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1.  Dynamin-related protein 1 is involved in micheliolide-induced breast cancer cell death 
OncoTargets and therapy  2015;8:3371-3381.
Dynamin-related protein 1 (Drp1) is a newly discovered therapeutic target for tumor initiation, migration, proliferation, and chemosensitivity. Thus, therapeutic strategies that focus on targeting Drp1 and its related signaling pathway pave a new way to address the ineffectiveness of traditional cancer therapies. Micheliolide (MCL), a guaianolide sesquiterpene lactone, can selectively eradicate acute myeloid leukemia stem or progenitor cells. But the effect of MCL on the mitochondrial dynamics of cancer cells is still not well demonstrated. In this study, we show that MCL inhibited the growth of MCF-7 human breast cancer cells, accompanied by increased mitochondrial fission and upregulation of Drp1. The results obtained from overexpression experiments of wild or dominant-negative mutant type of Drp1 demonstrate that Drp1 is both necessary and sufficient to induce MDA-MB-231 and MCF-7 cell death. Furthermore, mitochondrial membrane potential decreased, whereas reactive oxygen species (ROS) generation, cytochrome c release, and PARP cleavage were enhanced after overexpression of Drp1 wild type. On the other hand, overexpression of Drp1-K38A (a dominant-negative mutant of Drp1) rescued cells from increased apoptosis, confirming the role of MCL-induced Drp1 in the observed apoptosis. Finally, MCL-induced Drp1-mediated cell death could be reversed by N-acetyl-L-cysteine (the ROS scavenger) in breast cancer cells. Taken together, the present study shows a novel role for Drp1 in MCL-induced breast cancer cell death, potentially through regulation of ROS–mitochondrial apoptotic pathway.
doi:10.2147/OTT.S91805
PMCID: PMC4654538  PMID: 26622184
Drp1; breast cancer; apoptosis; mitochondrial dynamics
2.  National consensus in China on diagnosis and treatment of patients with advanced breast cancer 
The recently available guidelines on the management of advanced breast cancer (ABC) organized by Chinese Anti-Cancer Association, Committee of Breast Cancer Society (CACA-CBCS) do not elucidate ABC in details. To instruct clinicians in treatment of ABC, a Chinese expert consensus meeting on diagnosis and treatment of ABC was held in June 2014 and a consensus is developed. The following consensus provides the level of evidence and supporting documents for each recommendation, and introduces research topics to be urgently addressed. Notably, the consensus on diagnosis and treatment of ABC in China is developed to be applied nationwide. In different areas, multidisciplinary treatment (MDT) tailored to the each patient and the disease itself should be applied based on the basic principles of modern oncology.
doi:10.3978/j.issn.2305-5839.2015.09.47
PMCID: PMC4620095  PMID: 26605288
Advanced breast cancer (ABC); consensus; national; China
3.  miR-429 mediates δ-tocotrienol-induced apoptosis in triple-negative breast cancer cells by targeting XIAP 
Vitamin E δ-tocotrienol has been reported to possess anticancer activity both in vitro and in vivo. However, the underlying molecular mechanisms of δ-tocotrienol induced apoptosis in triple-negative breast cancer are not fully understood. Here, we reported that microRNA-429 (miR-429) is up-regulated in two TNBC cell lines (MDA-MB-231 and MDA-MB-468), treated with δ-tocotrienol. Inhibition of miR-429 may partially rescue the apoptosis induced by δ-tocotrienol in MDA-MB-231 cells. We also showed that the forced expression of miR-429 was sufficient to lead to apoptosis in MDA-MB-231 cells. Furthermore, we identified X-linked inhibitor of apoptosis protein (XIAP) as one of miR-429’s target genes. These results suggest that the activation of miR-429 by δ-tocotrienol may be an effective approach for the prevention and treatment of triple-negative breast cancer.
PMCID: PMC4658948  PMID: 26629059
δ-Tocotrienol; triple-negative breast cancer (TNBC); microRNA-429 (miR-429); X-linked inhibitor of apoptosis protein (XIAP); apoptosis
4.  Micheliolide overcomes KLF4-mediated cisplatin resistance in breast cancer cells by downregulating glutathione 
OncoTargets and therapy  2015;8:2319-2327.
Micheliolide (MCL) is a promising novel compound with broad-spectrum anticancer activity. However, little is known regarding its action and mechanism in breast cancer. To explore the potential therapeutic application of MCL as a chemosensitivity modulator, this study investigated the effects of MCL on cisplatin sensitivity in breast cancer and the underlying mechanisms. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay and a xenograft tumor model, MCL enhanced the cisplatin sensitivity of the breast cancer cell line MCF-7 both in vitro and in vivo. Treatment of MCF-7 cells with low-dose cisplatin (10 µM) was sufficient to enrich the proportion of ALDH+ cells and upregulate Krüppel-like factor 4 (KLF4) expression. The results obtained from knockdown and overexpression experiments demonstrate that KLF4 is both necessary and sufficient to induce a cisplatin resistance phenotype in breast cancer cells. Furthermore, the glutathione (GSH) content was elevated in MCF-7 cells after overexpression of KLF4. KLF4-mediated resistance to cisplatin was found to be abrogated by treatment with buthionine sulfoximine, an inhibitor of GSH synthesis. MCL induced GSH depletion and severe cell death in KLF4-overexpressing MCF-7 cells following exposure to cisplatin. Therefore, these results suggest that MCL-mediated direct depletion of GSH represents a major mechanism in reversing KLF4-induced cisplatin resistance in MCF-7 cells.
doi:10.2147/OTT.S88661
PMCID: PMC4559251  PMID: 26356142
KLF4; cisplatin resistance; glutathione; breast cancer; Micheliolide
5.  The comparison of maintenance treatment with capecitabine (CMT) and non-maintenance treatment with capecitabine (non-CMT) in patients with metastatic breast cancer 
Aim: The study examined the response rate, response duration and toxicity of maintenance treatment (CMT) and non-maintenance treatment with capecitabine (non-CMT) in metastatic breast cancer (MBC). Material and methods: Between September 2009 and July 2013, a group of 82 patients with MBC, who had progressed after anthracycline/taxane chemotherapy, was treated with a capecitabine-based chemotherapy and divided into two groups. 54 patients received CMT 1.5 g twice a day from days 1 to 14, and 28 patients achieved non-CMT. Treatment was continued until disease progression or unacceptable toxicity. The median age of patients treated with CMT and non-CMT was 57 years (range 38-78) and 50 years (range 37-77). The evaluation of treatment effect was possible in all patients. Results: The overall response rate (ORR) was 29.7% (16 cases), including 3 (5.6%) complete responses (CR) and 13 (24.1%) partial responses (PR). Stable disease (SD) was observed in 7.4% of patients receiving CMT (54 patients). In the group receiving non-CMT, ORR was 3.6% (1 case). The median PFS in CMT group was 36 weeks, while in non-CMT group was 24 weeks. The most common adverse event was hematologic toxicity (74.1%), with the incidence of grade 1-2/3-4 was 70.4% and 3.7%. Hand-foot syndrome was the most frequent non-hematologic form of toxicity, occurring in 70.4% of cases. There were no treatment-related deaths. Conclusions: CMT is an effective and safe treatment for pretreated metastatic breast cancer patients. And CMT appears to be a more efficacious treatment than non-CMT.
PMCID: PMC4509356  PMID: 26221411
Metastatic breast cancer; CMT; capecitabine; chemotherapy
6.  A Chitin-Like Component on Sclerotic Cells of Fonsecaea pedrosoi Inhibits Dectin-1-Mediated Murine Th17 Development by Masking β-Glucans 
PLoS ONE  2014;9(12):e114113.
Fonsecaea pedrosoi (F. pedrosoi), a major agent of chromoblastomycosis, has been shown to be recognized primarily by C-type lectin receptors (CLRs) in a murine model of chromoblastomycosis. Specifically, the β-glucan receptor, Dectin-1, mediates Th17 development and consequent recruitment of neutrophils, and is evidenced to have the capacity to bind to saprophytic hyphae of F. pedrosoi in vitro. However, when embedded in tissue, most etiological agents of chromoblastomycosis including F. pedrosoi will transform into the sclerotic cells, which are linked to the greatest survival of melanized fungi in tissue. In this study, using immunocompetent and athymic (nu/nu) murine models infected subcutaneously or intraperitoneally with F. pedrosoi, we demonstrated that T lymphocytes play an active role in the resolution of localized footpad infection, and there existed a significantly decreased expression of Th17-defining transcription factor Rorγt and inefficient recruitment of neutrophils in chronically infected spleen where the inoculated mycelium of F. pedrosoi transformed into the sclerotic cells. We also found that Dectin-1-expressing histocytes and neutrophils participated in the enclosure of transformed sclerotic cells in the infectious foci. Furthermore, we induced the formation of sclerotic cells in vitro, and evidenced a significantly decreased binding capacity of human or murine-derived Dectin-1 to the induced sclerotic cells in comparison with the saprophytic mycelial forms. Our analysis of β-glucans-masking components revealed that it is a chitin-like component, but not the mannose moiety on the sclerotic cells, that interferes with the binding of β-glucans by human or murine Dectin-1. Notably, we demonstrated that although Dectin-1 contributed to the development of IL-17A-producing CD3+CD4+ murine splenocytes upon in vitro-stimulation by saprophytic F. pedrosoi, the masking effect of chitin components partly inhibited Dectin-1-mediated Th17 development upon in vitro-stimulation by induced sclerotic cells. Therefore, these findings extend our understanding of the chronicity of chromoblastomycosis.
doi:10.1371/journal.pone.0114113
PMCID: PMC4260783  PMID: 25490199
7.  Multicenter phase II study of Apatinib in non-triple-negative metastatic breast cancer 
BMC Cancer  2014;14:820.
Background
Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). This study was conducted to assess the efficacy and safety of apatinib in patients with non-triple-negative metastatic breast cancer who had received prior chemotherapy for their metastatic disease.
Methods
This multicenter, open-label, single arm study enrolled patients with non-triple-negative breast cancer, pretreated with anthracycline, taxanes and capecitabine, and who failed in the metastatic setting at least 1 and at most 4 prior chemotherapy regimens and at least one endocrine drug for hormone receptor-positive patients as well as at least one anti-Her2 drug for Her2-positive patients. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Apatinib was administered as 500 mg daily on days 1 through 28 of each 4-week cycle.
Results
38 patients were enrolled with a median age of 49 years (range, 35 to 62 years) and received apatinib for a median of 4 cycles (range from 0 to 10 cycles). 18 (47.4%) patients experienced dose reduction during treatment. The median relative dose intensity (relative to assigned dose for each cycle) was 82% (range, 45.0% to 100.0%). Median follow-up time was 10.1 months. Median PFS of all 38 patients was 4.0 months (95% confidence interval (CI), 2.8 m – 5.2 m). 36 patients were eligible for efficacy analysis. ORR was 16.7% (6/36). DCR was 66.7% (24/36). Median OS was 10.3 months (95% CI, 9.1 m – 11.6 m). The most common grade 3/4 treatment-related AEs were hypertension (20.5%), hand-foot syndrome (10.3%), and proteinuria (5.1%). Of three possibly drug-related SAEs recorded in the study, 2 (3.4%) deaths occurred within 28 days of last treatment and were both considered to be the result of disease progression. The other one was grade 2 diarrhea needing hospitalization.
Conclusions
Apatinib exhibited objective efficacy in heavily pretreated, metastatic non-triple-negative breast cancer with manageable toxicity, and it might be better to be tested in breast cancer with high angiogenesis dependency.
Trial registration
ClinicalTrials.gov: NCT01653561.
doi:10.1186/1471-2407-14-820
PMCID: PMC4237755  PMID: 25376790
Apatinib; Metastatic breast cancer; VEGF
8.  A prospective, randomized study on hepatotoxicity of anastrozole compared with tamoxifen in women with breast cancer 
Cancer Science  2014;105(9):1182-1188.
Tamoxifen and anastrozole are widely used as adjuvant treatment for early stage breast cancer, but their hepatotoxicity is not fully defined. We aimed to compare hepatotoxicity of anastrozole with tamoxifen in the adjuvant setting in postmenopausal breast cancer patients. Three hundred and fifty-three Chinese postmenopausal women with hormone receptor-positive early breast cancer were randomized to anastrozole or tamoxifen after optimal primary therapy. The primary end-point was fatty liver disease, defined as a liver–spleen ratio <0.9 as determined using a computed tomography scan. The secondary end-points included abnormal liver function and treatment failure during the 3-year follow up. The cumulative incidence of fatty liver disease after 3 years was lower in the anastrozole arm than that of tamoxifen (14.6% vs 41.1%, P < 0.0001; relative risk, 0.30; 95% CI, 0.21–0.45). However, there was no difference in the cumulative incidence of abnormal liver function (24.6% vs 24.7%, P = 0.61). Interestingly, a higher treatment failure rate was observed in the tamoxifen arm compared with anastrozole and median times to treatment failure were 15.1 months and 37.1 months, respectively (P < 0.0001; HR, 0.27; 95% CI, 0.20–0.37). The most commonly reported adverse events were ‘reproductive system disorders’ in the tamoxifen group (17.1%), and ‘musculoskeletal disorders’ in the anastrozole group (14.6%). Postmenopausal women with hormone receptor-positive breast cancer receiving adjuvant anastrozole displayed less fatty liver disease, suggesting that this drug had a more favorable hepatic safety profile than tamoxifen and may be preferred for patients with potential hepatic dysfunction.
doi:10.1111/cas.12474
PMCID: PMC4462391  PMID: 24975596
Anastrozole; breast cancer; clinical trial; fatty liver disease; hepatotoxicity; tamoxifen
9.  Analysis of Clinical Features and Outcome of 356 Triple-Negative Breast Cancer Patients in China 
Breast Care  2012;7(1):13-17.
Background
The purpose of this study was to investigate the clinicopathological features and analyze the prognostic factors of triple-negative breast cancer (TNBC).
Patients and Methods
The clinical data of 1,788 breast cancer patients was collected and analyzed. The Kaplan-Meier method was used to estimate survival. Multivariate analysis of the prognostic factors for survival was performed using the Cox regression model.
Results
Patients with TNBC exhibited characteristics significantly differing from those with non-TNBC. There was a higher proportion of patients with age < 35 years, stage III disease, tumor size > 5 cm, lymph node positivity, and histological grade 3. The 5-year disease-free survival (DFS) rates of TNBC and non-TNBC patients were 75.7 and 79.6%, respectively (p < 0.05). 5-year overall survival (OS) was 86.6 and 93.5%, respectively (p < 0.05). In multivariate Cox regression analysis, the independent prognostic factors for shorter DFS were age < 35 years (hazard ratio (HR) 2.105), positive lymph nodes (HR 7.039), histological grade 3 (HR 1.841), and for shorter OS positive lymph nodes (HR 4.626).
Conclusion
The proportion of TNBC in breast cancer in China is higher than in other areas. TNBC is correlated with younger age, larger tumor size, positive lymph nodes, higher clinical stage and histological grade, and lower DFS and OS, which is consistent with previous reports.
doi:10.1159/000336539
PMCID: PMC3335351  PMID: 22553467
Triple-negative breast cancer: clinical features, prognosis; Multivariate analysis
10.  MBL-Mediated Opsonophagocytosis of Candida albicans by Human Neutrophils Is Coupled with Intracellular Dectin-1-Triggered ROS Production 
PLoS ONE  2012;7(12):e50589.
Mannan-binding lectin (MBL), a lectin homologous to C1q, greatly facilitates C3/C4-mediated opsonophagocytosis of Candida albicans (C. albicans) by human neutrophils, and has the capacity to bind to CR1 (CD35) expressed on circulating neutrophils. The intracellular pool of neutrophil Dectin-1 plays a critical role in stimulating the reactive oxygen species (ROS) generation through recognition of β-1,3-glucan component of phagocytized zymosan or yeasts. However, little is known about whether MBL can mediate the opsonophagocytosis of Candida albicans by neutrophils independent of complement activation, and whether MBL-mediated opsonophagocytosis influence the intracellular expression of Dectin-1 and ROS production. Here we showed that the inhibited phagocytic efficiency of neutrophils as a result of blockage of Dectin-1 was compensated by exogenous MBL alone in a dose-dependent manner. Furthermore, the expressions of Dectin-1 at mRNA and intracellular protein levels were significantly up-regulated in neutrophils stimulated by MBL-pre-incubated C. albicans, while the expression of surface Dectin-1 remained almost unchanged. Nevertheless, the stimulated ROS production in neutrophils was partly and irreversibly inhibited by blockage of Dectin-1 in the presence of exogenous MBL. Confocal microscopy examination showed that intracellular Dectin-1 was recruited and co-distributed with ROS on the surface of some phagocytized yeasts. The β-1,3-glucanase digestion test further suggested that the specific recognition and binding site of human Dectin-1 is just the β-1,3-glucan moiety on the cell wall of C. albicans. These data demonstrate that MBL has an ability to mediate the opsonophagocytosis of Candida albicans by human neutrophils independent of complement activation, which is coupled with intracellular Dectin-1-triggered ROS production.
doi:10.1371/journal.pone.0050589
PMCID: PMC3519760  PMID: 23239982
11.  Clinicopathological Characteristics and Survival Analysis of 87 Male Breast Cancer Cases 
Breast Care  2011;6(6):446-451.
Background
The aim of this study was to investigate the clinicopathologic characteristics, therapy methods, and prognosis of male breast cancer.
Patients and Methods
We retrospectively analyzed the clinicopathological characteristics, recurrence or metastasis, and survival information of 87 male breast cancer patients. Statistical analysis included the Kaplan-Meier method to analyze survivals, log-rank to compare curves between groups, and Cox regression for multivariate prognostic analysis. A p value of <0.05 was considered statistically significant.
Results
5-year disease free survival (DFS) and 5-year overall survival (OS) were 66.3 and 77.0%, respectively. Monofactorial analysis showed tumor size, stage, lymph node involvement, and adjuvant chemotherapy to be prognostic factors with regard to 5-year DFS and 5-year OS. Multivariate Cox regression analysis showed tumor size, stage, and adjuvant chemotherapy to be independent prognostic factors with regard to 5-year DFS and 5-year OS.
Conclusion
Male breast cancer has a lower incidence rate and poor prognosis. Invasive ductal carcinoma is the main pathologic type. Operation-based combined therapy is the standard care for these patients. Tumor size, stage, and adjuvant chemotherapy are independent prognostic factors. More emphasis should be placed on early diagnosis and early therapy, and adjuvant chemotherapy may improve survival.
doi:10.1159/000335204
PMCID: PMC3290016  PMID: 22419898
Male breast cancer; Clinical characteristics; Therapy; Prognosis
12.  Quality of Life after Autologous Peripheral Blood Stem Cell Transplantation and High-Dose Chemotherapy in High-Risk Breast Cancer Patients 
Breast Care  2009;4(6):379-386.
Summary
Background
As long-term survivors of breast cancer after autologous peripheral blood stem cell transplantation (ASCT) are becoming more numerous, studies addressing the issue of long-term follow-up are necessary. In this study, we report on the quality of life (QOL) after ASCT and high-dose chemotherapy (HDCT).
Patients and Methods
The QOL questionnaire version 3.0 by the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30 version 3.0) was filled in by patients and healthy controls at 5 time points. After obtaining the results, we analyzed the correlation between QOL and the effect factors.
Results
Some functions got significantly worse, and some symptoms got more serious after ASCT and HDCT. However, most of them improved with time and were comparable to the healthy controls after 5 years. QOL was in part related to age, tumor characteristics, educational level, marriage status, and income.
Conclusions
Evaluating QOL allows medical workers to fully understand a patient's state of health, and aid the estimation and selection of clinical treatment methods as well as improve recovery.
doi:10.1159/000266759
PMCID: PMC2942001  PMID: 20877673
Quality of life; Autologous peripheral blood stem cell transplantation; High-risk breast cancer
13.  Assignment of Reference 5’-end 16S rDNA Sequences and Species-Specific Sequence Polymorphisms Improves Species Identification of Nocardia 
16S rDNA sequence analysis is the most accurate method for definitive species identification of nocardiae. However, conflicting results can be found due to sequence errors in gene databases. This study tested the feasibility of species identification of Nocardia by partial (5’-end 606-bp) 16S rDNA sequencing, based on sequence comparison with “reference” sequences of well-annotated strains. This new approach was evaluated using 96 American Type Culture Collection (n=6), and clinical (n=90) Nocardia isolates. Nucleotide sequence-based polymorphisms within species were indicative of “sequence types” for that species. Sequences were compared with those in the GenBank, Bioinformatics Bacteria Identification and Ribosomal Database Project databases. Compared with the reference sequence set, all 96 isolates were correctly identified using the criterion of ≥99% sequence similarity. Seventy-eight (81.3%) were speciated by database comparison; alignment with reference sequences resolved the identity of 14 (15%) isolates whose sequences yielded 100% similarity to sequences in GenBank under >1 species designation. Of 90 clinical isolates, the commonest species was Nocardia nova (33.3%) followed by Nocardia cyriacigeorgica (26.7%). Recently-described or uncommon species included Nocardia veterana (4.4%), Nocarida bejingensis (2.2%) and, Nocardia abscessus and Nocardia arthriditis (each n=1). Nocardia asteroides sensu stricto was rare (n=1). There were nine sequence types of N. nova, three of Nocardia brasiliensis with two each of N. cyriacigeorgica and Nocardia farcinica. Thirteen novel sequences were identified. Alignment of sequences with reference sequences facilitated species identification of Nocardia and allowed delineation of sequence types within species, suggesting that such a barcoding approach can be clinically useful for identification of bacteria.
doi:10.2174/1874285800903010097
PMCID: PMC2714554  PMID: 19639036
Nocardia spp.; species identification; 16S rDNA; reference sequences; sequence polymorphisms.
14.  Rapid Identification and Differentiation of Trichophyton Species, Based on Sequence Polymorphisms of the Ribosomal Internal Transcribed Spacer Regions, by Rolling-Circle Amplification▿  
Journal of Clinical Microbiology  2008;46(4):1192-1199.
DNA sequencing analyses have demonstrated relatively limited polymorphisms within the fungal internal transcribed spacer (ITS) regions among Trichophyton spp. We sequenced the ITS region (ITS1, 5.8S, and ITS2) for 42 dermatophytes belonging to seven species (Trichophyton rubrum, T. mentagrophytes, T. soudanense, T. tonsurans, Epidermophyton floccosum, Microsporum canis, and M. gypseum) and developed a novel padlock probe and rolling-circle amplification (RCA)-based method for identification of single nucleotide polymorphisms (SNPs) that could be exploited to differentiate between Trichophyton spp. Sequencing results demonstrated intraspecies genetic variation for T. tonsurans, T. mentagrophytes, and T. soudanense but not T. rubrum. Signature sets of SNPs between T. rubrum and T. soudanense (4-bp difference) and T. violaceum and T. soudanense (3-bp difference) were identified. The RCA assay correctly identified five Trichophyton species. Although the use of two “group-specific” probes targeting both the ITS1 and the ITS2 regions were required to identify T. soudanense, the other species were identified by single ITS1- or ITS2-targeted species-specific probes. There was good agreement between ITS sequencing and the RCA assay. Despite limited genetic variation between Trichophyton spp., the sensitive, specific RCA-based SNP detection assay showed potential as a simple, reproducible method for the rapid (2-h) identification of Trichophyton spp.
doi:10.1128/JCM.02235-07
PMCID: PMC2292936  PMID: 18234865
15.  Identification of Less-Common Streptococcus pneumoniae Serotypes by a Multiplex PCR-Based Reverse Line Blot Hybridization Assay▿  
Journal of Clinical Microbiology  2007;45(10):3411-3415.
We developed a multiplex PCR-based reverse line blot (mPCR/RLB) assay to identify 50 uncommon pneumococcal serotypes. In combination with a previously described mPCR/RLB assay (3), all 90 pneumococcal serotypes can be identified individually (32 serotypes) or, because of predictable cross-reactions, to within small groups of two to five related serotypes (58 serotypes), which can be distinguished using serotype-specific antisera.
doi:10.1128/JCM.01076-07
PMCID: PMC2045372  PMID: 17687009
16.  Comparison of Single- and Multilocus Sequence Typing and Toxin Gene Profiling for Characterization of Methicillin-Resistant Staphylococcus aureus▿  
Journal of Clinical Microbiology  2007;45(10):3302-3308.
We compared three novel methicillin-resistant Staphylococcus aureus (MRSA) genotyping methods with multilocus sequence typing (MLST) and spa typing to assess their utility for routine strain typing. The new methods were femA and nuc sequence typing and toxin gene profiling (TGP), using a multiplex-PCR-based reverse line blot assay to detect 13 pyrogenic superantigen and exfoliative toxin genes. Forty-two well-characterized MRSA strains, representing 15 MLSTs or 9 clonal clusters (CCs), were genotyped by all methods. Twenty-two spa, nine femA, and seven nuc sequence types were identified. The femA sequence types correlated exactly with CCs; nuc sequences types were less discriminatory but generally correlated well with femA types and CCs. Ten isolates contained none of 13 toxin genes; TGPs of the remainder comprised 1 to 5 toxin genes. The combination of spa typing and TGPs identified 26 genotypes among the 42 strains studied. A combination of two or three rapid, inexpensive genotyping methods could potentially provide rapid MRSA strain typing as well as useful information about clonal origin and virulence.
doi:10.1128/JCM.01082-07
PMCID: PMC2045362  PMID: 17715374
17.  In Vitro Activities of Miltefosine and Two Novel Antifungal Biscationic Salts against a Panel of 77 Dermatophytes▿  
The susceptibilities of 77 dermatophytes to miltefosine (MI), 1,12-bis(4-pentylpyridinium)dodecane (PYR), 1,12-bis(tributylammonium)dodecane (AM), itraconazole (ITC), terbinafine (TRB), and butenafine (BTF) were compared. Geometric mean MICs of TRB, BTF, ITC, MI, PYR, and AM were 0.039, 0.059, 1.718, 0.671, 6.006, and 4.771 μg/ml, respectively. MI was more active than ITC (P < 0.001).
doi:10.1128/AAC.01382-06
PMCID: PMC1891392  PMID: 17371821

Results 1-17 (17)