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SummaryEvaluation of the Janus kinase 2 (JAK2) V617F mutation has been widely used for the diagnosis of myeloproliferative neoplasms (MPN). However, its prognostic relevance to clinical outcome is not completely understood. We investigated the association of JAK2 V617F with vascular events in Korean patients with myeloproliferative neoplasms (MPN). We studied 283 patients from 15 centers, who were diagnosed with MPN. The JAK2 V617F status was evaluated by allele-specific polymerase chain reaction (PCR) and sequencing. The patients’ diagnoses were essential thrombocythemia (ET n=146), polycythemia vera (PV n=120), primary myelofibrosis (n=12), and unclassifiable MPN (MPNu n=5). JAK2 V617F was detected in 89 (61%) patients with ET, 103 (86%) with PV, four (33%) with myelofibrosis, and four (80%) with MPNu. A higher number of leukocytes, haemoglobin levels and BM cellularity as well as an older age, lower platelet counts, and diagnosis of PV were significantly correlated with JAK2 V617F. Eighty-three and 43 episodes of thrombosis and bleeding occurred in 100 patients each before and after the diagnosis. Vascular events more frequently occurred in 37% of patients with JAK2 V617F than in 29% of those without the mutation (p=0.045). Among 175 patients whose samples were available for sequencing, 28 patients with homozygous JAK2 V617F had vascular events more frequently (57%) than those who were heterozygotes (39%) or had the wild type (27%) (p=0.03). The multivariate analysis showed that a JAK2 homozygous mutation, hypercholesterolemia and older age were independent risk factors for a vascular event. The results of this study showed that Korean patients with MPN had a similar JAK2 mutation rate and frequency of vascular events when compared to Western patients. The presence of V617F was significantly related to vascular events. Therefore, initial evaluation for the JAK2 mutation and careful monitoring for vascular events should be performed in MPN patients.

This paper reported the establishment of mass production system of adventitious roots of Codonopsis lanceolata through shake flask and bioreactor culture. Induction of adventitious roots was started from the explants of leaf, stem and root on 1/2 strength Murashing and Skoog (MS) solid medium. Stem segments were the best explants for induction of adventitious roots compared to leaf and root segments. Among the different auxins tested (NAA, IBA and IAA), number of adventitious root per explant was highest on solid medium with 1.0 mg/L IBA, and produced roots per explant. However, growth of adventitious roots was fast in the presence of IBA at low concentration (0.1 mg/L). In shake flask culture, maximum production of adventitious roots (fresh weight) was obtained in half-strength MS medium compared to full-strength and one-third MS medium. When the adventitious roots produced in shake-flask culture were transferred to 5 L air-lift bioreactor, 16 times of fresh weight increase was gained after one month of culture. These results indicate that this protocol for the production of C. lanceolata adventitious roots can be applied to large scale culture for practical application.

It is essential for the valid design of a marine flow-control valve to exactly know its flow characteristics. The present study has numerically investigated the flow characteristics inside a marine throttle-type globe valve using a kind of commercial CFD code, CFX10.0, with an adoption of the SST (Shear-Stress Transport) turbulence model. To validate the numerical approach, the flow coefficients are compared with the experimental ones. Results show that the globe valve is effective in the control of flow rate according to the opening ratio in case of the forward-direction flow, whereas it is effective in the flow shutoff in case of the reverse-direction flow. Around the inlet of the valve, a recirculation region is formed due to the blunt body shape, the turbulence intensity becomes strengthened and then an abrupt pressure loss occurs.

The present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65 mg m(-2) plus oxaliplatin 120 mg m(-2) on day 1 based on a 3-week cycle. Forty-two patients were enrolled in the current study, among whom 39 were assessable for efficacy and all assessable for toxicity. One complete response and 18 partial responses were confirmed, giving an overall response rate of 45.2% (95% confidence interval (CI); 31.7-59.7%). At a median follow-up of 7.7 months, the median time to progression and median overall survival was 5.7 (95% CI; 4.3-7.2) months and 9.9 (95% CI; 7.8-12.0) months, respectively. Grade 3/4 neutropenia occurred in 11 patients (26.1%) and febrile neutropenia was observed in four patients (9.5%). The common non-haematologic toxicity was fatigue (grade 1/2, 61.9%) and nausea (grade 1/2, 47.7%). The combination of docetaxel and oxaliplatin was found to be well tolerated and effective in patients with advanced gastric cancer.

The objectives of the study were to investigate the phenotypic and genotypic characterization of the persistent Salmonella Enteritidis (S. Enteritidis) isolates in two integrated broiler chicken operations, with attention focused mainly on the epidemiological approach. In the distribution of virulence genes, Salmonella enterotoxin (stn), invading host cell (invA), and Salmonella plasmid virulence (spvC) genes were widely distributed among the S. Enteritidis irrespective of their source of isolation, and Salmonella fimbrial (sefC) and plasmid encoded fimbrial (pef) genes were present in 28 and 20 S. Enteritidis strains, respectively. A total of 5 different XbaI-PFGE types were obtained from 31 S. Enteritidis isolates. Twenty-one types were divided on the basis their PFGE pattern, phage type and antimicrobial resistance pattern determined. There was a significant difference in phenotypic and genotypic characterization by two integrated broiler operations. Also, 8 isolates shown susceptible to all antimicrobials and 11 isolates with resistance to nalidixic acid were partly classified by XbaI PFGE pattern and by the phage type.

We performed a phase II study to evaluate the efficacy of combination chemotherapy consisting of gemcitabine, dexamethasone and oxaliplatin (GemDOx) as a biweekly regimen and salvage therapy in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL).Gemcitabine (1000 mg/m(2) ) and oxaliplatin (85 mg/m(2) ) were administered intravenously on days 1 and 15, and dexamethasone (40 mg) was administered orally on days 1-4.Twenty-nine patients were enrolled, and most patients had diffuse large B-cell lymphoma (n = 18). The median age of the patients and median prior number of chemotherapy cycles were 53 (range, 26-74) years and 1 (range, 1-4) cycle, respectively. Only 17 (58.6%) and 9 (31.0%) patients completed two or more and four or more cycles, respectively, and the median number of received cycles was two (range, 1-8). Overall response rates were 27.6% (complete response in 13.8%) among intent-to-treat patients and 47.1% (complete response in 23.5%) among patients who had received at least two GemDOx cycles. Median progression-free survival and median overall survival were 3.9 and 20.5 months, respectively. The most-frequent grade 3 or 4 toxicity was neutropenia (22.9%), and no grade 3 or 4 peripheral neurotoxicity was noted.GemDOx chemotherapy, therefore, showed modest activity against relapsed or refractory aggressive NHL, although toxicities were acceptable.

Background To investigate the efficacy, safety, and tolerability of weekly docetaxel treatment in advanced non-small cell lung cancer (NSCLC) patients in Korea. Methods This prospective observational study included Korean advanced NSCLC patients with Eastern Cooperative Oncology Group performance status

This paper describes an experimental study on the droplet formation and the subsequent motion in a microchannel having a cross junction. While one kind of liquid (pure water or water-surfactant mixture) is drawn into a horizontal inlet channel, the other kind (oil) is introduced through two vertical inlet channels. Due to the effect of surface tension on the interface between the two fluids, the droplets of the first fluid are formed near the cross junction. In this study, we have found that the droplet formation is affected even by slight difference in the surface tension. When the surface tension between two fluids is decreased, the droplet size is decreased in order to keep the equilibration between the pressure and the surface tension. In addition, the time interval between each of the droplet formations is decreased and the distance between droplets is also decreased when the surface tension is decreased.

Primary retroperitoneal mucinous cystadenocarcinoma is a rare tumor. Only about 30 such cases have been reported in the worldwide literature, and a few Korean cases have been reported. The pathogenesis is not clear, and coelomic metaplasia of the retroperitoneal mesothelium has gained wide support. There is no consensus on the appropriate treatment, but surgical exploration is needed for the diagnosis and treatment, and adjuvant chemotherapy may be recommended following complete surgical excision. The long-term prognosis has not been established. We report here on a 32-year-old woman who was diagnosed as having a retroperitoneal mucinous cystadenocarcinoma with mural nodules of sarcomatoid change. Tumor excision and adjuvant chemotherapy were done and the patient is doing well without any evidence of recurrence at 42 months postoperatively.

The purpose of this study was to investigate the biological and genetic characterization of persistent Salmonella isolates in an integrated broiler chicken operation, in an attempt to elucidate the source of contamination. From the breeder farm, the hatchery, the broiler farm and the chicken slaughter house of an integrated broiler chicken operation, a total of 6 serotypes were observed. Although S. Heidelberg was not detected in the broiler farm, it was consistently found in the breeder farm, the hatchery and the chicken slaughter house. Also, S. Enteritidis and S. Senftenberg were found in the hatchery and the chicken slaughter house, and the hatchery and the broiler farm, respectively. S. Gallinarum and S. Blockley were found only in the broiler farm, and S. Virchow was only recovered in the chicken slaughter house. Isolated S. Heidelberg, S. Enteritidis and S. Senftenberg strains were divided into 3, 5 and 7 types, respectively, on the basis of all properties. Especially, S. Senftenberg isolates, divided into four types by their antimicrobial resistance patterns, were all obviously the XbaI PFGE pattern. Also, four S. Enteritidis isolates resistant to nalidixic acid showed a difference in phage type and PFGE pattern. Such a different pattern was shown despite Salmonella isolates originating from an integrated broiler operation, suggesting that further epidemiological studies on many integrated chicken companies in Korea are needed.

One of the members of the tyrosine kinase receptor family is the protein product of the c-met proto-oncogene, which is the receptor for hepatocyte growth factor (HGF). HGF is known as a potent mitogen and motogen for many kinds of carcinoma cells, and has been found to simulate the growth and progression of gastric cancer cells through HGF-receptors. In addition, the urokinase-type plasminogen activator (uPA) and receptor (uPAR) also play important roles in the invasion and metastasis.The expression of c-met protein was investigated using immunohistochemical staining of 50 paraffin embedded gastric cancers, and by measuring the serum uPAR levels, before and after an operation, in gastric cancer patients using an ELISA assay.Of the 50 cases, 32 (64%) expressed the c-met protein. The c-met protein expression was significantly correlated with the TNM staging (p0.05), but the other prognostic factors were not significant variables. According to a Kaplan-Meier's plot, the one and three year overall survival rates were 94 and 70% in patients not expressing the c-met protein, and 81 and 33% in those that did, and the Survival curves revealed a significantly different prognosis (p=0.04). Elevated serum uPAR levels (or=3257.8 pg/ml, control+/-mean 2SD) were observed in 9 (34.6%) of 26 gastric cancer patients, but in none of control subjects. Average serum uPAR levels were 2980.8+/-616.2 pg/ml before the operation and 2404.7+/-455.9 pg/ml after, and decreased significantly after surgical resection (p0.05). The serum uPAR level correlated significantly with lymph node metastasis and vessel invasion (p0.05).The expression of c-met protein, and the level of uPAR, may be prognostic factors in gastric cancer.

The effects of imatinib plus chemotherapy were assessed in 87 patients with newly diagnosed Philadelphia chromosome-positive (Ph(+) ) acute lymphoblastic leukemia (ALL). Imatinib was administered continuously, starting from the eighth day of remission induction chemotherapy, then through five courses of consolidation or until allogeneic hematopoietic cell transplantation (HCT). Patients who were not transplanted were maintained on imatinib for 2 years. Eighty-two patients (94.3%) achieved complete remission (CR). Among these 82 CR patients, 40 experienced recurrence of leukemia. The 5-year relapse free survival (RFS) rate and overall survival (OS) rates were 39.0% and 33.4%, respectively. In total, 56 patients underwent allogeneic HCT in first CR. The 5-year cumulative incidence of relapse and OS rate of them were 59.1% and 52.6%, respectively. Six of seven patients who were maintained on imatinib after completion of consolidation relapsed and the median time of RFS was 40.7 months. In total patient, cumulative molecular CR rate was 88.5% and median time of molecular CR duration was 13 months. Initial imatinib dose intensity was significantly associated with median CR duration (P0.0001), and overall survival (P = 0.002). During the initial phase of treatment of patients with Ph(+) ALL, it is important to maintain imatinib dose intensity.

The current phase II clinical study was conducted to evaluate the efficacy and safety of weekly docetaxel alone, and weekly docetaxel-plus-oxaliplatin, as a second-line chemotherapy in patients with cisplatin-refractory advanced gastric cancer.We enrolled patients with histologically confirmed gastric adenocarcinoma whose disease had progressed after cisplatin-based regimens. Patients were randomly assigned to receive docetaxel alone (36 mg/m(2), days 1 and 8) or docetaxel (36 mg/m(2), days 1 and 8) and oxaliplatin (80 mg/m(2), day 1) combination therapy every three weeks.This trial was terminated early due to poor patient accrual rate. From January 2009 to January 2012, a total of 52 patients were enrolled in the current study from six centers: 27 patients in the docetaxel monotherapy arm and 25 patients in the docetaxel/oxaliplatin combination arm. Fifty-two patients were assessable for efficacy, and response rates as follows (response rate: 14.8% in the monotherapy arm, 24.0% in the combination arm; disease control rate: 48.1% in the monotherapy arm, 76.0% in the combination arm. The median progression-free survival was 2.0 (95% confidence interval=1.2-2.9) months in the monotherapy arm and 4.9 (95% confidence interval=3.6-6.6) months in the combination arm (p=0.002). The most common grade 3 or 4 adverse event was neutropenia (14% for monotherapy versus 32% for combination). No treatment-related mortality was observed.Weekly docetaxel and weekly docetaxel-plus-oxalipaltin regimens were found to be well-tolerated and effective as a second-line chemotherapy for patients with advanced gastric cancer.

// Hyun Joo Chung 1, 2 , Young Eun Choi 1 , Eun Sook Kim 1, 2 , Young-Hoon Han 1 , Myung-Jin Park 1, 2 , In Hwa Bae 1, 2 1 Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul, Korea 2 Research Center for Radio-Senescence, Korea Institute of Radiological & Medical Sciences, Seoul, Korea Correspondence to: In Hwa Bae, e-mail: ihbae@kirams.re.kr Keywords: miR-29b, BCL2L2, tumorigenicity, stemness, GBM Received: March 24, 2015 Accepted: June 09, 2015 Published: June 19, 2015 ABSTRACT Glioblastoma multiforme (GBM) is the most common malignant brain tumor and exhibits aggressive and invasive behavior. We previously identified four miRNAs—miR-29b, 494, 193a-3p, and 30e—with enhanced expression in GBM following treatment of ionizing radiation by miRNA microarray analysis. In this study, we found that only miR-29b inhibited tumor cell migration and invasion by reducing MMP-2 activity via phospho-AKT/β-catenin signaling, and stimulated a more epithelial-like morphology. Moreover, miR-29b inhibits angiogenesis by attenuating tube formation and the expression of VEGF and Ang-2, and stemness maintenance in GBM cells, as demonstrated by decreasing neurosphere formation and cancer stem cell marker protein expression. These findings support the anti-tumor properties of miR-29b in human GBM cells. Furthermore, miR-29b expression was inversely proportional to that of BCL2L2 mRNA or protein in various cancer cell types. Interestingly, BCL2L2 mRNA is highly expressed in the mesenchymal type of GBM. To further elucidate the relationship between miR-29b and BCL2L2 in GBM, we performed co-transfection reporter assays and determined that miR-29b downregulates BCL2L2 expression by directly binding its 3′UTR. Finally, we confirmed that BCL2L2 repression is of central importance to miR-29b anti-tumor activity using functional assays to examine cell migration, invasion, angiogenesis, and stemness. From these data, we propose that miR-29b may be a useful therapeutic agent in GBM.

Cucumber mosaic virus(CMV) and Broad bean wilt virus 2(BBWV2) were isolated from Gentiana scabra plants showing typical mosaic and yellowing symptoms. When the inoculum of mosaic symptom propagated in Nicotiana benthamiana was inoculated to primary leaves of Vigna sinensis, the local lesions of different types was developed. Type one produced a small necrotic spot(SNS) of pinpoint type, while the other one showed a large necrotic spot(LNS) of halo type. LNS on primary leaves of V. sinensis was also induced by inoculum from yellowing symptom on G scabra. Single lesion from SNS induced a typical mosaic symptom on N. Benthamiana. On the other hand, LNS produced a chlorotic ring symptom on inoculated leaves and mosaic plus necrotic ringspot on upper leaves of N. benthamiana. An isolate of CMV from SNS and BBWV2 from LNS were detected by using dsRNA analysis, RT-PCR and agar gel double-diffusion test. Thus, our results should provide a tool of a simple method for discrimination from mixed infected plants by CMV and BBWV2.

The objective of this study was to review the natural history of extrapulmonary small cell carcinoma (EPSCC) with specific emphasis on clinical features, response to treatment and survival. The records of all patients (n=34) with EPSCC treated at Yeungnam University Medical Center and Catholic University of Daegu Medical Center between 1998 and 2005 were retrieved and reviewed. The primary sites of tumor were the esophagus and thymus in 6 patients (17.6%) each, pancreas and stomach in 5 patients each (14.7%); other sites included were the cervix, abdominal lymph nodes, abdominal wall, bladder, colon, maxillary sinus, nasal cavity, ovary, parotid gland and liver. Twenty three patients out of 34 had limited disease. The median survival of all patients was 14 months. Independent prognostic factors included stage and primary tumor location. The prognosis for the patients with extensive disease and in the gastrointestinal group was unfavorable. EPSCC is a non homogeneous disease entity. As a result of its frequent recurrence, multimodal therapy has a better outcome even in cases of limited disease. Combination chemotherapy plays a central role for treatment of extensive disease in EPSCC. Further multicenter studies are now needed to determine more details regarding disease sub-class and optimal treatment modality.

Ethephon at 50 microM enhanced both root growth and ginsenoside accumulation in ginseng (Panax ginseng C.A. Meyer) adventitious root cultures, but at 100 microM it inhibited only ginsenoside accumulation. Ginsenoside productivity with 50 microM ethephon was the highest at 1.7 mg l(-1) d(-1) after 8 days of elicitation. However, elicitation with 50 microM ethephon and 100 microM methyl jasmonate (MJ) improved productivity (6.3 mg l(-1) d(-1)) whereas elicitation with 100 microM MJ alone gave only 2.9 mg l(-1) d(-1).

Given a previous report that Bcl-w is expressed in gastric cancer cells, particularly in those of an infiltrative morphology, we investigated whether Bcl-w expression influences the invasiveness of gastric cancer cells. To accomplish this, Bcl-w was overexpressed in adherent types of gastric adenocarcinoma cell lines, and this was found to result in an increase in their migratory and invasive potentials. These effects were not induced when Bcl-2 was overexpressed in the same cell types. Consistently, Bcl-w, but not Bcl-2, overexpression increased matrix metalloproteinase-2 (MMP-2) expression, and synthetic or natural inhibitors of MMP-2 abolished Bcl-w–induced cell invasion. Bcl-w overexpression also activated phosphoinositide 3-kinase (PI3K), Akt, and Sp1, and the blocking effects of each of these components using pharmacologic inhibitors, dominant-negative mutants, or small interfering RNA abolished the ability of Bcl-w to induce MMP-2 and cell invasion. The inhibition of PI3K/Akt signaling also prevented Sp1 activation. Overall, our data suggest that Bcl-w, which was previously shown to enhance gastric cancer cell survivability, also promotes their invasiveness by inducing MMP-2 expression via the sequential actions of PI3K, Akt, and Sp1. (Cancer Res 2006; 66(10): 4991-5)

TNF-alpha mediated apoptosis of the hematopoietic cells has been thought to contribute to the ineffective hematopoiesis observed in myelodysplastic syndrome (MDS). The combination of pentoxifylline (P) and ciprofloxacin (C) has been shown to reduce the serum levels of TNF-alpha, and an earlier trial of P and C with dexamethasone (D) provided good palliation for patients with MDS. The purpose of this study is to assess the hematologic response to PCD therapy for patients suffering with MDS. 21 of 25 patients who completed at least of 12 weeks of treatment were evaluable for the treatment efficacy. At baseline, the patient's median age was 60 yr (range: 18-75 yr). The diagnoses according to WHO classification included: RA (n=5), RCMD (n=10), RARS (n=1), RCMD/RS (n=1), RAEB (3), and CMML (n=1). 11 patients (52%) had at least single lineage response. 3 patients (11%) showed improvement of triple lineage cytopenia. There were no differences in the response rates between the FAB subtypes. The median time to response was 4 weeks (range: 2-12 weeks), and it is interesting that 9 of 11 patients who had a response remained without relapse for a median of 177 days (range: 78-634 days). These preliminary results indicate that anti-cytokine therapy with PCD is an effective and well tolerated palliative treatment for patients with MDS.

During radiotherapy of cancer, neighboring normal cells may receive sub-lethal doses of radiation. To investigate whether such low levels of radiation modulate normal cell responses to death stimuli, primary cultured human fibroblasts were exposed to various doses of gamma-rays. Analysis of cell viability using an exclusion dye propidium iodide revealed that the irradiation up to 10 Gy killed the fibroblasts only to a minimal extent. In contrast, the cells efficiently lost their viability when exposed to 0.5-0.65 mM H(2)O(2). This type of cell death was accompanied by JNK activation, and was reversed by the use of a JNK-specific inhibitor SP600125. Interestingly, H(2)O(2) failed to kill the fibroblasts when these cells were pre-irradiated, 24 h before H(2)O(2) treatment, with 0.25-0.5 Gy of gamma-rays. These cytoprotective doses of gamma-rays did not enhance cellular capacity to degrade H(2)O(2), but elevated cellular levels of p21(Cip/WAF1), a p53 target that can suppress H(2)O(2)-induced cell death by blocking JNK activation. Consistently, H(2)O(2)-induced JNK activation was dramatically suppressed in the pre-irradiated cells. The overall data suggests that ionizing radiation can impart normal fibroblasts with a survival advantage against oxidative stress by blocking the process leading to JNK activation.

Thrombotic thrombocytopenic purpura (TTP) is a disseminated form of thrombotic micro-angiopathy. Although most cases are held to be idiopathic, its association with malignancy iswellrecognizedanditusuallyoccursattheterminalstageofcancer.Bonemarrownecrosis(BMN)is another rare disorder defined pathologically as the necrosis of myeloid tissue and medullarystromawithpreservationofbone.Whilehematologicmalignancyisthemostcommonunderlyingdisease associated with BMN, it can also be caused by solid tumors. Neither TTP nor BMNassociated with colon cancer has been reported. We describe here a patient with the rare asso-ciation of TTP and BMN displayed as the first manifestation of an advanced colon cancer. Theanemia and thrombocytopenia responded not to plasma exchange but to the combinationchemotherapy. This case indicates that metastatic cancer should be included in the differentialdiagnosis of TTP and BMN, and that the chemotherapy may improve the detrimental clinicalcourse.Key words: thrombotic thrombocytopenic purpura – bone marrow necrosis – colon cancer –microangiopathic hemolytic anemia

PURPOSE This study was conducted to evaluate the efficacy and safety of combination chemotherapy, with docetaxel and cisplatin, as a first line treatment for advanced non-small cell lung cancer. MATERIALS AND METHODS Between March 1998 and December 2001, 35 patients with advanced non-small cell lung cancer were enrolled in this study. The patients were treated at 3-week intervals, with one course of a regimen consisting of docetaxel (75 mg/m2 IV for 1 hours) on day 1 and cisplatin (60 mg/m2 IV) on day 2. RESULTS The median age of the patients was 60.3 years. Of the 35 patients, 20 and 15 had stage IIIb and stage IV diseases, respectively. A complete response was observed in 1 patient and partial response in 15, with an overall response rate of 46%. The overall median survival duration was 40.3+/-25.2 weeks. The median time to progression and response duration were 21.6+/-5.5 and 15.1+/-5.9 weeks, respectively. The survival duration was statistically significantly longer in the response group (50.6 weeks) than in the non-response group (31.6 weeks) (p

Staphylococci were isolated from dogs in animal hospitals, animal shelters, and the Daegu PET EXPO to investigate the characteristics of circulating methicillin-resistant Staphylococcal (MRS) strains in companion animals in Korea. A total of 36/157 isolates were classified as MRS, and subdivided as follows: 1 methicillin-resistant Staphylococcus aureus (MRSA), 4 methicillin-resistant Staphylococcus epidermidis, 2 methicillin-resistant Staphylococcus haemolyticus, and 29 MRS spp. Among the 36 MRS isolates tested, 100% were resistant to oxacillin and penicillin, and at least 50% were resistant to sulfamethoxazole/trimethoprim (69.4%), erythromycin (63.9%), tetracycline (58.3%), cefoxitin (55.6%), clindamycin (50.0%) or pirlimycin (50.0%). Additionally, 34/36 MRS isolates (94.4%) were mecA positive, 15 of which were further classified as SCCmec type V, 6 isolates as type I, 4 isolates as type IIIb, 1 isolate as type IVa, 1 isolate as type IV, with 7 isolates being non-classifiable. The results of multilocus sequence typing and spa typing for the one MRSA strain were ST 72 (1-4-1-8-4-4-3) and spa t148. Our results provide evidence that companion animals like dogs may be MRS carriers, and that continued surveillance of MRS in companion animals is required to prevent increased incidences in humans.

Taraxacum platycarpum has been used as a medicinal plant. We investigated optimal condition for efficient plant regeneration through adventitious shoot formation on medium with various kinds of growth regulators. Adventitious shoot formation was achieved when cytokinin was used alone. Shoot formation was higher on MS medium containing 2 mg/L BAP compared to that with 2 mg/L kinetin and 2 mg/L 2-ip. Among root, hypocotyl and cotyledon, roots were the best explant for the adventitious shoot induction. Adventitious shoot formation from roots declined markedly by the combination of both 0.1 mg/L NAA and 2 mg/L BAP, while shoot formation from cotyledons was stimulated by the same combination. Root formation from the regenerated shoots was achieved on 1/3MS medium containing 0.2 mg/L NAA. Regenerated plantlets was acclimatized and transplanted to the soil, showing 100% survival.

Zinc oxide (ZnO) nanoparticles (NPs) have been widely used for food fortification, because zinc is essential for many enzyme and hormone activities and cellular functions, but public concern about their potential toxicity is increasing. Interactions between ZnO and biomatrices might affect the oral absorption, distribution, and toxicity of ZnO, which may be influenced by particle size. In this study, ZnO interactions with biomatrices were investigated by examining the physicochemical properties, solubility, protein fluorescence quenching, particle–protein corona, and intestinal transport with respect to the particle size (bulk vs. nano) in simulated gastrointestinal (GI) and plasma fluids and in rat-extracted fluids. The results demonstrate that the hydrodynamic radii and zeta potentials of bulk ZnO and nano ZnO in biofluids changed in different ways, and that nano ZnO induced higher protein fluorescence quenching than bulk ZnO. However, ZnO solubility and its intestinal transport mechanism were unaffected by particle size. Proteomic analysis revealed that albumin, fibrinogen, and fibronectin play roles in particle–plasma protein corona, regardless of particle size. Furthermore, nano ZnO was found to interact more strongly with plasma proteins. These observations show that bulk ZnO and nano ZnO interact with biomatrices in different ways and highlight the need for further study of their long-term toxicity.

Radiotherapy represents the most effective non-surgical modality in cancer treatment. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression, and are involved in many biological processes and diseases. To identify miRNAs that influence the radiation response, we performed miRNA array analysis using MCF7 cells at 2, 8, and 24 h post irradiation. We demonstrated that miR-770-5p is a novel radiation-inducible miRNA. When miR-770-5p was overexpressed, relative cell number was reduced due to increased apoptosis in MCF7 and A549 cells. Transcriptomic and bioinformatic analyses revealed that PDZ-binding kinase (PBK) might be a possible target of miR-770-5p for regulation of radiosensitivity. PBK regulation mediated by direct targeting of miR-770-5p was demonstrated using luciferase reporter assays along with wild-type and mutant PBK-3′untranslated region constructs. Radiation sensitivity increased and decreased in miR-770-5p- and anti-miR-770-5p-transfected cells, respectively. Consistent with this result, transfection of short interfering RNA against PBK inhibited cell proliferation, while ectopic expression of PBK restored cell survival from miR-770-5p-induced cell death. In addition, miR-770-5p suppressed tumor growth, and miR-770-5p and PBK levels were inversely correlated in xenograft model mice. Altogether, these data demonstrated that miR-770-5p might be a useful therapeutic target miRNA that sensitizes tumors to radiation via negative regulation of PBK.

Patients receiving red blood cell (RBC) transfusions are at risk of iron overload, which can cause significant organ damage and is an important cause of morbidity and mortality.This study was an open-label, single-arm, prospective clinical study to evaluate the efficacy and safety of deferasirox (DFX) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML). Patients with serum ferritin levels of at least 1000 ng/mL and ongoing transfusion requirements were enrolled. DFX was administered for up to 1 year. A total of 100 patients were enrolled.Serum ferritin levels decreased significantly following treatment (from 2000 to 1650 ng/mL, p = 0.004). The median absolute reduction in serum ferritin levels was -65 ng/mL in AA (p = 0.037), -647 ng/mL in lower-risk MDS (MDS-LR; p = 0.007), and -552 ng/mL in higher-risk MDS (MDS-HR)/AML (p = 0.482). Mean labile plasma iron (LPI) levels decreased from 0.24 μmol/L at baseline to 0.03 μmol/L at 1 year in all patients (p = 0.036). The mean LPI reduction in each group was -0.17 μmol/L in AA, -0.21 μmol/L in MDS-LR, and -0.30 μmol/L in MDS-HR/AML. Gastrointestinal disorders were commonly observed among groups (16.0%). DFX was temporarily skipped for adverse events in seven patients (7.0%) and was permanently discontinued in 11 patients (11.0%).DFX reduced serum ferritin and LPI levels in patients with transfusional iron overload. Despite the relatively high percentage of gastrointestinal side effects, DFX was tolerable in all subgroups.

Background. Combination chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma (NTCL). Methods. Forty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m2 on days 1–3; methotrextate 30 mg/m2 on days 3 and 10; etoposide 100 mg/m2 on days 1–3; and prednisolone 60 mg/m2 per day on days 1–5) followed by involved field radiotherapy (IFRT). Results. Overall response rates were 73% (complete remission [CR] in 11 of 41 evaluable patients [27%]) after IMEP chemotherapy and 78% (CR 18 of 27 evaluable patients [67%]) after IMEP followed by IFRT. Neutropenia and thrombocytopenia were documented in 33 patients (75%) and 7 patients (16%), respectively. Only 8 patients (18%) experienced febrile neutropenia. Three-year progression-free survival (PFS) and overall survival (OS) were 66% and 56%, respectively. High Ki-67 (≥70%) and Ann Arbor stage II independently reduced PFS (p = .004) and OS (p = .001), respectively. Conclusion. Due to the high rate of progression during IMEP chemotherapy, IFRT needs to be introduced earlier. Moreover, active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL.

This paper presents calibration and user test results of a 3-D tip-force sensing needle with haptic feedback. The needle is a modified MRI-compatible biopsy needle with embedded fiber Bragg grating (FBG) sensors for strain detection. After calibration, the needle is interrogated at 2 kHz, and dynamic forces are displayed remotely with a voice coil actuator. The needle is tested in a single-axis master/slave system, with the voice coil haptic display at the master, and the needle at the slave end. Tissue phantoms with embedded membranes were used to determine the ability of the tip-force sensors to provide real-time haptic feedback as compared to external sensors at the needle base during needle insertion via the master/slave system. Subjects were able to determine the position of the embedded membranes with significantly better accuracy using FBG tip feedback than with base feedback using a commercial force/torque sensor (p = 0.045) or with no added haptic feedback (p = 0.0024).

We evaluated the clinical outcomes and relapse patterns of 80 patients with primary sinonasal tract diffuse large B-cell lymphoma (SN-DLBCL) treated with rituximab-cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy at 22 institutions. A total of 59 (73.8%) patients received R-CHOP chemotherapy alone, whereas 21 (26.3%) were treated with R-CHOP followed by involved field radiotherapy (IFRT). In 73 patients with Ann Arbor stage I-II disease, no significant difference was found in the response rate or overall survival (OS) between R-CHOP alone (n = 52) and R-CHOP followed by IFRT (n = 21). Among 11 relapsed patients in this study, the most common pattern of relapse was local (n = 8, 11.8%), whereas central nervous system (CNS) relapse was observed in only one (1.9%) patient. These results suggest that patients with primary SN-DLBCL treated with R-CHOP have a relatively low CNS relapse rate and better OS compared to previous studies before the introduction of R.

Background Breast metastasis from extramammary malignancy is uncommon and often presents diagnostic challenges. Herein, we report a case of a patient with metachronous isolated breast metastasis from pulmonary adenocarcinoma with micropapillary component. Case presentation A 47-year-old woman presented with left breast nodule detected on a screening breast ultrasonography. She had surgery for pulmonary adenocarcinoma 3 years ago, and was disease-free state in the follow up studies. The patient was diagnosed with invasive micropapillary carcinoma of the breast by core needle biopsy. She underwent left breast lumpectomy and sentinel lymph node biopsy, and the histologic findings revealed micropapillary carcinoma. Based on the immunohistochemical study, the final diagnosis was solitary breast metastasis from pulmonary adenocarcinoma with micropapillary component. Conclusions The diagnosis of metastasis to the breast from extramammary malignancies is difficult but important for proper management and prediction of prognosis. A careful clinical history with a thorough clinical examination is needed to make the correct diagnosis.

3-Hydroxy-3',4'-dimethoxyflavone (HDMF) is a natural chemical product that is not currently regarded as a drug. In our study, we employed glioblastoma cells and cell biology and biochemistry approaches to investigate the potential of HDMF as a natural anticancer therapy option. FACS analysis showed that treatment concentration of HDMF does not exert cytotoxicity on U251 cells. Wound-healing and invasion assays showed that HDMF dose-dependently decreased the migratory and invasive potentials of these cells, likely by indirectly inhibiting MMP-3 activity as a result of the inhibition of p38 and ERK signaling proteins - an effect of HDMF also shown by Western blotting. HDMF inhibits Bcl-w-induced neurosphere formation and the expression of glioma stem cell markers, such as Musashi, Sox-2 and c-myc. These results indicate that HDMF suppresses migratory or invasive potentials and stemness and functions as a negative agent against the aggressiveness of glioblastoma cells. We propose that HDMF has potential as anticancer drug for inhibiting the aggressiveness of glioblastoma multiforme (GBM).

The practical usefulness of Helicobacter pylori eradication for immune thrombocytopenia (ITP) patients is still controversial. However, some ITP patients respond to H. pylori eradication. We conducted a multi-center, open label, prospective phase II study to define the efficacy and toxicities of H. pylori eradication as the first line treatment for persistent or chronic ITP patients with moderate thrombocytopenia. Patients with persistent or chronic ITP showing moderate thrombocytopenia (30 × 10(9)/L ≤ platelet count ≤ 70 × 10(9)/L) and positive C(13)-urea breath test (UBT) were selected. Medication consisted of lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg orally twice daily for a week. Complete response (CR) rate at 4 weeks, 3 months, 6 months, 12 months, and maximal response was 19.2, 50.0, 50.0, 26.9, and 65.4%, respectively. Overall response rate (ORR) at 4 weeks, 3 months, 6 months, 12 months, and maximal response was 19.2, 57.7, 65.4, 30.8, and 69.2%, respectively. Median maximal platelet count during the first 3 months was 110 × 10(9)/L (range, 40-274). Median time to CR was 8 weeks (95% CI = 5.429-10.571). Median time to ORR was 4 weeks (95% CI = 1.228-6.772). Only per-protocol population was a response predictor for ORR at 3 months (70.0%, p = 0.054) and maximal ORR (80.0%, p = 0.051), but not for CR at 3 months (60.0%, p = 0.160). Therefore, eradication of H. pylori is an effective and durable first line treatment for persistent or chronic ITP with moderate thrombocytopenia with high ORR and rapid onset in this study.

This paper describes phase noise analysis of the double-conversion heterodyne TV tuner system for 8VSB digital terrestrial broadcasting. It is proposed an accurate simulation model of the phase noise of the PLL-based frequency synthesizers. Using the proposed model, we evaluate the performance of the digital TV receiver system in terms of symbol error rate in conjunction with the matched filter and the frequency-and-phase locked loop.

The aim of this study was to determine whether gamma-rays affect differentiation in mouse epidermal cells. After a pre-treatment with the PKC inhibitor staurosporin (STS) or 1-(5-isoquinolinesulfomyl)-2-methylpiperazine (H7), gamma-rays were irradiated with or without an elevation of 0.12 mM Ca2+ and expressions of differentiation markers and each PKC isozyme were examined in normal primary and v-rasHa transformed mouse keratinocytes. Gamma-rays induced the expressions of differentiation markers of keratin 1 and 10 (K1 and 10), filaggrin, loricrin and SPR-1 in normal keratinocytes when the Ca2+ concentration was increased, and these phenomena were augmented in H7 pretreated cells. Similar results were obtained in STS pretreated cells; in this case, gamma-rays enhanced the expressions of the differentiation markers even without an elevated Ca2+ concentration. In v-rasHa transformed cells, gamma-rays induced the expression of differentiation markers not only at 0.05 mM Ca2+, but in 0.12 mM Ca(2+)-shifted cells, and in H7 pretreated cells, these phenomena were augmented. The translocation of PKC alpha to the particulate fraction was seen in H7 pretreated normal keratinocytes. Radiation also induced PKC alpha expression in STS pretreated cells, independent of Ca(2+)-shift, as well as altered expressions of PKC delta and -eta, while expressions of PKC alpha, -delta, -epsilon, and -eta were enhanced in v-rasHa transformed cells. In conclusion, gamma-rays augmented the expressions of both spinous and granular differentiation markers in normal and v-rasHa transformed keratinocytes and this effect was augmented when PKC inhibitors were used, which may be mediated by the cellular redistribution of PKC isozymes.

The present study sought to elucidate the role of induction and consolidation therapy in elderly patients. We retrospectively collected data of 477 patients who were aged over 60 years at the time of acute myeloid leukemia (AML) diagnosis. The median overall survival (OS) was 339 days in the induction group (n = 266) and 86 days in the best supportive care group (n = 211) (P0.001). In the induction group, the complete remission (CR) rate was 58.3 %, and treatment-related death was 15.4 %. Successful induction was related to good performance [Eastern Cooperative Oncology Group (ECOG2)] [hazard ratio (HR) 3.215; P = 0.002]. Mortality correlated with failure to achieve CR (HR 4.059; P0.001) and poor performance status (ECOG2) (HR 2.731; P = 0.035). In CR patients, poor karyotype and absence of consolidation (HR 2.313; P = 0.003) correlated with mortality. More than one cycle of consolidation was associated with better OS (P0.001). Lack of salvage therapy was associated with mortality in patients who did not achieve CR (HR 3.223; P = 0.005). Intensive induction in patients with good performance and1 cycle of consolidation after CR may be the best strategy for improving OS in elderly AML patients.

We determined the antimicrobial resistance of Salmonella serovars from a total of 154 (44 chilling waters and 110 carcasses) samples collected from 22 poultry slaughterhouses. Standard culture techniques, Kauffmann-White slide agglutination and disc diffusion tests were used to isolate, and identify the serovars and to assess the antimicrobial activity, respectively. A total of 88 isolates belonging to 34 Salmonella serovars from 67 (43.5%) positive samples were identified. Among the samples examined, 68.2% (15/22), 22.7% (5/22), and 42.7% (47/110) from the first chilling waters, the last chilling waters, and carcasses were found contaminated with Salmonella, respectively. The prevalent serovars were S. Enteritidis (12.5%) followed by S. Montevideo and S. Senftenberg (8.0%). Rare Salmonella serovars such as S. Aba, S. Malmoe, S. Westhampton, S. Takoradi, and S. Baiboukoum in chicken slaughterhouses and S. Newbrunswick, S. Huddinge S. Glostrup, S. Dujugu, S. Goettingen and S. II in duck slaughterhouses were also detected. Among the serovars, 52.3% (46/88) and 21.6% (19/88) were resistant to one antibiotic and more than two antibiotics, respectively. High antimicrobial resistance rates against sulfamethoxazole (39.8%) followed by tetracycline (22.7%), nalidixic acid (21.6%), ampicillin and amoxicillin-clavulanic acid (8.0%), and chloramphenicol (4.5%) were observed. These results suggest more stringent hygienic measures should be taken to reduce the incidence of pathogen contamination in the food chain.

Localized radiotherapy (RT) can cause immune dysfunction. Bojungikki-tang is known to restore immune function. We investigated the absolute counts and percentages of peripheral blood (PB) lymphocyte subtypes in end stage cancer patients before and after RT and after oral administration of Bojungikki-tang water extract (BJITE) and to evaluate the changes mediated by RT and BJITE. Absolute counts and percentages of lymphocyte and lymphocyte subsets were determined in whole blood using the TetraONE System (Beckman Coulter, USA). Flow cytometry results were compared before and after RT and after administration of BJITE. Absolute numbers of CD3+, CD4+, and CD8+ T cells and CD19+ B cells decreased significantly after RT (P<0.05). Absolute numbers of CD3-CD56+ cells did not change in both groups. No significant differences were observed in the absolute counts of lymphocyte subtypes before and after administration of BJITE or vitamin group. When BJITE group was compared with vitamin group, absolute numbers of CD19+ B cells increased. RT-induced decrease in T cells and B cells in PB suggests that immune deterioration occurs after RT. Administration of BJITE might be effective in the restoration of number of B cells.

Summary We investigated the prognostic value of the magnetic resonance imaging (MRI) pattern of bone marrow involvement in patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). 126 patients with untreated MM indicated for ASCT underwent spine MRI and cytogenetic analysis at diagnosis. All patients received ASCT after induction therapy of VAD (vincristine, doxorubicin, dexamethasone; n = 55) or a thalidomide-based regimen (TCD; n = 71). Thalidomide maintenance therapy was performed in 68 patients. The MRI pattern was normal in 27, focal in 47, and diffuse/variegated in 52 patients. Patients with the diffuse/variegated pattern showed significantly higher stage (P = 0·038), higher β-2 microglobulin level (P = 0·001) and severe anaemia (P = 0·015). However, the cytogenetics were not different among the MRI patterns (P = 0·890). Progression-free survival (PFS) was lower in the diffuse/variegated pattern (P = 0·002) than other patterns, but not overall survival (OS) (P = 0·058). Thalidomide maintenance therapy was correlated only with PFS (P = 0·001). High-risk cytogenetics were associated with both poorer PFS (P

Background The number of CD34+ cells in a peripheral blood stem cell collection is the key factor in predicting successful treatment of hematologic malignancies. Korean Red Ginseng (KRG) (Panax ginseng C.A. Meyer) is the most popular medicinal herb in Korea. The objective of this study was to determine the effect of KRG on hematopoietic colony formation. Methods Bone marrow (BM) samples were obtained from 8 human donors after acquiring informed consent. BM mononuclear cells (MNCs) were isolated, and CD34+ cells were sorted using magnetic beads. The sorted CD34+ cells were incubated with or without total extract of KRG (50 µg/mL, 100 µg/mL) or Ginsenoside Rg1 (100 µg/mL), and the hematopoietic colony assay was performed using methylcellulose semisolid medium. The CD34+ cell counts were measured by a single platform assay using flow cytometry. Results The numbers of human BM-MNCs and CD34+ cells obtained after purification were variable among donors (5.6×10(7) and 1.3-48×10(7) and 8.9×10(4) and 1.8-80×10(4), respectively). The cells expanded 1,944 times after incubation for 12 d. Total extract of KRG added to the hematopoietic stem cell (HSC)-specific medium increased CD34+ cell counts 3.6 times compared to 2.6 times when using HSC medium alone. Total numbers of hematopoietic colonies in KRG medium were more than those observed in conventional medium, especially that of erythroid colonies such as burst forming unit-erythroid. Conclusion Total extract of KRG facilitated CD34+ cell expansion and hematopoietic colony formation, especially of the erythroid lineage.

This study was undertaken to identify and characterize amino acid substitutions in gyrA and parC related with quinolone resistance of 27 nalidixic acid-resistant (NaR) Salmonella isolates collected in poultry slaughterhouses in Korea. A total of 51 Salmonella isolates were detected from 44.8% (47/105) of the total samples from 15 poultry slaughterhouses examined, among which 27 (52.9%) NaR isolates were detected while ciprofloxacin (Cip) resistance was not present in the isolates. These 27 NaR isolates of DNA sequencing revealed that it contained three types of gyrA mutations in only D87 codon. Mutations in the D87 codon resulted in substitutions to G in most of the isolates, but D87Y and D87N exchanges were also detected. Although Cip resistance was absent, reduced susceptibility characterized by mutations in gyrA was apparent among Salmonella isolates from poultry slaughterhouses in Korea.

Poultry products have consistently been identified as important sources of Salmonella infection in humans, because vertical transfer of infection from breeding hens to progeny is an important aspect of the epidemiology of Salmonella spp. infection within the poultry industry. The aim of this study was to estimate the prevalence of Salmonella contamination in poultry products from 15 different located geographical areas from among the 50 poultry slaughterhouses authorized to operate in Korea and to characterize all the isolates by genotyping, phage typing and antibiotic resistance pattern. Salmonella was isolated from 10 (66.7%) of the first and 5 (33.3%) of the last chilling waters and from 32 (42.7%) carcasses originating from 9 slaughterhouses. The major prevalent serotypes of Salmonella originating from 2 duck slaughterhouses and 13 chicken slaughterhouses tested were S. Typhimurium and S. Enteritidis, respectively. Regarding the characteristics of their antibiotic resistance, 8 of the 11 ampicillin resistant (AmR) isolates carried blaTEM only, two carried blaTEM and blaCTX-M-14 and one carried blaCTX-M-3 and only one AmR isolate with the blaCTX-M-3 β-lactamase gene was an ESBL-producing Salmonella strain. Twenty-seven Salmonella isolates showed nalidixic acid resistance with a mutation at amino acid codon Asp87 in gyrA and no mutation in the parC gene. In all the phenotypic and genotypic properties of the 18 S. Enteritidis and 8 S. Typhimurium based on PFGE, phage types and antibiotic resistance pattern, the predominant patterns were XEI/BEI-PT32a-NaR (n = 5) and XTI/BTI-RNDC-no resistant antibiotics (n = 6), respectively.

We retrospectively investigated the incidence, risk factors, and outcomes of SOS (sinusoidal obstruction syndrome; previously veno-occlusive disease [VOD]) after allogeneic hematopoietic stem cell transplantation (alloHSCT) in aplastic anemia. Two hundred and sixty patients were included in the analysis. SOS developed in 7.3% (n=19/260) of patients. Classical Cy (200 mg/m(2))-ATG was the most common conditioning regimen (84.2%) in the SOS group. The SOS mortality rate was 4/19 (21.1%). Univariate analyses revealed that Cy 200 mg/m(2) conditioning (p=0.035), classical Cy-ATG conditioning (p=0.007), and horse ATG conditioning (p0.001) were significant risk factors for developing SOS. Multivariate analysis revealed that only horse ATG conditioning was a poor prognostic factor (HR=3.484; 95% CI 1.226-9.904; p=0.002). Rabbit ATG (HR 12.719; 95% CI 2.332-69.373; p=0.003) and weight gain10% (HR 35.655; 95% CI 2.208-575.805; p=0.012) were risk factors in the overall SOS group. Both rabbit ATG conditioning and weight gain of more than 10% were associated with poor overall survival with a median of 1.2 months (5Y survival rate, any risk factor vs. none: 74.6% vs. 0.0%; p0.001; Fig. 2) in the SOS group. In conclusion, SOS is a relatively rare (7.3%) but highly fatal (21.1%) acute complication of alloHSCT in AA, and the horse ATG conditioning regimen was a significant risk factor for developing SOS.