bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recognition of Live Phosphatidylserine-Labeled Tumor Cells by Dendritic Cells: A Novel Approach to Immunotherapy of Skin Cancer
Authors: Shurin Michael R. , Potapovich Alla I. , Tyurina Yulia Y. , Tourkova Irina L. , Shurin Galina V. , Kagan Valerian E. 
Published: March 2009

AbstractDendritic cells (DC) loaded with tumor antigens from apoptotic/necrotic tumor cells are commonly used as vaccines for cancer therapy. However, the use of dead tumor cells may cause both tolerance and immunity, making the effect of vaccination unpredictable. To deliver live tumor “cargoes” into DC, we developed a new approach based on the “labeling” of tumors with a phospholipid “eat-me” signal, phosphatidylserine. Expression of phosphatidylserine on live tumor cells mediated their recognition and endocytosis by DC resulting in the presentation of tumor antigens to antigen-specific T cells. In mice, topical application of phosphatidylserine-containing ointment over melanoma induced tumor-specific CTL, local and systemic antitumor immunity, and inhibited tumor growth. Thus, labeling of tumors with phosphatidylserine is a promising strategy for cancer immunotherapy. [Cancer Res 2009;69(6):2487–96]
Hypoxia-Inducible Factor-1α Suppresses Squamous Carcinogenic Progression and Epithelial-Mesenchymal Transition
Authors: Scortegagna Marzia , Martin Rebecca J. , Kladney Raleigh D. , Neumann Robert G. , Arbeit Jeffrey M. 
Published: March 2009

Abstract
Hypoxia-inducible factor-1 (HIF-1) is a known cancer progression factor, promoting growth, spread, and metastasis. However, in selected contexts, HIF-1 is a tumor suppressor coordinating hypoxic cell cycle suppression and apoptosis. Prior studies focused on HIF-1 function in established malignancy; however, little is known about its role during the entire process of carcinogenesis from neoplasia induction to malignancy. Here, we tested HIF-1 gain of function during multistage murine skin chemical carcinogenesis in K14-HIF-1αPro402A564G (K14-HIF-1αDPM) transgenic mice. Transgenic papillomas appeared earlier and were more numerous (6 ± 3 transgenic versus 2 ± 1.5 nontransgenic papillomas per mouse), yet they were more differentiated, their proliferation was lower, and their malignant conversion was profoundly inhibited (7% in transgenic versus 40% in nontransgenic mice). Moreover, transgenic cancers maintained squamous differentiation whereas epithelial-mesenchymal transformation was frequent in nontransgenic malignancies. Transgenic basal keratinocytes up-regulated the HIF-1 target N-myc downstream regulated gene-1, a known tumor suppressor gene in human malignancy, and its expression was maintained in transgenic papillomas and cancer. We also discovered a novel HIF-1 target gene, selenium binding protein-1 (Selenbp1), a gene of unknown function whose expression is lost in human cancer. Thus, HIF-1 can function as a tumor suppressor through transactivation of genes that are themselves targets for negative selection in human cancers. [Cancer Res 2009;69(6):2638–46]
CBL Exon 8/9 Mutants Activate the FLT3 Pathway and Cluster in Core Binding Factor/11q Deletion Acute Myeloid Leukemia/Myelodysplastic Syndrome Subtypes
Authors: Reindl Carola , Quentmeier Hilmar , Petropoulos Konstantin , Greif Philipp A. , Benthaus Tobias , Argiropoulos Bob , Mellert Gudrun , Vempati Sridhar , Duyster Justus , Buske Christian , Bohlander Stefan K. , Humphries Keith R. , Hiddemann Wolfgang , Spiekermann Karsten 
Published: March 2009

Abstract
Purpose: CBL is a negative regulator of activated receptor tyrosine kinases (RTK). In this study, we determined the frequency of CBL mutations in acute leukemias and evaluated the oncogenic potential of mutant CBL.
Experimental Design: The cDNA of 300 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and acute lymphoblastic leukemia (ALL) patients and 82 human leukemic cell lines was screened for aberrations in the linker and RING finger domain of CBL. The oncogenic potential of identified mutants was evaluated in hematopoietic cells.
Results: We identified 3 of 279 AML/MDS patients expressing CBL exon 8/9 deletion mutants. Three of four cases at diagnosis expressed deleted transcripts missing exon 8 or exon 8/9. In remission samples a weak or no expression of mutant CBL was detected. No aberrations were found in normal hematopoietic tissues. One of 116 sequenced AML/MDS cases carried a R420G missense mutation. All AML/MDS patients with identified CBL mutants belonged to the core binding factor and 11q deletion AML subtypes. Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo. Expression of CBLΔexon8 and CBLΔexon8+9 in FLT3-WT-Ba/F3 cells induced growth factor–independent proliferation associated with autophosphorylation of FLT3 and activated the downstream targets signal transducer and activator of transcription 5 (STAT5) and protein kinase B (AKT). FLT3 ligand–dependent hyperproliferation of CBL mutant cells could be abrogated by treatment with the FLT3 PTK inhibitor PKC412 (midostaurin).
Conclusion: CBL exon8/9 mutants occur in genetically defined AML/MDS subtypes and transform hematopoietic cells by constitutively activating the FLT3 pathway. This phenotype resembles the one of mutated RTKs and suggests that CBL mutant AML patients might benefit from treatment with FLT3 PTK inhibitors.
The Topoisomerase I Poison CPT-11 Enhances the Effect of the Aurora B Kinase Inhibitor AZD1152 both In vitro and In vivo
Authors: Nair Jayasree S. , de Stanchina Elisa , Schwartz Gary K. 
Published: March 2009

Abstract
Purpose: AZD1152 is an Aurora B kinase inhibitor currently in clinical trials. As the topoisomerase I poison CPT-11 induces a G2 arrest, a mechanistic understanding of the cell cycle interactions between these agents may prove critical for combination therapy.
Methods: AZD1152 was tested in vitro and in vivo with SN-38 and CPT-11 against HCT-116 cells. Inhibition of clonogenicity, induction of apoptosis, effects on polyploidy, and tumor growth were examined.
Results: AZD1152 alone induced polyploidy of HCT-116 cells at low nanomolar concentrations. The induction of apoptosis required prolonged exposure (48 hours) and higher concentrations of drug. When SN-38 was given before or concomitantly with AZD1152, SN-38 blocked the AZD1152 effect by arresting cells in G2 and inhibiting cells from undergoing polyploidy. With the reverse combination (AZD1152 followed by SN-38), there was a significant induction of polyploidy and apoptosis, even with shorter exposure (24 hours) of AZD1152. In vivo, AZD1152 alone suppressed HCT-116 xenograft tumor growth in a dose-dependent manner with target inhibition of phosphoH3, induction of multinucleated giant cells, but without induction of apoptosis. In combination, both sequences in vivo (CPT-&gt;AZD, AZD-&gt;CPT, P = 0.008, AUC/d) proved superior to either single agent therapy. However, AZD-&gt;CPT still showed a greater increase in apoptosis and greater suppression of tumor regrowth than CPT-&gt;AZD (P = 0.02, AUC/d).
Conclusions: The results from these studies indicate a promising therapeutic strategy for combining AZD1152 with CPT-11, and suggest that the sequence of drug administration is pivotal when an Aurora B kinase inhibitor is administered with a topoisomerase I poison.
Effective Prostate Cancer Chemopreventive Intervention with Green Tea Polyphenols in the TRAMP Model Depends on the Stage of the Disease
Authors: Adhami Vaqar Mustafa , Siddiqui Imtiaz Ahmad , Sarfaraz Sami , Khwaja Sabih Islam , Hafeez Bilal Bin , Ahmad Nihal , Mukhtar Hasan 
Published: March 2009

Abstract
Purpose: We have shown previously that oral feeding of green tea polyphenols (GTP) to transgenic adenocarcinoma of the mouse prostate mice in a purely chemopreventive setting significantly inhibits prostate cancer development. To translate this to a human situation, the present study was designed to identify the stage of prostate cancer that is most vulnerable to chemopreventive intervention by GTP.
Experimental Design: GTP infusion (0.1% in drinking water) to transgenic adenocarcinoma of the mouse prostate was initiated at ages representing different stage of the disease: (a) 6 weeks (group 1, normal prostate), (b) 12 weeks (group 2, prostatic intraepithelial neoplasia), (c) 18 weeks (group 3, well-differentiated adenocarcinoma), and (b) 28 weeks (group 4, moderately differentiated adenocarcinoma). At age 32 weeks, subsets of animals were evaluated by magnetic resonance imaging, ultrasound, and prostate weight and for serum insulin-like growth factor (IGF)-I/IGF binding protein-3 and IGF signaling.
Results: Tumor-free survival was extended to 38 weeks (P &lt; 0.001) in group 1, 31 weeks (P &lt; 0.01) in group 2, and 24 weeks (P &lt; 0.05) in group 3 compared with 19 weeks in water-fed controls. Median life expectancy was 68 weeks in group 1, 63 weeks in group 2, 56 weeks in group 3, and 51 weeks in group 4 compared with 42 weeks in the control mice. IGF-I and its downstream targets including phosphatidylinositol 3-kinase, pAkt, and phosphorylated extracellular signal-regulated kinase were significantly inhibited only when intervention was initiated early when prostatic intraepithelial neoplasia lesions were common.
Conclusions: Our studies indicate that chemopreventive potential of GTP decreases with advancing stage of the disease and underscore the need to design appropriate chemoprevention clinical trails.
p27Kip1 in Stage III Colon Cancer: Implications for Outcome following Adjuvant Chemotherapy in Cancer and Leukemia Group B Protocol 89803
Authors: Bertagnolli Monica M. , Warren Robert S. , Niedzwiecki Donna , Mueller Elke , Compton Carolyn C. , Redston Mark , Hall Margaret , Hahn Hejin P. , Jewell Scott D. , Mayer Robert J. , Goldberg Richard M. , Saltz Leonard B. , Loda Massimo 
Published: March 2009

Abstract
Background: In retrospective studies, loss of p27Kip1 (p27), a cyclin-dependent kinase inhibitor, has been associated with poor prognosis following colorectal cancer treatment. In a prospective study, we validated this relationship in patients enrolled on a trial of adjuvant chemotherapy for stage III colon cancer.
Methods: Cancer and Leukemia Group B protocol 89803 randomized 1,264 stage III colon cancer patients to receive weekly bolus 5-fluorouracil/leucovorin or weekly bolus irinotecan, 5-fluorouracil, and leucovorin (IFL). The primary endpoint was overall survival (OS); disease-free survival was a secondary endpoint. Expression of p27 and DNA mismatch repair proteins were determined by immunohistochemistry in primary tumor and normal tissue from paraffin blocks. Data were analyzed using log-rank test.
Results: Of 601 tumors analyzed, 207 (34.4%) showed p27 loss, 377 (62.8%) retained p27, and 17 (2.8%) were indeterminate. Patients with p27-negative tumors showed reduced OS [5-year OS 66%: 95% confidence interval (95% CI), 0.59-0.72 versus 75%: 95% CI, 0.70-0.79; log-rank P = 0.021]. This relationship was not influenced by treatment arm. Combination of p27 status with mismatch repair status, however, identified a small subset of patients that may benefit from IFL (n = 36; 5-year disease-free survival 81%: 95% CI, 0.64-0.98 versus 47%: 95% CI, 0.21-0.72; log-rank P = 0.042; 5-year OS 81%: 95% CI, 0.64-0.98 versus 60%: 95% CI, 0.35-0.85; log-rank P = 0.128).
Conclusions: Loss of p27 is associated with reduced survival in stage III colon cancer but by itself does not indicate a significant difference in outcome between patients treated IFL or 5-fluorouracil/leucovorin.
Inhibition of vimentin or β1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo
Authors: Zhang Xueping , Fournier Marcia V. , Ware Joy L. , Bissell Mina J. , Yacoub Adly , Zehner Zendra E. 
Published: March 2009

Abstract
Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphologic changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the immortalized, prostate epithelial P69 cell line by selection in athymic, nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the parental, nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to β-catenin, E-cadherin, or α6 and β1 integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via small interfering RNA interference or the expression of α6 and β1integrins by the addition of blocking antibodies, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by s.c. injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in three-dimensional lrECM gels. These studies suggest that the levels of vimentin and β1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis. [Mol Cancer Ther 2009;8(3):499–508]
Modulation of the Period of the Quasi-Biennial Oscillation by the Solar Cycle
Authors: Kuai Le , Shia Run-Lie , Jiang Xun , Tung Ka Kit , Yung Yuk L. 
Published: March 2009

Abstract
The authors examine the mechanism of solar cycle modulation of the Quasi-Biennial Oscillation (QBO) period using the Two-and-a-Half-Dimensional Interactive Isentropic Research (THINAIR) model. Previous model results (using 2D and 3D models of varying complexity) have not convincingly established the proposed link of longer QBO periods during solar minima. Observational evidence for such a modulation is also controversial because it is only found during the period from the 1960s to the early 1990s, which is contaminated by volcanic aerosols. In the model, 200- and 400-yr runs without volcano influence can be obtained, long enough to establish some statistical robustness. Both in model and observed data, there is a strong synchronization of the QBO period with integer multiples of the semiannual oscillation (SAO) in the upper stratosphere. Under the current level of wave forcing, the period of the QBO jumps from one multiple of SAO to another and back so that it averages to 28 months, never settling down to a constant period. The “decadal” variability in the QBO period takes the form of “quantum” jumps; these, however, do not appear to follow the level of the solar flux in either the observation or the model using realistic quasi-periodic solar cycle (SC) forcing. To understand the solar modulation of the QBO period, the authors perform model runs with a range of perpetual solar forcing, either lower or higher than the current level. At the current level of solar forcing, the model QBO period consists of a distribution of four and five SAO periods, similar to the observed distribution. This distribution changes as solar forcing changes. For lower (higher) solar forcing, the distribution shifts to more (less) four SAO periods than five SAO periods. The record-averaged QBO period increases with the solar forcing. However, because this effect is rather weak and is detectable only with exaggerated forcing, the authors suggest that the previous result of the anticorrelation of the QBO period with the SC seen in short observational records reflects only a chance behavior of the QBO period, which naturally jumps in a nonstationary manner even if the solar forcing is held constant, and the correlation can change as the record gets longer.
Decadal Response of Global Circulation to Southern Ocean Zonal Wind Stress Perturbation
Authors: Klinger Barry A. , Cruz Carlos 
Published: March 2009

Abstract
A substantial component of North Atlantic Deep Water formation may be driven by westerly wind stress over the Southern Ocean. Variability of this wind stress on decadal time scales may lead to circulation variability far from the forcing region. The Hybrid Coordinate Ocean Model (HYCOM), a numerical ocean model, is used to investigate the spatial patterns and the time scales associated with such wind variability. The evolution of circulation and density anomalies is observed by comparing one 80-yr simulation, forced in part by relatively strong Southern Hemisphere westerlies, with a simulation driven by climatological wind.
The volume transport anomaly takes about 10 yr to reach near-full strength in the entire Southern Hemisphere; however, in the Northern Hemisphere, it grows for the duration of the run. The Southern Hemisphere Indo-Pacific volume transport anomaly is about twice the strength of that found in the Atlantic. In the thermocline, water exits the southern westerlies belt in a broad flow that feeds a western boundary current (WBC) in both the Atlantic and Pacific Oceans. These WBCs in turn feed an Indonesian Throughflow from the Pacific and cyclonic gyres in the far north, which are broadly consistent with the Stommel–Arons theory. The deep return flow in each hemisphere is strongly affected by deep-sea ridges, which leads to a number of midocean “WBCs.” The wind perturbation causes isopycnals to sink over most of the basin. After about 20 yr, this sinking is very roughly uniform with latitude, though it varies by basin.
Gfi1 regulates miR-21 and miR-196b to control myelopoiesis
Authors: Velu Chinavenmeni S. , Baktula Avinash M. , Grimes H. Leighton 
Published: March 2009

AbstractThe zinc finger protein growth factor independent-1 (Gfi1) is a transcriptional repressor that is critically required for normal granulocytic differentiation. GFI1 loss-of-function mutations are found in some patients with severe congenital neutropenia (SCN). The SCN-associated GFI1-mutant proteins act as dominant negatives to block granulopoiesis through selective deregulation of a subset of GFI1 target genes. Here we show that Gfi1 is a master regulator of microRNAs, and that deregulated expression of these microRNAs recapitulates a Gfi1 loss-of-function block to granulocyte colony-stimulating factor (G-CSF)–stimulated granulopoiesis. Specifically, bone marrow cells from a GFI1-mutant SCN patient and Gfi1−/− mice display deregulated expression of miR-21 and miR-196B expression. Flow cytometric analysis and colony assays reveal that the overexpression or depletion of either miR induces changes in myeloid development. However, coexpression of miR-21 and miR-196b (as seen in Gfi1−/− mice and a GFI1N382S SCN patient) completely blocks G-CSF–induced granulopoiesis. Thus, our results not only identify microRNAs whose regulation is required during myelopoiesis, but also provide an example of synergy in microRNA biologic activity and illustrate potential mechanisms underlying SCN disease pathogenesis.
Key to the Paraplatyptilia species of eastern Canada with description of a new species (Lepidoptera: Pterophoridae)
Authors: Landry Bernard , Gielis Cees 
Published: March 2009

AbstractParaplatyptilia atlanticasp. nov. is described as new from northwestern Newfoundland and the Gaspé Peninsula, Quebec, Canada. A key to the four species of Paraplatyptilia Bigot and Picard known to occur in eastern Canada (east of Manitoba) is provided.
Serendipity with chewing lice (Phthiraptera: Menoponidae, Philopteridae) infesting rock pigeons and mourning doves (Aves: Columbiformes: Columbidae) in Manitoba, with new records for North America and Canada
Authors: Galloway Terry D. , Palma Ricardo L. 
Published: March 2009

AbstractAn extensive survey of chewing lice from rock pigeon,Columba liviaGmelin, and mourning dove,Zenaida macroura(L.), carried out from 1994 to 2000 and from 2003 to 2006 in Manitoba, Canada, produced the following new records:ColocerastovornikaeTendeiro for North America;Columbicola macrourae(Wilson),Hohorstiellalata(Piaget),H.paladinellaHill and Tuff, andPhysconelloides zenaidurae(McGregor) for Canada; andBonomiella columbaeEmerson,Campanulotes compar(Burmeister),Columbicola baculoides(Paine), andC. columbae(L.) for Manitoba. We collected 25 418 lice of four species (C. compar,C. columbae,H.lata, andC.tovornikae) from 322 rock pigeons. The overall prevalence of infestation was 78.9%, 52.5%, and 23.3% forC.compar,C.columbae, andH.lata, respectively.Coloceras tovornikaewas not discovered until 2003, after which its prevalence was 39.9% on 114 pigeons. We collected 1116 lice of five species (P.zenaidurae,C.baculoides,C. macrourae,H.paladinella, andB.columbae) from 117 mourning doves.Physconelloides zenaiduraewas encountered most often (prevalence was 36.7%), while the prevalence of the other four species was 26.3%, 18.4%, 3.5%, and 2.6%, respectively.
Review of the Nearctic Lonchopteridae (Diptera), including descriptions of three new species
Authors: Klymko John , Marshall S.A. 
Published: March 2009

AbstractThe Nearctic species of Lonchoptera Meigen are reviewed, including three new species: L. barberi Klymko sp. nov. from Manitoba, Newfoundland, Ontario, Quebec, Iowa, Michigan, Minnesota, and New Hampshire, L. megaloba Klymko sp. nov. from British Columbia and California, and L. longiphallus Klymko sp. nov. from British Columbia and the Northwest Territories. Lonchoptera borealis Curran is proposed as a new junior synonym of L. impicta Zetterstedt, and L. occidentalis Curran is proposed as a new junior synonym of L. uniseta Curran. Lonchoptera nigrociliata Duda, formerly known only from the Palaearctic Region, is recorded from the Yukon and Alaska. Descriptions, a key, and Nearctic distribution maps are presented. Phylogenetic relationships are briefly discussed and two sister species pairs are documented.
Biology of Caloptilia fraxinella (Lepidoptera: Gracillariidae) on ornamental green ash, Fraxinus pennsylvanica (Oleaceae)
Authors: Evenden M.L. 
Published: March 2009

AbstractThe ash leaf cone roller, Caloptilia fraxinella (Ely), is a leaf-mining moth that has recently become a significant pest of horticultural ash, Fraxinus L., species in communities throughout the western prairie provinces of Canada. The study examines the spatial and temporal within-host distribution of immature stages of C. fraxinella on green ash, Fraxinus pennsylvanica Marsh. Female C. fraxinella showed a preference for oviposition sites in the lower canopy and on the south side of the tree at the beginning and middle of the 3-week oviposition period, respectively, but no preference at the end of the period. Oviposition was constrained temporally and occurred mainly just after green ash bud flush. Immature stages were sampled throughout the growing season, and measured widths of larval head capsules showed five instars. Fourth-instar larvae disperse from the mined leaflet to a new leaflet, roll it into a cone, and pupate. Neither canopy height nor ordinal direction affected the position of larvae in the canopy, but numbers of immature stages varied by tree within a site. Female and male moths eclose from rolled leaf cones synchronously throughout the emergence period. The study provides some of the basic biological information required to design an integrated pest management program to target this emerging pest of horticultural ash trees.