Comparison of survival outcome of open, total laparoscopic, and laparoscopy-assisted radical vaginal hysterectomy for stage IB2 cervical cancer patients: A multicenter retrospective study.

The aim of this study was to compare survival outcomes of 3 different radical hysterectomy (RH) types, namely total abdominal radical hysterectomy (TARH), total laparoscopic radical hysterectomy (TLRH), and laparoscopy-assisted radical vaginal hysterectomy (LARVH), in patients with FIGO stage IB2 cervical cancer. We retrospectively identified a cohort of patients who underwent RH for cervical cancer between 2010 and 2017. Patients with stage IB2 cervical cancer were included and were classified into TARH, TLRH, and LARVH treatment groups. Survival outcomes were estimated by the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards models were fit to estimate the independent association of RH technique with outcome. 194 patients were included in this study: 79 patients in the TARH group, 55 in the TLRH group, and 60 in the LARVH group. No significant differences were found in clinicopathological characteristics between the 3 RH groups. On comparing survival outcomes with TARH, both TLRH and LARVH showed no significant difference in terms of 5-year overall survival (TARH vs TLRH, P = .121 and TARH vs LARVH, P = .436). Conversely, compared to the TARH group, 5-year progression-free survival (PFS) was significantly worse in the TLRH group (P = .034) but not in the LARVH group (P = .288). Multivariate analysis showed that TLRH surgical approach (hazard ratio, 3.232; 95% confidence interval, 1.238-8.438; P = .017) was an independent prognostic factor for PFS in patients with IB2 cervical cancer. Our study suggests that in patients with FIGO stage IB2 cervical cancer, among the minimally invasive RH approaches, TLRH and LARVH, only TLRH approach was associated with worse PFS when compared with the TARH approach.

Immediate-release tablet formulation of rebamipide and a pharmacokinetic study in healthy human subjects.

OBJECTIVE: To develop an immediate-release tablet preparation containing rebamipide (RBM) and perform the bioavailability assessment in the healthy human subjects. MATERIALS AND METHODS: Raw RBM powder was characterized using differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy (SEM). RBM tablets were manufactured by the wet granulation method, and their dissolution behavior was compared with the reference tablet (Mucosta). A phase I study (n = 47; sequence-randomized, open-label, single-dose, and two-way cross-over design) was designed for oral administration of a test formulation (F4) and Mucosta to healthy human male subjects, and pharmacokinetic parameters including the maximum plasma concentration (Cmax) and area under the curve from 0 to 12 hours (AUC0-12h) were compared. RESULTS: RBM powder had a multimodal size distribution with typical crystallinity, and the needle-like and elongated morphologies of RBM were visualized using SEM. Various tablet formulations (F1 - F6) were successfully manufactured using wet granulation method. F4 formulation was selected based on the dissolution profile most equivalent to that of Mucosta. F4 was stable for 6 months under accelerated and long-term storage conditions. Based on one-way analysis of variance, the AUC0-12h (F(1,92) = 2.40, p = 0.13) and tmax (F(1,92) = 0.04, p = 0.85) were not significantly different; however, the Cmax (F(1,92) = 5.45, p = 0.022) showed significant difference between F4 and reference tablets. CONCLUSION: Despite similar in vitro dissolution profiles, in vivo pharmacokinetic results revealed a partial difference between F4 and reference tablets. Thus, further study on formulation development is still needed.

Prognostic factors of oncologic outcomes after fertility-preservative management with progestin in early-stage of endometrial cancer.

BACKGROUND: The aim of this study was to evaluate efficacy of various fertility-preservative treatments with progestin and analyze prognostic factors in Stage 1A of endometrial cancer. MATERIALS AND METHODS: This retrospective study involved four Korean university hospitals. Data were collected from 43 women who were under the age of 40 with presumed stage IA endometrial cancer determined by magnetic resonance imaging and treated from January 2014 to December 2017. All of the patients were administered hormonal therapy for fertility preservation. Twenty-five patients received oral progestin with a levonorgestrel-releasing intrauterine system (LNG-IUS) for 6-24 months, and 18 patients received high-dose oral progestin for the same period of time. Oncologic outcomes were evaluated. Prognostic factors for pathologic response to progestin were identified by logistic regression analysis. RESULTS: Complete response (CR) was achieved by 72.1% of patients (31/43), and the average time to CR was 4.2 (Stable disease [SD] 3.4) months (range, 3-9 months). Partial response was achieved by 7.0% of patients (3/43), SD by 9.3% (4/43), and progressive disease by 11.6% (5/43). Of the CR patients, 41.9% (13/31) achieved pregnancy with the median follow-up period of 12.5 (SD 7.6) months (range: 3-50 months). No irreversible toxicity or therapy-associated death occurred. Multivariate analysis showed that high endometrial thickness ratio of pre- and posttreatment measured at 2 months from the treatment initiation (≥0.55, Odds ratio [OR]: 19.018; 95% confidence intervals (CI): 1.854-195.078; P = 0.013) and oral progestin without LNG-IUS (OR: 13.483; 95% CI: 1.356-134.069; P = 0.026) might be related with unfavorable prognostic factors for CR. CONCLUSION: This study shows that progestin-based fertility-preservative treatment might be a feasible option for stage 1A endometrial cancer. It also identifies that low endometrial thickness ratio and oral progestin with LNG-IUS combination therapy might be related with favorable response to hormonal treatment.

Preoperative Blood Inflammatory Markers for the Differentiation of Uterine Leiomyosarcoma from Leiomyoma.

PURPOSE: Preoperative diagnosis of uterine leiomyosarcoma (LMS) is challenging because the disease can mimic benign leiomyoma (LM). The objective of the present study was to investigate the role of preoperative clinical characteristics and hematologic parameters to differentiate uterine LMS and LM. METHODS: Preoperative clinical and laboratory variables were reviewed retrospectively in patients with LMS or LM, and the significances of intergroup differences were assessed. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values for each variable. Logistic regression analysis was applied to identify variables predicting the presence of LMS. RESULTS: The preoperative clinical and laboratory variables of 336 patients with uterine tumor were analyzed. Seventy-nine patients had LMS and 257 had LM. A significant difference was observed between LMS and LM in terms of the median value of age at diagnosis, menopausal status, white blood cell (WBC) count, absolute neutrophil count (ANC), C-reactive protein (CRP), lactate dehydrogenase (LDH), and neutrophil-to-lymphocyte ratio (NLR) (all P < 0.001). Multivariate analyses showed that menopausal status (odds ratio [OR] = 3.40, P= 0.002), WBC count (OR = 2.09, P = 0.012), ANC (OR = 3.17, P < 0.001), CRP (OR = 21.74, P < 0.001), LDH (OR = 10.77, P < 0.001), and NLR (OR = 2.58, P = 0.001) predicted the presence of LMS. CONCLUSION: Our results suggest that in older or postmenopausal patients, high WBC count, ANC, CRP, LDH, and NLR could be useful biomarkers for the differentiation of LMS and LM, which indicate that serum markers might be useful, cost-effective, and broadly available diagnostic markers for uterine LMS.

The association between expression of p53 and aggressiveness of serous adenocarcinoma of the uterine cervix.

BACKGROUND: Serous adenocarcinoma of the uterine cervix is an extremely rare variant of cervical adenocarcinoma. This study aimed to evaluate the clinicopathological and molecular features and outcomes of serous adenocarcinoma of the uterine cervix (SACC). MATERIALS AND METHODS: This was a retrospective study conducted based on the clinical and pathological data of seven patients diagnosed with SACC after hysterectomy, who were evaluated at the gynecologic oncologic centers between 2010 and 2019. RESULTS: Five cases were diagnosed at Stage IB and two at Stage IV. All patients underwent radical hysterectomy with bilateral salpingo-oophorectomy and subsequently received postoperative radiotherapy or chemotherapy. One patient showed persistent disease, and two patients suffered recurrence. Immunohistochemical study showed that three (43%) of the seven patients were positive for p53, and among these three patients, two with diffuse strong p53 expression experienced an aggressive course with recurrences at pelvic lymph nodes, lung, and brain. CONCLUSION: High p53 expression and advanced stage may be associated with poorer clinical outcomes in SACC, which suggest that immunohistochemistry may contribute to the prediction of prognosis.

Current Trends in Nursing Research Across Five Locations: The United States, South Korea, Taiwan, Japan, and Hong Kong.

PURPOSE: Despite the importance of research in the discipline of nursing, current trends in nursing research have rarely been discussed across countries. The purpose of this article was to identify current trends in nursing research across five countries, including the United States, South Korea, Taiwan, Japan, and Hong Kong, in order to provide directions for future global nursing research. ORGANIZING CONSTRUCT: A discussion article. METHODS: To identify the current trends, seven leaders from the five countries had discussions through a series of workshops and conference presentations. After the most recent conference, all the leaders reflected for a month on their presentations and compiled the exemplars and cases from their experience and the existing literature in individual countries into a table. The tables and supporting references were collected at the completion of the reflection period. Then, the PowerPoint (Microsoft Corporation, Redmond, WA, USA) slideshows of the conference presentations by the leaders and the collected tables were analyzed using a content analysis. FINDINGS: Six themes reflecting the current trends in nursing research were extracted: (a) demographic alterations; (b) increasing diversities and globalization; (c) technology innovation; (d) individualized or personal care and population health initiatives; (e) health policies and regulations; and (f) nursing workforce changes. CONCLUSIONS: Future directions for nursing research across the countries were proposed: (a) cost-effectiveness research; (b) implementation science; (c) data science; (d) training of the future generation of nurse researchers; (e) population health; and (f) team science. CLINICAL RELEVANCE: This topic could be applied to any clinical settings.

Enhanced docetaxel delivery using sterically stabilized RIPL peptide-conjugated nanostructured lipid carriers: In vitro and in vivo antitumor efficacy against SKOV3 ovarian cancer cells.

Docetaxel (DTX) has poor solubility, low specificity, and severe side effects. For efficient targeting of DTX to hepsin-overexpressing SKOV3 ovarian cancer cells, PEGylated and RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated nanostructured lipid carriers (PEG-RIPL-NLCs) were examined for in vitro and in vivo antitumor efficacy. DTX-loaded plain NLCs (DTX-pNLCs), RIPL-NLCs (DTX-RIPL-NLCs), and PEG-RIPL-NLCs (DTX-PEG-RIPL-NLCs) were prepared using a solvent emulsification-evaporation technique. DTX was successfully loaded with high encapsulation efficiency (>93%), and all NLCs showed homogeneous dispersion with zeta potentials varying from -17 to 15 mV. Drug release was biphasic: initial rapid release, then gradual release. In vitro cytotoxicity was time- and dose-dependent: DTX-RIPL-NLCs and DTX-PEG-RIPL-NLCs exhibited greater cytotoxicity, enhanced cell apoptosis owing to the cell cycle arrest in the G2/M phase, and increased activation of the mitochondria-related intrinsic apoptosis pathway compared to DTX-pNLCs. Pharmacokinetic experiments in male Sprague-Dawley rats revealed that DTX-PEG-RIPL-NLCs increased the mean residence time of DTX but reduced total body clearance and volume of distribution. In a SKOV3-bearing xenograft Balb/c athymic mouse model, DTX-PEG-RIPL-NLCs suppressed tumors, evidenced by tumor volume change and histopathological examination. Thus, we conclude that PEG-RIPL-NLCs have an advantage of high payload of poorly water-soluble drugs and are a good candidate for drug targeting to SKOV3-derived ovarian cancer.

Clinical and Genetic Characteristics of BRCA1/2 Mutation in Korean Ovarian Cancer Patients: A Multicenter Study and Literature Review.

PURPOSE: We investigated the clinical relevance and spectrum of BRCA1/2 mutations in Korean ovarian cancer (KoOC) patients. MATERIALS AND METHODS: Two hundred seventy-nine KoOC patients were enrolled from three university hospitals between 2012 and 2017. Their peripheral blood samples were obtained for BRCA1/2 mutation analysis by direct sequencing. Clinicopathological characteristics were retrospectively reviewed, and spectrum analyses of BRCA1/2 mutation were assessed by systematic literature review. RESULTS: Frequency of BRCA1/2 mutations was 16.5% in KoOC patients. BRCA1/2 mutations were significantly associated with family history of breast/ovarian cancer (p<0.001), serous histology (p=0.044), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV, p=0.018) but not with early age-of-onset (age < 50, p=0.729). Literature review of BRCA1/2 mutations in KoOC patients found 111 (55 distinct) mutations with high proportion of Korean-specific mutations (24/55, 43.6%). Comparing the spectrum of BRCA1/2 mutation between KoOC and Korean breast cancer (KoBC) patients, the ratio of BRCA1-to-BRCA2 mutations was different, with BRCA1 (78.4%) being predominant in KoOC and BRCA2 in KoBC (59.2%). The most common mutation also differed between the two (c.3627insA of BRCA1 in KoOC and c.7480C>T of BRCA2 in KoBC). CONCLUSION: The clinical relevance of BRCA1/2 mutations in KoOC patients was confirmed but that of early age-of-onset was not. Possible inconsistency in the ratio of BRCA1-to-BRCA2 mutations and the most common mutation between KoOC and KoBC may probably suggest presence of mutation sequence-associated penetrance tendency in hereditary Korean breast and ovarian cancer. These data may provide insights for optimal genetic counseling and prophylactic treatment for at-risk relatives of KoOC patients.

Ciprofloxacin Enhances TRAIL-Induced Apoptosis in Lung Cancer Cells by Upregulating the Expression and Protein Stability of Death Receptors through CHOP Expression.

Ciprofloxacin (CIP) is a potent antimicrobial agent with multiple effects on host cells and tissues. Previous studies have highlighted their proapoptotic effect on human cancer cells. The current study showed that subtoxic doses of CIP effectively sensitized multiple cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Although TRAIL alone mediated the partial proteolytic processing of procaspase-3 in lung cancer cells, co-treatment with CIP and TRAIL efficiently restored the complete activation of caspases. We found that treatment of lung cancer with CIP significantly upregulated the expression and protein stability of death receptor (DR) 5. These effects were mediated through the regulation of transcription factor CCAT enhancer-binding protein homologous protein (CHOP) since the silencing of these signaling molecules abrogated the effect of CIP. Taken together, these results indicated that the upregulation of death receptor expression and protein stability by CIP contributed to the restoration of TRAIL-sensitivity in lung cancer cells.

Prognostic value of preoperative lymphocyte-monocyte ratio in patients with ovarian clear cell carcinoma.

Objective: The aim of the present study was to determine the prognostic significances of markers of preoperative systemic inflammatory response (SIR) in patients with ovarian clear cell carcinoma (OCCC). Methods: A total of 109 patients diagnosed with OCCC that underwent primary cytoreductive surgery and adjuvant platinum-based chemotherapy from 2009 to 2012 were enrolled in this retrospective study. SIR markers were calculated from complete blood cell counts determined before surgery. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). Prognostic significances with respect to overall survival (OS) and progression-free survival (PFS) were determined by Kaplan-Meier curve and multivariate Cox regression analysis. Results: The optimized NLR, LMR and PLR cut-off values as determined by ROC curve analysis for PFS and OS were 2.3, 4.2, and 123.6, respectively. When the cohort was divided using these optimized cut-offs, NLR and LMR were found to be significantly associated with clinicopathologic factors, NLR with FIGO stage, the presence of malignant ascites, and platinum response, and LMR with FIGO stage, lymph node metastasis, malignant ascites, and platinum response. Kaplan-Meier analysis revealed a high NLR (> 2.3) was significantly associated with low 5-year PFS and OS rates and that a high LMR was significantly associated with high 5-year PFS and OS rates. Multivariate analysis identified FIGO stage, residual mass, and platinum response as independent prognostic factors of PFS, and FIGO stage, residual mass, platinum response, and LMR as independent prognostic factors of OS. Conclusions: Markers of systemic inflammatory response provide useful prognostic information and lymphocyte-to-monocyte ratio is the most reliable independent prognostic factor of overall survival in patients with ovarian clear cell carcinoma.

Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer.

AIM: To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score (AMLPS) in patients with gastric cancer. METHODS: We retrospectively examined the combination of absolute monocyte count (AMC) and absolute lymphocyte count (ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution. Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis. An AMLPS was generated, which stratified patients into three risk groups: low risk (both low AMC and high ALC), intermediate risk (either high AMC or low ALC), and high risk (both high AMC and low ALC). The primary objective of the study was to validate the impact of AMLPS on both disease-free survival (DFS) and overall survival (OS), and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors. RESULTS: Using data from the entire cohort, the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/µL and 1734/µL for DFS and OS. AMLPS risk groups included 158 (52.8%) patients in the low-risk, 128 (42.8%) in the intermediate-risk, and 13 (4.3%) in the high-risk group. With a median follow-up of 37.2 mo (range: 1.7-91.4 mo), five-year DFS rates in the low-, intermediate-, and high-risk groups were 83.4%, 78.7%, and 19.8%, respectively. And five-year OS rates in the low-, intermediate-, and high-risk groups were 89.3%, 81.1%, and 14.4%, respectively. On multivariate analysis performed with patient- and tumor-related factors, we identified AMLPS, age, and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS. CONCLUSION: AMLPS identified patients with a poor DFS and OS, and it was independent of age, pathologic stage, and various inflammatory markers.

Dyadic Effects of Individual and Friend on Physical Activity in College Students.

OBJECTIVE: Physical activity (PA) tends to decline throughout the college years, and close friends' influence is known to be an important factor in maintaining PA. This study examined the actor effect and partner effect between an individual and his/her friend regarding the influence of self-efficacy and social support on PA among Korean college students. DESIGN AND SAMPLE: Cross-sectional survey data from 108 pairs of individual students and friends were analyzed. MEASURES: The survey questionnaire measured PA, self-efficacy toward exercise, social support for PA, anxiety and depression, community environments, and perceived health status. Structural equation modeling with path analysis was conducted to test Actor-Partner Interdependence Model (APIM) explaining close relationships on PA. RESULTS: One-sided partner effect that friends' perceived friend support was directly related to individual's PA (ß = 0.20, p < .05) was revealed. Regarding actor effects, self-efficacy was directly related to higher levels of PA for individual and friend. Perceived health status was related to higher level of individuals' PA. CONCLUSIONS: These results suggest a role for public health nurses in developing interventions for college-aged young adults that promotes friend support for PA as well as individual self-efficacy toward PA, to engage young adults in establishing lifelong health-promoting PA.

Krukenberg tumors of gastric origin versus colorectal origin.

OBJECTIVE: The aim of this study is to compare the each clinical manifestation related with its mean survival time of Krukenberg tumors (KTs) of gastric origin versus with that of colorectal origin. METHODS: A total of 156 consecutive patients diagnosed with KTs of the ovary who underwent surgical treatment at a single institution between 2001 and 2010 were retrospectively evaluated. Each clinical manifestation related with its mean survival time compared two different groups. Survival analyses and comparisons were performed using the Kaplan-Meier method. RESULTS: Among the 156 patients with KT, 111 patients with KTs of gastric origin and 45 patients with KTs of colorectal origin were identified. For all patients with KTs, median survival time was 22.7 months. Each mean survival time among all patients with KTs of gastric origin and colorectal origin was 19.2 months and 27.3 months. The results showed that mean survival time of postmenopausal patients was 19.0 months compared with 32.5 months for premenopausal patients (P=0.015). Among all patients, mean survival time of those with metachronous cancer was longer than those with synchronous cancer (P=0.001). In all cases, especially when only one ovary was invaded, the mean survival time was relatively higher (P=0.001). CONCLUSION: Patients with KTs of colorectal origin had a better prognosis than those of gastric origin. In all cases of KT, the mean survival time was significantly longer in postmenoposal patients, metachronous disease and unilateral ovarian involvement. Notably, synchronous, ascites positive, and ovary only metastasis showed more longer mean survival time in the KTs of colorectal origin than KTs of gastric origin.

Phenethyl isothiocyanate sensitizes glioma cells to TRAIL-induced apoptosis.

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is a promising antitumor therapy. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL, highlighting the need for strategies to overcome TRAIL resistance. Here we show that in combination with phenethyl isothiocyanate (PEITC), exposure to TRAIL induced apoptosis in TRAIL-resistant glioma cells. Subtoxic concentrations of PEITC significantly potentiated TRAIL-induced cytotoxicity and apoptosis in glioma cells. PEITC dramatically upregulated DR5 receptor expression but had no effects on DR4 receptor. PEITC enhances TRAIL-induced apoptosis through the downregulation of cell survival proteins and the upregulation of DR5 receptors through actions on the ROS-induced-p53.

Digitoxin sensitizes glioma cells to TRAIL-mediated apoptosis by upregulation of death receptor 5 and downregulation of survivin.

Glioblastoma multiforme is the most lethal and aggressive astrocytoma among primary brain tumors in adults. However, most glioblastoma cells have been reported to be resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Here, we have shown that digitoxin (DT), a clinically approved cardiac glycoside for heart failure, can induce TRAIL-mediated apoptosis of glioblastoma cells. DT in noncytotoxic doses (20 nmol/l) can increase TRAIL-induced apoptosis in TRAIL-resistant U87MG glioblastoma cells. Treatment with DT led to apoptosis and a robust reduction in the levels of the antiapoptotic protein survivin by inducing its proteasomal degradation; however, it did not affect the levels of many other apoptosis regulators. Moreover, silencing survivin with small interfering RNAs sensitized glioma cells to TRAIL-induced apoptosis, underscoring the functional role of survivin depletion in the TRAIL-sensitizing actions of DT. We demonstrate that inactivation of survivin and death receptor 5 expression by DT is sufficient to restore TRAIL sensitivity in resistant glioma cells. Our results suggest that combining DT with TRAIL treatments may be useful in the treatment of TRAIL-resistant glioma cells.

Neuroprotective effects of Schisandrin B against transient focal cerebral ischemia in Sprague-Dawley rats.

Fruits of Schisandra have been traditionally used in East Asia for the treatment of dyspnea, cough, dysentery, insomnia, tonic-clonic seizures, and amnesia. Schisandrin B, a dibenzocyclooctadiene derivative isolated from Fructus Schisandrae, has been shown to produce antioxidant effect on rodent liver and heart. In the present study, we investigated the neuroprotective effects of Schisandrin B, a constituent drug of the fruit of Schisandra, against focal cerebral ischemia in rats. Schisandrin B (10, 30 mg/kg, i.p.) was twice administered 30 min before the onset of ischemia and 2h after reperfusion. Schisandrin B 10 and 30 mg/kg treated groups showed infarct volumes reduced by 25.7% and 53.4%, respectively, 2h after occlusion. Also, Schisandrin B treated animal treatment abrogated protein expression of TNF-α and IL-1ß and degradation of MMP-2 and MMP-9 in ischemic hemispheres. These results suggest that Schisandrin B treatment provides a neuroprotective effect to rats after transient focal cerebral ischemia by inhibiting inflammation and by protecting against metalloproteinase degradation.

Wogonin induces apoptosis by activating the AMPK and p53 signaling pathways in human glioblastoma cells.

We investigated the molecular basis of the ability of wogonin to control the intracellular signaling cascades of AMP-activated protein kinase (AMPK). This activity induces antitumor activities in glioblastoma multiforme (GBM) cells. Recently, the evolutionarily conserved serine/threonine kinase AMPK has emerged as a possible target for tumor control. We investigated the effects of wogonin on apoptosis regulation and the activation of AMPK. Wogonin treatment resulted in a series of antitumor effects such as cell death and apoptotic appearance. Activation of AMPK suppressed downstream substrates, such as the mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), and resulted in a general decrease in translation. Moreover, wogonin-activated AMPK decreased the activity and/or expression of lipogenic enzymes such as acetyl-CoA carboxylase. Furthermore, in GBM cells, wogonin blocked cell cycle progression at the G1 phase and induced apoptosis by inducing p53 expression and further upregulating p21 expression. Taken together, our findings demonstrated that wogonin has the potential to be a chemopreventive and therapeutic agent against human GBM.

Effects of visiting nurses' individually tailored education for low-income adult diabetic patients in Korea.

OBJECTIVE: To describe the effects of individually tailored education by visiting nurses for low-income adult diabetic patients. DESIGN AND SAMPLE: This one-group pretest-posttest study included 96 newly registered low-income adult diabetic patients in a public health center in DJ-gu (similar to a county in the United States) in 2006; the patients met the selection criteria. MEASURES: Diabetes knowledge, self-management, and blood glucose levels were compared before and after education. INTERVENTION: 15 visiting nurses delivered individually tailored education for 60-90 min/month for 7 months. RESULTS: After education, diabetes knowledge (p<.001) and self-management in all categories of lifestyle (p<.001), diet (p<.001), exercise (p<.001), foot care (p<.001), medication (p=.004), and insulin therapy (p=.022) significantly improved. The mean fasting blood glucose (FBG) level decreased by 14.53 mg/dl; this decrease was insignificant (p=.117). However, the relationship between education and FBG levels was significant (χ(2)=40.11, p=.005). CONCLUSIONS: Tailored education effectively improved the patients' knowledge of diabetes and self-management. Therefore, regular, individually tailored education on a long-term basis by visiting nurses can provide essential education to low-income adult diabetic patients for maintaining self-management.

Triptolide inactivates Akt and induces caspase-dependent death in cervical cancer cells via the mitochondrial pathway.

Triptolide, the main active component of the traditional Chinese herbal medicine Tripterygium wilfordii Hook F, has been shown to have potent immunosuppressive and anti-inflammatory properties. Here, we investigated the pro-apoptotic effect of triptolide in human cervical cancer cells and its underlying mechanisms. Exposure of cervical cancer cells to triptolide induced apoptosis, which was accompanied by loss of mitochondrial membrane potential, caspase processing (caspase-8, -9 and -3), and cleavage of the caspase substrate, poly(ADP-ribose) polymerase. The cytotoxic effects of triptolide were significantly inhibited by the caspase inhibitor, z-VAD-fmk. Triptolide-induced apoptosis was associated with a marked reduction in Akt phosphorylation and was exacerbated by LY294002 (phosphatidylinositol-3'-kinase inhibitor). Conversely, it was attenuated by Akt overexpression. Triptolide-induced apoptosis was also associated with downregulation of Mcl-1 and was significantly inhibited by Mcl-1 overexpression. These findings show that triptolide induces caspase-dependent, mitochondria-mediated apoptosis in cervical cancer cells, in part, by negatively regulating Akt and Mcl-1.