Objective: Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models. Methods: EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC. Results: FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well. Conclusion FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials.

Background: Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). Methods: A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. Results: Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). Conclusion Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

Background: Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). Methods: A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. Results: Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). Conclusion Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

BACKGROUND: The colitis-associated cancer exhibits different characteristics according to sex in the initiation and progression of the tumors. The aim of this study was to investigate the sex-associated difference in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer model. METHODS: The AOM/DSS ICR mouse model was established to compare male with female, and then the severity of colitis-associated carcinogenesis was examined macroscopically and histologically regarding the number, size, and location of tumors. Subsequently, levels of colonic mucosal cytokine, interleukin (IL)-1β and myeloperoxidase (MPO) were assessed. RESULTS: At the 16th week, the tumor multiplicity and the pro-inflammatory factors differed according to sex. The total tumor number was significantly higher in male (P = 0.020) and the number of large tumors (diameter > 2 mm) was higher in male (P = 0.026). In male, the tumors located more in distal colon (P = 0.001). MPO was significantly higher in AOM/DSS-treated male mice compared to the control group (P = 0.003), whereas the corresponding female group showed no significant change (P = 0.086). Colonic IL-1β level significantly increased in AOM/DSS groups compared to control groups both in male and female (male, P = 0.014; female, P = 0.005). It was higher in male group; however, there was no statistical significance (P = 0.226). CONCLUSIONS: In AOM/DSS murine model, colitis-associated colon tumorigenesis are induced more severely in male mice than female probably by way of inflammatory mediators such as IL-1β and MPO. The sex-related differences at the animal model of colon cancer suggest the importance of approach to disease with sex-specific medicine in human.
Animals ; Carcinogenesis ; Colitis ; Colon* ; Colonic Neoplasms* ; Female ; Humans ; Interleukins ; Male ; Mice* ; Mice, Inbred ICR ; Models, Animal ; Peroxidase ; Sodium

We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinson's disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7+/-16.8 spikes/sec, n=78) and the right side MERs (35.5+/-17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinson's Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinson's disease improving the overall experience of the patients.
Aged ; Anesthetics, Intravenous/*pharmacology ; *Deep Brain Stimulation ; Electrodes, Implanted ; Female ; Fentanyl/*pharmacology ; Humans ; Magnetic Resonance Imaging ; Male ; Microelectrodes ; Middle Aged ; Parkinson Disease/*prevention & control ; Propofol/*pharmacology ; Severity of Illness Index ; Subthalamic Nucleus/*drug effects/physiology ; Tomography, X-Ray Computed

PURPOSE: This study was conducted to evaluate the readmission rate of preterm infants of 30-33 weeks gestational age (GA) within 1 year following discharge from the neonatal intensive care unit (NICU). METHODS: This research was a part of the Retrospective Study to Evaluate Rehospitalization & Health Care Utilization after NICU Discharge in Preterm Infants (< or =33 weeks) II (RHANPI II) project conducted by the Committee on Data Collection and Statistical Analysis of the Korean Society of Neonatology. Enrolled infants (n=1,257) of 46 hospitals from April to September 2012, were retrospectively studied. RESULTS: The average GA and birth weight of the study population was 32(+2)+/-1(+1) weeks and 1,785+/-386 g, respectively. The cumulative readmission rate during the 360 days following discharge from the NICU was 27.3%. The cumulative readmission rate according to GA was 36.4%, 30.1%, 25.9% and 22.7% for infants born at 30, 31, 32 and 33 weeks GA, respectively. The corresponding respiratory readmission rate was 16.3%; this was 59.8% of total readmissions. There was no significant difference in the respiratory readmission rate according to GA group (log-rank test for trend, P-value=0.0558). Of the infants who were readmitted with respiratory problems, 57.0% (n=53/93) tested positive for respiratory syncytial virus (RSV). CONCLUSION: The cumulative readmission rate during the 360 days following discharge from the NICU was 27.3%. Respiratory problems were the most common cause of readmission, and RSV was the most common virus associated with respiratory readmission. Additionally, there was no difference in the rate of respiratory readmission according to GA group.
Birth Weight ; Data Collection ; Delivery of Health Care ; Gestational Age* ; Humans ; Infant ; Infant, Newborn ; Infant, Premature* ; Intensive Care, Neonatal* ; Korea ; Neonatology ; Respiratory Syncytial Viruses ; Retrospective Studies

Mitochondrial functions are essential for the survival and function of neurons. Recently, it has been demonstrated that mitochondrial functions are highly associated with mitochondrial morphology, which is dynamically changed by the balance between fusion and fission. Mitochondrial morphology is primarily controlled by the activation of dynamin-related proteins including dynamin-related protein 1 (Drp1), which promotes mitochondrial fission. Drp1 activity is regulated by several post-translational modifications, thereby modifying mitochondrial morphology. Here, we found that phosphorylation of Drp1 at serine 616 (S616) is mediated by cyclin-dependent kinase 5 (CDK5) in post-mitotic rat neurons. Perturbation of CDK5 activity modified the level of Drp1S616 phosphorylation and mitochondrial morphology in neurons. In addition, phosphorylated Drp1S616 preferentially localized as a cytosolic monomer compared with total Drp1. Furthermore, roscovitine, a chemical inhibitor of CDKs, increased oligomerization and mitochondrial translocation of Drp1, suggesting that CDK5-dependent phosphorylation of Drp1 serves to reduce Drp1's fission-promoting activity. Taken together, we propose that CDK5 has a significant role in the regulation of mitochondrial morphology via inhibitory phosphorylation of Drp1S616 in post-mitotic neurons.
Animals ; Cells, Cultured ; Cyclin-Dependent Kinase 5/*metabolism ; Dynamins/analysis/*metabolism ; HeLa Cells ; Humans ; Mitochondria/metabolism ; Mitosis ; Neurons/*cytology/*metabolism ; Phosphorylation ; Rats

PURPOSE: Due to the availability of serum prostate specific antigen (PSA) testing, the detection rate of insignificant prostate cancer (IPC) is increasing. To ensure better treatment decisions, we developed a nomogram to predict the probability of IPC. MATERIALS AND METHODS: The study population consisted of 1,471 patients who were treated at multiple institutions by radical prostatectomy without neoadjuvant therapy from 1995 to 2008. We obtained nonrandom samples of n = 1,031 for nomogram development, leaving n = 440 for nomogram validation. IPC was defined as pathologic organ-confined disease and a tumor volume of 0.5 cc or less without Gleason grade 4 or 5. Multivariate logistic regression model (MLRM) coefficients were used to construct a nomogram to predict IPC from five variables, including serum prostate specific antigen, clinical stage, biopsy Gleason score, positive cores ratio and maximum % of tumor in any core. The performance characteristics were internally validated from 200 bootstrap resamples to reduce overfit bias. External validation was also performed in another cohort. RESULTS: Overall, 67 (6.5%) patients had a so-called "insignificant" tumor in nomogram development cohort. PSA, clinical stage, biopsy Gleason score, positive core ratio and maximum % of biopsy tumor represented significant predictors of the presence of IPC. The resulting nomogram had excellent discrimination accuracy, with a bootstrapped concordance index of 0.827. CONCLUSION: Our current nomogram provides sufficiently accurate information in clinical practice that may be useful to patients and clinicians when various treatment options for screen-detected prostate cancer are considered.
Aged ; Asian Continental Ancestry Group ; Humans ; Logistic Models ; Male ; Middle Aged ; *Nomograms ; Prostatectomy ; Prostatic Neoplasms/*diagnosis/surgery

BACKGROUND/AIMS: This study was performed to evaluate whether the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates and the eradication rate of H. pylori could be different between cancer and non-cancer patients. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens obtained from 269 Koreans, who did not have any eradication therapy history and were diagnosed as one of the following diseases; chronic gastritis, benign gastric ulcer, duodenal ulcer or gastric cancer. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin were examined with the agar dilution method. In addition, eradication rate of H. pylori was evaluated. RESULTS: There was no significant difference in the primary antibiotic resistance to above eight antibiotics among chronic gastritis, peptic ulcer disease and gastric cancer. Furthermore there was no difference of antibiotic resistance between cancer and non-cancer patients, and there was no difference of eradication rate of H. pylori according to disease. CONCLUSIONS: Primary antibiotic resistance and H. pylori eradication rate were not different between cancer and non-cancer patients.
2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use ; Adult ; Aged ; Amoxicillin/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Chronic Disease ; Clarithromycin/therapeutic use ; *Drug Resistance, Bacterial ; Drug Therapy, Combination ; Duodenal Ulcer/complications/microbiology ; Female ; Gastritis/complications/microbiology ; Helicobacter Infections/drug therapy/*epidemiology/microbiology ; Helicobacter pylori/*drug effects/isolation & purification ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Omeprazole/therapeutic use ; Peptic Ulcer/complications/microbiology ; Proton Pump Inhibitors/therapeutic use ; Republic of Korea ; Stomach Neoplasms/complications/microbiology

A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the highest CV risk such as congestive heart failure, which resulted commonly from the impaired cardiac pumping due to a disrupted excitation-contraction (E-C) coupling. We investigated the effects of diclofenac on the L-type calcium channels which are essential to the E-C coupling at the level of single ventricular myocytes isolated from neonatal rat heart, using the whole-cell voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and ibuprofen, significantly reduced inward whole cell currents. At concentrations higher than 3 micrometer, diclofenac inhibited reversibly the Na+ current and did irreversibly the L-type Ca2+ channels-mediated inward current (IC50=12.89+/-0.43 micrometer) in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type Ca2+ currents but not the Na+ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type Ca2+ channel, leading to the impairment of E-C coupling in cardiac myocytes.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Calcium Channels, L-Type ; Diclofenac ; Heart ; Heart Failure ; Ibuprofen ; Muscle Cells ; Myocytes, Cardiac ; Naproxen ; Nifedipine ; Patch-Clamp Techniques ; Rats