Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells

Ethnopharmacological relevance

The expression of matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2) are pivotal steps in breast cancer pathogenesis. In a previous study, we reported that silibinin suppresses TPA-induced MMP-9 expression through the Raf/MEK/ERK pathway.

Aims of the study

Herein we determined the co-relationship between MMP-9 and COX-2, as well as the effect of silibinin on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 and COX-2 expression in the human breast cancer cells, MCF-7 and MDA-MB231.

Methods

The toxicity of silibinin was evaluated by Quick Cell Proliferation Assay Kit II. MMP-9 and COX-2 expression were analyzed by Zymography and Western blotting, respectively. Adenoviral constitutively active (CA)-MEK was used to activate MEK/ERK pathway.

Results

The expression of MMP-9 and COX-2 in response to TPA was increased, whereas TPA-induced MMP-9 and COX-2 expression was decreased by silibinin. Our results showed that TPA-induced MMP-9 expression was inhibited by celecoxib in a dose-dependent fashion, but not MMP-1-expression. Both MMP-9 and COX-2 expression were significantly increased by CA-MEK overexpression. In contrast, TPA-induced MMP-9 and COX-2 expression was decreased by UO126 (MEK1/2 inhibitor).

Conclusion

Silibinin down-regulates TPA-induced MMP-9 expression through inhibition of COX-2 expression in breast cancer cells.     

Impact of graft type on remnant liver regeneration: right hepatectomy versus extended right hepatectomy

Right hepatectomy with the middle hepatic vein (MHV) affects venous return and function of the remaining liver. We compared the remnant liver volume in the donors of resection with or without the MHV on the remnant liver volume regeneration. Living donors who had undergone right hepatectomy without MHV (RH group; n = 36) and those with MHV (ERH group; n = 19) were reviewed. Volume regeneration of segments I-III, segment IV, and total remnant liver volume was assessed at postoperative day (POD) 7 and 30 using a computed tomography-based volumetry program. According to the measured volume data, we calculated the liver remnant volume and the rate of liver remnant volume increase. The regeneration rate of segment IV was significantly low in the ERH group compared with that in the RH group at POD 7 and POD 30 (160% vs 141%; P = .018 and 189% vs 154%; P = .007). In contrast, the regeneration rate of the total remnant liver volume was not significantly different between the 2 groups (173% vs 175%; P = .758 and 199% vs 198%; P = .880). In conclusion, extended right hepatectomy can be safely performed with careful preoperative evaluation without significant impairment of remnant liver regeneration.     

Robotic versus laparoscopic coloanal anastomosis with or without intersphincteric resection for rectal cancer

Robotic surgery is increasingly used in the field of rectal cancer surgery. This study aimed to compare the short- and long-term outcomes between robotic and laparoscopic ultralow anterior resection (uLAR) and coloanal anastomosis (CAA). Between January 2007 and December 2010, a retrospective chart review was performed for all patients with low rectal cancer who underwent curative uLAR and CAA with or without intersphincteric resection using either a robotic or a laparoscopic approach. The study excluded patients with tumors invading the levator ani or external sphincter, patients with T4 cancers invading the prostate or vagina, and patients for whom an open approach was used. Patients’ short- and long-term outcomes were evaluated. This study enrolled 84 consecutive patients (47 in the robotic group and 37 in the laparoscopic group). The patient characteristics and operative data did not differ significantly between the groups except for the rate of conversion to open surgery (robot, 2.1 % vs laparoscopy, 16.2 %; p = 0.02). The postoperative outcomes also were similar in the two groups, but the hospital stay was shorter in the robotic group than in the laparoscopic group (robot, 9 days vs laparoscopy, 11 days; p = 0.011). No postoperative mortality occurred. The median follow-up period was 31.5 months. No difference was shown in local recurrence, 3-year overall survival, or disease-free survival between the two groups. Robotic uLAR and CAA with or without ISR is a safe and feasible surgical approach with a lower conversion rate, a shorter hospital stay, and similar oncologic outcomes compared with a laparoscopic approach. Further prospective and case–control cohort studies with longer follow-up periods are required.     

Staged diabetes management according to individual patient insulin resistance and beta-cell function ameliorates glycaemic control in type 2 diabetes mellitus

Objective The current consensus algorithm for management of type 2 diabetes is based on the fasting glucose concentration and glycated haemoglobin A_1c (HbA_1c) level. We applied a new therapeutic strategy by assessing insulin secretion and insulin resistance, in addition to glucose concentrations in individual patients. Design and patients We enrolled 193 patients with type 2 diabetes. The patients were assigned to one of six groups according to insulin secretion measured by the serum fasting C‐peptide concentration and insulin resistance measured by an insulin tolerance test (ITT). The two groups were treated differently: 108 patients were treated using a new staged diabetes management (SDM) strategy and 85 patients continued with conventional therapy. Measurements We compared metabolic variables in the two groups at baseline and 12 months after enrolment. Results In patients treated with the SDM strategy, fasting glucose concentration decreased from 9·8 ± 2·1 to 8·2 ± 1·7 mmol/l (P < 0·001). Postprandial 2‐h glucose concentration decreased from 14·19 ± 3·34 to 12·27 ± 3·24 mmol/l (P < 0·001). HbA_1c level decreased from 8·37 ± 1·42% to 7·72 ± 1·39% (P < 0·001). About 43% of the new SDM group achieved an HbA_1c of < 7·0% compared with 25% of patients in the conventional treatment group. Conclusions The new SDM strategy, based on individual data on insulin resistance and insulin secretion, may provide valuable clinical benefits in non‐obese Korean patients with type 2 diabetes.