bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biocompatibility of Solid-Dosage Forms of Anti-Human Immunodeficiency Virus Type 1 Microbicides with the Human Cervicovaginal Mucosa Modeled Ex Vivo
Authors: Trifonova Radiana T. , Pasicznyk Jenna-Malia , Fichorova Raina N. 
Published: November 2006

ABSTRACTTopical anti-human immunodeficiency virus (HIV) microbicides are being sought to reduce the spread of HIV type 1 (HIV-1) during sexual intercourse. The success of this strategy depends upon the selection of formulations compatible with the natural vaginal mucosal barrier. This study applied ex vivo-modeled human cervicovaginal epithelium to evaluate experimental solid-dosage forms of the anti-HIV-1 microbicide cellulose acetate 1,2-benzenedicarboxylate (CAP) and over-the-counter (OTC) vaginal products for their impact on inflammatory mediators regarded as potential HIV-1-enhancing risk factors. We assessed product-induced imbalances between interleukin-1α (IL-1α) and IL-1β and the natural IL-1 receptor antagonist (IL-1RA) and changes in levels of IL-6, tumor necrosis factor alpha, IL-8, gamma interferon inducible protein 10 (IP-10), and macrophage inflammatory protein 3α (MIP-3α), known to recruit and activate monocytes, dendritic cells, and T cells to the inflamed mucosa. CAP film and gel formulation, similarly to the hydroxyethylcellulose universal vaginal placebo gel and the OTC K-Y moisturizing gel, were nontoxic and caused no significant changes in any inflammatory biomarker. In contrast, OTC vaginal cleansing and contraceptive films containing octoxynol-9 or nonoxynol-9 (N-9) demonstrated similar levels of toxicity but distinct immunoinflammatory profiles. IL-1α, IL-1β, IL-8, and IP-10 were increased after treatment with both OTC vaginal cleansing and contraceptive films; however, MIP-3α was significantly elevated by the N-9-based film only (P< 0.01). Although both films increased extracellular IL-1RA, the cleansing film only significantly elevated the IL-1RA/IL-1 ratio (P< 0.001). The N-9-based film decreased intracellular IL-1RA (P< 0.05), which has anti-inflammatory intracrine functions. This study identifies immunoinflammatory biomarkers that can discriminate between formulations better than toxicity assays and should be clinically validated in relevance to the risk of HIV-1 acquisition.
Prevalence of
Trichomonas vaginalis
Isolates with Resistance to Metronidazole and Tinidazole
Authors: Schwebke Jane R. , Barrientes Frank J. 
Published: November 2006

ABSTRACT

Clinical isolates of
Trichomonas vaginalis
were obtained from women consecutively enrolled in a study of partner notification. Testing of susceptibility to metronidazole and tinidazole was performed. Resistance to metronidazole and tinidazole was present in 17/178 (9.6%) and 1/178 (0.56%) strains, respectively. In vitro resistance was poorly correlated with clinical response to treatment.
Functional Analysis of DNA Gyrase Mutant Enzymes Carrying Mutations at Position 88 in the A Subunit Found in Clinical Strains of
Mycobacterium tuberculosis
Resistant to Fluoroquinolones
Authors: Matrat Stéphanie , Veziris Nicolas , Mayer Claudine , Jarlier Vincent , Truffot-Pernot Chantal , Camuset Juliette , Bouvet Elisabeth , Cambau Emmanuelle , Aubry Alexandra 
Published: November 2006

ABSTRACT

We investigated the enzymatic efficiency and inhibition by quinolones of
Mycobacterium tuberculosis
DNA gyrases carrying the previously described GyrA G88C mutation and the novel GyrA G88A mutation harbored by two multidrug-resistant clinical strains and reproduced by site-directed mutagenesis. Fluoroquinolone MICs and 50% inhibitory concentrations for both mutants were 2- to 43-fold higher than for the wild type, demonstrating that these mutations confer fluoroquinolone resistance in
M. tuberculosis
.
Activity of DX-619 Compared to Other Agents against Viridans Group Streptococci,
Streptococcus bovis
, and
Cardiobacterium hominis
Authors: Kosowska-Shick Klaudia , Smith Kathy , Bogdanovich Tatiana , Ednie Lois M. , Jones Ronald N. , Appelbaum Peter C. 
Published: November 2006

ABSTRACT

Against 198 viridans group streptococci, 25
Streptococcus bovis
strains, and 5
Cardiobacterium hominis
strains, MICs of DX-619, a des-F(6)-quinolone, were between 0.004 and 0.25 μg/ml. These MICs were lower than those of other quinolones (≤0.008 to >32 μg/ml). β-Lactam MICs were between ≤0.008 and 16 μg/ml. Azithromycin resistance was found in most species, while most were telithromycin susceptible. Glycopeptides and linezolid were active against viridans group strains but inactive against
C. hominis
.
Diversity of
Archaea
in Marine Sediments from Skan Bay, Alaska, Including Cultivated Methanogens, and Description of
Methanogenium boonei
sp. nov
Authors: Kendall Melissa M. , Wardlaw George D. , Tang Chin F. , Bonin Adam S. , Liu Yitai , Valentine David L. 
Published: November 2006

ABSTRACT

Methanogenesis in cold marine sediments is a globally important process leading to methane hydrate deposits, cold seeps, physical instability of sediment, and atmospheric methane emissions. We employed a multidisciplinary approach that combined culture-dependent and -independent analyses with geochemical measurements in the sediments of Skan Bay, Alaska (53°N, 167°W), to investigate methanogenesis there. Cultivation-independent analyses of the archaeal community revealed that uncultivated microbes of the kingdoms
Euryarchaeota
and
Crenarchaeota
are present at Skan Bay and that methanogens constituted a small proportion of the archaeal community. Methanogens were cultivated from depths of 0 to 60 cm in the sediments, and several strains related to the orders
Methanomicrobiales
and
Methanosarcinales
were isolated. Isolates were psychrotolerant marine-adapted strains and included an aceticlastic methanogen, strain AK-6, as well as three strains of CO
2
-reducing methanogens: AK-3, AK7, and AK-8. The phylogenetic positions and physiological characteristics of these strains are described. We propose a new species,
Methanogenium boonei
, with strain AK-7 as the type strain.
A Genomic Island of the Pathogen
Leptospira interrogans
Serovar Lai Can Excise from Its Chromosome
Authors: Bourhy Pascale , Salaün Laurence , Lajus Aurélie , Médigue Claudine , Boursaux-Eude Caroline , Picardeau Mathieu 
Published: November 2006

ABSTRACT

An examination of the two
Leptospira interrogans
genomes sequenced so far reveals few genetic differences, including an extra DNA region, 54 kb in length, in
L. interrogans
serovar Lai. This locus contains 103 predicted coding sequences that are absent from the genome of
L. interrogans
serovar Copenhageni, of which only 20% had significant BLASTP hits in GenBank. By analyzing the
L. interrogans
serovar Lai genome by pulsed-field gel electrophoresis, we also found that this 54-kb DNA fragment exists as a circular plasmid. This was confirmed by amplification of a DNA fragment corresponding to that of the predicted fragment if this region excised from the chromosome and its left and right ends joined together. In addition, cloning of the putative
rep
gene of this DNA region was responsible for autonomous replication in
Leptospira
spp., therefore generating a new
Escherichia coli-Leptospira
sp. shuttle vector. Taken together, our results show that this genomic island can excise from the chromosome and form a replicative plasmid. Analysis of the distribution of this genomic island revealed that highly related sequences exist in other
L. interrogans
virulent strains. This genomic island, containing a high proportion of novel genes, may have an important role in spreading genes, including virulence factors, among bacterial populations.
Intranasal Vaccination with a Secreted Chlamydial Protein Enhances Resolution of GenitalChlamydia muridarumInfection, Protects against Oviduct Pathology, and Is Highly Dependent upon Endogenous Gamma Interferon Production
Authors: Murthy Ashlesh K. , Chambers James P. , Meier Patricia A. , Zhong Guangming , Arulanandam Bernard P. 
Published: November 2006

ABSTRACTThere is currently no licensed vaccine againstChlamydia trachomatis, the leading cause of sexually transmitted bacterial disease worldwide. Conventional vaccination attempts using surface-exposed chlamydial antigens have achieved only partial success. We have employed a novel vaccination strategy using a secreted protein, chlamydial protease-like activity factor (CPAF), which has been shown to degrade host major histocompatibility complex transcription factors and keratin-8 and therefore may allow immune evasion and establishment of a productive infection. Intranasal immunization using recombinant CPAF (rCPAF) plus interleukin-12 (IL-12) (rCPAF+IL-12 immunization) was used to assess the protective immunity against genitalChlamydia muridaruminfection in BALB/c mice. rCPAF+IL-12 immunization induced robust gamma interferon (IFN-γ) production and minimal IL-4 production by splenocytes upon in vitro recall with rCPAF. The total and immunoglobulin G2a (IgG2a) anti-rCPAF antibody levels in serum were significantly elevated after rCPAF+IL-12 vaccination, as were the total antibody, IgG2a, and IgA levels in bronchoalveolar lavage and vaginal fluids when the animals were compared to animals that received rCPAF alone. rCPAF+IL-12-vaccinated mice displayed significantly reduced bacterial shedding upon chlamydial challenge and accelerated resolution of infection compared to mock-immunized (phosphate-buffered saline) animals. Moreover, rCPAF+IL-12-immunized animals exhibited protection against pathological consequences of chlamydial infection, including the development of hydrosalpinx and oviduct dilatation. This vaccination regimen also reduced the development of fibrosis and the influx of neutrophils into the upper genital tract when the animals were compared to mock-immunized (phosphate-buffered saline) animals after bacterial challenge. rCPAF+IL-12-mediated resolution of the bacterial infection and protection againstChlamydia-induced inflammatory disease were highly dependent on endogenous IFN-γ production. Together, these results demonstrate that secreted chlamydial antigens may be novel vaccine candidates to induce protective immunity.
Combined Transcriptional and Translational Targeting of EWS/FLI-1 in Ewing's Sarcoma
Authors: Mateo-Lozano Silvia , Gokhale Prafulla C. , Soldatenkov Viatcheslav A. , Dritschilo Anatoly , Tirado Oscar M. , Notario Vicente 
Published: November 2006

Abstract
Purpose: To show the efficacy of targeting EWS/FLI-1 expression with a combination of specific antisense oligonucleotides and rapamycin for the control of Ewing's sarcoma (EWS) cell proliferation in vitro and the treatment of mouse tumor xenografts in vivo.
Experimental Design: EWS cells were simultaneously exposed to EWS/FLI-1–specific antisense oligonucleotides and rapamycin for various time periods. After treatment, the following end points were monitored and evaluated: expression levels of the EWS/FLI-1 protein, cell proliferation, cell cycle distribution, apoptotic cell death, caspase activation, and tumor growth in EWS xenografts implanted in nude mice.
Results: Simultaneous exposure of EWS cells in culture to an EWS/FLI-1–targeted suppression therapy using specific antisense oligonucleotides and rapamycin resulted in the activation of a caspase-dependent apoptotic process that involved the restoration of the transforming growth factor-β–induced proapoptotic pathway. In vivo, individual administration of either antisense oligonucleotides or rapamycin significantly delayed tumor development, and the combined treatment with antisense oligonucleotides and rapamycin caused a considerably stronger inhibition of tumor growth.
Conclusions: Concurrent administration of EWS/FLI-1 antisense oligonucleotides and rapamycin efficiently induced the apoptotic death of EWS cells in culture through a process involving transforming growth factor-β. In vivo experiments conclusively showed that the combined treatment with antisense oligonucleotides and rapamycin caused a significant inhibition of tumor growth in mice. These results provide proof of principle for further exploration of the potential of this combined therapeutic modality as a novel strategy for the treatment of tumors of the Ewing's sarcoma family.
Loss of Breast Cancer Metastasis Suppressor 1 Protein Expression Predicts Reduced Disease-Free Survival in Subsets of Breast Cancer Patients
Authors: Hicks David G. , Yoder Brian J. , Short Sarah , Tarr Shannon , Prescott Nichole , Crowe Joseph P. , Dawson Andrea E. , Budd G. Thomas , Sizemore Steven , Cicek Muzaffer , Choueiri Toni K. , Tubbs Raymond R. , Gaile Daniel , Nowak Norma , Accavitti-Loper Mary Ann , Frost Andra R. , Welch Danny R. , Casey Graham 
Published: November 2006

AbstractPurpose: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes.Experimental Design: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining.Results: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P = 0.006) or HER2 positive (P = 0.039) and &lt;50 years old at diagnosis (P = 0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P = 0.008) or PR (P = 0.029) or HER2 overexpression (P = 0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status.Conclusions: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.
CXCR4 Inhibition Synergizes with Cytotoxic Chemotherapy in Gliomas
Authors: Redjal Navid , Chan Jennifer A. , Segal Rosalind A. , Kung Andrew L. 
Published: November 2006

Abstract
Purpose: The chemokine receptor CXCR4 is expressed in many different cancers. In malignant brain tumors, CXCR4 signaling has been implicated in tumor growth, survival, and migration, and pharmacologic inhibition of CXCR4 results in decreased tumor growth in preclinical models. To understand how CXCR4 inhibitors may be incorporated into clinical therapy, we examined determinants of responsiveness to CXCR4 inhibition. Because optimal use of CXCR4 inhibition will likely be a part of multimodality therapy, we also investigated the efficacy of CXCR4 inhibition combined with conventional cytotoxic chemotherapy.
Experimental Design: CXCR4 protein levels and responsiveness to the CXCR4 inhibitor AMD3100 were determined in a panel of glioblastoma multiforme cell lines. The effects of AMD3100, alone or in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), on cell growth were determined for several of these cell lines in vitro. We used an orthotopic model of glioblastoma multiforme to evaluate the antitumor efficacy of AMD3100 combined with BCNU in vivo.
Results: The level of CXCR4 protein expression in glioblastoma multiforme cells predicts the dose at which there is a response to AMD3100; cells that express higher levels of CXCR4 protein require higher doses for equivalent response. In all cell lines tested, treatment of glioblastoma multiforme cells with BCNU followed by AMD3100 results in synergistic antitumor efficacy in vitro. This synergy can also be seen in an orthotopic glioblastoma multiforme model. Treatment with subtherapeutic doses of BCNU in combination with AMD3100 results in tumor regression in vivo, and this reflects both increased apoptosis and decreased proliferation following combination therapy.
Conclusion: These studies support testing CXCR4 inhibitors in patients with glioblastoma multiforme and establish that inhibition of CXCR4 synergizes with conventional cytotoxic therapies in a clinically relevant combinatorial strategy.
Reprimo Methylation Is a Potential Biomarker of Barrett's-Associated Esophageal Neoplastic Progression
Authors: Hamilton James P. , Sato Fumiaki , Jin Zhe , Greenwald Bruce D. , Ito Tetsuo , Mori Yuriko , Paun Bogdan C. , Kan Takatsugu , Cheng Yulan , Wang Suna , Yang Jian , Abraham John M. , Meltzer Stephen J. 
Published: November 2006

Abstract
Purpose: Reprimo, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression Reprimo methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether Reprimo expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC).
Experimental Design: Quantitative methylation-specific PCR for Reprimo was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on esophageal carcinoma cells before and after treatment with 5AzaC.
Results: In Barrett's esophagus (BE; P = 0.001), high-grade dysplasia (HGD; P = 0.001), and esophageal adenocarcinoma (EAC; P = 0.00003), the level and frequency of Reprimo methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between BE and EAC, HGD and EAC, or NE and esophageal squamous cell carcinoma (ESCC). Reprimo methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 ESCC, 9 (36%) of 25 BE, 7 (64%) of 11 HGD, and 47 (63%) of 75 EAC. Analysis of Reprimo methylation in EAC versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P &lt; 0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 EAC cells reduced Reprimo methylation and increased Reprimo expression.
Conclusions: Reprimo methylation occurs significantly more frequently in BE, HGD, and EAC than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia.
Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model
Authors: Younes Maher N. , Park Young Wook , Yazici Yasemin Dakak , Gu Meirong , Santillan Alfredo A. , Nong Xiaolin , Kim Seungwon , Jasser Samar A. , El-Naggar Adel K. , Myers Jeffrey N. 
Published: November 2006

Abstract
We hypothesized that epidermal growth factor (EGF) receptor (EGFR) activation and vascular endothelial growth factor (VEGF)–induced angiogenic signals are important for the progression and metastasis of human salivary adenoid cystic carcinoma (ACC). To test this hypothesis, we evaluated the therapeutic effect of AEE788, a dual inhibitor of EGF and VEGF receptor (VEGFR) tyrosine kinases, on human salivary ACC. In clinical specimens of salivary ACC, EGF and VEGF signaling proteins were expressed at markedly higher levels than in adjacent normal glandular tissues. We examined the effects of AEE788 on salivary ACC cell growth and apoptosis and on the phosphorylation of EGFR and VEGFR-2 in salivary ACC cells. Treatment of salivary ACC cells with AEE788, alone or in combination with chemotherapy, led to growth inhibition, induction of apoptosis, and dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation. To determine the in vivo antitumor effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 alone, paclitaxel alone, cisplatin alone, a combination of AEE788 plus paclitaxel, a combination of AEE788 plus cisplatin, or a placebo. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. To study the mechanism of interaction between AEE788 and chemotherapy, AEE788 was found to potentiate growth inhibition and apoptosis of ACC tumor cells mediated by chemotherapy. Tumors of mice treated with AEE788 and AEE788 plus chemotherapy exhibited down-regulation of activated EGFR and VEGFR-2, increased tumor and endothelial cell apoptosis, and decreased microvessel density, which correlated with a decrease in the level of matrix metalloproteinase-9 and matrix metalloproteinase-2 expression and a decrease in the incidence of vascular metastasis. These data show that EGFR and VEGFR can be molecular targets for therapy of salivary ACC. [Mol Cancer Ther 2006;5(11):2696–705]
Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer
Authors: Sørlie Therese , Perou Charles M. , Fan Cheng , Geisler Stephanie , Aas Turid , Nobel Andrew , Anker Gun , Akslen Lars A. , Botstein David , Børresen-Dale Anne-Lise , Lønning Per Eystein 
Published: November 2006

Abstract
Neoadjuvant treatment offers an opportunity to correlate molecular variables to treatment response and to explore mechanisms of drug resistance in vivo. Here, we present a statistical analysis of large-scale gene expression patterns and their relationship to response following neoadjuvant chemotherapy in locally advanced breast cancers. We analyzed cDNA expression data from 81 tumors from two patient series, one treated with doxorubicin alone (51) and the other treated with 5-fluorouracil and mitomycin (30), and both were previously studied for correlations between TP53 status and response to therapy. We observed a low frequency of progressive disease within the luminal A subtype from both series (2 of 36 versus 13 of 45 patients; P = 0.0089) and a high frequency of progressive disease among patients with luminal B type tumors treated with doxorubicin (5 of 8 patients; P = 0.0078); however, aside from these two observations, no other consistent associations between response to chemotherapy and tumor subtype were observed. These specific associations could possibly be explained by covariance with TP53 mutation status, which also correlated with tumor subtype. Using supervised analysis, we could not uncover a gene profile that could reliably (&gt;70% accuracy and specificity) predict response to either treatment regimen. [Mol Cancer Ther 2006;5(11):2914–8]