Purpose: Phosphorylated AKT1 (p-AKT1) at Ser473 is a functional isoform of AKT and a key component of the PI3K/mTOR/AKT pathway. This study aimed to evaluate the prognostic significance of p-AKT1 (Ser473) based on the molecular subtypes of breast cancer. Methods: To investigate the prognostic value of p-AKT1 (Ser473), we performed a retrospective chart review of patients with breast cancer. Data on p-AKT1 (Ser473) positivity, hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) expression status, and other clinicopathological factors were obtained. Furthermore, the therapeutic effect of blocking p-AKT1 (Ser473) in breast cancer cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis assay, apoptosis protein array, and western blot analysis. Results: A total of 3,044 patients were evaluated, and the median follow-up time was 43 (range: 0–125) months. In patients with HR-positive and HER2-positive disease, the p-AKT1 (Ser473)-positive group had worse disease-free survival (DFS) than the p-AKT1 (Ser473)-negative group (hazard ratio, 1.9; 95% confidence interval, 1.1–3.5; p = 0.024). In the multivariate analysis, p-AKT1 (Ser473) remained a significantly worse prognostic factor in patients with HR-positive/HER2-positive breast cancer (p = 0.03). There was no difference in DFS according to p-AKT1 (Ser473) status among patients with other breast cancer subgroups.In vitro analysis showed that blocking p-AKT1 (Ser473) levels enhanced trastuzumab-induced cell death in HR-positive/HER2-positive and p-AKT1 (Ser473)-positive breast cancer cells. Conclusion p-AKT1 (Ser473) is a prognostic marker for poor outcomes in patients with HRpositive/HER2-positive breast cancer and may have a potential value as a therapeutic target.

The accuracy and convenience of continuous glucose monitoring (CGM), which efficiently evaluates glycemic variability and hypoglycemia, are improving. There are two types of CGM: professional CGM and personal CGM. Personal CGM is subdivided into real-time CGM (rt-CGM) and intermittently scanned CGM (isCGM). CGM is being emphasized in both domestic and foreign diabetes management guidelines. Regardless of age or type of diabetes, CGM is useful for diabetic patients undergoing multiple insulin injection therapy or using an insulin pump. rt-CGM is recommended for all adults with type 1 diabetes (T1D), and can also be used in type 2 diabetes (T2D) treatments using multiple insulin injections. In some cases, short-term or intermittent use of CGM may be helpful for patients with T2D who use insulin therapy other than multiple insulin injections and/or oral hypoglycemic agents. CGM can help to achieve A1C targets in diabetes patients during pregnancy. CGM is a safe and cost-effective alternative to self-monitoring blood glucose in T1D and some T2D patients. CGM used in diabetes management works optimally with proper education, training, and follow up. To achieve the activation of CGM and its associated benefits, it is necessary to secure sufficient repetitive training and time for data analysis, management, and education. Various supports such as compensation, insurance coverage expansion, and reimbursement are required to increase the effectiveness of CGM while considering the scale of benefit recipients, policy priorities, and financial requirements.

Objective To investigate the effect of Gymnema sylvestre extract (GS) on initial anti-obesity, liver injury, and glucose homeostasis induced by a high-fat diet (HFD). Methods The dry powder of GS was extracted with methanol, and gymnemic acid was identified by high performance liquid chromatography as deacyl gymnemic acid. Male C57BL/6J mice that fed on either a normal diet, normal diet containing 1 g/kg GS (CON+GS), HFD, or HFD containing 1.0 g/kg GS (HFD + GS) for 4 weeks were used to test the initial anti-obesity effect of GS. Body weight gain and food intake, and serum levels about lipid and liver injury markers were measured. Histopathology of adipose tissue and liver stained with hematoxylin and eosin (H&E) and oil-red O were analyzed. After 4 weeks of GS extract feeding, intraperitoneal glucose tolerance test (IPGTT) was performed. Results The methanol extracts of GS exerted significant anti-obesity effects in HFD + GS group. They decreased body weight gain, a lower food and energy efficiency ratio, and showed lower serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL)-cholesterol, very-low density lipoprotein (VLDL)-cholesterol and leptin compared with the HFD group. The decreases of abdominal as well as epididymal fat weight and adipocyte hypertrophy, lipid droplets in liver, and serum levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) were also observed. The CON + GS group showed an effect of glucose homeostasis compared to the CON group. Conclusions This study shows that GS provide the possibility as a key role in an initial anti-obesity effects feeding with a HFD.

Entamoeba histolytica is an enteric tissue-invading protozoan parasite that can cause amebic colitis and liver abscess in humans. E. histolytica has the capability to kill colon epithelial cells in vitro; however, information regarding the role of calpain in colon cell death induced by ameba is limited. In this study, we investigated whether calpains are involved in the E. histolytica-induced cell death of HT-29 colonic epithelial cells. When HT-29 cells were co-incubated with E. histolytica, the propidium iodide stained dead cells markedly increased compared to that in HT-29 cells incubated with medium alone. This pro-death effect induced by ameba was effectively blocked by pretreatment of HT-29 cells with the calpain inhibitor, calpeptin. Moreover, knockdown of m- and micro-calpain by siRNA significantly reduced E. histolytica-induced HT-29 cell death. These results suggest that m- and micro-calpain may be involved in colon epithelial cell death induced by E. histolytica.
Calpain/antagonists & inhibitors/genetics/*metabolism ; *Cell Death ; Cell Line ; Cell Survival/drug effects ; Dipeptides/metabolism ; Entamoeba histolytica/*pathogenicity ; Epithelial Cells/*parasitology ; Gene Knockdown Techniques ; Humans

The cystic lesions of the gastrointestinal (GI) tract demonstrate the various pathologic findings. Some lesions may present a diagnostic challenge because of non-specific imaging features; however, other lesions are easily diagnosed using characteristic radiologic features and anatomic locations. Cystic masses from the GI tract can be divided into several categories: congenital lesions, neoplastic lesions (cystic neoplasms, cystic degeneration of solid neoplasms), and other miscellaneous lesions. In this pictorial review, we describe the pathologic findings of various cystic lesions of the GI tract as well as the radiologic features of GI cystic lesions from several imaging modalities including a barium study, transabdominal ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging.
Contrast Media ; Cysts/*diagnosis/pathology ; *Diagnostic Imaging ; Gastrointestinal Diseases/*diagnosis/pathology ; Humans

PURPOSE: This study is to review the initial 5-years of breast cancer management in a single hospital using the clinical data warehouse (CDW). METHODS: We reviewed the electronic medical records of 754 patients with breast cancer who were treated by a single surgeon between June 2003 and December 2007 in Seoul National University Bundang Hospital. We analyzed the epidemiological, clinical and therapeutic profiles of the breast cancer patients which were encoded and stored at the CDW. RESULTS: The mean age of the patients was 49.3 years and the peak incidence was in the fifth decade (36.6%). Symptomatic breast cancer was 74.6% and screening-detected breast cancer was 25.4%. Breast conserving surgery (BCS) was performed in 54.1% of all cases and the BCS rate increased annually. Immediate reconstruction after mastectomy was performed in 62 cases (17.7%). Sentinel lymph node (SLN) biopsy for nodal staging was performed in 501 cases (72.1%) and 160 cases (23.0%) underwent complete axillary lymph node dissection. The proportion of in situ and early stage invasive breast cancer was 85.0%. Six hundred and ninety three patients (92.5%) received more than one adjuvant therapy. Thirty one patients experienced local or systemic relapse after surgery and ipsilateral breast tumor recurrence (IBTR) occurred in 6 cases. The median follow-up period was 29.5 months. Two-year and 3-year disease-free survival rates were 95.9% and 94.4%. CONCLUSION: BCS and SLN biopsy continuously increased and immediate reconstruction after mastectomy was performed widely. Most patients received more than one adjuvant therapy. Moreover, we saved the time and human power to review the medical record by using the CDW.
Biopsy ; Breast ; Breast Neoplasms ; Disease-Free Survival ; Electronic Health Records ; Follow-Up Studies ; Humans ; Incidence ; Lymph Node Excision ; Lymph Nodes ; Mastectomy ; Mastectomy, Segmental ; Medical Records ; Medical Records Systems, Computerized ; Nitriles ; Pyrethrins ; Recurrence

PURPOSE: This study is to review the initial 5-years of breast cancer management in a single hospital using the clinical data warehouse (CDW). METHODS: We reviewed the electronic medical records of 754 patients with breast cancer who were treated by a single surgeon between June 2003 and December 2007 in Seoul National University Bundang Hospital. We analyzed the epidemiological, clinical and therapeutic profiles of the breast cancer patients which were encoded and stored at the CDW. RESULTS: The mean age of the patients was 49.3 years and the peak incidence was in the fifth decade (36.6%). Symptomatic breast cancer was 74.6% and screening-detected breast cancer was 25.4%. Breast conserving surgery (BCS) was performed in 54.1% of all cases and the BCS rate increased annually. Immediate reconstruction after mastectomy was performed in 62 cases (17.7%). Sentinel lymph node (SLN) biopsy for nodal staging was performed in 501 cases (72.1%) and 160 cases (23.0%) underwent complete axillary lymph node dissection. The proportion of in situ and early stage invasive breast cancer was 85.0%. Six hundred and ninety three patients (92.5%) received more than one adjuvant therapy. Thirty one patients experienced local or systemic relapse after surgery and ipsilateral breast tumor recurrence (IBTR) occurred in 6 cases. The median follow-up period was 29.5 months. Two-year and 3-year disease-free survival rates were 95.9% and 94.4%. CONCLUSION: BCS and SLN biopsy continuously increased and immediate reconstruction after mastectomy was performed widely. Most patients received more than one adjuvant therapy. Moreover, we saved the time and human power to review the medical record by using the CDW.
Biopsy ; Breast ; Breast Neoplasms ; Disease-Free Survival ; Electronic Health Records ; Follow-Up Studies ; Humans ; Incidence ; Lymph Node Excision ; Lymph Nodes ; Mastectomy ; Mastectomy, Segmental ; Medical Records ; Medical Records Systems, Computerized ; Nitriles ; Pyrethrins ; Recurrence

Previous studies have demonstrated that rottlerin, a specific PKCdelta inhibitor, potentiates death receptor- mediated apoptosis through a cytochrome c-dependent or -independent pathway. However, its ability to regulate necrotic cell death, as well as the underlying mechanism, remains unknown. We found that in murine fibrosarcoma L929 cells, treatment with rottlerin protected the cells against TNF-induced necrosis, whereas it sensitized the cells to apoptosis induced by co-treatment with Hsp90 inhibitor geldanamycin and TNF, in a manner independent of its ability to inhibit PKC-delta. TNF treatment induced rapid accumulation of mitochondrial superoxide (O2") through the Nox1 NADPH oxidase when cells undergo necrosis. Moreover, pretreatment with rottlerin failed to induce the GTP-bound form of small GTPase Rac1 by TNF treatment, and subsequently suppressed mitochondrial O2(-) production and poly(ADP-ribose) polymerase activation, thus inhibiting necrotic cell death. Therefore, our study suggests that Nox1 NADPH oxidase is a new molecular target for anti-necrotic activity of rottlerin upon death-receptor ligation.
Acetophenones/*pharmacology ; Animals ; Benzopyrans/*pharmacology ; Cell Death/*drug effects ; Cell Line, Tumor ; Mice ; Protein Kinase Inhibitors/*pharmacology ; Superoxides/metabolism ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors/pharmacology

Activation of c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is an important cellular response that modulates the outcome of the cells which are exposed to the tumor necrosis factor (TNF) or the genotoxic stress including DNA damaging agents. Although it is known that JNK is activated in response to genotoxic stress, neither the pathways to transduce signals to activate JNK nor the primary sensors of the cells that trigger the stress response have been identified. Here, we report that the receptor interacting protein (RIP), a key adaptor protein of TNF signaling, was required to activate JNK in the cells treated with certain DNA damaging agents such as adriamycin (Adr) and 1-beta-D-arabinofuranosylcytosine (Ara-C) that cause slow and sustained activation, but it was not required when treated with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and short wavelength UV, which causes quick and transient activation. Our findings revealed that this sustained JNK activation was not mediated by the TNF (tumor necrosis factor) receptor signaling, but it required a functional ATM (ataxia telangiectasia) activity. In addition, JNK inhibitor SP-600125 significantly blocked the Adr-induced cell death, but it did not affect the cell death induced by MNNG. These findings suggest that the sustained activation of JNK mediated by RIP plays an important role in the DNA damage-induced cell death, and that the duration of JNK activation relays a different stress response to determine the cell fate.
Cell Death ; DNA ; DNA Damage ; Doxorubicin ; Humans ; JNK Mitogen-Activated Protein Kinases ; Methylnitronitrosoguanidine ; Necrosis ; Protein Kinases ; Tumor Necrosis Factor-alpha