We determined the fecal carriage rate of serotype K1
Klebsiella pneumoniae
in healthy Koreans and studied their genetic relationship with liver abscess isolates. We compared the carriage according to ...the country of residence. The stool specimens were collected through health promotion programs in Korea.
K. pneumoniae
strains were selected and tested for K1 by PCR. Serotype K1 isolates were characterized by multilocus sequence typing and pulsed field gel electrophoresis. A total of 248
K. pneumoniae
isolates were obtained from 1,174 Koreans. Serotype K1 was identified in 57 (4.9%), of which 54 (94.7%) were ST 23 and were closely related to the liver abscess isolates. Participants aged >25 years showed a higher fecal carriage rate than those ≤ 25 (
P
= 0.007). The proportion of serotype K1 out of
K. pneumoniae
isolates in foreigners of Korean ethnicity who had lived in other countries was lower compared with those who had lived in Korea (5.6% vs 24.1%,
P
= 0.024). A substantial proportion of Koreans >25 years carries serotype K1
K. pneumoniae
ST23 strains, which are closely related to liver abscess isolates. Differences in carriage rates by country of residence suggests that environmental factors might play an important role in the carriage of this strain.
The enhancement of the functional properties of materials at reduced dimensions is crucial for continuous advancements in nanoelectronic applications. Here, we report that the scale reduction leads ...to the emergence of an important functional property, ferroelectricity, challenging the long-standing notion that ferroelectricity is inevitably suppressed at the scale of a few nanometers. A combination of theoretical calculations, electrical measurements, and structural analyses provides evidence of room-temperature ferroelectricity in strain-free epitaxial nanometer-thick films of otherwise nonferroelectric strontium titanate (SrTiO3). We show that electrically induced alignment of naturally existing polar nanoregions is responsible for the appearance of a stable net ferroelectric polarization in these films. This finding can be useful for the development of low-dimensional material systems with enhanced functional properties relevant to emerging nanoelectronic devices.
The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate ...changes in the CSC populations before and after primary systemic therapy (PST) and their prognostic role in human breast cancer.
Paired samples (before and after PST) of breast cancer tissue were obtained from clinical stage II or III patients (n=92) undergoing PST with the regimen of doxorubicin plus docetaxel (AD) (n=50) or doxorubicin plus cyclophosphamide (AC) (n=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24- or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry.
A higher proportion of CD44+/CD24- tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24- and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24- tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER negativity and p53 overexpression. Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen.
The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics.
In this study, we sought to identify a criterion for the intermediate-risk grouping of patients with cervical cancer who exhibit any intermediate-risk factor after radical hysterectomy.
In total, ...2158 patients with pathologically proven stage IB-IIA cervical cancer with any intermediate-risk factor after radical hysterectomy were randomly assigned to two groups, a development group and a validation group, at a ratio of 3 : 1 (1620 patients:538 patients). To predict recurrence, multivariate models were developed using the development group. The ability of the models to discriminate between groups was validated using the log-rank test and receiver operating characteristic (ROC) analysis.
Four factors (histology, tumour size, deep stromal invasion (DSI), and lymphovascular space involvement (LVSI)) were significantly associated with disease recurrence and included in the models. Among the nine possible combinations of the four variables, models consisting of any two of the four intermediate-risk factors (tumour size ≥3 cm, DSI of the outer third of the cervix, LVSI, and adenocarcinoma or adenosquamous carcinoma histology) demonstrated the best performance for predicting recurrence.
This study identified a 'four-factor model' in which the presence of any two factors may be useful for predicting recurrence in patients with cervical cancer treated with radical hysterectomy.
Background: To determine the clinical and pathologic prognostic factors in surgically treated patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB–IIA small cell ...neuroendocrine carcinoma of the uterine cervix (SCNEC). Patients and methods: We retrospectively reviewed a total of 68 patients with FIGO stage IB–IIA SCNEC surgically treated from January 1997 to December 2003 in Korea. Results: Of the 68 patients, 43 had FIGO stage IB1 SCNEC, 15 had stage IB2, and 10 had stage IIA. Seven were treated with radical surgery alone; 11 with neoadjuvant chemotherapy (NACT) followed by radical surgery; 24 with radical surgery followed by adjuvant chemotherapy; and 26 with radical surgery followed by adjuvant radiation or chemoradiation. After a median follow-up of 44 months (range, 6–113 months), the 2-year and 5-year survival rates for all patients were 64.6% and 46.6%, respectively. Univariate and multivariate analysis showed that FIGO stage was predictive of poor prognosis. Patients who received NACT showed poorer prognosis than those who did not receive NACT. Adjuvant chemoradiation did not improve survival compared with adjuvant chemotherapy alone. Conclusions: FIGO stage may act as a surrogate for factors prognostic of survival. Primary radical surgery followed by adjuvant chemotherapy is the preferred treatment modality for patients with early stage SCNEC.
Aims
Aggressive meningioma remains incurable with neither chemo‐ nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving ...the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression.
Methods
Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression‐free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked‐down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM‐Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)‐pretreated or control IOMM‐Lee cells were implanted subcutaneously in nude mice.
Results
FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of β‐catenin, cyclin D1, p21, interleukin‐8, vascular endothelial growth factor‐A, PLAU, and epithelial‐to‐mesenchymal transition‐related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model.
Conclusions
Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.
Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, ...and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure.
Patients were randomized 1:1 to DHP107 (200mg/m2 orally twice daily days 1, 8, 15 every 4weeks) or i.v. paclitaxel (175mg/m2 day 1 every 3weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25.
Baseline characteristics were balanced in the 236 randomized patients (n=118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7–4.0) months for DHP107 and 2.6 (95% CI 1.8–2.8) months for paclitaxel (hazard ratio HR=0.85; 95% CI 0.64–1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR=0.93; 95% CI 0.70–1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1−11.5) months for DHP107 versus 8.9 (95% CI 7.1–12.2) months for paclitaxel (HR=1.04; 95% CI 0.76–1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%).
DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC.
NCT01839773.
Background
The aim of this study was to compare the results of laparoscopy‐assisted total gastrectomy with those of open total gastrectomy for early gastric cancer.
Methods
Patients with gastric ...cancer who underwent total gastrectomy with curative intent in three Korean tertiary hospitals between January 2003 and December 2010 were included in this multicentre, retrospective, propensity score‐matched cohort study. Cox proportional hazards regression models were used to evaluate the association between operation method and survival.
Results
A total of 753 patients with early gastric cancer were included in the study. There were no significant differences in the matched cohort for overall survival (hazard ratio (HR) for laparoscopy‐assisted versus open total gastrectomy 0·96, 95 per cent c.i. 0·57 to 1·65) or recurrence‐free survival (HR 2·20, 0·51 to 9·52). The patterns of recurrence were no different between the two groups. The severity of complications, according to the Clavien–Dindo classification, was similar in both groups. The most common complications were anastomosis‐related in the laparoscopy‐assisted group (8·0 per cent versus 4·2 per cent in the open group; P = 0·015) and wound‐related in the open group (1·6 versus 5·6 per cent respectively; P = 0·003). Postoperative death was more common in the laparoscopy‐assisted group (1·6 versus 0·2 per cent; P = 0·045).
Conclusion
Laparoscopy‐assisted total gastrectomy for early gastric cancer is feasible in terms of long‐term results, including survival and recurrence. However, a higher postoperative mortality rate and an increased risk of anastomotic leakage after laparoscopic‐assisted total gastrectomy are of concern.
Feasible but high risk of anastomotic complication
Lightweight nanofibrous assemblies with high protection ability against chemical warfare agents (CWAs) were developed using laminated outer and inner layers based on nanofibre composites. The outer ...layer was composed of a meta -aramid nanofibre and CWA adsorbents (MgO and POM), and possessed high mechanical strength and an amphiphobic surface capable of repelling liquid CWAs. The inner layer, consisted of a polyamide 66 nanofibre and CWA adsorbents, exhibited low permeability to gas CWAs and high permeability to water vapor. These outer and inner layers were prepared by simultaneous electrospinning and electrospraying processes. By controlling the stacking of the inner and outer layers, the characteristics of their assemblies, such as thickness, weight density, and cool/warm feeling, were improved. In addition, the assemblies resisted the invasion of CWAs, while still maintaining considerable water vapor transmission to allow evaporative cooling of the wearer. Based on these results, assemblies composed of nanofibrous composite can be used as in garments that protect wearers from various contaminants such as organic pollutants and harmful particulates, as well as from CWAs.
Structural abnormalities include various types of translocations, inversions, deletions, duplications and isochromosomes. Structural abnormalities of the Y chromosome are estimated to affect less ...than 1% of the newborn male population and are particularly hazardous for male reproductive function. The objective of this study was to characterize a group of patients with structural abnormalities of the Y chromosome. All patients who visited our laboratory between 2007 and 2010 underwent cytogenetic investigations. Among these, we detected 26 patients with structural abnormalities of the Y chromosome. To confirm the structural Y chromosome alterations, we used special bandings, FISH and multiplex PCR to detect Y chromosome microdeletions. Of the 26 patients presented here, 11 had an isodicentric Y chromosome, 7 had an inversion, 3 had a translocation, 2 had a derivative, 2 had a Yqs and 1 had a deletion. Sixteen were diagnosed with azoospermia, 8 as normal fertile males and 1 as a man who was unable to donate semen due to mental retardation. One of the patients having 45,X/46,X,idic(Y) was reported to be phenotypically female with primary amenorrhea and without uterus. Deletions of the AZFbc region were correlated with the sperm concentration (p < 0.05), but no correlation with the levels of FSH, LH, testosterone, prolactin and estradiol were found. The present report shows that the precise identification of structural Y chromosome aberrations may be clinically important for genetic counseling and assisted reproductive technology treatment.
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