Keloid is a fibrotic disease characterized by abnormal accumulation of extracellular matrix (ECM) in the dermis. It is a late spreading skin overgrowth and may be considered a plastic surgeon's nightmare. In nature, curcuminoid is composed of curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (bDMC). Curcuminoids have been found to inhibit fibrosis. However, their role in the synthesis of ECM in the keloid fibroblasts (KFs) has remained unclear. In this series of studies, a total of seven primary KFs cultures were used as the KFs model for investigating the inhibitory effect of curcuminoids on the expression of ECM and TGF-β1. A sensitive and reproducible HPLC method was developed to provide a quantitative analysis on the cellular uptake of curcuminoids onto the KF cells. The level of ECM in the primary KFs was elevated. The elevation of ECM and TGF-β1/p-SMAD-2 level was substantially blocked by the cellular uptake of curcumin in a dose-dependent manner in all the seven primary KFs. The results have led to the conclusion that the excessive production of ECM in the KF cells could be blocked and/or rapidly decreased by curcumin.
The genetic polymorphisms of ERCC1 and XRCC1 may be useful in predicting clinical outcome in Taiwanese mCRC patients treated with FOLFOX-4. However, further prospective studies will be needed for the potential clinical implication.
In consideration of the better ypT0-2 downstaging rate, less severe toxicities, and no need for indwelling intravenous device on oral capecitabine regimen, the administration of oral capecitabine with RT may be a more favorable option in the neoadjuvant treatment for LARC.
We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.
Simvastatin (SIM), a widely used cholesterol-lowering drug, also exhibits tumor-suppressive potentials in several types of malignancy. Colorectal cancer (CRC), the third most common malignant neoplasm, accounts for the second most leading cause of cancer-related deaths worldwide. In the present study, we investigated the anticancer effects of SIM on CRC using primary cancer cells lines (CPs: CP1 to CP5) isolated from five Taiwanese colorectal cancer patients as a model for colorectal cancer. We treated all five CPs with SIM for 24-72 hr and observed the respective cell viability by an MTT assay. SIM increased DNA content of the G phase, but did not induce apoptosis/necrosis in CPs as shown by flow cytometry with propidium iodide (PI)/annexin V double staining and PI staining. The expression of G phase-related proteins was analyzed by RT-PCR and Western blotting. SIM suppressed cell growth and induced cell cycle G -arrest by suppressing the expression of CDK4/cyclin D1 and CDK2/cyclin E1, but elevating the expression of glycogen synthase kinase 3β in CPs. Our findings indicate that SIM may have antitumor activity in established colorectal cancer.
Tension-free hernia repair with a mesh plug shows a low recurrence rate, but in a very few cases it can result in new complications including mesh migration and violation of the peritoneum. This report describes the case of a 79-year-old man who had undergone an inguinal hernioplasty using a polypropylene mesh plug 2 years earlier. He had a laparotomy for bowel ischemia 18 months later, and no evidence of bowel adhesion or a plug protruding through the peritoneum at that time. The patient remained asymptomatic until this admission. He presented with acute abdomen, and an emergency laparotomy revealed a plug-related bowel perforation. The plug had migrated and penetrated the peritoneum, presenting with bowel perforation and adhesions. Although the etiology was not clear, the use of nonabsorbable sutures for plug fixation may be recommended to avoid this complication. Less than 10 cases of mesh migration with bowel complications have been reported, and this is the first case study to demonstrate migration of the plug by serial tomography.
Two major issues encountered in the surgical resection of low rectal cancers (tumor located <6 cm from anal verge) are tumor-free surgical resection margin and adequate fields of colo-anal pull-through anastomosis. The clinical consequences of ensuring gross tumor-free surgical resection margin by transanal inside-out rectal resection technique were assessed for ultra-low rectal cancer patients. From February 2009 to September 2011, ultra-low anterior resection with a new method of eversion of the rectum through the anal canal after resecting the distal rectum and colo-anal anastomosis extracorporally performed in 30 patients (age range, 41-80 years) was reviewed. All patients received preoperative neoadjuvant concurrent chemoradiotherapy (CCRT) before the surgical resection. The median operating time was 265 min (range, 220-400 min), and the median intraoperative blood loss was 325 ml (range, 80-855 ml). No in-hospital mortality was noted among these patients. R0 resection (tumor-free margin range, 0.9-2.5 cm) was confirmed in all patients by pathologic reports, except one patient with 0.5 cm tumor-free margin. The new surgical technique of transanal inside-out rectal resection and colo-anal pull-through anastomosis for selected patients with ultra-low rectal cancers seems to be a safe and alternative procedure.
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