bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nosocomial Bacteremia Clinical Significance of a Single Blood Culture Positive for Coagulase-Negative Staphylococci
Authors: Favre Benoît , Hugonnet Stéphane , Correa Luci , Sax Hugo , Rohner Peter , Pittet Didier 
Published: April 2006

AbstractObjectives:To describe the epidemiology of nosocomial coagulase-negative staphylococci (CoNS) bacteremia and to evaluate the clinical significance of a single blood culture positive for CoNS.Design:A 3-year retrospective cohort study based on data prospectively collected through hospital-wide surveillance. Bacteremia was defined according to CDC criteria, except that a single blood culture growing CoNS was not systematically considered as a contaminant. All clinically significant blood cultures positive for CoNS nosocomial bacteremia were considered for analysis.Setting:A large university teaching hospital in Geneva, Switzerland.Results:A total of 2,660 positive blood cultures were identified. Of these, 1,108 (41.7%) were nosocomial; CoNS were recovered from 411 nosocomial episodes (37.1%). Two hundred thirty-four episodes of CoNS bacteremia in the presence of signs of sepsis were considered clinically relevant and analyzed. Crude mortality and associated mortality were 24.4% and 12.8%, respectively. Associated mortality was similar among patients with one positive blood culture and those with two or more (16.2% vs 10.8%, respectively;P= .3). Mortality rates after bacteremia for patients with a single positive blood culture and for those with two or more were 15.3% and 7.0%, respectively, at day 14 (RR, 2.2; CI%, 0.87-5.46) and 20.8% and 11.3%, respectively, at day 28 (RR, 1.9; CI95, 0.9-3.8). On multivariate analysis, only age and a rapidly fatal disease were independently associated with death.Conclusion:CoNS bacteremia harbor a significant mortality and a single positive blood culture in the presence of signs of sepsis should be considered as clinically relevant.
Cleaning and Sterilization Protocol for Reused Cardiac Electrophysiology Catheters Inactivates Hepatitis and Coxsackie Viruses
Authors: Druce Julian D. , Russell Jessica S. , Birch Christopher J. , Vickery Karen , Harper Richard W. , Smolich Joseph J. 
Published: April 2006

AbstractObjective:To assess the efficacy of a standard cleaning and sterilization protocol employed during reuse of cardiac electrophysiology catheters on the infectivity of duck hepatitis B virus (DHBV; a surrogate for human hepatitis B virus), bovine viral diarrhea virus (BVDV; a surrogate for human hepatitis B virus), and human Coxsackie type B3 virus (CB3).Setting:Public health virology laboratory.Methods:Studies were performed on the distal, electrode-containing segments of 120 electrophysiology catheters previously used in up to 10 clinical procedures. Catheter segments were immersed for 1 hour in blood infected with high titers of DHBV, BVDV, or CB3. After air drying for 2 hours, subgroups of 8 catheters were subjected to no treatment, washing in general-purpose detergent, washing in enzyme cleaner, sterilization in ethylene oxide, or the full protocol of sequential detergent-enzyme cleaner-ethylene oxide exposure. Presence of residual virus was assessed by nucleic acid detection and infectivity studies.Results:DHBV nucleic acid was detected on catheters after individual steps and the full protocol, whereas BVDV and CB3 nucleic acids were detected after individual steps but not the full protocol. These findings were associated with the presence of infectious DHBV and CB3, but not BVDV, on catheters after washing in detergent or enzyme cleaner. However, ethylene oxide alone or the full protocol reduced infectivity of all three viruses to undetectable levels.Conclusion:These experimental studies provide strong evidence that appropriate cleaning and sterilization of reused electrophysiology catheters inactivates blood-borne viruses such as hepatitis B and C and Coxsackie type B3.
A New Melanoma Antigen Fatty Acid–Binding Protein 7, Involved in Proliferation and Invasion, Is a Potential Target for Immunotherapy and Molecular Target Therapy
Authors: Goto Yasufumi , Matsuzaki Yuriko , Kurihara Sachiko , Shimizu Ayako , Okada Tsutomu , Yamamoto Kazuhiko , Murata Hiroshi , Takata Minoru , Aburatani Hiroyuki , Hoon Dave S.B. , Saida Toshiaki , Kawakami Yutaka 
Published: April 2006

Abstract
The identification of molecules that are preferentially expressed in melanoma cells and involved in their malignant phenotypes is important for understanding melanoma biology and the development of new diagnostic and therapeutic methods. By comparing the expression profile of a melanoma cell line with those of various normal tissues using GeneChip and by confirming the actual expression of the selected genes by reverse transcription-PCR and Northern and Western blot analyses, fatty acid–binding protein 7 (FABP7), which is frequently expressed in melanomas, was identified. Immunohistochemical examination revealed that FABP7 was expressed in 11 of 15 melanoma tissues. By down-regulating the FABP7 expression with FABP7-specific small interfering RNAs, in vitro cell proliferation and Matrigel invasion were suppressed in two of six melanoma cell lines. Overexpression of FABP7 in a FABP7-negative embryonic kidney cell line 293T by transfecting with the FABP7 cDNA resulted in enhanced cell proliferation and Matrigel invasion, indicating that FABP7 plays a role in the malignant phenotype of some melanoma cell lines. IgG antibodies specific for the phage or bacterial recombinant FABP7 protein were detected in 14 of 25 (56%) or in 8 of 31 (26%) sera from melanoma patients, respectively, but not in sera from healthy individuals, indicating that FABP7 is an immunogenic antigen in melanoma patients. These results showed that FABP7 is frequently expressed in melanoma, may be involved in cell proliferation and invasion, and may be a potential target for development of diagnostic and therapeutic methods. (Cancer Res 2006; 66(8): 4443-9)
High-throughput Loss-of-Heterozygosity Study of Chromosome 3p in Lung Cancer Using Single-Nucleotide Polymorphism Markers
Authors: Tai Amy L.S. , Mak William , Ng Phoebe K.M. , Chua Daniel T.T. , Ng Mandy Y.M. , Fu Li , Chu Kevin K.W. , Fang Yan , Qiang Song You , Chen Muhan , Zhang Minyue , Sham Pak C. , Guan Xin-Yuan 
Published: April 2006

Abstract
Loss of DNA copy number at the short arm of chromosome 3 is one of the most common genetic changes in human lung cancer, suggesting the existence of one or more tumor suppressor genes (TSG) at 3p. To identify most frequently deleted regions and candidate TSGs within these regions, a recently developed single-nucleotide polymorphism (SNP)-mass spectrometry-genotyping (SMSG) technology was applied to investigate the loss of heterozygosity (LOH) in 30 primary non–small-cell lung cancers. A total of 386 SNP markers that spanned a region of 70 Mb at 3p, from 3pter to 3p14.1, were selected for LOH analysis. The average intermarker distance in the present study is ∼180 kb. Several frequently deleted regions, including 3p26.3, 3p25.3, 3p24.1, 3p23, and 3p21.1, were found. Several candidate TSGs within these frequently detected LOH regions have been found, including APG7L at 3p25.3, CLASP2 at 3p23, and CACNA2D3 at 3p21.1. This study also showed that SMSG technology is a very useful approach to rapidly define the minimal deleted region and to identify target TSGs in a given cancer. (Cancer Res 2006; 66(8): 4133-8)
The Kinase Mirk/Dyrk1B Mediates Cell Survival in Pancreatic Ductal Adenocarcinoma
Authors: Deng Xiaobing , Ewton Daina Z. , Li Sheena , Naqvi Asghar , Mercer Stephen E. , Landas Steve , Friedman Eileen 
Published: April 2006

Abstract
Ductal adenocarcinoma of the pancreas is almost uniformly lethal as this cancer is invariably detected at an advanced stage and is resistant to treatment. The serine/threonine kinase Mirk/Dyrk1B has been shown to be antiapoptotic in rhabdomyosarcomas. We have now investigated whether Mirk might mediate survival in another cancer in which Mirk is widely expressed, pancreatic ductal adenocarcinoma. Mirk was an active kinase in each pancreatic cancer cell line where it was detected. Mirk knockdown by RNA interference (RNAi) reduced the clonogenicity of Panc1 pancreatic cancer cells 4-fold and decreased tumor cell number, showing that Mirk mediates survival in these cells. Mirk knockdown by synthetic duplex RNAis in Panc1, AsPc1, and SU86.86 pancreatic cancer cells induced apoptosis and enhanced the apoptosis induced by gemcitibine. Mirk knockdown did not increase the abundance or activation of Akt. However, four of five pancreatic carcinoma cell lines exhibited either elevated Mirk activity or elevated Akt activity, suggesting that pancreatic cancer cells primarily rely on Mirk or Akt for survival signaling. Mirk protein was detected by immunohistochemistry in 25 of 28 cases (89%) of pancreatic ductal adenocarcinoma, with elevated expression in 11 cases (39%). Increased expression of Mirk was seen in pancreatic carcinomas compared with primary cultures of normal ductal epithelium by serial analysis of gene expression and by immunohistochemistry. Thus, Mirk is a survival factor for pancreatic ductal adenocarcinoma. Because knockout of Mirk does not cause embryonic lethality, Mirk is not essential for normal cell growth and may represent a novel therapeutic target. (Cancer Res 2006; 66(8): 4149-58)
Suppression of Centrosome Amplification after DNA Damage Depends on p27 Accumulation
Authors: Sugihara Eiji , Kanai Masayuki , Saito Soichiro , Nitta Takayuki , Toyoshima Hideo , Nakayama Keiko , Nakayama Keiichi I. , Fukasawa Kenji , Schwab Manfred , Saya Hideyuki , Miwa Masanao 
Published: April 2006

Abstract
The centrosome plays a fundamental role in cell division, cell polarity, and cell cycle progression. Centrosome duplication is mainly controlled by cyclin-dependent kinase 2 (CDK2)/cyclin E and cyclin A complexes, which are inhibited by the CDK inhibitors p21Cip1 and p27Kip1. It is thought that abnormal activation of CDK2 induces centrosome amplification that is frequently observed in a wide range of aggressive tumors. We previously reported that overexpression of the oncogene MYCN leads to centrosome amplification after DNA damage in neuroblastoma cells. We here show that centrosome amplification after γ-irradiation was caused by suppression of p27 expression in MYCN-overexpressing cells. We further show that p27−/− and p27+/− mouse embryonic fibroblasts and p27-silenced human cells exhibited a significant increase in centrosome amplification after DNA damage. Moreover, abnormal mitotic cells with amplified centrosomes were frequently observed in p27-silenced cells. In response to DNA damage, the level of p27 gradually increased in normal cells independently of the ataxia telangiectasia mutated/p53 pathway, whereas Skp2, an F-box protein component of an SCF ubiquitin ligase complex that targets p27, was reduced. Additionally, p27 levels in MYCN-overexpressing cells were restored by treatment with Skp2 small interfering RNA, indicating that down-regulation of p27 by MYCN was due to high expression of Skp2. These results suggest that the accumulation of p27 after DNA damage is required for suppression of centrosome amplification, thereby preventing chromosomal instability. (Cancer Res 2006; 66(8): 4020-9)
Adeno-Associated Virus–Mediated Delivery of a Mutant Endostatin in Combination with Carboplatin Treatment Inhibits Orthotopic Growth of Ovarian Cancer and Improves Long-term Survival
Authors: Subramanian Indira V. , Bui Nguyen Tri Minh , Truskinovsky Alexander M. , Tolar Jakub , Blazar Bruce R. , Ramakrishnan Sundaram 
Published: April 2006

AbstractA human ovarian cancer cell line, which migrates to mouse ovaries and establishes peritoneal carcinomatosis, was used to evaluate the cooperative effect of an antiangiogenic gene therapy combined with chemotherapy. The ovarian carcinoma cell line MA148 was genetically modified by “Sleeping Beauty” transposon-mediated delivery of DsRed2 fluorescent protein. Stable, high-level expression of DsRed protein enabled in vivo imaging of peritoneal dissemination of ovarian cancer. Both external and internal imaging, along with histopathology, showed migration of i.p. injected human ovarian cancer cell line to mouse ovaries. Using this model, we evaluated the effect of adeno-associated virus (AAV)–mediated expression of a mutant endostatin either alone or in combination with carboplatin treatment. A single i.m. injection of recombinant AAV (rAAV)-mutant human endostatin with P125A substitution (P125A-endostatin) showed sustained expression of mutant endostatin. Antiangiogenic gene therapy inhibited orthotopic growth of ovarian cancer and resulted in 33% long-term tumor-free survival. A single cycle of carboplatin treatment combined with mutant endostatin gene therapy resulted in 60% of the animals remaining tumor free for &gt;200 days, which was significantly better than rAAV-LacZ and/or carboplatin. Combination treatment delayed tumor appearance in 40% of the animals, wherein the residual tumors were smaller in size with limited or no peritoneal metastasis. These studies suggest that AAV-mediated gene therapy of P125A-endostatin in combination with carboplatin is a useful method to inhibit peritoneal dissemination of ovarian carcinoma. (Cancer Res 2006; 66(8): 4319-28)
Chronic Exposure to Lead Chromate Causes Centrosome Abnormalities and Aneuploidy in Human Lung Cells
Authors: Holmes Amie L. , Wise Sandra S. , Sandwick Sarah J. , Lingle Wilma L. , Negron Vivian C. , Thompson W. Douglas , Wise John Pierce 
Published: April 2006

Abstract
Hexavalent chromium [Cr(VI)] compounds are established human lung carcinogens. The carcinogenicity of Cr(VI) is related to its solubility, with the most potent carcinogens being the insoluble particulate Cr(VI) compounds. However, it remains unknown why particulate Cr(VI) is more carcinogenic than soluble Cr(VI). One possible explanation is that particulates may provide more chronic exposures to chromate over time. We found that aneuploid cells increased in a concentration- and time-dependent manner after chronic exposure to lead chromate. Specifically, a 24-hour lead chromate exposure induced no aneugenic effect, whereas a 120-hour exposure to 0.5 and 1 μg/cm2 lead chromate induced 55% and 60% aneuploid metaphases, respectively. We also found that many of these aneuploid cells were able to continue to grow and form colonies. Centrosome defects are known to induce aneuploidy; therefore, we investigated the effects of chronic lead chromate exposure on centrosomes. We found that centrosome amplification in interphase and mitotic cells increased in a concentration- and time-dependent manner with 0.5 and 1 μg/cm2 lead chromate for 120 hours, inducing aberrant centrosomes in 18% and 21% of interphase cells and 32% and 69% of mitotic cells, respectively; however, lead oxide did not induce centrosome amplification in interphase or mitotic cells. There was also an increase in aberrant mitosis after chronic exposure to lead chromate with the emergence of disorganized anaphase and mitotic catastrophe. These data suggest that one possible mechanism for lead chromate–induced carcinogenesis is through centrosome dysfunction, leading to the induction of aneuploidy. (Cancer Res 2006; 66(8): 4041-8)
1-Methoxy-Canthin-6-One Induces c-Jun NH2-Terminal Kinase–Dependent Apoptosis and Synergizes with Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Activity in Human Neoplastic Cells of Hematopoietic or Endodermal Origin
Authors: Ammirante Massimo , Di Giacomo Rita , De Martino Laura , Rosati Alessandra , Festa Michela , Gentilella Antonio , Pascale Maria Carmela , Belisario Maria Antonietta , Leone Arturo , Caterina Turco Maria , De Feo Vincenzo 
Published: April 2006

Abstract
We investigated the effects of 1-methoxy-canthin-6-one, isolated from the medicinal plant Ailanthus altissima Swingle, on apoptosis in human leukemia (Jurkat), thyroid carcinoma (ARO and NPA), and hepatocellular carcinoma (HuH7) cell lines. Cultures incubated with the compound showed &gt;50% of sub-G1 (hypodiploid) elements in flow cytometry analysis; the apoptosis-inducing activity was evident at &lt;10 μmol/L and half-maximal at about 40 μmol/L 1-methoxy-canthin-6-one. The appearance of hypodiploid elements was preceded by mitochondrial membrane depolarization, mitochondrial release of cytochrome c, and Smac/DIABLO and procaspase-3 cleavage. We subsequently investigated the effect of 1-methoxy-canthin-6-one in combination with human recombinant tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in the four cell lines. Suboptimal concentrations (10 μmol/L 1-methoxy-canthin-6-one and 0.25 ng/mL TRAIL, respectively) of the two agents, unable to elicit apoptosis when used alone, induced mitochondrial depolarization, activation of caspase-3, and 45% to 85% of sub-G1 elements when added together to the cells. The synergism seemed to rely partly on the enhanced expression of TRAIL receptor 1 (TRAIL-R1; DR4), analyzed by immunofluorescence, by 1-methoxy-canthin-6-one. Cell incubation with 1-methoxy-canthin-6-one resulted in activating c-Jun NH2-terminal kinase (JNK), as revealed by Western blotting; induction of apoptosis and TRAIL-R1 up-regulation by 1-methoxy-canthin-6-one were &gt;80% prevented by the addition of the JNK inhibitor (JNKI) SP600125JNKI, indicating that both effects were almost completely mediated by JNK activity. On the other hand, synergism with TRAIL was reduced by about 50%, suggesting that besides up-regulating TRAIL-R1, 1-methoxy-canthin-6-one could influence other factor(s) that participated in TRAIL-induced apoptosis. These findings indicate that 1-methoxy-canthin-6-one can represent a candidate for in vivo studies of monotherapies or combined antineoplastic therapies. (Cancer Res 2006; 66(8): 4385-93)
Insulin-like Growth Factor I Secreted from Prostate Stromal Cells Mediates Tumor-Stromal Cell Interactions of Prostate Cancer
Authors: Kawada Manabu , Inoue Hiroyuki , Masuda Tohru , Ikeda Daishiro 
Published: April 2006

AbstractProstate cancer shows high expression of type I insulin-like growth factor (IGF-I) receptor (IGF-IR) and prostate stromal cells (PrSC) produce IGF-I. Although high plasma level of IGF-I is a risk factor of prostate cancer, the significance of the prostate stromal IGF-I in the regulation of prostate cancer remains elusive. Here we show that the stromal IGF-I certainly regulates the development of prostate cancer. Coinoculation of PrSC increased the growth of human prostate cancer LNCaP and DU-145 tumors in severe combined immunodeficient mice. The conditioned medium of PrSC, as well as IGF-I, induced phosphorylation of IGF-IR and increased the growth of LNCaP and DU-145 cells. PrSC, but not LNCaP and DU-145 cells, secreted significant amounts of IGF-I. Coculture with PrSC increased the growth of DU-145 cells in vitro but the pretreatment of PrSC with small interfering RNA of IGF-I did not enhance it. Furthermore, various chemical inhibitors consisting of 79 compounds with ∼60 different targets led to the finding that only IGF-IR inhibitor suppressed the PrSC-induced growth enhancement of DU-145 cells. Thus, these results show that the prostate stromal IGF-I mediates tumor-stromal cell interactions of prostate cancer to accelerate tumor growth, supporting the idea that the IGF-I signaling is a valuable target for the treatment of prostate cancer. (Cancer Res 2006; 66(8): 4419-25)
Down-regulation of CXCL5 Inhibits Squamous Carcinogenesis
Authors: Miyazaki Hiroshi , Patel Vyomesh , Wang Huixin , Edmunds Ryan K. , Gutkind J. Silvio , Yeudall W. Andrew 
Published: April 2006

Abstract
We report a novel role for the CXC-chemokine, CXCL5, in the proliferation and invasion of head and neck squamous cell carcinoma (HNSCC). Previously, we reported transcriptional up-regulation of CXCL5 in metastatic cells. In this study, we provide biological validation of these findings and show that CXCL5 is intimately involved in tumor cell proliferation, migration, and invasion. Cells derived from a lymph node metastasis, but not from a synchronous primary tumor, secreted CXCL5 as judged by Western blotting of conditioned media. We used RNA interference to generate cell lines (shL5) in which CXCL5 expression was greatly reduced, and tested whether this modulated the cell phenotype. shL5 cells showed decreased proliferation compared with cells harboring nontargeting control sequences. In addition, we found that the ability of shL5 cells to migrate and invade in vitro through a basement membrane substitute was greatly impaired compared with control cells. Finally, whereas control cells were highly tumorigenic in nude mice, the tumorigenic potential in vivo of shL5 cells was found to be ablated. Taken together, these data suggest that CXCL5 production contributes to both enhanced proliferation and invasion of squamous cell carcinomas and that targeting of chemokine pathways may represent a potential therapeutic modality for these lesions. (Cancer Res 2006; 66(8):4279-84)
Antiangiogenesis and Drug Delivery to Tumors: Bench to Bedside and Back
Authors: Duda Dan G. 
Published: April 2006

Abstract
After over 30 years of preclinical and clinical development, antiangiogenic agents have recently entered the clinic as attractive targeted therapeutics for the treatment of cancer. Fueled by exciting new developments in the field, the AACR Special Conference was designed to broadly survey critical scientific advances in the antiangiogenic therapy of cancer. Because these advances have come primarily with the use of combinations of antiangiogenic agents with chemotherapy, or with antiangiogenic agents that also directly target the cancer cells, the central theme included the issue of drug delivery to tumors. These two major issues were addressed in concert, from basic mechanisms of action of antiangiogenic agents to new combination approaches to cancer treatment. Nearly 300 participants from 20 countries registered for the conference, drawn both from academia and industry, with a wide range in experience and background. Dr. Rakesh Jain, along with conference co-chairs, Drs. Lee Ellis and Luisa Iruela-Arispe, assembled an outstanding lineup of speakers for this conference that included many of the pioneers in the fields of angiogenesis and drug delivery from the U.S. and abroad. This resulted in an excellent overview of the advances in our understanding of cellular and molecular aspects of tumor angiogenesis and antiangiogenic therapy of cancer in combination with conventional therapy. (Cancer Res 2006; 66(8): 3967-70)
Reactivation of Developmentally Expressed p63 Isoforms Predisposes to Tumor Development and Progression
Authors: Koster Maranke I. , Lu Shi-Long , White Lisa D. , Wang Xiao-Jing , Roop Dennis R. 
Published: April 2006

Abstract
Genes that are active during normal development are frequently reactivated during neoplastic transformation. We now report that developmentally expressed TAp63 isoforms are frequently reactivated in human squamous cell carcinomas. To determine the consequences of TAp63 reactivation, we induced TAp63α expression during chemically-induced skin carcinogenesis. Deregulated TAp63α expression dramatically accelerated tumor development and progression, frequently resulting in epithelial-mesenchymal transitions to spindle cell carcinomas and lung metastases. Consistent with this observation, we detected high levels of Twist and N-cadherin in tumors overexpressing TAp63α. Thus, as observed for other developmental pathways, aberrant reactivation of TAp63 predisposes to tumor development and progression. (Cancer Res 2006; 66(8): 3981-6)