Breast Tissue Reconstruction Using Polycaprolactone Ball Scaffolds in a Partial Mastectomy Pig Model.

BACKGROUND: Breast cancer patients suffer from lowered quality of life (QoL) after surgery. Breast conservancy surgery (BCS) such as partial mastectomy is being practiced and studied as an alternative to solve this problem. This study confirmed breast tissue reconstruction in a pig model by fabricating a 3-dimensional (3D) printed Polycaprolactone spherical scaffold (PCL ball) to fit the tissue resected after partial mastectomy. METHODS: A 3D printed Polycaprolactone spherical scaffold with a structure that can help adipose tissue regeneration was produced using computer-aided design (CAD). A physical property test was conducted for optimization. In order to enhance biocompatibility, collagen coating was applied and a comparative study was conducted for 3 months in a partial mastectomy pig model. RESULTS: In order to identify adipose tissue and fibroglandular tissue, which mainly constitute breast tissue, the degree of adipose tissue and collagen regeneration was confirmed in a pig model after 3 months. As a result, it was confirmed that a lot of adipose tissue was regenerated in the PCL ball, whereas more collagen was regenerated in the collagen-coated Polycaprolactone spherical scaffold (PCL-COL ball). In addition, as a result of confirming the expression levels of TNF-a and IL-6, it was confirmed that PCL ball showed higher levels than PCL-COL ball. CONCLUSION: Through this study, we were able to confirm the regeneration of adipose tissue through a 3-dimensional structure in a pig model. Studies were conducted on medium and large-sized animal models for the final purpose of clinical use and reconstruction of human breast tissue, and the possibility was confirmed.

Normal range albuminuria and metabolic syndrome in South Korea: the 2011-2012 Korean National Health and Nutrition Examination Survey.

BACKGROUND: It is well-known that there is a close relationship between metabolic syndrome (MetS) and microalbuminuria. However, some recent studies have found that even normal range albuminuria was associated with MetS and cardiometabolic risk factors. The purpose of this study is to analyze the relationship between MetS and normal range albuminuria and to calculate the cutoff value for albuminuria that correlates with MetS in the representative fraction of Korean population. METHODS: Data were obtained from the 2011-2012 Korea National Health and Nutrition Examination Survey and included 9,650 subjects aged ≥ 19 years. We measured metabolic parameters: fasting blood glucose, waist circumference, blood pressure, and lipids, and albumin-to-creatinine ratio (ACR). The optimal ACR cutoff points for MetS were examined by the receiver operating characteristic curve. Multivariate logistic regression was used to obtain the prevalence of MetS and its components according to the ACR levels. RESULTS: The first cutoff value of ACR were 4.8 mg/g for subjects with ≥ 3 components of MetS. There was a graded association between ACR and prevalence of MetS and its components. If ACR was <4 mg/g, there was no significant increase in the prevalence of MetS or its components. From the ACR level of 4-5 mg/g, the prevalence of MetS significantly increased after adjusting for age, sex, body mass index, smoking, alcohol intake, exercise, and medications for diabetes mellitus and hypertension (odds ratio; 95% confidence intervals = 1.416; 1.041-1.926). CONCLUSIONS: Albuminuria within the normal range (around 5 mg/g) was associated with prevalence of MetS in the Korean population.

Lysyl oxidase G473A polymorphism is closely associated with susceptibility to gastric cancer in a South Korean population.

The aim of this study was to determine whether a single nucleotide polymorphism at G473A (rs1800449) within the LOX-propeptide is associated with susceptibility to gastric cancer. We investigated the genotype and allele frequencies of this gene in tissue specimens from 458 gastric cancer patients and 282 healthy individuals. Polymorphism analysis was performed by amplifying the propeptide region of LOX and digestion with NotI followed by sequencing of the products. The frequencies of the LOX G473A G/G, G/A, and A/A genotypes were 54.4% (249/458), 34.3% (157/458), and 11.3% (52/458), respectively, in gastric cancer patients and 58.9% (166/300), 35.5% (100/282), and 5.7% (16/282), respectively, in the healthy controls. Statistically significant differences in the genotype and allele frequency of LOX rs1800449 were observed between the healthy controls and gastric cancer patients (p = 0.0294 and p = 0.0339). When the data were stratified according to gastric cancer histologic subtype, the risk of diffuse-type gastric cancer in carriers with an A allele (G/A or A/A genotypes) was statistically higher compared to that of carriers with the G/G genotype (p = 0.0001). Our findings suggest that G473A polymorphism of the LOX gene may be closely associated with susceptibility to the development and differentiation of gastric cancer in South Korean patients.

Endothelial dysfunction in the smokers can be improved with oral cilostazol treatment.

BACKGROUND: Smoking is one of well known environmental factors causing endothelial dysfunction and plays important role in the atherosclerosis. We investigated the effect of cilostazol could improve the endothelial dysfunction in smokers with the measurement of flow-mediated dilatation (FMD). METHODS: We enrolled 10 normal healthy male persons and 20 male smokers without any known cardiovascular diseases. After measurement of baseline FMD, the participants were medicated with oral cilostazol 100 mg bid for two weeks. We checked the follow up FMD after two weeks and compared these values between two groups. RESULTS: There was no statistical difference of baseline characteristics including age, body mass index, serum cholesterol profiles, serum glucose and high sensitive C-reactive protein between two groups. However, the control group showed significantly higher baseline endothelium-dependent dilatation (EDD) after reactive hyperemia (12.0 ± 4.5% in the control group vs. 8.0 ± 2.1% in the smoker group, p = 0.001). However, endothelium-independent dilatation (EID) after sublingual administration of nitroglycerin was similar between the two groups (13.6 ± 4.5% in the control group vs. 11.9 ± 4.9% in the smoker group, p = 0.681). Two of the smoker group were dropped out due to severe headache. After two weeks of cilostazol therapy, follow-up EDD were significantly increased in two groups (12.0 ± 4.5% to 16.1 ± 3.7%, p = 0.034 in the control group and 8.0 ± 2.1% to 12.2 ± 5.1%, p = 0.003 in the smoker group, respectively). However, follow up EID value was not significantly increased compared with baseline value in both groups (13.6 ± 4.5% to 16.1 ± 3.7%, p = 0.182 in the control group and 11.9 ± 4.9% to 13.7 ± 4.3%, p = 0.430 in the smoker group, respectively). CONCLUSION: Oral cilostazol treatment significantly increased the vasodilatory response to reactive hyperemia in two groups. It can be used to improve endothelial function in the patients with endothelial dysfunction caused by cigarette smoking.

Iatrogenic left internal mammary artery to great cardiac vein anastomosis treated with coil embolization.

Inadvertent left internal mammary artery (LIMA)-great cardiac vein (GCV) anastomosis is a rare complication of coronary artery bypass graft surgery. Patients with iatrogenic aortocoronary fistula (ACF) were usually treated surgical repair, percutaneous embolic occlusion with coil or balloon. We report a case of iatrogenic LIMA to GCV anastomosis successfully treated with coil embolization and protected left main coronary intervention through the percutaneous transfemoral approach.

Overexpression of serine-threonine receptor kinase-associated protein in colorectal cancers.

Transforming growth factor-beta (TGF-beta) regulates many cellular processes, including cellular proliferation and differentiation. Disruption of the TGF-beta signaling pathway can lead to cancer. Serine-threonine receptor kinase-associated protein (STRAP), an inhibitor of TGF-beta signaling, is an important regulator of cell proliferation. Here, in order to investigate the roles of STRAP in colorectal carcinogenesis, the expression of the STRAP protein was investigated in 59 colonic adenomas and 123 colorectal cancers by immunohistochemistry. Upregulation of STRAP protein was observed in 30 (50.8%) of 59 adenomas and 87 (70.7%) of 123 cancers, respectively. Statistically, overexpression of STRAP protein was not associated with clinicopathological parameters and 5 year survival (P > 0.05). Interestingly, significant association was observed between STRAP and Ki-67 positivity (P < 0.05), suggesting that STRAP contributes to an increased proliferate potential of tumor cells. These results indicate that upregulation of STRAP might play a role in tumor development as an early event for colorectal cancers.

Genetic and expression analysis of the KCNRG gene in hepatocellular carcinomas.

The potassium channels are ubiquitous multisubunit membrane proteins, and potassium-dependent alterations in the membrane potential play an important role in the proliferation of many types of cells. This study analyzed the mutation, allelic loss and expression patterns of the KCNRG gene in 77 HCCs in order to determine if the KCNRG gene, which encodes the potassium channel regulating protein, is involved in the tumorigenesis of hepatocellular carcinoma (HCC). One KCNRG missense mutation, CGT CAT (Arg His) was found at codon 92 within the T1 domain. Hep3B hepatoma cells were transfected with the wild- or mutant-KCNRG to determine the effect of this mutation in KCNRG. Interestingly, the suppressive cell growth activity of the mutant-type KCNRG was significantly lower than that of the wild-type KCNRG. In addition, allelic loss was detected in 17 out of 64 (26.5%) informative HCC cases, and all were hepatitis B virus (HBV)-positive. Moreover, the allelic loss was closely related to an intrahepatic metastasis (P=0.0247), higher grade (P=0.0078) and clinical stage (P=0.0071). Expression analysis revealed 22 tumor tissues to have a loss of expression of the KCNRG transcript. These results suggest that genetic alterations and the expression of KCNRG might play an important role in the development and/or progression of a subset of HCCs.

Comparative proteomics of ovarian epithelial tumors.

We analyzed 12 ovarian epithelial tumors using 2D PAGE-based comparative proteomics to construct intra- and inter-tumoral distance map trees and to discover surrogate biomarkers indicative of an ovarian tumor. The analysis was performed after laser microdissection of 12 fresh-frozen tissue samples, including 4 serous, 5 mucinous, and 3 endometrioid tumors, with correlation with their histopathological characteristics. Ovarian epithelial tumors and normal tissues showed an apparent separation on the distance map tree. Mucinous carcinomas were closest to the normal group, whereas serous carcinomas were located furthest from the normal group. All mucinous tumors with aggressive histology were separated from the low malignant potential (LMP) group. The benign-looking cysts adjacent to the intraepithelial carcinoma (IEC) showed an expression pattern identical to that of the IEC area. The extent of change on the lineages leading to the mucinous and serous carcinoma was 1.98-fold different. The overall gene expression profiles of serous or endometrioid carcinomas appeared to be less affected by grade or stage than by histologic type. The potential candidate biomarkers screened in ovarian tumors and found to be significantly up-regulated in comparison to normal tissues were as follows: NM23, annexin-1, protein phosphatase-1, ferritin light chain, proteasome alpha-6, and NAGK (N-acetyl glucosamine kinase). In conclusion, ovarian mucinous tumors are distinct from other ovarian epithelial tumors. LMP mucinous tumors showing histologically aggressive features belong to mucinous carcinoma on the proteomic basis.

A single nucleotide polymorphism in the E-cadherin gene promoter-160 is not associated with risk of Korean gastric cancer.

Recently, the -160 C/A polymorphism, located within the regulatory region of Ecadherin promoter, has been shown to influence E-cadherin transcription by altering transcription factor binding. We examined the effect of this polymorphism on risk of gastric cancer and on histological classification of intestinal- and diffuse-type gastric cancer in 146 normal healthy individuals and 292 Korean gastric cancer patients. Genomic DNA samples were examined by polymerase chain reaction (PCR)-single strand conformational polymorphism (SSCP)-sequencing and confirmed by restriction fragment length polymorphism (RFLP). Unexpectedly, there was no significant difference in the genotype frequencies of the polymorphism between normal control and gastric cancer patients (x(2) test, p=0.433). The estimated odd ratio of C/C to A/A genotype in gastric cancer cases was 1.07 (95% confidence interval, 0.396-2.870). We also found no evidence for differences in risk for the intestinal- and diffuse-type gastric cancer. These results suggest that the -160 C/A polymorphism of the E-cadherin has no direct effect on the risk of Korean gastric cancer development and on its histological classification.

7-Substituted-[1,4]dioxano[2,3-g]quinazolines as inhibitors of epidermal growth factor receptor kinase.

With the aim of developing inhibitors of EGFR tyrosine kinase, the 7-methoxymethyl-[1,4]dioxano[2,3-g]quinazolines (3a-b) and 7-mono- or di-alkylaminomethyl-[1,4]dioxano[2,3-g]quinazolines (4a-i) were prepared and evaluated for the inhibition of EGFR tyrosine kinase and the growth inhibition of human tumor cell lines. Among them, compounds 4d and 4h showed potencies against both EGFR tyrosine and the A431 cell line similar to that of PD153035 with greater aqueous solubilities of their HCl salts.