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1.  The Prognostic Role of STEAP1 Expression Determined via Immunohistochemistry Staining in Predicting Prognosis of Primary Colorectal Cancer: A Survival Analysis 
STEAP1 (six transmembrane epithelial antigen of the prostate 1) is a transmembrane protein that functions as a potential channel or transporter protein. It is overexpressed in certain cancers and is viewed as a promising therapeutic target. However, the prognostic role of STEAP1 is still controversial, and no role for STEAP1 has yet been indicated in colorectal cancer. The aim of this study was to investigate the possible association of STEAP1 expression with colorectal cancer prognosis. STEAP1 expression was analyzed by immunohistochemical staining of a tissue array of 165 cancer specimens from primary colorectal cancer patients. The mean and medium follow-up times after surgery were 5.1 and 3.9 years, respectively. A total of 139 patients died during the 13 years of follow-up in the survey period. The prognostic value of STEAP1 with respect to overall survival was analyzed by Kaplan-Meier analysis and Cox proportional hazard models. In total, 164 samples displayed detectable STEAP1 expression in the cytoplasm and membrane. Low STEAP1 expression was correlated with poor overall survival (five-year survival: 33.7% vs. 57.0%, low expression vs. high expression, p = 0.020). Accordingly, multivariate analysis identified low STEAP1 expression as an independent risk factor (hazard ratio = 1.500, p = 0.018), especially in elderly patients or those with late stage cancers, late T values, and early N values. We suggest that analysis of STEAP1 expression by immunohistochemical staining could serve as an independent prognostic marker for colorectal patients. This finding should be validated by other investigative groups.
PMCID: PMC4849046  PMID: 27104516
STEAP1; prognosis; colorectal cancer
2.  Primary Pulmonary Meningioma Simulating a Pulmonary Metastasis 
Case Reports in Pulmonology  2016;2016:8248749.
Primary pulmonary meningiomas represent a rare tumor entity. Few cases have been reported in the English medical literature, and they have almost all been solitary and benign in nature, with the exception of several extremely rare cases. We report herein a case of PPM that raised suspicion of a pulmonary metastatic tumor initially, as it was depicted as a single, round, small, ground-glass opacity pulmonary nodule on a chest computed tomography scan, in a 55-year-old man with a history of buccal cancer. Increased awareness of the clinical and radiologic characteristics of this rare category can assist a multidisciplinary team to perform adequate management.
PMCID: PMC5128704  PMID: 27974986
3.  Serum Osteopontin Level Correlates with Carotid-Femoral Pulse Wave Velocity in Geriatric Persons 
BioMed Research International  2014;2014:570698.
Osteopontin (OPN) is involved in the regulation of vascular calcification processes. The aim of this study was to evaluate the relationship between fasting serum OPN concentration and carotid-femoral pulse wave velocity (cfPWV) in geriatric persons. Fasting blood samples were obtained from 93 geriatric persons. cfPWV were performed by SphygmoCor system. Serum OPN levels were measured using a commercially available enzyme-linked immunosorbent assay. Geriatric adults who had diabetes (P = 0.007) or dyslipidemia (P = 0.029) had higher cfPWV levels than those without diabetes or dyslipidemia. The univariable linear regression analysis showed that age (P = 0.002), waist circumference (P = 0.048), body mass index (P = 0.004), systolic blood pressure (P = 0.001), diastolic blood pressure (P = 0.036), pulse pressure (P = 0.017), creatinine (P = 0.002), and log-OPN level (P = 0.001) were positively correlated with cfPWV levels, while the high-density lipoprotein cholesterol (HDL-cholesterol) level (P = 0.007) and glomerular filtration rate (P = 0.001) were negatively correlated with cfPWV levels among the geriatric adults. Multivariable forward stepwise linear regression analysis of the significant variables also showed that log-OPN (β = 0.233, R2 = 0.123, regression coefficient: 1.868, P = 0.011) was still an independent predictor of cfPWV levels in geriatric persons.
PMCID: PMC4123499  PMID: 25133167
4.  Different Effects of Six Antibiotics and Ten Traditional Chinese Medicines on Shiga Toxin Expression by Escherichia coli O157:H7 
This study compared the effects of ten types of traditional Chinese medicines (TCMs) and six different antibiotics on E. coli O157:H7 Shiga toxin gene (stx2) mRNA expression level based on real-time PCR and the expression level of Stx toxin using an ELISA quantitative assay. We also compared their effects on the induction of the SOS response. The results clearly indicated that all ten TCMs had negative results in the SOS response induction test, while most TCMs did not increase the levels of stx2 mRNA and the Stx toxin. Some TCMs did increase the mRNA levels of the stx2 gene and the Stx toxin level, but their increases were much lower than those caused by antibiotics. With the exception of cefotaxime, the six antibiotics increased the Stx toxin level and increased the stx2 gene mRNA level. With the exceptions of cefotaxime and tetracycline, the antibiotics increased the SOS induction response. These results suggest that TCMs may have advantages compared with antibiotics, when treating E. coli O157:H7; TCMs did not greatly increase Stx toxin production and release.
PMCID: PMC3730174  PMID: 23956764
5.  Novel CD8+ Treg suppress EAE by TGF-β- and IFN-γ-dependent mechanisms 
European journal of immunology  2009;39(12):3423.
Although CD8+ Treg-mediated suppression has been described, CD8+ Treg remain poorly characterized. Here we identify a novel subset of CD8+ Treg that express latency-associated peptide (LAP) on their cell surface (CD8+LAP+ cells) and exhibit regulatory activity in vitro and in vivo. Only a small fraction of CD8+LAP+ cells express Foxp3 or CD25, although the expression levels of Foxp3 for these cells are higher than their LAP− counterparts. In addition to TGF-β, CD8+LAP+ cells produce IFN-γ, and these cells suppress EAE that is dependent on both TGF-β and IFN-γ. In an adoptive co-transfer model, CD8+LAP+ cells suppress myelin oligodendrocyte glycoprotein (MOG)-specific immune responses by inducing or expanding Foxp3+ cells and by inhibiting proliferation and IFN-γ production in vivo. Furthermore, in vivo neutralization of IFN-γ and studies with IFN-γ-deficient mice demonstrate an important role for IFN-γ production in the function of CD8+LAP+ cells. Our findings identify the underlying mechanisms that account for the immunoregulatory activity of CD8+ T cells and suggest that induction or amplification of CD8+LAP+ cells may be a therapeutic strategy to help control autoimmune processes.
PMCID: PMC2814307  PMID: 19768696
Autoimmunity; Treg; Tolerance
6.  Association of serum leptin levels with central arterial stiffness in coronary artery disease patients 
Serum adipokines have roles in the development of arterial stiffness. Our aim was to investigate the relationship of leptin and the surrogate marker carotid-femoral pulse wave velocity (cfPWV) in coronary artery disease (CAD) patients.
Fasting blood samples were obtained from 105 CAD patients. cfPWV was measured with the SphygmoCor system. A cfPWV > 10 m/s was defined as high arterial stiffness, and ≤ 10 m/s as low arterial stiffness.
Thirty-seven patients (35.2 %) had high arterial stiffness, and had a higher percentage of diabetes (P = 0.001), hypertension (P = 0.010), older age (P = 0.001), and higher systolic blood pressure (SBP) (P < 0.001), diastolic blood pressure (DBP) (P = 0.021), pulse pressure (P = 0.014), and serum leptin level (P = 0.002) compared to patients with low arterial stiffness. Serum leptin levels correlated with the number of angiographically documented stenotic coronary artery vessels (P < 0.001). After adjusting for factors significantly associated with arterial stiffness, multivariate logistic regression analysis showed that leptin (odds ratio = 1.026, 95 % confidence interval: 1.002–1.051, P = 0.037) was a significant independent predictor of arterial stiffness.
Increasing serum concentration of leptin correlated positively with the total number of stenotic coronary arteries, and serum leptin level may predict the development of arterial stiffness in CAD patients.
PMCID: PMC4857286  PMID: 27151106
Arterial stiffness; Carotid-femoral pulse wave velocity; Coronary artery disease; Leptin
7.  Preparation of novel (-)-gossypol nanoparticles and the effect on growth inhibition in human prostate cancer PC-3 cells in vitro 
The aim of the present study was to investigate the antitumor effects and possible mechanism of (-)-gossypol nanoparticles, loaded with vv polyethylene glycol-maleimide (mPEG-Mal), in vitro. Emulsification-volatilization was used to prepare the loaded (-)-gossypol nanoparticles. The toxicity of blank nanoparticles on human prostate cancer PC-3 cells and human prostate RWPE-1 cells was measured. The antitumor effects of the nanoparticles on PC-3 cells were evaluated by an MTT assay, acridine orange staining and transmission electron microscopy in vitro, and the results were compared with those of free (-)-gossypol. In addition, the mRNA expression levels of Bcl-2 and Bak were measured using semi-quantitative reverse transcription polymerase chain reaction. The growth inhibition activity of the loaded (-)-gossypol nanoparticles was found to be dose- and time-dependent, and similar to the activity of free (-)-gossypol. The nanoparticles induced apoptotic morphological changes on the PC-3 cells, downregulating the mRNA expression level of Bcl-2 and upregulating the mRNA expression level of Bak. Blank nanoparticles exhibited no evident toxicity on PC-3 and RWPE-1 cells at a high dose. Therefore, the mPEG-Mal loaded (-)-gossypol nanoparticles demonstrated a favorable antitumor activity and no toxicity. The nanoparticles were able to induce the apoptosis of prostate cancer cells; thus, may be a potential antitumor nanodrug.
PMCID: PMC4316968  PMID: 25667612
(-)-gossypol; nanoparticle; apoptosis; prostate cancer
8.  [No title available] 
Acta Cardiologica Sinica  2014;30(5):485-489.
Saphenous vein graft (SVG) failure secondary to degeneration can cause significant problems after coronary artery bypass surgery (CABG). Repeat revascularization by percutaneous coronary intervention can be performed after SVG failure but is often associated with less favourable clinical outcome. Treatment for chronic total occlusion (CTO) of native vessels after SVG failure among patients with prior CABG is frequently performed. However, revascularization of CTO vessels in patients with prior CABG may be more complex and require more frequent use of the retrograde approach. Good septal or epicardial collateral channels are usually needed for the retrograde CTO approach. However, suitable native collateral channels may be absent and alternative retrograde routes should be considered. In this case report, we described a patient who had prior CABG and developed recurrent angina after SVG failure. His native CTO lesion was successfully revascularized by using a totally occluded vein graft as a retrograde conduit.
PMCID: PMC4834962  PMID: 27122823
Chronic total occlusions; Coronary artery bypass grafts; Percutaneous coronary intervention; Saphenous vein graft
9.  Impact of Osmotically Active Excipients on Bioavailability and Bioequivalence of BCS Class III Drugs 
The AAPS Journal  2013;15(4):1043-1050.
PMCID: PMC3787221  PMID: 23868749
BCS; bioavailability/bioequivalence; drug absorption; excipient; osmotic potential
10.  Delayed Infective Endocarditis with Mycotic Aneurysm Rupture below the Mechanical Valved Conduit after the Bentall Procedure  
Acta Cardiologica Sinica  2014;30(4):341-345.
The Bentall procedure is the gold standard for treating aortic dissection complicated with valvular and ascending aorta disease. Recent results for this procedure have been excellent; nearly 100% of patients remain free of infective endocarditis in long-term follow-up. We report a case of delayed Streptococcus agalactiae infective endocarditis complicated by mycotic aneurysm in a man who had undergone the Bentall procedure with a mechanical valve conduit 15 years previously. The mycotic aneurysm was located in the remnant aortic root, below the mechanical valve conduit, and later ruptured into the right atrium. The patient was treated conservatively and survived the acute period. Later, the aortic root defect was repaired successfully by means of a hybrid technique using a Amplatzer duct occluder.
PMCID: PMC4804998  PMID: 27122809
Amplatzer duct occluder; Aortic dissection; Bentall technique; Infective endocarditis; Mycotic aneurysm
11.  Use of Partial Area under the Curve Metrics to Assess Bioequivalence of Methylphenidate Multiphasic Modified Release Formulations 
The AAPS Journal  2012;14(4):925-926.
PMCID: PMC3475859  PMID: 22976173
attention deficit hyperactivity disorder; bioequivalence; generic drugs; methylphenidate; pAUC
12.  Implementation of a Reference-Scaled Average Bioequivalence Approach for Highly Variable Generic Drug Products by the US Food and Drug Administration 
The AAPS Journal  2012;14(4):915-924.
Highly variable (HV) drugs are defined as those for which within-subject variability (%CV) in bioequivalence (BE) measures is 30% or greater. Because of this high variability, studies designed to show whether generic HV drugs are bioequivalent to their corresponding HV reference drugs may need to enroll large numbers of subjects even when the products have no significant mean differences. To avoid unnecessary human testing, the US Food and Drug Administration’s Office of Generic Drugs developed a reference-scaled average bioequivalence (RSABE) approach, whereby the BE acceptance limits are scaled to the variability of the reference product. For an acceptable RSABE study, an HV generic drug product must meet the scaled BE limit and a point estimate constraint. The approach has been implemented successfully. To date, the RSABE approach has supported four full approvals and one tentative approval of HV generic drug products.
PMCID: PMC3475857  PMID: 22972221
bioequivalence; generic drugs; highly variable drugs; reference-scaled average bioequivalence; US Food and Drug Administration
13.  Association study between miR-149 gene polymorphism and nasopharyngeal carcinoma 
Biomedical Reports  2013;1(4):599-603.
Association studies between single-nucleotide polymorphism (SNP) rs2292832 on miR-149 gene and cancer risk have been previously analyzed in several types of cancer. The aim of this study was to evaluate the association between miR-149 polymorphism and risk of nasopharyngeal carcinoma (NPC). miR-149 gene polymorphism was genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 158 patients with NPC and 242 healthy individuals. Associations with cancer risk and clinicopathological characteristics were analyzed by χ2 test. No significant difference was observed for miR-149 gene polymorphism in NPC patients and healthy controls in either genotype (P=0.427 for CC vs. CT vs. TT, P=0.247 for CT vs. TT and P=0.323 for CC vs. TT, respectively) or allelic analysis (P=0.216). No significant difference was noted between the genotypes and the clinicopathological parameters examined with the exception of clinical stage. A significantly higher CC distribution in clinical stage I–II compared with III–IV was observed under the dominant model (CC vs. CT vs. TT, P=0.026) and the co-dominant model (CC vs. TT, P=0.030). The results of this study suggested that the CC genotype of miR-149 contributes to the progression and development, rather than the initiation of NPC.
PMCID: PMC3917026  PMID: 24648993
cancer risk; miR-149; nasopharyngeal carcinoma; polymorphism; single-nucleotide polymorphism
14.  Incidence of and Risk Factors for Infection or Colonization of Vancomycin-Resistant Enterococci in Patients in the Intensive Care Unit 
PLoS ONE  2012;7(10):e47297.
The prevalence of vancomycin-resistant enterococci (VRE) colonization or infection in the hospital setting has increased globally. Many previous studies had analysed the risk factors for acquiring VRE, based on cross-sectional studies or prevalent cases. However, the actual incidence of and risk factors for VRE remain unclear. The present study was conducted in order to clarify the incidence of and risk factors for VRE in the intensive care unit (ICU). From 1st April 2008 to 31st March 2009, all patients admitted to a surgical ICU (SICU) were put on active surveillance for VRE. The surveillance cultures, obtained by rectal swab, were taken on admission, weekly while staying in the SICU, and on discharge from the SICU. A total of 871 patients were screened. Among them, 34 were found to carry VRE before their admission to the SICU, and 47 acquired VRE during their stay in the SICU, five of whom developed VRE infections. The incidence of newly acquired VRE during ICU stay was 21.9 per 1000 patient-days (95% confidence interval [CI], 16.4–29.1). Using multivariate analysis by logistic regression, we found that the length of ICU stay was an independent risk factor for new acquisition of VRE. In contrast, patients with prior exposure to first-generation cephalosporin were significantly less likely to acquire VRE. Strategies to reduce the duration of ICU stay and prudent usage of broad-spectrum antibiotics are the keys to controlling VRE transmission.
PMCID: PMC3468570  PMID: 23071778
15.  Factors affecting the prognosis of small hepatocellular carcinoma in Taiwanese patients following hepatic resection 
Small hepatocellular carcinoma (HCC) affects millions of individuals worldwide. Surveillance of high-risk patients increases the early detection of small HCC.
To identify prognostic factors affecting the overall survival (OS) and recurrence-free survival (RFS) of patients with small HCC.
The present prospective study enrolled 140 Taiwanese patients with stage I or stage II small HCC. Clinical parameters of interest included operation type, tumour size, tumour histology, Child-Pugh class, presence of hepatitis B surface antigen and liver cirrhosis, hepatitis C status, alpha-fetoprotein, total bilirubin and serum albumin levels, and administration of antiviral and salvage therapies.
Tumour size correlated significantly with poorer OS in patients with stage I small HCC (P=0.014); however, patients with stage II small HCC experienced a significantly poorer RFS (P=0.033). OS rates did not differ significantly between patients with stage I and stage II small HCC. Tumour margins, tumour histology and cirrhosis did not significantly affect OS or RFS (P>0.05).
Increasing tumour size has generally been associated with poorer prognoses in cases of HCC. The present study verified the relationship between small HCC tumour size and OS; however, a reduction in OS with increasing tumour size was demonstrated for patients with stage I – but not for stage II – small HCC.
Patients with stage II small HCC may benefit from aggressive surveillance for tumour recurrence and appropriate salvage treatment. Further studies are needed for additional stratification of stage I patients to identify those at increased risk of death.
PMCID: PMC3202355  PMID: 21912759
Prognosis; Small hepatocellular carcinoma; Tumour size
16.  Harmonization of Regulatory Approaches for Evaluating Therapeutic Equivalence and Interchangeability of Multisource Drug Products: Workshop Summary Report 
The AAPS Journal  2011;13(4):556-564.
Regulatory approaches for evaluating therapeutic equivalence of multisource (or generic) drug products vary among different countries and/or regions. Harmonization of these approaches may decrease the number of in vivo bioequivalence studies and avoid unnecessary drug exposure to humans. Global harmonization for regulatory requirements may be promoted by a better understanding of factors underlying product performance and expectations from different regulatory authorities. This workshop provided an opportunity for pharmaceutical scientists from academia, industry and regulatory agencies to have open discussions on current regulatory issues and industry practices, facilitating harmonization of regulatory approaches for establishing therapeutic equivalence and interchangeability of multisource drug products.
PMCID: PMC3231855  PMID: 21845486
bioequivalence; harmonization; interchangeability; regulatory standards; therapeutic equivalence
17.  Complete Genome Sequence of Lactococcus lactis subsp. lactis CV56, a Probiotic Strain Isolated from the Vaginas of Healthy Women▿ 
Journal of Bacteriology  2011;193(11):2886-2887.
Lactic acid bacteria that exist in the urinogenital system play an important role in maintaining the health of the host. Here, we report the finished and annotated genome of a Lactococcus strain that was isolated from the vaginas of healthy women and shows probiotic properties, including nisin A production and adhesion to vaginal epithelial cells.
PMCID: PMC3133120  PMID: 21460077
18.  New immunosuppressive approaches: Oral administration of CD3-specific antibody to treat autoimmunity 
One of the major goals for the immunotherapy of autoimmune diseases is the induction of regulatory T cells that mediate immunologic tolerance. Parenteral administration of anti-CD3 monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We have found that oral administration of anti-CD3 monoclonal antibody is biologically active in the gut and suppresses experimental autoimmune encephalomyelitis both prior to disease induction and at the height of disease. Oral anti-CD3 antibody acts by inducing a unique type of regulatory T cell characterized by latency-associated peptide (LAP) on its cell surface that functions in vivo and in vitro via TGF-β dependent mechanism. Orally delivered antibody would not have side effects including cytokine release syndromes, thus oral anti-CD3 antibody is clinically applicable for chronic therapy. These findings identify a novel and powerful immunologic approach that is widely applicable for the treatment of human autoimmune conditions.
PMCID: PMC3167084  PMID: 18804221
regulatory cell; TGF-β; antibody; multiple sclerosis; autoimmunity
19.  Lipomatous apocrine adenoma with syringocystadenoma papilliferum arising from the external auditory canal 
Head & Neck Oncology  2011;3:36.
A case of lipomatous tubular adenoma (LTA) with syringocystadenom papilliferum (SCAP) arising from the external auditory canal in a 25-year-old man is described and to the best of our knowledge through literature review, this kind of morphologic entity has not been reported before. Herein we reported the first case in the English literature in the world.
PMCID: PMC3169502  PMID: 21854651
tubular adenoma; syringocystadenoma papilliferum; external auditory canal
20.  Construction of the yeast whole-cell Rhizopus oryzae lipase biocatalyst with high activity*  
Surface display is effectively utilized to construct a whole-cell biocatalyst. Codon optimization has been proven to be effective in maximizing production of heterologous proteins in yeast. Here, the cDNA sequence of Rhizopus oryzae lipase (ROL) was optimized and synthesized according to the codon bias of Saccharomyces cerevisiae, and based on the Saccharomyces cerevisiae cell surface display system with α-agglutinin as an anchor, recombinant yeast displaying fully codon-optimized ROL with high activity was successfully constructed. Compared with the wild-type ROL-displaying yeast, the activity of the codon-optimized ROL yeast whole-cell biocatalyst (25 U/g dried cells) was 12.8-fold higher in a hydrolysis reaction using p-nitrophenyl palmitate (pNPP) as the substrate. To our knowledge, this was the first attempt to combine the techniques of yeast surface display and codon optimization for whole-cell biocatalyst construction. Consequently, the yeast whole-cell ROL biocatalyst was constructed with high activity. The optimum pH and temperature for the yeast whole-cell ROL biocatalyst were pH 7.0 and 40 °C. Furthermore, this whole-cell biocatalyst was applied to the hydrolysis of tributyrin and the resulted conversion of butyric acid reached 96.91% after 144 h.
PMCID: PMC3134842  PMID: 21726061
Rhizopus oryzae lipase (ROL); Yeast surface display; Codon optimization; Whole-cell biocatalyst
21.  Quality of life in mothers of children with oppositional defiant symptoms: a community sample 
Background Children with oppositional defiant symptoms (ODS) are highly related to parental stress, especially in mothers. This study is the first to investigate the quality of life (QOL) of mothers of children with ODS in a community sample.
Methods Randomly selected mothers of children attending an elementary school were contacted, and 387 who completed the questionnaire participated in this study. The children's ODS status was determined by the maternal rating of the Chinese Swanson, Nolan, and Pelham rating scale, version IV. The mothers' QOL was estimated by maternal reports from the World Health Organization Quality of Life – BREF (WHOQOL‐BREF) instrument. The relationship between the children's ODS status and maternal QOL was examined by analysis of covariance (ANCOVA) with the participants' sociodemographic factors as covariables.
Results Sixty‐three children, mostly boys, met the screening criteria for ODS. The positive screening rate for ODS was 16.49%. The children's ODS status was a significant predictor for the maternal physical capacity, psychological wellbeing and environment domains of QOL. Mothers of children with ODS who rented a house were younger and had lower education levels and worse QOL in all domains.
Conclusion A high positive screening rate for ODS children in the elementary school and a relationship between poor maternal QOL and children's ODS were found in this study. Routine screening for ODS in children and mental health services for these children and their mothers are warranted.
PMCID: PMC2939462  PMID: 22477927
mother; oppositional defiant disorder; quality of life
22.  Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products: Workshop Summary Report 
The AAPS Journal  2010;12(3):371-377.
Modified release products are complex dosage forms designed to release drug in a controlled manner to achieve desired efficacy and safety. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current industry practices and regulatory expectations for demonstrating pharmaceutical equivalence and bioequivalence of MR products, further facilitating the establishment of regulatory standards for ensuring therapeutic equivalence of these products.
PMCID: PMC2895434  PMID: 20440588
bioequivalence; interchangeability; modified release; pharmaceutical equivalence; therapeutic equivalence
23.  Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis 
Cancer cell  2008;14(6):458-470.
Akt-deficiency causes resistance to replicative senescence, oxidative stress- or oncogenic Ras-induced premature senescence, and to reactive oxygen species (ROS)-mediated apoptosis. Akt activation induces premature senescence and sensitizes cells to ROS-mediated apoptosis by increasing intracellular ROS through increased oxygen consumption and by inhibiting the expression of ROS-scavengers downstream of FoxO, particularly sestrin3 expression. This uncovers an Achilles’ heel of Akt, since in contrast to its ability to inhibit apoptosis induced by multiple apoptotic stimuli; Akt could not inhibit ROS-mediated apoptosis. Furthermore, treatment with rapamycin that led to further Akt activation and resistance to etoposide, hypersensitized cancer cells to ROS-mediated apoptosis. Given that rapamycin alone is mainly cytostatic, this constitutes a strategy for cancer therapy that selectively eradicates cancer cells via Akt activation.
PMCID: PMC3038665  PMID: 19061837
24.  Comparison of an Automated Repetitive-Sequence-Based PCR Microbial Typing System with Pulsed-Field Gel Electrophoresis for Molecular Typing of Vancomycin-Resistant Enterococcus faecium▿ †  
Journal of Clinical Microbiology  2010;48(8):2897-2901.
Vancomycin-resistant Enterococcus faecium (VRE) has become an important health care-associated pathogen because of its rapid spread, limited therapeutic options, and possible transfer of vancomycin resistance to more-virulent pathogens. In this study, we compared the ability to detect clonal relationships among VRE isolates by an automated repetitive-sequence-based PCR (Rep-PCR) system (DiversiLab system) to pulsed-field gel electrophoresis (PFGE), the reference method for molecular typing of VRE. Two sets of VRE isolates evaluated in this study were collected by active microbial surveillance at a large teaching hospital in Taiwan during 2008. The first set included 90 isolates randomly selected from the surveillance cohort. The first set consisted of 34 pulsotypes and 10 Rep-PCR types. There was good correlation between the two methods (P < 0.001). The second set included 68 VRE isolates collected from eight clusters of colonization. A dominant clone was detected in five out of eight clusters by both methods. Two clusters were characterized by Rep-PCR as being caused by a dominant clone, whereas PFGE showed polyclonal origins. One cluster was shown to be polyclonal by both methods. A single Rep-PCR clone type was detected among 12 of 14 vancomycin-intermediate enterococci, whereas PFGE detected six pulsotypes. In conclusion, the Rep-PCR method correlated well with PFGE typing but was less discriminative than PFGE in defining clonal relationships. The ease of use and more rapid turnaround time of Rep-PCR compared to PFGE offers a rapid screening method to detect outbreaks of VRE and more rapidly implement control measures. PFGE remains the preferred method to confirm clonal spread.
PMCID: PMC2916582  PMID: 20554812
25.  Association between Contaminated Faucets and Colonization or Infection by Nonfermenting Gram-Negative Bacteria in Intensive Care Units in Taiwan▿  
Journal of Clinical Microbiology  2009;47(10):3226-3230.
This study was designed to determine the strength of the association between the isolation of nonfermentative gram-negative bacilli (NFGNB) from tap water faucet aerators and the prevalence of colonization or infection of patients in intensive care units (ICUs). Surveillance cultures were obtained during a 4-month period from 162 faucet aerators located in seven different ICUs. The prevalence of colonization or infection of ICU patients with NFGNB was determined by prospective surveillance during the same period. Fifty four (33%) of the faucet aerators contained NFGNB. Among the 66 NFGNB isolated from faucet aerators, the most frequently encountered ones were Sphingomonas paucimobili (26 isolates), Pseudomonas aeruginosa (14 isolates), Chryseobacterium meningosepticum (13 isolates), Achromobacter xylosoxidans (6 isolates), Burkholderia cepacia (4 isolates), and Stenotrophomonas maltophilia (3 isolates). Acinetobacter baumannii was not recovered. The most common NFGNB isolated from ICU patients were P. aeruginosa and A. baumannii. There was a significant correlation between the overall prevalence of NFGNB in faucet aerators and their prevalence in exposed ICU patients (Spearman r = 0.821, P = 0.02). There was also a significant correlation between the prevalence of C. meningosepticum in faucet aerators and its prevalence among ICU patients (Spearman r = 0.847, P = 0.016). The electrokaryotypes of four clinical isolates of C. meningosepticum were similar to those of faucet isolates. Measures directed at making the water supply safe may prevent infection by C. meningosepticum and other waterborne pathogens.
PMCID: PMC2756896  PMID: 19587299

Results 1-25 (36)