bluuebunny/crossref_metadata_2025_split huggingface dataset:
DJ-1 Binds Androgen Receptor Directly and Mediates Its Activity in Hormonally Treated Prostate Cancer Cells
Authors: Tillman J. Erin , Yuan Jialing , Gu Guangyu , Fazli Ladan , Ghosh Ritwik , Flynt Alex S. , Gleave Martin , Rennie Paul S. , Kasper Susan 
Published: May 2007

Abstract
The oncogene DJ-1 has been associated with multiple cancers, including prostate cancer, where it can be stabilized by androgens and antiandrogens. However, little data exist on the expression pattern and function of DJ-1 in prostate cancer. To address the function of DJ-1 in prostate, a yeast two-hybrid screen was done to identify novel DJ-1 binding proteins. The androgen receptor (AR) was identified and confirmed as a DJ-1 binding partner. This is the first evidence that DJ-1 directly interacts with AR. We also show that modulation of DJ-1 expression regulated AR transcriptional activity. Importantly, both the subcellular localization of DJ-1 and the interaction with AR are regulated by androgens and antiandrogens. Additionally, immunohistochemical staining on two human prostate cancer tissue arrays was done providing the first large-scale expression analysis of DJ-1 in prostate. DJ-1 expression did not change with Gleason pattern but increased after androgen deprivation therapy, indicating that it may be involved in the development of androgen independence. These data provide a novel mechanism where DJ-1–mediated regulation of AR may promote the progression of prostate cancer to androgen independence. [Cancer Res 2007;67(10):4630–7]
Prostate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor In vivo
Authors: Gu Guangyu , Yuan Jialing , Wills Marcia , Kasper Susan 
Published: May 2007

Abstract
Cancer may arise from a cancer stem/progenitor cell that shares characteristics with its normal counterpart. We report the reconstitution of the original human prostate cancer specimen from epithelial cell lines (termed HPET for human prostate epithelial/hTERT) derived from this sample. These tumors can be described in terms of Gleason score, a classification not applied to any of the transgenic mouse models currently developed to mimic human disease. Immunohistochemical and Western blot analyses indicate that they do not express androgen receptor or p63, similar to that reported for prostate stem cells. These cell lines also express embryonic stem markers (Oct4, Nanog, and Sox2) as well as early progenitor cell markers (CD44 and Nestin) in vitro. Clonally derived HPET cells reconstitute the original human tumor in vivo and differentiate into the three prostate epithelial cell lineages, indicating that they arise from a common stem/progenitor cell. Serial transplantation experiments reconstitute the tumors, suggesting that a fraction of parental or clonally derived HPET cells have self-renewal potential. Thus, this model may enhance our understanding of human tumor development and provide a mechanism for studying cancer stem/progenitor cells in differentiation, tumorigenesis, preclinical testing, and the development of drug resistance. [Cancer Res 2007;67(10):4807–15]
von Hippel-Lindau: A Tumor Suppressor Links Microtubules to Ciliogenesis and Cancer Development
Authors: Kuehn E. Wolfgang , Walz Gerd , Benzing Thomas 
Published: May 2007

Abstract
Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial and most sporadic renal cell carcinoma. The tumor suppressor role of the protein pVHL is based on its ability to target transcription factors of the hypoxia-inducible factor family for degradation, but other functions of pVHL are less clearly defined. New findings show that pVHL is necessary for cilia formation. pVHL interacts with PAR proteins, a complex that specifies the membrane domains of polarized epithelial cells, and directs the orientation of growing microtubules. Loss of pVHL results in aberrant orientation of newly formed microtubules and prevents ciliogenesis. These results add to a growing body of evidence linking cilia and the cell cycle and suggest that the tumor suppressor role of pVHL may involve previously unrecognized pathways. [Cancer Res 2007;67(10):4537–40]
Phase I Trial of Weekly Paclitaxel and BMS-214662 in Patients with Advanced Solid Tumors
Authors: Bailey Howard H. , Alberti Dona B. , Thomas James P. , Mulkerin Daniel L. , Binger Kimberly A. , Gottardis Marco M. , Martell Robert E. , Wilding George 
Published: May 2007

Abstract
Purpose: To assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacodynamics, and antitumor activity of continuous weekly-administered paclitaxel and BMS-214662, a novel farnesyl transferase inhibitor.
Experimental Design: Patients were treated every week as tolerated with i.v. paclitaxel (fixed dose, 80 mg/m2/wk) administered over 1 h followed by i.v. BMS-214662 (escalating doses, 80–245 mg/m2/wk) over 1 h starting 30 min after completion of paclitaxel.
Results: Twenty-six patients received 94 courses (one course, 21 days) of study treatment. Two patients received five courses of BMS-214662 as a weekly 24-h infusion (209 mg/m2/wk). The most common toxicities were grade 1 to 2 nausea/vomiting and/or diarrhea. DLTs observed at or near the MTD (200 mg/m2/wk) were grade 4 febrile neutropenia with sepsis occurring on day 2 of course 1 (245 mg/m2/wk), reversible grade 3 to 4 serum transaminase increases on day 2, and grade 3 diarrhea (200 and 245 mg/m2/wk). Objective partial responses were observed in patients with pretreated head and neck, ovarian, and hormone-refractory prostate carcinomas, and leiomyosarcoma. The observed pharmacokinetics of paclitaxel and BMS-214662 imply no interaction between the two. Significant inhibition (&gt;80%) of farnesyl transferase activity in peripheral mononuclear cells was observed at the end of BMS-214662 infusion.
Conclusions: Pretreated patients with advanced malignancies can tolerate weekly paclitaxel and BMS-214662 at doses that achieve objective clinical benefit. Due to multiple DLTs occurring at the expanded MTD, the recommended phase 2 dose and schedule is paclitaxel (80 mg/m2 over 1 h) and BMS-214662 (160 mg/m2 over 1 h) administered weekly.
Phase I and Pharmacokinetic Study of Vorinostat, A Histone Deacetylase Inhibitor, in Combination with Carboplatin and Paclitaxel for Advanced Solid Malignancies
Authors: Ramalingam Suresh S. , Parise Robert A. , Ramananthan Ramesh K. , Lagattuta Theodore F. , Musguire Lori A. , Stoller Ronald G. , Potter Douglas M. , Argiris Athanassios E. , Zwiebel James A. , Egorin Merrill J. , Belani Chandra P. 
Published: May 2007

Abstract
Purpose: The primary objective of this study was to determine the recommended phase II doses of the novel histone deacetylase inhibitor vorinostat when administered in combination with carboplatin and paclitaxel.
Experimental Design: Patients (N = 28) with advanced solid malignancies were treated with vorinostat, administered orally once daily for 2 weeks or twice daily for 1 week, every 3 weeks. Carboplatin and paclitaxel were administered i.v. once every 3 weeks. Doses of vorinostat and paclitaxel were escalated in sequential cohorts of three patients. The pharmacokinetics of vorinostat, its metabolites, and paclitaxel were characterized.
Results: Vorinostat was administered safely up to 400 mg qd or 300 mg bd with carboplatin and paclitaxel. Two of 12 patients at the 400 mg qd schedule experienced dose-limiting toxicities of grade 3 emesis and grade 4 neutropenia with fever. Non–dose-limiting toxicity included nausea, diarrhea, fatigue, neuropathy, thrombocytopenia, and anemia. Of 25 patients evaluable for response, partial responses occurred in 11 (10 non–small cell lung cancer and 1 head and neck cancer) and stable disease occurred in 7. Vorinostat pharmacokinetics were linear over the dose range studied. Vorinostat area under the concentration versus time curve and half-life increased when vorinostat was coadministered with carboplatin and paclitaxel, but vorinostat did not alter paclitaxel pharmacokinetics.
Conclusions: Both schedules of vorinostat (400 mg oral qd × 14 days or 300 mg bd × 7 days) were tolerated well in combination with carboplatin (area under the concentration versus time curve = 6 mg/mL × min) and paclitaxel (200 mg/m2). Encouraging anticancer activity was noted in patients with previously untreated non–small cell lung cancer.
CYP26 Inhibitor R115866 Increases Retinoid Signaling in Intimal Smooth Muscle Cells
Authors: Ocaya Pauline , Gidlöf Andreas C. , Olofsson Peder S. , Törmä Hans , Sirsjö Allan 
Published: May 2007

Objective—Intimal smooth muscle cells (SMCs) are dedifferentiated SMCs that have a powerful ability to proliferate and migrate. This cell-type is responsible for the development of intimal hyperplasia after vascular angioplasty. Retinoids, especially all-trans retinoid acid, are known to regulate many processes activated at sites of vascular injury, including modulation of SMC phenotype and inhibition of SMC proliferation. Intracellular levels of active retinoids are under firm control. A key enzyme is the all-trans retinoic acid-degrading enzyme cytochrome p450 isoform 26 (CYP26). Thus, an alternative approach to exogenous retinoid administration could be to increase the intracellular level of all-trans retinoic acid by blocking CYP26-mediated degradation of retinoids.Methods and Results—Vascular intimal and medial SMCs expressed CYP26A1 and B1 mRNA. Although medial cells remained unaffected, treatment with the CYP26-inhibitor R115866 significantly increased cellular levels of all-trans retinoic acid in intimal SMCs. The increased levels of all-trans retinoic acid induced retinoid-regulated genes and decreased mitogenesis.Conclusions—Blocking of the CYP26-mediated catabolism mimics the effects of exogenously administrated active retinoids on intimal SMCs. Therefore, CYP26-inibitors offer a potential new therapeutic approach to vascular proliferative disorders.
Direct Correlation Between Ischemic Injury and Extracellular Glycine Concentration in Mice With Genetically Altered Activities of the Glycine Cleavage Multienzyme System
Authors: Oda Masaya , Kure Shigeo , Sugawara Taku , Yamaguchi Suguru , Kojima Kanako , Shinka Toshikatsu , Sato Kenichi , Narisawa Ayumi , Aoki Yoko , Matsubara Yoichi , Omae Tomoya , Mizoi Kazuo , Kinouchi Hiroyuki 
Published: May 2007

Background and Purpose—Ischemia elicits the rapid release of various amino acid neurotransmitters. A glutamate surge activatesN-methyl-d-aspartate (NMDA) glutamate receptors, triggering deleterious processes in neurons. Although glycine is a coagonist of the NMDA receptor, the effect of extracellular glycine concentration on ischemic injury remains controversial. To approach this issue, we examined ischemic injury in mice with genetically altered activities of the glycine cleavage multienzyme system (GCS), which plays a fundamental role in maintaining extracellular glycine concentration.Methods—A mouse line with increased GCS activity (340% of C57BL/6 control mice) was generated by transgenic expression of glycine decarboxylase, a key GCS component (high-GCS mice). Another mouse line with reduced GCS activity (29% of controls) was established by transgenic expression of a dominant-negative mutant of glycine decarboxylase (low-GCS mice). We examined neuronal injury after transient occlusion of the middle cerebral artery in these mice by measuring extracellular amino acid concentrations in microdialysates.Results—High-GCS and low-GCS mice had significantly lower and higher basal concentrations of extracellular glycine than did controls, respectively. In low-GCS mice, the extracellular glycine concentration reached 2-fold of control levels during ischemia, and infarct volume was significantly increased by 69% with respect to controls. In contrast, high-GCS mice had a significantly smaller infarct volume (by 21%). No significant difference was observed in extracellular glutamate concentrations throughout the experiments. An antagonist for the NMDA glycine site, SM-31900, attenuated infarct size, suggesting that glycine operated via the NMDA receptor.Conclusions—There is a direct correlation between ischemic injury and extracellular glycine concentration maintained by the GCS.
Comparative Analysis of the Western Arctic Surface Climate among Observations and Model Simulations
Authors: Wu Wanli , Lynch Amanda H. , Drobot Sheldon , Maslanik James , McGuire A. David , Herzfeld Ute 
Published: May 2007

Abstract
Accurate estimates of the spatial and temporal variation in terrestrial water and energy fluxes and mean states are important for simulating regional hydrology and biogeochemistry in high-latitude regions. Furthermore, it is necessary to develop high-resolution hydroclimatological datasets at finer spatial resolutions than are currently available from global analyses. This study uses a regional climate model (RCM) to develop a hydroclimatological dataset for hydrologic and ecological application in the Western Arctic. The fifth-generation Penn State–NCAR Mesoscale Model (MM5) forced by global reanalysis products at the boundaries is used to perform 12 yr of simulation (1990 through 2001) over the Western Arctic. An analysis that compares the RCM simulations with independent observationally derived data sources is conducted to evaluate the temporal and spatial distribution of the mean states, variability, and trends during the period of simulation. The RCM simulation of sea level pressure agrees well with the reanalysis in terms of mean states, seasonality, and interannual variability. The RCM also simulates major spatial patterns of the observed climatology of surface air temperature (SAT), but RCM SAT is generally colder in the summertime and warmer in the wintertime in comparison with other datasets. Although there are biases in the mean state of SAT, the RCM simulations of the seasonal and interannual variability of SAT are similar to variability in observationally derived datasets. The RCM also simulates general spatial patterns of observed rainfall, but the modeled mean state of precipitation is characterized by large biases relative to observationally derived datasets. In particular, the RCM tends to overestimate coastal region precipitation but underestimates precipitation in the interior of the Western Arctic. The Arctic terrestrial surface climate trends for the period of 1992 to 2001 of the RCM are similar to those derived from observations, with sea level pressure decreasing 0.15 hPa decade−1, SAT increasing 0.10°C decade−1, and precipitation decreasing slightly in the RCM simulations. In summary, the RCM dataset produced in this study represents an improvement over data currently available from large-scale global reanalysis and provides a consistent meteorological forcing dataset for hydrologic and ecological applications.
Hot spots of retroviral integration in human CD34+ hematopoietic cells
Authors: Cattoglio Claudia , Facchini Giulia , Sartori Daniela , Antonelli Antonella , Miccio Annarita , Cassani Barbara , Schmidt Manfred , von Kalle Christof , Howe Steve , Thrasher Adrian J. , Aiuti Alessandro , Ferrari Giuliana , Recchia Alessandra , Mavilio Fulvio 
Published: May 2007

Abstract
Insertional oncogenesis is a possible consequence of the integration of gamma-retroviral (RV) or lentiviral (LV) vectors into the human genome. RV common insertion sites (CISs) have been identified in hematopoietic malignancies and in the nonmalignant progeny of transduced hematopoietic stem/progenitor cells (HSCs), possibly as a consequence of clonal selection in vivo. We have mapped a large number of RV and LV integrations in human CD34+ HSCs, transduced in vitro and analyzed without selection. Recurrent insertion sites (hot spots) account for more than 21% of the RV integration events, while they are significantly less frequent in the case of LV vectors. RV but not LV hot spots are highly enriched in proto-oncogenes, cancer-associated CISs, and growth-controlling genes, indicating that at least part of the biases observed in the HSC progeny in vivo are characteristics of RV integration, already present in nontransplanted cells. Genes involved in hematopoietic and immune system development are targeted at high frequency and enriched in hot spots, suggesting that the CD34+ gene expression program is instrumental in directing RV integration. The lower propensity of LV vectors for integrating in potentially dangerous regions of the human genome may be a factor determining a better safety profile for gene therapy applications.
Adenoviral vectors persist in vivo and maintain activated CD8+ T cells: implications for their use as vaccines
Authors: Tatsis Nia , Fitzgerald Julie C. , Reyes-Sandoval Arturo , Harris-McCoy Kimberly C. , Hensley Scott E. , Zhou Dongming , Lin Shih-Wen , Bian Ang , Xiang Zhi Quan , Iparraguirre Amaya , Lopez-Camacho Cesar , Wherry E. John , Ertl Hildegund C. J. 
Published: May 2007

AbstractCD8+ T cell-numbers rapidly expand and then contract after exposure to their cognate antigen. Here we show that the sustained frequencies of transgene product-specific CD8+ T cells elicited by replication-defective adenovirus vectors are linked to persistence of low levels of transcriptionally active adenovirus vector genomes at the site of inoculation, in liver, and lymphatic tissues. Continuously produced small amounts of antigen maintain fully active effector CD8+ T cells, while also allowing for their differentiation into central memory cells. The long-term persistence of adenoviral vectors may be highly advantageous for their use as vaccines against pathogens for which T-cell–mediated protection requires both fully activated T cells for immediate control of virus-infected cells and central memory CD8+ T cells that, because of their higher proliferative capacity, may be suited best to eliminate cells infected by pathogens that escaped the initial wave of effector T cells.
Comparative analysis of differentially expressed genes in normal and white spot syndrome virus infected Penaeus monodon
Authors: Leu Jiann-Horng , Chang Chih-Chin , Wu Jin-Lu , Hsu Chun-Wei , Hirono Ikuo , Aoki Takashi , Juan Hsueh-Fen , Lo Chu-Fang , Kou Guang-Hsiung , Huang Hsuan-Cheng 
Published: May 2007

Abstract

Background
White spot syndrome (WSS) is a viral disease that affects most of the commercially important shrimps and causes serious economic losses to the shrimp farming industry worldwide. However, little information is available in terms of the molecular mechanisms of the host-virus interaction. In this study, we used an expressed sequence tag (EST) approach to observe global gene expression changes in white spot syndrome virus (WSSV)-infected postlarvae of Penaeus monodon.

Results
Sequencing of the complementary DNA clones of two libraries constructed from normal and WSSV-infected postlarvae produced a total of 15,981 high-quality ESTs. Of these ESTs, 46% were successfully matched against annotated genes in National Center of Biotechnology Information (NCBI) non-redundant (nr) database and 44% were functionally classified using the Gene Ontology (GO) scheme. Comparative EST analyses suggested that, in postlarval shrimp, WSSV infection strongly modulates the gene expression patterns in several organs or tissues, including the hepatopancreas, muscle, eyestalk and cuticle. Our data suggest that several basic cellular metabolic processes are likely to be affected, including oxidative phosphorylation, protein synthesis, the glycolytic pathway, and calcium ion balance. A group of immune-related chitin-binding protein genes is also likely to be strongly up regulated after WSSV infection. A database containing all the sequence data and analysis results is accessible at http://xbio.lifescience.ntu.edu.tw/pm/.

Conclusion
This study suggests that WSSV infection modulates expression of various kinds of genes. The predicted gene expression pattern changes not only reflect the possible responses of shrimp to the virus infection but also suggest how WSSV subverts cellular functions for virus multiplication. In addition, the ESTs reported in this study provide a rich source for identification of novel genes in shrimp.
Global gene expression analysis of the mouse colonic mucosa treated with azoxymethane and dextran sodium sulfate
Authors: Suzuki Rikako , Miyamoto Shingo , Yasui Yumiko , Sugie Shigeyuki , Tanaka Takuji 
Published: May 2007

Abstract

Background
Chronic inflammation is well known to be a risk factor for colon cancer. Previously we established a novel mouse model of inflammation-related colon carcinogenesis, which is useful to examine the involvement of inflammation in colon carcinogenesis. To shed light on the alterations in global gene expression in the background of inflammation-related colon cancer and gain further insights into the molecular mechanisms underlying inflammation-related colon carcinogenesis, we conducted a comprehensive DNA microarray analysis using our model.

Methods
Male ICR mice were given a single ip injection of azoxymethane (AOM, 10 mg/kg body weight), followed by the addition of 2% (w/v) dextran sodium sulfate (DSS) to their drinking water for 7 days, starting 1 week after the AOM injection. We performed DNA microarray analysis (Affymetrix GeneChip) on non-tumorous mucosa obtained from mice that received AOM/DSS, AOM alone, and DSS alone, and untreated mice at wks 5 and 10.

Results
Markedly up-regulated genes in the colonic mucosa given AOM/DSS at wk 5 or 10 included Wnt inhibitory factor 1 (Wif1, 48.5-fold increase at wk 5 and 5.7-fold increase at wk 10) and plasminogen activator, tissue (Plat, 48.5-fold increase at wk 5), myelocytomatosis oncogene (Myc, 3.0-fold increase at wk 5), and phospholipase A2, group IIA (platelets, synovial fluid) (Plscr2, 8.0-fold increase at wk 10). The notable down-regulated genes in the colonic mucosa of mice treated with AOM/DSS were the peroxisome proliferator activated receptor binding protein (Pparbp, 0.06-fold decrease at wk 10) and the transforming growth factor, beta 3 (Tgfb3, 0.14-fold decrease at wk 10). The inflammation-related gene, peroxisome proliferator activated receptor γ (Pparγ 0.38-fold decrease at wk 5), was also down-regulated in the colonic mucosa of mice that received AOM/DSS.

Conclusion
This is the first report describing global gene expression analysis of an AOM/DSS-induced mouse colon carcinogenesis model, and our findings provide new insights into the mechanisms of inflammation-related colon carcinogenesis and the establishment of novel therapies and preventative strategies against carcinogenesis.