bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐Lasting Stability of Vaccinia Virus (Orthopoxvirus) in Food and Environmental Samples
Authors: Essbauer S. , Meyer H. , Porsch‐Özcürümez M. , Pfeffer M. 
Published: May 2007

SummaryPoxviruses are known to remain infectious in the scabs of patients for months to years. The aim of this study was to investigate viral stability in storm water, food or gauze spiked with vaccinia virus strain Munich 1 (VACV M1). Storm water, storm water supplemented with either fetal calf serum (FCS) or potting soil was stored at two different temperatures (refrigerator, room temperature; 4°C/25°C). In addition, we analysed the viability of VACV M1 on the surface of bread, salad, sausages and gauze bandages stored at 4°C. Samples were titrated in MA 104 cells and the presence of viral DNA was demonstrated by orthopoxvirus‐specific PCRs. After 2 weeks, reisolation of VACV M1 from all kinds of food, bandage and water samples except for storm water supplemented with potting soil was possible. Viral DNA was detected in almost all samples by PCR. Prolonged experiments with VACV M1‐spiked storm water and storm water supplemented with FCS revealed that samples kept at 4.5°C are infectious for up to 166 days. Our data demonstrate that VACV M1 has a longlasting stability in water and food. The results obtained during this study should be taken into account for risk assessment calculations for poxvirus transmission. Implying that variola virus and vaccinia virus behave in a similar way, our data call for sophisticated countermeasures in cases of a variola release in biological warfare.
Chromium Reactions and Transport in Solid Oxide Fuel Cells
Authors: Cruse Terry A. , Ingram Brian J. , Liu Di-Jia , Krumpelt Michael 
Published: May 2007

With solid oxide fuel cells operating at 800{degree sign}C or lower, metal alloy bipolar plates (interconnects) offer a number of advantages over ceramic interconnects.	However, these alloys rely on the formation of a protective chromium based scale, either chromia or a manganese chromium spinel.	As metallic bipolar plates have been explored, and used, over the last decade, a number of interactions have been observed between the bipolar plate and various cathode materials. This paper examines the interactions between E-Brite® and an LSM/YSZ composite active cathode. Tests examined direct contact of the E-Brite® with the cathode, and the effect of using gold foil as a physical barrier so only gas phase interactions were possible. Additionally, key observations on test fixture design and materials selection are discussed, which may shed light on why different researchers have observed a wide range of fuel cell degradation rates.
The Response of Hydrogen Sensor to Environment
Authors: Hu Cheng , Sun Colin , Shen Jun , Fan Lilian , Holland Robert M. , Kambo Perminder , Wong Darryl K. , Ng Chi W. , Comeault Chad , Chisholm John 
Published: May 2007

In many hydrogen sensor applications, the ambient environment applies effects on sensor response. Some environmental parameters may cause significant function changes in sensor performance. These parameters include temperature, humidity, pressure and gas flow rate, among others. Calibration and compensation for these effects are thus needed to acquire meaningful and accurate results from sensor measurements. In this report, a custom-designed hydrogen sensor test station is described. The test station provides simultaneous and accurate control of gas composition, gas flow rate, temperature, humidity and pressure.	The test procedures were designed to examine sensor response to the changes of these parameters. A number of hydrogen sensors of various types had been tested in a series of testing processes. The general behavior of these gas sensors was studied and gave a brief overview of hydrogen sensors in present market.
The High-Mobility Group A1 Gene Up-Regulates Cyclooxygenase 2 Expression in Uterine Tumorigenesis
Authors: Tesfaye Abeba , Di Cello Francescopaolo , Hillion Joelle , Ronnett Brigitte M. , Elbahloul Ossama , Ashfaq Raheela , Dhara Surajit , Prochownik Edward , Tworkoski Kathryn , Reeves Raymond , Roden Richard , Ellenson Lora Hedrick , Huso David L. , Resar Linda M. S. 
Published: May 2007

Abstract
Uterine cancer is the most common cancer of the female genital tract and is the fourth most frequent cause of cancer death in women in the U.S. Despite the high prevalence of uterine cancers, the molecular events that lead to neoplastic transformation in the uterus are poorly understood. Moreover, there are limited mouse models to study these malignancies. We generated transgenic mice with high-mobility group A1 gene (HMGA1a) expression targeted to uterine tissue and all female mice developed tumors by 9 months of age. Histopathologically, the tumors resemble human uterine adenosarcoma and are transplantable. To determine whether these findings are relevant to human disease, we evaluated primary human uterine neoplasms and found that HMGA1a mRNA and protein levels are increased in most high-grade neoplasms but not in normal uterine tissue, benign tumors, or most low-grade neoplasms. We also found that HMGA1a up-regulates cyclooxygenase 2 (COX-2) expression in transgenic tumors. Moreover, both HMGA1a and COX-2 expression are up-regulated in high-grade human leiomyosarcomas. Using chromatin immunoprecipitation, HMGA1a binds directly to the COX-2 promoter in human uterine cancer cells in vivo and activates its expression in transfection experiments. We also show that blocking either HMGA1a or COX-2 in high-grade human uterine cancer cells blocks anchorage-independent cell growth in methylcellulose. These findings show that HMGA1a functions as an oncogene when overexpressed in the uterus and contributes to the pathogenesis of human uterine cancer by activating COX-2 expression. Although a larger study is needed to confirm these results, HMGA1a may be a useful marker for aggressive human uterine cancers. [Cancer Res 2007;67(9):3998–4004]
p38 Mitogen-Activated Protein Kinase Pathway Is Involved in Protein Kinase Cα–Regulated Invasion in Human Hepatocellular Carcinoma Cells
Authors: Hsieh Yi-Hsien , Wu Trang-Tiau , Huang Chih-Yang , Hsieh Yih-Shou , Hwang Jin-Ming , Liu Jer-Yuh 
Published: May 2007

Abstract
Protein kinase Cα (PKCα) has been suggested to play an important role in tumorigenesis, invasion, and metastasis. In this study, we investigated the signal pathways selectively activated by PKCα in human hepatocellular carcinoma (HCC) cells to determine the role of mitogen-activated protein kinases (MAPK) in PKCα-mediated HCC migration and invasion. A stable SK-Hep-1 cell clone (siPKCα-SK) expressing DNA-based small interfering RNA (siRNA) PKCα was established and was then characterized by cell growth, migration, and invasion. The expression of PKCα was decreased in siPKCα-SK, and cell growth, migration, and invasion were reduced. These changes were associated with the decrease in p38 MAPK phosphorylation level, but not in c-jun-NH2-kinase-1/2 (JNK-1/2) and extracellular signal-regulated kinase-1/2 (ERK-1/2). This phenomenon was confirmed in the SK-Hep-1 cells treated with antisense PKCα olignucleotide. The p38 MAPK inhibitor SB203580 or dominant negative p38 mutant plasmid (DN-p38) was used to evaluate the dependency of p38 MAPK in PKCα-regulated migration and invasion. Attenuation of cell migration and invasion was revealed in the SK-Hep-1 cells treated with the SB203580 or DN-p38, but not with ERK-1/2 inhibitor PD98059 or JNK-1/2 inhibitor SP600125. Overexpression of constitutively active MKK6 or PKCα may restore the inactivation of p38 and the attenuation of cell migration and invasion in siPKCα-SK. Similar findings were observed in the stable HA22T/VGH cell clone expressing siRNA PKCα. This study provides new insight into the role of p38 MAPK in PKCα-mediated malignant phenotypes, especially in PKCα-mediated cancer cell invasion, which may have valuable implications for developing new therapies for some PKCα-overexpressing cancers. [Cancer Res 2007;67(9):4320–7]
Transgenic E2F1 Expression in the Mouse Brain Induces a Human-Like Bimodal Pattern of Tumors
Authors: Olson Melissa V. , Johnson David G. , Jiang Hong , Xu Jing , Alonso Marta M. , Aldape Kenneth D. , Fuller Gregory N. , Bekele B. Nebiyou , Yung W.K. Alfred , Gomez-Manzano Candelaria , Fueyo Juan 
Published: May 2007

Abstract
The Rb/E2F pathway is deregulated in most human brain tumors, and the finding that loss of E2F1 reduced pituitary tumorigenesis in Rb+/− mice suggests that loss of pRb induces brain tumors by activating E2F1. We therefore investigated the role of E2F1 in the development and maintenance of brain cancer using a transgenic mouse model engineered to express E2F1 specifically within glial cells (GFAP-tgE2F1). GFAP-tgE2F1 mice developed a highly penetrant phenotype characterized by neurologic defects, and examination of the brains revealed the presence of brain tumors in 20% of these animals. Importantly, the distribution of tumors according to mouse age suggests the existence of a bimodal pattern of tumor development, forcing a comparison with the human disease. Mice, at an early age, with deregulated E2F1 show the formation of embryonal brain tumors such as medulloblastoma, choroid plexus carcinoma, and primary neuroectodermal tumor. Conversely, at an older age, mice escaping embryonal tumor formation present with malignant gliomas, which are typically identified in the human adult population. Thus, this study offers the first evidence for a global role of E2F1 in the formation and maintenance of multilineage brain tumors, irrefutably establishing E2F1 as an oncogene in the brain. [Cancer Res 2007;67(9):4005–9]
A Coregulatory Role for the Mediator Complex in Prostate Cancer Cell Proliferation and Gene Expression
Authors: Vijayvargia Ravi , May Michael S. , Fondell Joseph D. 
Published: May 2007

Abstract
Androgen receptor (AR) signaling pathways are important for the survival and proliferation of prostate cancer cells. Because AR activity is facilitated by distinct coregulatory factors and complexes, it is conceivable that some of these proteins might also play a role in promoting prostate oncogenesis. The multisubunit Mediator complex is an important coactivator for a broad range of regulatory transcriptional factors including AR, yet its role in prostate cancer is unclear. Here, we used RNA interference to knock down the expression of two integral Mediator components, MED1/TRAP220 and MED17, in prostate cancer cells. MED1/TRAP220 plays a particularly important role in androgen signaling in that it serves as a direct binding target for AR. We found that the knockdown of either subunit markedly decreases transcription from transiently transfected androgen-responsive reporter genes, as well as inhibits androgen-dependent expression of endogenous AR target genes. We show for the first time that loss of either MED1/TRAP220 or MED17 in prostate cancer cells significantly decreases both androgen-dependent and -independent cellular proliferation, inhibits cell cycle progression, and increases apoptosis. Furthermore, we show that MED1/TRAP220 is overexpressed in both AR-positive and -negative prostate cancer cells lines, as well as in 50% (10 of 20) of the clinically localized human prostate cancers we examined, thus suggesting that MED1/TRAP220 hyperactivity may have implications in prostate oncogenesis. In sum, our data suggest that Mediator plays an important coregulatory role in prostate cancer cell proliferation and survival, and therefore, may represent a new target for therapeutic intervention. [Cancer Res 2007;67(9):4034–41]
Oligomerization Domain of the Multidrug Resistance–Associated Transporter ABCG2 and Its Dominant Inhibitory Activity
Authors: Xu Junkang , Peng Hui , Chen Qun , Liu Yang , Dong Zizheng , Zhang Jian-Ting 
Published: May 2007

Abstract
Overexpression of human ATP-binding cassette transporter ABCG2 in cancer cells causes multidrug resistance by effluxing anticancer drugs. ABCG2 is considered as a half transporter and is thought to function as a homodimer. However, recent evidence suggests that it may exist as a higher form of oligomer consisting of 12 subunits. In this study, we mapped the oligomerization domain of human ABCG2 to its transmembrane domain consisting of TM5-loop-TM6. This oligomerization domain, when expressed alone in HEK293 cells, also forms a homododecamer. Furthermore, this domain has activity that inhibits drug efflux and resistance function of the full-length ABCG2 likely by disrupting the formation of the homo-oligomeric full-length ABCG2. These findings suggest that human ABCG2 may exist and work as a homo-oligomer by interactions located in TM5-loop-TM6, and that ABCG2 oligomerization may be used as a target for therapeutic development to circumvent ABCG2-mediated drug resistance in cancer treatment. [Cancer Res 2007;67(9)4373:–81]
Her-2 Overexpression Increases the Metastatic Outgrowth of Breast Cancer Cells in the Brain
Authors: Palmieri Diane , Bronder Julie L. , Herring Jeanne M. , Yoneda Toshiyuki , Weil Robert J. , Stark Andreas M. , Kurek Raffael , Vega-Valle Eleazar , Feigenbaum Lionel , Halverson Douglas , Vortmeyer Alexander O. , Steinberg Seth M. , Aldape Kenneth , Steeg Patricia S. 
Published: May 2007

Abstract
Retrospective studies of breast cancer patients suggest that primary tumor Her-2 overexpression or trastuzumab therapy is associated with a devastating complication: the development of central nervous system (brain) metastases. Herein, we present Her-2 expression trends from resected human brain metastases and data from an experimental brain metastasis assay, both indicative of a functional contribution of Her-2 to brain metastatic colonization. Of 124 archival resected brain metastases from breast cancer patients, 36.2% overexpressed Her-2, indicating an enrichment in the frequency of tumor Her-2 overexpression at this metastatic site. Using quantitative real-time PCR of laser capture microdissected epithelial cells, Her-2 and epidermal growth factor receptor (EGFR) mRNA levels in a cohort of 12 frozen brain metastases were increased up to 5- and 9-fold, respectively, over those of Her-2–amplified primary tumors. Co-overexpression of Her-2 and EGFR was also observed in a subset of brain metastases. We then tested the hypothesis that overexpression of Her-2 increases the colonization of breast cancer cells in the brain in vivo. A subclone of MDA-MB-231 human breast carcinoma cells that selectively metastasizes to brain (231-BR) overexpressed EGFR; 231-BR cells were transfected with low (4- to 8-fold) or high (22- to 28-fold) levels of Her-2. In vivo, in a model of brain metastasis, low or high Her-2–overexpressing 231-BR clones produced comparable numbers of micrometastases in the brain as control transfectants; however, the Her-2 transfectants yielded 3-fold greater large metastases (&gt;50 μm2; P &lt; 0.001). Our data indicate that Her-2 overexpression increases the outgrowth of metastatic tumor cells in the brain in this model system. [Cancer Res 2007;67(9):4190–8]
Phosphatase and Tensin Homologue Deficiency in Glioblastoma Confers Resistance to Radiation and Temozolomide that Is Reversed by the Protease Inhibitor Nelfinavir
Authors: Jiang Zibin , Pore Nabendu , Cerniglia George J. , Mick Rosemarie , Georgescu Maria-Magdelena , Bernhard Eric J. , Hahn Stephen M. , Gupta Anjali K. , Maity Amit 
Published: May 2007

Abstract
Glioblastomas are malignant brain tumors that are very difficult to cure, even with aggressive therapy consisting of surgery, chemotherapy, and radiation. Glioblastomas frequently have loss of the phosphatase and tensin homologue (PTEN), leading to the activation of the phosphoinositide-3-kinase (PI3K)/Akt pathway. We examined whether PTEN deficiency leads to radioresistance and whether this can be reversed by nelfinavir, a protease inhibitor that decreases Akt signaling. Nelfinavir decreased Akt phosphorylation and enhanced radiosensitization in U251MG and U87MG glioblastoma cells, both of which are PTEN deficient. In the derivative line U251MG-PTEN, induction of wild-type PTEN with doxycycline decreased P-Akt expression and increased radiosensitivity to a similar extent as nelfinavir. Combining these two approaches had no greater effect on radiosensitivity than either alone. This epistasis-type analysis suggests that the nelfinavir acts along the Akt pathway to radiosensitize cells. However, nelfinavir neither decreased Akt phosphorylation in immortalized human astrocytes nor radiosensitized them. Radiosensitization was also assessed in vivo using a tumor regrowth delay assay in nude mice implanted with U87MG xenografts. The mean time to reach 1,000 mm3 in the radiation + nelfinavir group was 71 days, as compared with 41, 34, or 45 days for control, nelfinavir alone, or radiation alone groups, respectively. A significant synergistic effect on tumor regrowth was detected between radiation and nelfinavir. (P = 0.01). Nelfinavir also increased the sensitivity of U251MG cells to temozolomide. These results support the clinical investigation of nelfinavir in combination with radiation and temozolomide in future clinical trials for patients with glioblastomas. [Cancer Res 2007;67(9):4467–72]
MHC Class II–Transduced Tumor Cells Originating in the Immune-Privileged Eye Prime and Boost CD4+ T Lymphocytes that Cross-react with Primary and Metastatic Uveal Melanoma Cells
Authors: Bosch Jacobus J. , Thompson James A. , Srivastava Minu K. , Iheagwara Uzoma K. , Murray Timothy G. , Lotem Michal , Ksander Bruce R. , Ostrand-Rosenberg Suzanne 
Published: May 2007

AbstractUveal melanoma, the most common malignancy of the eye, has a 50% rate of liver metastases among patients with large primary tumors. Several therapies prolong survival of metastatic patients; however, none are curative and no patients survive. Therefore, we are exploring immunotherapy as an alternative or adjunctive treatment. Uveal melanoma may be particularly appropriate for immunotherapy because primary tumors arise in an immune-privileged site and may express antigens to which the host is not tolerized. We are developing MHC class II (MHC II)–matched allogeneic, cell-based uveal melanoma vaccines that activate CD4+ T lymphocytes, which are key cells for optimizing CD8+ T-cell immunity, facilitating immune memory, and preventing tolerance. Our previous studies showed that tumor cells genetically modified to express costimulatory and MHC II molecules syngeneic to the recipient are potent inducers of antitumor immunity. Because the MHC II–matched allogeneic vaccines do not express the accessory molecule, Invariant chain, they present MHC II–restricted peptides derived from endogenously encoded tumor antigens. We now report that MHC II–matched allogeneic vaccines, prepared from primary uveal melanomas that arise in the immune-privileged eye, prime and boost IFNγ-secreting CD4+ T cells from the peripheral blood of either healthy donors or uveal melanoma patients that cross-react with primary uveal melanomas from other patients and metastatic tumors. In contrast, vaccines prepared from metastatic cells in the liver are less effective at activating CD4+ T cells, suggesting that tumor cells originating in immune-privileged sites may have enhanced capacity for inducing antitumor immunity and for serving as immunotherapeutic agents. [Cancer Res 2007;67(9):4499–506]
DNA Double-Strand Breaks Form in Bystander Cells after Microbeam Irradiation of Three-dimensional Human Tissue Models
Authors: Sedelnikova Olga A. , Nakamura Asako , Kovalchuk Olga , Koturbash Igor , Mitchell Stephen A. , Marino Stephen A. , Brenner David J. , Bonner William M. 
Published: May 2007

AbstractThe “radiation-induced bystander effect,” in which irradiated cells can induce genomic instability in unirradiated neighboring cells, has important implications for cancer radiotherapy and diagnostic radiology as well as for human health in general. Although the mechanisms of this effect remain to be elucidated, we reported previously that DNA double-strand breaks (DSBs), directly measured by γ-H2AX focus formation assay, are induced in bystander cultured cells. To overcome the deficiencies of cultured cell studies, we examined α-particle microbeam irradiation–induced bystander effects in human tissue models, which preserve the three-dimensional geometric arrangement and communication of cells present in tissues in vivo. In marked contrast to DNA DSB dynamics in irradiated cells, in which maximal DSB formation is seen 30 min after irradiation, the incidence of DSBs in bystander cells reached a maximum by 12 to 48 h after irradiation, gradually decreasing over the 7-day time course. At the maxima, 40% to 60% of bystander cells were affected, a 4- to 6-fold increase over controls. These increases in bystander DSB formation were followed by increased levels of apoptosis and micronucleus formation, by loss of nuclear DNA methylation, and by an increased fraction of senescent cells. These findings show the involvement of DNA DSBs in tissue bystander responses and support the notion that bystander DNA DSBs are precursors to widespread downstream effects in human tissues. Bystander cells exhibiting postirradiation signs of genomic instability may be more prone than unaffected cells to become cancerous. Thus, this study points to the importance of considering the indirect biological effects of radiation in cancer risk assessment. [Cancer Res 2007;67(9):4295–302]
Identification of Novel Amplification Gene Targets in Mouse and Human Breast Cancer at a Syntenic Cluster Mapping to Mouse ch8A1 and Human ch13q34
Authors: Abba Martin C. , Fabris Victoria T. , Hu Yuhui , Kittrell Frances S. , Cai Wei-Wen , Donehower Lawrence A. , Sahin Aysegul , Medina Daniel , Aldaz C. Marcelo 
Published: May 2007

Abstract
Serial analysis of gene expression from aggressive mammary tumors derived from transplantable p53 null mouse mammary outgrowth lines revealed significant up-regulation of Tfdp1 (transcription factor Dp1), Lamp1 (lysosomal membrane glycoprotein 1) and Gas6 (growth arrest specific 6) transcripts. All of these genes belong to the same linkage cluster, mapping to mouse chromosome band 8A1. BAC-array comparative genomic hybridization and fluorescence in situ hybridization analyses revealed genomic amplification at mouse region ch8A1.1. The minimal region of amplification contained genes Cul4a, Lamp1, Tfdp1, and Gas6, highly overexpressed in the p53 null mammary outgrowth lines at preneoplastic stages, and in all its derived tumors. The same amplification was also observed in spontaneous p53 null mammary tumors. Interestingly, this region is homologous to human chromosome 13q34, and some of the same genes were previously observed amplified in human carcinomas. Thus, we further investigated the occurrence and frequency of gene amplification affecting genes mapping to ch13q34 in human breast cancer. TFDP1 showed the highest frequency of amplification affecting 31% of 74 breast carcinomas analyzed. Statistically significant positive correlation was observed for the amplification of CUL4A, LAMP1, TFDP1, and GAS6 genes (P &lt; 0.001). Meta-analysis of publicly available gene expression data sets showed a strong association between the high expression of TFDP1 and decreased overall survival (P = 0.00004), relapse-free survival (P = 0.0119), and metastasis-free interval (P = 0.0064). In conclusion, our findings suggest that CUL4A, LAMP1, TFDP1, and GAS6 are targets for overexpression and amplification in breast cancers. Therefore, overexpression of these genes and, in particular, TFDP1 might be of relevance in the development and/or progression in a significant subset of human breast carcinomas. [Cancer Res 2007;67(9):4104–12]