally injected, PGG also significantly inhibited tumor angiogenesis induced by Lewis lung carcinoma (LLC) and the growth of LLC by 57 and 91% of control tumor weight at 4 and 20 mg/kg, respectively. Immunohistochemical analysis revealed decreased microvessel density, decreased expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), reduced tumor cell proliferation and increased tumor cell apoptosis. Similarly, PGG significantly attenuated the expression of COX-2 and VEGF and reduced the secretion of VEGF and prostaglandin E2 in bFGF-treated HUVECs. Furthermore, the COX-2 inhibitor NS398 significantly inhibited tube formation and neo-vascularization in CAM, supporting the role of COX-2 in PGG inhibition of angiogenesis. PGG diminished the phosphorylation of extracellular signal regulated kinase 1/2, Jun NH2-terminal kinase and activated phospho-p38 mitogen-activated protein kinase (MAPK) in a dose-dependent manner in bFGF-treated HUVECs. In addition, p38 inhibitor SB203580 abolished the downregulation of COX-2, VEGF and the antiproliferative activity by PGG. Taken together, our data demonstrate that PGG exerts antitumor activity primarily via inhibition of angiogenesis through COX-2 and MAPK- dependent pathways.