bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depositional architecture and sequence stratigraphic correlation of Upper Ordovician glaciogenic deposits, Illizi Basin, Algeria
Authors: Lang Jörg , Dixon Richard J. , Le Heron Daniel P. , Winsemann Jutta 
Published: March 2012

Abstract
Upper Ordovician glaciogenic deposits are profoundly important as hydrocarbon reservoirs across North Africa, such as within the Illizi Basin of SE Algeria. In this study we present a new sedimentological and sequence stratigraphic model for Upper Ordovician glaciogenic deposits based on the analysis of core descriptions and wireline logs from 25 wells in the Tiguentourine Field. Within the glaciogenic succession, two ice advance–retreat cycles can be defined, consisting of glaciomarine ice-contact fan deposits and tillites. Deposits of the marine ice-contact fan systems generally show a retrogradational stacking pattern from ice-proximal to ice-distal deposits. This pattern is attributed to the deposition in front of a retreating ice sheet. The proximal marine ice-contact fan deposits consist of massive or low-angle cross-bedded pebbly sandstone. They are interpreted as the deposits of turbulent, high-energy plane-wall jets, emerging from subglacial meltwater conduits. These jet-efflux deposits are up to 60 m thick and interbedded with deposits of cohesive and non-cohesive debris flows. The jet-efflux deposits are overlain by fine-grained, thick-bedded massive sandstone. These mid-fan deposits build up the bulk of the glaciomarine fans and are interpreted as deposits of underflows, generated at the point of flow-detachment, where marine meltwater jets become buoyant and large volumes of sediment fall-out from suspension. In the upper part of the fan succession massive sandstones pass upwards into mud-prone massive sandstones, interpreted as deposits of cohesive sandy debris flows. The most ice-distal deposits are muddy sandstones and mudstones deposited by waning low-density turbulent flows and suspension fall-out. The best reservoir properties within the glaciogenic succession are attributed to the proximal and medial deposits of the ice-contact fans such as coarse-grained jet-efflux deposits and sustained high-density turbulent flow deposits. However, the mud content within the massive sandstones is highly variable and influences the reservoir quality. Both glacial depositional sequences infill 60–175 m deep, elongated depressions, which are interpreted as subglacial tunnel valleys. These tunnel valleys acted as depocentres for the glaciomarine fan deposits. After final deglaciation and post-glacial transgression, organic-rich shale was preferentially deposited in underfilled tunnel valleys.
Channelized sandstone bodies (‘cordons’) in the Tassili N'Ajjer (Algeria & Libya): snapshots of a Late Ordovician proglacial outwash plain
Authors: Girard F. , Ghienne J.-F. , Rubino J.-L. 
Published: March 2012

Abstract

The architecture, distribution and development of channelized sandstone bodies are described from Late Ordovician paraglacial successions of the Tassili N'Ajjer (SE Algeria and SW Libya) based on satellite images and field data (sedimentary logs, photomosaics). Sandstone bodies have a ribbon-like form at outcrop (often referred to as ‘cordons’ in the literature). They typify a fluvioglacial outwash plain deposited between a continental ice front and a marine delta-front zone. Channelized sandstone bodies are straight to sinuous, with widths (
W
) in the 60–600 m range, thicknesses (
T
) in the 5–30 m range and they have a mean
W
/
T
ratio of 16.5. They develop within an aggradational–progradational sand-dominated deltaic topset succession including at its distal end a terminal distributary channel and mouth-bar environments. The architecture of channel bodies and the related depositional facies, which includes climbing-dune cross-stratification, indicates that channelized sandstone bodies represent plugs of isolated channels related to high-magnitude flood events (glacier outbursts). These plugs form fossilized networks of both braided channels and interlaced anastomosed channels, offering snapshots of an outburst-related unconfined proglacial outwash braidplain constituted by the amalgamation of adjacent, elongated outwash fans.
Late Ordovician tunnel valleys in southern Jordan
Authors: Douillet G. , Ghienne J.-F. , Géraud Y. , Abueladas A. , Diraison M. , Al-Zoubi A. 
Published: March 2012

Abstract
The Upper Ordovician glacial record of southern Jordan (Ammar Fm.) essentially consists of palaeovalley infills and of a subordinate time-transgressive fluvial to shallow-marine succession overstepping both the palaeovalleys and interfluvial areas. Valley size (depth, 60–160 m; width, 1–3 km), steep (20–50°) margins, internal organization and depositional facies point to an origin as tunnel valleys. The tunnel valleys are infilled by either fluvioglacial sandstones or fluviodeltaic coarsening-upward successions including fine-grained clayey sediments. Re-occupation of previous valleys is evident in places. At least three generations of tunnel valleys are inferred from cross-cutting relationships, although they most probably only reflect temporary standstills and minor re-advances related to the overall recession following the main glacial advance recorded in Saudi Arabia. Petrophysical measurements indicate that higher permeabilities are located in the glacially related strata (1.5–3 darcy in fluvioglacial infills), with a somewhat reduced porosity (22–28%) relative to the preglacial sandstones owing to a higher clay content, probably of diagenetic origin. Sandstone amalgamation, however, gives the fluvioglacial sandstones a high reservoir quality.
Stem-like Tumor-Initiating Cells Isolated from IL13Rα2 Expressing Gliomas Are Targeted and Killed by IL13-Zetakine–Redirected T Cells
Authors: Brown Christine E. , Starr Renate , Aguilar Brenda , Shami Andrew F. , Martinez Catalina , D'Apuzzo Massimo , Barish Michael E. , Forman Stephen J. , Jensen Michael C. 
Published: March 2012

Abstract
Purpose: To evaluate IL13Rα2 as an immunotherapeutic target for eliminating glioma stem–like cancer initiating cells (GSC) of high-grade gliomas, with particular focus on the potential of genetically engineered IL13Rα2-specific primary human CD8+ CTLs (IL13-zetakine+ CTL) to target this therapeutically resistant glioma subpopulation.
Experimental Design: A panel of low-passage GSC tumor sphere (TS) and serum-differentiated glioma lines were expanded from patient glioblastoma specimens. These glioblastoma lines were evaluated for expression of IL13Rα2 and for susceptibility to IL13-zetakine+ CTL-mediated killing in vitro and in vivo.
Results: We observed that although glioma IL13Rα2 expression varies between patients, for IL13Rα2pos cases this antigen was detected on both GSCs and more differentiated tumor cell populations. IL13-zetakine+ CTL were capable of efficient recognition and killing of both IL13Rα2pos GSCs and IL13Rα2pos differentiated cells in vitro, as well as eliminating glioma-initiating activity in an orthotopic mouse tumor model. Furthermore, intracranial administration of IL13-zetakine+ CTL displayed robust antitumor activity against established IL13Rα2pos GSC TS-initiated orthotopic tumors in mice.
Conclusions: Within IL13Rα2 expressing high-grade gliomas, this receptor is expressed by GSCs and differentiated tumor populations, rendering both targetable by IL13-zetakine+ CTLs. Thus, our results support the potential usefullness of IL13Rα2-directed immunotherapeutic approaches for eradicating therapeutically resistant GSC populations. Clin Cancer Res; 18(8); 2199–209. ©2012 AACR.
Survivin Is a Viable Target for the Treatment of Malignant Peripheral Nerve Sheath Tumors
Authors: Ghadimi Markus P. , Young Eric D. , Belousov Roman , Zhang Yiqun , Lopez Gonzalo , Lusby Kristelle , Kivlin Christine , Demicco Elizabeth G. , Creighton Chad J. , Lazar Alexander J. , Pollock Raphael E. , Lev Dina 
Published: March 2012

Abstract
Purpose: To examine the role of survivin as a therapeutic target in preclinical models of human malignant peripheral nerve sheath tumors (MPNST)
Experimental Design: Survivin protein expression levels and subcellular localization were examined immunohistochemically in an MPNST tissue microarray. Human MPNST cells were studied in vitro and in vivo; real-time PCR, Western blotting, and immunocytochemical analyses were used to evaluate survivin expression and localization activation. Cell culture assays were used to evaluate the impact of anti-survivin–specific siRNA inhibition on cell growth and cell-cycle progression and survival. The effect of the small-molecule survivin inhibitor YM155 on local and metastatic MPNST growth was examined in vivo.
Results: Survivin was found to be highly expressed in human MPNSTs; enhanced cytoplasmic subcellular localization differentiated MPNSTs from their plexiform neurofibroma premalignant counterparts. Human MPNST cell lines exhibited survivin mRNA and protein overexpression; expression in both nuclear and cytoplasmic compartments was noted. Survivin knockdown abrogated MPNST cell growth, inducing G2 cell-cycle arrest and marked apoptosis. YM155 inhibited human MPNST xenograft growth and metastasis in severe combined immunodeficient (SCID) mice. Antitumor effects were more pronounced in fast-growing xenografts.
Conclusions: Our studies show an important role for survivin in human MPNST biology. Patients with MPNSTs should be considered for ongoing or future clinical trials that evaluate anti-survivin therapeutic strategies. Most importantly, future investigations should evaluate additional pathways that can be targeted in combination with survivin for maximal synergistic anti-MPNST effects. Clin Cancer Res; 18(9); 2545–57. ©2012 AACR.
Analysis of Spontaneous Tumor-Specific CD4 T-cell Immunity in Lung Cancer Using Promiscuous HLA-DR Telomerase-Derived Epitopes: Potential Synergistic Effect with Chemotherapy Response
Authors: Godet Yann , Fabre Elizabeth , Dosset Magalie , Lamuraglia Michele , Levionnois Emeline , Ravel Patrice , Benhamouda Nadine , Cazes Aurélie , Le Pimpec-Barthes Françoise , Gaugler Beatrice , Langlade-Demoyen Pierre , Pivot Xavier , Saas Philippe , Maillère Bernard , Tartour Eric , Borg Christophe , Adotévi Olivier 
Published: March 2012

Abstract
Purpose: To investigate the presence and impact of spontaneous telomerase-specific CD4 T-cell responses in cancer patients.
Experimental Design: A multistep approach was used to design novel pan-HLA-DR–restricted peptides from telomerase. T-cell clones isolated from cancer patients were used to characterize the polarization of telomerase-specific CD4 response. The presence of spontaneous CD4 T-cell response against telomerase was monitored in 84 metastatic non–small cell lung cancer (NSCLC) patients before first-line chemotherapy (CT) using IFN-γ ELISPOT assay. Then we analyzed the impact of the pretherapeutic telomerase-specific CD4 T immunity on clinical outcome in patients according to their respective response to CT.
Results: We described four novel telomerase-derived CD4 epitopes referred as universal cancer peptides (UCP) that effectively bind to most commonly found human MHC class II alleles. UCP-specific CD4 T-cell repertoire is present in human and UCP-specific CD4 T-cell clones generated from cancer patients exhibited high avidity and are Th1 polarized. Significant frequency (38%) of naturally occurring UCP-specific T-cell responses were detected before CT in advanced NSCLC but not in healthy volunteers. This response was shown to significantly increase overall survival (OS) of patients responding to CT (Median OS: 53 vs. 40 weeks, P = 0.034).
Conclusions: These results show for the first time a potential synergistic effect of telomerase-specific CD4 T-cell response with CT response in NSCLC and underline the potential role of tumor-specific CD4 T-cell response on the efficiency of conventional anticancer therapy. Clin Cancer Res; 18(10); 2943–53. ©2012 AACR.
Hyperactivation of 4E-Binding Protein 1 as a Mediator of Biguanide-Induced Cytotoxicity during Glucose Deprivation
Authors: Matsuo Junichi , Tsukumo Yoshinori , Saito Sakae , Tsukahara Satomi , Sakurai Junko , Sato Shigeo , Kondo Hiromichi , Ushijima Masaru , Matsuura Masaaki , Watanabe Toshiki , Tomida Akihiro 
Published: March 2012

Abstract
Biguanides, including metformin, buformin, and phenformin, are potential antitumorigenic agents and induce cell death during glucose deprivation, a cell condition that occurs in the tumor microenvironment. Here, we show that this selective killing of glucose-deprived cells is coupled with hyperactivation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), a negative regulator of translation initiation. We found, in fact, that the 4E-BP1 hyperactivation led to failure of the unfolded protein response (UPR), an endoplasmic reticulum–originated stress signaling pathway for cell survival. We also found that the 4E-BP1–mediated UPR inhibition occurred through a strong inhibition of the mTOR signaling pathway, a proven antitumor target. Importantly, the 4E-BP1 hyperactivation can be also seen in xenografted cancer cells through an in vivo biguanide treatment. Our findings indicate that antitumor action of biguanides can be mediated by 4E-BP1 hyperactivation, which results in UPR inhibition and selective cell killing when glucose is withdrawn. Mol Cancer Ther; 11(5); 1082–91. ©2012 AACR.
ERK Inhibition Overcomes Acquired Resistance to MEK Inhibitors
Authors: Hatzivassiliou Georgia , Liu Bonnie , O'Brien Carol , Spoerke Jill M. , Hoeflich Klaus P. , Haverty Peter M. , Soriano Robert , Forrest William F. , Heldens Sherry , Chen Huifen , Toy Karen , Ha Connie , Zhou Wei , Song Kyung , Friedman Lori S. , Amler Lukas C. , Hampton Garret M. , Moffat John , Belvin Marcia , Lackner Mark R. 
Published: March 2012

Abstract
The RAS/RAF/MEK pathway is activated in more than 30% of human cancers, most commonly via mutation in the K-ras oncogene and also via mutations in BRAF. Several allosteric mitogen-activated protein/extracellular signal–regulated kinase (MEK) inhibitors, aimed at treating tumors with RAS/RAF pathway alterations, are in clinical development. However, acquired resistance to these inhibitors has been documented both in preclinical and clinical samples. To identify strategies to overcome this resistance, we have derived three independent MEK inhibitor–resistant cell lines. Resistance to allosteric MEK inhibitors in these cell lines was consistently linked to acquired mutations in the allosteric binding pocket of MEK. In one cell line, concurrent amplification of mutant K-ras was observed in conjunction with MEK allosteric pocket mutations. Clonal analysis showed that both resistance mechanisms occur in the same cell and contribute to enhanced resistance. Importantly, in all cases the MEK-resistant cell lines retained their addiction to the mitogen-activated protein kinase (MAPK) pathway, as evidenced by their sensitivity to a selective inhibitor of the ERK1/2 kinases. These data suggest that tumors with acquired MEK inhibitor resistance remain dependent on the MAPK pathway and are therefore sensitive to inhibitors that act downstream of the mutated MEK target. Importantly, we show that dual inhibition of MEK and ERK by small molecule inhibitors was synergistic and acted to both inhibit the emergence of resistance, as well as to overcome acquired resistance to MEK inhibitors. Therefore, our data provide a rationale for cotargeting multiple nodes within the MAPK signaling cascade in K-ras mutant tumors to maximize therapeutic benefit for patients. Mol Cancer Ther; 11(5); 1143–54. ©2012 AACR.
miRNA-29b Suppresses Prostate Cancer Metastasis by Regulating Epithelial–Mesenchymal Transition Signaling
Authors: Ru Peng , Steele Robert , Newhall Philip , Phillips Nancy J. , Toth Karoly , Ray Ratna B. 
Published: March 2012

Abstract
Prostate cancer remains the second leading cause of cancer deaths among American men. Early diagnosis increases survival rate in patients; however, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment are necessary for inhibiting prostate cancer disease progression. Here, we have shown that miRNA-29b (miR-29b) expression was lower in prostate cancer cells (PC3 and LNCaP) as compared with immortalized prostate epithelial cells. Between these two prostate cancer cell lines, metastatic prostate cancer PC3 cells displayed lower expression of miR-29b. We also observed a significant downregulation of miR-29b expression in human prostate cancer tissues as compared with patient-matched nontumor tissues. PC3 cells ectopically expressing miR-29b inhibited wound healing, invasiveness, and failed to colonize in the lungs and liver of severe combined immunodeficient mice after intravenous injection, while PC3 cells expressing a control miRNA displayed metastasis. Epithelial cell marker E-cadherin expression was enhanced miR-29b transfected in prostate cancer cells as compared with cells expressing control miRNA. On the other hand, N-cadherin, Twist, and Snail expression was downregulated in PC3 cells expressing miR-29b. Together these results suggested that miR-29b acts as an antimetastatic miRNA for prostate cancer cells at multiple steps in a metastatic cascade. Therefore, miR-29b could be a potentially new attractive target for therapeutic intervention in prostate cancer. Mol Cancer Ther; 11(5); 1166–73. ©2012 AACR.
The Synthetic Triterpenoid CDDO-Methyl Ester Delays Estrogen Receptor–Negative Mammary Carcinogenesis in Polyoma Middle T Mice
Authors: Tran Kim , Risingsong Renee , Royce Darlene , Williams Charlotte R. , Sporn Michael B. , Liby Karen 
Published: March 2012

Abstract
Novel drugs are needed for the prevention and treatment of breast cancer. Synthetic triterpenoids are a promising new class of compounds with activity in a variety of preclinical cancer models. We tested activity of the methyl ester derivative of the synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me), in a relevant model of estrogen receptor–negative breast cancer, the polyoma-middle T (PyMT), in which the oncoprotein drives carcinogenesis. The developing tumors recapitulate key features of the human disease. Mice were fed CDDO-Me (50 mg/kg diet), starting at 4 weeks of age. CDDO-Me significantly increased the age of mice at onset of first tumor (P &lt; 0.001) by an average of 4.3 weeks and overall survival (P &lt; 0.001) by 5.2 weeks. The drug also inhibited the infiltration of tumor-associated macrophages into mammary glands of PyMT mice at 12 weeks of age and reduced levels of the chemokines CXCL12 and CCL2 in primary PyMT mammary tumor cells. Treatment with this multifunctional drug also inhibited secretion of matrix metalloproteinase-9 in primary tumor cells from PyMT mice and decreased proliferation of these cells by inhibiting cyclin D1 and decreasing phosphorylation of epidermal growth factor receptor and STAT3. Cancer Prev Res; 5(5); 726–34. ©2012 AACR.
Clinical Profiles Predict Early Nonadherence to Adjuvant Endocrine Treatment in a Prospective Breast Cancer Cohort
Authors: Markkula Andrea , Hietala Maria , Henningson Maria , Ingvar Christian , Rose Carsten , Jernström Helena 
Published: March 2012

AbstractNonadherence to adjuvant endocrine breast cancer treatment adversely affects disease-free and overall survival. Clinical predictors of nonadherence may allow for specific interventions to reduce nonadherence and improve survival. The aim was to investigate whether clinical characteristics predict nonadherence. Clinical characteristics and information on adherence were obtained from 417 patients with breast cancer in a population-based prospective cohort from southern Sweden using patient charts, pathology reports, and questionnaires filled out at the 1- and 2-year follow-up visits. At the 1- and 2-year follow-up visits, 36 (8.6%) and 33 (9.7%) patients were nonadherent, respectively. Thirteen of the nonadherent patients declined treatment and were never prescribed endocrine treatment. A body mass index (BMI) &lt; 25 kg/m2, preoperative current smoking, and drinking alcohol less often than twice a month predicted nonadherence at the 1-year [relative risk (RR), 5.24; 95% confidence interval (CI), 2.75–9.97] and the 2-year visits (RR, 4.07; 95% CI, 2.11–7.84) in patients with at least two of these clinical characteristics. When low histologic grade (I) was added to the model, having at least two of these four clinical characteristics predicted nonadherence at the 1-year (RR, 4.94; 95% CI, 2.46–10.00) and the 2-year visits (RR, 4.74; 95% CI, 2.28–9.87), the two profiles had a sensitivity ranging from 60.6% to 72.7%, whereas the specificity ranged from 68.0% to 78.4%. Nonadherence at the 1-year visit was associated with an increased risk for early breast cancer events (HR, 2.97; 95% CI, 1.08–8.15), adjusted for age and tumor characteristics. In conclusion, two clinical profiles predicted early nonadherence and may allow for targeted interventions to increase adherence if validated in an independent cohort. Cancer Prev Res; 5(5); 735–45. ©2012 AACR.
Regulation of Cardiac MicroRNAs by Bone Marrow Mononuclear Cell Therapy in Myocardial Infarction
Authors: Iekushi Kazuma , Seeger Florian , Assmus Birgit , Zeiher Andreas M. , Dimmeler Stefanie 
Published: March 2012

Background—
Cell therapy with bone marrow–derived mononuclear cells (BMCs) can improve recovery of cardiac function after ischemia; however, the molecular mechanisms are not yet fully understood. MicroRNAs (miRNAs) are key regulators of gene expression and modulate the pathophysiology of cardiovascular diseases.

Methods and Results—

We demonstrated that intramyocardial delivery of BMCs in infarcted mice regulates the expression of cardiac miRNAs and significantly downregulates the proapoptotic miR-34a. In vitro studies confirmed that the supernatant of BMC inhibited the expression of H
2
O
2
-induced miR-34a and cardiomyocytes apoptosis. These effects were blocked by neutralizing antibodies directed against insulin-like growth factor-1 (IGF-1). Indeed, IGF-1 significantly inhibited H
2
O
2
-induced miR-34a expression, and miR-34a overexpression abolished the antiapoptotic effect of IGF-1. Likewise, inhibition of IGF-1 signaling in vivo abolished the BMC-mediated inhibition of miR-34 expression and the protective effect on cardiac function and increased apoptosis and cardiac fibrosis. IGF-1 specifically blocked the expression of the precursor and the mature miR-34a, but did not interfere with the transcription of the primary miR-34a demonstrating that IGF-1 blocks the processing of miR-34a.

Conclusions—
Together, our data demonstrate that the paracrine regulation of cardiac miRNAs by transplanted BMCs contributes to the protective effects of cell therapy. BMCs release IGF-1, which inhibits the processing of miR-34a, thereby blocking cardiomyocyte apoptosis.