Young Hee Maeng

Protective effects of epigallocatechin gallate (EGCG) on streptozotocin-induced diabetic nephropathy in mice.

There is increasing evidence suggesting that antioxidants in green tea extracts may protect kidneys on the progression of end-stage renal disease. We investigated the protective impacts of (-)-epigallocatechin 3-O-gallate (EGCG) against streptozotocin (STZ)-induced diabetic nephropathy in mice. The mice were divided into 5 groups (n=10 per group): control (saline, i.p.), STZ (200mg/kg, i.p.), EGCG50 (50mg/kg, S.Q.), EGCG100 (100mg/kg, S.Q.), and EGCG200 (200mg/kg, S.Q.). Animals were sacrificed at scheduled times after EGCG administration and then quantitative and qualitative analysis were performed. Compared with the control group, the STZ group showed an increase in levels of blood glucose, blood urea nitrogen, creatinine and urine protein amounts with a decrease in body weight. All the above parameters were significantly reversed with EGCG treatment, especially in the EGCG100 group. After STZ injection, there was a mesangial proliferation with increased renal osteopontin accumulation and its protein expression in the glomeruli and the proximal tubules. Mice kidneys after EGCG-treatment showed a reduced expression of above parameters and relatively improved histopathological findings. These results indicated that EGCG 100mg/kg might provide an effective protection against STZ-induced diabetic nephropathy in mice by osteopontin suppression.

Induction of Heme Oxygenase-1 by Plant Extract KIOM-79 via Akt Pathway and NF-E2 Related Factor 2 in Pancreatic β-Cells

The objective of the present study was to determine the mechanism by which KIOM-79 induced heme oxygenase-1 (HO-1) in rat pancreatic β-cells (RINm5F). A mixture of plant extracts (KIOM-79) was obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis. HO-1, an antioxidant phase 2 enzyme, was previously reported to possess cytoprotective properties in pancreatic β-cells. KIOM-79 induced heme oxygenase-1 (HO-1) expression at the mRNA and protein levels, leading to increased HO-1 activity. The transcription factor, NF-E2 related factor 2 (Nrf2), regulates the antioxidant response element (ARE) of the phase 2 detoxifying and antioxidant enzymes, resulting in modulation of HO-1 expression. KIOM-79 increased nuclear translocation, ARE binding, and transcriptional activity of Nrf2. Furthermore, KIOM-79 also elicited activation of Akt (protein kinase B) and LY294004 (inhibitor of Akt)-suppressed KIOM-79-induced activation of Nrf2, which subsequently decreased HO-1 protein levels. Taken together, these data suggest that KIOM-79 augments the cellular antioxidant defense capacity through induction of HO-1 via the Akt-Nrf2-ARE signaling pathway, thereby protecting cells from streptozotocin-induced oxidative stress.

Involvement of heme oxygenase-1 in Korean colon cancer

Heme oxygenase-1 (HO-1) catabolizes heme into carbon monoxide, biliverdin, and free iron which mediate its protective effect against oxidative stress. The aim of the present study was to determine the expression level and activity of HO-1 in Korean colon cancer tissues and cell lines. HO-1 protein expression was higher (>1.5-fold) in tumor tissues than in adjacent normal tissues in 14 of 20 colon cancer patients, and HO-1 protein expression was closely correlated with HO-1 enzyme activity in cancer tissues. Immunohistochemical data confirmed that HO-1 protein was expressed at a higher level in colon cancer tissues than in normal mucosa. Furthermore, HO-1 mRNA and protein expression and enzyme activity were higher in the colon cancer cell lines Caco-2, SNU-407, SNU-1033, HT-29, and SW-403 than in the normal fetal human colon cell line FHC. Treatment with the HO-1 inhibitor zinc protoporphyrin decreased the viability of colon cancer cell lines. These data indicate that HO-1 may serve as a clinically useful biomarker of colon cancer and as a target for anticolon cancer drugs.

A completely isolated intestinal duplication cyst mimicking ovarian cyst torsion in an adult

Intestinal duplications are rare congenital anomalies that can occur anywhere in the gastrointestinal tract. They are most commonly located in the ileum and are usually detected in infancy or early childhood. Duplicated segments are usually firmly attached to and sometimes communicate with the normal gastrointestinal tract. Rarely, intestinal duplications are completely isolated, thus not associated at all with any part of the gastrointestinal tract. Such duplications do not share a common blood supply with the adjacent normal intestinal segment, unlike the usual form of duplication, but rather have a separate vascular pedicle. Reports of completely isolated duplication cysts in adults are extremely rare; we found only five such reports in the English-language medical literature. Here, we report a case of a completely isolated duplication cyst 12 cm long in an adult female. The cyst had no connection to any part of the intestinal tract and had a dedicated vascular pedicle.

Butin reduces oxidative stress-induced mitochondrial dysfunction via scavenging of reactive oxygen species

This study investigated the cytoprotective effect of butin, a flavonoid, on hydrogen peroxide (H(2)O(2))-induced mitochondrial dysfunction. Electron spin resonance (ESR) spectrometry revealed butins significant scavenging effects on superoxide radicals and hydroxyl radicals. When H(2)O(2) was used to induce an increase in mitochondrial reactive oxygen species (ROS) in Chinese hamster lung fibroblast (V79-4) cells, butin treatment decreased high level of ROS. Butin also attenuated intracellular Ca(2+) levels that have been induced by H(2)O(2). Furthermore, butin recovered ATP levels and succinate dehydrogenase activity that had been decreased by H(2)O(2) treatment. We conclude these results suggest butin decreased mitochondrial ROS accumulation, balanced intracellular Ca(2+) levels, and improved mitochondrial energy production, thus recovering mitochondrial function.

Epigenetic alterations are involved in the overexpression of glutathione S-transferase π-1 in human colorectal cancers

Glutathione S-transferase π-1 (GSTP-1) is a member of the glutathione S-transferase enzyme superfamily, which catalyzes the conjugation of electrophiles to glutathione during the process of detoxification. In this study, the epigenetic alterations of GSTP-1 expression in human colorectal cancers and the underlying mechanisms were investigated. In 10 colon cancer patients, proteomic analysis revealed that expression of GSTP-1 protein was higher in tumor tissues than in paired adjacent normal tissues. Likewise, in 7 of 10 colon cancer patients, GSTP-1 protein expression was more than 1.5-fold higher in tumor tissues than in adjacent normal tissues, as determined by western blotting. Immunohistochemical data confirmed that GSTP-1 protein was expressed at higher levels in colon cancer tissues compared to normal mucosa. GSTP-1 enzyme activity was closely correlated with GSTP-1 protein expression in colon cancer patients. Consistent with this, GSTP-1 mRNA, protein and activity levels were higher in the colorectal cancer cell lines Caco-2, HCT-116, HT-29, SNU-407 and SNU-1033 compared to the normal colon cell line FHC. Methylation-specific PCR results indicated that the high levels of GSTP-1 in human colorectal cancer cell lines were likely due to the lower degree of promoter methylation in colon cancer cell lines compared to the normal colon cell line, consistent with findings in colon cancer patients. Moreover, the levels of specific activator-protein complexes and histone marks were higher in human colorectal cancer cells compared to the normal human colon cell line, whereas the repressor protein complexes exhibited the opposite pattern. Furthermore, chromatin immunoprecipitation assays demonstrated that expression levels of the transcription factors AP-1 and SP-1 were correlated with the upregulation of GSTP-1 expression in colorectal cancer cells. Finally, knockdown of GSTP-1 promoted the sensitivity of SNU-407 cells to the anticancer agent 5-fluorouracil. These data indicate that GSTP-1 may serve as a clinically useful biomarker of colon cancer and a target for anti-colon cancer drugs.

Preoperative N Staging of Gastric Cancer by Stomach Protocol Computed Tomography

Purpose Clinical stage of gastric cancer is currently assessed by computed tomography. Accurate clinical staging is important for the tailoring of therapy. This study evaluated the accuracy of clinical N staging using stomach protocol computed tomography. Materials and Methods Between March 2004 and November 2012, 171 patients with gastric cancer underwent preoperative stomach protocol computed tomography (Jeju National University Hospital; Jeju, Korea). Their demographic and clinical characteristics were reviewed retrospectively. Two radiologists evaluated cN staging using axial and coronal computed tomography images, and cN stage was matched with pathologic results. The diagnostic accuracy of stomach protocol computed tomography for clinical N staging and clinical characteristics associated with diagnostic accuracy were evaluated. Results The overall accuracy of stomach protocol computed tomography for cN staging was 63.2%. Computed tomography images of slice thickness 3.0 mm had a sensitivity of 60.0%; a specificity of 89.6%; an accuracy of 78.4%; and a positive predictive value of 78.0% in detecting lymph node metastases. Underestimation of cN stage was associated with larger tumor size (P<0.001), undifferentiated type (P=0.003), diffuse type (P=0.020), more advanced pathologic stage (P<0.001), and larger numbers of harvested and metastatic lymph nodes (P<0.001 each). Tumor differentiation was an independent factor affecting underestimation by computed tomography (P=0.045). Conclusions Computed tomography with a size criterion of 8 mm is highly specific but relatively insensitive in detecting nodal metastases. Physicians should keep in mind that computed tomography may not be an appropriate tool to detect nodal metastases for choosing appropriate treatment.

Involvement of glutathione and glutathione metabolizing enzymes in human colorectal cancer cell lines and tissues

Reduced glutathione (GSH) is an abundant tripeptide present in the majority of cell types. GSH is highly reactive and is often conjugated to other molecules, via its sulfhydryl moiety. GSH is synthesized from glutamic acid, cysteine, and glycine via two sequential ATP‑consuming steps, which are catalyzed by glutamate cysteine ligase (GCL) and GSH synthetase (GSS). However, the role of GSH in cancer remains to be elucidated. The present study aimed to determine the levels of GSH and GSH synthetic enzymes in human colorectal cancer. The mRNA and protein expression levels of GSH, the catalytic subunit of GCL (GCLC) and GSS were significantly higher in the following five colon cancer cell lines: Caco‑2, SNU‑407, SNU‑1033, HCT‑116, and HT‑29, as compared with the normal colon cell line, FHC. Similarly, in 9 out of 15 patients with colon cancer, GSH expression levels were higher in tumor tissue, as compared with adjacent normal tissue. In addition, the protein expression levels of GCLC and GSS were higher in the tumor tissue of 8 out of 15, and 10 out of 15 patients with colon cancer respectively, as compared with adjacent normal tissue. Immunohistochemical analyses confirmed that GCLC and GSS were expressed at higher levels in colon cancer tissue, as compared with normal mucosa. Since GSH and GSH metabolizing enzymes are present at elevated levels in colonic tumors, they may serve as clinically useful biomarkers of colon cancer, and/or targets for anti-colon cancer drugs.

Diagnostic Value of Clinical T Staging Assessed by Endoscopy and Stomach Protocol Computed Tomography in Gastric Cancer: The Experience of a Low-Volume Institute

Purpose Clinical staging of gastric cancer appears to be important more and more for tailored therapy. This study aimed to verify the accuracy of clinical T staging in a low-volume institute. Materials and Methods We retrospectively reviewed prospectively collected data of gastric cancer patients who underwent resection. A total of 268 patients of gastric cancer were enrolled from March 2004 to June 2012. These demographics, tumor characteristics, and clinical stages were analyzed for identification of diagnostic value of clinical T staging. Results The predictive values for pT1 of endoscopy and computed tomography were 90.0% and 89.4%, respectively. In detail, the predictive values of endoscopy for pT1a, pT1b, and pT2 or more were 87%, 58.5%, and 90.6%, respectively. The predictive values of computed tomography for pT1a, pT1b, and pT2 or more were 68.8%, 73.9%, and 84.4%, respectively. The factors leading to underestimation of pT2 or more lesions by gastroscopy were the middle third location, the size greater than 2 cm, and younger age. Those for overestimation of pT1 lesion by computed tomography were male, age more than 70 years, elevated type, and size greater than 3 cm. Conclusions Diagnostic accuracy of early gastric cancer was 90%, which is comparable to those of high volume center. In patients with early gastric cancer, limited gastrectomy or minimal invasive surgery can be safely introduced at a low volume center also. However, the surgeon of low-volume institute should consider the accuracy of clinical staging before extending the indication of limited treatment.

Effect of KIOM-79 Against Mitochondrial Damage Induced by Streptozotocin in Pancreatic β-Cells

The present study examined the effects of KIOM-79 on streptozotocin (STZ)-induced mitochondrial oxidative stress in rat pancreatic β-cells (RINm5F). KIOM-79 is a mixture of plant extracts from parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix, and Euphorbiae radix. A marked increase in mitochondrial reactive oxygen species (ROS) was observed in STZ induced diabetic cells, which returned to control conditions after KIOM-79 treatment. Mitochondrial manganese superoxide dismutase (Mn SOD) activity and its protein expression were downregulated by STZ treatment but upregulated by KIOM-79 treatment. In addition, KIOM-79 treatment restored the loss of the mitochondrial membrane potential (Δψ) produced by STZ treatment. KIOM-79 induced an increase in Bcl-2 and a decrease in phospho Bcl-2 and Bax, which are related to permeability of the mitochondrial membrane. Further, KIOM-79 inhibited the translocation of cytochrome c from the mitochondria to the cytosol and elevated the ATP level, which was reduced by STZ treatment. These results suggest that KIOM-79 exhibits a protective effect through activation of antioxidant defense mechanisms and by attenuation of mitochondrial dysfunction in STZ-induced diabetic cells.